title: Combination of Peginterferon alpha-2b (12 kDa) and Lamivudine in difficult-to-treat chronic hepatitis B- an Indian experience.
abstract: BACKGROUND
  Treatment strategies for chronic hepatitis B (CHB) using either interferon or Lamivudine can achieve sustained response in 30-40 % in HBeAg positive CHB. Retreatment of treatment failure in CHB and treatment of HBeAg negative patients pose major therapeutic challenge. Because of success story of Peginterferon in hepatitis C and some preliminary data in CHB, we undertook this open-labeled prospective study to study the response of Peginterferon alpha-2b (PegIFN) and Lamivudine combination in patients of CHB.
  
  
  METHODS
  Following 4 groups of patients of CHB with persistently elevated transaminases were treated with Lamivudine 100 mg PO daily and PegIFN 1.5 microg/kg SC once a week- 1) HBeAg negative treatment naive patients- for 12 months 2) HBeAg negative patients who were nonresponsive to at least two treatment regimens for 12 months, 3) HBeAg positive treatment naive patients- for 6 months 4) HBeAg positive patients who were treatment failure at least with two regimens- for 6 months. Patients were tested for LFT, HBeAg, antiHBe, quantitative HBVDNA (only in HBeAg negative CHB) and liver biopsy when possible at inclusion. During treatment period, LFT was tested at monthly interval and HBeAg, antiHBe and HBVDNA (in HBeAg negative CHB) at 3 monthly intervals. End of treatment response (EOR) was assessed at end of treatment period and sustained response (SR) at 6 months post treatment. Treatment response was defined in HBeAg positive patients with normalization of enzymes and disappearances of HBeAg & in antiHBe positive patients with normalization of enzymes and loss of detectable HBVDNA.
  
  
  RESULTS
  Total 25 patients with CHB were included in this study with mean age of 37.9 +/- 4.6 years (range 20-56) and male: female= 11.5:1. 1) In HBeAg negative treatment naive patients, 4/6 patients achieved EOR (66.6%), whereas in 3/6 patients (50%) had SR. 2) In HBeAg negative treatment failure group, 4/5 patients had EOR (80%) and 3/5 patients achieved SR (60%), of which 1 patient lost HBsAg. 3) In HBeAg positive treatment naive patients, 4/5 patients achieved EOR (80%) and 3/5 patients obtained SR (60%). One patient in this group lost HBsAg. 4) In HBeAg positive treatment failure group, 5/9 patients achieved EOR (55.5%), whereas 3/9 patients (33.3%) obtained SR.
  
  
  CONCLUSIONS
  Overall, in difficult-to-treat patients (considering groups 1, 2 & 4- total 20 patients) with combination of PegIFN and Lamivudine, EOR was seen in 13 patients (65%), SR was obtained in 9 patients (45%) and loss of HBsAg was seen in 1 patient (5%).
authors.affiliation: Head Gastroenterology Department, Bombay Hospital and Medical Research Center, Mumbai, India.
authors.forename: Deepak N
authors.initials: DN
authors.lastname: Amarapurkar
authors.forename: Nikhil D
authors.initials: ND
authors.lastname: Patel
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007194:India; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D008111:Liver Function Tests; D008297:Male; D011092:Polyethylene Glycols; D011446:Prospective Studies; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b