Tissue-like cultures of rat hepatocytes in study of phase I and phase II drug metabolism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate phase I and phase II enzyme activities in drug metabolism with tissue-like cultures of rat hepatocytes.</p><p><b>METHODS</b>The gel entrapment and spheroid culture of hepatocytes were used as tissue-like cultures and the monolayer culture was used as a control. The metabolism of phenacetin and 7-hydroxycoumarin (7-HC) was evaluated as the activities of phase I and phase II enzymes after incubated in medium for a period of time. The metabolites were assayed by HPLC. The hepatocytes were exposed to beta-naphthoflavone (BNF, 50 micromol x L(-1)) before the phase I and phase II enzyme activities were analyzed.</p><p><b>RESULT</b>In monolayer culture, phase I parameters decreased quickly and did not detected at d 5, and the phase II enzyme activities were not detected at d 7. In other two models of tissue-like cultures, the activities of phase I and phase II enzyme maintained at 32%-50% of the initial value at d 7. Paracetamol formation rates in spheroid culture maintained at 96% of that at d 1. The phase I enzyme activities of the spheroid culture were maintained from d 1 to d 3 at a level of 2.7-3.9-fold higher than the monolayer culture. After exposure to BNF the activities on phase I enzyme increased by about 2.5-fold (P <0.05) in all three culture models, while the increase in phase II enzyme was not significant.</p><p><b>CONCLUSION</b>The gel entrapment culture and spheroid culture are superior to the monolayer culture in maintenance of drug metabolic enzyme activities.</p>

Adefovir dipivoxil in treatment of decompensated liver cirrhosis patients with YMDD mutation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of adefovir dipivoxil in treatment of decompensated liver cirrhosis patients with YMDD motif mutation during lamivudine therapy.</p><p><b>METHODS</b>The disease relapsed in 14 hepatitis B patients with decompensated liver cirrhosis during lamivudine treatment due to the YMDD motif mutation. All 14 patients had positive HVBDNA and active hepatitis, and were evaluated as Child-Pugh Score C (CPS-C). The patients were treated with lamivudine 50 mg/d and adefovir dipivoxil 10 mg/d for 6 months.</p><p><b>RESULTS</b>One patient signed off due to non-hypoxemic hyperlactacidemia; other 13 patients showed decreased serum HBVDNA. All patients had serum HBVDNA < or =10(5) copies/ml and 7 patients had HBVDNA < or =10(4) copies/ml. Six patients regained normal serum ALT level and Child-Pugh scores decreased in all patients.</p><p><b>CONCLUSION</b>Adefovir dipivoxil has satisfied efficacy and safety in treatment of decompensated liver cirrhosis patients with YMDD motif mutation during lamivudine treatment.</p>

Distribution of lamivudine- resistant variants in hepatitis B virus / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To observe the distribution of HBV variants resistant to lamivudine and their relation to clinical manifestations of chronic hepatitis.</p><p><b>METHODS</b>Using direct sequencing, YMDD (tyrosine-methionine-aspartate-aspartate) variants in patients with chronic HBV were detected before and during treatment with lamivudine. A statistical analysis of the distribution of HBV strains resistant to lamivudine was performed.</p><p><b>RESULT</b>Four variant strains existed in patients before lamivudine treatment, 128 variant resistant strains were noted after 6 mouths of lamivudine treatment including 42 YVDD (valine) variants, 20 YIDD (isoleusine) variants and 66 non-YMDD variants. According to the hepatitis severity, 8 patients were mild, 108 moderate and 12 severe. Viral loading was higher and clinical types were more severe in no-YMDD variants.</p><p><b>CONCLUSION</b>Variant strains including strains resistant to lamivudine exist naturally before lamivudine treatment, but lamivudine-resistant ones become more dominant after treatment. Liver inflammation is more severe in non-YMDD group.</p>

Preliminary observation on the efficiency and safety of Lamivudine used in decompensative hepatic cirrhosis (B) accompanied by hypersplenism / 浙江大学学报·医学版

OBJECTIVE: To study the efficacy and safety in patients with decompensative hepatic cirrhosis treated with Lamivudine. METHODS: Eighteen decompensative hepatic cirrhosis (B) (active phage) patients accompanied with hypeersplenism were treated with Lamivudine 100mg po. per day. The total course of treatment was 3 months to 6 months when HBVDNA became negative and HBeAg seroconversion occurred in these patients after Lamivudine treatment. The efficacy and safety in patients were evaluated as follows: HBVDNA were negative, HBeAg seroconversion occurred and hepatic cirrhosis child-stageing changed. The efficacy and safety between treated group and contrast group were compared during treatment with Lamifudine for 1 year and follow-up foe 1 year after completing treatment. RESULTS: The total efficacy of treated group was 27.7% and 71.43% respectively during the phase II trial and the safety was good in these patients. CONCLUSION: The efficacy and safety of Lamivudine are good while it is used in non-registered adaptation of decompensative hepatic cirrhosis with hypersplenism.