BACKGROUNDS/AIMS: Continuation of lamivudine therapy is controversial for patients with chronic hepatitis B when viral breakthrough occurs. Moreover, the effect of continuous lamivudine therapy is unknown in patients with acute exacerbation after viral breakthrough. We assessed clinical course of acute exacerbation after viral breakthrough in patients who continued and discontinued lamivudine therapy. METHODS: Medical records of 109 patients with viral breakthrough during lamivudine therapy were reviewed. Of 40 patients with acute exacerbation (ALT level > 5 x ULN), adefovir dipivoxil was unavailable in 38 patients. These 38 patients (mean age 42.6 years; male/female, 34/6) were divided into continuation (n=21) and discontinuation (n=17) groups. Clinical courses of the 2 groups were compared. RESULTS: During follow-up period (mean, 27 months; range, 6-60 months), ALT levels decreased to < 2 x ULN in 11 patients (52%) of continuation group and 9 patients (53%) of discontinuation group, varied from 2 x to 5 x ULN in 9 (43%) and 5 (29%), respectively, and increased to > 5 x ULN in 1 (5%) and 3 (18%), respectively, with no statistical significance (P=.417). CONCLUSIONS: When acute exacerbation of ALT levels occurs after viral breakthrough during lamivudine administration in patients with compensated chronic hepatitis B, continuation of lamivudine may have no advantage over discontinuation.
Phosphonic Acids/therapeutic use ; Middle Aged ; Male ; Lamivudine/*administration & dosage ; Humans ; Hepatitis B, Chronic/drug therapy/enzymology/*virology ; Hepatitis B virus/*isolation & purification ; Female ; Antiviral Agents/*administration & dosage ; Alanine Transaminase/blood ; Aged ; Adult ; Adenine/analogs & derivatives/therapeutic use ; Acute Disease

<b>OBJECTIVEb>To screen and clone the genes of protein interacting with the N-terminal protein (TP) of hepatitis B virus DNA polymerase.

<b>METHODSb>TP was amplified by polymerase chain reaction (PCR) and TP bait plasmid was constructed by using yeast two-hybrid system 3, then transformed into yeast AH 109. The transformed yeast was mated with yeast Y187 containing liver cDNA library plasmid in 2 x YPDA medium. Diploid yeast was plated on synthetic dropout medium (SD/-Trp-Leu-His-Ade) and that containing X-alpha-GAL for selecting two times and screening. Plasmids were extracted from blue colonies, and sequence analysis was performed by bioinformatics.

<b>RESULTSb>Forty-seven clones were obtained, these clones included human P36956 sterol regulatory element binding protein-1, RNA polymerase II subunit hsRPB7 mRNA, asialoglycoprotein receptor 2, transcript variant 3, ceruloplasmin (ferroxidase), transmembrane 4 superfamily member 2 and 19 of the hypothetical proteins and so on.

<b>CONCLUSIONb>Genes encoding TP interacting proteins in hepatocytes were successfully cloned and the results suggest that TP has a wide variety of biological functions.

Cloning, Molecular ; DNA-Directed DNA Polymerase ; chemistry ; genetics ; metabolism ; Gene Library ; Hepatitis B virus ; enzymology ; genetics ; Humans ; Liver ; metabolism ; Plasmids ; genetics ; Protein Binding ; Receptors, Virus ; genetics ; isolation & purification ; metabolism ; Transformation, Genetic ; Two-Hybrid System Techniques ; Viral Proteins ; chemistry ; genetics ; metabolism

BACKGROUND: Most mutations in the reverse transcriptase (RT) gene of the hepatitis B virus (HBV) are related to resistance to antiviral agents. Cross-sectional studies on the mutations of this gene are rare. Thus, we analyzed the mutation patterns of RT genes and their biochemical parameters. METHODS: From 2009 to 2012, 301 blood specimens from patients with chronic hepatitis B at Daegu Catholic University Medical Center were retrospectively analyzed for the RT gene sequence of HBV, ALT, hepatitis B e antigen (HBeAg), and HBV DNA. The mutation patterns of the RT gene were compared with the biochemical parameters. RESULTS: Of the 301 patients, 100 (33.2%) had no RT gene mutations. The remaining showed the following mutation patterns: rtM204I/V (50.2%), rtL180M (39.2%), and rtA181T/V (19.6%). Combined mutations were found in 146 cases (48.5%). Of these, the combination of amino acid changes at rt180+rt204 (49.3%) was most frequently detected, followed by rt181+rt236 (11.0%) and rt173+rt180+rt204 (9.6%). In the mutated group, HBV DNA and HBeAg positive rates were significantly higher (P<0.05 for both). Phenotypic analysis showed that lamivudine resistance was most frequently detected (34.6%), followed by adefovir resistance (15.6%). Multidrug resistance was detected in 48 cases (15.9%). The adefovir-resistant group had a higher proportion of cases with HBV loads greater than 2,000 IU/mL. CONCLUSIONS: We found correlations between the mutation status of the RT domain and biochemical parameters such as HBV DNA and HBeAg positive rate. The presence of RT gene mutations could therefore be utilized to predict clinical status.
Adenine/analogs & derivatives/therapeutic use ; Antiviral Agents/therapeutic use ; DNA, Viral/analysis ; Drug Resistance, Multiple, Viral ; Drug Resistance, Viral ; Hepatitis B e Antigens/blood ; Hepatitis B virus/*enzymology/isolation & purification ; Hepatitis B, Chronic/drug therapy ; Hospitals, University ; Humans ; Lamivudine/therapeutic use ; Mutation ; Organophosphonates/therapeutic use ; Phenotype ; RNA-Directed DNA Polymerase/*genetics ; Republic of Korea ; Retrospective Studies