Do different lamivudine-resistant hepatitis B genotypes carry the same risk of entecavir resistance?

Entecavir switch is one of the treatment options for lamivudine-resistant hepatitis B (HBV) patients in Asia. This study examined the outcome of patients with different baseline resistance genotypes in a cohort study. In this study, 14 patients with chronic HBV were treated with entecavir 1 mg/day for 5 years. Enrolment criteria include: documented lamivudine resistant mutations, treatment with adefovir 10 mg/day for at least 24 weeks, and Child-Pugh score <7. Most had previous failed adefovir therapy and compensated cirrhosis of the liver. Clinical outcomes, liver biochemistries, and HBV DNA were monitored regularly. Patients with virologic breakthrough were rescued with add-on adefovir. At the end of the treatment period, the mean HBV DNA fell from 5.92 × 10(6) (baseline) to 3.67 × 10(1) IU/ml. The presence of a HBV polymerase rtM204V mutation at the baseline was found to be the major risk factor for adverse outcomes. Compared to the patients with the rtM204I mutant, patients with the rtM204V mutant had increased risk of virologic breakthrough (80% vs. 0%, P = 0.010) requiring add-on adefovir, slower virologic responses (log rank test, P = 0.0011), failure to reach undetectable HBV DNA levels (60% vs. 0%, P = 0.045), and higher risk of entecavir-resistance (60% vs. 0%, P = 0.045). All the patients with rtM204I and rtA181 mutants had undetectable HBV DNA from 18th month. In summary, lamivudine-resistant HBV patients with the rtM204V mutation have the highest risk of developing entecavir resistance, and entecavir monotherapy should be avoided. Those with the rtM204I and rtA181V mutations may have lower risks, but regular surveillance for viral breakthrough is required.

Patient preferences for hepatitis B therapy.

BACKGROUND: Little is known about patient preferences for selection of chronic hepatitis B (CHB) treatment. This issue is important as it affects the therapeutic choices available for patients and, in the long term, the health of CHB patients. METHODS: The study was a questionnaire-led survey directed at patients attending a CHB follow-up clinic. Patients were asked questions regarding their knowledge on CHB treatment, preferred route and frequency of administration, duration of treatment, cost, adverse events, viral resistance, efficacy and whether treatment options were discussed with doctors. Patients were also asked to rank their priorities when selecting treatment for CHB. In addition, a summary of the profile of current agents was shown to patients who were then asked to select their preferred therapy. Finally, patients were asked questions regarding their willingness to pay for CHB treatment and expectations of treatment. Questionnaires were self-administered and statistical analysis was performed using SPSS (version 10.0). RESULTS: Lamivudine was the best-known drug among patients. Only 30% of patients were treatment-naive. Most patients preferred oral therapy with once-daily dosing and a fixed duration of treatment. Drug efficacy was considered the most important factor in drug selection. When shown the profile of the different drugs available for the treatment of CHB, entecavir was the preferred choice of therapy. The majority of patients were willing to spend no more than S$10 (USD 8) daily for therapy with expectation of cure for their disease. Overall, 92% of patients would follow doctor's recommendations. CONCLUSIONS: Patients' preferences are important in evaluating drug selection for CHB.

Clinical outcomes of lamivudine-adefovir therapy in chronic hepatitis B cirrhosis.

GOALS: To determine the clinical outcome of chronic hepatitis B cirrhotics on antiviral therapy. BACKGROUND: The long-term outcome of hepatitis B cirrhotics on therapy remains to be characterized. METHODS: A large clinic cohort of chronic hepatitis B cirrhotic patients were enrolled in a treatment program of lamivudine ± adefovir therapy. Patients were analyzed for clinical outcomes, and predictors of these outcomes were evaluated by multivariate analysis. Clinical outcomes of ascites, encephalopathy, hepatocellular carcinoma (HCC), and progression in Child-Pugh score, Model for End-stage Liver Disease score, and mortality were assessed. Data were analyzed by Kaplan-Meier graphs, log-rank test, and Cox regression. RESULTS: Of 143 chronic hepatitis B cirrhotics, 19.6% had decompensated cirrhosis. At 5 years, the mean survival was 83.6%, development of ascites, HCC, encephalopathy, and deterioration in Child-Pugh score were 7.0%, 15.9%, 10.8%, and 16.9%, respectively. The overall progression of liver-related complications was 32.8% at 5 years. Multivariate analysis showed that ascites, albumin ≤28 g/L, Child-Pugh score ≥7.9, Model for End-stage Liver Disease score ≥10.9 were significantly associated with liver-related complications. Low albumin and low hepatitis B virus DNA were independent factors for liver-associated mortality. Lamivudine resistance did not affect mortality or liver disease progression. When stratified by Child-Pugh status, the mean survival of those with Child C cirrhosis was worse than Child A and B cirrhosis (P<0.001, log-rank test). Early deaths (≤12 mo) were due to liver failure or sepsis, whereas deaths ≥12 mo were mainly due to HCC. CONCLUSION: Decompensated chronic hepatitis B cirrhotics may suffer early mortality despite antiviral treatment, and therefore should be considered for early liver transplantation.

Health-related quality of life in chronic hepatitis B patients.

