Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.653
Peer-review started: May 22, 2014
First decision: June 18, 2014
Revised: July 3, 2014
Accepted: July 25, 2014
Article in press: July 25, 2014
Published online: January 14, 2015
AIM: To observe the effect of response-guided add-on therapy with adefovir (ADV) and lamivudine (LAM) in cirrhotic hepatitis B (CHB) patients.
METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus (HBV) DNA level after 24 wk LAM monotherapy: Arm A (complete response, HBV DNA ≤ 60 IU/mL, n = 49), Arm B (partial response, HBV DNA: 60-2000 IU/mL, n = 31) and Arm C (inadequate response, HBV DNA > 2000 IU/mL, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.
RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24 was associated with maintained viral suppression (undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations (mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/mL. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.
CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.
Core tip: We conducted this prospective cohort study to explore an optimized strategy of adding adefovir (ADV) and lamivudine (LAM) at different time points according to the early virological response, and to observe its association with long-term treatment outcomes in cirrhotic hepatitis B (CHB) patients with compensated cirrhosis. We found that optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of hepatitis B virus DNA and improves liver function in CHB patients with compensated liver cirrhosis.