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Abstract

Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. The complexity and uncertainty related to the geographic distribution of HCV infection and chronic hepatitis C, determination of its associated risk factors, and evaluation of cofactors that accelerate its progression, underscore the difficulties in global prevention and control of HCV. Because there is no vaccine and no post-exposure prophylaxis for HCV, the focus of primary prevention efforts should be safer blood supply in the developing world, safe injection practices in health care and other settings, and decreasing the number of people who initiate injection drug use.

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... According to WHO, HCV-related diseases cause over 300,000 deaths annually, with 71 million people worldwide estimated to have chronic hepatitis C [10]. HCV is a common blood-borne illness, infecting 130-170 million people globally, and is the fastest-growing reason for liver transplants in wealthy nations, being a primary cause of chronic liver disease worldwide [11]. If untreated, 7-18% of individuals will develop severe liver damage within 20 years [12]. ...
... Equation (11) shows that V 1 (t) is positive for all t, with the initial value V 10 . Similarly, we can verify the positivity for the remaining variables of the system, which are: ...
... Finally, the coexisting equilibrium (E * ), where max[R 01 , R 02 ] > 1, is indicated by the blue zone. Figures 3,4,5,6,7,8,9,10,11,12, and 13 elegantly portray the intricate interplay between two basic reproduction numbers and the fluctuations in the values of parameters, a pivotal component of Eqs. (a) and (b). ...
Article
Hepatitis C virus (HCV) is a leading cause of morbidity and mortality worldwide, including in Bangladesh. Although the Ministry of Health in Bangladesh is implementing its nationwide HCV control policies, more specific and cost-effective interventions are needed to control HCV. In this study, we developed a two-strain HCV vaccination model to explore the dynamics of HCV infection transmission in Bangladesh. We calibrated the model with the number of HCV cases in Bangladesh to estimate some setting-specific parameters. We also derived the basic reproduction numbers (R01 and R02) and performed contour plots to find the most significant parameters and found that the transmission rate had the largest impact on HCV dynamics. We evaluated the cost-effectiveness of three basic control strategies: transmission control, vaccination, and treatment, all within the optimal control context. Our findings suggested that a triple control strategy combining transmission control, vaccination, and treatment is the most cost-effective way to reduce the burden of HCV. Our finding also indicated that the transmission control strategy is the most cost-effective for the single intervention strategies compared to vaccination and treatment. Alternative programmes can be adopted to curb HCV, depending on the availability of resources and policymakers' decisions.
... The hepatitis C virus (HCV) is a predominantly bloodborne virus that causes both acute and chronic infection [1]. Most acute infections are asymptomatic and do not lead to life-threatening complications. ...
... Most acute infections are asymptomatic and do not lead to life-threatening complications. While approximately one-third of infections clear within 6 months without any treatment, the remaining two-thirds develop chronic hepatitis C (CHC), which ranges in severity from mild to life-threatening disease and may lead to severe complications such as liver cirrhosis and cancer [1,2]. ...
Article
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In 2015, Spain launched a national eradication strategy for hepatitis C virus (HCV), resulting in the highest treatment rate in Europe and substantial reductions in HCV prevalence. However, to achieve the goal of HCV elimination, it is necessary to scale-up the diagnosis, treatment, and management of HCV infection. Our aim was to assess the prevalence, incidence, and cost effectiveness of scaling-up compared with status quo scenarios. A compartmental dynamic transmission model was developed comprising of a cascade of care and a liver progression module. Cost and quality-of-life inputs were sourced from the literature. Key outcomes were the prevalence and incidence of HCV and the incremental cost per quality-adjusted life-year (QALY) and per life-year (LY). Outcomes for a hypothetical elimination strategy were compared with the status quo. The base-case analysis found that scaling-up testing and treatment reduced both the prevalence and incidence of HCV over time, resulting in incremental costs per QALY and LY of €13,291 and €12,285 respectively, compared with the status quo. The main drivers of the cost-effectiveness results included cost of diagnosis, cost of treatment, proportion of people who are unaware, percentage of population who inject drugs, and calibration parameters related to HCV infection prevalence. This analysis demonstrated that scaling-up testing and treatment with direct-acting antivirals may be an efficient strategy for reducing the incidence and prevalence of HCV and may help achieve HCV elimination goals in Spain.
... Hepatitis C virus (HCV) is a hepatotropic avivirus and a major cause of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) [15]. Approximately 55-85% of cases presenting with acute HCV infection progress to chronicity, with 20-30% developing liver cirrhosis, and 1-4% progressing to hepatocellular carcinoma [10]. ...
... The CD56 surface antigen is typically expressed by NK cells [16]. It is an isoform of the human neural cell adhesion molecule that has been found on a subset of T lymphocytes and on cells derived from neural, muscle and embryonic tissue [15]. ...
Preprint
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Hepatitis C virus (HCV) infection develops into chronic hepatitis in over two-thirds of acute infections. While current treatments with Sovaldi and ribavirin achieve HCV eradication in >95% of cases, no vaccine is available and re-infection can readily occur. Natural killer (NK) cells represent a key cellular component of the innate immune system, participating in early defence against infectious diseases, viruses, and cancers. When acute infection becomes chronic, however, NK cell function is altered. the NK immune response is a double-edged sword that is a significant component of the innate immune antiviral response, but persistent activation can drive tissue damage during chronic infection. Natural killer (NK) and lymphocytes with NK receptors (NKRs) is thought to play a key role in determining whether host immune responses to hepatitis C virus (HCV) infection result in viral clearance or disease progression. The aim of the present work was to Study of some immunological cells (cd 16, cd 56), genetic factors (HLA-C) in hepatitis C virus infected patients. A total number of 60 patients were included in this study. Their age ranged from 38-62 years old. The included patients were classified into 3 groups: group IA and IB (n=40) including cases with positive HCV antibodies (HCV-Ab), but negative real-time PCR for HCV after treatment with Sovaldi and Ribavirin, and they were considered as Responders, group IA Infected with covid 19, while group IB not Infected with covid 19. While group II (n=20) including patients with HCV infection ( HCV-Ab positive and real-time PCR for HCV is positive ) after treatment with Sovaldiand Ribavirin ( Non responders ) Considered as Non Responders. And group III ( n=60 ) healthy persons with matched age, sex and environmental status also included as controls.
... Nearly half of this mortality is attributed to hepatitis C virus (HCV) (1), a blood-borne virus whose transmission is largely preventable (2,3). Infection with HCV can cause acute hepatitis, fibrosis, cirrhosis, and liver cancer among other disease sequelae (4,5). ...
... However, HCV-TasP was shown to provide still a strategic approach to control the epidemic and to reach the elimination target by 2030 in these 19 countries. While HCV treatment is indicated at the individual level to prevent disease sequelae such as fibrosis, cirrhosis, and liver cancer (4,5), the impact of the treatment on reducing (indirectly) the onward transmission of the infection is substantial and could lead to elimination if carriers of this infection are identified and treated. ...
Article
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Background Direct-acting antivirals opened an opportunity for eliminating hepatitis C virus (HCV) infection in the Middle East and North Africa (MENA), the region most affected by HCV infection. Impact of HCV treatment as prevention (HCV-TasP) was investigated in 19 MENA countries. Methods An age-structured mathematical model was used to assess program impact using epidemiologic and programming measures. The model was fitted to a database of systematically gathered HCV antibody prevalence data. Two main scenarios were investigated for the treatment roll-out to achieve (i) 80% reduction in HCV incidence by 2030, and (ii) incidence rate < 1 per 100,000 person-years by 2030. Results In the target-80%-incidence-reduction scenario, number of treatments administrated by 2030 ranged from 2,610 in Lebanon to 180,416 in Sudan with a median of 53,079, and treatment coverage ranged between 40.2 and 78.4% with a median of 60.4%. By 2030, prevalence of chronic infection ranged between 0.0 and 0.3% with a median of 0.1%, and incidence rate, per 100,000 person-years, ranged between 0.9 and 16.3 with a median of 3.2. Program-attributed reduction in incidence rate ranged between 47.8 and 81.9% with a median of 68.5%, and number of averted infections ranged between 401 and 68,499 with a median of 8,703. Number of treatments needed to prevent one new infection ranged from 1.7 in Oman to 25.9 in Tunisia with a median of 6.5. In the target incidence rate < 1 per 100,000 person-years scenario, number of treatments administrated by 2030 ranged from 3,470 in Lebanon to 211,912 in Sudan with a median of 54,479, and treatment coverage ranged between 55.5 and 95.9% with a median of 87.5%. By 2030, prevalence of chronic infection was less than 0.1%, and incidence rate, per 100,000 person-years, reached less than 1. Program-attributed reduction in incidence rate ranged between 61.0 and 97.5% with a median of 90.7%, and number of averted infections ranged between 559 and 104,315 with a median of 12,158. Number of treatments needed to prevent one new infection ranged from 1.3 in Oman to 25.9 in Tunisia with a median of 5.5. Conclusion HCV-TasP is an effective and indispensable prevention intervention to control MENA’s HCV epidemic and to achieve elimination by 2030.
... Bovine viral diarrhea/mucosal disease (BVD-MD) is caused by bovine viral diarrhea/mucosal disease virus (BVDV) and occurs mainly in cattle, but also in sheep, pigs, goats, and other even-toed ungulates. Pestivirus is most closely related to hepatitis C virus (HCV), a serious and persistent threat to global health (Shepard et al. 2005). ...
... Hepatitis C virus (HCV) is a significant public health concern with a worldwide prevalence of 3% and the resulting infection leads to chronic hepatitis and liver cirrhosis Shepard et al., 2005). Gonzalez et al. demonstrated that QRC (50 µM) significantly inhibited HCV production possibly via a decrease in heat shock protein 40 (HSP40) and HSP70 and their potential involvement in internal ribosome entry site (IRES) translation, as well as viral morphogenesis or secretion in 293T, Huh-7, and Huh-7.5 cell lines. ...
Article
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Liver metabolizes and detoxifies xenobiotics and toxicity in this organ can lead to dysfunctionality. Flavonoids such as quercetin (QRC) have been shown to possess protective effects against different liver disorders. This flavonol exerts its hepatoprotective effects via different mechanisms including increase of nuclear factor (erythroid-derived 2)-like 2 protein expression, sirtuin 1, thioredoxin and thioredoxin reductase and decrease in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and myeloid differentiation primary response gene 88 (MYD88). The aim of the current review was to examine the possible protective effects of QRC against different natural and chemical toxic agents-induced hepatotoxicity, so that it could be considered as a hepatoprotective agent in clinical trials. Based on a variety of keywords, Medline, Scopus, Web of Science and Google scholar were searched for all related published literature. Because of insufficient clinical trials on this topic, this review contains only in vivo and in vitro investigations. In this regard, more clinical trials are required to be performed to confirm QRC beneficial properties in human hepatotoxicity. Collectively, QRC could be a promising natural compound in reversing the toxic effects of different toxic agents in the liver. Hepatitis C virus; HepG2: hepatocellular carcinoma G2; HMGB1: high-mobility group box 1 protein; HO-1: heme oxygenase 1; HSP: heat shock protein; i.v.-intravenously; IF-γ: interferon-γ; IgG: immunoglobin g; IL-1β: interleukin 1 beta; IL-6: interleukin 6; iNOS: inducible nitric oxide synthase; IRES: internal ribosome entry site; IκBα: inhibitor of kappa B protein-alpha; Keap1: kelch-like ECH-associated protein-1; LDH: lactate dehydrogenase; LMP: lysosomal membrane permeabilization; LPS: lipopoly-saccharide; MAP Kinase: mitogen-activated protein kinase; MAP1LC3: microtubule-associated proteins 1A/1B light chain 3B; MMP: metalloproteinase; MPO: myeloperoxidase; MYD88: myeloid differentiation primary response gene 88; NAPQI: N-acetyl-p-benzoquinone imine; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NPs: nanoparticles; NQO1: NADPH: Quinone Oxidoreductase 1; Nrf2/ARE: nuclear factor (erythroid-derived 2)-like 2/antioxidant response element; p.o.: per os; PCBs: polychlorinated biphenyls; P-JNK: phosphor-ylated c-Jun N-terminal kinase; PLA2: phospholipase A2; PLIN2: perilipin 2; PON1: paraoxonase 1; Prx: peroxiredoxin; QRC: quercetin; ROR-γt: retinoid related orphan receptor-γt; ROS: reactive oxygen species; SDH: sorbitol dehydrogenase; SOD: superoxide dismutase; STAT1: signal transducer and activator of transcription 1; SULTs: sulfotransferases; TAA: thioacetamide;
... However, the global prevalence of HBV infection depends on vaccination coverage, with HBV vaccination ranging from 90% in the Western Pacific and the Americas to 56% in Southeast Asia [44]. According to recent studies, the global incidence of HBV and HCV infection is higher in the Asian population compared to the Western hemisphere, especially the United States, as well as European countries [45,46]. Therefore, it seems logical that most studies have been done in Asia. ...
