Journal
JOURNAL OF VIRAL HEPATITIS
Volume 28, Issue 10, Pages 1431-1442Publisher
WILEY
DOI: 10.1111/jvh.13577
Keywords
cirrhosis; HCC; HDV; hepatitis B; hepatitis delta; hepatocellular carcinoma; meta-analysis; systematic review
Funding
- foundation of Cancerfonden
- foundation of ALF
- foundation of Becas-Chile, (ANID, National Agency of Investigation and Research, Chile)
- Stockholm County Council [K2017-4579]
- Center for innovative medicine [CIMED 20180889]
- Swedish Cancer Society [170690]
- AbbVie
- Gilead
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Hepatitis D virus (HDV) infection is associated with a 2-fold higher risk of hepatocellular carcinoma (HCC) development compared to hepatitis B virus (HBV) mono-infection, with a significant 6-fold increased risk noted among HIV/HBV/HDV triple-infected individuals. Adjusting for study design, quality, publication year, and follow-up duration did not significantly change the risk estimate. Surveillance strategies and new treatment options against HDV are warranted.
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.
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