Efficacy and safety of three adefovir-based combination therapies in HBeAg-positive chronic hepatitis B patients with suboptimal response to adefovir monotherapy.

Although high potent nucleos(t)ide analogues are strongly recommended as first-line therapy for chronic hepatitis B (CHB) in China, some patients are still being treated with adefovir disoproxil (ADV), especially those low-income patients whose health insurance could not reimburse the drug cost. Therefore, the management of patients who have failed ADV therapy or who sustained renal damage during ADV therapy remains an important clinical problem in China. This retrospective study aimed to compare the efficacy and safety of lamivudine (LAM), telbivudine (LdT) or entecavir (ETV) add-on strategies to optimize the treatment of patients with prior suboptimal response to ADV monotherapy. A total of 277 eligible patients were included in this study, and the baseline characteristics were similar among the LAM + ADV (n = 116), LdT + ADV (n = 72) and ETV + ADV (n = 89) groups. At week 96, both the proportion of undetectable HBV DNA (81.03% for LAM + ADV, 84.72% for LdT + ADV and 88.76% for ETV + ADV; P = .317) and ALT elevation (5.17% for LAM + ADV, 4.17% for LdT + ADV and 4.49% for ETV + ADV; P = 1.000) were similar among the three groups; also, a significant decline in liver stiffness was observed in each group from baseline to week 96. At week 96, the rate of HBeAg seroconversion was significantly higher in LdT + ADV than in LAM + ADV (26.39% vs 13.79%, P = .031) and ETV + ADV (26.39% vs 10.11%, P = .007). During the 96 weeks, no obvious renal injury was reported in any of the three groups, but an improvement in eGFR was found in LdT + ADV compared with LAM + ADV and ETV + ADV. In summary, all three combination strategies provide good control of virus replication, but the LdT + ADV combination therapy may yield better HBeAg seroconversion and eGFR improvement.

Combination of Lamivudine and adefovir therapy in HBeAg-positive chronic hepatitis B patients with poor response to adefovir monotherapy.

At present, there is no consensus treatment for patients who have poor response to Adevofir dipivoxil (ADV) monotherapy and no ADV-associated mutation. The purpose of this study was to evaluate the effect of a new therapeutic strategy combining Lamivudine (LAM) and ADV in patients with HBeAg-positive chronic hepatitis B (CHB) and poor response to ADV monotherapy. Thirty-one patients with chronic hepatitis B with HBV DNA > or = 10(4) copies/mL after 48 weeks of ADV monotherapy were included and received ADV plus LAM for 24 weeks. Compared with ADV monotherapy, ADV + LAM had an improved response rate at weeks 12 and 24 - compared with baseline, the median decrease in HBV-DNA level at week 12 and 24 were 1.27 and 2.03 log respectively. The virological response (VR) rate (HBV-DNA level <10(3) copies/mL) was 6.5% and 35.5% at weeks 12 and 24, respectively; the biochemical response (BR) rate (normalization of alanine aminotransferase levels) was 67.8% and 100%, respectively; the HBeAg loss rate was 6.9% and 34.5%, respectively; and the seroconversion rate (from HBeAg to HBeAb) was 3.5% and 6.9% respectively. No ADV-associated mutation was detected at baseline. After combination therapy for 24 weeks, no LAM-resistant or ADV-resistant mutations were detected. Only one patient had a mild adverse reaction. In conclusion, optimization of therapy combining LAM and ADV may be a good choice for patients with hepatitis B who have a poor response to ADV monotherapy.

Accumulation of ofloxacin and tosufloxacin in fluoroquinolone-resistant E coli.

AIM: To make sure whether there is a difference in mechanism existed in the resistant E coli strains accumulated hydrophilic fluoroquinolone ofloxacin and hydrophobic fluoroquinoline tosufloxacin. METHODS: Fluoroquinolone accumulation in bacteria and effect of active efflux were measured by fluorescence method. Analysis of outer membrane proteins was made by SDS-PAGE. E coli strains included JF701 and JF703 that are OmpC- or OmpF-deficient mutants of E coli K-12 respectively, and the susceptible strain Ecs and its in-vitro selected resistant strains R2, R256, and clinical resistant isolates R5, R6. RESULTS: Ecs accumulated ofloxacin almost at the same concentration as JF701, but JF703 did about 1/2 of that lower than JF701. However, four resistant strains accumulated ofloxacin about 5 to 7-fold lower than those susceptible strains. On the other hand, there was no significant difference for the accumulation of tosufloxacin between fluoroquinolone-resistant and -susceptible strains. After addition of proton ionophore DNP for 5 min and 10 min, the accumulation of tosufloxacin slowly decreased in E coli strains, whereas the accumulation of ofloxacin was increased, especially in the resistant strains. A good relevance exists between the accumulation increment of ofloxacin and its MIC for each E coli strain after addition of DNP for 5 min and 10 min (r=0.9623 and 0.8006 respectively). Furthermore, both OmpF and OmpC in Ecs, OmpF-deficiency in R2, R256 and OmpC-deficiency in R5, R6 were observed. CONCLUSION: The accumulation of ofloxacin other than tosufloxacin could be reduced by OmpF-deficiency and active efflux, and the latter may be an important factor in the development of resistance to hydrophilic fluoroquinolone in E coli.

[Relationship between HBcAg in the liver and mechanisms of chronic type B hepatitis HBVM in serum].

We detected the presence and distribution of HBcAg in the liver by immunohistochemistry (ABC method) and the presence of HBV-DNA in serum (spot hybridization) and anti-HBe in serum (ELISA) from 59 cases of hepatitis B hospitalized in our hospital, including 47 cases of CAH, 5 cases of CPH, and 7 cases of subacute fulminant hepatitis. 1. HBcAg in the liver was detected in 25 out of 47 cases (53%) of CAH, in 2 out of 5 cases of CPH and in 4 out of 7 cases of subacute fulminant hepatitis. The total percentage was 53% (31/59). 2. There was no positive correlation between HBV replication activity and liver disease activity (P greater than 0.05). Our results did not support the hypothesis that suggests a direct cytopathic effect of HBV. Oppositely, the fact was that the presence, the amount and the patterns of HBcAg in the liver, and the presence of HBV-DNA in serum were predominant in mild CAH compared with those in severe CAH, predominant in CAH without cirrhosis compared with those in CAH with cirrhosis. There was a tendency of inverse correlation between HBV replication activity and liver disease activity. The results above were in line with the concept that HBcAg expressed on the surface of infected hepatocytes may be relevant target for T lymphocyte cytotoxicity. The results have suggested that an immune response to HBV is present, leading to the destruction of most infected cells. 3. There was a positive correlation between HBV-DNA in serum and HBcAg in the liver (P less than 0.005), indicating that HBV-DNA in serum can represent HBV replication.(ABSTRACT TRUNCATED AT 250 WORDS)