Deuffic-Burban SF, Poynard TF, Sulkowski MS, Wong JBEstimating the future health burden of chronic hepatitis C and human immunodeficiency virus infections in the United States. J Viral Hepat 14(2): 107-115
The aim of this work was to estimate the future disease burden of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections in the United States until the year 2030. Two back-calculation models of the HIV and the HCV epidemic were developed. They were based on US epidemiological data regarding prevalence, age and gender of incident cases, AIDS, hepatocellular carcinoma (HCC) mortality and general population mortality from the Centers for Disease Control and WHO. Based on the HCV back-calculation model, HCV incidence peaked in 1984 at 350,000 new infections and then fell to about 77,000 in 1998. Based on the HIV back-calculation model, HIV incidence reached its maximum in 1989 at 142,000 new infections and then declined to 79,000 in 1998. Mortality related to HCV (death from liver failure or HCC) rose from about 3,700 in 1998 and is expected to peak at about 13,000 in 2030. Predicted HCV mortality would fall only if increased access to or more effective antiviral therapy occurs. For comparison, observed HIV-related mortality was 14,400 in 1998 and projected to be 4,200 for 2030. With the availability of effective highly active antiretroviral therapy for HIV infection, mortality from HIV appears to have declined substantially, whereas HCV-related deaths as a result of pre-1999 infections will likely continue to increase over the next 25 years.
"There are 7 major genotypes divided into >100 subtypes [3,4], with genotype 1 being responsible for the majority of HCV-infections world-wide . Approximately 70%-80% of HCV-infected patients fail to clear the virus, and develop chronic HCV infections, which is a risk factor for liver diseases such as fibrosis, cirrhosis and hepatocellular carcinoma . Liver fibrosis, which results from an excessive connective tissue built up in the liver (fibrogenesis), can gradually exacerbate during the course of the infection and lead to scarring of the tissue (i.e., cirrhosis) and more severe liver dysfunction. "
[Show abstract][Hide abstract] ABSTRACT: Background
Chronic infection with hepatitis C virus (HCV) is a risk factor for liver diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. HCV genetic heterogeneity was hypothesized to be associated with severity of liver disease. However, no reliable viral markers predicting disease severity have been identified. Here, we report the utility of sequences from 3 HCV 1b genomic regions, Core, NS3 and NS5b, to identify viral genetic markers associated with fast and slow rate of fibrosis progression (RFP) among patients with and without liver transplantation (n = 42).
A correlation-based feature selection (CFS) method was used to detect and identify RFP-relevant viral markers. Machine-learning techniques, linear projection (LP) and Bayesian Networks (BN), were used to assess and identify associations between the HCV sequences and RFP.
Both clustering of HCV sequences in LP graphs using physicochemical properties of nucleotides and BN analysis using polymorphic sites showed similarities among HCV variants sampled from patients with a similar RFP, while distinct HCV genetic properties were found associated with fast or slow RFP. Several RFP-relevant HCV sites were identified. Computational models parameterized using the identified sites accurately associated HCV strains with RFP in 70/30 split cross-validation (90-95% accuracy) and in validation tests (85-90% accuracy). Validation tests of the models constructed for patients with or without liver transplantation suggest that the RFP-relevant genetic markers identified in the HCV Core, NS3 and NS5b genomic regions may be useful for the prediction of RFP regardless of transplant status of patients.
The apparent strong genetic association to RFP suggests that HCV genetic heterogeneity has a quantifiable effect on severity of liver disease, thus presenting opportunity for developing genetic assays for measuring virulence of HCV strains in clinical and public health settings.
