Alcohol Related Liver Disease

When alcohol is absorbed from the GI tract, it is distributed throughout the body according to what

Volume of fluid in tissues

What % alcohol is eliminated through lungs/kidneys

<10%

What happens the alcohol that isn’t eliminated through lungs/kidneys

Oxidised in the body (mostly in the liver)

Ethanol is broken down to what which is broken down to what

Ethanol → Acetaldehyde → Acetate

What 3 ways is ethanol broken down to Acetaldehyde

1. Alcohol dehydrogenase pathway (ADH)

2. Microsomal ethanol oxidising system (MEOS)

3. Catalase pathway

Which pathways breaking down Ethanol → Acetaldehyde is associated with carcinogenicity

Microsomal ethanol oxidising system (MEOS)

How is Microsomal ethanol oxidising system (MEOS) associated with carcinogenicity

MEOS → increased CYP2E1 for increased ethanol clearance

CYP2E1 is associated with carcinogenicity

Name the 3 phases/stages of alcoholic liver disease

1. Steatosis

2. Alcoholic hepatitis

3. Alcoholic cirrhosis

What % of chronic alcoholics have cirrhosis at presentation

40%

Steatosis

Accumulation of fat in liver → fat spaces

Other than alcohol related liver disease, name some causes for steatosis

diabetes mellitus, HCV, drugs, pregnancy, TPN, Non alcoholic fatty liver disease (NAFLD)

Alcoholic Steatosis is seen in __% patients with chronic alcoholism

90%

Is Alcoholic Steatosis reversible

Yes

How long does Alcoholic Steatosis take to disappear after stopping dirnking

2-4 weeks

Does acute ‘binge’ drinking lead to steatosis

Yes - It becomes a yellow swollen greasy fatty liver

Alcoholic steatosis can lead to what

fibrosis /cirrhosis

How is Alcoholic Hepatitis diagnosed

Can only be diagnosed on liver biopsy

What changes are seen in LFTs in Alcoholic Hepatitis

Non specific changes in LFTs

Alcoholic Hepatitis is present in what % of chronic alcoholics

20%

Symptoms of Alcoholic Hepatitis

Non specific GI symptoms, hepatomegaly

May be asymptomatic → patients present with cirrhosis

Describe the steatosis associated with Alcoholic Hepatitis (mostly micro/macrovesicular)

Predominantly macrovesicular (steatohepatitis)

Name 5 histological features of Alcoholic Hepatitis

Liver cell necrosis- spotty necrosis

Ballooning degeneration of hepatocytes

Neutrophil polys- associated with necrotic hepatocytes and in sinusoids

Mallory-Denk bodies- in cytoplasm

+/- perivenular fibrosis

Which of the 5 histological features of Alcoholic Hepatitis increases risk of cirrhosis

Perivenular fibrosis

What do Mallory-Denk bodies look like

Cytoplasmic irregular pink material with Cytokeratin filaments

Where are Mallory-Denk bodies usually found

Usually in ballooned hepatocytes

What 2 other conditions could cause formation of Mallory-Denk bodies

Tumours

NASH

How are Mallory-Denk bodies hyaline identified

IHC

How are Mallory-Denk bodies visualised - what highlights them

Ubiquitin

Cirrhosis definition

-Diffuse change

-Entire liver

-Hepatocyte loss

-Nodular regeneration

(All of criteria must be present)

Describe pathology of liver Cirrhosis

Fibrosis of liver with nodule formation

True/False Alcohol is commonest cause of cirrhosis in Europe and US

True

In US in 35-54 year age group cirrhosis (predominantly alcohol) is the what placed commonest cause of death in men and what placed commonest cause in women

In US in 35-54 year age group cirrhosis (predominantly alcohol) is the 4th commonest cause of death in men and 5th commonest cause in women

What size nodules are considered micronodular cirrhosis

Nodules < = 3mm

Is micro/macronodular cirrhosis easier to diagnose? Why?

