Original Contribution
The American Journal of Gastroenterology (2007) 102, 96–104; doi:10.1111/j.1572-0241.2006.01006.x
Effect of Lowering HBV DNA Levels by Initial Antiviral Therapy Before Adding Immunomodulator on Treatment of Chronic Hepatitis B
Shiv Kumar Sarin MBBS, MD, DM1, Ajit Sood MBBS, MD, DM2, Manoj Kumar MBBS, MD, DM1, Anil Arora MBBS, MD, DM3, Deepak Amrapurkar MD, DN4, Barjesh Chander Sharma MBBS, MD, DM1, Ashokananda Konar MD, MRCP5, Yogesh Kumar Chawla MBBS, MD, DM6, Rajendra Kumar Jain MD, DM7, Vijay Nanda MD, DM, MRCP (UK)8, Arun Kumar MD, DM9, Syed Hissar MBBS1, Piramal Lavate MD, DM10, Deepak Lahoti MBBS, MD, DM11 and the National Collaborative Group on Hepatitis B, India.
- 1Department of Gastroenterology and Hepatology, G.B. Pant Hospital, New Delhi, India
- 2Department of Gastroenterology and Hepatology, Dayanand Medical College and Hospital, Ludhiana, India
- 3Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India
- 4Bombay Hospital, Mumbai, India
- 5Peerless Hospital and B.K. Roy Research Centre, Kolkata, India
- 6Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
- 7Department of Gastroenterology, Gandhi Medical College and Associated Hospital, Bhopal, M.P., India
- 8Life Line Hospital, Jalandhar, India
- 9Pushpawati Singhania Research Institute, Sheikh Sarai, New Delhi, India
- 10Gastrointestinal Endoscopy, Jahangir Hospital and Medical Centre in Association with Apollo Hospitals, Pune, India
- 11Department of Gastroenterology, Railway Hospital, New Delhi, India
Correspondence: Dr SK Sarin, MD, DM FNA, FNASc, Room No. 201, Academic Block, Department of Gastroenterology, G.B. Pant Hospital, New Delhi 110002, India.
Received 29 April 2006; Accepted 24 July 2006.
Abstract
BACKGROUND:
Lower hepatitis B virus DNA (HBV DNA) levels are associated with better responses in chronic hepatitis B (CHB). It is unclear whether an initial phase of antiviral treatment to lower HBV DNA levels before adding immunomodulator therapy is more effective than the strategy of using immunomodulators from the beginning.
AIM:
The aim of the study was to compare the efficacy of lamivudine followed by pegylated-interferon (peg-IFN) therapy with placebo followed by peg-IFN therapy in HBeAg-positive CHB patients.
PATIENTS AND METHODS:
Sixty-three treatment-naive HBeAg-positive patients with histologically proven CHB and alanine aminotransferase (ALT) > 1.2 
upper limit of normal (ULN) received placebo for 4 wk followed by peg-IFN 1.0 
g/kg/wk for next 24 wk (group A, N = 27; age 32 
11yr; M:F = 25:2) or lamivudine 100 mg per day for 4 wk followed by peg-IFN 1.0 g/kg/wk for next 24 wk (group B, N = 36; age 32.5 10.5 yr; M:F = 31:5). Patients were followed for next 24 wk after completion of treatment. Biochemical and virologic responses were assessed at weeks 4, 28, and 52 and analysis was done on intention-to-treat basis.
RESULTS:
At wk 4, mean SD of log change in DNA from baseline was 0.2594 1.7873 in group A and 1.2186 1.6347 in group B, respectively (P = 0.032). At week 28, undetectable HBV DNA was seen in eight (29.6%) and 16 (44.4%) patients in groups A and B, respectively (P = 0.298). At week 28, HBeAg loss occurred in eight (29.6%) in group A and 15 (41.7%) in group B (P = 0.43). Six months posttherapy, at week 52, undetectable HBV DNA was seen in four (14.8%) and 18 (50%) in groups A and B, respectively (P = 0.028) and HBeAg loss was maintained in four (14.8%) and 14 (38.9%) (P = 0.05) patients. Normal ALT was seen in five (18.5%) and 10 (27.8%) at week 28 (P = 0.552) and five (18.5%) and 13 (36.1%) at week 52 (P = 0.159) in groups A and B, respectively. There was a significant correlation among achievement of HBeAg loss, anti-HBe appearance, and undetectable HBV DNA levels at week 28 (P = 0.008) and 52 (P < 0.001) and HBV DNA levels at week 4.
CONCLUSIONS:
The strategy of using an antiviral initially to decrease HBV DNA levels before adding an immunomodulatory agent leads to improved sustained virological response as compared with using immunomodulator from the start.
