Hepatitis D Virus Infection Markedly Increases the Risk of Hepatocellular Carcinoma in Patients with Viral B Cirrhosis.

Background & aims: The specific causative role of hepatitis delta virus (HDV) infection in the development of hepatocellular carcinoma (HCC) remains debated and was not specifically demonstrated in patients with cirrhosis. Here we compared HCC incidence in hepatitis B virus (HBV)-HDV coinfected and HBV monoinfected patients with cirrhosis.

Methods: A total of 142 HBV-HDV and 271 HBV-infected patients with cirrhosis 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 comorbidities and more altered liver tests. After adjustment for age, cumulative incidences of HCC in coinfected and monoinfected patients at 1, 3, and 5 years were 5.2%, 11.8%, and 20.2% versus 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 (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.19-7.25; P = .019). Other independent factors were age (HR, 1.08; 95% CI, 1.05-1.11; P < .001), overweight (HR, 0.45; 95% CI, 0.22-0.93; P = .031), smoking (HR, 2.26; 95% CI, 1.23-4.16; P = .009), increased γ-glutamyltransferase (HR, 2.73; 95% CI, 1.24-6.00; P = .013), total bilirubin >17 μmol/L (HR, 2.68; 95% CI, 1.33-5.42; P = .006), and platelet count <150.000/mm³ (HR, 3.11; 95% CI, 1.51-6.41; P = .002). HDV coinfection was not an independent factor of liver decompensation, transplantation, or death.

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