Article
Background In recent years, the increase in prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with viral chronic hepatitis due to hepatitis B virus (HBV) and hepatitis C virus (HCV) has been alarming. The pattern of liver histological changes in patients with HBV and HCV infections resembles those of NAFLD, leading to potential misdiagnosis. Methods Using global databases such as Scopus and PubMed, relevant studies were retrieved and those studies found to be eligible based on inclusion criteria were analyzed. Statistical analysis was done by comprehensive meta-analysis software. Results The results suggested an inverse association between HBV and HCV infections and hepatic steatosis risk, but not significant. The risk of hepatic steatosis in patients with concurrent chronic viral hepatitis is significantly associated performed with metabolic syndrome and biochemical parameters particularly body mass index > 25 kg/m ² , arterial hypertension, dyslipidemia, type 2 diabetes, hypertriglyceridemia, and hypercholesterolemia. Conclusion According to the results of the present study, viral hepatitis (viral load) has a protective role against the development of hepatic steatosis. Nevertheless, hepatic steatosis in patients infected with HBV and HCV was associated with metabolic syndrome.
... Hepatitis C virus (HCV) is a major public health concern with over 71 million people chronically infected globally (1). HCV is responsible for more than half of chronic liver disease cases worldwide (2,3). To date, no vaccine is available to prevent HCV infections but directacting antivirals (DAAs) are highly efficacious treatments with minimal side effects (4)(5)(6). ...
Article
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Despite having a higher risk of hepatitis C virus (HCV) infections, people who inject drugs (PWID) in sub-Saharan Africa (SSA) have limited access to HCV treatment. There is scarce literature on treatment delivery modalities that overcome logistical and financial barriers. We utilized different service delivery modalities to provide direct-acting antivirals (DAAs) to PWIDs infected with HCV through methadone clinics and needle and syringe program (NSP) sites in Kenya. In collaboration with Kenya’s National AIDS and STI Control Programme (NASCOP), we enrolled individuals with active HCV infection confirmed by HCV RNA detection from methadone and NSP sites in Nairobi, Mombasa, and Kilifi counties. Liver function and hepatitis B virus (HBV) status were assessed at baseline. Those eligible for treatment were offered ledipasvir-sofosbuvir treatment provided by NASCOP through directly observed therapy (DOT). Participants completed a follow-up visit 12 weeks after completing treatment to measure sustained viral response (SVR-12). Challenges faced while delivering HCV treatment at participating sites included the limited availability and reliability of laboratory assays, and financial constraints faced by PWIDs to attend daily DOT. Based on our experience, strategies to deliver HCV treatment for PWID in Kenya should consider improving the availability of laboratory tests and prioritizing treatment through methadone centers to achieve good outcomes.
... [29][30][31][32] This finding underscores the need for further investigation into the underlying factors contributing to these disparities. Encouragingly, the global anti-HCV prevalence has decreased from 2% to 0.7% in recent years, [33,34] highlighting the potential effectiveness of control strategies. ...
Article
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A BSTRACT Background Hepatitis B virus (HBV) and Hepatitis C virus (HCV) show similarity in the transmission, distribution, hepatotropism, and leading to chronic asymptomatic infection. Coinfection of HBV and HCV can lead to more severe liver disease and an increased risk for progression to hepatocellular carcinoma (HCC). Most of the people with chronic infection are unaware of their HBV and HCV infections, hence facilitating these to go undiagnosed until these viruses have caused serious liver damage and they act as a potential source of infection for the community at large. Therefore, the present study aimed to find the prevalence of HBV and HCV along with incidences of coinfection of HBV and HCV in patients seeking hospital care in central India. Methods A five-year hospital-based study was carried out at the tertiary care hospital in Central India from 2018 to 2022. A total of 72402 patients attending the outdoor patients and admitted indoor patients who were advised for HBV and HCV for screening before any invasive/surgical procedure and patients who presented with symptoms of acute or chronic liver disease were included in this study. Screening was done by immunochromatography-based card test followed by the confirmation of all samples by enzyme immunoassay. Results Seroprevalence of HBV and HCV was found to be 3.71% and 1.91%, respectively. Coinfection with HBV/HCV was seen in 0.13% of the individuals. The overall prevalence of HBV, HCV, and HBV-HCV coinfection was significantly higher in the male population as compared to females. Conclusion The study findings of seroprevalence of HBV and HCV among the hospital-based population will help to get a baseline understanding of the disease burden in central India. The HBV/HCV coinfection rate also raises serious concerns owing to its high prevalence rate among the younger age.
... Until the late 1980s, blood and blood-derived products were not screened for HCV, resulting in a transmission rate of approximately one case in every 50 blood units, even in high-income countries [47]. Shortly after the introduction of the first assay for HCV detection (first-generation ELISA) in blood donors, subsequent generations of assays (second-and third-generation ELISA) nearly eliminated the risk of HCV transmission through blood transfusion [48]. These newer assays were highly sensitive, reducing the serological window phase of detection. ...
Article
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Hepatitis C virus infection affects over 58 million individuals and is responsible for 290,000 annual deaths. The infection spread in the past via blood transfusion and iatrogenic transmission due to the use of non-sterilized glass syringes mostly in developing countries (Cameroon, Central Africa Republic, Egypt) but even in Italy. High-income countries have achieved successful results in preventing certain modes of transmission, particularly in ensuring the safety of blood and blood products, and to a lesser extent, reducing iatrogenic exposure. Conversely, in low-income countries, unscreened blood transfusions and non-sterile injection practices continue to play major roles, highlighting the stark inequalities between these regions. Currently, injection drug use is a major worldwide risk factor, with a growing trend even in low- and middle-income countries (LMICs). Emerging high-risk groups include men who have sex with men (MSM), individuals exposed to tattoo practices, and newborns of HCV-infected pregnant women. The World Health Organization (WHO) has proposed direct-acting antiviral (DAA) therapy as a tool to eliminate infection by interrupting viral transmission from infected to susceptible individuals. However, the feasibility of this ambitious and overly optimistic program generates concern about the need for universal screening, diagnosis, linkage to care, and access to affordable DAA regimens. These goals are very hard to reach, especially in LMICs, due to the cost and availability of drugs, as well as the logistical complexities involved. Globally, only a small proportion of individuals infected with HCV have been tested, and an even smaller fraction of those have initiated DAA therapy. The absence of an effective vaccine is a major barrier to controlling HCV infection. Without a vaccine, the WHO project may remain merely an illusion.
... Worldwide, around 50 million individuals are carrying chronic HCV infection; each year, around one million individuals get new HCV infections [13]. HCV causes a wide range of liver disorders, such as acute viral hepatitis, chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma [14]. The World Health Organization aims to eliminate hepatitis C as a risk to community health by 2030 by reducing deaths and new infections [15]. ...
Article
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Introduction: Hepatitis C is a global health burden with significant morbidity and mortality. It primarily affects the liver and causes acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Common modes of transmission of hepatitis C virus (HCV) infection are blood transfusion, needlestick injury, and mother-fetus transmission, among which transmission, blood transfusion is one of the most important causes. Blood transfusion is one of the pillars in the management of patients that saves lives and improves morbidity. Blood donation in India is done by voluntary and replacement blood donors of both sexes. The aim of this study is to determine the seroprevalence of HCV among blood donors in the Jharkhand state, a tribal-preponderant region of India, and to see the trend over the years.
... After infecting nearly 170 million people (3% of the world's population), it was recognized as a major global public health problem in 1989. [1] Hepatitis C is a parenterally transmitted hepatotropic virus and it is more commonly associated with chronic active hepatitis whereas due to the paucity of symptoms, the acute phase of the disease remains mostly unnoticed. It impacts the global health system to a large extent and it is responsible for significant morbidity and mortality as HCV can lead to chronic liver disease among 5%-20% of infected persons causing cirrhosis, hepatocellular carcinoma, and end-stage liver disease. ...
... After infecting nearly 170 million people (3% of the world's population), it was recognized as a major global public health problem in 1989. [1] Hepatitis C is a parenterally transmitted hepatotropic virus and it is more commonly associated with chronic active hepatitis whereas due to the paucity of symptoms, the acute phase of the disease remains mostly unnoticed. It impacts the global health system to a large extent and it is responsible for significant morbidity and mortality as HCV can lead to chronic liver disease among 5%-20% of infected persons causing cirrhosis, hepatocellular carcinoma, and end-stage liver disease. ...
Article
A BSTRACT Introduction Hepatitis C virus (HCV) infection is the most common chronic blood-borne disease and is more commonly associated with chronic active hepatitis leading to cirrhosis, hepato-cellular carcinoma and end-stage liver disease. Methodology 160 consecutive screening positive (Enzyme linked immuno sorbent assay positive) Hepatitis C samples were tested by HCV RNA Real Time-PCR for confirmation. Result Prevalence of confirmed hepatitis C among screening positive patient in the present study was found to be 24.4%. Vaccinated individual with Hepatitis A and Hepatitis B had significant association with PCR positivity in screening positive Hepatitis C patient ( p < 0.05). IV drug users and patient having multiple sex partners have significant association with PCR positivity among screening positive Hepatitis C patients ( p < 0.05). Conclusion Due to the lack of an effective vaccine and the increased risk of serious complications, it is important to focus on prevention and early detection of HCV.
... Eastern Europe and central Asia account for the largest proportion of HIV-infected persons who have serological evidence of past or present HCV infection (27%), because of injection drug use. HIV coinfection doubles the risk of mother-to-child transmission of HCV (56,57), and is associated with less spontaneous HCV clearance, higher HCV viral loads, and more rapid progression of liver disease (58)(59)(60)(61). People living with HIV should be tested for HCV infection (54,62). . ...
Technical Report
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Status of viral hepatitis in the world, 2015
... In 2015, viral hepatitis killed 1.45 million people, almost as many as tuberculosis (1.8 million deaths), and more than the human immunodeficiency virus (HIV, 1.1 million) with 47% of deaths caused by viral hepatitis B and 48% death due to viral hepatitis C [1] [9]. ...
... Hepatitis C virus (HCV) infection still maintains its importance since it is one of the most important causes of liver cirrhosis and hepatocellular carcinoma, and there is limited access to effective treatment options (1). According to the 2016 global report of the World Health Organization (WHO), it has been reported that 71 million people worldwide are infected with HCV, causing 400,000 deaths annually (2). ...
... Introduction epatitis B (HBV) and C (HCV) are serious global health problems. Approximately 500 million people i.e. one fifth of the world population are chronically infected with HBV and HCV 1,2 . About 1.5 million people die every year from HBV and HCV related chronic liver disease such as end stage cirrhosis and HCC (Hepatocellular carcinoma). ...
