title: Combination of pegylated interferon and lamivudine for patients with chronic hepatitis B who have failed treatment.
abstract: BACKGROUND
  Treatment of chronic hepatitis B (CHB) alone with interferon or lamivudine alone or in combination is effective in only a small proportion of patients. Treatment of patients in whom antiviral therapy fails is challenging. This study was made to determine the efficacy of combined pegylated interferon alpha (peg-IFN) and lamivudine in patients with CHB who had failed to respond to antiviral treatment.
  
  
  METHODS
  Twenty patients with CHB proven by liver biopsy, with ALT levels >1.5 X ULN, HBV DNA levels>141,500 copies/ml, and previous treatment failure with an adequate regimen were treated with a combination of peg-IFN 1.5 microg/kg and lamivudine 100 mg/day for 52 weeks and followed up for a further 24 weeks. Biochemical response was defined as normalization of ALT and DNA response as HBV DNA<141,500 copies/ml. Secondary efficacy measures included HBsAg loss, HBeAg loss and appearance of anti-HBe (in cases of HBeAg-positive patients).
  
  
  RESULTS
  Twenty patients were treated, of whom 16 were HBeAg positive. At 52 weeks, normal ALT was seen in 10 (50%) (8 of 16 HBeAg+ and 2 of 4 HBeAg-), HBV DNA response in 5 (25%) (5 of 16 in HBeAg+ and none in HBeAg-), and HBeAg loss with appearance of anti-HBe in 5 (31.3%) of the 16 HBeAg positive patients. At 76 weeks, 8 (80%) of the 10 patients with normal ALT at 52 weeks relapsed, with normal ALT only in 2 (10%) (1 of 16 HBeAg+ and 1 of 4 HBeAg-), and all 5 patients who had a DNA response at 52 weeks relapsed at 76 weeks and had no DNA response. HBeAg loss with appearance of anti-HBe was seen in 1 (6.3%) of 16 HBeAg-positive patients. None of the patients lost HBsAg.
  
  
  CONCLUSIONS
  The combination of peg-IFN and lamivudine for 52 weeks is not effective for treatment of CHB patients with a failed treatment. New treatment strategies need to be developed.
authors.affiliation: Department of Gastroenterology, G.B. Pant Hospital, New Delhi, 110002, India. sksarin@nda.vanl.net.in
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sarin
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Syed
authors.initials: S
authors.lastname: Hissar
authors.forename: Barjesh C
authors.initials: BC
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D016898:Interferon-alpha; D019259:Lamivudine; D011092:Polyethylene Glycols; D000410:Alanine Transaminase