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 x age (yr) + 0.094 x BMI (kg/m(2)) + 1.13 x impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 x AST/ALT ratio-0.013 x platelet (x10(9)/L)-0.66 x 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.

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-alpha) levels are associated with the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the genetic polymorphisms of adiponectin and TNF-alpha in Chinese NAFLD patients and their association with disease severity. METHODS: Seventy-nine patients with histology-proven NAFLD (61 with simple steatosis and 18 with stage 2-4 fibrosis) and 40 controls were tested for the nucleotide polymorphisms at adiponectin -11 391, -11 377, +45, and +276 and TNF-alpha promoters -863, -308, and -238. RESULTS: There was no significant deviation in the adiponectin and TNF-alpha gene polymorphisms between NAFLD patients and controls, or between patients with simple steatosis and those with stage 2-4 fibrosis. NAFLD patients with -11377G and +45G at the adiponectin gene were more likely to have hypertriglyceridemia. On multivariate analysis, older age, higher body mass index, and higher fasting glucose were independent factors associated with stage 2-4 fibrosis in NAFLD patients. CONCLUSIONS: Adiponectin and TNF-alpha gene polymorphisms were not shown to be associated with NAFLD or significant fibrosis in Chinese people. The adiponectin -11377G and +45G alleles were associated with hypertriglyceridemia in NAFLD patients. Since the current study is not adequately powered to detect smaller differences in allele frequencies, larger-sized studies in different ethnic groups are required.

Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response.

BACKGROUND & AIMS: We aimed to evaluate serum hepatitis B surface antigen (HBsAg) quantitation as a surrogate marker for covalently closed circular DNA (cccDNA) and intrahepatic hepatitis B virus (HBV) DNA, and as a predictor of sustained virologic response to peginterferon and lamivudine combination therapy. METHODS: Twenty-six hepatitis B e antigen-positive chronic hepatitis B patients receiving combination treatment of 32-week peginterferon alfa-2b and 2-year lamivudine were studied. All patients had liver biopsy before and after treatment for cccDNA and intrahepatic HBV DNA measurement. Sustained virologic response was defined as sustained hepatitis B e antigen seroconversion and HBV DNA less than 10,000 copies/mL at the end of treatment until 1 year posttreatment. RESULTS: Seven patients developed sustained virologic response. At baseline, HBsAg correlated well with both log (cccDNA) (r = 0.54, P = .004) and log [total intrahepatic HBV DNA] (r = 0.43, P = .028). The median reduction of HBsAg was 1287 IU/mL (range, 12,223-26,763 IU/mL). Reduction of HBsAg has good correlation with reduction in log [cccDNA] (r = 0.68, P < .0001) and reduction in log [total intrahepatic HBV DNA] (r = 0.65, P < .0001). Patients with lower baseline cccDNA, intrahepatic HBV DNA, and HBsAg level but not serum HBV DNA level tend to develop sustained virologic response. A baseline HBsAg level of less than 10,000 IU/mL had sensitivity, specificity, and positive and negative predictive values for sustained virologic response of 86%, 56%, 43%, and 92%, respectively. CONCLUSIONS: Serum HBsAg levels correlate well with the cccDNA and intrahepatic HBV DNA. Low pretreatment HBsAg is better than HBV DNA to predict good response to peginterferon and lamivudine treatment.

Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are reaching epidemic levels worldwide, but data in Asia remain scarce. This cross-sectional study examined the metabolic and adipokine profiles of Chinese patients with biopsy-proven NAFLD and factors associated with severe disease. METHODS: Eighty ethnic Chinese with NAFLD and 41 healthy controls were recruited. Metabolic parameters and fasting adiponectin, tumor necrosis factor-alpha (TNF-alpha), leptin, and resistin levels were measured on the day of liver biopsy. Histology was scored according to Brunt's criteria. Metabolic syndrome was assessed by using both the International Diabetes Federation and Adult Treatment Panel III criteria. RESULTS: Twenty-eight patients had simple steatosis, and 52 patients had nonalcoholic steatohepatitis (NASH), defined as necroinflammatory grade >/=2 and/or fibrosis by Brunt's criteria. The ethnic-specific International Diabetes Federation criteria identified more cases of metabolic syndrome among NAFLD patients than the Adult Treatment Panel III criteria (70% vs 56%, P < .0001). On multivariate analysis, low adiponectin level, increased leptin level, and diabetes mellitus were associated with NAFLD. High TNF-alpha level and high body mass index were independent factors associated with NASH. TNF-alpha level had positive correlation with necroinflammatory grade (R = .35, P = .002) and fibrosis stage (R = .31, P = .005). CONCLUSIONS: Hypoadiponectinemia and elevated TNF-alpha levels are associated with the development of NAFLD and NASH, respectively, independent of other metabolic factors. Ethnic-specific definition of metabolic syndrome is more useful in the assessment of NAFLD patients.

Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion after lamivudine treatment.

AIM: To investigate the association of hepatitis B virus (HBV) genotype and HBeAg seroconversion after nucleotide analogue treatment. METHODS: Chronic hepatitis B patients receiving lamivudine followed up for at least 6 months post-treatment were studied. Consecutive treatment-naïve patients who were prospectively followed up in the clinic for at least 18 months were studied as controls. HBeAg seroconversion was defined as loss of HBeAg, appearance of anti-HBe and normalization of alanine aminotransferase for at least 6 months. RESULTS: Thirty-five patients on lamivudine and 96 control patients followed up for 39 (18-49) months were studied. Lamivudine was given for 12 (10-18) months, and patients were followed up for 15 (6-34) months after drug cessation. Genotype B and C HBV were found in 43 and 88 patients and HBeAg seroconversion occurred in 12 (28%) and 16 (18%) patients, respectively (P=0.30). There was no difference in HBeAg seroconversion between patients infected by genotype B and C HBV in the control (35% vs 21%, P=0.25) and lamivudine-treated (14% vs 10%, P=1.00) groups. CONCLUSION: HBeAg seroconversion after treatment by lamivudine was not influenced by the HBV genotype.