Pathogenesis, Diagnosis, and Treatment of Alcoholic Liver Disease

Abstract

Alcohol-related liver disease is a major cause of morbidity and mortality in the United States. Alcoholic liver disease encompasses a clinicohistological spectrum, including fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver is a benign and reversible condition, but progression to alcoholic hepatitis and cirrhosis is life-threatening. Alcoholic hepatitis is diagnosed predominantly on clinical history, physical examination, and laboratory testing, although liver biopsy is often necessary to secure the diagnosis. The major focus of management is abstinence from alcohol, supportive care, treatment of complications of infection and portal hypertension, and maintenance of positive nitrogen balance through nutritional support. Corticosteroid therapy is controversial but should be considered in patients with a discriminant function greater than 32 and/or presence of spontaneous hepatic encephalopathy in the absence of infection, gastrointestinal bleeding, and renal failure. The only curative therapy for advanced alcoholic cirrhosis is liver transplantation. Several recent advances in understanding the pathogenesis of alcoholic liver disease may lead to novel future treatment approaches, including inhibition of tumor necrosis factor a, antioxidant therapy, stimulation of liver regeneration, and stimulation of collagen degradation.

Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

“…This mechanistic focus in the lung contrasts the intense study of the effects of EtOH on metabolic homeostatic processes in other organs, such as the liver. It has been shown that EtOH induces significant metabolic disturbances in the liver, and these perturbations are thought to contribute to the pathogenesis of EtOHrelated liver diseases, such as alcoholic fatty liver disease, steatohepatitis, and cirrhosis (12)(13)(14).…”

Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease

“…Both diseases encompass a spectrum of histopathology, ranging from steatosis to cirrhosis. 4,5 Steatohepatitis is believed to be an intermediate stage in the progression from steatosis to cirrhosis, because the probability of developing advanced hepatic fibrosis is significantly greater in individuals with steatohepatitis than in those with simple steatosis. 4,6,7 Efforts have focused on delineating the pathogenesis of steatohepatitis so that effective treatments to interrupt progression from relatively occult to clinically significant liver disease might be developed.…”

Alcohol and hepatocyte-Kupffer cell interaction (Review)

“…In addition, a large body of literature indicates the role of alcohol metabolites, reactive oxygen/ nitrogen species (RNS/ROS), bacterial translocation from the gut, TNF-α and hepatic stellate cell (HSC) activation as the combined cause of alcohol-induced hepatic damage. Therefore, a consensus has been emerging concerning the general pathway culminating in severe ALD involving a complex orchestration between Kupffer cells (KCs), HSC and hepatocytes (7,9,16). This study reviews these concepts and highlights the key role played by the noradrenergic stimuli NE and its receptor in the causation of alcohol-derived injury in the liver.…”

“…Alcohol, however, has also beneficial effects, and moderate alcohol consumption has been shown to improve digestion and cholesterol profile, and to lower the risk of ischemic heart disease (12,13). Epidemiological data has shown a clear correlation between excessive and prolonged alcohol consumption and liver disease (6,7). The molecular mechanisms underlying these interactions are still being elucidated.…”

“…ALD covers a spectrum of increasing hepatic dysfunction, ranging from steatosis to liver failure and malignant hepatic disease. The most prevalent types of ALD are fatty liver, alcoholic hepatitis and cirrhosis (6,7). As a major synthetic and metabolic organ, the liver plays an essential role in the body.…”