Hepatitis B viral factors in HBeAg-Negative carriers with persistently normal serum alanine aminotransferase levels

Abstract

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

Should chronic HBV infected patients with normal ALT treated: debate

“…Many initial studies had shown that among patients with CHBV infection with normal ALT, about 50-90% of patients had either minimal changes or chronic persistent hepatitis on biopsy [17][18][19][20]. Recently, however, studies have described contrary findings also [21][22][23][24].…”

“…However in a recent study, that investigated the correlation between serum ALT level and hepatitis B viral factors in HBeAg-negative patients with persistently normal serum ALT level (PNALT), it was found that 47.5% of patients with low-normal ALT (levels of less than 0.5x upper limit of normal) and 63.4% with high-normal ALT had serum HBV DNA level[10 4 copies/ ml. Also compared with HBV carriers with low-normal ALT, those with high-normal ALT were older (41 vs. 37 years, P \ 0.001) [21]. Another study from china showed that serum levels of HBV DNA of the patients in the immune-tolerant stage were high and 94% of them had a HBV DNA higher than 10 6 copies/ml [22].…”

Viral load in hepatitis B e antigen-negative carriers with normal aminotransferase level

“…In the subgroup analysis, however, only 12 of their 76 subjects with detectable HBV-DNA at study entry went from lownormal to high-normal ALT levels after a follow-up period of 12-77 months, but none of them encountered ALT elevation to abnormal level. 1 This finding is also contradictory to earlier observations: abnormal ALT level was observed between the third and twelfth month of follow-up in all 25 HBeAg-negative subjects with normal baseline ALT but higher HBV-DNA level 5 ; the only 4 subjects with serum HBV-DNA Ͼ10 4 copies/mL at presentation in another study all exhibited ALT elevation during follow-up. 6 We recently followed 1241 asymptomatic HBeAg-negative HBsAg carriers with PNALT for 14,484 person-years and found that the cumulative probability of hepatitis relapse was 5% at the 2-year follow-up and 10% at the 5-year follow-up.…”

“…Of these studies, only Lin's HBeAg-negative subjects had HBV-DNA levels Ͼ10 5 copies/mL despite that the duration of PNALT was at least 2 years before entry to the study. 1 It appears that age, sex, ethnicity, and duration of PNALT are not likely the reason(s) for this discrepancy (Fig. 1).…”

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In the May issue of HEPATOLOGY, Lin et al 1 addressed an important clinical issue of hepatitis B e antigen (HBeAg)-negative hepatitis B surface antigen (HBsAg) carriers with persistently normal serum alanine aminotransferase (ALT) levels (PNALT) using a highly sensitive quantitative assay for hepatitis B virus (HBV) DNA. They found that serum HBV-DNA level Ͼ10 4 copies/mL was independently associated with high-normal ALT (0.5-1 times upper limit of normal).

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