Gene Products, tat ; genetics ; Gene Targeting ; Hepatitis B virus ; genetics ; growth & development ; Humans ; Recombinant Fusion Proteins ; genetics ; Ribonucleases ; genetics ; Transduction, Genetic ; Virus Replication ; drug effects

BACKGROUND/AIMS: Long-term lamivudine therapy can induce the emergence of lamivudine resistant hepatitis B virus (HBV) mutants. Clinically emergence of the mutant is expressed by the reappearance of disappeared HBV DNA in serum. Continued lamivudine treatment has been usually recommended in cases of viral breakthrough. However, the clinical outcome in patients with viral breakthrough is not clear. The aim of this study was to investigate the clinical course of chronic hepatitis B patients after viral breakthrough during lamivudine therapy. METHODS: A total of 74 patients with chronic hepatitis B who showed viral breakthrough after at least 6 months of lamivudine treatment were included in this study. They had positive HBeAg and HBV DNA before treatment. The median follow-up duration after breakthrough was 13 months. RESULTS: After viral breakthrough, only 8 patients (11%) maintained normal ALT levels and 66 patients (89%) showed elevation of ALT. 30 patients (41%) showed acute exacerbation of hepatitis (ALT increase over five-times upper normal limit). These acute exacerbations occurred within three months after breakthrough in 19 patients (63%). In the cases of acute exacerbation, 6 patients showed decompensated progression such as elevation of serum total bilirubin. One of them died of hepatic failure. A predictive factor for acute exacerbation was not found. HBeAg seroconversion occurred in 8 patients after viral breakthrough but their clinical course was highly variable. CONCLUSIONS: Chronic hepatitis B patients who had viral breakthrough during lamivudine therapy should be followed carefully and regularly in mind of potential clinical deterioration. New strategies are needed to manage the cases of acute exacerbation after viral breakthrough.
Adult ; Antiviral Agents/*therapeutic use ; Drug Resistance, Viral ; English Abstract ; Female ; Hepatitis B Virus/drug effects/growth & development ; Hepatitis B, Chronic/drug therapy/*virology ; Human ; Lamivudine/*therapeutic use ; Male ; Middle Aged

<b>OBJECTIVEb>To investigate the changes in serum hepatitis B viral load (HBV DNA) and transformer growth factor-β(1)(TGF-β1) in patients with chronic hepatitis B after entecavir treatment and evaluates the therapeutic effect of entecavir.

<b>METHODSb>Sixty-three patients with chronic hepatitis B were randomly assigned into entecavir group (n=33) and control group (n=30). The entecavir group consisted of 9 mild, 17 moderate, and 7 severe cases, all treated with oral entecavir (0.5 mg daily) and general hepatoprotective drugs; the control group, consisting of 13 mild, 12 moderate and 5 severe cases, was treated with the hepatoprotective drugs only. Serum HBV DNA and TGF-β(1)were determined before and at 3 and 6 months during the treatment.

<b>RESULTSb>Entecavir treatment reduced serum HBV DNA load in all the cases in entecavir group, and the difference was statistically significant between the levels measured at 3 and 6 months (P<0.05). The treatment also resulted in decreased serum TGF-β(1)levels in moderate and severe cases, and the severe cases showed a significant TGF-β(1)reduction after a 6-month treatment (P<0.05).

<b>CONCLUSIONb>Entecavir can lower serum HBV DNA load levels in patients with chronic hepatitis B. Entecavir is also effective to reduce serum TGF-β(1)levels in moderate and severe cases, especially in the latter.

Adult ; Aged ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B virus ; drug effects ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Middle Aged ; Serum ; metabolism ; Transforming Growth Factor beta1 ; blood ; Viral Load ; Young Adult

<b>OBJECTIVESb>By culturing primary early (8 to 12-weeks-old) human fetal hepatocytes with different conditions, to study the status of cell susceptibility to HBV.

<b>METHODSb>During primary culture of 10-weeks-old human fetal hepatocytes with serum-free medium adding different differentiation-induced ingredients, to inoculate cell with HBV at certain time. Cell shape, function and markers of HBV infection are measured.

<b>RESULTSb>6 days after seeding, markers of mature hepatocytes are observed in cells cultured with 2.5mmol/L phenobarbital sodium, and these cells show susceptibility to HBV. Other ingredients cannot render hepatocytes susceptible to HBV.

<b>CONCLUSIONb>Phenobarbital sodium induces differentiation and susceptibility to HBV in primary culture of early human fetal hepatocytes.

Cell Differentiation ; drug effects ; Cells, Cultured ; Female ; Fetus ; virology ; Hepatitis B virus ; growth & development ; Hepatocytes ; cytology ; physiology ; virology ; Humans ; Phenobarbital ; pharmacology ; Pregnancy ; Pregnancy Trimester, First

<b>OBJECTIVEb>To observe the anti-HBV activity of Carboxymethyl Pachymaram (CMP) on the culturing of 2.2.15 cell line.

<b>METHODSb>Concentrations of 20.0 g/L, 12.0 g/L, 6.0 g/L, 3.0 g/L, 1.5 g/L of CMP were used to evaluate its toxicity to the cell line and the inhibition rates of the secretion of HBsAg and HBeAg in the cultured 2.2.15 cell line.

