Alcoholic hepatitis

A treatable form of alcoholic liver disease.

Alcoholic hepatitis is an inflammatory process based on the presence of steatosis, hepatocyte ballooning, he amorphous eosinophilic inclusions (Mallory bodies) and neutrophilic infiltration.

A common complication of alcohol abuse.

Severity ranges from mild to severe liver inflammation, and can lead to jaundice, prolonged prothrombin time, and liver failure.

Up to 40% of patients with severe disease die within 6 months after the onset of the clinical process.

A syndrome of jaundice and liver failure that occurs after decades of heavy alcohol use with a mean intake of approximately 100 gm per day.

Typical age of presentation 40-60 years of age.

Patients may present several weeks after stopping alcohol abuse.

Because more men than women abuse alcohol, it is more common in men, but female sex is an independent risk factor.

Type of alcohol used is does not affect the risk.

Prevalence of 20% in patients with alcoholism (Naveau).

Severe AH is life-threatening.

Cardinal sign is rapid onset of jaundice.

Clinical features include fever, hepatomegaly, jaundice, and anorexia.

May be associated with fever, ascites, proximal muscle loss, elevated alkaline phosphatase levels and hyperbilirubinemia..

Long-term alcohol consumption increases intestinal permeability, worsens endotoxemia, stimulates Kupffer cells activity and increases pro-inflammatory cytokines.

Associated with high levels of tumor necrosis factor-alpha , which activate apoptosis pathways and induce production of reactive oxygen species, especially superoxide anions, by liver mitochondria leading to cell death.

The above process is accompanied by mitochondrial depletion of glutathione, the primary antioxidant in cells.

Hepatocytes are increasingly sensitive to TNF-alpha, when antioxidant reserves are low.

May be associated with hepatic encephalopathy.

Clinically associated with enlarged and tender liver.

Laboratory evaluation reveals elevated aspartate aminotransferase more than twice normal, but rarely is higher than 300 IU per milliliter.

Serum alanine aminotranferase elevations are lower than that of aspartate aminotranferase and the ratio of the aspartate aminotranferase level to the alanine transferase is usually greater than 2.

High ratio of aspartate aminotranferase: alanine aminotranferase ratio possible related to reduced hepatic alanine aminotranferase activity , alcohol induced depletion of hepatic pyridoxal 5’phosphate and increased hepatic mitochondria aspartate.

White blood count elevation, neutrophil count elevation, serum bilirubin elevation, and elevated serum INR are present.

When associated with elevation of creatinine may portend the onset of the hepatorenal syndrome.

Associated with hepatocellular injury characterized by ballooned hepatocytes that often have amorphous eosinophilic inclusion bodies, Mallory bodies, surrounded by neutrophils.

Fat globules in hepatocytes, steatosis, is common finding in alcoholic hepatitis.

A characteristic lesion is intrasinusoidal fibrosis, which is fibrosis between the endothelial cell and the hepatocytes.

Features of alcoholic fibrosis of perivenular fibrosis, periportal fibrosis, and cirrhosis often coexist with findings of alcoholic hepatitis.

May have microscopic findings of foamy degeneration of hepatocytes and acute sclerosing hyaline necrosis.

Treatment includes alcohol abstinence, nutritional support and corticosteroids.

Corticosteroids are thought to reverse hepatic inflammation by decreasing circulating levels of pro-inflammatory cytokines including IL-8 and TNF.

Pentoxifillin is thought to improve alcoholic hepatitis by protecting against the hepatorenal syndrome, possibly by modulation of TNF transcription.

The outcome of a four week treatment study with a combination of pentoxifylline and prednisolone did not improve six-month survival compared to prednisolone treatment alone (Mathurin P et al ), and the combination therapy is not recommended.

Approximately 40% of patients with alcohol hepatitis are responsive to corticosteroids.

Many patients have contraindications to the use of corticosteroids, such as acute infections.

Pentoxifylline reduces short term mortality in acute hepatitis.

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