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Year 3 Gastrointestinal > Autoimmune hepatic disease > Flashcards

Autoimmune hepatic disease Flashcards

1
Q

What is autoimmune hepatitis? Characterised by? (x4)

A

CHRONIC inflammatory disease of the liver of unknown aetiology. It is characterised by the presence of circulating auto-antibodies, hyperglobulinaemia, inflammatory changes on liver histology, and a favourable response to immunosuppressive treatment.

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2
Q

What is hyperglobulinaemia?

A

High concentration of circulating globulins – mostly this concerns immunoglobulins.

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3
Q

What is the difficulty with identifying and managing autoimmune hepatitis clinically?

A

Disease has variable course and different clinical manifestations.

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4
Q

What is the aetiology of autoimmune hepatitis? (x4)

A
  • Unknown but likely a complex interaction between the following:
  • (1) Genetic predisposition: HLA genes on Chr6 – Type 1 associated with HLA-DR3 and HLA-DR4; Type 2 with HLA-DQB1 and HLA-DRB.
  • (2) Environmental triggers including viruses (measles, hepatitis) and drugs (some antibiotics and statins)
  • (3) Auto-antigens (normal protein that is abnormally recognised by the immune system): autoantibodies against ASGP-R, CYP2D6, and UDP-glucuronosyltransferases.
  • (4) Dysfunction of immunoregulatory mechanisms e.g., as part of APECED syndrome’s pathophysiology.
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5
Q

What is the pathophysiology of autoimmune hepatitis?

A

Hepatocyte expression of HLA antigens become the focus of a principally T-cell mediated autoimmune response. Auto-antibodies lead to chronic inflammatory changes of the liver, lymphoid infiltration of the portal tracts and hepatocyte necrosis, leading to cirrhosis.

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6
Q

What are the classifications of autoimmune hepatitis? (x2)

A
  • Classified according to the pattern of autoantibodies present
  • Type 1: ANA, anti-smooth muscle antibody (ASMA), perinuclear anti-neutrophil cytoplasmic autoantibody, anti-actin antibodies (AAA), and anti-soluble liver antigen (anti-SLA)
  • Type 2: anti-liver kidney microsomal-1 (anti-LKM) and anti-liver cytosol specific-positive (ALC-1)
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7
Q

What is the epidemiology of autoimmune hepatitis: Ethnicity? Prevalence? Age? (x2) Gender?

A

Highest prevalence in northern European ancestries. 16.9 per 100,000. Most commonly 10-30 y/o and 40-60 y/o for Type 1; 2-14 y/o for Type 2. Very high ratio are females.

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8
Q

What percentage of autoimmune hepatitis patients present acutely?

A

25% with acute hepatitis. Remaining are asymptomatic or have insidious onset and picked up on abnormal LFTs.

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9
Q

What are the symptoms of autoimmune hepatitis? (x4)

A
  • Remember, presentation is variable.
  • Insidious onset: malaise, anorexia, nausea, jaundice, amenorrhoea, epistaxis
  • Acute hepatitis: fever, anorexia, jaundice, nausea, diarrhoea, RUQ pain. Some may also present serum sickness e.g., arthralgia, polyarthritis, maculopapular rash.
  • May be associated with keratoconjunctivitis sicca.
  • Personal or family history of autoimmune disease such as T1DM.
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10
Q

What is keratoconjunctivitis sicca?

A

Dryness of conjunctiva and cornea.

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11
Q

What are the signs of autoimmune hepatitis?

A
  • Stigmata for chronic liver disease such as spider naevi
  • Ascites, oedema and encephalopathy are late features – all associated with portal hypertension
  • Cushingoid features e.g., rounded face, cutaneous striae, acne, hirsutism, may be present even before the administration of steroids
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12
Q

What are the blood investigations for autoimmune hepatitis? (x4)

A
  • LFT: in serious disease – very increased AST, ALT and GGT, high AlkPhos, high bilirubin, low albumin
  • Clotting: increased PT in severe disease
  • FBC: mild decreased Hb, low platelets, low WCC (latter two from hypersplenism if portal hypertension present).
  • Hypergammaglobulinemia is typical (polyclonal gammopathy) with the presence of ANA, ASMA (Type 1) or anti-LKM antibodies (Type 2).
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13
Q

What is hypergammaglobulinemia?

