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Serum Elabela Level as a Reliable Biomarker for Predicting of Liver Fibrosis in Iraqi Patients with Chronic Hepatitis C
Abstract
Background
Elabela is a newly discovered peptide hormone that has been implicated in liver disease.
Objective
The main objective of the current work is to assess whether variations in blood Elabela levels among chronic hepatitis C (CHC) patients from Iraq might be used as a biomarker for liver fibrosis.
Materials and Methods
A case-control study was conducted in Baghdad, Iraq. The overall sample size ( n = 80) that met the inclusion criteria was divided into two groups as follows: 40 patients who were diagnosed with CHC and 40 healthy matched individuals. The aspartate aminotransferase-to-platelet ratio index (APRI) was used to identify the group of patients at risk for liver fibrosis. The routine complete blood count, liver function, and serum Elabela tests were performed. Serum Elabela level was evaluated by using the enzyme-linked immunosorbent assay technique.
Results
Serum Elabela was significantly higher in the CHC group (33.89 ± 8.51 ng/mL) than in the control group (18.11 ± 5.27 ng/mL). In addition, the percentage of CHC patients at a high risk of developing fibrosis was 42.5%. Also, the high-risk fibrosis group showed a significantly higher concentration of Elabela and APRI than the other groups (low-risk and control) at P < 0.0001. Alanine aminotransaminase and aspartate aminotransaminase showed a high increase while a low decrease in both Hb and platelet count against the healthy group ( P < 0.0001).
Conclusion
High serum Elabela level in CHC patients compared to the control group was associated with liver fibrosis and could be used clinically as a reliable biomarker to determine the high-risk patient in need of invasive liver biopsy and hazardous therapeutics.
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Background: Hepatitis B virus and hepatitis C virus are two of the most commonly transmitted infectious agents by Blood transmitting so it is still remains a considerable global health problem, this prospective cross-sectional study was conducted between 2015 and 2019 at the directorate of main Blood Bank, dialysis center, thalassemia center and public health laboratory in Thi-Qar Province-Iraq, during that period a total of 1323 patients, 948 (71.7%) males and 375 (28.3%) females, they suffering from signs and symptoms of liver diseases.
The diagnostic assessment of liver injury is an important step in the management of patients with chronic liver disease (CLD). Although liver biopsy is the reference standard for the assessment of necroinflammation and fibrosis, the inherent limitations of an invasive procedure, and need for repeat sampling, have led to the development of several non-invasive tests (NITs) as alternatives to liver biopsy. Such non-invasive approaches mostly include biological (serum biomarker algorithms) or physical (imaging assessment of tissue stiffness) assessments. However, currently available NITs have several limitations, such as variability, inadequate accuracy and risk factors for error, while the development of a newer generation of biomarkers for fibrosis may be limited by the sampling error inherent to the reference standard. Many of the current NITs were initially developed to diagnose significant fibrosis in chronic hepatitis C, subsequently refined for the diagnosis of advanced fibrosis in patients with non-alcoholic fatty liver disease, and further adapted for prognostication in CLD. An important consideration is that despite their increased use in clinical practice, these NITs were not designed to reflect the dynamic process of fibrogenesis, differentiate between adjacent disease stages, diagnose non-alcoholic steatohepatitis, or follow longitudinal changes in fibrosis or disease activity caused by natural history or therapeutic intervention. Understanding the strengths and limitations of these NITs will allow for more judicious interpretation in the clinical context, where NITs should be viewed as complementary to, rather than as a replacement for, liver biopsy.
Background:
An escalation, as three times more, had been recognized in cases of hepatitis A (HAV) from 2009 to 2014 among Iraqi people. Regarding hepatitis B and C, Iraq is considered as a low endemic country comparing to neighbors.
Study design:
A retrospective cohort study.
Methods:
Data incorporated from 2007 to 2016 were collected through a federal survey conducted by the Health Directorate of Karbala, who administrates all hospitals (three public hospitals and five private hospitals) and 40 health centers in Karbala City, Iraq. The four types of hepatitis and demographic information of all cases were included.
