alcohol-related%20liver%20disease
ALCOHOL-RELATED LIVER DISEASE

Alcoholic liver disease diagnosis is suggested by an established history of habitual alcohol intake of sufficient length and intensity.
Signs of alcohol abuse and hepatic injury include malnutrition and muscle wasting, cutaneous telangiectasia, palmar erythema, finger clubbing, Dupuytren's contracture, peripheral neuropathy, parotid gland enlargement and signs of gynecomastia and hypogonadism may also be present. Patient may also be asymptomatic.

 

Alcohol-related%20liver%20disease Diagnosis

Diagnosis

Cofactors in the Development of Alcohol-related Liver Disease (ALD)

  • The amount (>30 g/day) and type of alcohol ingested and drinking pattern (eg daily drinking, binge drinking)
    • Red wine was less likely to be associated with cirrhosis than other alcoholic drinks 
  • Genetic factors
    • Genetic variants PNPLA3, TM6SF2, MBOAT7, HSD17B13 
    • Rate of alcohol metabolism plays a role
  • Gender
    • Women are more susceptible compared to men
  • Diet and nutrition
    • Undernutrition
    • Overnutrition and obesity are established independent risk factors for hepatic steatosis and steatohepatitis
  • Cigarette smoking
  • Co-morbid conditions [eg nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), viral hepatitis and hemochromatosis] 
    • Concomitant hepatitis B virus (HBV) infection accelerates the progression of ALD and may hasten mortality
    • Hepatitis C virus (HCV) infection increases probability of development of cirrhosis by 8- to 10-fold and HCV infection accelerates progression of ALD

Laboratory Tests

  • Liver function tests (LFTs)
    • Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT); AST>ALT usually >2x upper limit of normal 
    • AST:ALT ratio >1.5 gives a likely diagnosis of ALD; if ratio ≥3, this is strongly suggestive of ALD
    • Alkaline phosphatase and gamma-glutamyl transpeptidase (GGT) (>100 U/mL) are both usually elevated; the latter is a marker for detection of previous alcohol consumption
    • Total bilirubin >3 mg/dL and albumin <3 g/L
  • Alcohol biomarkers
    • Eg urine ethyl sulfate, urine and hair ethyl glucuronide, phosphatidylethanol (PEth) 
    • Direct markers for alcohol consumption which aid in the diagnosis and support recovery 
    • Measurement of urine or hair ethyl glucuronide can accurately monitor abstinence 
  • Transient elastography
    • Measures liver stiffness in the evaluation of liver fibrosis in ALD
  • Metabolic alterations that may be present:
    • Hyperglycemia, hypertriglyceridemia, hyperuricemia, electrolyte abnormalities
  • Hematological abnormalities
    • Macrocytic anemia may be seen in 75% of patients
    • Thrombocytopenia that may be transitory only; but if with progression to cirrhosis, it may persist
    • Leukocytosis (leukemoid reaction in the absence of infection)
  • May utilize Child-Pugh classification which is a scoring system that uses albumin level, PT, international normalized ratio (INR) bilirubin level, presence of ascites and encephalopathy severity to determine evidence of hepatic dysfunction

Liver Biopsy

  • Liver biopsy is rarely needed to establish the diagnosis
  • May be used to:
    • Clarify atypical cases or uncertain diagnosis
    • Determine if concomitant disease is present
    • Establish stage and severity of the disease and define the prognosis
    • Aid in therapeutic decisions

Infectious Disease Work-up  

  • Eg Blood tests, sputum cultures, urinalysis and urine culture, ascitic fluid cell counts and culture, hepatitis serology

Imaging

  • Eg Ultrasound, CT scan, or MRI cannot document alcohol as the etiology of the liver disease but can help in ruling out other causes of abnormal test results such as biliary obstruction, infiltrative and neoplastic liver diseases

