Highlights
- •HDV infection is associated with an increased risk of HCC in HBV-infected patients.
- •The association is stronger in high quality and/or prospective cohort studies.
- •The association between HDV and HCC is stronger in the setting of HIV coinfection.
Background & Aims
Chronic hepatitis D (CHD) is the most severe form of chronic viral hepatitis but its
role in the development of hepatocellular carcinoma (HCC) remains debated. We conducted
a systematic review and meta-analysis of epidemiological studies to examine whether
CHD is associated with an increased risk of HCC.
Methods
We searched PubMed, Embase and Web of Science, as well as study references and conference
proceedings. We considered cohort and case-control studies allowing the calculation
of effect estimates for the association between CHD (exposure) and HCC (outcome) in
comparison to chronic hepatitis B. Data extraction and quality evaluation (using the
Newcastle-Ottawa scale) were performed independently by 2 authors. Data were pooled
using random-effects models.
Results
Ninety-three studies (68 case-control studies including 22,862 patients and 25 cohort
studies including 75,427 patients) were included. Twelve studies accounted for confounders,
in either study design or analysis (10 of which were cohorts), and 11 cohorts were
prospective. The overall analysis showed a significantly increased risk of HCC in
patients with CHD, despite substantial study heterogeneity (pooled odds ratio 1.28;
95% CI 1.05–1.57; I2 = 67.0%). The association was particularly strong in the absence of heterogeneity
for prospective cohort studies (pooled odds ratio 2.77; 95% CI 1.79–4.28; I2 = 0%), and studies with HIV-infected patients (pooled odds ratio 7.13; 95% CI 2.83–17.92;
I2 = 0%).
Conclusions
We found a significantly higher risk of HCC in patients with CHD. Although further
studies are needed to definitively exclude a potential bias due to antiviral treatments,
our findings highlight the rationale for improved screening of hepatitis D virus infection
in patients with chronic hepatitis B, and the urgent need for novel and effective
antiviral therapies.
Lay summary
Hepatitis D virus (HDV) is a defective pathogen requiring hepatitis B virus (HBV)
to complete its life cycle. Chronic hepatitis D is the most severe form of chronic
viral hepatitis, increasing the risk of cirrhosis, liver decompensation and death
compared to HBV monoinfection. However, the association between HDV infection and
increased risk of hepatocellular carcinoma is debated. We conducted a systematic review
and found that patients with HDV infection had a significantly higher risk of developing
hepatocellular carcinoma than those with HBV monoinfection.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 06, 2020
Accepted:
February 26,
2020
Received in revised form:
February 18,
2020
Received:
August 22,
2019
Identification
Copyright
© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
