Antiviral treatment and liver‐related complications in hepatitis delta

Hepatitis delta virus (HDV) is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG‐IFNα) is effective in only 25%‐30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long‐term outcome of hepatitis delta in relation to different antiviral treatment strategies. We studied 136 anti‐HDV‐positive patients who were followed for at least 6 months in a retrospective single‐center cohort (mean time of follow‐up, 5.2 years; range, 0.6‐18.8). Liver cirrhosis was already present in 62 patients at first presentation. Twenty‐nine percent of patients did not receive any antiviral treatment, 38% were treated with interferon alfa (IFNα)‐based therapies, and 33% received nucleos(t)ide analogues (NAs) only. Clinical endpoints defined as hepatic decompensation (ascites, encephalopathy, and variceal bleeding), hepatocellular carcinoma, liver transplantation, and liver‐related death developed in 55 patients (40%). Patients who received IFNα‐based therapies developed clinical endpoints less frequently than those treated with NA (P = 0.02; HR, 4.0) or untreated patients (P = 0.05; HR, 2.2; 17%, 64%, and 44%), respectively, which was significant in both chi‐square and Kaplan‐Meier analysis. In addition, considering various clinical and virological parameters, IFNα therapy was independently associated with a more benign clinical long‐term outcome in multivariate logistic regression analysis (P = 0.04; odds ratio, 0.25; 95% confidence interval, 0.07‐0.9). Loss of HDV RNA during follow‐up was more frequent in IFNα‐treated patients and strongly linked with a lower likelihood to experience liver‐related complications. Conclusion: IFNα‐based antiviral therapy of hepatitis delta was independently associated with a lower likelihood for clinical disease progression. Durable undetectability of HDV RNA is a valid surrogate endpoint in the treatment of hepatitis delta. (Hepatology 2017;65:414‐425).