Because generation of acetaldehyde and free radicals is maximal in the centrilobular region, this region is most susceptible to toxic injury. Pericellular and sinusoidal fibrosis develop first in this area of the lobule. Concurrent viral hepatitis, particularly hepatitis C, is a major accelerator of liver disease in alcoholics. The prevalence of hepatitis C among individuals with alcoholic liver disease is about 30% (and vice versa).
For unknown reasons, cirrhosis develops in only a small fraction of chronic alcoholics. With complete abstinence, at least partial regression of scarring occurs, and the micronodular liver transforms though parenchymal regeneration into a macronodular cirrhotic organ (see 16.6 ); rarely, there is regression of cirrhosis altogether.
Alcoholic steatosis may be innocuous or give rise to hepatomegaly with mild elevations of serum bilirubin and alkaline phosphatase. Severe hepatic compromise is unusual. Alcohol withdrawal and the provision of an adequate diet are sufficient treatment.
It is estimated that 15 to 20 years of excessive drinking are necessary to develop alcoholic cirrhosis, but alcoholic hepatitis can occur after just weeks or months of alcohol abuse. The onset is typically acute and often follows a bout of particularly heavy drinking. Symptoms and laboratory abnormalities range from minimal to severe. Most patients present with malaise, anorexia, weight loss, upper-abdominal discomfort, tender hepatomegaly, and fever. Typical findings include hyperbilirubinemia, elevated serum alkaline phosphatase levels, and neutrophilic leukocytosis. Serum alanine and aspartate aminotransferases are elevated but usually remain below 500 U/mL. The outlook is unpredictable; each bout of alcoholic hepatitis carries a 10% to 20% risk for death. With repeated bouts, cirrhosis appears in about one-third of patients within a few years.
The manifestations of alcoholic cirrhosis are similar to those of other forms of cirrhosis. In chronic alcoholics, ethanol may be the major source of calories in the diet, displacing other nutrients and leading to malnutrition and vitamin deficiencies (e.g., thiamine, vitamin B12). Compounding these effects is impaired digestive function, primarily related to chronic gastric and intestinal mucosal damage and pancreatitis.
The long-term outlook for alcoholic patients with liver disease is variable. The most important aspect of treatment is abstinence from alcohol. The 5-year survival rate approaches 90% in abstainers who are free of jaundice, ascites, and hematemesis, but drops to 50% to 60% in individuals who continue to imbibe. Among those with end-stage alcoholic liver disease, the immediate causes of death are as follows:
Intercurrent infection (to which affected individuals are predisposed)
Hepatocellular carcinoma (3%–6% of cases)
Alcoholicliverdiseasehasthreemainmanifestations,hepaticsteatosis,alcoholichepatitis,andcirrhosis,whichmayoccuraloneorincombination.
Cirrhosistypicallydevelopsaftermorethan10yearsofheavydrinking,butonlyoccursinasmallproportionofchronicalcoholics;alcoholiccirrhosishassimilarclinicalsignsandsymptomsascirrhosiscausedbyviralhepatitis.
Themultiplepathologiceffectsofalcoholincludechangesinlipidmetabolism,decreasedexportoflipoproteins,andcellinjurycausedbyreactiveoxygenspeciesandmetabolitesofalcohol.
NAFLD is a common condition in which fatty liver disease develops in individuals who do not drink alcohol.