Autoimmune liver diseases

Question 1

Autoimmune hepatitis (AIH) 1

Answer 1

• Chronic inflammatory disease due to immune (cytokine, T cell, and Ab) mediated destruction of hepatocytes
• Female heavily favored, often associated w/ other autoimmune d/os, diagnosed at all times of life
• Hepatocellular injury: R factor >5, AST/ALT >300
• R factor: (ALT/ALT ULN)/(AP/AP ULN), if >5 is hepatocellular, if <2 is cholestatic, if btwn 5 and 2 is mixed (drug-induced damage or overlap d/os)
• IgG and total globulin elevation

Question 2

Autoimmune hepatitis 2

Answer 2

• Clinical course: often ASx, common Sxs are fatigue, arthralgias, fluctuating jaundice
• May have Sx of extra hepatic disease: IDB, celiac disease, thyroid, hematologic (TPA, ITP, HA), DM, RA, synovitis
• Can progress to cirrhosis and HCC, acute or subacute liver failure
• Dx via clinical labs and positive anti-SmM Ab (Anti-SMA), ANA may be positive (but not specific)
• Should respond to Rx (immunosuppression) and should flair w/ Rx withdrawal

Question 3

Autoimmune hepatitis 3

Answer 3

• 2 types: type 1 is better (DR4), type 2 is more common in young females, worse prognosis (DR3)
• Histologically looks like viral hepatitis: piecemeal necrosis and periportal lymphocytic infiltration/fibrosis
• Rx is prednisone (to inhibit cytokine transcription), azathioprine (6MP; to inhibit cellular proliferation by impairing cell cycle)
• Failure to normalize aminotransferases indicates a poor outcome
• Relapsing occurs (AST/ALT >3x ULN), and surveillance for relapse should be life-long (most occur w/in 28 mo of Rx)
• Can also do liver Tx, recurrence occurs in 30% of cases

Question 4

Similarities and differences of autoimmune diseases of biliary tract (PSC vs PBC)

Answer 4

• Similarities: immune mediated injury of cholangiocytes w/ progressive bile duct injury and loss, both have severe pruritus
• Cholestatic picture w/ eventual hepatocyte damage, progressive fibrosis, portal HTN, CA, cirrhosis
• Differences: PBC occurs in females mostly, PSC occurs in males mostly
• PBC only adults, PSC both adults and children
• PBC affects small-medium bile ducts, PSC affects ducts of all size
• PBC associated w/ a range of other autoimmune d/os, PSC associated specifically w/ UC
• PBC has specific auto Ab (AMA), PSC has non-specific autoAb (p-ANCA)
• PBC complicated by HCC (cirrhosis->HCC), PSC complicated by CCA (don’t need cirrhosis before getting CCA)

Question 5

PSC 1

Answer 5

• Diffuse inflammation, obstruction and fibrosis of intra and extra hepatic bile ducts
• Male predominant, >70% associated w/ UC, usually presents in 4-5th decade, usually caucasian
• 50% are ASx at time of Dx, 10-15% progress to CCA
• Sxs: fatigue, pruritus (severe in both PSC and PBC), pain, fever
• Dx by labs, clinical and imaging biliary tree (MRCP)
• Labs: high AP, AST/ALT modestly elevated or nl, R factor <2, may be p-ANCA+, may have elevated bili if advanced
• GGT positive indicating high AP is from liver not bone
• MCRP will show multiple strictures and ballooning of IH and EH biliary tree
• Micro shows chronic inflammation, fibrosis and obliteration of large and small bile ducts

Question 6

PSC 2

Answer 6

• Complications: bacterial cholangitis, progression to cirrhosis, CCA
• Rx: no Rx prolongs survival except liver Tx, Rx is directed at Sxs and complications (no use for immunosuppression)
• UDCA improves liver tests and is used to increase bile flow/reduce stone formation
• Rx pruritus w/ cholestyriamine
• Must consider fat/ADEK malabsorption and replace vitamins
• ADEK def: osteopenia/osteomalacia, night blindness, coagulopathy
• GCCs only used when there is PSC/AIH overlap
• ERCP to place stents to relieve strictures

Question 7

PBC 1

Answer 7

• Heavily predominant in women (10x), usually in middle age, common to caucasians
• There is immune mediated intrahepatic (small) bile duct injury, portal inflammation, progressive destruction w/ bile duct loss, fibrosis and cirrhosis
• Characteristic autoAb is anti-mito Ab (AMA), which targets the PDH complex
• Sxs include pruritus, fatigue, fractures, Sxs of liver failure/portal HTN
• Only get high bili/jaundice in advanced disease
• Associated w/ many autoimmune diseases (sjogren’s, RA, thyroiditis)
• Dx via cholestatic picture, AMA+, compatible histology, absence of bile duct obstruction on MRCP
• There will be elevated IgM and total globulin

Question 8

PBC 2

Answer 8

• Natural Hx: preclinical but AMA+ can last for decades, ASx phase w/ gradual elevation in AP (most become Sx w/in 5 yrs), Sx phase and median survival is 6-10 yrs, advanced disease w/ progressive jaundice/rise in bili (lasts up to 2 yrs)
• Rx of PBC: immunosuppression (GCCs, 6MP), UDCA to increase bile flow/prevent stones, only cure is liver Tx
• Rx Sxs: cholestyramine to decrease pruritus
• Must consider fat/ADEK malabsorption and replace vitamins
• Complications: liver failure, cirrhosis, HCC, bone loss (vit D def)