Antiviral therapy for the treatment of hepatitis C virus (HCV) infection is used before and after liver transplantation. The objective of this study was to determine the most cost-effective timing for pegylated interferon/ribavirin therapy in patients with advanced liver disease infected with genotype 1 HCV. A Markov model was constructed to compare treatment strategies: (1) no treatment, (2) antiviral therapy in patients with compensated cirrhosis, (3) antiviral therapy in patients with decompensated cirrhosis, and (4) antiviral therapy in patients with progressive fibrosis due to recurrent HCV post-transplantation. Outcomes of interest included the total cost per patient, number of quality-adjusted life years (QALYs) saved, cost per QALY saved, number of deaths and hepatocellular carcinomas (HCCs), and number of transplants required. Compared to the no-antiviral treatment strategy, treatment during compensated cirrhosis increased QALYs by 0.950 and saved $55,314. Treatment during decompensated cirrhosis increased QALYs by 0.044 and saved $5511. Treatment during posttransplant advanced recurrence increased QALYs by 0.061 and saved $3223. Treatment of patients with compensated cirrhosis resulted in 119 fewer deaths, 54 fewer HCCs, and 66 fewer transplants with respect to the no-treatment strategy. The model was sensitive to the rate of graft failure in patients with and without sustained virological response. The model was otherwise robust to all variables tested in sensitivity analysis. In conclusion, the treatment of patients with compensated cirrhosis was found to be the most cost-effective strategy and resulted in improved survival and decreased cost in comparison with all other strategies. This study provides pharmacoeconomic evidence in support of treating HCV in patients with compensated cirrhosis before progression to more advanced liver disease. Liver Transpl 16:748-759,

Viral hepatitis is a common problem in the incarcerated population. It causes significant morbidity and mortality, and incarcerated inmates receive their health care almost exclusively from corrections-based health systems. The seroprevalence of hepatitis B and C infections is increased in this population, and a number of risk factors for viral hepatitis are particularly common and infer higher risk among inmates, including injection drug use (IDU), high-risk sexual activity, and tattoos. IDU, in particular, has been identified as an important and common risk factor for viral hepatitis in inmates, and variable rates of IDU among inmates have been found to be the most important cause of the marked variability of seroprevalence rates for exposure to hepatitis C virus. A number of risk reduction and management strategies have been identified that can decrease transmission to other inmates. Prison-based hepatitis A and hepatitis B vaccination programs, needle exchange programs, methadone maintenance programs, risk education programs, and hepatitis C virus antiviral programs, for example, have been shown to be safe and effective risk reduction and management strategies. Preliminary studies have shown that these strategies are underutilized in the United States. Reasons for this phenomenon are multifactorial, involving financial as well as ethical and political considerations. Additional funding, research, and formal consideration / discussion of the complex issues involving viral hepatitis in the US incarcerated population are clearly important for the sake of inmates and the community at large. In this article, the published medical literature regarding this important topic is reviewed.

A number of promising new hepatitis C virus (HCV) antiviral regimens have emerged during the last few years, with a trend toward increased efficacy, safety, and tolerability, when compared with currently available therapies. The focus of recent HCV antiviral drug development has been on inhibition of HCV replication, largely by targeting specific components of the HCV replication complex itself. A significant effort has been put into generating drugs that inhibit the NS5B polymerase. A number of such drugs have been developed, and NS5B polymerase inhibitors can be divided into nucleoside polymerase inhibitors and nonnucleoside polymerase inhibitors, with each group carrying specific pharmacologic and clinical characteristics. Additional research has explored the efficacy of drugs that inhibit the HCV replication complex via other mechanisms. Second-generation NS3-4A protease inhibitors have been developed, which have generally improved on the efficacy of the currently available FDA-approved first-generation agents. NS5A inhibitors have also been studied. These medications impede HCV replication and viral particle assembly and enhance host immune activation via novel mechanisms. Alternatively, medications that target a host protein, cyclophillin B, are under evaluation. These medications block HCV replication via modification of the effects of NS5B and via other poorly understood mechanisms. Detailed below are the most important HCV antiviral agents under development, many of which show promise for use within the next few years.