Article
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Objectives: To compare rapid tests (ICT) with 4 th generation ELISA (gold standard) for hepatitis B and C infection. Graduate Medical Centre, Karachi. Study was done over six months. Materials and Methods: ELISA confirmed 200 samples for HBsAg and 200 for Anti-HCV were selected, making a total of 400 samples. Out of 400 samples, 200 were positive and 200 negative on ELISA. These samples were further tested on three different brands of most frequently used rapid ICT Kits for HBsAg and Anti HCV. The sensitivity, specificity, negative predictive value, positive predictive value and cost effectiveness were compared using 4 th generation ELISA as gold standard. The Rapid kits for HBsAg that were analysed included Acon (USA), Determine (Abbott) and Intec (China) and for Anti HCV they were Acon (USA), Membrane (Canada) and Nobis (Germany). Results: Out of 100 positive and 100 negative tests for HBsAg confirmed on ELISA, all rapid kits showed comparable results with ELISA. The sensitivity and negative predictive value of Intec China (98%) and Determine Abbot (98%) were similar to each other however, these were higher when compared to Acon USA (95%). The rapid kit by Intec China was cheaper to the other two rapid kits and was therefore, the most cost effective rapid kit. The specificity and positive predictive value of all three HBsAg ICT kits was 100% and in agreement with ELISA. Out of 100 HCV positive and 100 HCV negative cases confirmed on ELISA, the rapid test by Acon USA showed maximum sensitivity. The sensitivity and negative predictive values of Acon USA were higher (93%) as compared to Membrane-Canada (89%) and Nobis-Germany (86%). The specificity and positive predictive values of Acon were comparatively lower (93%) but did not significantly vary when compared with Membrane Canada (97%) and Nobis German (96%). Conclusions: The rapid ICT Kits for HbsAg and anti HCV were equally sensitive and specific when compared with ELISA. These rapid kits are cheaper and easy to perform and their use should be encouraged especially in rural setting. Policy statement: ELISA confirmed rapid HBV, HCV kits being cheaper but sensitive and specific should be used for screening cases especially in rural setting.
... HCV is a blood-borne virus, and its transmission can be substantially reduced through proper preventive measures (2). Contracting HCV can lead to various health complications, including acute hepatitis, fibrosis, cirrhosis, and potentially liver cancer (3,4). ...
Article
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Background Hepatitis C virus (HCV) infection levels in Jordan remain uncertain. No HCV national population-based survey has ever been conducted in the country. To meet the World Health Organization’s target of reducing HCV incidence to ≤5 per 100,000 people per year by 2030, it is essential to determine the infection levels, identify affected individuals and populations, and provide appropriate treatment using direct-acting antivirals to individuals carrying the virus. Methods The study utilized the HCV testing database of 28,798 attendees of Biolab Diagnostic Laboratories in Jordan, covering the period from January 19, 2010, to May 26, 2023. Cross-sectional and cohort study analyses were conducted, including estimating HCV antibody (Ab) prevalence, examining associations with HCV Ab positivity, determining the HCV viremic rate, and estimating HCV incidence rate using a retrospective cohort study design. Results A total of 27,591 individuals, with a median age of 31.3 and 52.9% being females, underwent HCV Ab testing, while 1,450 individuals, with a median age of 42.2 and 32.8% being females, underwent HCV RNA PCR testing. The study sample HCV Ab prevalence was 4.0% (95% CI: 3.7–4.2%). After applying probability weights, the weighted HCV Ab prevalence was 5.8% (95% CI: 4.6–7.3%). Age was strongly associated with HCV Ab positivity, particularly among individuals aged 50 years or older, who had 10-fold higher odds of being HCV Ab positive compared to those aged 10–19 years. Males had 2.41-fold higher odds of testing positive for HCV Ab compared to females. The HCV viremic rate was 54.1% (95% CI: 43.0–65.0%). The cumulative incidence of HCV infection, after 5 years of follow-up, was estimated to be 0.41% (95% CI: 0.17–0.99%). The HCV incidence rate was calculated at 1.19 per 1,000 person-years (95% CI, 0.50–2.87). Conclusion Prevalence and incidence of HCV infection were substantial, estimated at ~5% and 1 per 1,000 person-years, respectively, and highlighting the presence of core groups actively engaged in the virus’ acquisition and transmission. The high observed viremic rate indicates the need for expanding HCV treatment efforts to effectively control HCV transmission in Jordan. Utilizing quality diagnostic laboratories and innovative testing strategies is key to identifying infection carriers and facilitating linkage to treatment and care.
... Hepatitis c viruses is very common problem in Pakistan and all over world more than thousands death reported every day from different complication. 1,2 there are five different types of genotype hcv viruses, like genotype type 1, 2, 3, 4, 5. In Pakistan genotype 2 and 3 are more common type of genotype found in all male and female patients while hcv genotype 1,3,5 more found in other part of world. ...
... 70 Differences in risk behaviors such as injection drug use, blood transfusion, unprotected sex, differences in HCV laboratory testing, national socioeconomic status, healthcare policies, and cultural practices like tattooing and piercing could contribute to differences in prevalence worldwide. 68,71 Pakistan, as one of the countries in the Eastern Mediterranean region, had one of the highest prevalence rates (9.02%) among pregnant women in our study. A meta-analysis conducted in 2018 estimated HCV pooled prevalence in Pakistan at 6.2% among the general population (populations at low risk) including pregnant women. ...
Article
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Background Monitoring progress towards the WHO global target to eliminate hepatitis C virus (HCV) infection by 2030, entails reliable prevalence estimates for HCV infection in different populations. Little is known about the global burden of HCV infection in pregnant women. Here, for the first time to our knowledge, we estimated the global and regional seroprevalence of HCV antibody (Ab) and determinants in pregnant women. Methods In this systematic review and meta-analysis study, we searched PubMed/MEDLINE, Web of Science, Embase, Scopus, and SciELO databases for peer-reviewed observational studies between January 1, 2000 and April 1, 2023, without language or geographical restrictions. Pooled global seroprevalence (and 95% confidence interval, CI) were estimated using random-effects meta-analysis and seroprevalences were categorised according to World Health Organization regions and subregions, publishing year, countries’ income and human development index (HDI) levels. We used sensitivity analysis to assess the effect of four large sample size studies on pooled global prevalence through the “leave-one-out” method. We also investigated the association of potential risk factors with HCV seropositivity in pregnant women by subgroup and meta-regression analyses. The Protocol was registered in PROSPERO CRD42023423259. Findings We included 192 eligible studies (208 datasets), with data for 148,509,760 pregnant women from 53 countries. The global seroprevalence of HCV Ab in pregnant women was 1.80% (95% CI, 1.72–1.89%) and 3.29% (3.01–3.57%) in overall and sensitivity analyses, respectively. The seroprevalence was highest in the Eastern Mediterranean region (6.21%, 4.39–8.29%) and lowest in the Western Pacific region (0.75%, 0.38–1.22%). Subgroup analysis indicated that the seroprevalence of HCV Ab among pregnant women was significantly higher for those with opioid use disorder (51.94%, 95% CI: 37.32–66.39) and HIV infection (4.34%, 95% CI: 2.21–7.06%) than for the general population of pregnant women (1.08%, 95% CI: 1.02–1.15%), as confirmed by multivariable meta-regression (p < 0.001). A significant decreasing trend was observed with increasing human development index levels. Other important risk factors for HCV seropositivity included older age, lower educational levels, poly sexual activity, history of blood transfusion, hospitalization, surgery, abortion and sexual transmitted diseases, having scarification/tattoo or piercing, and testing hepatitis B positive. Interpretation This meta-analysis showed relatively high burden of exposure to HCV infection (2.2–5.3 million) in pregnant women globally. However, due to substantial heterogeneity between studies, our estimates might be different than the true seroprevalence. Our findings highlighted the need to expand HCV screening for women of reproductive age or during pregnancy, particularly in countries with high prevalence; as well as for more studies that assess safety of existing therapeutic drugs during pregnancy or potentially support development of drugs for pregnant women. Funding There was no funding source for this study.
... However, the latter evidence is mostly circumstantial and an increased risk of transmission from HCV-positive patients to household members also includes siblings, parents, and offspring, which suggests that long and close contact represent a risk in itself [27][28][29][30] . Most cases of new HCV infection identified currently in Western Europe and USA have been associated with a history of injecting drug use and iatrogenic exposure in health-care facilities, but in a large proportion of cases no clear risk factor can be identified 19,31,32 . ...
Article
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Most Hepatitis C virus (HCV)-infected subjects develop chronic infection, whereas a minority clear the virus in the early phase of infection. We analyzed factors associated with outcome (chronicity vs clearance) during the preclinical seronegative phase of community-acquired HCV infection. Among 17.5 million blood donations in the years 2000–2016, 124 blood donors were found to be HCV RNA-positive/anti-HCV-negative. All were contacted after 0.5–12.7 years and 40 responded and provided blood sample. Hypervariable region 1 was analyzed by ultradeep pyrosequencing and cytokines in serum were quantified by Luminex (R&D Systems) multiplex immunoassay. Twenty-one (52.5%) donors were found to be HCV-RNA-positive, while 19 (47.5%) were HCV RNA negative (none received antiviral treatment). All but one seroconverted to anti-HCV. Donors with resolving hepatitis did not differ significantly from donors with chronic infection with respect to age, genotypes, IL28B polymorphisms, number of viral variants, nucleotide diversity per site or the overall number of nucleotide substitutions. However, the former group had significantly higher levels of IL-1beta, IL-1RA, IL-6, IFN-gamma and FGF-2 in serum. In our study of community-acquired acute hepatitis C approximately half of all subjects eliminated the virus spontaneously, and this clearance was associated with marked cytokine response in the early seronegative stage of infection.
... Resveratrol prevents the respiratory syncytial virus from binding to receptors on respiratory tract cells 45 . It also inhibits the intracellular replication of hepatitis C virus 46 . The inhibitory effect of resveratrol on HIV-1 is manifested through the obstruction of reverse transcription in CD4 T cells 47 . ...
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Polyphenols are nutrients that are classified as phytochemicals because they are found exclusively in foods of plant origin. They are divided into flavonoids (flavonols, flavones, isoflavones, anthocyanins, flavon-3-ols, and flavones) and nonflavonoids (phenolic acids, stilbenes, lignans, dihydrochalcones, and coumarins). Research shows that polyphenols have multiple positive health effects. This paper aims to systematize recent scientific results on the effects of polyphenols on health. A search of the scientific literature of the last 20 years in the English language on the health effects of polyphenols was performed in the "PubMed" database using the keywords: "polyphenols"; "microbiota"; "diabetes mellitus"; "cardiovascular diseases"; "cognitive functions"; "viral diseases"; "cancer"; "mental health" and "dyslipidemias". There is a mutual positive influence of polyphenols and microbiota. Polyphenols affect the composition of the microbiota, especially the growth of beneficial microbiotic strains. In epidemiological studies, polyphenols have shown a protective effect concerning DM type 2 by lowering blood glucose and glycosylated hemoglobin, reducing insulinemia and increasing insulin sensitivity, reducing inflammation and oxidative stress in cells. By reducing arterial stiffness, oxidative stress, inflammation, and endothelial dysfunction, and regulating the production of nitrogen monoxide and cytokines, they reduce the risk of hypertension, myocardial infarction, and cerebral insult. Polyphenols have a positive effect on cognitive functions and executive functioning and reduce the risk of Parkinson's disease. Their antiviral effect is based on the inhibition of the enzyme helicase, which is necessary for viral replication and recombination, reduction of oxidative stress, virucidal effect, interaction with the structural proteins of the virus, and interference with the fusion of the virus with the cell membrane, reduction of inflammation and increase of immunity and reduction of dysbiosis in the intestines and lungs. The protective effect of polyphenols concerning cancer is based on induced apoptosis, inhibition of the matrix-metalloproteinase enzyme that enables metastases, inhibition of tumor growth, and inhibition of angiogenesis. In terms of mental health, polyphenols reduce the risk of depression and ADHD (Attention Deficit Hyperactivity Disorder) and have a beneficial effect on the reduction of tardive dyskinesia in patients with schizophrenia. They also have a positive effect on dyslipidemia, by reducing the level of LDL cholesterol and increasing the level of HDL cholesterol. Polyphenols are phytochemicals with multiple positive health effects. They work synergistically with the gut microbiota. Epidemiological studies have shown that polyphenols reduce the risk of diabetes mellitus type 2, hypertension, myocardial infarction, cerebral insult, viral diseases, Parkinson's disease, cognitive disorders, cancer, depression, and dyslipidemia. Nutritional support or supplementation with polyphenols can be recommended in the primary and secondary prevention of the mentioned diseases.
