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 Physiologic puberty, pregnancy

Medications Anabolic steroids Chlorpromazine Erythromycin Oral contraceptives

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 CT …. Normal – hepatitis(immune,

viral disease)… Liver biopsy

CT ….. Dilated ducts, stone or massProceed with ERCP/ CT Bx or Surg

( Bile duct obstruction, PSC, PBC )

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

PBC: Associated Diseass Keartoconjuntivitis sicca 75% Arthritis 4 – 40 Scleroderma 15 Thyroiditis 20 RTA 50 Gallstones 33

Diag: Liver Profile Alk phosphatase elevation AST / ALT less than 5 x N

Increase in bilirubin, albumin and prothrombin time = poor prognosis

Diag: Serology Antimitochondrial antibodies

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

Liver Histology Ludwig’s Classification

Stage I. Inflammation within portal space Focussed on bile ductsStage II.Inflam extending into hepatic

parenchymaStage III. FibrosisStage IV. Regenerative nodules ( cirrhosis)

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

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

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 Glucocorticoids Budeonide D-Penicillamine Colchicene no improvent in

Azathioprine survival

Cyclosporine Methotrexate

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 Bone Disease: osteoporosis and fractures

vitamin D 25,000 to 50,000 iu / week Fat-Soluble Vit Deficiency

vit A 25,000 IU 3/WKvit K 5 mg/dvit E 50 – 200 u / d

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

transplant.