Very low probability of significant liver inflammation in chronic hepatitis B patients with low ALT levels in the absence of liver fibrosis

Aliment Pharmacol Ther. 2020 Oct;52(8):1399-1406. doi: 10.1111/apt.16067. Epub 2020 Sep 4.

Abstract

Background: Guidelines recommend liver biopsy to rule out significant inflammatory activity in chronic hepatitis B (CHB) patients with elevated hepatitis B virus (HBV) DNA but without other indications for treatment.

Aim: To study rates and determinants of clinically significant liver inflammation.

Methods: We selected patients with HBV DNA > 2000 IU/mL from the SONIC-B database. The presence of significant inflammation (METAVIR ≥ A2 or HAI ≥ 9) was assessed by liver biopsy and correlated with alanine aminotransferase (ALT) levels (according to AASLD upper limits of normal [ULN]) and stratified by the presence of significant liver fibrosis (Ishak ≥ 3 or METAVIR ≥ F2).

Results: The cohort included 2991 patients; 1672 were HBeAg-positive. ALT was < ULN in 270 (9%), 1-2 times ULN in 852 (29%) and > 2 times ULN in 1869 (63%). Significant fibrosis was found in 1419 (47%) and significant inflammatory activity in 630 (21%). Significant inflammatory activity was found in 34% of patients with liver fibrosis, compared to 9.5% of those without (P < 0.001). Among patients without fibrosis, significant inflammatory activity was detected in 3.6% of those with normal ALT, 5.0% of those with ALT 1-2 times ULN and in 13% of those with ALT > 2 times ULN (P < 0.001). ALT < 2 times ULN had a negative predictive value of 95% for ruling out significant inflammatory activity among patients without liver fibrosis.

Conclusions: Among patients without significant fibrosis, an ALT level < 2 times ULN is associated with < 5% probability of significant inflammatory activity. If fibrosis can be ruled out using non-invasive methods, liver biopsy solely to assess inflammatory activity should be discouraged.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood*
  • Biopsy
  • Cohort Studies
  • Female
  • Hepatitis / blood
  • Hepatitis / diagnosis*
  • Hepatitis / epidemiology
  • Hepatitis / etiology*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / epidemiology
  • Humans
  • Inflammation / blood
  • Inflammation / diagnosis
  • Inflammation / epidemiology
  • Inflammation / etiology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / epidemiology
  • Male
  • Middle Aged
  • Probability
  • Prognosis
  • Risk Factors
  • Young Adult

Substances

  • Alanine Transaminase