... Hepatitis C Virus (HCV) belongs to the family Flaviviridae and the genus Flavivirus. It is one of the main causes of liver inflammation and hepatocellular carcinoma (Shepard et al., 2005). Long-term HCV infection can lead to serious complications which may result in the need for liver transplantation (Beld et al., 1999). ...
Article
NS3-4A, a serine protease, is a primary target for drug development against Hepatitis C Virus (HCV). However, the effectiveness of potent next-generation protease inhibitors is limited by the emergence of mutations and resulting drug resistance. To address this, in this study a structure-based drug design approach is employed to screen a large library of 7320 natural compounds against both wild-type and mutant variants of NS3-4A protease. Telaprevir, a widely used protease inhibitor, was recruited as the control drug. The top 10 compounds with favorable binding affinities underwent drug-likeness evaluation. Based on ADMET studies, complexes of NP_024762 and NP_006776 were selected for molecular dynamic simulations. Principal component analysis (PCA) was employed to explore the conformational space and protein dynamics of the protein-ligand complex using a Free Energy Landscape (FEL) approach. The cosine values obtained from FEL analysis ranged from 0 to 1, and eigenvectors with cosine values below 0.2 were chosen for further analysis. To forecast binding free energies and evaluate energy contributions per residue, the MM-PBSA method was employed. The results highlighted the crucial role of amino acids in the catalytic domain for the binding of the protease with phytochemicals. Stable associations between the top compounds and the target protease were confirmed by the formation of hydrogen bonds in the binding pocket involving residues: His1057, Gly1137, Ser1139, and Ala1157. These findings suggest the potential of these compounds for further validation through biological evaluation.Communicated by Ramaswamy H. Sarma.
... It is known that anti-HCV seropositivity from population-based studies is used to compare levels of HCV infection [9]. According to WHO, countries in Africa and Asia have the highest rate of anti-HCV carriage, whereas industrialized countries in North America, Western Europe, and Australia are known to be lower endemic [48,49,50]. [54]. ...
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Background: The global Viral hepatitis elimination by 2030 is uncertain in resource-limited settings (RLS), due to high burdens and poor diagnostic coverage. This sounds more challenging for hepatitis C virus (HCV) given that antibody (HCVAb) sero-positivity still lacks wide access to HCV RNA molecular testing. This warrants context-specific strategies for appropriate management of liver impairment in RLS. We herein determine the association between anti-HCV positivity and liver impairment in an African RLS. Methods: A facility-based observational study was conducted from July-August 2021 among individuals attending the St Monique Health Center at Ottou, a rural community of Yaounde,Cameroon. Following a consecutive sampling, consenting individuals were tested for anti-HCV antibodies, hepatitis B surface antigen (HBsAg) and HIV antibodies (HIVAb) as per the national guidelines. After excluding positive cases for HBsAg and/or HIVAb, liver function tests (ALT/AST) were performed on eligible participants (HBsAg and HIVAb negative) and outcomes were compared according to HCVAb status; with p<0.05 considered statistically significant. Results: Out of 306 eligible participants (negative for HBsAg and HIVAb) enrolled, the mean age was 34.35±3.67 years. 252(82.35%) were female and 129 (42.17%) were single. The overall HCVAb sero-positivity was 15.68%(48/306), with 17.86% (45/252) among women vs. 5.55%(3/54) among men [OR (95%CI)=3.69(2.11-9.29),p=0.04]. HCVAb Carriage was greater among participants aged >50 years compared to younger ones [38.46%(15/39) versus 12.36% (33/267) respectively, OR(95%CI)=4.43(2.11-9.29), p<0.000] and in multipartnership [26.67%(12/45)vs.13.79%(36/261) monopartnership, OR (95%CI)= 2.27(1.07-4.80),p=0.03]. The liver impairment rate (abnormal ALT+AST levels) was 30.39%(93/306), with 40.19%(123/306) of abnormal ALT alone. Moreover, the burden of Liver impairment was significantly with aged>50 versus younger ones [69.23% (27/39) versus 24.72%(66/267) respectively, p<0.000). Interestingly, the burden of liver impairment (abnormal AST+ALAT) was significantly higher in HCVAb positive (62.5%, 30/48) versus HCVAb negative (24.42%, 63/258) participants, OR: 3.90 [1.96; 7.79], p=0.0001. Conclusions: In this rural health facility, HCVAb is highly endemic and the burden of liver impairment is concerning. Interestingly, HCVAb carriage is associated with abnormal liver levels of enzyme (ALT/AST), especially among the elderly populations. Hence, in the absence of nuclei acid testing, ALT/AST are relevant sentinel markers to screen HCVAb carriers who require monitoring/care for HCV-associated hepatocellular carcinoma in RLS. Keywords Hepatitis C Virus antibodies (HCVAb), ASAT/ALAT, liver impariment, hepatotoxicity, Cameroon.
... Estimated global prevalence of hepatitis C virus infection is 2-3% which accounts about 122 million to 185 million infected cases worldwide. [6][7][8][9][10][11] It is seen that 80% of the patients develop chronicity in acute liver disease caused by HCV. [5] Many studies have been done in past to study the peri-operative complications in different types of major surgeries other than ocular surgery, in patients having chronic liver disease. ...
Article
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Introduction: Small Incision Cataract surgery (SICS) is one of the most commonly performed surgery and the Hepatitis C virus infection in the country like ours is an upcoming health hazard. Undiagnosed asymptomatic HCV sero-positive cases outnumber the diagnosed cases. Hypocoagulability because of hepatitis, can cause detrimental effect on cataract surgery. Objective: To analyze the cataract surgery complications in HCV infected cases. Methods: This was a prospective, observational study conducted in the department of Ophthalmology of Muzaffarnagar Medical College, Uttar Pradesh from January 2019 to January 2020. After taking permission from the ethical committee and informed-written consent from the patients, total 200 eyes of 158 patients having (116 unilateral and 42 bilateral) cataract and incidentally diagnosed positive for HCV infection were enrolled in the study. Results: Out of 200 eyes, 48 eyes had no complications and 152 (76%) eyes had one or more complications like intra-operative bleed (68%), difficulty in wound closure (19.5%), post-operative AC reaction (61.5%), delayed healing (49%), hyphema (48%), leaky wound (37%) and keratitis (34%).Conclusion: Significant number of asymptomatic HCV sero-positive patients undergoing cataract surgery had peri-operative complications. It is recommended that pre-operative viral marker screening of all cataract patients should be done and measures to combat the difficulties during and after the surgery should be taken care of.
... These deaths were largely caused by the hepatitis C virus (HCV) and the hepatitis B virus (HBV). In response, the World Health Organization (WHO) set goals in 2016 for the "elimination of HBV and HCV as a public health concern by 2030 [32]. These goals include a 65% decrease in HCV-related morbidity and an 80% decrease in HCV infections when contrasted to a baseline year of 2015. ...
Conference Paper
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The conceptual formulation for diabetes & hepatitis in what seems like a fuzzy & neural network is investigated in this article. Because certain facts in a real-world situation cannot be recognized with precision, the metrics are used as approximate values. The membership functions and set of rules that make up the diabetes framework include fuzzy logic as their beginning premise. Fuzzy logic is just an augmentation of propositional logic which works with uncertainty and ambiguity in systems and offers a powerful mathematical tool to express data in a fashion that mimics naturally occurring human consciousness. ANN is a computational structure with biological inspiration made up of intricately linked adaptable simple processing units that can process information and convey information in a highly comparable manner. Investigators and academics from a diverse range of scientific and engineering disciplines were drawn to the emerging need for responsive intelligent machines because of the integration of Fuzzy Inference algorithms with Artificial Neural Networks. Fuzzy Systems, that can rationalize with imperfect information, are more adept at explaining their choices than artificial neural networks, which struggle to do so. Nevertheless, fuzzy systems are unable to learn the rules they employ to make decisions. Owing to these restrictions, intelligent hybrid systems have been developed to solve the issues using specific methodologies. The much more popular hybrid Neuro-Fuzzy approaches are discussed in this questionnaire survey, along with their benefits and drawbacks.
... It is now known to be the most important risk factor of HCC in Western Europe and North America where epidemiological studies have shown up to 70% of patients with HCC have anti-HCV antibody in the serum. However African and Asian countries report lower though rising rates 17,18 . Egypt has the highest prevalence of HCV in the world and this has been attributed to previous public health eradication schemes for schistosomiasis. ...
... 38 Successful eradication of the virus was achieved for only 15%-20% of newly infected individuals, with the remainder developing a chronic infection. 39 The ability of the HCV to persist within the host is impressive, which is attributed to its efficient ability to evade the adaptive and innate components of the host's immune system. 40 In the past 10 years, therapeutic agents against HCV were developed, with huge success. ...
Article
Persistent viruses (PV) are hard to be eradicated, even using effective medications, and can persist for a long time in humans, sometimes regardless of treatment. Hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) infections, the most common in our era, is still a challenge despite the increased knowledge about their biology. Most of them are highly pathogenic, some causing acute disease or, more often, leading to chronic persistent infections, and some of the occult, carrying a high risk of morbidity and mortality. However, if such infections were discovered early, they might be eradicated in the near future with effective medications and/or vaccines. This perspective review points out some specific characteristics of the most important chronic persistent viruses. It seems that in the next few years, these PV may have control by either by vaccination, epidemiological strategies and/or treatment.
... The HCV seropositivity levels in the US were 1.8%, Japan with around 1−3% seropositivity levels, and Italy recorded 2.2% seropositivity levels. 122,123 Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for 70−80% of cases. Chronic infection with the hepatitis C virus (HCV) has been identified as a key driver of HCC. ...
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Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Recent studies revealed several cellular events and molecular pathways taken over by viruses that promote the development and initiation of malignancy. The use of antiviral treatment to eliminate viral infections and prevent the activation of oncogenesis in the first place becomes a proactive approach. Understanding the molecular pathogenesis of various oncogenic viruses like Hepatitis virus, HIV, HPV, HSV, EBV, etc., against which efforts are being made to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Contemporary therapies like engineered antibodies, antiviral agents, signaling pathways, and cell biomarkers can inhibit viral oncogenesis. This review elaborates on the recent advances in both natural and synthetic antivirals to control viral oncogenesis. We also highlight the challenges and future perspectives of using antivirals in viral oncogenesis.
... Chronic viral hepatitis, including chronic hepatitis B (CHB) and C (CHC), has become a major public health problem worldwide [1,2]. Both viruses infect liver cells, replicate within them and activate hepatic stellate cells, leading to inflammatory cascades, production of excessive collagen and fibrosis [3,4]. ...
Article
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The stages of liver fibrosis can reflect the severity of chronic viral hepatitis and the probability of liver cancer. Biopsy is still regarded as the reference for staging fibrosis, but the invasive method is not suitable for first-line screening. In recent years, noninvasive methods for detecting virus-driven liver fibrosis have been developed rapidly, which mainly include biological (serum biomarkers indexes) and physical (imaging assessment of liver stiffness) strategies. In this review, we introduce these noninvasive methods, enumerate their diagnosis performances and discuss the role of ferroptosis. At last, we propose directions for future researches.
... The worldwide prevalence is estimated to be around 2-3% [7,8]. The World Health Organization estimates that every year 3-4 million individuals are infected with HCV [9]. In the case of HCV infection, up to 85% of individuals subsequently develop a chronic infection [7,10]. ...
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In the present research, chronic viral hepatitis in children is approached from a multidisciplinary point of view, considering social status, economic and medical aspects. We conducted a 4-year observational prospective study. A questionnaire regarding the socio-economic status of pediatric patients diagnosed with chronic viral hepatitis B or C was applied. In total, 159 patients were included, 52 % from urban areas, 2.5 % coming from centres for abandoned children. Among 119 school-aged children, 66% were attending classes. All patients are registered with a general practitioner. Regarding the monthly income per family, 49% had less than 1000 RON (5 RON = 1$), of which 17% had no income, 28% had an income ranging between 1000 and 2000 RON and in only 23% of cases the income exceeded 2000 RON (5% had more than 4000 RON). There were between 3 and 12 members per family. Concerning parents` educational level, the average years of study for mothers was 7.8, while for fathers, it was 8.2. For 17 % of children, at least one of the parents was illiterate, and for 5.6 %, both parents were illiterate. For a third of patients, both parents were unemployed. Regarding social living conditions, 38.4% did not have water facilities or sewerage, and 32 % used personal objects (scissors, nail clippers) in common. The socio-economic level can have a significant impact on disease epidemiology (infectiousness) and access to treatment, and it is tightly related to educational level and access to information, which are critical factors in disease prevention through general and specific measures and in disease management (treating infected patients and limiting the transmission).
