Alcoholic Liver Disease
GENERAL PRINCIPLES
• Excessive alcohol intake can be defined as gt;30 g/d (one standard drink contains 14 g).
• The spectrum of alcoholic liver disease includes fatty liver, alcoholic steatohepatitis, severe alcoholic hepatitis, and cirrhosis.
Fatty liver is the most common and occurs in up to 90% of alcoholics.• Of all excessive alcohol users, between 10% and 20% will develop cirrhosis and 35% will develop alcoholic hepatitis. More than half of the latter will progress to cirrhosis.
DIAGNOSIS
Clinical Presentation
• Hepatic steatosis
î Patients are usually asymptomatic.
î Clinical findings may include hepatomegaly and liver enzyme abnormalities.
• Alcoholic hepatitis
° Alcoholic hepatitis may be clinically silent or severe enough to lead to rapid development of hepatic failure and death.
î Symptoms include fever, abdominal pain, anorexia, nausea, vomiting, weight loss, and jaundice.
î In severe cases, patients may develop transient portal hypertension.
• Alcoholic cirrhosis
î The presentation is variable, from clinically silent disease to stigmata of chronic liver disease to decompensated cirrhosis.
Diagnostic Testing
Laboratories
• In alcoholic hepatic steatosis, LFTs may be normal or demonstrate mild elevation in serum aminotransferases (AST gt;ALT) and ALP.
• In alcoholic hepatitis, LFTs typically demonstrate elevation in serum aminotransferases (AST gt;ALT with a 2:1 ratio) and ALP. Hyperbilirubinemia (conjugated) and elevated prothrombin time (PT)Zinternational normalized ratio (INR) may also be observed.
• Laboratory abnormalities associated with a poor prognosis include renal failure, leukocytosis, a markedly elevated total bilirubin, and elevation of PTZINR that does not normalize with SC or IV vitamin K. Administration of oral vitamin K is not recommended because of poor gut absorption in patients with jaundice.
• A number of classification systems have been developed to risk-stratify patients with alcoholic hepatitis and assess response to treatment:
° Maddrey's discriminant function (DF) = 4.6 ? (PTpatient - PTcontrol) + serum bilirubin. Scores lt;32 and gt;32 have 93% and 68% 1-month survival, respectively.
î The Glasgow Alcoholic Hepatitis Score (GAHS) incorporates patient age, white blood cell count, blood urea, PT/INR, and serum bilirubin. A score lt;9 has no difference in survival between untreated and steroid-treated patients. A score gt;9 has a difference in short-term survival between untreated (52% 1-month survival) and steroid-treated (78% 1-month survival) patients.7
î The Lille model incorporates age, renal insufficiency, albumin, PT, bilirubin, and the difference in bilirubin level (day 0 vs. day 7) to predict 6-month mortality in patients with severe alcoholic hepatitis who have received steroids. In a prospective study, a score of #8805;0.45 was associated with a lower 6-month survival compared with a score lt;0.45 (25% vs. 85%). A score gt;0.45 suggests that a patient is not responding to steroid therapy.8
DIAGNOSTIC PROCEDURES
• Liver biopsy may be indicated if the diagnosis of alcoholic hepatitis is unclear.
• Typical histopathologic findings in alcoholic liver disease include hepatocyte ballooning with or without Mallory-Denk bodies, lobular inflammation with neutrophilic infiltrates, hepatocyte necrosis, periportal fibrosis, perivenular and pericellular fibrosis, ductal proliferation, and fatty changes.
TREATMENT
• Encourage alcohol abstinence.
• Referral to programs or counselors for alcohol rehabilitation.
• Naltrexone is most strongly supported by placebo-controlled clinical trials for medication treatment in alcohol use disorder.
• Evaluate and correct nutrient deficiencies. Nutrition support can be given orally via a small-bore feeding tube or via peripheral parenteral nutrition or total parenteral nutrition.
Good nutrition improves nitrogen balance, may improve LFTs, and may decrease hepatic fat accumulation, but it generally does not enhance survival.Medications
Treatment of acute alcoholic hepatitis with corticosteroids is controversial. However, there is evidence that patients with a DF gt;32 and GAHS gt;9 may have a short-term benefit from steroid therapy. An early decrease in bilirubin levels after 1 week of steroids portends a better prognosis (Lille score).
• Oral prednisolone (40 mg/d PO for 4 weeks, followed by a taper over 2-4 weeks) is a steroid treatment for patients with severe alcoholic hepatitis. Prednisolone is preferred over prednisone (but not proven to be better) as the latter requires conversion to its active form, prednisolone, within the liver. Prednisolone demonstrated a reduction in short-term mortality (28 days), though this did not reach significance. There was no benefit with regard to medium- or long-term mortality (90 days and 1 year, respectively).9
• Pentoxifylline (400 mg PO tid for 4 weeks) is a nonselective phosphodiesterase inhibitor that, in a previous randomized controlled trial, did not improve survival.
Surgical Management
Patients with cirrhosis and ESLD can be evaluated for liver transplantation but, historically, have been required to abstain from alcohol for 6 months prior to evaluation, maintain abstinence, and participate in a rehabilitation program. Recent data are emerging regarding the benefits and safety of early liver transplantation for highly selected patients with severe alcoholic hepatitis who have not attained 6 months of sobriety.
OUTCOME AND PROGNOSIS
• Hepatic steatosis (fatty liver) may be reversible with abstinence.
• In alcoholic hepatitis, prognosis depends on the severity of presentation and alcohol abstinence. The inhospital mortality for severe cases is high because of complications including sepsis and renal failure. Liver transplantation may be offered in highly selected patients with severe disease at initial
presentation and excellent social support.10
In alcoholic cirrhosis, prognosis is variable and depends on the degree of liver decompensation. Abstinence from alcohol may promote significant liver chemistry improvement.