[Tissue-like cultures of rat hepatocytes in study of phase I and phase II drug metabolism].

OBJECTIVE: To investigate phase I and phase II enzyme activities in drug metabolism with tissue-like cultures of rat hepatocytes. METHODS: 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. RESULT: 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. CONCLUSION: The gel entrapment culture and spheroid culture are superior to the monolayer culture in maintenance of drug metabolic enzyme activities.

[Adefovir dipivoxil in treatment of decompensated liver cirrhosis patients with YMDD mutation].

OBJECTIVE: To evaluate the efficacy and safety of adefovir dipivoxil in treatment of decompensated liver cirrhosis patients with YMDD motif mutation during lamivudine therapy. METHODS: 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. RESULTS: 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. CONCLUSION: Adefovir dipivoxil has satisfied efficacy and safety in treatment of decompensated liver cirrhosis patients with YMDD motif mutation during lamivudine treatment.

Efficacy and safety of lamivudine treatment for chronic hepatitis B in pregnancy.

AIM: To evaluate the efficacy and safety of lamivudine treatment of chronic hepatitis B disease in pregnancy. METHODS: The study group was comprised of 38 chronic HBV patients who were diagnosed pregnant during lamivudine treatment and voluntary to continue the same therapy. The control group was from documented patient data in the literatures. We compared the following parameters with those of a control group: anti-HBV efficacy, complications of pregnancy (abortion, preterm birth, neonatal asphyxia, fetal death, and congenital anomaly), incidence of HBV-positive babies and developmental anomalies in pregnant women treated with lamivudine. RESULTS: The blocking rate of lamivudine treatment was significantly higher than that of active vaccine immunization for babies with double-positive (HBsAg/HBeAg) mothers with 30-30-10 mug doses of vaccine (74.07%) and with 30-20-10 mug (64.87%). The natural vertical HBV transmission from mother to infant of "double-positive" mothers was 100% (10/10). No pregnancy complication was noted during the observation period, but in the control group the incidences of pregnancy complication were 16.67% (abortion), 43.02%(preterm), 15.62% (neonatal asphyxia), and 4.49% (fetal death), 10.0% (congenital anomaly). No HBV-positive newborn was detected and no developmental anomaly was found in the study group. CONCLUSION: Lamivudine is helpful to prevent maternal-infant HBV transmission and may reduce the complications of HBV-infected pregnant patients.

[Preliminary observation on the efficiency and safety of Lamivudine used in decompensative hepatic cirrhosis (B) accompanied by hypersplenism]

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.

[Distribution of lamivudine- resistant variants in hepatitis B virus].

OBJECTIVE: To observe the distribution of HBV variants resistant to lamivudine and their relation to clinical manifestations of chronic hepatitis. METHODS: 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. RESULT: 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. CONCLUSION: 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.