... Hepatitis C is a blood transmitted and serious infectious disease caused by HCV, which has a prevalence rate of 2.8% globally [15]. HCV infection usually progresses towards two outcomes: acute infection leading to spontaneous virus clearance and chronic infection developing to viral persistence. ...
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The major mechanism for determination of HCV infection outcomes has not been fully described, particularly in the early phase of the “window-period” of infection. Based on two groups of marmosets infected with HCV-CE1E2p7/GBV-B chimeric virus (HCV chimera) or GBV-B, the immune mechanism correlating with the different outcomes of virus infections was explored in this study. HCV chimera containing the entire HCV core and envelope proteins (CE1E2p7) and GBV-B RNA were intrahepatically injected into four marmosets in each group, respectively. Blood samples were taken from individual animals in an interval of 2 weeks. Viral load and specific T cell responses were detected in two groups of HCV chimera- and GBV-B-infected marmosets. HCV chimera-infected marmosets appeared to have a virally persistent infection over 6 months post inoculation of the virus. Of these, the specific IFN-γ-secretion T cell response slowly developed over 13 to 19 weeks and was maintained at a relatively low level with 40–70 SFC/106 PBMCs, while the specific Treg cell response was rapidly activated over 3 weeks and was maintained at a high level around 5% among lymphocytes. In contrast, GBV-B-infected marmosets presented spontaneous viral clearance within 6 months; the specific IFN-γ-secretion T cell response was quickly established over 5 to 7 weeks and was maintained at a high level with 50–130 SFC/106 PBMCs, while the specific Treg cell response was inactivated and maintained at a baseline below 3% among lymphocytes. In conclusion, the HCV structural proteins inducing immune suppression in the early phase of HCV infection contributed to the viral persistence, of which the activation of Treg cells might play an important role in the inhibition of an effective T cell antiviral response.
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Hepatitis C is a disease for which in approximately 30 years we have gone from the discovery of the causative agent in 1989, to the introduction of direct-acting antiviral (DAAs) therapies starting from 2011, and to a proposal for its elimination in 2016, with some countries being on track for this goal. Elimination efforts, in the absence of a vaccine, rely on prevention measures and antiviral therapies. However, treatment rates have declined in recent years and are not considered adequate to achieve this goal at a global level. This poses a great epidemiological challenge, as HCV in many countries still causes a significant burden and most infected people are not yet diagnosed. Consequently, efforts are needed at different levels with common purposes: to facilitate access to screening and diagnosis and to improve linkage to care pathways. In this review, we discuss the latest epidemiological findings on HCV infection, the obstacles to its elimination, and strategies that are believed to be useful to overcome these obstacles but are applied unevenly across the world.
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The umpolung of aldimines using N‐heterocyclic carbenes (NHCs) is less explored compared to the established polarity reversal of aldehydes. Described herein is an NHC‐catalyzed imine umpolung /6π‐electrocyclization cascade, which leads to the atom‐ and pot‐economic synthesis of biologically important dihydrochromeno indoles. For the first time, the nucleophilic aza‐Breslow intermediates have been intercepted with unactivated alkynes. Preliminary mechanistic and DFT studies shed light on the role of the phenolic −OH moiety in promoting the addition of the aza‐Breslow intermediate to the unactivated alkyne via an intramolecular proton transfer in a stepwise manner. DFT studies also support the regioselectivity preference for the 5‐ exo‐dig cyclization pathway, leading to the exclusive formation of the indole products. Moreover, a comparison of Gibbs free energies provides insight into a thermodynamically preferred 6π‐electrocyclization over a competing oxa‐Michael pathway. Further, this strategy is applied to the formal synthesis of a Hepatitis C Virus (HCV) NS5A inhibitor in a step‐economical method.
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The umpolung of aldimines using N‐heterocyclic carbenes (NHCs) is less explored compared to the established polarity reversal of aldehydes. Described herein is an NHC‐catalyzed imine umpolung /6π‐electrocyclization cascade, which leads to the atom‐ and pot‐economic synthesis of biologically important dihydrochromeno indoles. For the first time, the nucleophilic aza‐Breslow intermediates have been intercepted with unactivated alkynes. Preliminary mechanistic and DFT studies shed light on the role of the phenolic −OH moiety in promoting the addition of the aza‐Breslow intermediate to the unactivated alkyne via an intramolecular proton transfer in a stepwise manner. DFT studies also support the regioselectivity preference for the 5‐exo‐dig cyclization pathway, leading to the exclusive formation of the indole products. Moreover, a comparison of Gibbs free energies provides insight into a thermodynamically preferred 6π‐electrocyclization over a competing oxa‐Michael pathway. Further, this strategy is applied to the formal synthesis of a Hepatitis C Virus (HCV) NS5A inhibitor in a step‐economical method.
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Background Bovine viral diarrhea/mucosal disease (BVD-MD) is widely distributed worldwide. The disease causes serious economic losses to animal husbandry every year. Finding targeted antiviral drugs proves to be an effective strategy. Purpose This study was based on network pharmacology and in vitro studies to analyze the potential of traditional Chinese medicine (TCM) in the treatment of BVD-MD. Methods The intersection targets between TCM and the disease were identified. Network topology analysis and protein–protein interaction (PPIs) networks were performed. Intersection targets were analyzed for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment. The molecular docking and molecular dynamics simulation methods were used to reveal the degree of binding of core components to key target genes. Characterization of the anti-Bovine viral diarrhea virus (BVDV) effect of TCM by cytotoxicity and in vitro studies. Results The results revealed the selection of five key Chinese medicines, along with 206 targets associated with BVD-MD. The toll-like receptor, PI3K-AKT, and tumor necrosis factor (TNF) signaling pathways were closely related to the five TCMs. AKT1, EGFR, HSP90AA1, and MAPK1 had good binding with quercetin, the core component of Chinese medicine. Molecular dynamics analysis showed that quercetin exhibited complex stability with AKT1. In vitro studies have demonstrated that the inhibitory effect of quercetin on BVDV is mainly in the initial phase. Quercetin inhibited the expression of AKT1. Conclusion The mechanism of BVDV inhibition by the core Chinese medicines is closely related to MAPK1, AKT1, TNF, and HSP90AA1, with the reduction of AKT1 ultimately affecting viral expression.
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Background: Hepatitis C virus (HCV) is a growing health problem worldwide. Egypt has the highest HCV prevalence in the world. In the last decade, HCV-related morbidity doubled, and HCC related to HCV increased almost threefold. The desired goal with combination antiviral therapy is to obtain a sustained virologic response (SVR). The predictors of SVR of genotype-4 are not well represented because most of the data were on genotype-1; therefore, there is a need for further studies. Aim: To clarify the predictors of SVR to combination therapy in patients with HCV infection genotype-4 before initiating treatment. Patients and Methods: This retrospective study included 530 HCV patients treated with combination therapy pegylated interferon plus ribavirin. The patients were divided into two groups: SVR patients (Group I) and Non-SVR patients (Group II). Results: A significantly higher age was found in group II when compared with group I (P=0.0008). Also, a significantly higher pretreatment ALT, AST, alkaline phosphatase and HCV-RNA viral load levels were found in group II when compared with group I (P< 0.0001) for all. Patients with (age >40 years, pretreatment ALT level >2 folds, bilharziasis history, late fibrosis stages and late activity stages) were prone to be non-SVR than the others. Conclusion: Patients with (age >40 years, pretreatment ALT level >2 folds, bilharziasis history, late fibrosis stages and late activity stages) were prone to be non-SVR than the others. These findings may have important prognostic, cost saving and therapeutic implications in HCV patients treatment.
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A hepatite C é uma das principais causas de doença hepática crônica, cirrose e carcinoma hepatocelular. Estima-se que 58 milhões de pessoas tenham infecção crônica com cerca de 1,5 milhão de novas infecções por ano. Em 2016, a OMS estipulou a meta de eliminar as hepatites virais até 2030, reduzindo em 90% as novas infecções e em 65% as mortes. Este relato de experiência se propõe a apresentar os avanços no diagnóstico e tratamento da hepatite C no período de 2000 a 2023 e discutir os desafios ainda presentes para atingir a meta da OMS. O diagnóstico da Hepatite C envolve o uso de técnicas sorológicas para a triagem e de biologia molecular para confirmação do diagnóstico, além de avaliar a eficácia do tratamento. O único tratamento disponível até 2011 era a combinação de Interferon alfa peguilado e Ribavirina. A disponibilidade e a evolução das drogas antivirais de ação direta a partir de 2011 contribuíram com o avanço no tratamento, apresentando alta eficácia, período mais curto de terapia, menos contraindicações e poucos efeitos adversos. Mesmo com esses avanços, apenas 20% das pessoas que vivem com Hepatite C no mundo foram diagnosticadas e 7% receberam tratamento. Conclui-se por tanto que para atingir a meta da OMS será necessário um diagnóstico acessível e rápido, no local de atendimento, além de campanhas de triagem e tratamento em massa como parte do programa de vigilância nacional desse agravo.
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Introduction: The rate of acute hepatitis C increased by 7% between 2020 and 2021, after the number of cases doubled between 2014 and 2020. With the current adoption of pan-genotypic HCV therapy, there is a need for improved availability and accessibility of this therapy. However, double and triple DAA-resistant variants have been identified in genotypes 1 and 5 with resistance-associated amino acid substitutions (RAASs) in NS3/4A, NS5A, and NS5B ¹. The role of this research was to screen for novel potential NS5B inhibitors from the cannabis compound database (CBD) using Deep Learning. Methods Virtual screening of the CBD compounds was performed using a trained Graph Neural Network (GNN) deep learning model. Re-docking and conventional docking were used to validate the results for these ligands since some had rotatable bonds > 10. 31 of the top 67 hits from virtual screening and docking were selected after ADMET screening. To verify their candidacy, six random hits were obtained for FEP/MD and Molecular Simulation Dynamics. Results The top 200 compounds from the deep learning virtual screening were selected, and the virtual screening results were validated by re-docking and conventional docking. The ADMET profiles were optimal for 31 hits. Simulated complexes indicate that these hits are likely inhibitors with suitable binding affinities and FEP energies. Phytil Diphosphate and glucaric acid were suggested as possible ligands against NS5B.
