Alcohol-related Liver Disease

Background

• Alcohol-related liver disease (ALD) conceptually encompasses a spectrum of liver injury that ranges from asymptomatic laboratory abnormalities to advanced liver disease with cirrhosis, and in the most severe form, life-threatening end-stage liver disease with multi-organ failure.
• ALD has indistinct stages that may be simultaneously present:
  • steatosis (fatty liver)
  • inflammation (steatohepatitis)
  • fibrosis of varying degrees
  • cirrhosis (widespread, severe fibrosis)
• Alcohol-associated fatty liver is considered to be a relatively mild and potentially reversible form of liver disease.
• Alcohol-associated hepatitis is associated with inflammation, with clinical presentation ranging from asymptomatic steatohepatitis to the syndrome of acute alcoholic hepatitis, characterized by acute jaundice with the potential for progression to liver failure and a high risk for short-term mortality.
• The relationship between the quantity of alcohol consumed and the development of ALD is nonlinear, but an intake of about > 30-50 g/day (> 2 drinks/day in females and > 3 drinks/day in males) for at least 1 year is considered to place an individual at risk for ALD.

Evaluation

• Obtain a detailed alcohol consumption history that includes current and prior alcohol use.
• The severity of ALD may be affected by factors other than lifetime volume of consumptions, such as female sex, concomitant smoking, fat accumulation in the liver (partly driven by genes such as PNPLA3, TM6SF2, and MBOAT7), drinking patterns (bing drinking, drinking on empty stomach vs. with meals), and comorbidities such as viral hepatitis, iron overload, and obesity. Coffee drinking seems partly protective against ALD.
• Patients with harmful alcohol use should be screened for ALD using clinical evaluation, hepatic biochemical profile, complete blood count, and ultrasound liver imaging.
• If liver disease is identified, the diagnosis of ALD is determined after excluding other causes of liver disease (hepatitis B and C, nonalcoholic fatty liver disease, autoimmune liver disease, drug-induced liver injury, hemochromatosis, Wilson disease, and alpha-1 antitrypsin deficiency).
• A typical biochemical liver profile during an inflammatory stage includes aspartate aminotransferase (AST) levels of 50-400 IU/L with an AST to alanine aminotransferase (ALT) ratio of > 1.5.
• Patients diagnosed with ALD should have fibrosis assessment using the noninvasive serological markers and Fibroscan or elastography, although the value of this testing seems most valuable for distinguishing compensated cirrhosis from mild or moderate fibrosis.
• Evaluation of patients with high risk fibrosis or cirrhosis includes clinical findings (spider nevi or splenomegaly), decompensation events (ascites, jaundice, hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma), laboratory abnormalities (elevated bilirubin, decreased synthetic function of liver with low serum albumin or elevated prothrombin time, thrombocytopenia or pancytopenia), imaging findings (nodular liver surface or margins, portosystemic collaterals), elastography (>15 kilopascals [kPa] liver stiffness measurement), and screening for liver cancer or esophagogastric varices. See Cirrhosis of the Liver for general management of cirrhosis.
• Consider alcoholic hepatitis in patients with jaundice and/or common suggestive symptoms such as fatigue, fever, nausea, anorexia, and right upper quadrant tenderness.
• Ascites, upper gastrointestinal bleeding, and hepatic encephalopathy may be manifestations of either chronic cirrhosis or acute alcoholic hepatitis.
• The diagnosis of symptomatic acute alcoholic hepatitis can be determined among ALD patients using a set of clinical criteria: elevated serum bilirubin is > 3 mg/dL, active use of alcohol until at least 6-8 weeks prior to presentation, and exclusion of liver cancer or bile duct obstruction.
• Among those diagnosed with alcoholic hepatitis, stratify the disease severity using the Maddrey Discriminant Function score (severe disease ≥ 32) or MELD score (severe disease > 20). Patients with alcoholic hepatitis complicated by hepatic encephalopathy qualify for diagnosis of severe disease irrespective of Maddrey or MELD score (Strong recommendation).
• The presence of systemic inflammatory response syndrome (SIRS) may predict 90-day mortality and multiple organ failure.
  • Assess for SIRS by presence of ≥ 2 inflammatory markers:
    • temperature < 36 degrees C (96.8 degrees F) or > 38 degrees C (100.4 degrees F)
    • respiration rate > 20 breaths/minute (or venous partial pressure of carbon dioxide [pCO₂] < 32 mm Hg
    • heart rate > 90 beats/minute
    • leukocyte count < 4,000 cells/mm³ or > 12,000/mm³ or bands > 10%

Management

• Counsel patients to neither drink nor smoke (Strong recommendation), and address other potential exacerbating factors such as viral hepatitis (through treatment of vaccination as indicated), obesity (including possibility of sarcopenic obesity if present) and medication or metabolic-induced liver injury.
• Ensure proper nutrition including liberal multivitamins and minerals (Strong recommendation). It is recommended to have at least 35-40 kcal/kg and 1.2-1.5 g/kg protein per body weight (oral route first line). Particularly address thiamine deficiency to avoid Wernicke-Korsakoff syndrome and Wernicke encephalopathy.
• Patients found to have high risk fibrosis or cirrhosis, alcoholic hepatitis, and those with decompensated cirrhosis should have expedited referral to hepatology, preferably with a center of expertise in liver transplantation.
• Recommendations for patients with mild-to-moderate alcoholic hepatitis (Maddrey score of < 32 or MELD score < 20, and no hepatic encephalopathy):
  • Consider close monitoring with potential hospitalization.
  • Provide nutritional support and supplementation when needed.
  • Currently, there are no pharmacological therapies for this group.
• Recommendations for severe alcoholic hepatitis (Maddrey score ≥ 32 or MELD score > 20, or presence of hepatic encephalopathy):
  • Corticosteroid (prednisolone 40 mg/day orally or methyprednnisolone IV 32 mg) is the treatment of choice if there are no contraindications for their use such as active infection/sepsis, gastrointestinal bleeding, very poorly controlled diabetes mellitus, hepatorenal syndrome, or acute pancreatitis (Strong recommendation).
  • If steroids are initiated, response should be determined at 1 week using Lille score. For non-responders (Lille score ≥ 0.45), it is recommended to stop corticosteroids at 1 week and refer to a heptologist. Among responders, treatment should continue for another 3 weeks (Strong recommendation).
  • Among patients with severe alcoholic hepatitis who are either ineligible for or are unresponsive to corticosteroids therapy, early liver transplantation (without 6 months of alcohol abstinence) should be considered for highly select patients, especially those who have excellent psychosocial support as determined by a multidisciplinary team (Weak recommendation).
• Complementary or alternative medicines should not be used out of context of clinical trials (Strong recommendation).
• Neither propylthiouracil nor colchicine should be used in treating patients with alcoholic liver disease (Strong recommendation).