Results:
A vivid shifting in the prevalence of HAV showed a decreasing pattern, that is, from 632 cases (PR=61) in 2007 to 314 cases (PR=33) in 2008. In 2012, its prevalence was twice greater (695 cases, PR=63.2). The PR of HBV also changed from 52 cases (PR=5.8) in 2007 to 26 cases (PR=2.8) in 2008. Regarding HCV, a decreasing pattern with 13 cases (PR=1.4) in 2007 and 12 cases (PR=1.2) in 2009 was seen. This number increased to 60 cases (PR=3.9) in 2016. For HEV, more cases were reported (47 cases, PR=4.7) in 2010.
Conclusion:
The four types of hepatitis have been highly prevalent since 2010. The high number of migrants to Karbala Governorate and unavailability of immunization might be reasons behind the high prevalence of the four-types of hepatitis.
Treatment of hepatitis C virus (HCV) infection has been revolutionized with the introduction of pangenotypic, interferon‐ and ribavirin‐free regimens associated with high cure rates and a low side effect profile. Additionally, there is evidence that HCV cure reduces HCV complications, improves patient‐reported outcomes and is cost‐saving in most western countries in the long term. This is a review of the comprehensive burden of HCV and the value of eliminating HCV infection. With the introduction of the interferon‐free all‐oral, once a day pill treatment regimen for the cure of HCV, the potential to eliminate HCV by 2030 has become a possibility for some regions of the world. Nevertheless, there are barriers to screening, linkage to care, and treatment in many countries that must be overcome in order to reach this goal. In conclusion, globally, work must continue to ensure national policies are in place to support screening, linkage to care and affordable treatment in order to eliminate HCV.
Renal ischemia-reperfusion (I/R) injury is the most common cause of AKI, which associates with high mortality and has no effective therapy. ELABELA (ELA) is a newly identified 32-residue hormone peptide highly expressed in adult kidney. To investigate whether ELA has protective effects on renal I/R injury, we administered the mature peptide (ELA32) or the 11-residue furin-cleaved fragment (ELA11) to hypoxia-reperfusion (H/R)-injured or adriamycin-treated renal tubular cells in vitro ELA32 and ELA11 significantly inhibited the elevation of the DNA damage response, apoptosis, and inflammation in H/R-injured renal tubular cells and suppressed adriamycin-induced DNA damage response. Similarly, overexpression of ELA32 or ELA11 significantly inhibited H/R-induced cell death, DNA damage response, and inflammation. Notably, treatment of mice with ELA32 or ELA11 but not an ELA11 mutant with a cysteine to alanine substitution at the N terminus (AE11C) inhibited I/R injury-induced renal fibrosis, inflammation, apoptosis, and the DNA damage response and markedly reduced the renal tubular lesions and renal dysfunction. Together, our results suggest that ELA32 and ELA11 may be therapeutic candidates for treating AKI.
Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy.
Hepatic fibrosis is an inclusion indicator for treatment and a major independent predictor of treatment response in patients with chronic hepatitis C. Liver biopsy, considered as the "gold standard" for evaluating liver fibrosis, has carried some drawbacks. Currently used noninvasive predictors of fibrosis are considered less accurate than liver biopsy.
Our aim was to assess noninvasive predictors of fibrosis in patients with chronic hepatitis C using the routine laboratory pre-treatment workup.
Cross sectional study including 4289 Egyptian patients with chronic hepatitis C were assessed for the need to interferon and ribavirin therapy. Routine pre-treatment workup and reference needle liver biopsy were performed. FIB-4 index, APRI and modified APRI scores were validated. Patients were divided into two groups, first with no or minimal fibrosis, and second with moderate and marked fibrosis using the Metavir score.
Multivariate logistic regression analysis showed that age, body mass index, aspartate aminotransferase, alpha fetoprotein, platelets count, FIB-4 index, APRI and modified APRI score were significant independent predictors of fibrosis. Age > 43 years, aspartate aminotransferase > 47U/L, platelets < 205×103/mm(3), and alpha fetoprotein > 2.6 ng/ml had the highest cutoff points in receiver operator characteristic curves. Taking into account the four variables together; the presence of ≥ 2 variables is associated with moderate and advanced fibrosis with a sensitivity of 0.81, specificity of 0.5, positive predictive value of 0.53 and negative predictive value of 0.79. FIB-4 index represented the best performing receiver operator characteristic curve for diagnosing moderate and marked fibrosis among other independent factors with a sensitivity of 0.74, specificity of 0.6, positive predictive value of 0.56 and negative predictive value of 0.76.
Chronic HCV pre-treatment routine work up and composite fibrosis scores are good noninvasive predictor of liver fibrosis and can be used as an alternative method to invasive liver biopsy without adding more financial expenses to the treatment.
