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• Future use of the Glasgow alcoholic hepatitis score
  I N Guha
  Published on: 18 April 2016

• Published on: 18 April 2016

  Future use of the Glasgow alcoholic hepatitis score

  • I N Guha
  • Other Contributors:
    • William M Rosenberg

  Dear Editor,

  We read with interest the findings of Forrest et al ; Gut 2005; 54: 1174-1179, regarding their prognostic algorithm for alcoholic hepatitis; Glasgow alcoholic hepatitis score (GAHS). The study uses robust clinical end-points to develop an algorithm that has diagnostic advantages over the modified discriminant function score (DFS). We would like to discuss some of the future implications of this importa...

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  Dear Editor,

  We read with interest the findings of Forrest et al ; Gut 2005; 54: 1174-1179, regarding their prognostic algorithm for alcoholic hepatitis; Glasgow alcoholic hepatitis score (GAHS). The study uses robust clinical end-points to develop an algorithm that has diagnostic advantages over the modified discriminant function score (DFS). We would like to discuss some of the future implications of this important study.

  The overall death rate in the study was 23% at 28 days and the death rate of patients with a DFS >32 was 29% at 28 days in the derivation population. The latter figure is lower than the placebo arms of many of the RCTs of alcoholic hepatitis that range between 35 to 50%.[1-3] This difference compared to the published literature may be attributable to case definition. It is possible that there were a fewer number of patients in the derivation cohort for GAHS with true alcoholic hepatitis. Some of the previous studies of alcoholic hepatitis have required liver biopsy evidence of alcoholic hepatitis as part of the case definition. This was not the case for entry into the derivation cohort for the GAHS study and the case definition was based solely on clinical and biochemical evidence of liver dysfunction in patients with heavy alcohol consumption. In the validation population there was biopsy evidence of alcoholic hepatitis in only 33%.

  While this may invalidate the GAHS as a means for identifying cases of alcoholic hepatitis it does not invalidate its use in identifying patients at risk of death when admitted to hospital with liver dysfunction on a background of heavy alcohol use. This makes it far more pragmatic than tests based on biopsies as many hospitals do not have access to specialised services to perform transjugular liver biopsies in the acute setting. Furthermore, there are published RCTs which have not required histological evidence of alcoholic hepatitis before allocating treatment.[1,4] The corollary to this is that although alcoholic hepatitis often presents with clinical features of fever, leucocytosis and hyperbilirubinaemia, there remains a differential diagnosis which may require a biopsy to resolve.[5]

  It is important to differentiate between true alcoholic hepatitis and severe liver dysfunction in patients with heavy alcohol consumption because it will influence the choice of intervention. Randomised controlled trials that use GAHS to identify patients with alcoholic hepatitis might be greatly underpowered if the therapy, e.g. steroids, is effective in alcoholic hepatitis but ineffective or harmful in other clinical conditions where abnormal clinical parameters might be associated with heavy alcohol consumption. The selection of risk stratification models should be determined by the severity of the adverse effects of the therapy under trial. Those with more severe adverse effects will warrant models with high specificity whereas drugs with minimal side effects will benefit from a model with a high sensitivity. Compared to the DFS, the GAHS has an increased specificity, decreased sensitivity and improved accuracy making it suited to the selection of subjects in studies using more toxic therapies.

  The utility of the GAHS will depend upon the effect of its use in the care of patients. We suggest that the next step in the evaluation of GAHS should be a clinical trial to see if patients randomised to risk stratification with GAHS followed by appropriate interventions have a better outcome than those managed conventionally.

  We think this is an excellent study using robust clinical end points. It is a practical model which can be used easily at the bed side, to give valuable prognostic information. Success of future therapeutic trials in alcoholic hepatitis will not only depend on the efficacy of the drug but also the appropriate selection of patients by models and their respective cut-off points.

  Yours sincerely,

  I N Guha
  WM Rosenberg

  University of Southampton Liver Unit
  Mail point 811
  Level D
  Southampton General Hospital
  Trenoma Road
  S016 6YD

  References

  1. Carithers RL, Jr., Herlong HF, Diehl AM, Shaw EW, Combes B, Fallon HJ, Maddrey WC. Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Ann Intern Med 1989;110:685-690.

  2. Mathurin P, Mendenhall CL, Carithers RL, Jr., Ramond MJ, Maddrey WC, Garstide P, Rueff B, Naveau S, Chaput JC, Poynard T. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol 2002;36:480-487.

  3. Ramond MJ, Poynard T, Rueff B, Mathurin P, Theodore C, Chaput JC, Benhamou JP. A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med 1992;326:507-512.

  4. Mendenhall CL, Anderson S, Garcia-Pont P, Goldberg S, Kiernan T, Seeff LB, Sorrell M, Tamburro C, Weesner R, Zetterman R. Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone. N Engl J Med 1984;311:1464-1470.

  5. Oxford Textbook of Clinical Hepatology 2nd Edition. Edited by Bircher J, Benhamou J, Mcintyre N, Rizetto M and Rodes J. Volume 2, Chapter 15.3; 1185-1238.

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  Conflict of Interest:
  None declared.

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