Published online Jun 14, 2013. doi: 10.3748/wjg.v19.i22.3481
Revised: March 23, 2013
Accepted: March 28, 2013
Published online: June 14, 2013
AIM: To investigate the efficacy and safety of combined de novo lamivudine (LAM) and adefovir dipivoxil (ADV) therapy in hepatitis B virus (HBV)-related decompensated liver cirrhosis patients.
METHODS: One hundred and forty patients with HBV-related decompensated cirrhosis were recruited, 70 patients were treated with combined LAM and ADV de novo therapy, and the other 70 patients were treated with LAM alone as controls. The follow-up period was 144 wk. All patients with LAM resistance were shifted to ADV.
RESULTS: The percentage of HBV-related decompensated cirrhosis patients with undetectable HBV DNA in de novo combination group was 51.6% (33/64), 84.2% (48/57), and 92.3% (49/53) by weeks 48, 96, and 144, respectively. In monotherapy group, HBV DNA negativity rate was 46.1% (30/65), 56.1% (32/57), and 39.2% (20/51) by weeks 48, 96 and 144, respectively. There was a significant difference between the two groups by weeks 96 and 144 (P = 0.012 and 0.001). The hepatitis B e antigen seroconversion rate was 28.1% (9/32), 40.0% (12/30), and 53.6% (15/28) in the combination group by weeks 48, 96 and 144, respectively, and 24.2% (8/33), 31.0% (9/29), and 37.0% (10/27) by weeks 48, 96 and 144, respectively, in monotherapy group. A total of 68.6% (44/64), 84.2% (48/57), and 92.5% (49/53) patients achieved alanine aminotransferase (ALT) normalization by weeks 48, 96 and 144, respectively in the combination group. In monotherpy group, the ALT normalization rate was 64.6% (42/65) by week 48, 73.7% (42/57) by week 96, and 80.4% (41/51) by week 144. No patients in the combination group exhibited detectable resistance for at least 144 wk. The cumulative resistance rate in monotherapy group at weeks 48, 96, and 144 was 20.0%, 36.8%, and 56.9%. Both combination group and monotherapy group demonstrated an improvement in Child-Turcotte Pugh and Model for End-Stage Liver Disease scores at weeks 48, 96, and 144. All patients tolerated both combination and monotherapy. The ceratinine levels and glomerular filtration rate remained normal in all patients during the follow-up period.
CONCLUSION: In HBV-related decompensated liver cirrhosis patients, the combined de novo LAM and ADV therapy is more efficacious and safer compared to LAM alone.
Core tip: Present treatment guidelines advocate oral nucleos(t)ide analogues in decompensated chronic hepatitis B (CHB) patients. Studies with lamivudine (LAM) have demonstrated decreased mortality and improved liver function in CHB decompensated patients. However, LAM resistance mutations emerging during monotherapy can negate therapeutic benefit. Adefovir dipivoxil had no cross resistance with LAM. Consistent with outcomes in patients with LAM-resistance, no patient in de novo combination therapy group showed detectable resistance up to 144 wk in this study. The de novo combination therapy markedly improved liver function, reduced Child-Turcotte Pugh and Model for End-Stage Liver Disease scores in hepatitis B virus-related decompensated cirrhosis patients.