Ferri – Alcoholic Hepatitis

Mar 13, 2020 admin TIÊU HÓA 0

Alcoholic Hepatitis

  • Daniel K. Asiedu, M.D., PH.D.

 Basic Information

Definition

Alcoholic hepatitis (AH) is a severe, progressive, inflammatory, and cholestatic liver disease occurring in patients with long-term ethanol abuse.

Synonym

  1. AH

ICD-10CM CODES
K70.10 Alcoholic hepatitis without ascites
K70.9 Alcoholic liver disease, unspecified

Epidemiology & Demographics

  1. •

    Approximately 2 million people in the U.S. (about 1% of the population) are affected by alcoholic liver disease.

  2. •

    Alcoholic hepatitis accounts for 0.8% of all admissions in the U.S.

  3. •

    Typical presentation age: 40 to 50 yr. Majority occurs before age 60.

  4. •

    Patients with alcoholic hepatitis typically drink more than 80 g of alcohol daily for at least 5 years.

Prevalence

Approximately 25% to 30%

Predominant Sex and Age

The majority of patients are males. Males are two times as likely as women to abuse alcohol. However, women develop alcoholic hepatitis after a shorter time and smaller amount of alcoholic exposure than men.

Genetics

No genetic predilection for any one race. In the U.S., however, there is increased incidence in minority groups.

Risk Factors

Drinking multiple alcohol types, drinking alcohol between meal times, poor nutrition, female gender, obesity, Hispanic ethnicity, long-term ingestion of >10 to 20 g/day of alcohol in women and >20 to 40 g/day in men

Physical Findings & Clinical Presentation

Common presenting symptoms include:

  1. •

    Rapid onset of jaundice

  2. •

    Nausea/vomiting

  3. •

    Malaise

  4. •

    Low-grade fever

  5. •

    Anorexia

  6. •

    Abdominal distention/pain

  7. •

    Weight loss or malnourishment

  8. •

    Complications of liver impairment (GI bleed; confusion, lethargy, ascites)

Findings on physical examination include:

  1. •

    Jaundice and ascites

  2. •

    Hepatomegaly, with tender liver on palpation

  3. •

    Fever

  4. •

    Asterixis (a flapping tremor)

  5. •

    Splenomegaly

  6. •

    Tachycardia

  7. •

    Hypotension

  8. •

    Peripheral edema

  9. •

    Abdominal distention with shifting dullness (ascites)

  10. •

    Hepatic bruit

  11. •

    With coexistent cirrhosis, look for:

    1. 1.

      Gynecomastia

    2. 2.

      Proximal muscles wasting

    3. 3.

      Spider angiomata

    4. 4.

      Altered hair distribution

Diagnosis

Differential Diagnosis

  1. •

    Hepatitis B

  2. •

    Hepatitis C

  3. •

    Nonalcoholic steatohepatitis (NASH)

  4. •

    Chronic pancreatitis

  5. •

    Drug-induced liver injury

  6. •

    Hemochromatosis

  7. •

    Cholangitis

Workup

  1. •

    A thorough and detailed history is needed.

  2. •

    Relevant questions may include:

    1. 1.

      When patient started drinking

    2. 2.

      Number of times patient drinks per day

    3. 3.

      How many years of regular/daily drinking

    4. 4.

      Types of alcohol

    5. 5.

      Home or bar drinking

    6. 6.

      Rehabilitation for drinking

    7. 7.

      Social problems (e.g., arrest for public intoxication or driving under the influence, marital discord due to alcoholism)

Laboratory Tests

  1. •

    Elevated transaminase (AST >45 U/L but <300 U/L; AST:ALT ratio ≥2.0) but some patients may not have elevations in ALT, AST in early phases

  2. •

    S-bilirubin >2 mg/dl

  3. •

    Increased PT/INR

  4. •

    Elevated gamma glutamyltransferase (GGT)

  5. •

    Carbohydrate-deficient transferrin (CDT) is a reliable marker for chronic alcoholism

  6. •

    Elevated C-reactive protein

  7. •

    Electrolyte disorder (hypokalemia, hypomagnesemia, low zinc, hypophosphatemia)

  8. •

    Hypoalbuminemia

  9. •

    Hyperferritinemia

  10. •

    CBC (may reveal leukocytosis with bandemia or anemia or thrombocytopenia); MCV may be elevated

  11. •

    Screening tests to rule out other conditions include checking:

    1. 1.

