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. 2012;7(2):e32622.
doi: 10.1371/journal.pone.0032622. Epub 2012 Feb 28.

A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B

Wai-Kay Seto  1 , Ching-Lung Lai, Philip P C Ip, James Fung, Danny Ka-Ho Wong, John Chi-Hang Yuen, Ivan Fan-Ngai Hung, Man-Fung Yuen
Affiliations

A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B

Wai-Kay Seto et al. PLoS One. 2012.

Abstract

Objective: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients.

Methods: From 1994 to 2008, liver biopsy was performed on 319 treatment-naïve CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis.

Results: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading ≥ 7 or fibrosis score ≥ 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 × upper limit of normal (ULN) and > × 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease.

Conclusion: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Distribution of liver necroinflammation (graded by Knodell histologic activity index) among 319 chronic hepatitis B patients.
Figure 2
Figure 2. Distribution of liver fibrosis (staged by Ishak fibrosis score) in 319 chronic hepatitis B patients.
Figure 3
Figure 3. Distribution of significant liver fibrosis (Ishak fibrosis score ≥3) among different age groups.
Figure 4
Figure 4. Comparison of Ishak fibrosis scores among HBeAg-positive patients with normal ALT (p = 0.024).
Figure 5
Figure 5. Comparison of Ishak fibrosis scores between ALT 1–2×ULN and ALT >2×ULN in both HBeAg-positive and HBeAg-negative patients.
See this image and copyright information in PMC

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