Is a liver biopsy necessary in alcoholic hepatitis?

The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosisJournal of HepatologyVol. 55Issue 5PreviewThe aim of this study was to systematically assess the diagnostic and prognostic value of early liver biopsy in patients who require hospital admission with acute deterioration of alcoholic cirrhosis. Full-Text PDF Reply to: “Is a liver biopsy necessary in alcoholic hepatitis?”Journal of HepatologyVol. 56Issue 6PreviewWe thank Drs. Forrest and Gleeson for their interest in our paper [1]. Their letter makes two points; one clinical and the other logistical, which will be addressed in turn. Full-Text PDF Open Access The paper by Mookerjee et al. allowed a fascinating insight into the prognostic relevance of the systemic inflammatory response (SIRS) in decompensated alcoholic liver disease (ALD), especially the presence of alcoholic steatohepatitis (ASH) [[1]Mookerjee R.P. Lackner C. Stauber R. Stadlbauer V. Deheragoda A. Jalan R. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis.J Hepatol. 2011; 55: 1103-1111Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar]. However, the paper makes some assertions which require further discussion. The main assertion is that a liver biopsy is essential to determine the diagnosis and prognosis in patients with ASH. Not only is this contrary to recently published guidelines [[2]O’Shea R.S. Dasarathy S. McCullough A.J. et al.AASLD practice guideline: alcoholic liver disease.Hepatology. 2010; 51: 307-328Crossref PubMed Scopus (930) Google Scholar], there are practical issues in obtaining and interpreting transjugular liver biopsies. Few liver centres in the United Kingdom can readily provide such a service. In 2009/10 there were 14,700 hospital admissions in England alone for alcoholic liver disease: 5700 with “alcoholic cirrhosis” and 1600 with “alcoholic hepatitis” [[3]Statistics on alcohol: England (Published May 26 2011), NHS Information Centre. Available at: <http://www.ic.nhs.uk/pubs/alcohol11> [accessed 30.10.11].Google Scholar]. Mookerjee et al. describe biopsies in 71 patients over a 3-year period. The provision of transjugular liver biopsies throughout the rest of the United Kingdom and Europe for the thousands of additional ALD patients is unrealistic. A management strategy based upon an impractical level of investigation will not benefit most patients with ALD. We must ensure that we can assess and effectively manage these patients in all hospitals and not solely in limited specialist centres. With regards to the need for biopsy for diagnosis of alcoholic hepatitis, the figure of 70–80% accuracy of a clinical diagnosis subsequently confirmed by biopsy is often quoted [[2]O’Shea R.S. Dasarathy S. McCullough A.J. et al.AASLD practice guideline: alcoholic liver disease.Hepatology. 2010; 51: 307-328Crossref PubMed Scopus (930) Google Scholar]. However, the most consistent difference between patients with alcoholic hepatitis and other patients with decompensated ALD is the degree of hyperbilirubinaemia [4Verma S. Ajudia K. Mendler M. Redeker A. Prevalence of septic events, type 1 hepatorenal syndrome, and mortality in severe alcoholic hepatitis and utility of discriminant function and MELD score in predicting these adverse events.Dig Dis Sci. 2006; 51: 1637-1643Crossref PubMed Scopus (36) Google Scholar, 5Rincon D. Lo Iacono O. Ripoll C. Gomez-Camarero J. Salcedo M. Catalina M.V. et al.Prognostic value of hepatic venous pressure gradient for in-hospital mortality of patients with severe acute alcoholic hepatitis.Aliment Pharmacol Ther. 2007; 25: 841-848Crossref PubMed Scopus (66) Google Scholar]. 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 μmol/L) or whose patient population had a lower limit of bilirubin greater than 80 μmol/L, were considered, the accuracy of a clinical diagnosis rose to 96% [[6]Hamid R. Forrest E.H. Is histology required for the diagnosis of alcoholic hepatitis: a review of published randomized controlled trials.Gut. 2011; 60: A233Crossref Google Scholar]. 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 μmol/L) as a major tenant of its definition [[7]Katoonizadeh A. Laleman W. Verslype C. Wilmer A. Maleux G. Roskams T. et al.Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study.Gut. 2010; 59: 1561-1569Crossref PubMed Scopus (206) Google Scholar]. In this group of patients again, 96% had features of ASH. In the paper by Mookerjee, the criteria for a clinical diagnosis of ASH appear to have been decompensated ALD with the presence of SIRS without a minimum value of bilirubin stipulated. “Progressive jaundice” was just one of three criteria used to define the patient group studied. Furthermore, no information was provided regarding duration of liver disease at time of biopsy. Previous experience indicates that the accuracy of clinical diagnosis of alcoholic hepatitis is highest if the biopsy is performed within 4 weeks of initial presentation [[8]Elphick Dube A.K. McFarlane E. Jones J. Gleeson D. Spectrum of liver histology in presumed decompensated alcoholic liver disease.Am J Gastroenterol. 2007; 102: 780-788Crossref PubMed Scopus (55) Google Scholar]. Whilst Maddrey’s Discriminant Function (DF) has been a landmark advance in the assessment of alcoholic hepatitis, its accuracy is in question not least of all because it relies upon the measured prolongation of the prothrombin time, which is prone to significant laboratory variation. Additionally, in the paper by Mookerjee, the DF was not found to be predictive of 28-day outcome. More recently, the MELD score and the Glasgow Alcoholic Hepatitis Score (GAHS) have been shown to identify poor outcome from alcoholic hepatitis [2O’Shea R.S. Dasarathy S. McCullough A.J. et al.AASLD practice guideline: alcoholic liver disease.Hepatology. 2010; 51: 307-328Crossref PubMed Scopus (930) Google Scholar, 9Forrest E.H. Evans C.D.J. Stewart S. Phillips M. Oo Y.H. McAvoy N. et al.Analysis of factors related to mortality in alcoholic hepatitis and the derivation and validation of the glasgow alcoholic hepatitis score.Gut. 2005; 54: 1174-1179Crossref PubMed Scopus (294) Google Scholar]. These have similar AUC values to those described for the histological ASH grade described in the paper by Mookerjee et al. The paper did not demonstrate that their histological data were independently predictive of survival or added significantly to the predictive value of these scores. The development of a reproducible histological score for alcoholic hepatitis is to be applauded. However, even in this specialist centre there was a delay of up to 7 days before the biopsies were obtained. With the additional time for preparation and interpretation of the specimens, the delay in obtaining a prognosis from histological criteria is significant and the opportunity to intervene early in those patients who may benefit may be lost. However, clinical scores such as the GAHS, readily calculable on the day of admission and over subsequent days, are not only accurate from a prognostic point of view but also appear to be able to identify those patients likely to benefit from therapeutic intervention [9Forrest E.H. Evans C.D.J. Stewart S. Phillips M. Oo Y.H. McAvoy N. et al.Analysis of factors related to mortality in alcoholic hepatitis and the derivation and validation of the glasgow alcoholic hepatitis score.Gut. 2005; 54: 1174-1179Crossref PubMed Scopus (294) Google Scholar, 10Forrest E.H. Morris A.J. Stewart S. Phillips M. Oo Y.H. Fisher N.C. et al.The Glasgow alcoholic hepatitis score identifies patients who may benefit from corticosteroids.Gut. 2007; 56: 1743-1746Crossref PubMed Scopus (102) Google Scholar]. The prognostic utility of the presence of SIRS criteria has previously been described in ALD patients with ACLF [[7]Katoonizadeh A. Laleman W. Verslype C. Wilmer A. Maleux G. Roskams T. et al.Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study.Gut. 2010; 59: 1561-1569Crossref PubMed Scopus (206) Google Scholar]. This may in part explain the prognostic accuracy of the GAHS as white cell count is a principle component of both SIRS and GAHS. In conclusion, it is unrealistic to suggest that biopsy is essential for the diagnosis and prognosis of patients with alcoholic hepatitis. Whilst biopsy may be necessary in cases of diagnostic uncertainty and for the characterisation of patients for research purposes, clinical criteria for diagnosis and identification of patients for treatment are readily available for the majority of patients with alcoholic hepatitis. The aim should be to assess such patients promptly on presentation rather than to rely upon strategies based upon histology which may delay assessment or be difficult to obtain outside specialist centres. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.