Alex Yui Hui

Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma

Background: Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients. Patients and methods: Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of α fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy. Results: In total, 426 patients were followed up for 1664 person years; median 225 (range 12–295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14–236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39–23.89; p<0.001) and 2.84 (95% CI 1.05–7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period. Conclusion: Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.

Identification of Chronic Hepatitis B Patients without Significant Liver Fibrosis by a Simple Noninvasive Predictive Model

OBJECTIVE:Histological assessment of liver fibrosis is important in the management of chronic hepatitis B (CHB) infection but poorly accepted by patients because of its invasiveness. The aim of this study was to develop a noninvasive model to assess liver fibrosis in CHB patients using clinical and routine laboratory data.PATIENTS AND METHODS:This was a retrospective study on 235 treatment-naïve viremic CHB patients. Univariate analysis of data from the training cohort (n = 150) followed by multivariate logistic regression were performed to identify independent predictors of significant fibrosis and generate predictive models. The models were validated with the remaining patients or validation cohort (n = 85) and by receiver operating characteristics (ROC) analysis.RESULTS:Body mass index (BMI), platelet count, serum albumin, and total bilirubin levels were identified as independent predictors of bridging fibrosis or cirrhosis (Ishak stage 3–6). ROC analysis was performed using the predictive probabilities derived from the regression models. The area under the ROC curve of the best model was 0.803 (95% CI: 0.729–0.878) for the training cohort, 0.765 (95% CI: 0.644–0.885) for the validation cohort, and 0.791 (95% CI: 0.728–0.854) for the entire cohort. Using the low cut-off probability of 0.15, significant fibrosis could be excluded in 83 patients of the total patient population (negative predictive value 0.92).CONCLUSIONS:Our noninvasive model comprising BMI and three routine laboratory tests was accurate in predicting absence of significant fibrosis. Application of this model could provide useful additional information on the stage of disease, guide future management decisions, and potentially decrease the need for liver biopsy in some CHB patients.

Hepatitis B Virus Genotype C Takes a More Aggressive Disease Course Than Hepatitis B Virus Genotype B in Hepatitis B e Antigen-Positive Patients

ABSTRACT One hundred forty-six hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were followed up for 32 ± 13 months. All six patients with hepatocellular carcinoma had hepatitis B virus (HBV) genotype C. Disease activity was greater in patients infected by HBV genotype C than in those infected by HBV genotype B in the HBeAg-positive phase but not after HBeAg seroconversion.

Validation of the NAFLD Fibrosis Score in a Chinese Population With Low Prevalence of Advanced Fibrosis

OBJECTIVES:Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. This study aimed to validate the NAFLD fibrosis score in the Chinese population.METHODS:NAFLD patients were prospectively recruited for liver biopsy and blood tests. The NAFLD fibrosis score was calculated as −1.675 + 0.037 × age (yr) + 0.094 × BMI (kg/m2) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio–0.013 × platelet (×109/L)−0.66 × albumin (g/dL). Advanced fibrosis was defined as stage 3 to 4 fibrosis.RESULTS:One hundred sixty-two patients (age 46 ± 10 yr, male 59%) were included in the study. Advanced fibrosis was found in 18 (11%) patients. Only 11 of 128 patients with the NAFLD fibrosis score below the proposed low cutoff point (<−1.455) were under-staged, resulting in a high negative predictive value of 91%. Only two patients exceeded the proposed high cutoff point (>0.676), but neither had advanced fibrosis. If the NAFLD fibrosis score was implemented in the Chinese population, 79% of liver biopsies could be avoided.CONCLUSIONS:The NAFLD fibrosis score has high negative predictive value in excluding advanced fibrosis in the Chinese population, and can reduce the burden of liver biopsy in the vast majority of cases. Since there were few cases of advanced fibrosis in this cohort, this study had limited power in validating the high cutoff point.

Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease.

Non‐alcoholic fatty liver disease is prevalent in affluent countries and is strongly associated with metabolic syndrome.

Survival and prognostic indicators in patients with hepatitis B virus-related cirrhosis after onset of hepatic decompensation.

