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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

Patients dually infected with hepatitis C virus (HCV)/hepatitis B virus (HBV) have a higher risk of developing advanced liver disease or hepatocellular carcinoma compared with monoinfected patients. Yet, there is a similar rate of sustained virologic response (SVR) after peginterferon alfa-2a and ribavirin combination therapy in these patients compared with HCVmonoinfected patients and a high hepatitis B surface antigen (HBsAg) seroclearance rate. The durability of hepatitis C and B clearance in coinfected patients was investigated in a 5-year follow-up study. Patients with active HCV genotype 1, both HBV-coinfected (n 5 97) and HBVmonoinfected (n 5 110), underwent 48-week combination therapy with peginterferon alfa-2a plus ribavirin. In patients with active HCV genotype 2 or 3, both HBV-coinfected (n 5 64) and monoinfected (n 5 50) patients underwent 24-week combination therapy. A total of 295 (91.9%) patients completed treatment and 24 weeks posttreatment follow-up; 264 (89.5%) patients agreed to receive additional follow-up for up to 5 years after the end of treatment. After a median follow-up of 4.6 6 1.0 years, six of the 232 patients achieving SVR developed HCV RNA reappearance, including five HCV genotype 1/HBV-coinfected patients and one HCV genotype 2/3-monoinfected patient. Subgenomic analysis of the HCV core gene indicated that five patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI], 0.9%-5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI, 21.5%-42.0%); with 33.1% (95% CI, 21.8%-50.1%) in the 48-week combination therapy group and 24.3% (95% CI, 13.7%-42.9%) in the 24-week therapy group. Conclusion: Peginterferon alfa-2a and ribavirin therapy provides good HCV SVR durability and a high accumulative HBsAg seroclearance rate in patients who are coinfected with HCV and HBV. (HEPATOLOGY 2013;57:2135-2142

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The risk of development of liver cirrhosis and HCC is significantly increased in patients with advanced age as well as with basal core-promoter mutant of HBV. In addition, basal core-promoter mutant might contribute to the gender difference of the progression of liver disease in HBeAg-negative chronic hepatitis B in Taiwan.

Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.

Our data suggest a high prevalence of precore stop codon and basal core promoter mutation in Taiwanese patients with HBeAg-negative chronic hepatitis B, and the influence of the basal core promoter mutation on HBV replication is modulated by the emergence of the precore stop codon mutation.

HBsAg quantification appears to be a useful indicator of posttreatment outcome in patients dually infected with HBV and hepatitis C virus.