<b>RESULTSb>Experiments showed that the mean half toxicity concentration of CMP for 2.2.15 cell line was 13.6 g/L and concentration for 50% inhibition of the secretion of HBsAg and HBeAg were 4.45 g/L, 5.61 g/L and TI were 3.06 and 2.42. CMP showed stronger effect on anti-HBV than aciclovir.

<b>CONCLUSIONb>CMP has good inhibitory effect on the secretion of HBsAg and HBeAg on cultured cell line 2.2.15.

Antiviral Agents ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Glucans ; pharmacology ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B e Antigens ; metabolism ; Hepatitis B virus ; drug effects ; growth & development ; immunology ; Humans ; Time Factors

BACKGROUND/AIMS: The clinical outcome of patients with a partial virological response (PVR) to entecavir (ETV), in particular nucloes(t)ide analogue (NA)-experienced patients, has not been thoroughly investigated. The aim of the present study was to assess long-term outcomes in NA-naive and NA-experienced chronic hepatitis B patients with a PVR to ETV. METHODS: Chronic hepatitis B patients treated with ETV (0.5 mg/day) for at least 1 year were enrolled retrospectively. PVR was defined as a decrease in hepatitis B virus (HBV) DNA titer of more than 2 log10 IU/mL, yet with residual serum HBV DNA, as determined by real time-polymerase chain reaction, at week 48 of ETV therapy. RESULTS: A total of 202 patients (127 NA-naive and 75 NA-experienced, male 70.8%, antigen positive 53.2%, baseline serum HBV DNA 6.2 +/- 1.5 log10 IU/mL) were analyzed. Twenty-eight patients demonstrated a PVR. The PVR was associated with a high serum HBV DNA titer at baseline and at week 24. Virological response (< 60 IU/mL) was achieved in 46.2%, 61.5%, 77.6%, and 85% of patients with PVR at week 72, 96, 144, and 192, respectively. Resistance to antivirals developed in two NA-experienced patients. Failure of virological response (VR) in patients with PVR was associated with high levels of serum HBV DNA at week 48. CONCLUSIONS: Patients with PVR to ETV had favorable long-term virological outcomes. The low serum level of HBV DNA (< 200 IU/mL) at week 48 was associated with subsequent development of a VR in patients with PVR to ETV.
Adult ; Antiviral Agents/adverse effects/*therapeutic use ; Biomarkers/blood ; DNA, Viral/blood ; Drug Resistance, Viral ; Female ; Guanine/adverse effects/*analogs & derivatives/therapeutic use ; Hepatitis B virus/*drug effects/genetics/growth & development ; Hepatitis B, Chronic/diagnosis/*drug therapy ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Viral Load

Adult ; Cell Differentiation ; drug effects ; Cells, Cultured ; DNA, Viral ; analysis ; Female ; Fetus ; virology ; Hepatitis B virus ; genetics ; growth & development ; isolation & purification ; Hepatocytes ; cytology ; physiology ; virology ; Humans ; Nucleic Acid Hybridization ; methods ; Phenobarbital ; pharmacology ; Pregnancy ; Pregnancy Trimester, First

<b>OBJECTIVEb>To study the mechanism of signal transduction in anti-HBV action of IFN-alpha.

<b>METHODSb>The HBV DNA in HepG 2.2.15 cell line supernatant with/without IFNalpha-2b were monitored by fluorescence real-time quantitive PCR. STAT1, STAT2, ISGF3-gamma, PKR, 2'5'-OAS mRNA levels from HepG 2 and HepG 2.2.15 cell lines that were treated with/without IFNalpha-2b at different times were detected by semi-quantitive RT-PCR. And the ISGF3-gamma protein was detected by Western blot. Then, these items were detected again after inhibiting the JAK-STAT pathway with genistein.

<b>RESULTSb>The HBV DNA in 2215 supernatant that were treated with IFNalpha-2b for 8 hours decreased 0.72 log 10 copies/ml. But the basal levels of DNA in cells pretreated with genistein? followed by IFNalpha-2b did not decrease. The STAT1, STAT2, ISGF3-gamma, 2'5'-OAS, PKR mRNA levels were upregulated by IFNalpha-2b. The same phenomena were observed with STAT1, STAT2, ISGF3-gamma mRNA when pretreated with genistein then treated with IFNalpha-2b, but the levels of 2'5'-OAS, PKR mRNA were decreased in this situation. The expression of the protein of ISGF3-gamma was also augmented by IFNalpha-2b, and was blocked by genistein.

<b>CONCLUSIONb>The JAK-STAT pathway seems to be a critical pathway in IFNalpha-2b action against HBV? and ISGF3 is most probably a key factor of the route.

Antiviral Agents ; pharmacology ; Blotting, Western ; Cell Line, Tumor ; DNA, Viral ; genetics ; isolation & purification ; Gene Expression Regulation, Neoplastic ; drug effects ; Hepatitis B virus ; drug effects ; genetics ; growth & development ; Humans ; Interferon-Stimulated Gene Factor 3 ; genetics ; metabolism ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; genetics ; metabolism ; Interferon-alpha ; pharmacology ; Polymerase Chain Reaction ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; STAT1 Transcription Factor ; genetics ; metabolism ; STAT2 Transcription Factor ; genetics ; metabolism ; Signal Transduction