Goals To determine the 2-year survival and prognostic indicators of hepatitis B virus–related cirrhosis after the onset of hepatic decompensation. Background Chronic hepatitis B (CHB) patients with cirrhosis and resultant hepatic decompensation have reduced survival. However, the natural history of these patients has not been well characterized in previous studies. Better understanding of survival and prognostic indicators is essential in management of these patients, especially in determining who should be candidates for orthotopic liver transplantation. Study This is a retrospective longitudinal study of 96 patients with CHB-related cirrhosis after the onset of hepatic decompensation. The overall survival was ascertained, and clinical and laboratory variables were analyzed. Significant prognostic indicators for survival at 2 years were determined using univariate and multivariate analyses with Cox regression model. Results The overall survival was 80% at 2 years after onset of decompensation. With univariate and multivariate analyses, hepatic encephalopathy and hypoalbuminemia less than 2.8 g/dL were significant prognostic indicators of poor survival probability. The hazard ratios were 5.22 (95% confidence interval, 1.67–16.3) and 8.57 (95% confidence interval, 1.94–37.8), respectively. Patients with hypoalbuminemia less than 2.8 g/dL had a 2-year survival of only 62%. Conclusions Our study showed that of CHB patients who developed the first episode of hepatic decompensation, those with hepatic encephalopathy or significant hypoalbuminemia or both have worse prognoses. They should be considered potential candidates for liver transplantation.

Long-term follow-up of peginterferon and lamivudine combination treatment in HBeAg-positive chronic hepatitis B.

We have previously demonstrated that combination peginterferon and lamivudine treatment has superior antiviral efficacy to lamivudine monotherapy in chronic hepatitis B. In this study, we investigated the long‐term posttreatment virological response to this combination treatment. Sustained virological response of patients who completed 32‐week peginterferon and 52‐week lamivudine combination treatment was compared to patients who completed 52‐week lamivudine monotherapy. Sustained response was defined as sustained hepatitis B e antigen (HBeAg) loss and HBV DNA < 100,000 copies/mL from treatment cessation until the end of follow‐up. Forty‐eight patients receiving combination treatment and 47 patients receiving lamivudine monotherapy were studied. The posttreatment follow‐up of patients who received combination treatment was 117 ± 34 weeks and that of patients receiving lamivudine monotherapy was 124 ± 29 weeks. At the end of treatment, HBeAg loss occurred in 63% of patients in the combination group and 28% of patients in the lamivudine group (P = .001). The probabilities of sustained response for combination treatment and lamivudine monotherapy were 33% and 13% at week 24, 31% and 11% at week 52, and 29% and 9% at week 76, respectively (log‐rank test, P = .0015). No patients developed virological relapse after week 76 until the last visit in either treatment group. All sustained responders had no biochemical relapse (alanine aminotransferase [ALT] > 2 times upper limit of normal) during follow‐up. Among the non‐sustained responders, biochemical relapse occurred in 32 patients (94%) in the combination group and 38 patients (88%) in the lamivudine group, respectively. In conclusion, combination treatment of peginterferon and lamivudine has a higher sustained virological response than lamivudine monotherapy up to 3 years after treatment. (HEPATOLOGY 2005.)

Histological progression of non‐alcoholic fatty liver disease in Chinese patients

Background : Non‐alcoholic fatty liver disease is an important cause of chronic hepatitis and cryptogenic cirrhosis. The natural history of non‐alcoholic fatty liver disease is not well understood especially in Asian populations.

Metabolic and histological features of non‐alcoholic fatty liver disease patients with different serum alanine aminotransferase levels

Background  Non‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear.

Genetic polymorphisms of adiponectin and tumor necrosis factor‐alpha and nonalcoholic fatty liver disease in Chinese people

Background and Aim:  Hypoadiponectinemia and high tumor necrosis factor‐alpha (TNF‐α) levels are associated with the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the genetic polymorphisms of adiponectin and TNF‐α in Chinese NAFLD patients and their association with disease severity.