Alcohol-related liver disease: ALEH 2019 Clinical practice guidelines

Latin American Association for the Study of the Liver(ALEH) has released its 2019 Clinical practice guidelines on Alcohol-related liver disease.

Alcohol-related liver disease (ALD) is a major cause of chronic liver disease in Latin-America. Although data on prevalence in Latin-America is scarce, alcohol is reported to have been the main cause of cirrhosis in Argentina, Brazil, Chile, Mexico, and Peru. According to the WHO Global Status Report on Alcohol and Health of 2018, individuals above 15 years of age drink 8 litres of pure alcohol per year in the WHO Region of the Americas and over 6.4 l globally. Researchers have largely neglected this disease, and as a result, the treatment has remained unaltered for many years. Recently, there has been a renewed interest in understanding the pathophysiology and natural history of ALD, which has yielded the discovery of novel targets. The current concepts and recent advances in ALD have been summarized in clinical practice guidelines (CPG) from important international scientific societies.

Following are the major recommendation:

A. Definition and natural history

Recommendations/key concepts

• ALD is the main cause of cirrhosis in Latin-America. Excessive alcohol consumption should be actively sought as a cause of cirrhosis (Key concept/Expert's opinion).

B. Risk factors

Recommendations/key concepts

• The amount of alcohol consumed is the most important risk factor for the development of ALD (Key concept/Expert's opinion).


• Subjects consuming more than 3 standard drinks per day in men, and more than 2 drinks per day in women or repeated binge drinking (defined as more than 5 drinks in men and more than 4 in women over a 2 h period) are at risk of developing liver disease and should receive counselling (Grade of evidence: low quality; grade of recommendation: strong).


• The impact of the type of alcoholic drink consumed (i.e. liquor, beer or wine) and the pattern of drinking on the risk of developing ALD is not well known (Key concept/Expert's opinion).


• Patients with any chronic liver disease and protein-calorie malnutrition should be advised to avoid regular alcohol consumption (Grade of evidence: low quality; grade of recommendation: strong).

C. Epidemiology and burden of the disease

Recommendations/key concepts

• Latin-America is one of the regions with a high prevalence of excessive alcohol consumption and the resulting health consequences represent a major public health concern. Implementation of public health policies aimed at reducing the burden of alcohol-related cirrhosis is urgently needed (Key concept/Expert's opinion).

D. Diagnosis of alcohol-use disorder and alcohol-related liver disease

Recommendations/key concepts

• Alcohol use disorder should be assessed in all patients presenting with newly recognized liver dysfunction, by application of specific questionnaires (i.e. AUDIT or CAGE) that can be easily applied in daily clinical practice (Key concept/Expert's opinion).


• In patients with AUD, clinical, biochemical and radiological evaluation is mandatory for early detection of underlying ALD (Grade of evidence: low quality; grade of recommendation: strong).


• A liver biopsy may be considered when the ALD diagnosis is unclear due to the existence of other potential etiological factors (Grade of evidence: low quality; grade of recommendation: weak).


• In patients with excessive alcohol use and obesity-related metabolic syndrome, the Alcoholic liver disease/Nonalcoholic Fatty Liver Disease Index (ANI) could be helpful in differentiating ALD and NAFLD (Grade of evidence: moderate quality; grade of recommendation: strong).


• Liver stiffness measurement or patented serum biomarkers may be useful for assessing liver fibrosis in patients with ALD, however, certain conditions, such as the presence of ASH, cholestasis, and active alcohol intake can overestimate the degree of fibrosis (Grade of evidence: moderate quality; grade of recommendation: strong).

E. Alcoholic hepatitis: diagnosis and prognosis

Recommendations/key concepts

• AH is clinically defined as abrupt onset of progressive jaundice and liver-related complications with hyperbilirubinemia (>3 mg/dL), AST/ALT ratio > 1.5 with levels of AST > 1.5 times the upper limit of normal but <400 IU/L; and heavy alcohol drinking until 60 days before onset of symptoms and absence of other causes of liver disease (Key concept/Expert's opinion).


