Evolution of hepatitis B virus quasispecies during lamivudine-entecavir sequential therapy / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the evolution of HBV quasispecies under the pressures of lamivudine (LAM) - entecavir (ETV) sequential therapy and its clinical significance.</p><p><b>METHODS</b>Consecutive serum samples from 2 patients underwent LAM-ETV sequential therapy were extensively studied for HBV quasispecies composition and evolution, using PCR-cloning-sequencing method. Maximum likelihood trees were built to analyze the genetic relationship between representative sequences. Correlation between HBV quasispecies evolution and serological/virological data was analyzed to determined the clinical significance of the evolution of HBV quasispecies during prolonged nucleotide analog therapy.</p><p><b>RESULTS</b>Virological breakthrough was observed in both patients. Patient I acquired sustained virological response after switching to ETV rescue therapy, whereas Patient II suffered from virological breakthrough after 72 weeks of ETV therapy. Each virological breakthrough was accompanied with the replacement of previous drug susceptible dominant quasispecies with a drug resistant variant, indicating a close correlation between quasispecies composition and drug susceptibility. The rtL180M+S202G+M204V triple mutant, which was most likely a descendant of the LAM resistant rtL180M+M204V variant, was closely correlated with ETV resistant in Patient II.</p><p><b>CONCLUSION</b>Quasispecies composition of HBV is closely correlated with nucleotide analog susceptibility. ETV resistant variant can emerge from a LAM resistant viral population. Dynamic monitoring of HBV quasispecies composition is of great importance during nucleotide analog therapy.</p>

Application of non-bioartificial liver combined with liver transplantation in treating mid-or end-stage chronic serious hepatitis / 中华传染病杂志

Objective To evaluate the application of non-bioartificial liver support system (ALSS) combined with liver transplantation(LT) in treating mid-or end-stage chronic severe hepati- tis.Methods ALSS plus liver transplantation were employed in treating 28 patients with mid-or end- stage chronic severe hepatitis.Clinical data from the patients before and after treatment were collect- ed.The survive rate of ALSS plus LT group were compared with that of medication group 99 cases and medication plus ALSS group 30 cases.The data were analyzed with t test and X~2 test.Results After 57 times ALSS treatment,the serum total bilirubin(TBil),prothromin time(PT),bile acid, blood urea nitrogen(BUN),creatnine(Cr) and ammonia of all the 28 patients got improved(P 0.05).The clinical symptoms and signs of the patients were ameliorated at median 3 d(1～153 d). All patients were bridged to liver transplantation successfully after median 20 d(1～153 d).The 3 and 6 months post-operation survival rate of ALSS plus LT group(71.4%,71.4%) were significantly higher than those in medication group(18.2%,11.1%) and medication plus ALSS group(36.7%, 26.6%)(P