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Background: Data on histological activity and HBV DNA levels in patients with chronic HBV infection and persistently normal alanine aminotransferase levels are sparse. We aimed to investigate the histological activity and HBV DNA levels in these patients., Methods: There were 132 patients with HBeAg negative chronic HBV infection and persistently normal alanine aminotransferase levels that were included prospectively. Data were dichotomized according to the median levels. Associations of histology with HBV DNA and other variables were assessed., Results: A total of 80 patients were male. The median age was 36 years. The median baseline HBV DNA was 2.9Log10 IU/mL. There were 50 cases (38%) with a total score > or = 5, 53 cases (40.2%) had grade > or = 4 and 40 cases (30.3%) had stage > or = 2. A baseline HBV DNA <2000 IU/mL was seen in 24 cases (48%) of those with total score > or = 5, 28 cases (53%) of those with grade > or = 4 and 9 cases (22.5%) with stage > or = 2. Multivariate analysis of baseline HBV DNA above the median level significantly predicted the total score, grade and stage with an adjusted odds ratio of 5.43, 3.47, and 4.23, respectively when compared to below median values. A second liver biopsy was performed in 61 patients. The median time interval between the two biopsies was 40 months. Total scores of 23 cases (38%) progressed by > or = 2 scores and the HBV DNA of 18 cases (22.5%) increased by > or = 1 Log10 IU when compared to baseline values., Conclusion: HBeAg negative chronic HBV infection with persistently normal alanine aminotransferase is not a silent disease. Active liver disease may be seen in such patients with viral loads less than 2000 IU/mL.

Background/aims: Noninvasive markers for predicting significant fibrosis and inflammation have not yet been validated in an unselected group of chronic hepatitis B virus (HBV) carriers. The aim of this study was to create noninvasive models to predict significant fibrosis and inflammation in chronic HBV carriers., Methods: A total of 276 (229 HBeAg negative, 47 HBeAg positive) unselected consecutive treatment naïve patients chronically infected with HBV who attended our center over a 36-month period underwent liver biopsy. HBeAg negative patients were randomly divided into two cohorts: training group (N = 130) and validation group (N = 99). HBeAg positive patients were analyzed as a whole without separation. Thirteen parameters were analyzed separately in HBeAg negative and HBeAg positive patients to predict significant fibrosis (Ishak stage >or=3) and inflammation (Ishak grade >or=7)., Results: In HBeAg negative patients significant liver fibrosis was best predicted using the variables HBV DNA levels, alkaline phosphatase, albumin, and platelet counts with an area under ROC curve (AUC) of 0.91 for the training group and 0.85 for the validation group. Using the low cutoff probability of 4.72, significant fibrosis could be excluded with negative predictive value of 99% in the entire cohort, and liver biopsy would have been avoided in 52% of patients. The best model for predicting significant inflammation included the variables age, HBV DNA levels, AST, and albumin with an AUC of 0.93 in the training and 0.82 in the validation group. In HBeAg positive patients no factor could predict accurately stages of liver fibrosis, but the best factor for predicting significant inflammation was AST with an AUC of 0.87., Conclusions: Significant hepatic fibrosis and necroinflammation can reliably be predicted using routinely checked tests and HBV DNA levels.