UNLABELLED: The relationship between stages of chronic hepatitis B liver disease and health-related quality of life (HRQoL) is an important aspect of the overall management of hepatitis B virus (HBV) infection, yet is not well characterized. Consequently we sought to examine HRQoL in HBV patients, stratified by disease severity, compared with normal controls and hypertensive patients, using the Short Form 36 Health Survey (SF-36) and the EQ-5D self-report questionnaire. Univariate and multivariate analyses were then performed. A total of 432 HBV (156 asymptomatic carriers, 142 chronic hepatitis B, 66 compensated cirrhosis, 24 decompensated cirrhosis, 22 hepatocellular carcinoma, and 22 post-liver transplant) patients, 93 hypertensive patients, and 108 normal controls participated in the study. Multivariate analysis showed that normal controls and asymptomatic carriers had similar SF-36 scores, which were better than those for hypertensive patients, but with development of chronic hepatitis B and compensated cirrhosis, showed a significant decrease in general health and the mental dimension, whereas those with advanced liver disease (decompensated cirrhosis and hepatocellular carcinoma) had significantly lower scores in all components (P < 0.05), indicating that the physical component deteriorates only with advanced liver disease. Similar results were obtained with EQ5D. Post-liver transplant patients had similar HRQoL to patients with decompensated cirrhosis and hepatocellular carcinoma, although there was a trend toward improvement. CONCLUSION: Our results showed that HRQoL in asymptomatic carriers is comparable to those of normal controls and better than hypertensive patients, but deteriorates with disease progression, initially in general health and mental dimensions, but with advanced disease all dimensions are affected.

Public misperceptions about transmission of hepatitis B virus in Singapore.

INTRODUCTION: Hepatitis B virus (HBV) infection is endemic in Asia. Good public knowledge on disease transmission is one way of controlling spread of HBV. We aimed to study the general knowledge on HBV among the general public in Singapore, which is moderately prevalent with HBV. MATERIALS AND METHODS: Before conducting a public education seminar on liver diseases, a 16-point questionnaire survey was conducted among the participants. Misperceptions (if any) were identified, and factors associated with knowledge score were analysed by multivariate analysis. RESULTS: One hundred and ninety-two subjects completed the questionnaire. The mean age was 52 years, 78 (41%) were male, 183 (95%) were Chinese, 17 (9%) were known hepatitis B carriers and 73 (38%) had completed college education. The mean knowledge score was 10.7 (out of a maximum of 16). Most misperceptions were in the category of HBV transmission. At multivariate analysis, having college education was the only independent factor associated with a high knowledge score. CONCLUSION: Although HBV infection is moderately prevalent in Singapore, many misperceptions existed among the general public, especially on the mode of transmission. Better education was related to better knowledge of HBV. Further public education should be targeted to clear the misperceptions identified, and be specifically targeted to the less educated.

Non-invasive models for predicting histology in patients with chronic hepatitis B.

BACKGROUND AND AIM: In contrast to chronic hepatitis C (CHC), few studies had been performed in assessing non-invasive models for predicting significant fibrosis or cirrhosis in chronic hepatitis B (CHB) patients. We aimed to evaluate non-invasive markers for diagnosing significant fibrosis/cirrhosis in patients with CHB, and to evaluate accuracy of models from CHC in CHB patients. PATIENTS AND METHODS: Liver biopsies from consecutive treatment-naïve CHB patients were evaluated histologically by a pathologist blindly, using the Ishak score. Patients were divided randomly into a training (65%) and a validation sets (35%). Markers of fibrosis were evaluated by univariate followed by multivariate analysis in the training set. Area under receiver operating characteristics curve (AUROC) was assessed and validated in the training set. AUROC of aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT) ratio, and AST-platelets ratio index (APRI) (derived from studies from CHC) in diagnosing significant fibrosis/cirrhosis were also assessed. RESULTS: Two-hundred and eighteen CHB patients were evaluated: 83% male, 86% Chinese, 47% having significant fibrosis, 19% having cirrhosis. Platelets were the only factor significantly associated with significant fibrosis and cirrhosis at multivariate analysis but the AUROC was only modest at 0.63 and 0.73, respectively. Models derived from studies from CHC were even less accurate. CONCLUSION: Models with non-invasive markers in predicting histology from CHC patients were unsuitable for CHB patients. No variables consisting of simple and readily available markers were able to predict cirrhosis accurately in patients with CHB.

Misperceptions among patients with chronic hepatitis B in Singapore.

AIM: To identify the misperceptions among CHB patients, as well as to determine the factors associated with better knowledge. METHODS: A telephone interview was conducted on 192 adult CHB patients, who earlier responded to an advertisement for free screening. The questionnaire included items about socio-demographic factors and a 14-item quiz on knowledge of general aspects, transmission, and management of HBV infection. RESULTS: The mean knowledge score on HBV was 10.4/14. Common misperceptions included availability of treatment for HBV infection and early liver cancer, as well as on transmission. Having completed tertiary education was the only independent factor associated with a high knowledge score, after controlling other demographic factors. CONCLUSION: More educational efforts should be focused on patients' misperceptions and target the less educated HBV carriers.