Diagnosis and Treatment of Alcohol-Associated Liver Disease

Abstract

ImportanceAlcohol-associated liver disease results in cirrhosis in approximately 10% to 20% of patients. In 2017, more than 2 million people had alcohol-associated cirrhosis in the US. Alcohol-associated liver disease is the primary cause of liver-related mortality and the leading indication for liver transplant, representing 40% to 50% of all liver transplant in high-income countries.ObservationsSteatosis, alcoholic hepatitis, and fibrosis are the 3 pathologic findings that are associated with progression to cirrhosis, with highest risk in patients with alcoholic hepatitis. The amount and duration of alcohol consumption, female sex, obesity, and specific genetic polymorphisms such as patatin-like phospholipase domain protein 3, membrane bound O-acyltransferase, and transmembrane 6 superfamily member 2 genes are risk factors for alcohol-associated liver disease progression. Ten-year survival of patients with alcohol-associated liver disease is 88% among those who are abstinent and 73% for those who relapse to alcohol consumption. Symptomatic alcoholic hepatitis is characterized by rapid onset of jaundice and a 30% risk of mortality 1 year after diagnosis. Severe alcoholic hepatitis, defined as a modified discriminant function score greater than or equal to 32 or Model for End-Stage Liver Disease score (starts at 6 and capped at 40; worst = 40) greater than 20, is associated with the development of acute-on-chronic liver failure and multiorgan failure. Corticosteroid therapy is associated with improved 1-month survival from 65% in untreated patients to 80% in treated patients. Early liver transplant may be appropriate in highly select patients with severe alcoholic hepatitis who do not respond to medical therapy. In patients with decompensated cirrhosis, liver transplant should be considered if the Model for End-Stage Liver Disease score remains greater than 17 after 3 months of alcohol abstinence. Between 2014 and 2019, the proportion of patients waiting for liver transplantation who had alcohol-associated liver disease increased from 22% to 40%. Alcohol-associated cirrhosis accounted for approximately 27% of 1.32 million deaths worldwide related to cirrhosis in 2017.Conclusions and RelevanceAlcohol-associated liver disease is among the most common liver diseases and more than 2 million people in the US in 2017 had alcohol-associated cirrhosis. Corticosteroid therapy improves survival in select patients with severe alcoholic hepatitis. Liver transplantation is the most effective therapy in patients with decompensated liver disease.

Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver

“…AALD encompasses a large spectrum of liver lesions including microvesicular and macrovacuolar steatosis, steatohepatitis, extensive fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [ 57 , 58 ]. AALD is the primary cause of liver-related mortality and the leading indication for liver transplantation [ 58 ].…”

“…AALD encompasses a large spectrum of liver lesions including microvesicular and macrovacuolar steatosis, steatohepatitis, extensive fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [ 57 , 58 ]. AALD is the primary cause of liver-related mortality and the leading indication for liver transplantation [ 58 ]. As already mentioned, CYP2E1 plays a major role in the development and progression of AALD, in particular via the generation of acetaldehyde, free radicals and ROS [ 2 , 8 , 9 , 36 ].…”

Treating Alcohol Use Disorder in Patients with Alcohol-Associated Liver Disease: Controversies in Pharmacological Therapy

“…(140). BI consists of one to four sessions of 5-30 minutes motivational interviewing aimed at delivering information on the risks associated with unhealthy alcohol consumption and the goal to reinforce the subject's motivation to achieve abstinence or to reduce drinking (17,141). BI can be delivered by general practitioners or by specialized addiction services.…”

“…adolescents) showing alcohol use, even if the effect size was modest (142). Data supporting the effectiveness of BI for patients with moderate-severe AUD and for those with ALD are contrasting, limiting this approach to the general practice for at risk patients (17).…”

The Gut–Liver Axis in Chronic Liver Disease: A Macrophage Perspective

“…Corticosteroid therapy was shown to improve survival in severe AH, although only in select patients. For patients with decompensated alcohol-related cirrhosis, liver transplantation, to date, remains the most effective therapy [ 210 ].…”