ABSTRACT
INTRODUCTION: Among the available nucleos(t)ide analogues adefovir dipivoxil (ADV) is relatively cheap and widely used in rural area in China. However, there are insufficient data on recommendation for patients with suboptimal response to ADV after 48 weeks of treatment in order to reduce the resistance rate in the long term. The aim of this study was to compare the efficacy and safety of LAM add-on combination therapy versus ETV monotherapy for patients with suboptimal response to ADV. MATERIAL AND METHODS: 136 patients with suboptimal response to ADV were randomly assigned to the add-on LAM with ADV combination therapy (68 patients) group and the ETV monotherapy (68 patients) group. Patients in the add-on group were prescribed 100 mg LAM and 10 mg ADV per day, while the monotherapy group received 0.5 mg ETV per day for 48 weeks. Tests for liver and kidney function, HBV serum markers, HBV DNA load, were performed every 3 months. RESULTS: The mean patient age in LAM add-on group and ETV monotherapy was 38.59 ± 7.65 and 37.56 ± 8.67 years respectively. The HBV DNA undetectable rate in the LAM add-on group and the ETV group were not significant difference at week 4, 12 and 24 (P > 0.05). However, the HBV undetectable rate in the ETV group was higher than that in the LAM add-on group at week 36 and 48 (P = 0.043 for week 36 and P = 0.038 for week 48). There was no significant difference both for HBeAg loss and HBeAg seroconversion between two groups (P > 0.05) at 48 weeks. Meanwhile, our study also demonstrated that the mean eGFR levels in LAM add-on group was decreased from 99.6 ± 8.71 at baseline to 86.4 ± 9.83 at the end of 48 weeks, which was significantly higher than that in the ETV monotherapy group (P < 0.05). 8.8% of patients in LAM add-on group experienced eGFR reduction by 20-30% from baseline at 48 weeks. No patients developed hyposphosphatemia in our study. CONCLUSION: Our study clearly showed that switch to ETV monotherapy was the more effective and more safe than that of LAM add-on combination therapy for patients with suboptimal response to ADV.
Subject(s)
Adenine/analogs & derivatives , Antiviral Agents/therapeutic use , Drug Substitution , Guanine/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Lamivudine/therapeutic use , Organophosphonates/therapeutic use , Adenine/adverse effects , Adenine/therapeutic use , Adult , Antiviral Agents/adverse effects , Biomarkers/blood , China , Drug Therapy, Combination , Female , Guanine/adverse effects , Guanine/therapeutic use , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/diagnosis , Humans , Lamivudine/adverse effects , Male , Middle Aged , Organophosphonates/adverse effects , Prospective Studies , Time Factors , Treatment Outcome , Viral LoadABSTRACT
Five strains of fungi and 18 strains of bacteria were isolated from the soil and horse manure with cellulose as the sole carbon source. Among them, two fungal, F9 and F13, and two bacterial, B16 and B21, showed the highest filter paper activities, which were 7.79 U g-1, 9.84 U g-1, 7.34 U g-1 and 9.68 U g-1, respectively. Four microbial systems, designed as FH1 (F13+B21), FH2 (F13+B16+B21), FH3 (F9+B16+B21) and FH4 (F13+F9+B16+B21) were developed. The fermentation studies showed that the filter paper activity of the composite microbial system FH3 was higher than the others, which was 21.34 U g-1. The medium with bran and filter paper as the carbon source and peptone as nitrogen source was optimal and the maximum cellulase activity was reached at 30~35ºC and pH 6.0~6.5 when FH3 was incubated for 48 h. The enzymatic reaction conditions were estimated at 45~55 ºC, pH 4.5~5.5 and the thermal stability temperature was up to 60 ºC.