ALCOHOLIC HEPATITIS

Patrick D. Hung, M.D.

Alcoholic hepatitis is a disease entity that occurs in 15-20% of chronic alcohol abusers.  It is uncertain why more chronic abusers are not affected, however, it is postulated that genetic differences allow some to tolerate the toxic effects of alcohol better.  Clinically these patients present with jaundice, right upper quadrant pain, fever, tender hepatomegaly, and in severe cases, overt liver failure.  Patients who suffer even one bout of alcoholic hepatitis are prone to develop cirrhosis.  It is felt that 50% of these patients will develop cirrhosis even with continued abstinence.  On laboratory evaluation these patients manifest liver function derangements such as elevated prothrombin time and bilirubin.  It is important to note that liver function tests are not synonymous with liver enzymes, such as AST, ALT, and AP.  Prothrombin time and bilirubin represent only a couple of markers of liver function, which signify significant liver disease in alcohol abusers if they are abnormal.  Patients who abuse alcohol, without evidence of alcoholic hepatitis, will have elevation in the transaminases, classically in a 2:1 ratio of AST>ALT.  Alkaline phosphatase can be elevated, and if it is, this represents a cholestatic variant of alcoholic hepatitis that denotes a worse prognosis.  The transaminase elevations in alcoholic hepatitis are typically between 100-300’s.  It is important to emphasize that the diagnosis of alcoholic hepatitis is a clinical diagnosis and not strictly based on laboratory values, however, if the transaminases are elevated beyond 500 another etiology needs to be sought. 

            The pathogenesis in alcoholic hepatitis can be viewed as a disruption in homeostasis.  There are three main sites of alcohol metabolism in the liver: Cytosolic, CYP2E1, and catalase system.  The catalase system plays a minor role and will not be discussed further.  The cytosolic system works via the alcohol dehydrogenase pathway (ADH) converting alcohol to acetylaldehyde and finally to acetate.  The CYP2E1 system, which is an inducible system, normally serves to detoxify any toxic metabolites such as acetominophen.  The problem arises when chronic alcohol abuse overwhelms the ADH pathway and induces increased activity of the CYP2E1 system.  The net result a disruption of homeostasis, which leads to a cascade of ill effects, such as the release of cytokines.  One of the main culprits in liver damage is Tumor Necrosis Factor Alpha or TNF-a.  This causes a multitude of problems such as attracting and activating neutrophils, damaging mitochondria, which is important for cellular respiration, and apoptosis.  It is important to mention that patients with chronic alcohol abuse, who take normal doses of acetominophen, are at higher risk of developing liver failure.  As stated above, alcohol induces the CYP2E1 system, which normally detoxifies acetominophen.  Since alcohol has disrupted the balance, detoxification mechanisms are not functional and the toxic metabolites of acetominophen will damage the liver. 

            Novel therapies do exist for the treatment of alcoholic hepatitis; however, the standard of care is to use corticosteroids in severe cases.  Those patients deemed to be a severe case have a Discriminant Index >32.  This is derived from a formula that takes into consideration liver function parameters such as prothrombin time and bilirubin, and values >32 should be treated with steroids.  Steroids are shown to decrease the short-term mortality in severe cases.  If the patients do not meet the criteria management is supportive care with emphasis on proper nutrition and alcohol cessation.  Patients can have a 30-40% mortality rate with alcoholic hepatitis and need to be counseled about the serious consequences of their actions.