It is estimated
,as shown in Figure 1, that although 90-100% of heavy drinkers show evidence
of fatty liver, only 10-35% develop alcoholic hepatitis and 8-20% develop
of liver disease
Acute Alcoholic hepatitis
In alcoholic hepatitis , the typical histologic picture includes hepatocellular necrosis and ballooning degeneration, alcoholic Mallory's hyaline bodies and an inflammatory reaction with many polymorphonuclear leukocytes (sattelitosis). It is estimated that 15-20 years of excessive drinking is necessary to develop alcoholic hepatitis. Cholestasis is prominent. It is more severe in females and also in Nothern Europeans and unrelated to pattern of drinking or type of alcohol drink. High mortality rates are seen (30-60%) and patients often deteriorate after hospital admission despite abstinence. Alcoholic hepatitis has been established as an important precursor to the formation of cirrhosis.
The most severe form of alcoholic liver injury and usually of the micronodular type. The risk is increased in continuous drinkers. Survival for patients is 60%-70% at one year and 35%-50% at five years.
evidence indicates that the principal cause of alcohol-induced liver injury
is cellular toxicity resulting from acetaldehyde.
of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-a),
transforming growth factor-beta (TGF-ß), interleukin (IL)-1ß and IL-6
are increased in alcoholic liver injury while the anti-inflammatory cytokine,
IL-4 is decreased.
presentation of alcoholic hepatitis varies greatly with the severity of
disease. Common symptoms are weakness, anorexia, weight loss, nausea,
vomiting and diarrhea. Patients with alcoholic hepatitis are often malnourished
gastrointestinal bleeding does occur but is usually due to gastric erosions
or peptic ulceration on a backgroung of coagulopathy Infections are very
scanning can help eliminate the possibility of biliary tract disease in
jaundiced and febrile patients.
biopsy is necessary to confirm the diagnosis, to assess the extend of
liver injury and to provide a prognostic guide.
In patients with severe disease, the 30-day mortality rate approaches 50% but in all patients with alcoholic hepatitis the overall 30-day mortality rate is about 15%.
The Maddrey's discriminant
function following the below formula has the best correlation and the
highest positive predictive value to predict the 30-day mortality. Discriminant
function: (4,6 X ptothrombin time prolongation in seconds) + bilirubin
Others factors that correlate with poor prognosis include older age, impaired renal function, encephalopathy, and a rise in the white blood cell count in the first 2 weeks of hospitalization.
Patients with mild to moderate disease usually survive this stage of their illness as long as they abstain from alcohol use.
Patients with severe alcoholic hepatitis (Maddrey's score above 32) require active, specific treatment to alter the grim, high short-mortality rate.
As shown in table
2, there have been a number of therapeutic agents that have undergone
clinical testing for alcoholic hepatitis. Among all of these therapies,
only corticosteroids and total enteral nutrition have clearly shown benefit.
Corticosteroids have been the most controversial therapy in alcoholic hepatitis. More than 40 studies have been conducted to test the effect of this treatment. Recent two meta-analyses of 11 randomized control trials are more in favor of corticosteroid therapy for patients with severe disease and spontaneous hepatic encephalopathy. However steroids seems to have a beneficial effect on short term survival but not on long-term survival. Recent study has shown that enteral nutrition was associated with a better long-term outcome compared with corticosteroids. Actually no single therapy had had universally miraculous success.
Because patients with alcoholic hepatitis often have protein-calorie malnutrition, nutritional support has been a tempting therapeutic option. Recent data have clearly shown that total enteral nutrition (20-30 kcal/kg/day) is actually the treatment of choice because of the beneficial effect on long-term outcome with a decrease of the infections rate.
Orthotopic liver transplantation has been shown to be the chief therapeutic option for patients with end-stage alcoholic liver disease. An abstinence of 3 to 6 months before operation is required to have a low rate of alcohol abuse recidivism after transplantation.
Alcoholic hepatitis is a necrotizing, inflammatory process often leading to cirrhosis or death. The diagnosis of this severe condition necessitates to perform liver biopsy.
The pathogenesis is not fully understood although significant progress has been achieved recently. The prognosis is poor in severe disease when alterations of prothombin time and serum bilirubin levels are marked. Abstinence from alcohol and appropriate total enteral nutrition are probably the most effective current treatment.
There is renewed interest in the use of corticosteroids in severe disease. Orthotopic liver transplantation is appropriate for some patients with end-stage liver disease.