Objective:
Highlighting the apelin system would present a new therapeutic target for liver disease. Apelin; endogenous ligand for the orphan receptor APJ, was recently suggested to be associated with fibrosis progression and cirrhosis in addition to insulin resistance (IR) and inflammation. The present study was conducted to evaluate blood apelin level changes among 73 chronic hepatitis C (CHC) Egyptian patients and if associated with body mass index (BMI), IR, and tumor necrosis factor-alpha (TNF-α). Serum apelin levels were significantly higher in patients with CHC with median value (3.25) when compared with controls (1.11), at P < 0.0001, with significant apelin variations among asymptomatic carriers (ASC), fibrosis, and cirrhosis patients, and also among obese and nonobese patients. Multiple regression analysis depicted that BMI, triglycerides, and total cholesterol were independent correlation factors to apelin levels, whereas TNF-α was found to be significantly negatively correlated to adjusted apelin in CHC patients (r = -0.5944, P < 0.0001). IR was positively correlated to adjusted apelin in CHC patients (r = 0.2663, P < 0.05).
Conclusion:
Apelin level varies among stages of CHC, which may contribute to fibrosis progression. In addition, obesity and IR could act as comorbid factors affecting apelin level in patients with CHC.
The diagnosis, grading and staging, and management of chronic hepatitis and fibrosis are dependent on many investigative studies and tests including imaging techniques, molecular biological methods and serologic or biochemical tests. However, in spite of recent advances in non-invasive techniques, liver biopsy continues to be the "gold standard" method in evaluating chronic hepatitis and fibrosis. This is true because the basic concepts and widely used fundamental classification of liver disease is based on the morphology and histological alterations in normal hepatic structures. This is also logical because examining a liver biopsy under the microscope is a direct way of visualizing a patient's liver abnormality and identifying the exact changes in hepatic tissue. In addition, the emphasis before was primarily on diagnosing the liver disease, but now pathologists are required and repeatedly asked, to evaluate patients for possible treatment. In addition they must monitor those already receiving medical therapy of various kinds including liver transplant. Liver biopsy is considered an invasive procedure and is usually performed on inpatients, although it is also done as an outpatient procedure on carefully selected cases. General guidelines are established and should be followed to minimize the risk of complications such as bleeding and hematomas. Operator skills and professional training are also essential to safeguard against complications. The low mortality and morbidity rates reflected in practice and review studies during the last two decades have facilitated the widespread use of liver biopsy procedure (1). The excellent paper by Sporea et al in the last issue of the Journal of Gastrointestinal and Liver Diseases (2), very nicely demonstrated that, in experienced hands, percutaneous liver biopsy can obtain "good" histological material in the vast majority of cases. In their study, they retrospectively analyzed 250 echoassisted percutaneous liver biopsies obtained for staging of chronic hepatitis concerning the length and number of portal areas of the biopsy. In 87% of cases, the biopsy had 8-10 portal areas (good biopsy) and in 69% the biopsy had at least 11 portal areas (very good biopsy). In 13% of cases the biopsy was suboptimal containing less than 8 portal areas, and only 1.6% was inadequate with less than 4 portal areas. As for the length, 88% of cases had a biopsy longer than 2 cm,
Background
Hepatitis C is a disease that has a significant global impact. The World Health Organization estimates that over 150 million people are chronically infected with the hepatitis C virus (HCV).
Objectives
The purpose of the study was to make a quantitative determination of the hepatitis C viral load and genotype using real-time polymerase chain reaction (RT-PCR) and to determine how these factors relate to the HCV chronicity.
Materials and Methods
A cross-sectional hospital-based study was carried out in Kirkuk city, Iraq. A total of 50 patients with chronic hepatitis C whose ages ranged from 20 to 75 years were the subjects of the study. The control group consisted of 30 apparently healthy persons admitted to the blood bank for blood donation. Five milliliters of blood were drawn for the molecular detection of HCV load and genotype by RT-PCR, detection of hepatitis C antibodies by enzyme-linked immunosorbent assay (ELISA), and biochemical analysis of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total serum bilirubin (TSB).
