Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase ≤40 IU/L and significant hepatic fibrosis

BackgroundChronic hepatitis B (CHB) may lead to cirrhosis, hepatocellular carcinoma and premature death. Elevated alanine transaminase (ALT) levels the upper limit of normal (ULN) are a major determinant for initiating anti-viral therapy; however, ALT levels alone may not be predictive of hepatic fibrosis. AimTo determine the proportion of CHB patients with ALT 40IU/L and liver fibrosis stage 2. Secondary goals include subgroup analysis by hepatitis B e antigen (HBeAg) status, high hepatitis B virus (HBV) DNA levels, Asian ethnicity, lower ULN of 30IU/L (males) and 19IU/L (females), and advanced age. MethodsStudies identified in EMBASE and MEDLINE (1/1990-6/2012) using the search criteria: Hepatitis B[Mesh] OR Hepatitis B virus[Mesh] OR Hepatitis B, Chronic[Mesh])) AND Alanine Transaminase[Mesh]) and abstracts containing the term hepatitis' from recent major U.S. gastroenterology and liver society meetings were considered. ResultsAmong nine studies (N=830 patients), a significant proportion (20.7%; 95% CI: 16.2-26.0%) of CHB patients with ALT levels 40IU/L had significant fibrosis irrespective of HBeAg status, high HBV DNA levels, ethnicity or age, although this proportion may be higher in patients older than 30-40years old. The corresponding proportion was 27.8% even when the newer ULN of 30IU/L (males) and 19IU/L (females) was applied. ConclusionsApproximately one fifth of CHB patients with ALT 40IU/L may have significant hepatic fibrosis. The approach to such patients should be individualised, as further evaluation and treatment may be appropriate.