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The objective of the research is to create a rapid, uncomplicated, accurate, and cost-effective RP-HPLC technique for quantifying the quantities of Grazoprevir and Elbasvir concurrently in both pharmaceutical products and bulk materials. This approach has successfully accomplished the separation of Grazoprevir and Elbasvir in significant quantities. The separation was conducted with a Waters C18 (250 x 4.6 mm x 5 μ particle size) analytical column, with detection at a wavelength of 260 nm. The mobile phase included a blend of Methanol and Phosphate Buffer pH 4.0 at a volumetric ratio of 60:40. The separation was conducted using isocratic elution mode at a flow rate of 1.0 ml/min. Grazoprevir had a retention time of 2.400 minutes, whereas Elbasvir showed a retention length of 3.016 minutes. The quantification of Grazoprevir and Elbasvir was performed by utilizing PDA detection at a wavelength of 260 nm, employing a linear calibration curve. For accurate quantification, the concentration ranges of 20-100 µg/ml (with a correlation value of 0.9999) and 10-50 µg/ml (with a correlation coefficient of 0.999) were used. The suggested approach is well-suited for use in quality-control labs for the quantitative examination of medicines, both when employed Journal of Cardiovascular Disease Research
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The objective of the research is to create a rapid, uncomplicated, accurate, and cost-effective RP-HPLC technique for quantifying the quantities of Grazoprevir and Elbasvir concurrently in both pharmaceutical products and bulk materials. This approach has successfully accomplished the separation of Grazoprevir and Elbasvir in significant quantities. The separation was conducted with a Waters C18 (250 x 4.6 mm x 5 μ particle size) analytical column, with detection at a wavelength of 260 nm. The mobile phase included a blend of Methanol and Phosphate Buffer pH 4.0 at a volumetric ratio of 60:40. The separation was conducted using isocratic elution mode at a flow rate of 1.0 ml/min. Grazoprevir had a retention time of 2.400 minutes, whereas Elbasvir showed a retention length of 3.016 minutes. The quantification of Grazoprevir and Elbasvir was performed by utilizing PDA detection at a wavelength of 260 nm, employing a linear calibration curve. For accurate quantification, the concentration ranges of 20-100 µg/ml (with a correlation value of 0.9999) and 10-50 µg/ml (with a correlation coefficient of 0.999) were used. The suggested approach is well-suited for use in quality-control labs for the quantitative examination of medicines, both when employed Journal of Cardiovascular Disease Research
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The relative contribution of various risk factors to the incidence of acute hepatitis B in Italy was estimated using a special surveillance system (SEIEVA) for type-specific acute viral hepatitis. At present 146 health departments (USLs) which contain 21% of the Italian population participate in SEIEVA out of the total of 650. Data on 2460 hepatitis B cases and 708 hepatitis A cases were compared. Hospitalization, surgical intervention, dental therapy, other percutaneous exposures, barber shop shaving, i.v. drug abuse and household contact with HBsAg carriers were associated with acute hepatitis B and a large number of cases were attributable to these risk factors. Because the control programme based on vaccination will not be effective in the short term at reducing hepatitis B incidence, other additional interventions are recommended.
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AIM This study describes the long term follow up of haemophilic patients infected with hepatitis C virus (HCV) between 1961 and 1985. METHODS Clinical and treatment records from 310 patients with inherited coagulation disorders treated with blood product before 1985 were reviewed. Standard survival analysis methods were used to model progression to liver failure and death. RESULTS A total of 298/305 (98%) patients tested were anti-HCV positive. Twenty seven (9%) individuals consistently HCV polymerise chain reaction negative were considered to have cleared the virus. By 1 September 1999, 223/310 (72%) were alive, 26 (8%) had died a liver related death, and 61 (20%) had died from other, predominantly human immunodeficiency virus (HIV) related, causes. Kaplan-Meier progression rates to death from any cause and liver related deaths 25 years after exposure to HCV were 47% (95% confidence intervals (CI) 34–60) and 19% (95% CI 10–27), respectively. After 13.3 years from 1985, by which time all patients had seroconverted to HIV, progression rates to death from any cause and liver related deaths were, respectively, 8% (95% CI 4–13) and 3% (95% CI 0.4–6) for those HIV negative, and 57% (95% CI 48–66) and 21% (95% CI 13–31) for those HIV positive (p=0.0001). Using Cox proportional hazard models, the adjusted relative hazard of death for individuals coinfected with HIV compared with those infected with HCV alone was 19.47 (95% CI 9.22–41.10), 0.99 (95% CI 0.39–2.53), 3.47 (95% CI 1.40–8.63), and 9.74 (95% CI 3.91–24.26) for the age groups at infection 10–19 years, 20–29 years, and >30 years, respectively, compared with the age group <10 years. The adjusted relative hazard for genotype 1 compared with other genotypes was 2.7 (95% CI 1.36–5.15) . CONCLUSIONS While 25 year follow up of 310 haemophilic patients has shown the potentially lethal combination of HIV and HCV coinfection, HCV singly infected individuals show slow progression of liver disease.
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Context Use of antiretroviral drugs, including protease inhibitors, for treatment of human immunodeficiency virus (HIV) infection has been anecdotally associated with hepatotoxicity, particularly in persons coinfected with hepatitis C or B virus.Objectives To ascertain if incidence of severe hepatotoxicity during antiretroviral therapy is similar for all antiretroviral drug combinations, and to define the role of chronic viral hepatitis in its development.Design Prospective cohort study.Setting University-based urban HIV clinic.Patients A total of 298 patients who were prescribed new antiretroviral therapies between January 1996 and January 1998, 211 (71%) of whom received protease inhibitors as part of combination therapy (median follow-up, 182 days) and 87 (29%) of whom received dual nucleoside analog regimens (median follow-up, 167 days). Chronic hepatitis C and B virus infection was present in 154 (52%) and 8 (2.7%) patients, respectively.Main Outcome Measure Severe hepatotoxicity, defined as a grade 3 or 4 change in levels of serum alanine aminotransferase and aspartate aminotransferase, evaluated before and during therapy.Results Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients (95% confidence interval [CI], 7.2%-14.4%). Ritonavir use was associated with a higher incidence of toxicity (30%; 95% CI, 17.9%-44.6%). However, no significant difference was detected in hepatotoxicity incidence in other treatment groups, ie, nucleoside analogs (5.7%; 95% CI, 1.2%-12.9%), nelfinavir (5.9%; 95% CI, 1.2%-16.2%), saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir (6.8%; 95% CI, 3.0%-13.1%). Although chronic viral hepatitis was associated with an increased risk of severe hepatotoxicity among patients prescribed nonritonavir regimens (relative risk, 3.7; 95% CI, 1.0-11.8), most patients with chronic hepatitis C or B virus infection (88%) did not experience significant toxic effects. Rate of severe toxicity with use of any protease inhibitor in patients with hepatitis C infection was 12.2% (13/107; 95% CI, 6.6%-19.9%). In multivariate logistic regression, only ritonavir (adjusted odds ratio [AOR], 8.6; 95% CI, 3.0-24.6) and a CD4 cell count increase of more than 0.05 × 109/L (AOR, 3.6; 95% CI, 1.0-12.9) were associated with severe hepatotoxicity. No irreversible outcomes were seen in patients with severe hepatotoxicity.Conclusions Our data indicate that use of ritonavir may increase risk of severe hepatotoxicity. Although hepatotoxicity may be more common in persons with chronic viral hepatitis, these data do not support withholding protease inhibitor therapy from persons coinfected with hepatitis B or C virus.
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In 1996 the prevalence, risk factors, and genotype distribution of hepatitis C virus (HCV) infection were assessed in the general population of a town in southern Italy. The sample was selected from the census by a systematic 1:4 sampling procedure. The participation rate was 96.6%. Among the 1,352 subjects enrolled, 195 (14.4%) tested reactive to antibody to HCV (anti-HCV) with enzyme immunoassay (EIA 3). When further tested with recombinant immunoblot assay (RIBA 3), 170 subjects (87.2%) tested positive, 23 subjects (11.8%) had indeterminate results, and 2 subjects (1%) tested negative. Thus, the overall anti-HCV EIA-positive RIBA-confirmed prevalence was 12.6% (170 of 1,352 subjects) and increased from 1.3% in subjects younger than 30 years to 33.1% in those > or =60 years of age. This latter age group accounted for 72.3% of all anti-HCV-positive subjects. Females tested positive more frequently than males (14.1% vs. 10.5%; P < .05). Alanine transaminase (ALT) concentrations were abnormal in only 4.1% (7/170) of anti-HCV EIA-positive RIBA-confirmed subjects. This suggests that ALT screening is not useful in the detection of anti-HCV-positive subjects in a general population. The results of multiple logistic regression analysis showed that an age of less than 45 years, the use of glass syringes, and dental therapy were all independent predictors of anti-HCV positivity. HCV RNA was detected by polymerase chain reaction in 75.9% of the 195 anti-HCV EIA-positive subjects: in 84.7% (144/170) of the RIBA-confirmed subjects; in 17.4% (4/23) tested as RIBA indeterminate; and in neither of the two subjects who tested RIBA negative. HCV type 1b was detected in 75 subjects (50.7%), type 2b in 1 subject (0.7%), type 2c in 66 subjects (44.6%), type 3a in 4 subjects (2.7%), and type 4 in two subjects (1.3%). These figures differ from those of Italian patients with chronic liver disease in whom genotype 2 is more rare. None of the individuals was infected with more than one genotype. The distribution of the two most common HCV viral types (1b and 2c) was not statistically different in terms of mean age, sex, or risk factors and suggests that they may have had a parallel spread in this community. These findings provide one of the highest overall anti-HCV prevalence rates in a general population with a likely cohort effect, i.e., decreased risk of infection along generations. These observations may indicate an epidemic or focus of hepatitis C that occurred several years earlier. The majority of anti-HCV-positive subjects in the oldest age group and with no clinical evidence suggests that HCV infection is a very prolonged and indolent disease. (Hepatology 1997 Oct;26(4):1006-11)
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The prevalence of hepatitis C and other infections is increasing in urban areas of developing countries. Data on such diseases are often limited to facility-based information. However, even this is not available in a usable form to health care providers, health managers and policy makers. We present a simple technique for visually displaying facility based prevalence information on hepatitis C using basic geographic information system (GIS) techniques. We display the prevalence of hepatitis C for the city of Karachi, Pakistan for the first time. The distribution tends to indicate that there are areas of higher prevalence located in specific districts. There is also a trend of higher prevalence in less affluent urban areas. Such simple applications of mapping technology are useful for rapidly summarizing and displaying information in a contextually and spatially meaningful fashion, and its use should be encouraged for displaying health indicators in developing countries. Public Health (2000) 114, 413–415
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Objective To determine the clinical course of hepatitis C virus in the first decade of infection in a group of patients who acquired their infections on a known date. Design Cohort study. Setting Clinical centres throughout the United Kingdom. Participants 924 transfusion recipients infected with the hepatitis C virus (HCV) traced during the HCV lookback programme and 475 transfusion recipients who tested negative for antibodies to HCV (controls). Main outcome measures Clinical evidence of liver disease and survival after 10 years of infection. Results All cause mortality was not significantly different between patients and controls (Cox's hazards ratio 1.41, 95% confidence interval 0.95 to 2.08). Patients were more likely to be certified with a death related to liver disease than were controls (12.84, 1.73 to 95.44), but although the risk of death directly from liver disease was higher in patients than controls this difference was not significant (5.78, 0.72 to 46.70). Forty per cent of the patients who died directly from liver disease were known to have consumed excess alcohol. Clinical follow up of 826 patients showed that liver function was abnormal in 307 (37.2%), and 115 (13.9%) reported physical signs or symptoms of liver disease. Factors associated with developing liver disease were testing positive for HCV ribonucleic acid (odds ratio 6.44, 2.67 to 15.48), having acquired infection when older (at age ≥ 40 years; 1.80, 1.14 to 2.85), and years since transfusion (odds ratio 1.096 per year, 1.00 to 1.20). For patients with severe disease, sex was also significant (odds ratio for women 0.38, 0.17 to 0.88). Of the 362 patients who had undergone liver biopsy, 328 (91%) had abnormal histological results and 35 (10%) of these were cirrhotic. Conclusions Hepatitis C virus infection did not have a great impact on all cause mortality in the first decade of infection. Infected patients were at increased risk of dying directly from liver disease, particularly if they consumed excess alcohol, but this difference was not statistically significant. What is already known on this topic What is already known on this topic The clinical course of HCV infection is unclear because most information has come from studies of patients with established chronic liver disease Studies that follow patients from disease onset are rare because most HCV infections are asymptomatic What this study adds What this study adds HCV infection does not have a great impact on all cause mortality in the first decade of infection Infected patients have an increased risk of dying from a liver related cause, particularly if they consumed excess alcohol
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Acute hepatitis C virus infection accounts for approximately 20% of cases of acute hepatitis today. The aim of this study was to define the natural course of the disease and to contribute to the development of treatment strategies for acute hepatitis C virus. The diagnosis of acute hepatitis C virus in 60 patients was based on seroconversion to anti-hepatitis C virus antibodies or clinical and biochemical criteria and on the presence of hepatitis C virus RNA in the first serum sample. Fifty-one of 60 (85%) patients presented with symptomatic acute hepatitis C virus. In the natural (untreated) course of acute symptomatic hepatitis C (n = 46), spontaneous clearance was observed in 24 patients (52%), usually within 12 weeks after the onset of symptoms, whereas all asymptomatic patients (n = 9) developed chronic hepatitis C. The start of antiviral therapy (interferon-alpha with or without ribavirin) beyond 3 months after the onset of acute hepatitis induced sustained viral clearance in 80% of treated patients. The management of acute hepatitis C has to take into account the high rate of spontaneous viral clearance within 12 weeks after the onset of symptomatic disease. Treatment of only those patients who remain hepatitis C virus RNA positive for more than 3 months after the onset of disease led to an overall viral clearance (self-limited and treatment induced) in 91% of patients, and unnecessary treatment was avoided in those with spontaneous viral clearance. Patients with asymptomatic acute hepatitis C virus infection are unlikely to clear the infection spontaneously and should be treated as early as possible.