Results
According to the research, 86% of chronic hepatitis C patients with ELISA-detected anti-HCV obtained positive PCR results. Statistically significant ( P = 0.01). According to the study, more chronic hepatitis C patients (31 out of 43) had genotype 4 HCV than genotype 1a (27.91%). According to the study, genotype 4 chronic hepatitis C patients exhibited significantly higher viral loads than genotype 1a patients (1901.3 vs. 1693.41 IU/mL; P = 0.01). About 41.94% of men and 58.06% of females with chronic hepatitis C had genotype 4, whereas 33.3% of males and 66.67% of females had genotype 1a. Chronic hepatitis C patients had higher ALT, AST, ALP, and TSB levels than the control group, and the difference was very significant. ALT values were 64.69, 54.8, 285.5, and 4.33 mg/dL. This study found a connection between chronic hepatitis C viral load and ALT, AST, ALP, and TSB levels. Viral load rose as fibrosis progressed, according to this study. Patients without fibrosis had the lowest mean viral load (1235.5 IU/mL), followed by those with stage 1 fibrosis, whereas cirrhosis (stage 4) had the highest (2088.1 IU/mL). Non-fibrotic patients had the lowest virus burden.
Conclusions
Genotype 4 of HCV was the most predominant genotype in Kirkuk city and there was a strong positive correlations of ALT and viral load with stages of fibrosis in patients with chronic hepatitis C.
Many hypotheses underlie the pathogenesis of preeclampsia. This study aims to evaluate Neutrophil gelatinase-associated lipocalin (a marker of immune hypothesis) and Neutrophil / Lymphocyte ratio (a marker of inflammation) in the diagnosis of preeclampsia and its severity and to determine the correlation between them.
Study design : This randomized case-control study involved 132 pregnant women ; 88 were diagnosed with PE (divided into non-severe and severe groups), and 44 healthy pregnant women as a control group. Results : The mean serum level of NGL was significantly higher in PE (535.37 ± 158.61 ng / ml for severe PE, 522.5 ± 106.3 ng / ml for non-severe PE, and 161.96 ± 17.48 ng / ml for the control group). The ROC Curve NGL criteria of more than 204.4 ng / ml showed 100% sensitivity and specificity in both severe and non-severe cases versus control. The N / L ratio showed a significant difference (5.81 ± 5.24 for severe PE, 4.1 ± 3.41 for non-severe PE, and 3.89 ± 1.79 for the control group), but the ROC curve criterion was not significant. Both showed a non-significant positive correlation. Conclusion : NGL is an excellent diagnostic factor, whereas N / L might have lower diagnostic performance compared with NGL. Both are related independently to the pathophysiology of PE. J. Med. Invest. 68 : 321-325, August, 2021
Chronic viral hepatitis affects nearly one half billion people; it can result in hepatic fibrosis and cirrhosis if untreated. We investigated whether the polypeptides, adropin, apelin, elabela, asprosin and betatrophin, could be useful biomarkers for diagnosing chronic hepatitis and for the staging fibrosis. Patients 18−60 years old who underwent a liver biopsy for chronic hepatitis B (CHB) or C (CHC) from January 2014 to January 2019 were included in our study. The patients were divided into three groups: control group, CHB group, and CHC group. The CHB group comprised four subgroups based on the severity of the hepatic fibrosis. Liver biopsy specimens of all groups were evaluated for adropin, apelin, elabela, asprosin and betatrophin immunoreactivity by light microscopy. Adropin, apelin, elabela and betatrophin were immunoreactive in the hepatocytes, while asprosin was not in any group. In the CHB group, adropin and elabela immunoreactivity was increased significantly in stages III and IV patients compared to the other subgroups, whereas stages I and II patients were comparable to the control group. The CHC group exhibited decreased betatrophin immunoreactivity and increased elabela immunoreactivity compared to the control group. We suggest that adropin and elabela can provide clues for staging and monitoring fibrosis in CHB, and may be potentially useful biomarkers.
Viral hepatitis is a major global public health problem affecting hundreds of millions of people and is associated with significant morbidity and mortality. Five major biologically unrelated hepatotropic viruses cause most of the global burden of viral hepatitis. Hepatitis B and hepatitis C are associated with a significant number of chronic infections. Most deaths from viral hepatitis are due to hepatitis B and hepatitis C. An estimated 257 million people were living with HBV and 71 million people were living with HCV. Most people are asymptomatic. New diagnostics and highly effective, pangenotypic direct-acting antivirals provide opportunities to cure and eradicate chronic hepatitis C virus infection.
