Alcoholic liver disease​

Risk of developing alcoholic liver disease

All patients should be advised to consume alcohol only within the low-risk drinking guidelines. People who drink heavily every day are at greater risk of developing cirrhosis than people who binge drink. One study found that men with cirrhosis consumed an average of 6.2 drinks per day over 20 years, and women consumed an average of 4.4 drinks per day over nine years (Stokkeland et al., 2008).

Patients with hepatitis C should be advised to abstain from alcohol because they are at substantially greater risk of cirrhosis, even if they drink moderately.

The spectrum of alcoholic liver disease

Hepatocytes can regenerate following a toxic insult, and the liver can function even if most of it has been replaced with scar tissue. This explains why the early stages of alcoholic liver disease are reversible and asymptomatic, and even patients with extensive cirrhosis can often live normal lives if they abstain from alcohol.

Alcoholic fatty liver disease

• Is usually asymptomatic.
• Patients may have an enlarged, firm, mildly tender liver.
• Liver enzymes may be mildly elevated.
• Will often resolve with abstinence.

Alcoholic hepatitis

• Mild: Often asymptomatic, with elevation of liver enzymes to two to three times the upper limit of normal.
• Moderate: Presents with typical symptoms of hepatitis (fatigue, anorexia, weight loss, vomiting, jaundice, right upper quadrant pain).
• Severe: Presents with fever, jaundice, ascites, hyperdynamic circulation and encephalopathy.
• Patients with moderate or severe alcoholic hepatitis should go to the emergency department for investigations and management. Those with marked encephalopathy have a mortality rate of up to 50 per cent.
• Indicators of a poor prognosis include:
• low serum albumin
• elevated international normalized ratio (INR)
• elevated serum bilirubin
• signs of encephalopathy.

Cirrhosis

• Involves permanent destruction of the liver architecture and, thus, function; liver enzymes may be raised.
• Tests of liver function are abnormal (i.e., low albumin, raised INR).
• Patients may have hepatomegaly or a small, shrunken right lobe and hypertrophied left lobe (palpable in epigastrium).
• Stigmata of chronic liver disease may be present (gynecomastia, testicular atrophy, spider nevi, palmar erythema, splenomegaly, ascites).
• Complications include encephalopathy, ascites, bleeding varices, portal hypertension and subacute bacterial peritonitis.

Cirrhosis with hepatitis

• Patients sometimes develop a superimposed alcoholic hepatitis with elevation of liver enzymes; if severe, this can precipitate liver failure.
• Chronic or recurrent hepatitis accelerates the progression of cirrhosis.

Laboratory tests and diagnostic imaging for alcoholic liver disease

Gamma-glutamyl transferase (GGT), mean cell volume (MCV) and platelets

• Elevated GGT, macrocytosis and mild thrombocytopenia suggest continued alcohol use, but not necessarily chronic liver disease.
• Macrocytosis (with target cells) can occur in cirrhosis.
• Persistent or severe thrombocytopenia suggests splenomegaly.

Aspartate aminotransferase (AST), alanine aminotransferase (ALT)

• In alcoholic hepatitis, AST is more than ALT (often in a 2:1 ratio).
• In viral hepatitis, ALT is more than AST.
• AST of more than 100 implies moderate to severe alcoholic liver disease.

Hepatitis B and C

• The presence of viral hepatitis (hepatitis B or C) should be ruled out if liver enzymes are elevated.
• People who drink heavily have a higher prevalence of viral hepatitis.
• Chronic viral hepatitis worsens the prognosis of alcoholic liver disease.

Liver function tests: International normalized ratio (INR), albumin, bilirubin

• Increased INR or bilirubin, or decreased albumin, indicates liver dysfunction caused by cirrhosis or severe alcoholic hepatitis.

Blood alcohol concentration (BAC)

• Lab measurement of serum BAC can be used in the emergency department to follow the metabolism of alcohol and in the office to confirm intoxication or to assess alcohol dependence.
• A patient with a high alcohol tolerance from heavy use may not appear inebriated, but may have a high BAC.

Ultrasound

• Commonly identifies fatty liver.
• May be normal, even in cirrhosis.
• Nodularity indicates cirrhosis.
• Splenomegaly suggests portal hypertension due to cirrhosis.
• Can be used to detect ascites and to screen for hepatomas.

Endoscopy

• Detects varices and measures portal pressures in patients with cirrhosis.
• Also detects gastritis, esophagitis and ulcers.

Liver biopsy

• Rules out other causes of liver disease.
• Determines the extent of cirrhosis prior to long-term treatment.

Managing alcoholic liver disease

The American Association for the Study of Liver Diseases publishes practice guidelines for treating alcoholic liver disease. These recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care for alcoholic liver disease.

Alcoholic fatty liver disease

• Often reversible with alcohol abstinence or reduction to low-risk levels
• Fatty liver disease is often not related to alcohol (non-alcoholic fatty liver disease), so be careful in labelling patients. It may be related to concomitant obesity and reversible with weight loss.
• Eight to 20 per cent of patients with fatty liver progress to cirrhosis.

