[The effect of endotoxemia on gluconeogenesis in livers and kidneys during acute hepatic failure].

OBJECTIVES: To explore the effects of endotoxemia on gluconeogenesis in livers and kidneys during acute hepatic failure. METHOD: Twenty-four healthy male SD rats were randomly divided into four groups (6 rats in each group) and all of them were injected intraperitoneally with solutions: group I with normal saline, group II with 400 mg/kg of D-galactosamine (D-GaLN), group III with 400 mg/kg of D-GaLN plus 50 microg/kg lipopolysaccharide(LPS), and group IV with 400 mg/kg of D-GaLN plus 500 microg/kg LPS. At 6 hours after the administration of different solutions intraperitoneally, blood samples were collected to examine blood urea nitrogen (BUN) and serum creatinine. Realtime PCR was used to study the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the livers and kidneys. RESULTS: No endotoxemia developed in group I or group II but it was evident in group III and group IV. The level of endotoxemia in group IV was higher than in group III (8.05+/-0.43, 3.50+/-2.25, P<0.05). After 6 hours of administration of LPS in group IV, hypoglycemia appeared, and blood glucose was normal in the other three groups. BUN and serum creatinine were all normal in the four groups, except that blood urea nitrogen was elevated in group IV. The mRNA of PEPCK in livers decreased gradually in all the four groups (2.54+/-1.32 vs 1.87+/-0.15 vs 0.91+/-0.13 vs 0.44+/-0.42, P<0.05). In the kidneys there was no change in the expression of PEPCK in group I and group II (0.75+/-0.03 and 0.77+/-0.04, P>0.05), but it increased in group III (0.75+/-0.03 vs 1.63+/-0.86, P<0.05), and decreased in group IV (0.75+/-0.03 vs 0.13+/-0.07, P<0.05). CONCLUSION: During acute hepatic failure severe endotoxemia would damage the function of gluconeogenesis in livers and kidneys by inhibiting transcription of PEPCK and this can induce hypoglycemia.

[Emergence and clinical significance of YMDD and HBeAg-related mutations during lamivudine treatment].

OBJECTIVE: To explore YMDD and HBeAg related mutations of hepatitis B virus and its clinical significance during lamivudine therapy. METHODS: From sera of chronic hepatitis B patients with 9 - 30 months lamivudine therapy, signal-base mutations of YMDD motif, G1896A, A1814C, A1762T and G1764A were analyzed by gene chips technique. RESULTS: In the 102 patients with 18 months in average of lamivudine treatment, 22 were found to have YMDD mutations, including 8 with YMDD and HBeAg related mutants. 3 of the 8 patients had G1896A mutant, 2 had A1814C and the remaining had G1896A + A1814C, A1762T and G1764A, A1762T and G1764A + G1896A. The former 5 patients and signal YMDD mutant patients were HBeAg positive, while the latter 3 with YMDD and HBeAg related multiple mutants were HBeAg negative. One of the three patients with multiple mutants who continued lamivudine treatment 3 months more reversed to YMDD wide-type HBV with accompanying positive HBeAg. CONCLUSIONS: Mutant of YMDD associated with HBeAg related multiple mutations during lamivudine treatment may arise in patients with HBV DNA breakthrough and negative HBeAg. HBV DNA should be detected in the patients with HBeAg seroconversion to exclude the HBeAg related multiple mutations.

Effect of SEN virus coinfection on outcome of lamivudine therapy in patients with hepatitis B.

AIM: Interactions between hepatitis B virus (HBV) and other viral hepatitis infections are well known, whether the newly discovered SEN virus (SENV) has any effect on lamivudine antiHBV activity is unclear. Our aim was to clarify the effect on treatment outcome of coinfection with SEN virus in patients with hepatitis B during lamivudine therapy. METHODS: Nested polymerase chain reaction (PCR) amplification was used to detect SENV-D and SENV-H strains in serum from 45 patients with chronic hepatitis B treated with lamivudine 100 mg daily for 12 mo. HBV DNA load was detected with fluorescence quantitative PCR (FQ-PCR) and YMDD (tyrosine, methionine, aspartate, aspartate) motif mutation of HBV DNA was investigated with cDNA microarray. RESULTS: SENV DNA was detected in 5 of 45(11.1%) cases after 12 mo they received lamivudine treatment. SENV-D and SENV-H were 4.4% and 6.7% respectively. HBV DNA failed to respond to lamivudine therapy in 4 of 5 SENV coinfected patients while only 10 of 40 patients became SENV positive and the difference was statistically significant. Response of ALT and HBeAg to lamivudine had no significant difference between coinfection patients and single HBV infection ones. CONCLUSION: Coinfection with SEN virus in chronic hepatitis B patients may adversely affect the outcome of lamivudine treatment.

[Influence of SEN virus infection on their response to lamivudine in patients with chronic hepatitis B].

OBJECTIVE: To investigate the influence of SEN virus infection on their response to lamivudine in patients with chronic hepatitis B (CHB). METHODS: SEN virus-D and -H DNA were detected in 45 CHB patients who received lamivudine 12 months with nested-PCR, and YMDD motif mutations in HBV DNA were investigated with gene chip. RESULTS: The positive rate of SEN virus DNA was 11.1% (5/45), and there were four out of the five SEN virus DNA positive patients whose HBV DNA was positive, among them, two patients existed YMDD motif mutation. While ten out of the forty SEN virus DNA negative patients appeared HBV DNA positive. The response rate was significant lower in SEN virus-infected patients than that in uninfected patients (chi 2=3.97, P<0.05). CONCLUSION: Coinfection with SEN virus in chronic hepatitis B patients may adversely affect the outcome of treatment with lamivudine