Background:
Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis and its complications. Viral eradication is essential to prevent disease progression and reduces liver-related mortality and morbidity. Since the availability of direct-acting antivirals (DAA), HCV treatment has changed significantly. Current treatment strategies for different groups of patients as well as potential risks and caveats will be discussed in this review.
Summary:
Interferon-free (IFN-free) treatment not only shortens treatment duration, but also achieves high rates of viral clearance and is overall well tolerated. Genotype-restricted but also pangenotypic combinations are available. Usually two DAA of different drug classes are combined. For the majority of the patients, treatment duration ranges from 8 to 12 weeks. Liver and kidney function as well as prior treatment experience and potential drug-drug interactions influence substance choices and treatment duration. However, modern IFN-free treatment is not only safer, but also overall far more simplified and effective. Global HCV eradication might be an ambitious but not completely unrealistic goal to pursue.
Key messages:
IFN-free antiviral treatment is safe and well tolerated. Patients can be treated almost independently of liver function or concomitant disease. Viral eradication is associated with reduced morbidity and mortality and better quality of life.
PURPOSE:Percutaneous tissue biopsy is a mainstay of diagnostic and interventional radiology, providing a minimally invasive method for diagnosing malignant and benign disease. The purpose of this review was to collect and summarize the best available evidence regarding the risk factors associated with bleeding complications in image-guided liver biopsy.METHODS:A literature review was performed, searching Medline, EMBASE, CINAHL, the Cochrane Library, the National Institute for Health and Care Excellence (NICE) and Canadian Agency for Drugs and Technology in Health (CADTH) databases for any studies evaluating bleeding complications in image-guided liver biopsy. A total of 68 articles, published between January 1994 and April 2015, were reviewed in full, with 34 ultimately eligible for inclusion in the review.RESULTS:Bleeding of any kind occurred in up to 10.9% of image-guided liver biopsies, with major bleeding episodes ranging from 0.1% to 4.6% and minor bleeding events occurring in up to 10.9% of biopsies. The overall rate of bleeding was, however, found to be less than 2%. Several risk factors (patient, operator, and procedure-related) were identified as potentially indicative of an increased risk of post-biopsy bleeding. Patient-related risk factors included patient age (>50 years or 1.5, P < 0.001). There was no consensus on impact of operator experience (>200 biopsies/year vs.
Liver fibrosis observed in various chronic disorders is a risk factor of unfavorable prognosis and usually leads to cirrhosis. To date, liver biopsy is the gold standard for assessment of fibrosis. Its invasiveness and risk of hemorrhage incline to looking for noninvasive markers of liver fibrosis. The APRI index includes two simple and cheap laboratory tests performed routinely in clinical practice. Usefulness of this marker seems to depend on the etiology of liver damage. The predictive accuracy of APRI for significant fibrosis and cirrhosis was tested by the areas under the receiver operating characteristic curves (AUROC). The APRI score correlates significantly to fibrosis stage in patients with chronic hepatitis C. The APRI in patients with autoimmune hepatitis, chronic hepatitis B, and alcoholic liver disease is controversial and does not seem to have a diagnostic value in significant fibrosis. It showed promising results for predicting the presence of fibrosis in pediatric patients with NAFLD. Transient elastography, a noninvasive and objective but expensive method, showed higher performance in diagnosing significant fibrosis than APRI.
Among new peptides responsible for the pathogenesis of metabolic disorders and carbohydrate metabolism, adipokines are of great importance. Adipokines are substances of hormonal character, secreted by adipose tissue. Apart from the well-known adipokines, adropin and preptin are relatively newly discovered, hence their function is not fully understood. They are peptides not secreted by adipose tissue but their role in the metabolic regulations seems to be significant. Preptin is a 34-amino acid peptide, a derivative of proinsulin growth factor II (pro-IGF-II), secreted by pancreatic β cells, considered to be a physiological enhancer of insulin secretion. Additionally, preptin has a stimulating effect on osteoblasts, inducing their proliferation, differentiation and survival. Adropin is a 76-amino acid peptide, encoded by the energy homeostasis associated gene (Enho), mainly in liver and brain, and its expression is dependent on a diet. Adropin is believed to play an important role in metabolic homeostasis, fatty acids metabolism control, insulin resistance prevention, dyslipidemia, and impaired glucose tolerance. The results of studies conducted so far show that the diseases resulting from metabolic syndrome, such as obesity, type 2 diabetes mellitus, polycystic ovary syndrome, non-alcoholic fatty liver disease, or cardiovascular disease are accompanied by significant changes in the concentration of these peptides. It is also important to note that preptin has an anabolic effect on bone tissue, which might be preventive in osteoporosis.