      Hepatitis B surface antigen (HBsAg), HBcAb (IgM), Hepatitis A Ab (IgM)

    2. 2.

      Anti–hepatitis C antibody, hepatitis C RNA

    3. 3.

      Ferritin-transferrin saturation

    4. 4.

      Alpha-fetoprotein

    5. 5.

      Alkaline phosphatase

  12. •

    The severity of AH can be calculated with the Maddrey Discriminant Function (MDF) score, which is calculated as follows:

Imaging Studies

Ultrasonography is the preferred imaging study. The earliest histologic change in alcoholic liver disease is macrovesicular steatosis.

Liver Biopsy

  1. •

    Liver biopsy is rarely needed.

  2. •

    Useful to:

    1. 1.

      Confirm the diagnosis.

    2. 2.

      Evaluate the effect of coexisting disease.

    3. 3.

      Rule out cirrhosis.

    4. 4.

      Exclude other diagnoses (especially other causes of liver diseases, biliary obstruction, Budd-Chiari syndrome).

  3. •

    Typical findings include:

    1. 1.

      Macrovascular steatosis

    2. 2.

      Hepatocyte injury (ballooning degeneration and focal hepatocyte necrosis)

    3. 3.

      Mallory’s bodies (characteristic of alcoholic hepatitis)

    4. 4.

      Perivenular fibrosis

    5. 5.

      Portal and lobular inflammation

Treatment

An algorithm for the management of patients with alcoholic hepatitis is described in Fig. 1. Treatment can be divided into three main components:

  1. 1.

    Lifestyle modifications

  2. 2.

    Nutritional support

  3. 3.

    Pharmacologic therapy

FIG.1 

Algorithm for the management of patients with alcoholic hepatitis. ∗The DF is calculated as follows: 4.6 (prothrombin time of patient − prothrombin time of control) + serum bilirubin level (in mg/dl). †The Model for End-Stage Liver Disease score is based on the serum bilirubin level, INR, and serum creatinine level. ‡The Glasgow alcoholic hepatitis score is based on the patient’s age, white blood cell count, blood urea nitrogen level, ratio of prothrombin time to a control value, and serum bilirubin level. DF, Discriminant function. Online calculators for these various models are available at http://www.lillemodel.com.
From Feldman M, et al.: Sleisenger and Fortran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Elsevier.

Lifestyle Modifications

  1. •

    Abstinence from alcohol (this improves both short- and long-term survival). Fig. 2 describes the effect of subsequent alcohol intake on 5-year survival in patients with alcoholic hepatitis

    FIG.2 

    Effect of subsequent alcohol intake on 5-year survival in patients with alcoholic hepatitis and cirrhosis.
    From Day CP: Liver disorder part 1 of 2, Medicine 35(1):22–25, 2007.
  2. •

    Smoking cessation (to decrease oxidative stress)

  3. •

    Treatment of substance abuse

Nutritional Support

  1. •

    Good nutrition is an essential part of treatment because many patients with alcoholic hepatitis are usually in a catabolic state.

  2. •

    Nutritional support includes:

    1. 1.

      Liberal vitamin supplementation (especially thiamine, folic acid, vitamin K)

    2. 2.

      Mineral supplementation (but not iron)

    3. 3.

      Calorie counting is essential. A high calorie intake (1.2 to 1.4 times the normal resting intake) may be required.

    4. 4.

      Protein intake of 1.2 to 1.5 g/kg of ideal body weight per day will provide adequate support. Exception: in patients with severe encephalopathy, protein restriction may be required.

