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ABSTRACTIntroduction:Chronic hepatitis C virus (HCV) infection has become a curable disease. More than 90% sustained virologic response rates have been obtained with 8–24 weeks of treatment with distinct combinations of direct-acting antivirals (DAA) in most registration trials. However, outcomes in real-world patients tend to be lower and treatment of special patient populations is often challenging. Areas covered:We address the treatment of chronic hepatitis C with DAA in major special patient populations, such as HIV-positive persons, transplant recipients, patients with advanced cirrhosis, renal insufficiency, hepatitis B or D coinfection, injection drug users (IDUs) and prior DAA failures. Expert opinion:Drug interactions between DAA and medications given to persons with HIV infection or transplant recipients can result in treatment failure and adverse events. Severe organ dysfunction as in kidney insufficiency or decompensated cirrhosis may lead to DAA overexposure and toxicities. Dysfunctional social circumstances and behavior are associated to poor drug adherence and increased risk for HCV re-infection in active IDUs. Finally, DAA response might be impaired by viral interference in patients with hepatitis B or D coinfection or drug resistance in HCV either at baseline or after prior DAA failures.

Background Advanced liver fibrosis frequently develops in patients with chronic hepatitis C coinfected with HIV. Non-invasive techniques for staging liver fibrosis, such as transient elastometry, may allow both periodic monitoring and examination of large patient populations.Methods A programme of liver fibrosis assessment using transient elastometry has been ongoing at our institution since 2004. All HIV-HCV-coinfected patients having =2 examinations separated by >18 months were included. Liver fibrosis progression (LFP) was defined as an increase in liver stiffness from <9.5 kPa (Metavir F0-F2) to >9.5 kPa (Metavir F3-F4), or an increase >30% in patients with baseline Metavir F3-F4.Results A total of 545 HIV-HCV-coinfected patients were analysed (mean age 41 years, 71% male, 81% intravenous drug users, mean body mass index 23.3 kg/m2, 4.2% hepatitis B surface antigen-positive, 8.4% alcohol abuse, mean CD4+T-cell count 519 cells/µl). At baseline, 527 patients were on antiretroviral therapy, with the most frequent third drug being atazanavir (19.7%), efavirenz (15.9%), lopinavir (13.1%) or nevirapine (7.2%). A total of 99 (18%) patients experienced LFP during a mean (sd) follow-up of 70.9 (15.7) months. Use of protease inhibitors (OR 4.93, 95% CI 1.73, 14.0; P=0.03) and male gender (OR 5.12, 95% CI 1.37, 19.1; P=0.01) were associated with LFP. By contrast, the achievement of HCV clearance following pegylated interferon/ribavirin (PEG-IFN/RBV) therapy (OR 0.27, 95% CI 0.1, 0.79; P=0.02) was protective. Lopinavir exposure was significantly associated with LFP (OR 1.02, 95% CI 1.0, 1.04; P=0.03), whereas nevirapine was protective (OR 0.94, 95% CI 0.9, 0.99; P=0.02).Conclusions The use of protease inhibitors, mainly lopinavir, is associated with increased LFP in HIV–HCV-coinfected patients. By contrast, nevirapine therapy and, particularly, HCV clearance with PEG-IFN/RBV significantly reduce LFP.