Liver & intrahepatic bile ducts

Noninfectious hepatitis

Alcoholic liver disease


Editorial Board Member: Monika Vyas, M.D.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Anthony W.H. Chan, M.B.Ch.B.

Last author update: 17 March 2022
Last staff update: 4 August 2022

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PubMed Search: Alcoholic liver disease hepatitis pathology

Anthony W.H. Chan, M.B.Ch.B.
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Cite this page: Chan AWH. Alcoholic liver disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liveralcoholichep.html. Accessed January 28th, 2023.
Definition / general
  • Liver damage caused by excessive alcohol consumption
Essential features
  • Liver damage caused by excessive alcohol consumption
  • Steatosis, steatohepatitis or perivenular and pericellular fibrosis are typical histological features
Terminology
  • Alcoholic liver disease
ICD coding
  • ICD-10:
    • K70.0 - alcoholic fatty liver
    • K70.9 - alcoholic liver disease, unspecified
  • ICD-11:
    • DB94.0 - alcoholic fatty liver
    • DB94.Z - alcoholic liver disease, unspecified
Epidemiology
Sites
  • Liver
Pathophysiology
  • Alcohol enhances hepatic lipid biosynthesis
    • Excess NADH generation from alcohol dehydrogenase and acetaldehyde dehydrogenase
    • Impaired assembly / secretion of lipoproteins
    • Increased peripheral fat catabolism
  • P450 induction causes other drugs to be transformed to toxic metabolites; free radicals, from microsomal oxidation of alcohol, damage proteins and membranes
  • Alcohol directly affects microtubular and mitochondrial function, also induces immunologic attack on hepatic neoantigens
  • Acetaldehyde (alcohol metabolite) causes lipid peroxidation and acetaldehyde protein adduct formation
  • Collagen deposition by perisinusoidal hepatic stellate (Ito) cells is due to Kupffer cell activation (release of TNFα, IL1 / 6, TGFβ), platelet activating factor, influx of neutrophils into parenchyma
  • Alcohol also causes derangements of vascular perfusion
  • Alcohol consumption results in translocation of gut bacteria into the portal system along with lipopolysaccharides that interact with toll-like receptors and results in production of inflammatory and immunogenic mediators such as TNFα and interferons (World J Hepatol 2011;3:114)
Etiology
  • Excessive regular alcohol consumption (> 20 g/day for females and > 30 g/day for males)
Diagrams / tables

Images hosted on other servers:

Natural history of alcohol related liver disease

Clinical features
  • Nonspecific clinical features for any chronic liver disease
  • Odor of alcohol on breath
  • Alcohol withdrawal syndrome: fine tremor, psychomotor agitation, transient hallucinations or illusions, tachycardia
  • Reference: J Hepatol 2018;69:154
Diagnosis
  • Alcoholic liver disease (J Hepatol 2018;69:154):
    • Regular alcohol consumption of > 20 g/day for females and > 30 g/day for males
    • AND clinical or biological abnormalities suggestive of liver injury
  • Alcoholic hepatitis (Hepatology 2020;71:306):
    • Recent onset (< 8 weeks) of jaundice
    • Heavy alcohol consumption (> 40 g/day for females and > 60 g/day for males for ≥ 6 months or < 60 days of abstinence before the onset of jaundice)
    • Serum aspartate transaminase (AST) > 50 IU/L, AST/alanine transaminase (ALT) > 1.5 and both AST & ALT < 400 IU/L
    • Serum bilirubin > 50 µmol/L (3 mg/dL)
    • In presence of diagnostic uncertainly, liver biopsy is required to confirm histologically alcoholic steatohepatitis and rule out other diagnoses
Laboratory
  • Serum AST:ALT > 2
  • Elevated serum gamma glutamyltransferase (GGT; sensitivity 42 - 86%; specificity 40 - 84%) (J Hepatol 2018;69:154)
  • Elevated mean corpuscular volume (MCV; sensitivity 24 - 75%; specificity 56 - 96%) (J Hepatol 2018;69:154)
  • Elevated percentage of carbohydrate deficient transferrin per total transferrin (%CDT; sensitivity 25 - 84%; specificity 70 - 98%) (J Hepatol 2018;69:154)
Prognostic factors
  • Increasing the risk of alcohol related liver injury (Hepatology 2020;71:306):
    • Drinking pattern: daily drinking, drinking while fasting, binge drinking
    • Female
    • Genetics: PNPLA3, TM6SF2, MBOAT7, HSD17B13
    • Smoking cigarettes
    • Increased BMI
    • Concurrent liver disease: chronic viral hepatitis, genetic hemochromatosis, nonalcoholic fatty liver disease
  • Ameliorating the risk of alcohol related liver injury:
    • Coffee consumption
Case reports
  • 27 year old man with alcoholic hepatitis presenting with high levels of triglyceride, direct hyperbilirubinemia and elevated ALP without an obvious obstruction cause (Case Rep Gastroenterol 2020;14:448)
  • 47 year old woman with alcoholic hepatitis masquerading as tumor infiltration (Clin Case Rep 2019;7:2174)
  • 55 year old man with severe alcoholic hepatitis and superimposed Candida esophagitis, who was found to have leukemoid reaction during diagnostic workup (Cureus 2020;12:e9747)
  • 67 year old man with acute liver injury and false positive results of enzymatic ethanol assay secondary to lactic acidosis due to intravascular large B cell lymphoma (BMJ Case Rep 2019;12:e229814)
Treatment
Gross description
  • Early stage: enlarged liver with diffuse yellowish greasy appearance
  • Later stage:
    • Typical micronodular cirrhosis
    • Mixed micronodular and macronodular cirrhosis after abstinence
    • Yellowish greasy (due to steatosis) or greenish (due to cholestasis)
  • Reference: Clin Liver Dis 2016;20:473
Gross images