Micronodular = easier - can see entire nodule in liver core biopsy- core approx 2mm

Macronodular- often have part of nodule- more difficult to diagnose cirrhosis on Bx

What is the outcome of cirrhosis (3 options)

Extensive hepatocyte loss and replacement with fibrous tissue → ultimate liver failure (coagulopathy, metabolism, bile metabolism)

Altered hepatic circulation (fibrosis) → portal HTN → oesophageal varices → significant/fatal haemorrhage

Cirrhosis → increased long term risk hepatocellular carcinoma

What % of patients with alcoholic cirrhosis develops hepatocellular carcinoma

5-15%

5 features of End stage liver disease

Loss of normal function

Coagulopathy

Decreased protein production (albumin)

Cholestasis

Hepatic encephalopathy

Risk factors for alcoholic liver disease

Dose duration and pattern of alcohol consumption

Drinking outside mealtimes

Drinking multiple different alcoholic drinks

Female susceptibility >> males

Obesity & increased BMI

What’s the connection between Alcohol and Hepatitis C virus (HCV)

Alcohol accelerates progression of HCV liver disease → hepatocellular carcinoma (HCC)

There is an occurrence rate of HCC in ___% of patients with alcoholic cirrhosis & who were HCV positive compared with ___% in those with alcoholic cirrhosis alone

80.7%

18.5

When MEOS increases CYP2E1 , what other effect does this have

Increased CYP2E1 cytochrome → increased metabolism of other agents eg paracetamol → Paracetamol (therapeutic) injury in chronic alcoholics

Chronic low dose alcohol has what effect on drug action which leads to what

Potentiate effect of other drugs in therapeutic doses → cirrhosis

Is Cirrhosis reversible?

Not proved so yet in humans

5 year survival rate in cirrhosis patients who abstained from alcohol vs who continued to drink

68% of cirrhotics who abstained survived

41% of those who continued to drink survived

3 possible outcomes from Portal Hypertension

Oesophageal varices

Rectal hemorrhoids

Caput medusae (abdomen

2 standard stains for liver

Haematoxylin & Eosin

What stain is used to visualise glycogen

Periodic acid Schiff (PAS)

Other than glycogen, what is PAS useful for highlighting

steatosis (fat spaces)

What stain is used to visualise alpha 1 antitrypsin deficiency (globules)

PAS + diastase

What stain is used to visualise iron

Perls

True/False Iron deposition in small amounts in the liver is normal

False

Where in the liver can iron accumulate

hepatocytes / bile ductule cells

Iron deposition in the liver can be graded from what to what based on what

Grade 1-4 based on granule size

What is Iron deposition in the liver called

Siderosis

What % of ARLD patients show mild siderosis

57% patients

What % of ARLD patients show grade 3-4 siderosis

7%

How does ALRD cause siderosis

Due to increased iron absorbtion + high iron content of some alcoholic drinks

Complication of iron in the liver

Iron → oxidative stress → fibrosis progression

What stain is used to visualise interface hepatitis

Periodic acid Schiff (PAS)

Histological feature of interface hepatitis

irregular limiting plate

What stain is used to visualise architecture collapse

Reticulin

What stains are used to visualise collagen (2)

Haematoxylin van Gieson (HVG) or Massons Trichrome-

How does hereditary hemochromatosis affect the liver

Alcohol and hereditary hemochromatosis → accelerated progression to fibrosis/cirrhosis

Name a famous historical person who died of end stage liver disease- combined effect of alcohol & iron overload

Ludwig van Bethoven

Name a stain used to visualise architectural abnormality

Reticulin : silver stain → fine reticulin, condensation & collapse early in architectural abnormality

Name 2 stains used to visualise fibrosis

HVG haematoxylin van gieson

Massons trichrome

People with ARLD must be abstinent for how long prior to transplantation

Abstinence for 6 months prior to Tx

Rate of Acute cellular rejection within 1 year of transplantation

29%