Cholestatic liver diseases:

1. Cholestatic liver diseases: Dr. Mohammad Shaikhani. MBChB- CABM- FRCP.

2. Primary Biliary Cirrhosis : • PBC occurs primarily in women between 40- 60 years. • The most common symptom is persistent fatigue. • An antimitochondrial antibody titer of ≥1:40 is the serologic hallmark for the diagnosis

3. Primary sclerosing Cholangitis: • PSC occurs most often in men between 20 - 30 • Up to 80% also have an IBD. • The most common symptoms are pruritus, jaundice, abdominal pain, fatigue. • The diagnosis is confirmed by imaging studies showing a “string of beads” pattern of the intra- & extrahepatic bile ducts. • Patients are at increased risk for developing cholangiocarcinoma , HCC& CRC if with IBD. • Liver transplantation is associated with improved quality of life and survival.

4. Cholestatic liver disease: DD • Other causes of cholestasis as: • Cholestatic phase of viral hepatitis. • Drug-induced or herbals-induced cholestasis. • Intrahepatic cholestsis of pregnancy. • Alcoholic hepatitis. • Intrahepatic or extrahepatic biliary obstruction.

5. Primary Biliary Cirrhosis: EPIDEMIOLOGY • A chronic progressive cholestatic liver disease of unknown cause. • It is an autoimmune disorder occurs predominantly in women (80- 90%) between 40- 60 years. • The prevalence has been increasing, most likely because of earlier diagnosis & increased survival.

6. Primary Biliary Cirrhosis: Features • The most common symptom is persistent fatigue, occurs in 80%. • Either localized or general pruritus frequently develops. • The pruritus often begins in the perineal area or on the palmar / plantar surfaces typically worse at night or in a warm environment. • Jaundice / abdominal pain may also develop. • Many patients may be asymptomatic at presentation.

7. Primary Biliary Cirrhosis:Physical exam • Include skin thickening, hyperpigmentation from repeated excoriations, xanthomas, xanthelasma,hepatomegaly. • Patients with advanced disease may have clinical manifestations of portal hypertension. • Other autoimmune diseases are frequently present. • Metabolic bone disease, hypercholesterolemia, fat-soluble vitamin deficiencies are common.

8. Primary Biliary Cirrhosis: Diagnosis • The diagnostic triad includes cholestatic liver profile, positive antimitochondrial antibody titers&compatible histologic findings on liver biopsy. • SAP & γ-GT are usually elevated *10 or more above normal. • TSB increases as the disease progresses & a helpful prognostic marker. • An antimitochondrial antibody titer of ≥1:40 is the serologic hallmark occurs in 90-95% . • The titer does not appear to correlate with the severity or progression of the clinical disease. • The diagnosis is confirmed by liver biopsy, characteristically shows nonsuppurative cholangitis plus findings ranging from bile duct lesions to cirrhosis.

9. Primary Biliary Cirrhosis: Treatment • Treatment with ursodeoxycholic acid improves the biochemical profile, reduces pruritus, decreases progression to cirrhosis, and delays the need for liver transplantation. • Therapy is usually continued indefinitely. • