Liver & intrahepatic bile ducts
Noninfectious hepatitis
Alcoholic liver disease
Author: Anthony W.H. Chan, F.R.C.P.A.
Topic Completed: 1 November 2015
Minor changes: 27 July 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Alcoholic liver disease[TI] hepatitis free full text[sb]
Table of Contents
Definition / general | Epidemiology | Pathophysiology | Clinical features | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Differential diagnosisCite this page: Chan A. Alcoholic liver disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/liveralcoholichep.html. Accessed November 27th, 2020.
Definition / general
- Alcohol is a psychoactive substance, which may lead to alcohol dependence, causing various physical, psychological and social problems
- Excessive alcohol consumption causes a spectrum of alcoholic liver disease including steatosis, alcoholic hepatitis, fibrosis, alcoholic cirrhosis and hepatocellular carcinoma
Epidemiology
- 90 - 95% of heavy drinkers develop steatosis; up to 35% develop advanced alcoholic liver diseases (i.e. alcoholic hepatitis, fibrosis, cirrhosis or hepatocellular carcinoma) (J Hepatol 2012;57:399)
Pathophysiology
- 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 tumor necrosis factor α and interferons (World J Hepatol 2011;3:114)
- Alcohol consumption causes shunting of normal substrates away from catabolism and toward lipid biosynthesis due to:
- Excess NADH generation from alcohol dehydrogenase and acetaldehyde dehydrogenase
- Impaired assembly / secretion of lipoproteins and
- 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 TNF alpha, IL1 / 6, TGF-beta), platelet activating factor, influx of neutrophils into parenchyma
- Alcohol also causes derangements of vascular perfusion
Clinical features
- Global alcohol consumption among those > age 15 years is 6.2 liters of pure alcohol per year (13.5 g of pure ethanol per day) (WHO: Global Status Report on Alcohol and Health 2014 [Accessed 1 November 2017])
- Spirits account for 50.1% of global total recorded alcohol and are the most common alcoholic beverage in Southeast Asia and Western Pacific regions
- Beer accounts for 34.8% of global total recorded alcohol and is the most common alcoholic beverage in the U.S. (WHO: Global Status Report on Alcohol and Health 2014 [Accessed 1 November 2017])
- 5.9% of global deaths are attributable to alcohol, mainly cardiovascular disease (33.4%), unintentional injury (17.1%) and liver cirrhosis (16.2%) (WHO: Global Status Report on Alcohol and Health 2014 [Accessed 1 November 2017])
- 5.1% of the global burden of disease and injury is attributable to alcohol, mainly neuropsychiatric disorders (24.6%), unintentional injury (20.4%), cardiovascular disease (15.5%) and liver cirrhosis (13.6%) (WHO: Global Status Report on Alcohol and Health 2014 [Accessed 1 November 2017])
Prognostic factors
- Associated with disease progression (J Hepatol 2012;57:399):
- Female gender
- Obesity
- Daily or nearly daily heavy drinking
- Drinking at an early age
- Concurrent chronic liver diseases, especially HCV and genetic hemochromatosis
- Genetic susceptibility genotype PNPLA3 rs738409 (GG)
Case reports
- 30 year old woman with hyperbilirubinaemia and hemolytic anaemia in acute alcoholic hepatitis (BMJ Case Rep 2014 Apr 19;2014)
- 33 year old man with "pseudotumoral" hepatic pattern in acute alcoholic hepatitis (World J Gastroenterol 2009;15:4070)
- 49 year old woman with Budd-Chiari-like syndrome in decompensated alcoholic steatohepatitis and liver cirrhosis (World J Gastroenterol 2006;12:6564)
Treatment
- Abstinence is the most important treatment
- Prednisolone and pentoxifylline are recommended to treat severe alcoholic hepatitis by AASLD (Hepatology 2010;51:307) and EASL (J Hepatol 2012;57:399), although efficacy is controversial
- In a recent multicenter, double blind, randomized trial of 1,053 patients, pentoxifylline did not improve survival whereas prednisolone was associated with a reduction in 28 day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year (N Engl J Med 2015;372:1619)
Gross description
- Initially liver is 4 - 6 kg, yellow, greasy, easily fractured
- Later liver becomes red with bile stained areas
- May contain visible nodules and fibrosis
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 hepatitis:
- 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 cirrhosis:
- Classically micronodular cirrhosis
- Steatosis and ballooned hepatocytes may burn out in advanced fibrosis or cirrhosis
- Other pathological lesions in alcoholic liver disease:
- 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
Images hosted on other servers:
Liver biopsy
Natural history of ALD
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 NAFLD / NASH
- Drug induced liver injury: e.g. amiodarone, glucocorticoids, methotrexate, synthetic estrogens, tamoxifen
- Nonalcoholic fatty liver disease:
- Pathologically almost indistinguishable from ALD
- Alcoholic liver disease has few specific pathological changes and all are rare:
- Acute foamy degeneration
- Sclerosing hyaline sclerosis
- Acute / chronic cholestasis and sinusoidal obstruction syndrome
- 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 two standard drinks/day for men and one standard drink/day for women is endorsed as the acceptable threshold to define nonalcoholic
- Wilson disease:
- Mild steatosis, glycogenated nuclei and Mallory-Denk bodies mimic NAFLD / NASH
- Deposition of copper associated protein (particularly in hepatocytes out of periportal region) differentiates Wilson disease from NAFLD / NASH
- Other uncommon inherited metabolic diseases
