A 28-Year Study of the Course of Hepatitis Δ Infection: A Risk Factor for Cirrhosis and Hepatocellular Carcinoma
Received 29 July 2008; accepted 19 January 2009. published online 30 January 2009.
Background & Aims
Chronic infection with hepatitis Δ virus (HDV) is a risk factor for cirrhosis and hepatocellular carcinoma (HCC); predictors of disease outcome are, however, poorly defined. We tracked the course of HDV infection in 299 patients over a mean period of 233 months.
Methods
We analyzed data from patients who had been HDV positive for at least 6 months (230 males; mean age, 30 years) admitted from 1978 to 2006 to Maggiore Hospital, Milan. HDV infection was defined by the presence of HDV antigen in liver tissue or serum HDV RNA in anti-HDV/hepititis B surface antigen seropositive patients. At enrollment, 7 patients had acute hepatitis, 101 had mild-moderate chronic hepatitis, 76 had severe chronic hepatitis, and 104 had histologic or clinical cirrhosis. Ninety patients were treated with interferon, 62 with corticosteroids, and 12 with nucleoside analogues; 135 received no therapy.
Results
Over a mean period of 233 months, 82 patients developed cirrhosis. Among the 186 total patients with cirrhosis, 46 developed HCC, 43 ascites, 44 jaundice, and 1 encephalopathy. Female sex, alcohol abuse, and HDV replication were associated with liver decompensation; HBV replication and interferon were associated with HCC development. By the end of the study, 186 patients were still alive, 63 had died, and 29 had received liver transplants. The main cause of death was liver failure (n = 37, 59%); HDV replication was the only independent predictor of mortality.
Conclusions
Persistent HDV replication leads to cirrhosis and HCC at annual rates of 4% and 2.8%, respectively, and is the only predictor of liver-related mortality.
⁎A. M. Migliavacca Center, First Division of Gastroenterology, IRCCS Maggiore Hospital, University of Milan, Milan, Italy
‡Unit of Epidemiology and Medical Statistics, San Carlo Borromeo Hospital of Milan, Milan, Italy
§Third Division of Gastroenterology, IRCCS Maggiore Hospital, University of Milan, Milan, Italy
Reprint requests Address requests for reprints to: Raffaella Romeo, MD, PhD, First Division of Gastroenterology, IRCCS Maggiore Hospital, Pad. Granelli, Via F. Sforza, 35, 20122 Milan, Italy
Conflicts of interest The authors disclose the following: M. Colombo is advisor and served as a speaker bureau for Roche, Schering Plough, Glaxo Smith Kline, and Gilead. The remaining authors disclose no conflicts.
Funding Supported by a grant from University of Milan (“First Project”) and a grant from Fondazione IRCCS Maggiore Hospital Mangiagalli and Regina Elena (“Ricerca Corrente 2008”).
ABSTRACT
A 28-Year Study of the Course of Hepatitis Δ Infection: A Risk Factor for Cirrhosis and Hepatocellular Carcinoma