Term
| What are the 3 major autoimmune etiologies of liver disease and what autoantibodies are associated with each? |
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Definition
1) Autoimmune hepatitis (AIH)
- Females in adolescence or 35-40 Interface Hepatitis
- ANA, SMA (Type 1) and/or anti-liver/kidney microsomes (anti-LKM1) antibodies (Type 2)
- Negative AMA or M2G ELISA
2) Primary biliary cholangitis (PBC)
- Chronic inflammatory destruction of interlobular and septal bile ducts in middle-aged women leading to cholestasis
- AMA antibodies
3) Primary sclerosis cholangitis (PSC)
- Progressive, fibrosclerotic disease of bile ducts, with structuring of intra-hepatic and extra-hepatic ducts in young men with IBD.
- pANCA association |
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Term
38 year old female presents with Jaundice and a h/x of fatigue, nausea and joint pain.
What serological markers should you order and what do you expect to see? What about LFTs? |
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Definition
Age, jaundice and h/x of symptoms fits AIH (associated with autoimmune thyroiditis, IBD and RA)
**25% may be asymptomatic**
1) Order viral, IgG, y-globulin, ANA, SMA, anti-LKM1, and AMA/M2G tests
- AIH has negative viral (liver histology is like chronic viral hepatitis) and AMA/M2G
- Elevated IgG, y-globulin, ANA, SMA and/or AMA/M2G suggests AIH.
2)
- AIH has "hepatocellular" LFT pattern with elevated ALT/AST and only moderate increases in ALP and GGT
- Elevated direct bilirubin
- may also see coagulopathy and/or hypoalbuminemia |
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Term
| How can AST/ALT ratio be helpful in making a liver disease diagnosis? |
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Definition
1) Elevated
- Alcohol or drug
- Cirrhosis
- HCC
- Chronic hepatitis
2) Decreased
- Acute hepatitis
- Extrahepatic cholestasis |
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Term
| Provide examples of pre-hepatic, hepatic and post-hepatic causes of increased total bilirubin (TBIL) |
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Definition
Bilirubin is breakdown product of heme that is taken up by hepatocytes, conjugated/solubilized, secreted in bile and excreted in the intestine.
1) Pre-hepatic
- Increased production in hemolytic anemia and internal hemorrhage.
2) Hepatic
- Deficiencies in bilirubin metabolism in cirrhosis and viral hepatitis
3) Post-hepatic
- Obstruction of bile ducts reflected as deficiencies in excretion (intra-hepatic or extra-hepatic obstruction). |
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Term
| How can measuring direct bilirubin (DBIL) help to localize the cause of increased TBIL? |
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Definition
1) If DBIL is normal, then problem must be upstream of bilirubin excretion, indicating Hemolysis (pre-hepatic), viral hepatitis or cirrhosis (both hepatic).
2) If DBIL is elevated, then liver is conjugating bilirubin normally, but cannot excrete it. Bile duct obstruction by gallstones or cancer should be expected! |
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Term
| Why might you see elevated ALP levels? |
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Definition
ALP is enzyme in cells lining biliary ducts of liver.
1) ALP levels in plasma rise with large bile duct obstructions, intra-hepatic cholestasis or infiltrative disease of liver.
2) Normally increase in growing children (bone tissue remodeling). |
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Term
| How can GGT be useful clinically? |
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Definition
Most sensitive marker of alcoholism
If ALP is elevated, but GGT is normal, you know the issue is not in the liver. |
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Term
| What are the most sensitive markers of liver synthetic functioning? |
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Definition
Coagulation factors as measured by PT/INR (Albumin half-life is too long)
1) High PT
- anti-coagulants, antibiotics, inherited bleeding disorder, DIC or vitamin K deficiency
2) Low PT
- cancer, blood clots, birth control bills |
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Term
| What happens to total cholesterol and total protein in liver disease? What about LDH? |
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Definition
| Both are decreased. LDH is non-specific, but is elevated in liver disease. |
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Term
How can serum protein electrophoresis help to narrow down a differential in the case of abnormal LFTs? What do each of the following indicate?