"HCV is currently the most significant public health problem in Egypt with an infection prevalence of up to 20%, this is ten times greater than any other country in the world and the highest prevalence of HCV genotype 4, which is responsible for 90% of infections, with a predominance of subtype 4a (55%) [2-4]. Studies suggest that mortality related to HCV infection will increase over in the next two decades . A protective vaccine against HCV does not exist till now, and current standard treatment for chronic HCV infection is interferon α alone or in combination with ribavirin. "
[Show abstract][Hide abstract] ABSTRACT: Purpose
The prevalence of HCV infection has increased during recent years and the incidence reach 3% of the world's population, and in some countries like Egypt, may around 20%. The developments of effective and preventive agents are critical to control the current public health burden imposed by HCV infection. Lactoferrin in general and camel lactoferrin specifically has been shown to have a compatitive anti-viral activity against hepatitis C virus (HCV). The purpose of this study was to examine and compare the anti-infectivity of native human, camel, bovine and sheep lactoferrin on continuous of HCV infection in HepG2 cells.
Material and methods
Used Lfs were purified by Mono S 5/50 GL column and Superdex 200 5/150 column. The purified Lfs were evaluated in two ways; 1. the pre-infected cells were treated with the Lfs to inhibit intracellular replication at different concentrations and time intervals, 2. Lfs were directly incubated with the virus molecules then used to cells infection. The antiviral activity of the Lfs were determined using three techniques; 1. RT-nested PCR, 2. Real-time PCR and 3. Flowcytometric.
Human, camel, bovine and sheep lactoferrin could prevent the HCV entry into HepG2 cells by direct interaction with the virus instead of causing significant changes in the target cells. They were also able to inhibit virus amplification in HCV infected HepG2 cells. The highest anti-infectivity was demonstrated by the camel lactoferrin.
cLf has inhibitory effect on HCV (genotype 4a) higher than human, bovine and sheep lactoferrin.
"Approximately 80% of infected patients fail to clear the virus and less than 10% may develop severe liver diseases such as chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma, which can compromise patient survival . And the number of people requiring treatment for chronic HCV infection is expected to increase over the next 10–20 years . "
[Show abstract][Hide abstract] ABSTRACT: Chronic hepatitis C virus (HCV) infection is one of the leading causes of hepatic cirrhosis and hepatocellular carcinoma, and HCV genotype 1 is the most prevalent genotype and is resistant to current standard therapy. We performed this meta-analysis to evaluate the efficacy and safety of telaprevir-based therapy for chronic HCV genotype 1 infection.
We included randomized controlled trials with no year or language restriction. All data were analyzed using a random-effects model by Review Manager v5.0. The primary outcome was the proportion of patients achieving sustained virologic response (SVR), and the secondary outcomes were HCV relapse rate, incidence of severe adverse events (SAEs), and discontinuation due to adverse events.
The proportion of achieving SVR was significantly higher in the telaprevir group (odds ratio [OR] = 3.40 [1.92, 6.00], P<0.0001; I(2) = 87%) regardless of a patients' previous treatment status. It was also significantly higher in the 24-week and 48-week treatment groups (OR = 4.52 [2.08, 9.81], P<0.001; I(2) = 85%, and OR = 4.05 [1.56, 10.56], P = 0.004; I(2) = 92%, respectively), while it was comparable in the 12-week treatment group (OR = 1.32 [0.63, 2.75], P = 0.46; I(2) = 35%). In addition, the HCV relapse rate was significantly reduced in the telaprevir group (OR = 0.28 [0.16, 0.49], P<0.001; I(2) = 76%). However, the incidence of SAE (OR = 1.56 [1.15, 2.10], P = 0.004; I(2) = 0%) and study discontinuation due to adverse events (OR = 2.24 [1.43, 3.50], P<0.001; I(2) = 37%) were significantly higher in the telaprevir group.
Despite its higher incidence of SAEs and discontinuation due to adverse events, telaprevir-based therapy can increase the proportion of achieving SVR in both previously treated and untreated chronic HCV-1 infected patients.
PLoS ONE 12/2012; 7(12):e52158. DOI:10.1371/journal.pone.0052158 · 3.23 Impact Factor
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