Efficacy of 3 years of adefovir monotherapy in chronic hepatitis B patients with lamivudine resistance.

AIM: To study the effect of rescue monotherapy with adefovir (ADV) in patients with chronic hepatitis B (CHB) who developed drug resistance to lamivudine (LAM). METHODS: A total of 76 treated CHB patients with resistance to LAM were enrolled in the present study. The patients' baseline characteristics, such as age, gender, blood tests and hepatitis B virus (HBV) DNA were collected; therapy duration and the response of each patient were also recorded. ADV monotherapy was set as the observation group A. Twenty-four patients with LAM resistance, who were set as group B, accepted combined therapy with LAM + ADV. Patients were followed up at 0, 12, 24, 52, 104 and 156 wk. Hepatitis B surface antigen status, hepatitis B e antigen (HBeAg)/anti-HBe status, HBV DNA level and biochemical indexes were monitored. Sequencer of HBV polymerase gene was performed on the ABI 3730 automated sequencer. If no desired effects had been achieved during the course of treatment, patients' choices were also taken into account. The control group was tested at the same time. RESULTS: In the two groups, 27 cases developed viral breakthrough after LAM treatment response. The remaining 49 cases underwent biochemical rebound accompanied by rtM204I/V or rtL180M mutation. In group A, 52 cases finished 156 wk of ADV monotherapy; of whom, 36 cases were HBeAg positive and 16 HBeAg negative. In patients whose baseline HBV DNAs were 10(3)-10(5) copies/mL, 88.8% of patients' HBV DNAs were lower than the lower test limit (10(3) copies/mL) after 12 to 156 wk of ADV treatment. In patients whose baseline HBV DNAs were ≥ 10(6) copies/mL, 41.1%-47.0% of patients' HBV DNAs were lower than the lower test limit after the same course of ADV therapy (χ(2) were 4.35-5.4, 41.1%-47.0% vs 88.8% group 10(3)-10(5) copies/mL, P < 0.01). In group A, seroconversion of HBeAg developed in 8 of 36 cases (22.2%). In group B, 24 cases finished 156 wk of LAM + ADV; of whom, 17 cases were HBeAg positive and 7 HBeAg negative. In patients whose baseline HBV DNAs were 10(3)-10(5) copies /mL, 81.8% of patients' HBV DNAs were lower than the lower test limit (10(3) copies/mL) after 12 to 156 wk of treatment. In the patients whose baseline HBV DNAs were ≥ 10(6) copies/mL, 46.1%-53.8% of patients' HBV DNAs were lower than the lower test limit after the same course of LAM + ADV therapy (χ(2) were 4.1-5.0, 46.1%-53.8% vs 81.8% group 10(3)-10(5) copies/mL, P < 0.05-0.01). In group B, 4 of 17 cases (23.5%) developed seroconversion of HBeAg. Treatment outcomes in groups A and B were comparable. CONCLUSION: In both group A and B, the ratios of virological response have similar efficacy in patients with lower baseline HBV DNAs.

[Predictors and scoring system for sustained complete response to conventional interferon-alpha therapy on chronic hepatitis B].

OBJECTIVE: To establish a predictive scoring system which may serve for the prediction of sustained response to conventional interferon-alpha (IFN-alpha) treatment on chronic hepatitis B. METHODS: A total of 474 IFN-alpha treated hepatitis B virus e antigen (HBeAg)-positive patients were enrolled in the present study. The patients' baseline characteristics, such as age, gender, aminotransferases, activity grading (G) of intrahepatic inflammation, score (S) of liver fibrosis, hepatitis B virus (HBV) DNA and genotype were evaluated; therapy duration and response of each patient at the 24th wk after cessation of IFN-alpha treatment were also recorded. A predictive scoring system for a sustained complete response (CR) to IFN-alpha therapy was established based on genetic algorithm. About 10% of the patients were randomly drawn out as the test set. Responses to IFN-alpha therapy were divided into CR, partial response (PR) and non-response (NR). The mixed set of PR and NR was recorded as PR + NR. RESULTS: For the scoring system, the sensitivity and specificity were 78.8% and 80.6%, respectively. CONCLUSION: This SCR scoring system has satisfying prediction efficiency and is easily employed in clinical practice. With this scoring system, practitioners can propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.

