Is histology required for the diagnosis of alcoholic hepatitis? a review of published randomised controlled trials

Abstract

IntroductionThe need for liver biopsy to diagnose alcoholic hepatitis (AH) in the clinical setting remains controversial. Coagulopathy and/or ascites may preclude percutaneous biopsy and facilities for transjugular biopsy are not universally available. Despite this, some experts still advocate that biopsy confi rmation of AH is a prerequisite for determining diagnosis, prognosis and treatment strategy for this condition. Aim The authors aimed to review the already published literature in the form of randomised controlled trials (RCTs) of therapy for AH. This was primarily to determine if these data could determine the need for histology in the selection of patients for study. Methods Studies published from 1970 to 2010 were identifi ed through a MEDLINE computer search and manual search of the bibliographies of identifi ed articles. Inclusion and exclusion criteria for each study were determined. The number of biopsies performed and the patients excluded as a consequence of incompatible histology were recorded. Results The authors identifi ed 43 published RCTs trials, with adequate data available in 39. 11 of the trials required 'biopsy proven' AH prior to randomisation of patients, however the histological criteria for the diagnosis of AH varied widely between studies. Where fi gures were provided, it appears 1668 liver biopsies were undertaken in these trials with 1409 showing evidence of AH (84.5%). However if studies defi ned a minimum value of bilirubin (usually >80-85 μmol/l) as an entry criterion, or the minimum value of bilirubin described was >80 μmol/l, 96% of biopsies confi rmed AH (405 of 422 biopsies: p<0.0001 (95% CI 12.2% to 18.2% compared with studies without such stipulations). Where co-existent cirrhosis was mentioned, 839 of 1187 (70.7%) of biopsies had evidence of this. There was no correlation between the proportion of patients with cirrhosis and the mortality in the placebo treated patients (p=0.81; 95% CI −0.54 to 0.44). Conclusion Overall the diagnosis of AH is confi rmed in over 80% of cases, but this clinical diagnostic accuracy increases to over 95% with a minimum value of bilirubin. Co-existent cirrhosis does not infl uence short-term prognosis. These data indicate that in most cases histology is not necessary for the diagnosis and management of AH. Competing interests None.

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial

“…Other trials in this field 22,55 have required liver biopsy and histological confirmation of the diagnosis prior to inclusion; however, in the UK, the USA and much of Europe, liver biopsy is rarely performed for diagnostic confirmation and reserved only for diagnostic uncertainty. This strategy is vindicated by a number of studies 22,[55][56][57] that show that clinicians can accurately judge the diagnosis by the recent use of alcohol and also applying of strict criteria on the duration of jaundice. A trial requiring liver biopsy could not have recruited this number of subjects, as many centres do not have access to the transjugular technique that would be required in this group of patients or would have considered the procedure to be unethical.…”

Recurrent severe alcoholic hepatitis

“…Studies have identified that bilirubin of at least 5 Â ULN in the presence of ongoing alcohol use accurately differentiates SAH from decompensated cirrhosis [16]. In a review of randomized-controlled trials of therapy for SAH, bilirubin more than 80 mmol/l was associated with histological AH in 96% of patients [17]. Therefore, our criteria for the diagnosis of SAH were robust and evidence based.…”

Is a liver biopsy necessary in alcoholic hepatitis?

“…In relation to use of widely published scoring systems such as modified DF, MELD and more recently GAHS [6,7], we agree that…”

“…A recent review of all the randomised controlled trials of treatments for alcoholic hepatitis determined the accuracy of the clinical criteria used relative to subsequent histological confirmation. If only those studies, which used a minimum level of bilirubin (ranging from 80 to 100 lmol/ L) or whose patient population had a lower limit of bilirubin greater than 80 lmol/L, were considered, the accuracy of a clinical diagnosis rose to 96% [6]. This is very similar to a group of patients with ALD presenting with Acute-on-Chronic Liver Failure (ACLF) which has recent onset of hyperbilirubinaemia (>85 lmol/ L) as a major tenant of its definition [7].…”