Contributed by Anthony W.H. Chan, M.B.Ch.B. and @Andrew_Fltv on Twitter
Alcoholic cirrhosis Alcoholic cirrhosis

Alcoholic cirrhosis

Alcoholic liver disease

Alcoholic liver disease

Microscopic (histologic) description
  • Steatosis:
    • Most common and earliest form of alcoholic liver disease
    • Predominantly macrovesicular steatosis: large droplet (classical; a single large fat droplet displacing the nucleus to the periphery) and small / medium droplets
    • First appears in perivenular region (zone 3) and spreads to other regions if drinking persists; may disappear within 1 month after alcohol cessation
    • Whether it is a benign, nonprogressive lesion is controversial (J Hepatol 2012;57:399)
    • Association between degree of steatosis and disease progression is also controversial
  • Alcoholic steatohepatitis:
    • Steatosis with inflammation and ballooning degeneration, which is the hallmark of hepatocellular injury in steatohepatitis
    • Ballooning degeneration is characterized by cellular swelling, rarefaction of the hepatocytic cytoplasm and clumped strands of intermediate filaments
    • Satellitosis is featured by ballooned hepatocyte surrounded by neutrophils
    • Mallory-Denk body, also known as Mallory body or Mallory hyaline, is a deeply eosinophilic, ropy intracytoplasmic inclusion that represents aggregates of misfolded intermediate filaments with other different classes of proteins, including p62 and ubiquitin
      • Often but not necessarily found in ballooned hepatocytes (Exp Cell Res 2007;313:2033)
      • Persists for several months after cessation of drinking
      • Associated with increased risk of progression to cirrhosis
    • Fibrosis is not a necessary diagnostic feature; perivenular and pericellular (perisinusoidal) fibrosis is characteristic for fatty liver disease; as disease progresses, portal / periportal fibrosis, bridging fibrosis and cirrhosis will develop
    • Alcoholic hepatitis histologic score is proposed to predict 90 day mortality based on 4 parameters: fibrosis, bilirubinostasis, neutrophilic infiltration and giant mitochondria (Gastroenterology 2014;146:1231)
  • Alcoholic cirrhosis:
    • Classically micronodular cirrhosis
    • Steatosis and ballooned hepatocytes may burn out in advanced fibrosis or cirrhosis
  • Other pathological lesions:
    • Lipogranuloma
    • Giant mitochondria: associated with recent heavy alcohol intake and disease progression (J Clin Pathol 1992;45:412)
    • Acute foamy degeneration: rare, extensive microvesicular steatosis with no / minimal inflammatory activity; clinically presents with jaundice, abdominal pain and hepatomegaly (Gastroenterology 1983;84:683)
    • Sclerosing hyaline necrosis: fibrous obliteration of terminal hepatic venule (phlebosclerosis) due to perivenular fibrosis; severe form of alcoholic hepatitis associated with noncirrhotic portal hypertension
    • Iron deposition: usually mild; mainly in hepatocytes (grade 1 - 2) and occasionally in Kupffer cells
Microscopic (histologic) images

