Gastroenterology training and education

How is Alcoholic hepatitis diagnosed?
The ‘gold standard for diagnosis is liver biopsy. However this is often not feasible in the clinical setting due to the presence of ascites or coagulopathy. Transjugular liver biopsy is an option, but the expertise is often not available.

Can Alcoholic hepatitis be diagnosed clinically?
Suggested criterion:

• History of recent excessive alcohol ingestion
• Serum bilirubin more than 80umol/l
• ALT <300 IU (or AST<500 IU)
• Exclusion of autoimmune, chronic viral or malignant liver disease

NB- Characteristic features of alcoholic hepatitis (but not necessary for diagnosis) include pyrexia, hepatomegaly, a hepatic bruit, ascites, encephalopathy, an AST: ALT ratio greater than 1.5, and a peripheral leucocytosis.

How accurate is a clinical diagnosis of Alcoholic hepatitis?
An accuracy of about 80% has been quoted for the clinical diagnosis of alcoholic hepatitis when compared with histology. However if only those studies with a minimum level of bilirubin (>80 umol/l) as a criterion for diagnosis are looked at, the accuracy rises to nearly 100%.

Does alcoholic hepatitis with co-existing cirrhosis alters the prognosis or treatment?
Whilst nearly all patients who fulfil these criteria will have features of alcoholic hepatitis on biopsy, approximately 50-60% will also have established cirrhosis. There is no evidence that co-existing cirrhosis worsens the short term outcome of patients with alcoholic hepatitis, indicating that it is the acute inflammatory process which is primarily responsible for the poor prognosis of these patients. The presence of cirrhosis (confirmed or suspected) should therefore not prevent consideration of specific treatment for alcoholic hepatitis.

How do you assess the severity of Alcoholic Hepatitis?
American College of Gastroenterology defines severity as a modified Discriminant Function (mDF)> 32 and/or hepatic encephalopathy.

• mDF = 4.6 (PTpatient–PTcontrol)+ serum bilirubin (µmol/l)/17.1

This is based on recent studies where a mDF> 32 and/or hepatic encephalopathy was associated with a 65% 28-day survival in placebo treated patients. While those with a score less than 32 had a survival of 93%.

Where would you use steroids?
American College of Gastroenterology recommends prednisolone should be used in patients with severe alcoholic hepatitis in whom the diagnosis is certain. Severity is defined as a DF> 32 and/or hepatic encephalopathy.
Histologic confirmation of alcoholic hepatitis optimizes the selection of those patients being considered for corticosteroid therapy. However, if the risk of performing liver biopsy is considered too great, the diagnosis can usually be made reliably by clinical and laboratory evaluation in the majority of patients.
The efficacy of steroids has not been adequately evaluated in patients with severe alcoholic hepatitis who also have concomitant pancreatitis, gastrointestinal bleeding, renal failure, and active infection.
Patients with mDF >32 and treated with steroids had a 28 day survival of 84.6% compared with 65.1% for placebo treated patients.

Is there any other clinical guide to help us better direct our treatment?
A GAHS (Glasgow alcoholic hepatitis score) has been recently developed. The authors of GAHS points out a few shortcomings of mDF;

• Calculation of mDF relies on the absolute value of the PT & there exists significant variation in the absolute values of PT obtained using different assays in different countries. This may thereby affect the validity of the mDF score in countries such as the UK where a greater severity score will be generated based on the PT. This creates a definite inaccuracy in the mDF value and limits its translation between different facilities.
• The presence of encephalopathy has often been included when making a treatment decision, in addition to just calculating the mDF. This is problematic, as encephalopathy is very subjective in its milder forms.
• Apart from the positive reports on the relevance of an mDF cut off value of 32, its accuracy in predicting survival has been repeatedly questioned.
• In their analysis, mDF was highly sensitive in the prediction of death from alcoholic hepatitis but lacked specificity. This was dramatic as it incorrectly predicted the outcome at 28 days after admission in 51% of cases.
• They also suggests that even with a mDF greater than or equal to 32, patients with a GAHS less than nine do not benefit from such treatment.

What is GAHS?

Discuss GAHS Vs mDF?

Thus GAHS of 9 or more is much more discriminatory in identifying patients most at risk of death. A score of 9 or more can be used either on day 1 (admission day) or day6-9.

What is the steroid dose and duration?
Prednisolone 40 mg daily for four weeks followed by a taper.
Careful monitoring for evidence of infection, gastrointestinal bleeding, glucose intolerance, or renal failure is essential while the patient is on prednisolone therapy.

How do you assess response?
Any fall in serum bilirubin after one week of corticosteroid treatment is indicative of treatment response and good prognosis.

Are there any other treatments for Alcoholic Hepatitis?
The role for pentoxifylline whilst promising is as yet unproven. It acts by inhibiting TNF alpha.

What other supportive care can patients with Alcoholic hepatitis be provided?

• These patients are at risk of sepsis. Close vigilance for sepsis and a low threshold for the use of antibiotics is required.
• These patients have significant protein energy malnutrition. Nutritional support is vital for these patients.

Summary
Patients with severe disease (mDF > 32, or more specifically GAHS > 9) benefit from corticosteroids, and perhaps pentoxifylline.

References

1. McCullough AJ, O’Connor, JF. Alcoholic liver disease: Proposed recommendations for the American College of Gastroenterology. Am J Gastroenterol 1998; 93:2022.
2. Forrest EH. A clinical approach to alcoholic hepatitis. J R Coll Physicians Edinb 2007; 37:3-8 (archived copy at webcite)
3. Forrest EH et al. Analysis of factors predictive of mortality in alcoholic hepatitis and derivation and validation of the Glasgow alcoholic hepatitis score. Gut 2005; 54; 1174-1179 (archived copy at webcite)