1) Decreased total protein
2) Increased alpha-1 globulin
3) Decreased alpha-1 globulin
4) Increased alpha-2 globulin
5) Decreased alpha-2 globulin
6) Increased beta-globulin
7) Decreased beta-globulin
8) Increased y-globulin |
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Definition
Direct quantification of multiple different serum proteins.
1) Malnutrition, GI protein loss, nephrotic syndrome
2) Acute, chronic inflammatory disease or cancer
3) Alpha-1-anti-trypsin
4) Acute, chronic inflammation
5) Hemolysis
6) Hyper-lipotroteinemia or estrogen therapy.
7) DIC, congenital coagulation disorder
8) Multiple myeloma, chronic inflammatory disease, chronic liver disease (AIH) |
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Term
| What are the key characteristics of the 3 subtypes of autoimmune hepatitis (AIH)? |
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Definition
1) Type 1 (most common)
- SMA and/or ANA
- 70% women
- 34% have concurrent immune disease (Thryoiditis, Graves, UC)
2) Type 2
- anti-LKM1 (liver/kidney)
- Younger children in france and germany
- Concurrent immune diseases (Vitilgo, insulin-dependent diabetes, thyroiditis)
3) Type 3
- anti-SLA/LP
- young women with anti-LKM1, often with SMA or AMA as well.
- Extra-hepatic symptoms are similar to type 1 |
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Term
What autoimmune liver disease is associated with each of the following histological characteristics?
1) Interface hepatitis with "piecemeal necrosis", and plasma cell infiltration of the portal tracts without lymphoid aggregates, steatosis or bile duct injury
2) Destructive cholangitis ("florid duct lesion") that affects interlobular and septal bile ducts leading to biliary cirrhosis
3) Inflammation, destruction and fibrosis of intra-hepatic and extra-hepatic bile ducts |
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Definition
1) AIH- anti SMA/ANA (type 1) and/or anti-LKM1 (type 2) with increased y-globulin fraction
2) PBC- anti-AMA in middle-aged women
3) PSC- pANCA in young men with IBD |
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Term
| What are the indications/therapeutic options for treatment of the autoimmune liver disease that appears histologically as Interface hepatitis with "piecemeal necrosis", and plasma cell infiltration of the portal tracts without lymphoid aggregates, steatosis or bile duct injury |
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Definition
1) Treat if (Absolute and relative)
- AST >10X normal (symptomatic)
- >5X normal with >2x y-globulin (both elevated)
- bridging necrosis (interface hepatitis on biopsy)
**treatment is effective with or w/o cirrhosis and even for ESLD and HCC, but with chance of remission**
2) Anti-inflammatory/immunosuppression
- Prednisone, Azathioprine, UDCA
- also treat cirrhosis-related complications (PHTN, HCC, liver failure) and steroid side effects
**stop treatment if ALT < 1.5 upper limits of normal for 1-2 years |
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Term
What is the pathogenesis of the autoimmune liver disease that affects middle aged women and is associated with AMA antibodies?
How do patients typically present? |
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Definition
PBC is VERY RARE, mostly seen in england and sweden, but rising in US
1) Interlobular and septal bile duct destruction occurs through T-cell-mediated mechanisms, perhaps induced by anti-mitochondrial-antibodies.
2) Patients tend to be fatigued (60-70%), with pruritis (50%), but can also be asymptomatic (30%). |
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Term
What is the most common co-morbid autoimmune condition found with the autoimmune liver disease that is associated with florid duct lesions in middle-aged women?
2) How do you diagnose/treat this condition? |
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Definition
1) Sjogren's syndrome manifesting with Xerostomia (dry mouth) and xerophthalmia (dry eyes) of sicca syndrome
2) Cholestatic and immunologic diagnosis
- Elevated ALP and GGT with hyperbilirubinemia in later stages and + anti-AMA antibodies.
**AMA-M2 antigen is used as diagnostic test (ELISA)**
- Patients who also have CREST may have anti-ANA antibodies as well.
