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

Kamal, Habiba; Fornes, Romina; Simin, Johanna; Stål, Per; Duberg, Ann-Sofi; Brusselaers, Nele; Aleman, Soo

doi:10.1111/JVH.13577

Title

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

Author

Kamal, Habiba

Fornes, Romina

Simin, Johanna

Stål, Per

Duberg, Ann-Sofi

Brusselaers, Nele

Aleman, Soo

Abstract

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, I-2 = 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.

Language

English

Source (journal)

Journal of viral hepatitis. - Oxford

Publication

Hoboken : Wiley , 2021

ISSN

1352-0504 [print]

1365-2893 [online]

DOI

10.1111/JVH.13577

Volume/pages