Risk of hepatocellular carcinoma in hepatitis B and D virus co‐infected patients: A systematic review and meta‐analysis of longitudinal studies.

Hepatitis D virus (HDV) infection causes a severe chronic viral hepatitis with accelerated development of liver cirrhosis and decompensation, but whether it further increases the risk of hepatocellular carcinoma (HCC) is unclear. We performed a comprehensive systematic review of the published literature and meta‐analysis to assess the risk of HCC in HDV and hepatitis B virus (HBV) co‐infected, compared to HBV mono‐infected patients. The study was conducted per a priori defined protocol, including only longitudinal studies, thus excluding cross‐sectional studies. Random‐effects models were used to determine aggregate effect sizes (ES) with 95% confidence intervals (CI). Meta‐regression was used to examine the associations among study level characteristics. Twelve cohort studies comprising a total of 6099 HBV/HDV co‐infected and 57,620 chronic HBV mono‐infected patients were analysed. The overall pooled ES showed that HBV/HDV co‐infected patients were at 2‐fold increased risk of HCC compared to HBV mono‐infected patients (ES = 2.12, 95% CI 1.14–3.95, I2 = 72%, N = 12). A six‐fold significant increased risk of HCC was noted among HIV/HBV/HDV triple‐infected, compared to HIV/HBV co‐infected patients. The magnitude of ES did not differ significantly after adjustment for study design and quality, publication year and follow‐up duration in univariable meta‐regression analysis. This systematic review and meta‐analysis shows that infection with HDV is associated with a 2‐fold higher risk of HCC development compared to HBV mono‐infection. HCC surveillance strategies taking this increased risk into account, and new treatment options against HDV, are warranted. [ABSTRACT FROM AUTHOR]