Long‐Term Study of Hepatitis Delta Virus Infection at Secondary Care Centers: The Impact of Viremia on Liver‐Related Outcomes

Abstract

Background & aims Hepatitis delta virus (HDV) infection is associated with fast progression to liver cirrhosis and liver complications. Previous studies have though been mainly from tertiary care centers, with risk for referral bias towards patients with worse outcomes. Furthermore, the impact of HDV viremia per se on liver‐related outcomes is not really known outside HIV co‐infection setting. We have therefore evaluated the long‐term impact of HDV viremia on liver‐related outcomes in a nationwide cohort of hepatitis B and D co‐infected patients, cared for at secondary care centers in Sweden. Approach & Results In total 337 anti‐HDV positive patients including 233 patients with HDV RNA viremia and 91 without HDV viremia at baseline were retrospectively studied, with a mean follow‐up of 6.5 years (range 0.5‐33.1). The long‐term risks for liver‐related events (i.e. hepatocellular carcinoma [HCC], hepatic decompensation, or liver‐related death/transplantation) were assessed, using Cox regression analysis. The risk for liver‐related events and HCC was 3.8 and 2.6 fold higher, respectively, in patients with HDV viremia compared to those without viremia, although the latter was not statistically significant. Among HDV viremic patients with no baseline cirrhosis, the cumulative risk of being free of liver cirrhosis or liver‐related events was 81.9% and 64.0%, after 5 and 10 years of follow‐up, respectively. This corresponds to an incidence rate of 0.04 per person‐year. Conclusion HDV RNA viremia is associated with a 3.8 fold higher risk for liver‐related outcomes. The prognosis was rather poor for non‐cirrhotic patients with HDV viremia at baseline, but it was nevertheless more benign than previous estimates from tertiary centers. Our findings can be of importance when treatment decision making, and evaluating outcomes of upcoming new antivirals against HDV.