Hepatitis D virus infection markedly increases the risk of hepatocellular carcinoma in patients with viral B cirrhosis.

Background and aims: The specific causative role of HDV infection in the development of hepatocellular carcinoma (HCC) remains debated and was not specifically demonstrated in cirrhotic patients. Here we compared HCC incidence in HBV-HDV co-infected and HBV mono-infected cirrhotic patients.

Methods: A total of 142 HBV-HDV and 271 HBV-infected cirrhotic patients from the French ANRSCO12 CirVir and DeltaVir cohorts, with histologically proven cirrhosis and no history of decompensation, were included in the study.

Results: HBV-HDV patients were younger than HBV patients (37.2 vs. 53.8 years), they were more often immigrants from sub-Saharan Africa, and displayed less co-morbidities and more altered liver tests. After adjustment for age, cumulative incidences of HCC in co-infected and mono-infected patients at 1, 3 and 5 years were 5.2%, 11.8% and 20.2% vs. 1.1%, 2.5% and 4.4%, respectively (P< .001). In multivariate analysis, HDV infection was an independent factor associated with the development of HCC (HR 2.94, 95% CI 1.19-7.25; P= .019). Other independent factors were age (HR 1.08, 1.05-1.11; P< .001), overweight (HR 0.45, 0.22-0.93; P= .031), smoking (HR 2.26, 1.23-4.16; P= .009), increased GGT (HR 2.73, 1.24-6.00; P= .013), total bilirubin >17 μmol/L (HR 2.68, 1.33-5.42; P= .006) and platelet count <150.000/mm³ (HR 3.11, 1.51-6.41; P= .002). HDV co-infection was not an independent factor of liver decompensation, transplantation or death.

Conclusion: The incidence of HCC appears significantly higher in HBV-HDV than in HBV-infected cirrhotic patients. HDV infection emerges as an independent risk factor for HCC, indicating that in cirrhotic patients, HDV plays a causative role for HCC independently of HBV.