A

Increase in serum gamma globulins. Gamma globulins include immunoglobulins, though not all immunoglobulins are gamma globulins, and not all gamma globulins are immunoglobulins.

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14
Q

What is polyclonal gammopathy?

A

A gammopathy is an abnormal increase in the body’s ability to produce antibodies. A monoclonal gammopathy is an abnormal increase in the production of antibodies using the same type of cell. A polyclonal gammopathy is an abnormal increase in the production of antibodies using many different types of cells.

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15
Q

What are the other investigations for autoimmune hepatitis? Definitive diagnosis? (x2)

A
  • Liver biopsy: needed to establish the diagnosis. Shows interface hepatitis or cirrhosis
  • USS, CT or MRI of liver and abdomen: to visualise lesions
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16
Q

What are the investigations to rule out differentials in autoimmune hepatitis? (x6)

A
  • Viral serology: to rule out HepB and C.
  • Caeruloplasmin or urinary copper to rule out Wilson’s disease
  • Ferritin and transferrin saturation to rule out haemochromatosis
  • Alpha1-antitrypsin to rule out alpha1-antitrypsin deficiency
  • Antimitochondrial antibodies to rule out primary biliary cirrhosis
  • ERCP: to rule out primary sclerosing cholangitis
17
Q

What is primary biliary cirrhosis?

A

AKA PRIMARY BILIARY CHOLANGITIS. Chronic disease of the small intrahepatic bile ducts characterised by progressive bile duct damage occurring in the context of chronic portal tract inflammation.

18
Q

What is the aetiology of primary biliary cirrhosis? (x3)

A
  • Autoimmune disease – almost all patients have antimitochondrial antibodies directed predominantly against pyruvate dehydrogenase complex E2 subunit (PDC-E2).
  • There is also high personal and family incidence of other autoimmune processes such as Sjogren’s syndrome, arthritis, coeliac disease.
  • Onset is believed to occur from an environmental trigger such as infection, chemical or toxin.
19
Q

What is the pathophysiology of primary biliary cirrhosis?

A

Biliary epithelial cells lining the bile ducts become damaged from portal tract inflammation in a T-cell mediated autoimmune response. Fibrosis develops as a consequence of the direct bile duct damage and the secondary effects of cholestasis (toxic bile acids retained in the liver – reduced bile flow). Fibrosis over time leads to cirrhosis.

20
Q

What is the epidemiology of primary biliary cirrhosis: Prevalence? Gender? Age? Location?

A

35 in 100,000. 9:1, women:men. Peak age of diagnosis is 55-65 years though can present from 20s. Higher prevalence in Europe and US.

21
Q

What are the symptoms of primary biliary cirrhosis? (x6)

A
  • Insidious onset
  • Fatigue, weight loss and pruritus
  • Postural dizziness: from associated autonomic dysfunction. You may also see memory and concentration problems
  • Rarely, discomfort in RUQ
  • May present with complication of liver decompensation e.g., jaundice, ascites, variceal haemorrhage
  • Symptoms of associated conditions: Sjogren’s syndrome (dry eyes and mouth), arthritis, coeliac disease.
22
Q

What are the signs of primary biliary cirrhosis?