• Liver biopsy to diagnose AH is recommended in patients with suspected AH, but who do not meet the abovementioned criteria, in the presence of confounding factors or when another aetiology is also suspected (Grade of evidence: moderate quality; grade of recommendation: strong).

Recommendations/key concepts

• Alcohol-related cirrhosis is one of the main causes of HCC in Latin-America (Key concept/Expert's opinion).


• The risk of HCC in ALD-related cirrhosis is similar to other etiologies and surveillance should be performed by ultrasonography every 6 months with or without serum alpha-fetoprotein levels (Grade of evidence: moderate quality; grade of recommendation: strong).

G. Management of alcohol-related liver disease

Management of long-term complications of alcohol-related liver disease

Recommendations/key concepts

• Complete abstinence is the major therapeutic approach that decreases mortality and liver-related complications in patients with ALD (Grade of evidence: high quality; grade of recommendation: strong).


• In patients with severe ALD, baclofen has been proven to be effective and safe in preventing alcohol relapse (Grade of evidence: moderate quality; grade of recommendation: strong).


• Protein-calorie malnutrition is common in patients with ALD. Adequate food intake with proper protein and caloric content should be considered (Grade of evidence: high quality; grade of recommendation: strong).


• Medical treatment of ALD should be performed by multidisciplinary teams, including alcohol addiction specialists (Key concept/Expert's opinion).


• General recommendations for screening and management of cirrhosis complications should be applied to patients with alcohol-related cirrhosis (Grade of evidence: moderate quality; Grade of recommendation: strong).


• No specific pharmacological therapy for alcohol-related fibrosis has demonstrated consistent benefits and should only be used in the context of clinical trials (Key concept/Expert's opinion).

Management of alcoholic hepatitis

Recommendations/key concepts

• Corticosteroids are the first-line therapy in patients with severe AH (Grade of evidence: high quality; Grade of recommendation: strong).


• Pentoxifylline treatment has limited impact improving short and long-term survival of patients with severe AH and is not currently recommended (Grade of evidence: high quality; Grade of recommendation: strong)


• The use of biological anti- TNF-α drugs has no role in the treatment of severe AH. Their use is not recommended because of their deleterious effects on increasing the rate of severe infections and death in these patients (Grade of evidence: high quality; Grade of recommendation: strong).


• Antioxidants, such as metadoxine and NAC, may be useful for improving short-term mortality of patients with severe AH receiving corticosteroids (Grade of evidence: moderate quality; Grade of recommendation: weak).


• Artificial liver supportive systems do not improve short and long-term survival rates in patients with severe AH (Grade of evidence: moderate quality; Grade of recommendation: strong).


• G-CSF should not be used outside of clinical studies until further supportive evidence is available (Grade of evidence: low quality; Grade of recommendation: weak).


• Intensive enteral nutrition in patients with AH has showed no benefit on short-term survival when added to corticosteroid treatment. However, patients with higher calorie intake do have a better survival at 6 months (Grade of evidence: moderate quality; Grade of recommendation: weak).

H.Liver transplantation

Recommendations/key concepts

• Liver transplantation should be considered in the management of patients with end-stage ALD (Key concept/Expert's opinion).


• In patients with end-stage ALD, candidacy for transplantation criteria should be comprehensive and not only based on the 6-month rule of abstinence, since this may not be feasible in patients with severe AH or severe decompensated ALD where survival is limited (Grade of evidence: moderate quality; Grade of recommendation: weak).


• Patients undergoing liver transplantation evaluation for ALD should be assessed by multidisciplinary teams, including addiction specialists, and should be screened for use of alcohol and other substances (Key concept/Expert's opinion).


• Immunosuppression should be prescribed at the lowest possible dose and smoking cessation should be advised and assisted to reduce the risk of cancer in this group of patients. Also, a complete cardiovascular evaluation is advised (Key concept/Expert's opinion).