Hepatitis C virus is a serious infection causing cirrhosis, liver cancer, and death. The recent development of direct-acting antivirals has dramatically improved tolerability of treatment and rates of cure. However, the high price of these medications has often limited access to care and resulted in rationing of medications in the United States to those with advanced liver disease, access to specialist care, and without active substance use. This review assesses the way pharmaceutical prices are established and how pricing of directly acting antiviral regimens in the United States has impacted access to treatment for hepatitis C virus.

Persons with human immunodeficiency virus (HIV) and hepatits C virus (HCV) coinfection are at increased risk for progression to cirrhosis compared with persons with HCV alone, but the reasons for this are unclear. In chronic HCV, the mechanism of liver injury is presumed to be due to HCV-specific T cell destruction of hepatocytes, so it is paradoxical that immunosuppressed hosts have higher rates of fibrosis progression. We examined intrahepatic cellular immune responses to HCV antigens to determine whether there were qualitative or quantitative differences in subjects with and without HIV. Expanded, CD4-enriched, liver-infiltrating lymphocytes from 18 subjects with chronic HCV and 12 subjects with HIV/HCV were cultured in the presence of HCV core protein, nonstructural proteins NS3 and NS5, and recall antigens tetanus toxoid and Candida. Secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), and interleukin (IL) 10 was determined using enzyme-linked immunosorbent spot assay. There were no significant differences in liver biopsy grade or stage for HIV/HCV versus HCV groups. There were no significant differences between groups in the secretion of IFN-γ or TNF-α in response to HCV or recall antigens. However, there was a significant increase in IL-10 secretion in response to NS3 and NS5 in subjects with HCV compared with HIV and HCV coinfection. In conclusion, subjects with coinfection have an alteration of intrahepatic HCV-specific IL-10 cytokine response that may have implications for HCV-related disease progression. (Hepatology 2004;40:125-132.)

Objective: To test the hypothesis that antigen-specific interferon (IFN)γ responses are correlated with milder liver disease in subjects coinfected with HIV-1 and hepatitis C virus (HCV). Design: Cellular immune responses were studied in a cohort with HIV/HCV coinfection (n = 107) who underwent liver biopsy. Methods: We measured HCV-specific and recall responses in peripheral blood mononuclear cells using IFNγ and interleukin (IL)-10 ELISpots, and correlated these immune responses with liver histology. The relationship of immunologic, virologic and clinical variables to inflammation and fibrosis was modeled using recursive partitioning. Results: There were significant negative correlations between inflammatory scores and IFNγ production in response to the HCV proteins core, NS5 and summed HCV responses. Lower fibrosis scores were also correlated with higher IFNγ production in response to NS5 and summed HCV proteins. Higher IFNγ production in response to Candida was significantly associated with lower inflammatory and fibrosis scores. In multivariable models, factors associated with severe fibrosis were lower IFNγ responses to Candida and summed HCV proteins. Factors associated with severe inflammation were detectable HIV viral load and lower HCV viral load, while predictors of mild inflammation included undetectable HIV viral load and higher IFNγ response to Candida. Conclusions: In this cohort of subjects coinfected with HIV and HCV, antigen-specific IFNγ responses are correlated with milder inflammation and fibrosis. Immunological responses best predicted severity of fibrosis, while clinical variables and recall antigen responses best predicted severity of inflammation.

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In this issue of JAMA, the US Preventive Services Task Force (USPSTF) has issued new recommendations for hepatitis C virus (HCV) infection screening in the asym