    5. 5.

      Fluid management

Pharmacologic Therapy

Severe alcoholic hepatitis may require treatment. Severity can be assessed by calculating the Model for End-Stage Liver Disease (MELD) score or Maddrey’s discriminant function (MDF) score or the Glasgow score.

  1. •

    An MDF score >32 indicates significant or severe alcoholic hepatitis (30-day mortality of 50%).

  2. •

    MELD score can easily be calculated (visit http://www.unos.org/resources/meldpeldcalculator.asp?index=98). This score predicts short-term survival in patients with cirrhosis. A score ≥20 predicts increased short-term mortality.

  3. •

    Glasgow score: contains four variables (BUN, PT, WBC count, and bilirubin). A score ≥9 indicates increased mortality.

Indications for initiating therapy include:

  1. •

    MDF >32

  2. •

    MELD >20

  3. •

    Glasgow score >8

  4. •

    Hepatic encephalopathy

Patients with severe alcoholic hepatitis may be treated with glucocorticosteroids (prednisolone 40 mg/day for 28 days with a 2-wk taper). Glucocorticosteroids reduce hepatic injury, suppress inflammation, and promote liver regeneration. However, not all studies have demonstrated consistent therapeutic benefits for steroids, even in high risk patients. An alternative first-line agent (especially for patients with contraindications to corticosteroids) in patients with severe alcoholic hepatitis is pentoxifylline. There are various other treatments, but these are mainly experimental.

Liver Transplantation

  1. •

    Usually reserved for patients with end-stage liver disease. Patients whose hepatitis is not responding to medical therapy have a 6-month survival rate of approximately 30%. Since most hepatitis deaths occur within 2 months, early liver transplantation is attractive but controversial.

  2. •

    Patients with alcoholic hepatitis must be sober for at least 6 mo before they can be eligible for consideration for liver transplantation.

Referral

Severe acute alcoholic hepatitis may require ICU care and referral to different subspecialists:

  1. •

    GI/hepatology (for patients with evidence of GI hemorrhage)

  2. •

    Nutritional services

  3. •

    Nephrology (for acute renal failure, hepatorenal syndrome)

  4. •

    Neurology (for change in mental status, seizures)

  5. •

    Infectious disease (for fever/leukocytosis)

Pearls & Considerations

Comments

  1. •

    Referral to substance abuse treatment programs may be helpful.

    1. 1.

      Stress to patients that there are limited long-term drug treatments for alcoholic hepatitis.

    2. 2.

      Maintaining good general nutrition is important.

    3. 3.

      Advise patient about the risk of taking certain medications, especially acetaminophen.

  2. •

    Periodic follow-up to monitor patient’s response to check BMP and LFTs.

  3. •

    Encourage alcohol abstinence. Abstinence improves long-term survival.

  4. •

    If patient develops liver cirrhosis, check serum alpha-fetoprotein every 6 mo and liver ultrasound annually to rule out hepatocellular carcinoma.

  5. •

    Vaccinate patient against hepatitis A and B viruses, pneumococci, influenza A virus, and routine adult vaccinations, if appropriate.

Suggested Readings

  • M. Chayanupatkul, et al.: Alcoholic hepatitis: a comprehensive review of pathogenesis and treatment. World J Gastroenterol. 20 (20):6279–6286 2014 24876748

  • P. Mathurin, et al.: Early liver transplantation for severe alcoholic hepatitis. N Engl J Med. 365:1790–1800 2011 22070476

  • A. Maziya, B.A. Runyon: Alcoholic hepatitis 2010: a clinician’s guide to diagnosis and therapy. World J Gastroenterol. 16 (39):4905 2010 20954276

  • CS. Pavlov, et al.: Glucocorticosteroids for people with alcoholic hepatitis. Cochrane Database Syst Rev. 11:CD001511 2017 29096421

Related Content

  1. Alcoholic Hepatitis (Patient Information)

 

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