3) Treat (anyone with abnormal liver biochemistry)
- Ursodeoxycholic acid (UDCA) reduces intracellular hydrophobic BA levels and protects membranes as immuno-modulator
- No immunosuppression. |
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Term
| How is PBC staged clinically? |
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Definition
1) Florid duct lesion/intra-hepatic bile duct damage
2) Ductural proliferation
3) Ductural proliferation and scarring
4) Cirrhosis |
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Term
Patient presents with chronic cholestatic LFTs (ALP and GGT elevation with hyperbilirubinemia).
What is your next step in workup of the patient? |
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Definition
Could be extra-hepatic obstruction, intra-hepatic cholestatic liver disease or PBC.
1) Order sonogram or cholangiography to rule out extrahepatic obstruction
2) Order serum anti-AMA to rule out intra-hepatic cause other than PBC.
- If AMA negative, probably need cholangiography |
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Term
| What are the common complications and outcomes of patients with PBC? |
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Definition
1) Pruritis fluctuates, Osteorosis and ADEK deficiency (poor bile salt excretion).
2) Most eventually progress to cirrhosis and many die soon thereafter (2 years for bilirubin > 6) |
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Term
35 year old male presents with mild fatigue and pruritis.
You order LFTs and find elevated ALP (400), AST (90) and ALT (94), but normal serum bilirubin.
What serological tests should you run and what will you most likely find? |
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Definition
Elevated ALP >3x with AST/ALT elevation and normal bilirubin suggests PSC (as well as gender and age).
Serology should show elevated IgG and IgM (40-60% of time) and pANCA is generally found. |
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Term
What are the classic histological features of the autoimmune liver disease associated with elevated ALP, AST and ALT, but normal bilirubin?
What about radiology? |
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Definition
PSC- Diagnosis is based on Cholangiography!
1) Inflammation, destruction and fibrosis of intra-hepatic and extra-hepatic bile ducts
2) Biopsy
- Peri-ductal fibrosis with inflammation and bile duct proliferation alternating with ductopenia
- This fibroobliterative cholangiopathy is most diagnostic, but only found in 10% of cases!
3) Cholangiography (MRCP may be safer than ERCP, but may need to be followed by ERCP)
- "Beads on a string" appearance. |
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Term
What are the most common extrahepatic manifestations of each of the following?
1) AIH
2) PBC
3) PSC |
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Definition
1) Type 1 with ANA/SMA (thyroid, graves, UC)
Type 2 with LMK1 (vitiligo, insulin-dependent DM, thyroid)
2) Sjogrens with xerostoma and xeropthalmia
3) UC most common
- also CD, pancreatitis, DM, thyroid |
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Term
| Describe a basic diagnostic workup for PSC. |
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Definition
1) Cholestatic biochemistry leads to selection MRCP
2) If non-diagnostic, order ERCP
3) If ERCP is normal, get a liver biopsy for small duct PSC |
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Term
| What might indicate to you that an autoimmune liver condition is more likely AIH than PSC? |
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Definition
1) Predominant ALT/AST elevations compared to ALP/bilirubin
2) Elevated ANA/SMA
3) EInterface or lobular lymphoplasmacytic inflammation
4) Normal cholangioraphy. |
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Term
| How can you treat the autoimmune liver disease that affects 40 year old men with IBD? |
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Definition
Remember, even asymptomatic patients have median survival of only 75% at 7 years!
1) Liver t/x is only effect treatment for ESHD
2) Endoscopy may relieve cholestasis from mechanical biliary obstruction
3) Biliary reconstructive surgery can work in pre-cirrhotic patients with extra-hepatic biliary strictures refractory to endoscopy and PCI |
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Term
| What factors can best distinguish PSC from PBC? |
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Definition
1) Age (PBC 53, PSC 41)
2) gender (PBC F, PSC M
3) IBD (PSC)
4) Sicca (PBC)
5) AMA (PBC)
6) Cholangiography (PSC- multifocal strictures)
7) Histology (PBC is granulomatous, PSC is Fibrous) |
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