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Cholestatic Liver Disease. Primary Biliary Cirrhosis. Causes of Alk Phosphatase Elevation. Hepatic: cirrhosis,tumors,Steatosis,PBC, PSC, drugs, TPN Biliary: Cholangitis, Obstruction Bone: Paget’s,Hyperparathyroid, Mets Septicemia cholestasis of sepsis

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cholestatic liver disease

Cholestatic Liver Disease

Primary Biliary Cirrhosis

causes of alk phosphatase elevation
Causes of Alk Phosphatase Elevation
  • Hepatic: cirrhosis,tumors,Steatosis,PBC,

PSC, drugs, TPN

  • Biliary: Cholangitis, Obstruction
  • Bone: Paget’s,Hyperparathyroid, Mets
  • Septicemia cholestasis of sepsis
  • Physiologic puberty, pregnancy
medications
Medications
  • Anabolic steroids
  • Chlorpromazine
  • Erythromycin
  • Oral contraceptives
alp of hepatic origin
ALP of hepatic origin
  • < 2 x Normal
  • Repeat in 4 wks
  • Normal ____ No action
  • Unchanged ___ US__ dil ducts __ ERCP

CT = mets__ FNA

alp 2 x normal
ALP > 2 x Normal
  • CT …. Normal – hepatitis(immune,

viral disease)… Liver biopsy

CT ….. Dilated ducts, stone or mass

Proceed with ERCP/ CT Bx

or Surg

( Bile duct obstruction, PSC, PBC )

primary biliary cirrhosis
Primary Biliary Cirrhosis
  • Autoimmune cholestatic disorder
  • Female to male ratio of 9 : 1
  • Inflammatory destruction of bile ducts, leads to cholestasis and cirrhosis
  • Autoantibodies reactive with antigens on the surface of biliary epithelium
  • Antimitochondrial antibodies
pbc symptoms and signs
PBC: Symptoms and Signs
  • Fatigue 70 %
  • Pruritis 55
  • Jaundice 10
  • Hepatomegaly 25
  • Splenomegall 15
  • Xanthelasma 10
  • None 25
pbc associated diseass
PBC: Associated Diseass
  • Keartoconjuntivitis sicca 75%
  • Arthritis 4 – 40
  • Scleroderma 15
  • Thyroiditis 20
  • RTA 50
  • Gallstones 33
diag liver profile
Diag: Liver Profile
  • Alk phosphatase elevation
  • AST / ALT less than 5 x N
  • Increase in bilirubin, albumin and prothrombin time = poor prognosis
diag serology
Diag: Serology
  • Antimitochondrial antibodies 90-95%
  • M2 antibody 98 %
  • Rh factor 70
  • Anti smooth muscle 66
  • Antithyroid 41
  • ANA 35
liver histology
Liver Histology
  • Ludwig’s Classification

Stage I. Inflammation within portal space

Focussed on bile ducts

Stage II. Inflam extending into hepatic parenchyma

Stage III. Fibrosis

Stage IV. Regenerative nodules ( cirrhosis)

natural history asymptomatic pbc
Natural History: Asymptomatic PBC
  • Mitchison et al 1986
  • 29 patients with normal LFT’s
  • Followed for 17.8 years (11 – 24 yrs)
  • Abnormal LFT’s in 5.6 yrs
  • Symptoms developed in 76 %
natural history symptomatic pbc
Natural History: Symptomatic PBC

Once symptoms develop, life expectancy falls sigficantly, with a median survival time of approximately 10 years.

prediction of survival mayo risk score
Prediction of SurvivalMayo Risk Score
  • Advanced age
  • Serum bilirubin
  • Serum albumin
  • Fluid retention ( ascites and edema)
  • Variceal bleeding
  • Advanced histologic stage
  • Bilirubin > 10 mg = Life expectancy < 2 yrs
medical treatment
Medical Treatment
  • Glucocorticoids
  • Budeonide
  • D-Penicillamine
  • Colchicene no improvent in Azathioprine survival
  • Cyclosporine
  • Methotrexate
treatment
treatment
  • Ursodeoxycholic acid
  • Small quantities in bile --- < 4 %
  • Endogenous Bile acids ( cholic, cheno, litho) hepatoxic
  • Treatment increases Urso content to 30-60%
  • Level of Urso parallels improvement in liver profile and Mayo Risk Score
  • Dose : 13 – 15 mg/kg/day
  • If pt on Cholestyramine, Urso to be taken 2 hrs before or after cholestyramine administration
pbc complications
PBC: Complications
  • Bone Disease: osteoporosis and fractures

vitamin D 25,000 to 50,000 iu / week

  • Fat-Soluble Vit Deficiency

vit A 25,000 IU 3/WK

vit K 5 mg/d

vit E 50 – 200 u / d

  • Steatorrhea Low fat diet, substitute MCT
  • Hypercholestrolemia RX Urso
  • Pruritis Cholystyramine, Rifampin, liver transplant.