What is the relationship between indirect bilirubin and alcoholic liver disease?

From the Guidelines

Patients with indirect bilirubin elevation due to alcoholic liver disease should immediately stop all alcohol consumption, as abstinence is the cornerstone of treatment and has the most significant impact on reducing morbidity, mortality, and improving quality of life. When alcohol damages the liver, it impairs the liver's ability to process bilirubin, a yellow pigment produced during the breakdown of red blood cells. Indirect (unconjugated) bilirubin specifically increases when the liver cannot properly convert it to direct (conjugated) bilirubin. In alcoholic liver disease, this occurs because alcohol damages hepatocytes (liver cells) and disrupts their normal metabolic functions.

Key Considerations

• The most recent and highest quality study, 1, emphasizes the importance of abstinence from alcohol, nutritional support, and vitamin supplementation in the management of alcoholic hepatitis.
• The study also highlights the need for early recognition and treatment of complications such as hepatic encephalopathy, coagulopathy, and infections.
• Patients with severe alcoholic hepatitis, as defined by a Maddrey discriminant function (MDF) score > 32 or a MELD score > 20, may benefit from treatment with glucocorticoids or pentoxifylline, but the benefits are modest and the risks of treatment should be carefully weighed against the potential benefits.

Treatment Approach

• Abstinence from alcohol is the most critical intervention, and patients should be encouraged to stop drinking completely.
• Nutritional support with a balanced diet and vitamin supplementation, particularly B vitamins including thiamine 100mg daily, is essential for recovery.
• In severe cases, medications like acamprosate (666mg three times daily) or naltrexone (50mg daily) may help maintain abstinence.
• Patients should be monitored for complications like hepatic encephalopathy or coagulopathy, and treated promptly if they occur.

Prognosis and Outcome

• The liver has remarkable regenerative capacity, and bilirubin levels often improve within weeks to months of alcohol cessation, though this depends on the extent of liver damage already sustained.
• Early recognition and treatment of alcoholic liver disease can significantly improve outcomes and reduce the risk of complications and mortality, as highlighted in 1 and 1.
• Patients with mild to moderate alcoholic hepatitis, as defined by a MELD score < 20 and MDF < 32, should be referred for abstinence counseling and prescribed a high protein diet supplemented with B vitamins and folic acid, as recommended in 1.

From the Research

Alcoholic Liver Disease and Indirect Bilirubin

• Alcoholic liver disease (ALD) is a significant cause of liver-related mortality and a leading indication for liver transplant, representing 40% to 50% of all liver transplants in high-income countries 2.
• The pathogenesis of ALD includes hepatic steatosis, oxidative stress, acetaldehyde-mediated toxicity, and cytokine and chemokine-induced inflammation 3.
• Indirect bilirubin levels are an important prognostic factor in severe alcoholic hepatitis treated with prednisolone, with early change in bilirubin levels (ECBL) at 7 days being a significant predictor of survival 4.

Diagnosis and Treatment of ALD

• Diagnosis of ALD involves assessing patients for alcohol use disorder and signs of advanced liver disease, with the degree of liver fibrosis determined by ultrasonography, transient elastography, MRI, measurement of serum biomarkers, and liver biopsy histology 3.
• Alcohol abstinence is the cornerstone of ALD therapy, with psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, helping to support abstinence 5.
• Corticosteroid therapy is associated with improved 1-month survival in patients with severe alcoholic hepatitis, and liver transplantation is the most effective therapy in patients with decompensated liver disease 2.

Prognosis and Complications of ALD

• The 10-year survival of patients with ALD is 88% among those who are abstinent and 73% for those who relapse to alcohol consumption 2.
• Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension 5.
• Alcoholic cirrhotics have an increased risk of developing hepatomas, and liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 months of proven abstinence for eligibility 5, 6.