Article
The Veterans Administration has been conducting a cooperative randomized, double-blind, controlled trial to evaluate the efficacy of conventional and hepatitis B immune serum globulin for the prevention of post-transfusion hepatitis. Data collected between 1969 and 1974 provide the opportunity to describe the annual incidence and characteristics of the hepatitis that has developed, and the risk factors which have been identified. Anicteric hepatitis has developed four times more frequently than icteric hepatitis, the total incidence for all six years being 11.3 per cent. The incidence of HBS Agassociated hepatitis declined dramatically after 1973 with the institution of routine screening of donor blood by radioimmunoassay techniques, although no change in the incidence of antigen-negative hepatitis has occurred. There is indirect evidence to suggest that an undefined agent is responsible for the majority of instances of post-transfusion hepatitis occurring presently. The most important risk factor responsible for the development of hepatitis is the use of commercial blood, and it is strongly urged that this form of blood be removed from general use.
Article
We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease.
Article
Background and Objectives: In Indian blood banks, screening for hepatitis B virus (HBV) is currently done by the EIA method, but no routine screening is done for hepatitis C virus (HCV). Materials and Methods: To determine the incidence of transfusion–associated HCV hepatitis, and of any residual transfusion–associated hepatitis (TAH) after HBsAg screening, we prospectively studied 182 patients who underwent surgery and received blood transfusion. These recipients had normal alanine aminotransferase (ALT) and were negative for HBsAg (monoclonal EIA), and anti–HCV (third–generation EIA) before receiving transfusion. Results: Of the 818 blood units transfused after routine screening (average 4.49±3.3 U&sol;patient, range 1–14), 14 (1.7&percnt; of units) were found to be infected. Of the 182 recipients, 14 (7.69&percnt;) developed TAH during a follow–up of 6 months, 3 (21.4&percnt;) from HBV, 10 (71.5&percnt;) from HCV, and 1 (1.7&percnt;) from a coinfection of HBV and HCV. All patients with TAH due to HCV were asymptomatic. One patient with TAH due to HBV (33&percnt;) and 5 with TAH due to HCV (50&percnt;) developed chronic infection with persistently elevated ALT at 6 months. Conclusions: With the current screening practices, the incidence of TAH remains high in India and is mainly due to HCV infection. Furthermore, the screening methods for HBV also need to be improved.
Article
Context Conflicting reports exist regarding the effect of hepatitis C virus (HCV) on the progression of human immunodeficiency virus (HIV) disease.Objective To assess the effect of HCV infection on clinical and immunologic progression of HIV disease and immunologic response to highly active antiretroviral therapy (HAART).Design Prospective cohort study.Setting University-based, urban HIV clinic in the United States.Patients There were 1955 patients enrolled between January 1995 and January 2001 who were eligible for analysis because of having at least 1 return visit to the clinic and being free of acquired immunodeficiency syndrome (AIDS) at enrollment. Median (interquartile range) length of follow-up was 2.19 (1.00-3.50) years for HCV-infected and 2.00 (1.00-3.00) years for HCV-uninfected patients.Main Outcome Measures Progression to an AIDS-defining illness, survival, and progression to a CD4 cell count below 200/µL; CD4 cell count change following initiation of effective HAART (resulting in a viral load of <400 copies/mL recorded at ≥75% of measurements).Results No difference was detected in the risk of acquiring an AIDS-defining illness (HCV-infected patients, 231 events [26.4%] and HCV-uninfected patients, 264 events [24.4%]; relative hazard [RH], 1.03; 95% confidence interval [CI], 0.86-1.23) or in the risk of death (HCV-infected patients, 153 deaths [17.5%] and HCV-uninfected patients, 168 deaths [15.5%]; RH, 1.05; 95% CI, 0.85 -1.30). Although an increased risk of death was detected in the subgroup of 429 HCV-infected patients with a baseline CD4 cell count of 50/µL through 200/µL (RH, 1.51; 95% CI, 1.01-2.27), after adjustment for exposure to HAART and its effectiveness in a multivariate Cox regression analysis, death was not independently associated with HCV infection in this subgroup (RH, 1.01; 95% CI, 0.65-1.56). Similarly, in those receiving effective HAART (n = 208), there was no difference in the increase in CD4 cell count or CD4 percentage during HAART in HCV-infected compared with HCV-uninfected patients.Conclusions Among patients in this urban US cohort, we did not detect evidence that HCV infection substantially alters the risk of dying, developing AIDS, or responding immunologically to HAART, especially after accounting for differences in its administration and effectiveness. Figures in this Article Due to shared routes of transmission, an estimated 15% to 30% of human immunodeficiency virus (HIV)-infected persons are coinfected with hepatitis C virus (HCV) in the United States and Europe.1- 2 Human immunodeficiency virus infection appears to increase the persistence of the hepatitis C virus, the level of HCV RNA, and, in most studies, progression of HCV-related liver disease.3- 9 However, there are conflicting reports regarding the effect of HCV on the natural history of HIV disease. Prior to the availability of highly active antiretroviral therapy (HAART), increased rates of progression of HIV disease were detected in some studies5,10- 11 but not others.12- 17 Recently, Greub et al18 reported that, in a study involving HIV-infected patients in Switzerland, among patients receiving HAART, HCV-coinfected patients had decreased survival rates, increased risk of progression to acquired immunodeficiency syndrome (AIDS), and impaired CD4 cell recovery. The objective of this study was to assess the effect of HCV coinfection on clinical and immunologic progression of HIV-1 disease and immunologic response to HAART in a large, urban US patient cohort observed before and during the advent of HAART.
Article
Hepatitis C occurs worldwide and in all age and racial/ethnic groups studied. The most efficient transmission is through percutaneous exposure to infectious blood, but may also occur as a result of inapparent parenteral and mucosal exposure. Although hepatitis C virus may be inefficiently transmitted in some settings, the high rate of persistent infection with this virus creates a large reservoir of persons who are infectious to others, resulting in multiple opportunities for transmission to occur. (C) Lippincott-Raven Publishers.
Article
Objective: To study the influence of hepatitis C virus (HCV) co-infection on clinical and immunological evolution of HIV-infected patients. Design: A longitudinal study of HIV-infected individuals with or without HCV infection, identified at the Infectious Diseases Department of Dijon University Hospital and enrolled in a historical cohort, was performed. Methods: One hundred and nineteen HIV-infected people co-infected with HCV and 119 matched individuals infected with HIV alone were included in the cohort (median participation time 3 years; range, 2 months to 11.5 years). Clinical progression was defined as one or more of the following: a 30% decrease in the Karnofsky index; a 20% loss of body weight; an AIDS-defining illness (for non-AIDS patients); death (except by accident, suicide or overdose). Immunological progression was defined as a 50% decrease in the initial CD4 T-cell count (for patients with an initial count > 100 × 106 cells/l). Effects of HCV co-infection were evaluated using Kaplan-Meier survival analysis and significance was tested using univariate (log-rank and Peto's tests) and multivariate methods (Cox's model). Results: In univariate analysis, immunological progression was not statistically different between the HCV-positive group and the HCV-negative group, whereas clinical progression was significantly faster in HCV-positive patients (P < 0.005, log-rank test). In a multivariate Cox model, clinical progression remained significantly associated with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI), 1.06-2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09-109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16-4.62; P < 0.02) for patients with an initial CD4 count above 600 × 106 cells/l. Conclusions: Clinical progression is more rapid in HIV-HCV co-infected patients than in HIV-seropositive patients are not infected by HCV. The prognostic value of HCV infection for both clinical and immunological progression is significant at early stages of HIV infection. These findings may argue for active management of hepatitis C infection in co-infected individuals, especially for asymptomatic patients whose CD4 count is above 600 × 106 cells/l, to predict and prevent accelerated progression of HCV and HIV diseases.
Article
We carried out this study to assess the risk of hepatitis C virus (HCV) transmission after needlestick injuries in medical personnel, and to evaluate the efficacy of short-duration interferon administration to prevent HCV transmission. A total of 684 personnel who had been occupationally exposed to an anti-HCV-positive source and followed for more than 3 months were retrospectively examined. Of the 684 subjects, 279 (41%) were treated with 1 to 3 days of interferon either just after or 1 to 12 days after the injury. One case of HCV infection was found in each of the treated (1/279; 0.4%) and nontreated (1/405; 0.2%) groups. There was no significant difference in the transmission of HCV between the two groups. Both infected patients were treated with interferon after developing acute hepatitis, and HCV was subsequently cleared. There is a lower risk of HCV transmission after needlestick accident than previously reported, and short-duration interferon administration at an early stage after the needlestick injury, to prevent HCV transmission, is unnecessary.
Article
The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio. The heterogeneous geographic distribution reflects the epidemiologic impact of the main etiologic factors and environmental risk, which are the hepatitis B (HBV) and hepatitis C (HCV) viruses. The percentage of cases of hepatocellular carcinoma attributable to HBV worldwide is 52.3% and is higher in Asia where the seroprevalence of HBsAg in the population is high. However, the vaccination campaign against this virus in some eastern countries has tended to lower the incidence of new cases of hepatocellular carcinoma. The percentage of cases of hepatocellular carcinoma attributable to HCV is 25%, and it is more prevalent in Japan, Spain, and Italy where the association between hepatocellular carcinoma and antibodies to HCV ranges between 50 and 70%. In most cases hepatocellular carcinoma develops in cirrhotic livers, where the persistent proliferation of liver cells represents the key factor of progression to hepatocellular carcinoma independent of the etiology. Another minor risk factor is aflatoxin B1 consumption, which is responsible for most cases of hepatocellular carcinoma in Africa, where the consumption of contaminated foods is common. Other known risk factors are some hereditary diseases, such as hemochromatosis, porphyria cutanea tarda, hereditary tyrosinemia, and α1 anti-trypsin deficiency. The natural history of hepatocellular carcinoma is heterogeneous and is influenced by nodule dimension, the mono- or plurifocality of lesions at diagnosis, the growth rate of the tumor, and the stage of the underlying cirrhosis. Available data to date suggest that tumor growth in a cirrhotic liver is variable and that the time in which a lesion in undetectable until it becomes 2 cm is between 4 and 12 months. Therefore, the suggested interval for surveillance screening with ultrasound in patients with liver cirrhosis has been set at 6 months. Patients who should benefit from screening programs are those who would be treated with curative therapy if diagnosed with hepatocellular carcinoma. Thus, the ideal target population should be limited to Child-Pugh's class A cirrhotic patients without significant comorbidity.
Article
Using data from the surveillance system for type-specific acute viral hepatitis, the temporal incidence trend of non-A, non-B acute hepatitis and risk factors for acute hepatitis C have been evaluated in Italy. The association between hepatitis C and the potential risk factors (odds ratios, OR) was estimated using hepatitis A patients as controls. The independent roles of the different risk factors were estimated by multiple logistic regression analysis. The incidence of non-A, non-B acute hepatitis declined from 5 per 100 000 to 1 per 100 000 between 1985 and 1996. Anti-HCV data collected by SEIEVA since 1991 showed that 60% of patients with non-A, non-B acute hepatitis were positive for antibodies to the hepatitis C virus (anti-HCV) at the time of hospitalization. During the 6 months prior to the disease onset, the most frequently reported risk factors were multiple sexual partners, other parenteral exposure and intravenous drug use; transmission by blood transfusion declined from 20% in 1985 to 2% in 1996. On multivariate analysis, intravenous drug use (OR=35.5; 95% CI=23.1–54.4), surgical intervention (OR=4.6; 95% CI=3.3–6.5), dental treatment (OR=1.5; 95% CI=1.1–1.9) and two or more sexual partners (OR=2.2; 95% CI=1.6–3.0) were all independent predictors of hepatitis C. These findings indicate that HCV infection is decreasing in Italy. Intravenous drug use, multiple sexual partners, surgical intervention and dental therapy are the main modes of transmission.