Screening for Alcohol Use Disorder

  • Alcohol use disorder (AUD) is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a problematic pattern of alcohol use which leads to clinically significant distress or impairment
    • AUD replaces the former categories of alcohol abuse and dependence
    • There are 11 diagnostic criteria and the presence of at least 2 of these in the last year indicates an AUD 
    • Severity of AUD ranges from mild (2-3 criteria met) to moderate (4-5 criteria met) and severe (≥6 criteria met)   
  • The US National Institute of Alcohol Abuse and Alcoholism (NIAAA) recommends a single initial screening question, “How many times in the last year have you had ≥5 drinks in a day (for men) or ≥4 drinks in a day (for women)?” 
    • A positive answer warrants administration of the Alcohol Use Disorders Identification Test (AUDIT) tool 
  • The AUDIT is a widely used, validated, 10-question screening tool to recognize alcohol consumption 
    • An AUDIT score of >8 indicates harmful alcohol use while a score of >20 indicates alcohol dependence or moderate to severe AUD 
    • AUDIT-C is a shorter version which uses the 1st 3 questions of AUDIT on alcohol consumption and is better in identifying alcohol misuse than the CAGE and other questionnaires 
  • Patient with an AUDIT score of >8, an AUDIT-C score of ≥4, or is a binge drinker (≥5 drinks in men and ≥4 drinks in women consumed in 2 hours) should be offered brief intervention and referral to treatment
  • Other screening tools include the Michigan Alcoholism Screening Test (MAST) and the Lifetime Drinking History
  • It is suggested to standardize the measure of alcohol in a drink to 10 g as used by the European standard and the World Health Organization 
  • Toxic daily threshold of alcohol consumption is 40-80 g for males and 20-40 g for females x 10-12 years (≥5 drinks/ day for males and ≥4 drinks/day for females)
    • Heavy alcohol use for >5 years, ie >3 drinks/day for males and >2 drinks/day for females, increases risk for ALD
  • Patients with AUD should also be screened for coexisting psychiatric disorders and other addictions, eg nicotine

Staging

  • Alcohol-related liver disease (ALD) consists of a clinical-histologic spectrum which includes fatty liver, alcoholic hepatitis and cirrhosis with its various complications 
  • Signs, symptoms and severity of liver disease can be variable between individuals and histological stages 

Fatty Liver 

  • Fatty liver or alcohol-related steatosis develops after 2 weeks in about 90% of individuals with an alcoholic intake of >60 g/day
  • Patients are usually asymptomatic 
  • An enlarged liver may be present without jaundice or signs of advanced liver disease 
  • Elevated AST and GGT levels indicate recent excessive alcohol use 
  • Steatosis can be identified on ultrasonography, CT and MRI scan with ultrasound having the lowest sensitivity and specificity while MRI is more accurate in quantifying fat 
  • May be reversible following abstinence of 4-6 weeks, though a few may lead to progression to steatohepatitis or to fibrosis and cirrhosis 

Alcoholic Hepatitis

  • Recent onset of progressive jaundice (with or without signs of liver decompensation such as encephalopathy or ascites) that is often accompanied by fever, malaise, weight loss and malnutrition 
  • Clinical diagnosis of alcoholic hepatitis includes jaundice in the last 8 weeks, daily alcohol use of >60 g (males) or >40 g (females) for ≥6 months with abstinence of <60 days prior to developing jaundice, AST >50, AST/ALT ratio of >1.5 with both levels <400 IU/L, and serum total bilirubin >3 mg/dL 
  • Potential confounding factors are possible hepatic disease (metabolic or drug-induced liver disease or ischemic hepatitis), ambiguous history of alcohol intake, or atypical lab tests 
  • Categories of alcoholic hepatitis include the following:  
    • Possible: Clinically diagnosed with potential confounding factors
    • Probable: Clinically diagnosed but with no potential confounding factors  
    • Definite: Clinically diagnosed with features of alcoholic hepatitis (ie steatohepatitis) histologically confirmed

Cirrhosis

  • Liver fibrosis and up to >75% of patients with steatohepatitis can progress to ALD cirrhosis 
  • Risk of developing hepatocellular carcinoma is increased in patients with ALD cirrhosis

Well-compensated Cirrhosis

  • May be asymptomatic with normal physical exam
  • Steatosis or steatohepatitis are often coexistent and patient may have hepatomegaly and/or splenomegaly
  • Signs of portal hypertension may dominate
  • In more advanced disease, the liver decreases in size and the left hepatic lobe becomes more prominent
    • Entire liver has hard and nodular consistency
  • Splenomegaly of various degrees is frequent

Decompensated Cirrhosis

  • Jaundice, variceal bleeding, infections 
  • Muscle wasting and cachexia
  • Ascites and venous collateral circulation
  • Spider angiomata, palmar erythema and Dupuytren’s palmar contracture
  • Parotid and lacrimal gland enlargement
  • If with hypoalbuminemia, patient may have Muehrcke’s nails or white nails
  • Clubbing of fingers in patients with arteriovenous pulmonary shunting
  • Hepatic encephalopathy or hepatorenal syndrome may be present
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