Higher levels of androgen signaling, reflected by higher testosterone levels and 20 or fewer AR-CAG repeats, may be associated with an increased risk of HBV-related HCC in men.

Chronic hepatitis B patients with high-normal serum ALT (levels of 0.5-1؋ upper limit of normal) are still at risk of liver disease progression. We thus investigated the correlation between serum ALT level and hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum ALT level (PNALT). Baseline clinical and virological features of 414 HBeAg-negative carriers, including 176 (42.5%) with low-normal ALT (levels of less than 0.5؋ upper limit of normal) and 238 (57.5%) with high-normal ALT, were compared. Compared with HBV carriers with low-normal ALT, those with high-normal ALT were older (41 vs. 37 years, P < 0.001) and had a greater frequency of serum HBV DNA level >10 4 copies/ml (63.4% vs. 47.5%, P < 0.001) as well as a higher prevalence of basal core promoter T1762/A1764 mutant (36.5% vs. 24.2%, P ‫؍‬ 0.01). Multivariate analysis showed that factors associated with a high-normal serum ALT level included male sex [odds ratio ( T he natural history of chronic HBV infection could be generally divided into three chronological stages. 1 During the immune tolerance stage, serum HBV DNA levels are high and hepatitis B e antigen (HBeAg) is present. In the immune clearance stage, most carriers eventually seroconvert from HBeAg to anti-HBe. After HBeAg seroconversion, patients were in the integration or residual stage, serum level of HBV DNA decreased, and ALT became normal. Accordingly, HBeAgnegative carriers were usually considered to have lowreplicative HBV infection, and normal or nearly normal serum ALT levels. However, progressive liver disease still develops in HBeAg-negative carriers because of bouts of hepatitis flare. Thus, the clinical spectrum of HBeAgnegative chronic HBV infection may range from inactive carrier to aggressive chronic hepatitis with or without cirrhosis. 2 The differential diagnosis of HBeAg-negative chronic hepatitis from an inactive carrier mainly depends on sequential determinations of serum ALT. 3 However, slightly increased serum ALT level, although within the normal range, has been reported to be significantly associated with risk of liver-related mortality in the general population. 4 Furthermore, recent large-scale cohort studies showed that chronic hepatitis B patients with a normal serum ALT level, irrespective of HBeAg status, were also at a risk for the development of cirrhosis and HCC. 5,6 Therefore, chronic hepatitis B patients with high-normal serum ALT levels (0.5-1 ϫ upper limit of normal) may be From the

This longitudinal cohort study indicates that excess body weight is involved in the transition from healthy HBV carrier state to HCC and liver-related death among men.

Little is known about the longitudinal course of hepatitis B virus (HBV) load and its relationship with the development of hepatocellular carcinoma (HCC). We conducted a case-cohort study nested within a cohort of 2874 HBV surface antigen-positive male Taiwanese government employees aged 30 years or older. HBV genotype and DNA levels (i.e. viral load) were tested using polymerase chain reaction-based assays on plasma samples from 112 cases and 1031 non-cases. Prediagnostic plasma levels of HBV DNA were measured in multiple samples collected from each man (total 7706 samples), taken over periods of up to 16 years before diagnosis. Baseline viral load influenced HBV genotype-specific HCC risks and predicted the persistence of high viral load (>/=4.39 log copies/ml) that can cause HCC. Moderate to high tracking of viral load was observed within 9 years. Hepatitis B e antigen (P < 0.0001), genotype C HBV infection (P = 0.0369) and longitudinal alanine aminotransferase (ALT) elevation (defined as ALT abnormality in >/=50% of the visits) (P = 0.0005) were positively related to longer duration of persistence for high viral load. After multivariate adjustment, HBV genotype C [odds ratio (OR) = 5.97, 95% confidence interval (CI) = 3.44-10.34], high viral load detected at >/=50% of the visits (compared with sustained low viral load: OR = 5.04, 95% CI = 2.31-11.00) and longitudinal ALT elevation (compared with sustained normal ALT levels: OR = 2.84, 95% CI = 1.46-5.51) accounted for 43.5, 57.2 and 24.9% of HCCs, respectively. The results suggest that maintenance of viral load <4.39 log copies/ml was associated with sustained normalization of ALT levels and decreased risk of HCC.