Cholestatic Liver Disease

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Cholestatic Liver Disease

• Primary Biliary Cirrhosis

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Causes of Alk Phosphatase Elevation

• Hepatic cirrhosis,tumors,Steatosis,PBC,
• PSC, drugs, TPN
• Biliary Cholangitis, Obstruction
• Bone Pagets,Hyperparathyroid, Mets
• Septicemia cholestasis of sepsis
• Physiologic puberty, pregnancy

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Medications

• Anabolic steroids
• Chlorpromazine
• Erythromycin
• Oral contraceptives

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ALP of hepatic origin

• lt 2 x Normal
• Repeat in 4 wks
• Normal ____ No action
• Unchanged ___ US__ dil ducts __ ERCP
• CT mets__ FNA

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ALP gt 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 )

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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

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PBC Symptoms and Signs

• Fatigue 70
• Pruritis 55
• Jaundice 10
• Hepatomegaly 25
• Splenomegall 15
• Xanthelasma 10
• None 25

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PBC Associated Diseass

• Keartoconjuntivitis sicca 75
• Arthritis 4 40
• Scleroderma 15
• Thyroiditis 20
• RTA 50
• Gallstones 33

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Diag Liver Profile

• Alk phosphatase elevation
• AST / ALT less than 5 x N
• Increase in bilirubin, albumin and prothrombin
  time poor prognosis

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Diag Serology

• Antimitochondrial antibodies 90-95
• M2 antibody 98
• Rh factor 70
• Anti smooth muscle 66
• Antithyroid 41
• ANA 35

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Liver Histology

• Ludwigs 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)

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Natural History Asymptomatic PBC

• Mitchison et al 1986
• 29 patients with normal LFTs
• Followed for 17.8 years (11 24 yrs)
• Abnormal LFTs in 5.6 yrs
• Symptoms developed in 76

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Natural History Symptomatic PBC

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

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Prediction of SurvivalMayo Risk Score

• Advanced age
• Serum bilirubin
• Serum albumin
• Fluid retention ( ascites and edema)
• Variceal bleeding
• Advanced histologic stage
• Bilirubin gt 10 mg Life expectancy lt 2 yrs

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Medical Treatment

• Glucocorticoids
• Budeonide
• D-Penicillamine
• Colchicene no improvent in
  Azathioprine survival
• Cyclosporine
• Methotrexate

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treatment

• Ursodeoxycholic acid
• Small quantities in bile --- lt 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

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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.