title: A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma.
abstract: OBJECTIVE
  Chronic infection with hepatitis Delta 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/hepatitis 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.
authors.affiliation: A. M. Migliavacca Center, First Division of Gastroenterology, IRCCS Maggiore Hospital, University of Milan, Milan, Italy. raffaella.romeo@unimi.it
authors.forename: Raffaella
authors.initials: R
authors.lastname: Romeo
authors.forename: Ersilio
authors.initials: E
authors.lastname: Del Ninno
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Rumi
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Angelo
authors.initials: A
authors.lastname: Sangiovanni
authors.forename: Roberto
authors.initials: R
authors.lastname: de Franchis
authors.forename: Guido
authors.initials: G
authors.lastname: Ronchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D003699:Hepatitis D / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000821:virology*; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult