Alcohol associated liver disease (ALD) is among the most common hepatic diseases worldwide.
ALD contributes approximately 25% of deaths from cirrhosis.
The number of individuals with alcohol associated liver disease is increasing.
Individuals with harmful alcohol use of greater than two drinks per day for women and greater than three drinks per day for men or at risk for ALD.
ALD begins with the development of hepatic steatosis from the accumulation of triglycerides in hepatocytes.
Chronic alcoholism and liver injury are related by a two-hit system: the first hit is direct toxicity of ethanol and its metabolic byproducts, the second hit is indirect, mediated by increased uptake of lipopolysaccharide, as endotoxin, from the intestine.
The presence of endotoxin induces a strong polarization of Kupffer cells, and a large amount of reactive oxygen species, pro-inflammatory cytokines and chemokines are produced by the activated Kupffer cells which lead to liver injury.
Ethanol increases permeability of the intestinal epithelium, resulting in endotoxin produced by the intestinal flora leaking from the intestinal lumen into the liver via the portal vein.
The presence of endotoxin induces a strong polarization of Kupffer cells, and a large amount of reactive oxygen species, pro-inflammatory cytokines and chemokines are produced by the activated Kupffer cells which lead to liver injury.
There is an endotoxin-mediated activation of the Toll-like receptor 4 (TLR4) and CD14, receptors on the Kupffer cell that internalize endotoxin, which activates the transcription of pro-inflammatory cytokines and tumor necrosis factor-alpha (TNFα), with concurrent production of superoxides.
Cytokines and superoxides cause inflammation and oxidizing damage respectively, while TNFα triggers the stellate cells in the liver to initiate collagen synthesis.
These processes result in fibrosis, or scarring of the liver.
Fibrosis will eventually cause cirrhosis, a loss of function of the liver due to extensive scarring.
Subsequently, alcoholic hepatitis and fibrosis may develop.
Alcoholic hepatitis is an inflammatory process based on the presence of the steatosis, hepatocyte ballooning, he amorphous eosinophilic inclusions (Mallory bodies) and neutrophilic infiltration.
Approximately 10 to 20% of patients with ALD develop cirrhosis, with alcoholic hepatitis being at the highest risk for progression of fibrosis.
There is a dose response association between the amount of alcohol consumed and the risk of cirrhosis.
There is a higher rate of alcohol liver disease for a given alcohol intake for women compared with men.
The risk of cirrhosis in men and women at age 40 who have been drinking mote than 10 drinks per day for more than 15 years is 3.1% and 4.7%, respectively.
There is a higher rate of alcohol liver disease for a given alcohol intake for women compared with men.
Alcohol drinking patterns, minority status, low socioeconomic status, and comorbidities of obesity and hepatitis C and B, increase the risk and severity of alcohol related liver disease.
There is an increased risk of alcohol associated liver disease in the presence of genetic polymorphisms (PNPLA 3), the gene involved in lipolysis in adipocytes and hepatic fat metabolism.
Alcohol is metabolized in the liver to acetaldehyde buy alcohol dehydrogenase by the CYP2E1 enzyme complex.
Steatosis, the initial histological finding mainly develops because of alcohol induced down regulation of hepatic beta oxidation of fatty acids.
Alcohol down regulates hepcidin, resulting in increased liver on continent in approximately 50% of patients.
Alcohol and its metabolites in the intestinal lumen alter the gut microbiome by decreasing synthesis of long chain fatty acids by microbes.
Excessive consumption of alcohol increases the permeability of tight intestinal epithelial junctions, and indices profound changes in the microbiome, including increasing increased pathogenic bacteria.
The subsequent translocation of viable bacteria and microbial products to the liver, Induces and Inflammation, favors how to say death, and stimulate a fibrotic response.
Alcohol increases gut permeability and enhances entry to the portal circulation of bacterial lipopolysaccharides.
Macrophage recognition of these lipopolysaccharides result in inflammatory signaling pathways exacerbating hepatocyte injury resulting in lipid peroxidation, mitochondrial damage, and oxidative stress.
The resulting hepatocyte death results in release of pro-inflammatory cytokines and chemokines, including tumor necrosis factor mediating hepatic inflammation and recruit neutrophils and other immune cells further damaging the liver.
Activated stellate cells promote fibrosis of the liver and are the main source of extracellular matrix tissue.
Hepatic regeneration is impaired by alcohol inhibition of liver DNA synthesis and microRNA signaling: so imbalance from the pro inflammatory response, hepatocyte injury, and insufficient regeneration determines the outcome of severe forms of alcohol induced liver disease.
More than 90% of patients with alcohol associated liver disease are asymptomatic or have nonspecific symptoms.
ALD is frequently diagnosed by the presence of steatosis on liver imaging or abnormal liver tests.
ALD is defined by features of alcohol induced liver injury, such as steatosis, alcoholic hepatitis, liver fibrosis or cirrhosis, either alone or in combination in patients with harmful alcohol consumption.
Approximately 70% of patients with compensated cirrhosis are asymptomatic.
ALD may be associated with physical findings suggesting cirrhosis such as enlarged, firm liver, spiders, splenomegaly, and muscle wasting.
Laboratory abnormalities in ALD include: elevated MCV, elevated liver function tests, elevated bilirubin or prothrombin time, decreased albumin or thrombocytopenia.
Individuals with harmful alcohol consumption should be screened for ALD with biochemical liver tests: ALT, AST, alkaline phosphatase, gamma GT, and total bilirubin, along with liver ultrasonography.
Transaminase levels are elevated with ALD, but they are usually less than 400 international units per liter with the ratio of AST to ALT greater than 1.
Liver ultrasound can detect moderate to severe steatosis, defined as fat droplets in more than 33% of parasites, with the sensitivity and specificity of approximately 90%.
Liver biopsy stratifies fibrosis stages as early, or advanced.
Steatosis is associated with a significant increase risk of liver related mortality.
Alcoholic hepatitis is associated with the fastest hepatic disease progression, a higher risk of symptomatic disease, and acute on chronic liver failure in severe cases.
The prevalence of asymptomatic alcoholic hepatitis is 17% among hospitalized patients with alcohol related liver disease acute on chronic liver failure.
The liver fibrosis stage is associated with long term outcome.
Activated stellate cells promote fibrosis of the liver and are the main source of extracellular matrix tissue.
Hepatic regeneration is impaired by alcohol inhibition of liver DNA synthesis and microRNA signaling: so imbalance from the pro inflammatory response, hepatocyte injury, and insufficient regeneration determines the outcome of severe forms of alcohol induced liver disease.
More than 90% of patients with alcohol associated liver disease are asymptomatic or have nonspecific symptoms.
ALD is frequently diagnosed by the presence of steatosis on liver imaging or abnormal liver tests.
ALD is defined by features of alcohol induced liver injury, such as steatosis, alcoholic hepatitis, liver fibrosis or cirrhosis, either alone or in combination in patients with harmful alcohol consumption.
Approximately 70% of patients with compensated cirrhosis are asymptomatic.
ALD may be associated with physical findings suggesting cirrhosis such as enlarged, firm liver, spiders, splenomegaly, and muscle wasting.
Laboratory abnormalities in ALD include: elevated MCV, elevated liver function tests, elevated bilirubin or prothrombin time, decreased albumin or thrombocytopenia.
Individuals with harmful alcohol consumption should be screened for ALD with biochemical liver tests: ALT, AST, alkaline phosphatase, gamma GT, and total bilirubin, along with liver ultrasonography.
Transaminase levels are elevated with ALD, but they are usually less than 400 international units per liter with the ratio of AST to ALT greater than 1.
Liver ultrasound can detect moderate to severe steatosis, defined as fat droplets in more than 33% of parasites, with the sensitivity and specificity of approximately 90%.
Liver biopsy stratifies fibrosis stages as early, or advanced.
Steatosis is associated with a significant increase risk of liver related mortality.
Alcoholic hepatitis is associated with the fastest hepatic disease progression, a higher risk of symptomatic disease, and acute on chronic liver failure in severe cases.
The prevalence of asymptomatic alcoholic hepatitis is 17% among hospitalized patients with alcohol related liver disease acute on chronic liver failure.
The liver fibrosis stage is associated with long term outcome.
Transient elastography is the most widely used radiologic marker to evaluate fibrosis.
Ultrasound elastography measures liver stiffness by detecting the velocity of microdisplacement, or shear waves, in liver tissue.
Ultrasound elastography has a sensitivity and specificity for advanced fibrosis with cirrhosis of 86% and 94%, respectively.
There are multiple other elastography techniques as well.
The prevalence of alcohol use disorder in patients with alcohol associated cirrhosis is 38%.
The long-term prognosis of ALD is determined primarily by alcohol relapse, which occurs by one year and o cuts in as many is 30 to 50% of patients with severe alcoholic hepatitis who survive the index hospitalization.
Management of patients with early ALD relates to the stage of fibrosis, while patients with advanced ALD are managed according to the degree of decompensation and the type of associated complications.
Oral steroids are indicated in patients with severe alcoholic hepatitis.
Liver graft and patient survival at five years after liver transplant in alcoholic liver disease are 74 and 79%, respectively.
Liver transplant is considered in abstinent patients with a MELD score of greater than 17 or in patients with complications that are refractory yo medical treatment.