Alcoholic hepatitisAlcoholic hepatitis

How is Alcoholic hepatitis How is Alcoholic hepatitis diagnosed?diagnosed?

History of recent excessive alcohol History of recent excessive alcohol ingestion ingestion

Serum bilirubin more than 80umol/l Serum bilirubin more than 80umol/l

ALT <300 IU (or AST<500 IU) ALT <300 IU (or AST<500 IU)

Exclusion of autoimmune, chronic viral or Exclusion of autoimmune, chronic viral or malignant liver disease malignant liver disease

Characteristic features of alcoholic hepatitis (but not Characteristic features of alcoholic hepatitis (but not necessary for diagnosis)necessary for diagnosis)

Pyrexia, Pyrexia,

Hepatomegaly, Hepatomegaly,

A hepatic bruit, A hepatic bruit,

Ascites, Ascites,

Encephalopathy, Encephalopathy,

AST: ALT ratio greater than 1.5, AST: ALT ratio greater than 1.5,

Peripheral leucocytosis. Peripheral leucocytosis.

How accurate is a clinical How accurate is a clinical diagnosis of Alcoholic hepatitis?diagnosis of Alcoholic hepatitis?

An accuracy of about 80% has been An accuracy of about 80% has been quoted for the clinical diagnosis of quoted for the clinical diagnosis of alcoholic hepatitis when compared with alcoholic hepatitis when compared with histology. histology.

Does alcoholic hepatitis with co-Does alcoholic hepatitis with co-existing cirrhosis alters the existing cirrhosis alters the

prognosis or treatment?prognosis or treatment?

Approximately 50-60% will also have Approximately 50-60% will also have established cirrhosis. established cirrhosis.

There is no evidence that co-existing There is no evidence that co-existing cirrhosis worsens the short term outcome cirrhosis worsens the short term outcome of patients with alcoholic hepatitis, of patients with alcoholic hepatitis, indicating that it is the acute inflammatory indicating that it is the acute inflammatory process which is primarily responsible for process which is primarily responsible for the poor prognosis of these patients. the poor prognosis of these patients.

How do you assess the severity How do you assess the severity of Alcoholic Hepatitis?of Alcoholic Hepatitis?

Modified discriminant function (mDF)Modified discriminant function (mDF)

Glasgow alcoholic hepatitis score (GAHS)Glasgow alcoholic hepatitis score (GAHS)

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

American College of Gastroenterology American College of Gastroenterology defines severity as a modified Discriminant defines severity as a modified Discriminant Function (mDF)Function (mDF)>> 32 and/or hepatic 32 and/or hepatic encephalopathy.encephalopathy.

Where would you use steroids?Where would you use steroids?

American College of Gastroenterology American College of Gastroenterology recommends prednisolone should be used recommends prednisolone should be used in patients with severe alcoholic hepatitis in patients with severe alcoholic hepatitis in whom the diagnosis is certain. Severity in whom the diagnosis is certain. Severity is defined as a DF> 32 and/or hepatic is defined as a DF> 32 and/or hepatic encephalopathy encephalopathy

mDFmDF>> 32 and/or hepatic encephalopathy 32 and/or hepatic encephalopathy was associated with a 65% 28-day was associated with a 65% 28-day survival survival

<32 had a survival of 93%.<32 had a survival of 93%.

Patients with mDF Patients with mDF >>32 and treated with 32 and treated with steroids had a 28 day survival of 84.6% steroids had a 28 day survival of 84.6% compared with 65.1% for placebo treated compared with 65.1% for placebo treated patients. patients.

The efficacy of steroids has not been The efficacy of steroids has not been adequately evaluated in patients with adequately evaluated in patients with severe alcoholic hepatitis who also havesevere alcoholic hepatitis who also have– concomitant pancreatitis, concomitant pancreatitis, – gastrointestinal bleeding, gastrointestinal bleeding, – renal failurerenal failure– active infection. active infection.

What is the steroid dose and What is the steroid dose and duration?duration?

Prednisolone 40 mg daily for four weeks Prednisolone 40 mg daily for four weeks followed by a taper.followed by a taper.

Careful monitoring for evidence of Careful monitoring for evidence of infection, gastrointestinal bleeding, infection, gastrointestinal bleeding, glucose intolerance, or renal failure is glucose intolerance, or renal failure is essential while the patient is on essential while the patient is on prednisolone therapy.prednisolone therapy.

How do you assess response?How do you assess response?

Any fall in serum bilirubin after one week Any fall in serum bilirubin after one week of corticosteroid treatment is indicative of of corticosteroid treatment is indicative of treatment response and good prognosis.treatment response and good prognosis.

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

These patients are at risk of sepsis. Close These patients are at risk of sepsis. Close vigilance for sepsis and a low threshold for vigilance for sepsis and a low threshold for the use of antibiotics is required. the use of antibiotics is required.

These patients have significant protein These patients have significant protein energy malnutrition. Nutritional support is energy malnutrition. Nutritional support is vital for these patients. vital for these patients.

What is GAHS?What is GAHS?

Criticism of mDFCriticism of mDF

mDF relies on the absolute value of the PT mDF relies on the absolute value of the PT The presence of encephalopathy has often been The presence of encephalopathy has often been included when making a treatment decision, in addition included when making a treatment decision, in addition to just calculating the mDF. to just calculating the mDF.

mDF was highly sensitive in the prediction of death from mDF was highly sensitive in the prediction of death from alcoholic hepatitis but lacked specificity. This was alcoholic hepatitis but lacked specificity. This was dramatic as it incorrectly predicted the outcome at 28 dramatic as it incorrectly predicted the outcome at 28 days after admission in 51% of cases. days after admission in 51% of cases. They also suggests that even with a mDF greater than or They also suggests that even with a mDF greater than or equal to 32, patients with a GAHS less than nine do not equal to 32, patients with a GAHS less than nine do not benefit from such treatment. benefit from such treatment.

Are there any other treatments for Are there any other treatments for Alcoholic Hepatitis?Alcoholic Hepatitis?

Pentoxifylline, a phosphodiesterase Pentoxifylline, a phosphodiesterase inhibitorinhibitor

It acts by inhibiting TNF alpha.It acts by inhibiting TNF alpha.

Dose 400mg tds Dose 400mg tds

One hundred one patients with severe One hundred one patients with severe alcoholic hepatitis (Maddrey discriminant alcoholic hepatitis (Maddrey discriminant factor > or = 32) entered a 4-week double-factor > or = 32) entered a 4-week double-blind randomized trial of PTX (400 mg blind randomized trial of PTX (400 mg orally 3 times daily) vs. placebo orally 3 times daily) vs. placebo

Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil O (2000). "Pentoxifylline Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil O (2000). "Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial". placebo-controlled trial". GastroenterologyGastroenterology 119119 (6): 1637–48 (6): 1637–48

Twelve (24.5%) of the 49 patients who Twelve (24.5%) of the 49 patients who received PTX and 24 (46.1%) of the 52 received PTX and 24 (46.1%) of the 52 patients who received placebo died during patients who received placebo died during the index hospitalization (P = 0.037; the index hospitalization (P = 0.037; relative risk, 0.59; 95% confidence relative risk, 0.59; 95% confidence interval, 0.35-0.97). interval, 0.35-0.97).

SummarySummary

Non cirrhotic vs cirrhoticNon cirrhotic vs cirrhotic

Typical blood testTypical blood test

Assess severityAssess severity

Treatment with steroid and Treatment with steroid and pentoxyphyllinepentoxyphylline

Nutrition and alcohol detoxNutrition and alcohol detox