Alcoholic hepatitis

• Use a scoring system to establish severity.

Mild or low risk:

• Reversible with abstinence
• Requires nutritional assessment and supportive care
• Treatment is supportive and often involves managing symptoms of withdrawal.

Severe or high risk:

• Patients generally need hospitalization, often requiring admission to an intensive care unit.
• Requires nutritional assessment
• Prednisolone improves short-term survival in alcoholic hepatitis with spontaneous hepatic encephalopathy, but is contraindicated in patients with renal failure, gastrointestinal bleeding or infection.
• If steroids are contraindicated or in case of early renal failure, use Pentoxifylline.

Cirrhosis

Diagnosis:

• Clinical: Firm liver edge, splenomegaly, spider nevae
• Lab: High INR, low albumin, high bilirubin, low platelets (splenomegaly)
• Ultrasound: Cirrhosis is hard to detect on ultrasound, but splenomegaly confirms portal hypertension
• Investigate to rule out other contributing causes: As many as 20 per cent of patients with alcoholic liver disease have another contributing condition.

Management:

• Emphasize abstinence and involvement in treatment; even small amounts of alcohol consumption can accelerate liver damage.
• In patients with cirrhosis, risk of variceal bleed is 10 times higher in those who drink heavily than in those who abstain (Lucey et al., 2008).
• Review indications for a liver transplant.

Prescribing medications:

• Avoid hepatotoxic medications, including acetaminophen and NSAIDs.
• Most common medications can be used in patients with cirrhosis. Some medications may require dose adjustments.If in doubt, check with a gastroenterologist.
• Avoid benzodiazepines and other sedating drugs because they can trigger encephalopathy.

Choosing medications:

• Disulfiram and naltrexone can be used with patients who have mild liver dysfunction with careful monitoring of liver enzymes.
• Acamprosate is safe in patients with severe liver dysfunction.

Laboratory monitoring:

• Monitor bilirubin, INR, albumin, AST, ALT and platelets every three to six months.
• Monitor progression of cirrhosis and check for hepatomas with an ultrasound every six months.

Diet:

• All patients should have a nutritional assessment. Protein calorie malnutrition is associated with major complications of alcoholic liver disease and a poor prognosis.
• Aggressive nutritional therapy may improve nutritional status and reduce complications.

Immunization:

Hepatitis A and B immunization, if indicated.

Patients with hepatitis C:

Patients should be given treatment when indicated.

Patients should be clearly advised to abstain from alcohol, even if they do not currently have an alcohol problem. If they do not want to abstain completely, they should have no more than one to two drinks per week (Blixen et al., 2008).

Referral:

• Refer the patient to a gastroenterologist who is knowledgeable about alcoholic liver disease and who understands alcohol use disorders.

Liver transplant:

• Patients who receive liver transplants have a low relapse rate and a good long-term survival rate.
• Most transplant programs require that the patient has been abstinent for six months. However, because the evidence base to support this requirement is not strong, refer patients early for consideration for liver transplant, as you would for other patients with decompensated liver disease. The transplant team should assess the patient's likelihood of achieving long-term abstinence.

Managing complications of cirrhosis

Prevention of first-time bleeding and rebleeding from portal hypertension

• Refer for yearly endoscopy.
• Patients with varices should be prescribed a non-selective beta-blocker or, if appropriate, have endoscopic variceal ligation.

Hepatic encephalopathy

Clinical features:

• Grade 1: Subclinical with normal examination, except for subtle changes on psychometric tests. Patient may experience fatigue, day-night reversal, personality or mood changes, inattention, and poor work and driving performance.
• Grade 2: Asterixis, lethargy
• Grade 3: Somnolence, confusion, disorientation, hypoactive reflexes, muscle rigidity
• Grade 4: Coma

Possible underlying causes:

• Altered nitrogen load to GI tract (e.g., increased dietary protein, constipation, GI bleeding)
• Sedating drugs (e.g., benzodiazepines, opioids)
• Metabolic causes (e.g., hypoxia, electrolyte disturbances, dehydration, hypothyroidism, hypoglycemia, anemia)
• Infections (e.g., spontaneous bacterial peritonitis)

Treatment of chronic, low-grade encephalopathy:

• Treat underlying cause.
• Refer patient for nutritional assessment.
• Avoid sedating drugs, especially benzodiazepines.
• Use diuretics judiciously to avoid dehydration and electrolyte imbalance.
• Prescribe lactulose (osmotic laxative): 30–45 mL three or four times per day until the patient has two or three soft stools daily.

Ascites

Diagnosis:

• Increased abdominal girth, confirmed with clinical examination and ultrasound.

Treatment:

• Recommend low-sodium diet.
• Prescribe diuretics (spironolactone, furosemide; however, aggressive diuresis can cause encephalopathy and other complications). Use furosemide with caution; avoid use if no pedal edema.
• Initial dose of spironolactone: 25 mg twice per day. Increase to 50 mg twice per day, or add second diuretic if little response after five days.
• Non-selective beta-blockers (used to treat esophageal varices) may increase mortality.