Effect of lowering HBV DNA levels by initial antiviral therapy before adding immunomodulator on treatment of chronic hepatitis B.
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.


OBJECTIVE
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.


METHODS
Sixty-three treatment-naive HBeAg-positive patients with histologically proven CHB and alanine aminotransferase (ALT) > 1.2 x upper limit of normal (ULN) received placebo for 4 wk followed by peg-IFN 1.0 mug/kg/wk for next 24 wk (group A, N = 27; age 32 +/- 11 yr; M:F = 25:2) or lamivudine 100 mg per day for 4 wk followed by peg-IFN 1.0 mug/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.
Sarin
Shiv Kumar
SK
Department of Gastroenterology and Hepatology, G.B. Pant Hospital, New Delhi, India.
Sood
Ajit
A
Kumar
Manoj
M
Arora
Anil
A
Amrapurkar
Deepak
D
Sharma
Barjesh Chander
BC
Konar
Ashokananda
A
Chawla
Yogesh Kumar
YK
Jain
Rajendra Kumar
RK
Nanda
Vijay
V
Kumar
Arun
A
Hissar
Syed
S
Lavate
Piramal
P
Lahoti
Deepak
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004279:DNA, Viral / Q000032:analysis / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine