Review Discusses Growing Problem of Alcoholic Liver Disease

The problem of alcoholic liver disease is growing in the United States, and obtaining treatment is difficult.

A review published in JAMA Tuesday gave an update on the epidemiology, diagnosis, and treatment of alcoholic liver disease (ALD), which is among the most common liver diseases in the United States.

The problem is growing: in a study of a little more than a million US hospitalizations for chronic liver disease between 2012 and 2016, the proportion of ALD-related hospitalizations surged from 19.4% in 2012 to 37.7% in 2016. Hospital costs and mortality for ALD is higher than for hepatitis B and hepatitis C, the authors noted.

More than 2 million people in the United States in 2017 had alcohol-associated cirrhosis, and in high-income countries, ALD makes up 40% to 50% of all liver transplants.

The authors reviewed 97 articles, including 9 randomized clinical trials, 13 meta-analyses, 51 prospective observational studies, 15 reviews, and 11 clinical practice guidelines to review the current state of this disease.

The Path to ALD

Rick factors for disease progression include female sex, amount and duration of alcohol consumption, obesity, low socioeconomic status, and certain genetic polymorphisms.

Binge drinking and drinking outside of meals are also risk factors.

However, coffee drinking is protective, the authors found. In a case-control study of 2047 heavy drinkers, 754 without liver disease were more likely to drink coffee (67% vs 53%) and drink more cups of coffee (2.2 vs 1.9) compared with 1293 drinkers with cirrhosis.

For women, risk climbs when alcohol use rises to 2 or more drinks per day. For men, it’s 3 or more drinks per day.

The pathway to cirrhosis begins with steatosis and in 4% to 8% of cases, alcoholic hepatitis. The next stage in progression is stage 2 liver fibrosis, then cirrhosis.

Most individuals with ALD are asymptomatic or have nonspecific symptoms such as fatigue. It is frequently diagnosed by the identification of steatosis on liver imaging or abnormal liver test results. Elevated liver aminotransferase levels are usually < 400 IU/L, with AST:ALT ratio > 1.

Surviving ALD

Ten-year survival rates of individuals with alcohol-associated liver disease were 88% among those who quit drinking, but 73% for those continued, according to one study.

Patients with ALD should be screened for alcohol use disorder (AUD), such as with the AUD Identification Test (AUDIT), a 10-item questionnaire with each item self-reported by adults on a scale of 0 to 4. Those with AUD are likely to have certain comorbidities: in-person interviews of 10,001 noninstitutionalized individuals with lifetime AUD revealed that 47% reported anxiety, 44% had sleep disorders, 43% had depression, and 17% had psychiatric comorbidities.

The AUDIT score will assist with determining severity and treatment, ranging from brief counseling to more intense therapy. However, brief counseling was not associated with reduced mortality in a meta-analysis of 68 randomized and nonrandomized controlled intervention studies that included 36,528 patients, and only 1 in 7 adults who received such counseling drank within the recommended limit (< 14 drinks per week and < 2 per day), the authors found.

For patients who desire more intensive therapy, there are several barriers, including transportation, logistics, and financial issues. Only 10% to 15% of patients with advanced ALD received AUD treatment in one study. And although there are some FDA–approved drug therapies for AUD, including acamprosate, naltrexone, and disulfiram, none have been evaluated in patients with ALD, the authors said.

Given the problem of ALD, the authors also discussed what is known about early liver transplant for ALD.

To qualify for a transplant, most transplant centers have a minimum abstinence duration of 6 months, but the authors said that alone does not accurately predict drinking after a liver transplant, and transplant guidelines do not propose 6-month abstinence as an absolute requirement to pick candidates, the authors said.

In addition, the 6-month abstinence requirement jeopardizes patients with a first episode of alcoholic hepatitis who don’t respond to medical therapy; they can’t wait that long for a transplant because their 6-month mortality rates are approximately 75%.

Factors that are linked with alcohol relapse after transplant include lack of social support, psychiatric status, younger age, polysubstance use, and previous alcohol treatment.

Between 2014 and 2019, the proportion of patients waiting for liver transplantation who had alcohol-associated liver disease increased from 22% to 40%, the review said.


Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021;326(2):165-176. doi:10.1001/jama.2021.7683

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