1. Cholestatic Liver Disease Primary Biliary Cirrhosis

2. 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

3. Medications Anabolic steroids Chlorpromazine Erythromycin Oral contraceptives

4. ALP of hepatic origin < 2 x Normal Repeat in 4 wks Normal ____ No action Unchanged ___ US__ dil ducts __ ERCP CT = mets__ FNA

5. 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 )

6. 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

7. PBC: Symptoms and Signs Fatigue70 % Pruritis55 Jaundice10 Hepatomegaly25 Splenomegall15 Xanthelasma10 None25

8. PBC: Associated Diseass Keartoconjuntivitis sicca75% Arthritis 4 – 40 Scleroderma 15 Thyroiditis 20 RTA 50 Gallstones 33

9. Diag: Liver Profile Alk phosphatase elevation AST / ALT less than 5 x N Increase in bilirubin, albumin and prothrombin time = poor prognosis

10. Diag: Serology Antimitochondrial antibodies 90-95% M2 antibody 98 % Rh factor 70 Anti smooth muscle66 Antithyroid 41 ANA 35

12. 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)

13. 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 %

14. Natural History: Symptomatic PBC Once symptoms develop, life expectancy falls sigficantly, with a median survival time of approximately 10 years.

15. Prediction of Survival Mayo 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

16. Medical Treatment Glucocorticoids Budeonide D-Penicillamine Colchicene no improvent in Azathioprine survival Cyclosporine Methotrexate

17. 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

18. 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 SteatorrheaLow fat diet, substitute MCT Hypercholestrolemia RX Urso PruritisCholystyramine, Rifampin, liver transplant.