Contributed by Anthony W.H. Chan, M.B.Ch.B.
Micronodular cirrhosis Micronodular cirrhosis Micronodular cirrhosis

Micronodular cirrhosis

Micronodular cirrhosis after abstinence

Micronodular cirrhosis after abstinence

Iron deposition

Iron deposition

Virtual slides

Images hosted on other servers:

Alcoholic hepatitis

Perivenular and pericellular fibrosis

Positive stains
Sample pathology report
  • Liver, right lobe, biopsy:
    • Moderate steatosis with perivenular and pericellular fibrosis (see comment)
    • Negative for significant lobular necroinflammatory activity
    • Negative for bridging fibrosis or cirrhosis
    • Negative for malignancy
    • Comment: In view of significant alcoholic consumption in absence of metabolic risks, the overall features are consistent with alcoholic steatosis.
  • Liver, native, transplantation:
    • Cirrhotic liver, clinically alcoholic cirrhosis
    • Negative for significant steatosis, ballooning degeneration or Mallory-Denk bodies, consistent with abstinence
    • Negative for dysplasia or malignancy
Differential diagnosis
  • Chronic viral hepatitis C:
    • Steatosis is typically mild at most
    • Presence of lymphocyte predominant portal inflammation, portal lymph follicle, bead-like sinusoidal lymphocyte infiltration and mild bile duct injury differentiates hepatitis C from alcoholic liver disease
  • Drug induced liver injury (e.g., amiodarone, glucocorticoids, methotrexate, synthetic estrogens, tamoxifen)
  • Nonalcoholic fatty liver disease:
    • Pathologically almost indistinguishable from alcoholic liver disease
    • Alcoholic liver disease has few specific pathological changes and all are rare:
    • Alcoholic liver disease tends to have more Mallory-Denk bodies and giant mitochondria, much less glycogenated nuclei and has satellitosis (ballooned hepatocyte surrounded by neutrophils), although all of these are nonspecific
    • Key distinguishing feature is in fact the amount of alcohol consumption obtained from clinical history
    • Consumption of 2 standard drinks/day for men and 1 standard drink/day for women is endorsed as the acceptable threshold to define nonalcoholic
  • Wilson disease:
    • Mild steatosis, glycogenated nuclei and Mallory-Denk bodies
    • Deposition of copper associated protein (particularly in hepatocytes out of periportal region) differentiates Wilson disease from alcoholic liver disease
  • Other uncommon inherited metabolic diseases
Board review style question #1
Which of the following histological features is useful to differentiate alcoholic liver disease from nonalcoholic fatty liver disease?

  1. Acute foamy degeneration
  2. Ballooning degeneration
  3. Mallory-Denk body
  4. Satellitosis
  5. Severe steatosis
Board review style answer #1
A. Acute foamy degeneration. Acute foamy degeneration (diffuse microvesicular steatosis) is a rare presentation of severe acute alcoholic hepatitis presenting with jaundice and hepatomegaly. Rapid recovery occurs on abstinence from alcohol. Diffuse microvesicular steatosis is not a histological feature of nonalcoholic fatty liver disease.

Comment Here

Reference: Alcoholic liver disease
Board review style question #2

Which stain is helpful in highlighting the structures indicated by arrows in the image shown above?

  1. Alpha-1 antitrypsin
  2. CK5/6
  3. HepPar1
  4. Orcein
  5. p62
Board review style answer #2
E. p62. The highlighted structures are Mallory-Denk bodies, which are misfolded and aggregated intermediate filaments combined with other different classes of proteins, including p62 and ubiquitin. They are immunoreactive to CK8/18, p62 and ubiquitin.

Comment Here

Reference: Alcoholic liver disease
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