High Serum Levels of HDV RNA Are Predictors of Cirrhosis and Liver Cancer in Patients with Chronic Hepatitis Delta

• DOI: 10.1371/journal.pone.0092062
• Publication Date: 2014-03-21T20:45:41Z
• Authors: Raffaella Romeo; Barbara Foglieni; Giovanni Casazza; Marta Spreafico; Massimo Colombo; Daniele Prati
• Keywords: Liver Cirrhosis; 0301 basic medicine; Hepatitis B virus; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis D, Chronic; Science; Q; Liver Neoplasms; R; Hepatitis D; 3. Good health; Cohort Studies; 03 medical and health sciences; Italy; Carcinoma, Hepatocellular; Cohort Studies; DNA, Viral; Disease Progression; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis D; Hepatitis D, Chronic; Hepatitis Delta Virus; Humans; Italy; Liver Cirrhosis; Liver Neoplasms; RNA, Viral; Viremia; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all); DNA, Viral; Disease Progression; Medicine; Humans; RNA, Viral; Viremia; Hepatitis Delta Virus; Research Article

Chronic infection with the hepatitis delta virus (HDV) is a risk factor for cirrhosis and hepatocellular carcinoma (HCC), but little is known whether the outcome of hepatitis is predicted by serum markers of HDV and hepatitis B virus (HBV) infection. The aim of the study was to investigate these correlations in 193 patients with chronic HDV infection who had been followed up for a median of 9.5 years (4.8-19.3). HDV-RNA was first measured by qualitative in-house nested RT-PCR and quantified by in-house real-time PCR. HDV RNA levels only appeared significantly associated to HCC (univariate analysis: OR 1.32, 95% CI 1.02-1.71; p = 0.037; multivariate analysis: OR 1.42, 95% CI 1.04-1.95; p = 0.03). In non-cirrhotics at first presentation (n = 105), HDV RNA levels were associated with progression to cirrhosis (univariate analysis: OR = 1.57, 95% CI 1.20-2.05, p<0.001; multivariate analysis: OR = 1.60, 95% CI 1.20-2.12, p = 0.007) and development of HCC (univariate analysis: OR = 1.66, 95% CI 1.04-2.65, p = 0.033; multivariate analysis: OR = 1.88, 95% CI 1.11-3.19, p = 0.019). ROC analysis showed that approximately 600,000 HDV RNA copies/mL was the optimal cut-off value in our cohort of patients for discriminating the development of cirrhosis. High levels of HDV viremia in non-cirrhotic patients are associated with a considerable likelihood of progression to cirrhosis and the development of HCC. Once cirrhosis has developed, the role of HDV replication as a predictor of a negative outcome lessens.