Alcoholic Liver Disease

The Best Histopathology

Case Study Mr.T• 56 year old Male presented to A&E with

Abdominal distension, somnolence and haematemesis

• Orientated only to name• Family members disclose a history of

alcohol abuse (100 units / wk)• O/E: BP 90/60, Pulse 120. Jaundiced with

peripheral stigmata of liver disease and shifting dullness

Mr.T Cont…• Fluid resuscitation, abdominal

paracentesis and sclerosis of oesophageal varices at endoscopy

• CT scan revealed 6.0 cm homogenous liver mass with AFP level of 2500ng/ml (>50ng/ml = abnormal)

Pathology Ladder• Fatty liver (Alcoholic steatosis)• Alcoholic hepatitis• Fibrosis• Cirrhosis• Hepatocellular carcinoma

Steatosis (Macrovesicular)

• 65% of chronic drinkers

• Large sharp fat droplets in hepatocytes

• Accumulation due to defect of secretion of lipoprotein by hepatocytes

Microvesicular (Foamy) Steatosis• Much rarer – first

stage of hepatic decompensation

• Groups of foamy hepatocytes containing small droplets throughout cytoplasm

• Hepatocyte dropout due to apoptosis and pericellular fibrosis

Alcoholic Hepatitis• Necroinflammatoy lesion

in centrolobular area• Characterised by -

Necrosis, Inflammation and Fibrosis

• Infiltrate of neutrophil polymorphs surrounding Mallory bodies

• Acute alcoholic hepatitis has a mortality rate of 20-50%

Mallory Bodies

Fibrosis• Pericellular or “chicken wire” fibrosis in

hepatitis• Venous lesions; sclerosing hyaline

necrosis portal hypertension• Cytokine mediated transformation of Ito

cells into transitional cells, myofibroblasts and fibroblasts

• Interference with O2 and nutrient exchange between blood and hepatocyte = injury and dysfunction

Pericellular (Chicken Wire) Fibrosis

Prognosis • Initial fibrosis in steatosis will resolve

with abstinence• Severe fibrosis may progress to cirrhosis

even without continuation of alcohol consumption

• Factors affecting progression to cirrhosis include; continued alcohol consumption, severity of lesion and sex (F>M). There is also thought to be a genetic component

Cirrhosis• 10-20 % of chronic drinkers; irreversible• Parenchymal necrosis, re-generation and

fibrosis resulting in disorganisation of the acinar structure

• Usually micronodular, with uniform regenerative nodules <3mm

• 60-70% 5yr survival in abstinence• 40% in continued drinking• 5 - 10% develop Hepatocellular carcinoma

Micronodular Cirrhosis

Microscopic Micronodular

Hepatocellular Carcinoma• Progression of micro

to macronodular cirrhosis (often after period of abstinence)!

• Dysplasia in regenerative nodules -> Neoplasia

• Increased risk with Hepatitis

• Fatal within 10 months

Conclusion• Patient may present with a mixed

picture of pathology• Important to remember that

changes are often reversible• Serious consequences of continued

drinking – irreversible damage• Cirrhosis and hepatocellular

carcinoma

Questions?

References• Alcoholic liver disease, Pathology and Pathogenesis, 2nd Edition 1995 Ed. Pauline Hall • Cpmenet.columbia.edu • Gastroresource.com • Lieben CS.Pathogenesis and treatment of alcoholic liver disease:

progress over the last 50 years.Rocz Akad Med Bialymst. 2005;50:7-20.

• meddean.luc.edu• merck.com• Oxford Handbook Clinical Medicine• Sougioultzis S, Dalakas E, Hayes PC, Plevris JN.

Alcoholic hepatitis: from pathogenesis to treatment.Current Medical Research and Opinion, Volume 21, Number 9, September 2005, pp. 1337-1346(10)