title: High serum levels of HDV RNA are predictors of cirrhosis and liver cancer in patients with chronic hepatitis delta.
abstract: 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.
authors.affiliation: AM & A Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Romeo
authors.affiliation: Department of Transfusion Medicine and Hematology, Ospedale A. Manzoni, Lecco, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Foglieni
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casazza
authors.affiliation: Department of Transfusion Medicine and Hematology, Ospedale A. Manzoni, Lecco, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Spreafico
authors.affiliation: AM & A Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Department of Transfusion Medicine and Hematology, Ospedale A. Manzoni, Lecco, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Prati
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D003699:Hepatitis D / Q000821:virology; D019701:Hepatitis D, Chronic / Q000097:blood* / Q000150:complications*; D003698:Hepatitis Delta Virus / Q000235:genetics*; D006801:Humans; D007558:Italy; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000209:etiology; D012367:RNA, Viral / Q000097:blood*; D014766:Viremia / Q000150:complications
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D012367:RNA, Viral