Efficacy of combined therapy in patients with hepatitis B virus-related decompensated cirrhosis

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 HBVrelated 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 inde 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.

Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels

AIM:To evaluate the efficacy and safety of telbivudine(LDT) in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) patients who have high baseline alanine aminotransferase(ALT) levels between 10 and 20 times the upper limit of normal.METHODS:Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 wk.Another forty patients with baseline ALT levels between 2 and 10 times the upper limit of normal were included as controls.We compared the virological,biochemical,serological and side effect profiles between the two groups at 52 wk.RESULTS:By week 52,the mean decrease in hepatitis B virus(HBV) DNA level compared with baseline was 7.03 log10 copies/mL in the high baseline ALT group and 6.17 log10 copies/mL in the control group,respectively(P < 0.05).The proportion of patients in whom serum HBV DNA levels were undetectable by polymerase chain reaction assay was 72.5% in the high baseline ALT group and 60% in the control group,respectively(P < 0.05).In addition,45.0% of patients in the high baseline ALT group and 27.5% of controls became HBeAg-negative,and 37.5% of those in the high baseline group and 22.5% of controls,respectively,had HBeAg seroconversion(P < 0.05) at week 52.Moreover,in the high baseline group,4 out of 40 patients(10%) became hepatitis B surface antigen(HBsAg)-negative and 3(7.5%) of them seroconverted(became HBsAg-positive).Only 1 patient in the control group became HBsAg-negative,but had no seroconversion.The ALT normalization rate,viral breakthrough,genotypic resistance to LDT,and elevations in creatine kinase levels were similar in the two groups over the 52 wk.CONCLUSION:High baseline ALT level is a strong predictor for optimal results during LDT treatment.

Increased intestinal permeability in pathogenesis and progress of nonalcoholic steatohepatitis in rats

AIM: To investigate whether increased intestinal permeability contributes to the pathogenesis and progress of nonalcoholic steatohepatitis by observing its dynamic change in rat models. METHODS: Rat models of nonalcoholic steatohepatitis were established by giving a fat-rich diet. The rats were sacrificed at wk 8, 12 and 16 during the study. Rats fed with normal diet were taken as control. Plasma D-lactate, plasma diamine oxidase, serum lipids and liver transaminases were measured in blood of the femoral artery. Hepatic steatosis and inflammation were assessed by haematoxylin-eosin staining. RESULTS: A rat model of nonalcoholic steatohepatitis was established successfully. Plasma D-lactate level in model group at wk 8, 12 and 16 and diamine oxidase level in model group at wk 12, 16 increased significantly compared with those in control group. There were notable differences of D-lactate and diamine oxidase level in model group between wk 8 and 12 as well as between wk 12 and 16. Serum lipids, liver transaminases and liver injury also increased with disease development. CONCLUSION: Increased intestinal permeability caused by intestinal bacterial overgrowth and endotoxin-induced intestinal destruction exists in rats with nonalcoholic steatohepatitis, which may partially explain the pathogenesis and progress of this disease.