Estimating the future health burden of chronic hepatitis C and human immunodeficiency virus infections in the United States.
ABSTRACT 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.
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ABSTRACT: The current standard of care for patients infected with hepatitis C virus (HCV) is not effective universally and is associated with severe side effects. Direct-acting antiviral molecules have potential to transform treatment of HCV-infected individuals but emergence of drug-resistant virus will be problematic. It is anticipated that, to limit the emergence of drug-resistant virus, future HCV therapies must consist of multiple direct-acting antivirals. In the present study, cell culture-based colony-forming assays were used to demonstrate enhanced suppression of HCV RNA replication following simultaneous treatment of HCV replicon-containing cells with two direct-acting antivirals. Specifically, combinations of NS5Ai and Filibuvir (small molecule inhibitors of HCV-encoded NS5A and NS5B proteins respectively) were able to suppress colony formation fully at concentrations that individually they could not. HCV replicon RNA isolated from colonies that emerged following treatment with suboptimal concentrations of NS5Ai were found to encode resistance substitutions in the NS5A gene, which rendered them insensitive to subsequent high doses of NS5Ai. Furthermore, both NS5Ai and Filibuvir were effective at suppressing colony formation in combination with BILN 2061, an inhibitor of HCV-encoded NS3. Collectively, these data underscore the increased inhibitory capacity of direct-acting antivirals to suppress HCV RNA replication when present in combination.Journal of virological methods 06/2011; 174(1-2):153-7. DOI:10.1016/j.jviromet.2011.03.031
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ABSTRACT: The prevalence of chronic hepatitis C (CHC) is significantly higher in patients with end-stage renal disease undergoing hemodialysis than in the general population. CHC adversely affects survival in patients on hemodialysis and those who have undergone renal transplantation (RT); routine screening for hepatitis C virus infection is recommended for both groups. Treatment of CHC in post-RT patients and those undergoing hemodialysis remains challenging. Data on nonpegylated interferon alfa and pegylated interferon alfa monotherapies remain limited, and treatment-induced adverse effects are common. Ribavirin is contraindicated in these patients, but a combination of low-dose ribavirin with interferon is being assessed in clinical trials. Further studies are needed to clarify the pathogenesis and natural history of CHC in hemodialysis patients and post-RT patients and to develop effective treatment for hepatitis C virus infection in these patients.Current Hepatitis Reports 08/2009; 6(3):96-102. DOI:10.1007/s11901-007-0011-x
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ABSTRACT: Chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) are two frequently identified liver diseases worldwide. NAFLD is related to obesity and insulin resistance, which may also be a preexisting condition in patients with CHC. The complex relationship among obesity, steatosis, and insulin resistance as it pertains to the pathogenesis, treatment, and outcomes in CHC is discussed in this article.Current Hepatitis Reports 11/2009; 6(4):129-137. DOI:10.1007/s11901-007-0015-6