1 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
2 Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland.
3 Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland.
4 Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland; Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland. Electronic address: Francesco.Negro@hcuge.ch.
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 two authors. Data were pooled using random-effects models.
RESULTS: Ninety-three studies (68 case-control studies including 22862 patients and 25 cohort studies including 75427 patients) were included. Twelve studies accounted for confounders, in either study design or analysis (ten of which were cohorts), and 11 cohorts were prospective. The overall analysis showed a significantly increased risk of hepatocellular carcinoma 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 hepatocellular carcinoma in patients with chronic hepatitis D. 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 hepatitis B patients, and the urgent need of novel and effective antiviral therapies.