title: High doses of alpha-interferon are required in chronic hepatitis due to coinfection with hepatitis B virus and hepatitis C virus: long term results of a prospective randomized trial.
abstract: OBJECTIVE
  Coinfection with hepatitis B (HBV) and hepatitis C (HCV) viruses is associated with a more severe liver disease, increased frequency in the development of hepatocellular carcinoma, and resistance to interferon (IFN) therapy when performed with the standard dosages used in single infections. In the attempt to verify whether the outcome of IFN therapy in patients with hepatitis B and hepatitis C coinfection can be improved, we have planned a prospective, randomized trial with medium to high dosages of interferon three times a week for 6 months.
  
  
  METHODS
  Thirty patients with HBV-HCV coinfection, and chronic hepatitis were randomized to receive either 6 or 9 MU alpha-interferon three times a week for 6 months. Patients were HBsAg positive, anti-HBe positive, HBV DNA negative by dot blot (6/30 positive by polymerase chain reaction), and anti-HCV-positive, HCV RNA positive. Pretreatment and posttreatment liver biopsies were performed.
  
  
  RESULTS
  Five patients treated with 9 MU IFN consistently cleared HCV RNA and HBV DNA, whereas none of those treated with 6 MU reacted in a similar fashion (p = 0.045). Responders showed significant improvement of histological activity index in comparison with nonresponders (mean Ishak score pretreatment versus posttreatment p = 0.002). Long term follow-up showed that none of the patients treated with high doses developed cirrhosis whereas 4/14 treated with low doses did develop cirrhosis.
  
  
  CONCLUSIONS
  Even though the percentage was not very high, the sustained response, the striking histological improvement, and the lack of development of cirrhosis achieved in these patients, indicate that with HBV-HCV coinfection, a trial with high doses of interferon is strongly recommended.
authors.affiliation: Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Villa
authors.forename: A
authors.initials: A
authors.lastname: Grottola
authors.forename: P
authors.initials: P
authors.lastname: Buttafoco
authors.forename: A
authors.initials: A
authors.lastname: Colantoni
authors.forename: A
authors.initials: A
authors.lastname: Bagni
authors.forename: I
authors.initials: I
authors.lastname: Ferretti
authors.forename: C
authors.initials: C
authors.lastname: Cremonini
authors.forename: H
authors.initials: H
authors.lastname: Bertani
authors.forename: F
authors.initials: F
authors.lastname: Manenti
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha