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Aliment Pharmacol Ther. 2014 Feb;39(4):349-58. doi: 10.1111/apt.12590. Epub 2014 Jan 6.

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

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Department of Internal Medicine, University of Pittsburgh Medical Center, Shadyside, Pittsburgh, PA, USA.



Chronic 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.


To determine the proportion of CHB patients with ALT ≤ 40 IU/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 ≤ 30 IU/L (males) and 19 IU/L (females), and advanced age.


Studies 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.


Among nine studies (N = 830 patients), a significant proportion (20.7%; 95% CI: 16.2-26.0%) of CHB patients with ALT levels ≤ 40 IU/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 30-40 years old. The corresponding proportion was 27.8% even when the newer ULN of 30 IU/L (males) and 19 IU/L (females) was applied.


Approximately one fifth of CHB patients with ALT ≤ 40 IU/L may have significant hepatic fibrosis. The approach to such patients should be individualised, as further evaluation and treatment may be appropriate.

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