Non Alcoholic Liver Disease

Autoimmune Liver disease defn

Chronic inflammatory condition of liver associated with unknown etiology, autoantibodies and a genetic predisposition

4 main sub types of Autoimmune Liver Disease

Autoimmune hepatitis (AIH)

Primary biliary cholangitis (cirrhosis) (PBC) (bile ducts)

Primary sclerosing cholangitis (PSC) (bile ducts)

Autoimmune overlap syndromes (AIH-PBC) (AIH-PSC)

Name 6 Features common to all Autoimmune Liver diseases

• Associated with the presence of autoantibodies (against self antigens)

• Usually increased serum IgG +/- IgM

• May be associated with AI diseases at other sites – thyroid, adrenal,

• Typical inflammatory cells- lymphocytes, plasma cells +/- lymphoid aggregates

• General- immune mediated liver damage

• May respond to immune suppression

How many types of Autoimmune Hepatitis (AIH) are there

Type 1, 2a, 2b, 3

Targeted cells in AIH

hepatocyte

AIH is more common in what gender

female

Name the 2 main autoantibodies associated with Type 1

ANA, ASM

Name the 2 main autoantibodies associated with Type 2a

ANA, ASM

Name the 2 main autoantibodies associated with Type 2b

LKM-1

Name the 2 main autoantibodies associated with Type 3

Anti-SLA (soluble liver antigen)

Which immunoglobulin will have changed levels in AIH (up/down)

Increased IgG

Which liver enzyme will have changed levels in AIH (up/down)

Aminotransferases increased

What are the 2 genetic predispositions for AIH

HLA DR3, DR4

Treatment for AIH

Responds to immune suppression (steroids)

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Is Primary Biliary Cholangitis (PBC) autoimmune

Yes

2 risk factors for Primary Biliary Cholangitis (PBC)

F>>M 9:1

40-60yrs

What antibody is associated with PBC

Anti-mitochondrial antibodies (AMA) are present in >95% cases

What tissue is targeted in PBC

small bile ducts in liver

Pathology of PBC

Progressive bile duct damage → fibrosis

Cirrhosis develops quite late

2 symptoms of PBC

jaundice, pruritis (bile salts)

2 biochemical changes in PBC

Raised Alk Phophatase

Raised bilirubin

What immunoglobulin is affected by PBC & how

Raised Ig especialy IgM

3 histological features of PBC

Portal tract inflammation- lymphos and plasma cells +/- granulomas.

Hallmark = destruction of small (40-80um) bile ducts, inflammation, swelling in bile ducts may be focal hence need good Bx

Late stage → fibrosis-micronodular cirrhosis

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What is Primary Sclerosing Cholangitis (PSC)

Chronic disease of liver associated with fibrosis and inflammation in bile duct wall- intermittent areas of fibrosis and narrowing along bile duct

What is the eventual result of the progression of PSC

Eventual replacement of bile ducts with cord of fibrous tissue

Does PSC affect intra/extra hepatic bile ducts

Both

2 Risk factors for PSC

Associated with IBD especially UC

M>F (2-3:1)

How does PSC present

Cholangitis- recurrent inflammation due to obstruction

Cholestasis due to obstruction- jaundice

Fatigue, upper abdominal pain,intermittent/progressive jaundice

Usually <50 years at presentation, can present in adolescence

What is found in serology for PSC

pANCA + in >80% of cases (not specific)

What is found in radiology for PSC

ERCP imaging of biliary tree shows a ‘beaded’ biliary- narrowing along bile duct

What is found in histology for PSC

Inflammation in portal tract, damage to bile duct, progressive loss of bile ducts, peri-ductal ‘onion-skin’ fibrosis pattern (late stage)

(Early histological changes very non-specific)

Complications of PSC

Develop progressive fibrosis of liver with decreased function- liver cirrhosis, failure

10-20% develop cholangiocarcinoma after many years

Treatment for PSC

No effective treatment for PSC

Cirrhosis/failure stage-Transplantation

There is still a risk of recurrence of PSC with transplant

What is Alpha 1 anti-trypsin deficiency

Hereditary metabolic disease of liver

What is abnormal in Alpha 1 anti-trypsin deficiency

Abnormality on chromosome 14-protease inhibitor Pi

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What is Haemochromatosis

Deposition of iron in liver, pancreas, testes

What causes Haemochromatosis

Genetics

Inheritance pattern of Haemochromatosis

Autosomal recessive

Which chromosome, gene & homo/heterozygotes are associated with Haemochromatosis

Chromosome 6

Commonest C282Y gene

Homozygotes

Which gender is more at risk for Haemochromatosis

Male

Age of presentation for Haemochromatosis

Presents 40-60 yrs in men, later in women (periods → later presentation)

Where is iron initially deposited in Haemochromatosis

Peri-portal hepatocytes → then other hepatocytes

What does severe (grade 3–4) iron deposition look like

Coarse iron granules within hepatocytes

What stain is used to demonstrate iron?

Perls stain, which stains iron blue.

How does iron overload cause liver damage

Iron → irritation/injury → fibrosis → nodule formation → micronodular cirrhosis

3 steps to Haemochromatosis Diagnosis

1. High iron saturation in serum

2. Grade 3-4 iron on liver biopsy

3. Genetic abnormality (C282Y or H63D gene)

2 treatments for Haemochromatosis

1. Iron removal- venesection (therapeutic phlebotomy)

2. Transplantation- late stage liver failure

What is done first when Haemochromatosis is diagnosed

Must screen family as identification of cases can allow earlier intervention (phlebotomy) and decrease cirrhosis

Possible complication of Haemochromatosis

Haemochromatosis patients x200 increased risk of hepatocellular carcinoma (hepatocellular carcinoma surveillance in these patients)

Risk is associated with cirrhosis

True/False Hepatitis A virus (HAV) is only seen as acute hepatitis

True

Is HAV a DNA/RNA virus

RNA

How is HAV spread

spread fecal-oral- person to person contact or contaminated water

(decreased incidence with increased hygiene in countries)

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