Article
Unlabelled: Plasma samples from replacement and volunteer blood donors in Kumasi, Ghana were pooled and tested using a duplex human immunodeficiency virus (HIV) and hepatitis C virus (HCV) RNA detection Method: Individual plasmas constitutive of reactive pools were confirmed using reverse transcription-polymerase chain reaction. HIV and HCV infections were significantly higher in 1569 replacement donors than in 1169 volunteers; 2.4 and 1.7 versus 0.3 and 0.7% respectively (P < 0.01). Two duplex RNA-positive plasma pools contained a confirmed/seronegative HIV or HCV RNA individual plasma. The residual post-transfusion risk of HIV and HCV infection of blood collected from replacement blood donors ranged between 1:260 and 1:16 393 after screening for anti-HIV, p24 antigen and anti-HCV. These data indicate that in high-prevalence HIV and HCV blood donor populations, a substantial residual post-transfusion risk of infection remains. This risk might be reduced by collecting blood in younger volunteer donors or by genomic screening.
Article
The aim of the study was to assess whether co-infection by hepatitis-B virus (HBV) and hepatitis-C virus (HCV) is associated with a higher risk of developing hepatocellular carcinoma (HCC) than each infection alone. A meta-analysis of data published up to June 1997 was performed. HBsAg and anti-HCV antibodies or HCV RNA (anti-HCV/HCV RNA) were considered as serological markers of current HBV and HCV infection respectively. A total of 32 case-control studies were suitable for a quantitative overview. The summary odds ratios (OR) were 13.7 for HBsAg positivity and 11.5 for anti-HCV/HCV RNA positivity. The OR for anti-HCV was lower among studies using second- or third-generation anti-HCV or HCV RNA (OR, 8.2) with respect to studies with first-generation anti-HCV test (OR, 19.1). When combining data from the studies with second- or third-generation anti-HCV or HCV RNA, the OR for HBsAg positivity and anti-HCV/HCV RNA negativity was 22.5 (95% confidence interval (CI), 19.5–26.0), the OR for anti-HCV/HCV RNA positivity and HBsAg negativity was 17.3 (95% CI, 13.9–21.6), and the OR for both markers positivity was 165 (95% CI: 81.2–374, based on 191 cases and 8 controls exposed). A synergism was found between HBV and HCV infections, the OR for co-infection being greater than the sum and lower than the product of those for each infection alone. The interaction was therefore negative according to the multiplicative model, providing epidemiological evidence both of an independent effect and of interference between the 2 viruses in the carcinogenic process. Int. J. Cancer 75:347–354, 1998. © 1998 Wiley-Liss, Inc.
Article
A nationwide community-based survey on hepatitis C virus (HCV) was carried out in seven townships in Taiwan. A total of 11,904 men aged 30–64 years were recruited for testing for antibodies against HCV (anti-HCV) by second-generation enzyme immunoassay. A total of 272 seropositive cases and 282 seronegative controls were interviewed to explore risk factors for HCV infection in the study areas. Spouses of 214 seropositive cases were identified to assess the concordance of seropositivity of anti-HCV between spouses; genotypes of HCV were also tested in 26 couples who were both seropositive. A significant geographic variation in seroprevalence of anti-HCV was observed in the study townships (1.6–19.6%). Blood transfusions, medical injections, acupuncture and tattooing were related to an increased anti-HCV seroprevalence showing multivariate-adjusted odds ratios of 8.6, 2.5, 3.1, and 2.2, respectively, with corresponding population attributable risk percentages of 25%, 57%, 16%, and 3%, respectively. The anti-HCV prevalence in spouses of index cases (24%) was significantly higher than that observed in the general population of the study areas (4%). However, a striking interspousal discrepancy in HCV genotypes (20/26 = 77%) was observed among both seropositive couples. Common exposures to medical injections and acupuncture were reported by 15 (58%) of these couples. This study identified some endemic areas of HCV infection in Taiwan. Iatrogenic factors were common vehicles for HCV infection, and a concordance of anti-HCV seropositivity between spouses may primarily be due to extrafamilial iatrogenic infectious sources in study areas. J. Med. Virol. 59:290–296, 1999. © 1999 Wiley-Liss, Inc.
Article
We investigated underlying risks for hyperendemic hepatitis C virus (HCV) infection among the 1853 inhabitants of a mountainous village in Eastern Taiwan with high prevalence of HCV and hepatitis B virus (HBV). Among the 80 selected adults, we found that having resided away from the village before 1985 was protective against HCV infection, while residing in the village after 1985 posed little risk for HCV infection to children and young adults < 30 years of age. Among the 559 school children 7 through 14 years of age, anti-HCV prevalence was 1.9%, and the HBV carrier rate was 29%. Following up 270 children 1 year later, we found that new HCV infection occurred in 0.74% and new or repeated HBV infection occurred in 6.5% of the children, indicating distinct transmission patterns between HBV and HCV. Children of anti-HCV-positive mothers were either anti-HCV-negative or were infected by distinct genotypes of HCV from those infecting their mothers; most married couples in whom both were infected, were infected by HCV of discordant genotypes, indicating negligible importance of sexual or vertical HCV transmission. A case-control study comparing 13 anti-HCV-positive and 53 anti-HCV-negative children showed that having received parenteral medication in local clinics was a significant risk for HCV infection. Our data indicate that, unlike the case of HBV, HCV transmission by vertical or sexual route, or through casual contact are extremely inefficient, and our data further suggest that HCV hyperendemicity is unlikely to persist as a result of the more stringent practice of parenteral precautions in nearly all aspects of daily life. J. Med. Virol. 52:370–376, 1997. © 1997 Wiley-Liss, Inc.
Article
Viral hepatitis is a major public health problem in China and has a substantial impact on the health of people. To understand the distribution of hepatitis virus infection in the general Chinese population and provide basis for developing and evaluating preventive procedures and public health practices on viral hepatitis control, a nationwide cross-sectional seroepidemiologic study of hepatitis virus infections was carried out in China, 1992. Using two-stage cluster sampling, a total of 68 000 subjects were studied, aged 1–59 years, covering all 145 national disease surveillance points of 30 provinces, autonomous regions and municipalities. Serum specimens were assayed using commercial reagents. Tested markers include HBsAg, anti-HBc, anti-HBs, HBeAg and anti-HCV. The overall prevalence of HBsAg carrier was 9.75% of 61 702 subjects studied (range 4.49–17.85%) in 30 provinces of China. The rate in the 1–4 age group was as high as the overall rate. There were higher rates in both the 10–14 and 30–34 age groups, and lower in the 50–59 age group. There were considerable variations in the prevalence of HBsAg carrier in different regions and sex in China, with the highest rate being in middle south and lower rates in north China. The overall prevalence of HBV infection, anti-HBc and anti-HBs were 57.63%, 49.81% and 27.42%, respectively; increasing significantly with age from 38.47%, 30.08% and 15.75% in the 1–4 age group to 70.69%, 61.77% and 32.42% in 50–59 age group, respectively. The overall prevalence of HBeAg was 31.94% among HBsAg carriers. The overall prevalence of anti-HCV was 3.2% of 66975 subjects studied (range 0.9–5.1%) among 30 provinces of China, increasing significantly with age from 2.08% in the 1–4 age group to 3.96% in the 50–59 age group. There was no difference in the rate of anti-HCV by sex and living district. However, there were significant difference in rates of anti-HCV in different geographical areas and administrative divisions in China, with the highest rates being in the northeast of China. These results indicate that hepatitis B and C are hyperendemic in China. According to characteristics of distribution among age, sex and regions, we suggest that the main modes of transmission of the two virus are probably different in China.
Article
Background: In 1991, compulsory hepatitis B virus vaccination and screening for anti-hepatitis C virus of blood banks were introduced in Italy. Aim: To evaluate the impact of preventive measures on the incidence and risk factors for parenterally transmitted viral hepatitis. Methods: Data from the surveillance system for acute viral hepatitis for the period 1985-99 were used. Temporal trends in distribution of reported risk factors were analysed by comparing three-year periods: 1987-89 and 1997-99. Results: The incidence (no. cases per 100,000 population) of hepatitis B was 12 in 1985 and 3 in 1999; the incidence of hepatitis non-A, non-B decreased from 5 to 1 in the same period. These decreases were more evident among young adults and before rather than after 1991. Multiple sexual partners, other parenteral exposures and dental treatment remain the most common risk factors for parenterally transmitted viral hepatitis. An increase in frequency over time was observed for other parenteral exposures, whereas a marked decrease was evident for blood transfusion and household contact with an HB-sAg carrier. Invasive medical procedures continue to represent an important source of infection. Intravenous drug use was reported particularly by young adults with non-A, non-B hepatitis, with increased frequency over time. Conclusions: Non-immunologic measures for preventing hepatitis B and non-A, non B due to iatrogenic and other parenteral exposures, combined with hepatitis B virus vaccination, could further reduce parenteral transmission.
Article
The purpose of this study was to compare the epidemiological, biochemical, virological and histological characteristics of patients with chronic hepatitis B and C with those of patients suffering from chronic hepatitis C alone. Twenty-three patients with chronic hepatitis C, who were anti-HCV positive and HBs antigen positive, were studied and subdivided into two groups according to the presence or absence of HBV DNA replication. They were compared to 69 age- and sex-matched patients with chronic hepatitis who were anti-HCV positive and HBs antigen negative. All patients were HCV RNA positive by PCR, anti-HIV negative and anti-HDV negative. HBV DNA and HCV RNA were detected in serum by means of a branched DNA assay and PCR. The HCV serotypes were determined by the Chiron Riba HCV serotyping SIA technique. The histological characteristics included the Knodell score. Epidemiological, biochemical and virological parameters were not different between the two groups. Only the prevalence of cirrhosis was greater in chronic hepatitis B and C patients than in patients with chronic hepatitis C alone (p = 0.01). Among chronic hepatitis B and C patients, HCV RNA level was significantly lower in HBV DNA positive than in HBV DNA negative patients (p = 0.01). Indeed, histological lesions were more severe in HBV DNA positive than in HBV DNA negative patients, including prevalence of cirrhosis (p = 0.01), Knodell score (p = 0.05) and, among the latter, piecemeal necrosis (p = 0.01) and fibrosis (p = 0.05). The characteristics of patients with dual infection did not differ according to the mode of contamination and duration of HBV disease, except for a shorter duration in patients contaminated by drug abuse than in other patients. These results suggest that HBV DNA replication inhibits HCV RNA replication in patients with chronic active hepatitis B and C but increases the severity of histological lesions.
Article
The Veterans Administration has been conducting a cooperative randomized, double-blind, controlled trial to evaluate the efficacy of conventional and hepatitis B immune serum globulin for the prevention of post-transfusion hepatitis. Data collected between 1969 and 1974 provide the opportunity to describe the annual incidence and characteristics of the hepatitis that has developed, and the risk factors which have been identified. Anicteric hepatitis has developed four times more frequently than icteric hepatitis, the total incidence for all six years being 11.3 per cent. The incidence of HBs Ag-associated hepatitis declined dramatically after 1973 with the institution of routine screening of donor blood by radioimmunoassay techniques, although no change in the incidence of antigen-negative hepatitis has occurred. There is indirect evidence to suggest that an undefined agent is responsible for the majority of instances of post-transfusion hepatitis occurring presently. The most important risk factor responsible for the development of hepatitis is the use of commercial blood, and it is strongly urged that this form of blood be removed from general use.