Precise prediction model and simplified scoring system for sustained combined response to interferon-alpha.

AIM: To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-alpha (IFN-alpha) treatment. METHODS: A total of 474 IFN-alpha treated hepatitis B virus e antigen (HBeAg)-positive patients were enrolled in the present study. The patients' baseline characteristics, such as age, gender, blood tests, activity grading (G) of intrahepatic inflammation, score (S) of liver fibrosis, hepatitis B virus (HBV) DNA and genotype were evaluated; therapy duration and response of each patient at the 24th wk after cessation of IFN-alpha treatment were also recorded. A predictive algorithm and scoring system for a sustained combined response (CR) to IFN-alpha therapy were established. About 10% of the patients were randomly drawn as the test set. Responses to IFN-alpha therapy were divided into CR, partial response (PR) and non-response (NR). The mixed set of PR and NR was recorded as PR+NR. RESULTS: Stratified by therapy duration, the most significant baseline predictive factors were alanine aminotransferase (ALT), HBV DNA level, aspartate aminotransferase (AST), HBV genotype, S, G, age and gender. According to the established model, the accuracies for sustained CR and PR+NR, respectively, were 86.4% and 93.0% for the training set, 81.5% and 91.0% for the test set. For the scoring system, the sensitivity and specificity were 78.8% and 80.6%, respectively. There were positive correlations between ALT and AST, and G and S, respectively. CONCLUSION: With these models, practitioners may be able to propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.

[Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of liver failure in rat].

OBJECTIVE: To investigate the changes in serotonin (5-HT) and noradrenaline (NA) in hepatic encephalopathy as a result of acute and chronic liver failure in rat. METHODS: One hundred and ten Sprague-Dawley (SD) rats were randomly divided into groups of normal control (n=20), experimental group of acute liver failure (ALF) encephalopathy (n=45), and experimental group of chronic liver failure (CLF) encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA dosage was added or withheld according to the change in weekly body weight measurement. Animals were sacrificed and venous blood specimens were obtained after successful replication of model, and 5-HT, NA, ammonia, parameters of liver function were determined, and liver and brain were studied pathologically. RESULTS: The experiment showed that the liver functions of rats in groups ALF encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(P<0.05 or P<0.01). The clinical manifestations, liver and brain pathologies were identical to those of ALF and CLF encephalopathy. The values of 5-HT were increased in groups ALF encephalopathy and CLF encephalopathy [(16.06+/-1.08) micromol/L and (15.32+/-1.48) micromol/L] compared with the normal group [(2.75+/-0.26) micromol/L, both P<0.01], while the value of NA decreased in the group of CLF encephalopathy [(94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,P<0.05]. CONCLUSION: The levels of 5-HT are elevated in the groups of ALF encephalopathy and CLF encephalopathy. The content of NA decreases remarkably in CLF encephalopathy.

[Influence of plasma replacement on the hepatic failure with infection].

OBJECTIVE: To investigate the influence of artificial liver support system on severe hepatic failure with infection, 37 cases of severe hepatic failure and 80 cases times of plasma replacement were analyzed. METHODS: The volume of plasma replacement was 2,000-2,600 ml/time. Japanese Plasauto-iQ Blood Purifying Device was used. Blood samples were observed before and after plasma replacement to determine liver function and prothrombin time. PBMCs were isolated and cultured, and the supernatants were collected to determine the levels of interleukin-10 (IL-10), IL-12 and gamma-interferon (gamma-IFN). RESULTS: Before plasma replacement, 32 cases of 80 case times had infection, 5 cases of them had fever, the temperature was 37.5-38.0 centigrade. Four cases of them were fungus infection, 1 case was lung infection. After plasma replacement, liver function was improved, temperature was normal infection was controlled. The levels of IL-10, IL-12 and gamma-IFN in supernatants before and after plasma replacement were significantly higher than normal control, and the IL-10 level after plasma replacement was markedly higher than that before plasma replacement. The levels of IL-12 and gamma-IFN after plasma replacement were higher than plasma replacement, but they didn't reached statistic difference. CONCLUSION: Plasma replacement might be helpful to control infection and therefore to stabilized the hepatic failure.