A
  • Early: may be no signs
  • Late: jaundice, skin pigmentation, scratch marks, xanthomas (secondary to hypercholesteremia), hepatomegaly, ascites, and other signs of liver disease
23
Q

What are the blood investigations for primary biliary cirrhosis? (x5)

A
  • LFTs: high Alk Phos, high GGT (both from cholestasis), bilirubin may be normal or high in later stages, hypoalbuminemia, transaminases initially normal but increase with development of cirrhosis (latter three associated with general decrease in liver function from cirrhosis – hence why they occur in later stages)
  • Clotting: high PT
  • Antimitochondrial antibodies (AMA), increased IgM, anti-smooth MUSCLE antibodies (all the ‘M’ antibodies).
  • High cholesterol
  • TFTs: PBC is associated with autoimmune thyroid disease
24
Q

What other investigations are there for primary biliary cirrhosis? (x2)

A
  • USS: to exclude extrahepatic biliary obstruction e.g., gallstones or strictures
  • Liver biopsy: chronic inflammatory cells and granulomas around the intrahepatic bile ducts, destruction of bile ducts, fibrosis, and regenerating nodules of hepatocytes.
25
Q

What is primary sclerosing cholangitis?

A

Chronic progressive cholestatic liver disease characterised by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts, resulting in diffuse, multi-focal stricture formation (areas of tight narrowing).

26
Q

What is the aetiology of primary sclerosing cholangitis? (x5)

A
  • Associated with serum autoantibodies
  • Associated with increased frequency of autoimmune diseases
  • Associated with IBD, particularly UC (present in 5% of UC patients), and Wilson’s disease.
  • Associated with over-representation of certain HLA haplotypes (unlike primary biliary cirrhosis)
  • Believed to be triggered by (1) translocation of lymphocytes activated in the colon of patients with colitis to the liver via the enterohepatic circulation, and (2) bacterial infection of the bile.
27
Q

What suggests primary sclerosing cholangitis may not be autoimmune? (x2)

A

Occurs in predominantly males and does not respond to immunosuppressive treatment.

28
Q

What is the pathophysiology of primary sclerosing cholangitis?

A

Characterised by inflammation of bile ducts leading to fibrosis, thickening of duct walls, and multi-focal stricturing of the ducts. There is periductal concentric fibrosis (‘onion skin’), portal oedema, bile duct proliferation and expansion of portal tracts, leading to progressive fibrosis and cholestasis. This ultimately results in development of biliary cirrhosis.

29
Q

What is the epidemiology of primary sclerosing cholangitis: Prevalence? Where? Gender? Age?

A

Rare: 6 in every 100,000 in the UK. More common in Northern Europe and US. More common in men with 2:1 ratio. Typically presents at 40 y/o.

30
Q

What are the symptoms of primary sclerosing cholangitis? (x5 points)

A
  • May be asymptomatic. Picked up because of abnormal LFTs.
  • Intermittent jaundice, pruritus, RUQ pain, weight loss and fatigue
  • Episodes of fever and rigors caused by acute cholangitis, though not that common as pathology is more chronic
  • Hx of UC
  • Symptoms of complications such as portal hypertension (encephalopathy, ascites, oedema, variceal bleeding)
31
Q

What are the signs of primary sclerosing cholangitis? (x5)

A
  • May have no signs
  • Jaundice
  • Hepatosplenomegaly
  • Spider naevi
  • Palmar erythema
  • Ascites
32
Q

What are the blood investigations for primary sclerosing cholangitis? (x5)

A
  • LFTs: high AlkPhos, high GGT, mildly increased transaminases (differential from primary biliary cirrhosis). In later stages, hypoalbuminemia and high bilirubin because of cirrhosis.
  • Serology: pANCA (antineutrophil cytoplasmic autoantibody) present, ASM and ANA present, AMA usually absent. IgM elevated, IgG normal or elevated.
  • FBC: thrombocytopenia and leukopenia as indicators of liver dysfunction or portal hypertension
  • Clotting: PT normal or prolonged from liver dysfunction
  • Copper: serum and urine copper high as disease has an associated with Wilson’s disease.
33
Q

What are the other investigations for primary sclerosing cholangitis? (x4)

A
  • ERCP: structuring and interspersed dilation (beading) of intrahepatic and extrahepatic bile ducts, small diverticula on the common bile duct
  • MRCP: study biliary tree
  • USS: study bile ducts and for cirrhotic liver
  • Liver biopsy: confirms diagnosis and allows staging of the disease

Year 3 Gastrointestinal (29 decks)

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