Transient elastography (TE) is a reliable tool for the non-invasive assessment of liver fibrosis in routine clinical practice. TE is currently approved for use in Europe, Asia and the United States. The widespread adoption of this technology is certain to increase the use of TE worldwide. Although TE has been well validated in chronic viral hepatitis, its clinical role in other liver diseases remains less clear. The advent of new treatment for chronic hepatitis C and emerging prevalence of non-alcoholic steatohepatitis raises new questions on the role of TE in current clinical practice. This review aims to examine the clinical applications, limitations and future role of TE in current clinical practice in light of the changing epidemiology of liver diseases and new clinical management paradigms. In current clinical practice, TE is the most accurate non-invasive method for diagnosis of liver cirrhosis. TE is useful to rule out fibrosis and cirrhosis but does not have sufficient accuracy to discern between various stages of fibrosis. The clinical role of TE has evolved from cross-sectional point-in-time assessment of fibrosis and cirrhosis to the more relevant role of prediction of vital clinical end-points. This provides clinicians with the ability to modify treatment strategies based on the information provided by TE. TE has evolved over the past decade to become an essential tool to assist the clinician in the management of chronic liver disease.
The family of apelin peptides is derived from a single gene and activates the 7-transmembrane G-protein-coupled receptor (GPCR) APJ. Apelins have been shown to be involved in the regulation of cardiovascular function and fluid homeostasis and interestingly represent substrates for ACE2, a carboxypeptidase recently described as a novel key enzyme in the renin-angiotensin-aldosterone system (RAS). APJ has further been reported to be a coreceptor for the infection of CD4-positive cells with HIV in the central nervous system (CNS). Apelin-36 and shorter C-terminal sequences have different potencies and efficacies in regulating these functions. Shorter sequences, especially (Pyr(1))apelin-13, are potent regulators of cardiovascular function, while longer peptides such as apelin-36 are more effective in inhibiting human immunodeficiency virus (HIV) infection by blocking the HIV coreceptor APJ. The pyroglutamate modification characteristic of the short apelin peptide (Pyr(1))apelin-13 indicates paramount biological importance of this peptide. The aim of this review is to compile conclusive evidence for the involvement of apelin/APJ in the regulation of cardiovascular function and HIV pathology, emphasizing the properties of this receptor system that may make it a successful future drug target.
The development of noninvasive markers of liver fibrosis is a clinical and research priority. The aspartate aminotransferase-to-platelet ratio index (APRI) is a promising tool with limited expense and widespread availability. Our objective was to systematically review the performance of the APRI in hepatitis C virus (HCV)-infected patients. Random effects meta-analyses and areas under summary receiver operating characteristic curves (AUC) were examined to characterize APRI accuracy for significant fibrosis (stages 2-4) and cirrhosis. In 22 studies (n = 4,266), the summary AUCs of the APRI for significant fibrosis and cirrhosis were 0.76 [95% confidence interval (CI), 0.74-0.79] and 0.82 (95%CI, 0.79-0.86), respectively. For significant fibrosis, an APRI threshold of 0.5 was 81% sensitive and 50% specific. At a 40% prevalence of significant fibrosis, this threshold had a negative predictive value (NPV) of 80%, but could reduce the necessity of liver biopsy by only 35%. For cirrhosis, a threshold of 1.0 was 76% sensitive and 71% specific. At a 15% cirrhosis prevalence, the NPV of this threshold was 91%. Higher APRI thresholds had suboptimal positive predictive values except in settings with a high prevalence of cirrhosis. APRI accuracy was not affected by the prevalence of advanced fibrosis, or study and biopsy quality. However, the accuracy for cirrhosis was greater in studies including human immunodeficiency virus (HIV)/HCV-co-infected patients. CONCLUSION: The major strength of the APRI is the exclusion of significant HCV-related fibrosis. Future studies of novel markers should demonstrate improved accuracy and cost-effectiveness compared with this economical and widely available index.
A narrative review of natural history, epidemiology and risk factors for hepatitis C infection
- Suan
A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C
- Wai