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

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

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.

Conflict of interest statement

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

Figures

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

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Source: PubMed

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