The Diagnostic and Prognostic Significance of Liver Histology in Alcoholic Hepatitis

Ewan Forrest; Gemma Petts; Andrew Austin; Kirsty Lloyd; Mark Wright; Nikhil Vergis; Stephen Atkinson; Steven Masson; David Patch; Alberto Quaglia; Mark Thursz; Robert Goldin


Aliment Pharmacol Ther. 2021;53(3):426-431. 

In This Article

Abstract and Introduction


Background: Liver biopsy may be of diagnostic and prognostic value but its role in alcoholic hepatitis (AH) has been controversial.

Aim: To assess the utility of liver biopsy in the assessment of clinically severe AH

Methods: The histological features of alcoholic steatohepatitis (ASH) were recorded and scored in patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial who underwent liver biopsy. These features were then assessed relative to outcome and established clinical prognostic scores.

Results: The STOPAH trial recruited 1068 patients; biopsies were obtained in 182 (17%). One hundred and sixty-one biopsies were adequate for histological assessment and 140 (87%) were diagnostic for ASH. Only three biopsies (2%) did not have histological features of alcohol-related liver injury. In biopsies performed prior to randomisation, ASH was identified in 92.5% of patients meeting clinical trial definitions of severe AH. In biopsies with ASH, taken before or within 48 hours of randomisation, survival differences between Alcoholic Hepatitis Histological Score (AHHS) groups were not significant: comparison of mild/moderate (91%: 21 of 23 patients) with severe (78%: 29 of 37 patients) groups: P = 0.18. The AHHS was not superior to clinical scores of prognosis: area under the curve for 28-day mortality was 0.728, compared with 0.799 for the Glasgow alcoholic hepatitis score and 0.728 for the MELD score.

Conclusion: Liver histology taken before treatment rarely changes the diagnosis in patients meeting strict criteria for a clinical diagnosis of AH. The AHHS is similar to clinical scores in determining prognosis.

Clinical trial registration

EudraCT reference number: 2009-013897-42.

ISRCTN reference number: 88782125.

MREC number: 09/MRE09/59.

UKCRIN ID: 9143.


Alcoholic hepatitis (AH) is a clinical syndrome characterised by acute onset jaundice on the background of prolonged and excessive alcohol consumption. Histologically alcoholic steatohepatitis (ASH) is diagnosed when all the following morphological characteristics are present alongside a clinical history of significant alcohol use: hepatocyte steatosis, ballooning of hepatocytes and immune cell infiltration. It is important to note however, these histological features are not exclusive to patients with clinically defined AH and may be present in liver biopsies from patients with excess alcohol use but without significant jaundice, or in patients without a significant alcohol history (non-alcoholic steatohepatitis).

European Association for Study of the Liver guidelines updated in 2018 suggest that biopsy is only required in cases of diagnostic uncertainty.[1] This is largely in agreement with the recent recommendations of the American College of Gastroenterology[2] and the American Association for the Study of Liver Disease.[3] Despite these guidelines, concern remains about the accuracy of a clinical diagnosis. Some observational studies with broad clinical diagnostic criteria suggest that as many as 50% of such patients may not fulfil the biopsy criteria for ASH.[4,5] In addition to the diagnosis of ASH, there are reports that histology may be able to provide prognostic information and/or predict the response to corticosteroid therapy. The Alcoholic Hepatitis Histological Score (AHHS), a histological grading system for liver histology from patients with AH, stratifies the appearance of ASH into mild, moderate and severe disease categories that have been shown to correlate with 90-day survival.[6]

The purpose of this study was therefore to determine the utility of liver histology in patients given a clinical diagnosis of severe AH and to assess the prognostic role of the AHHS.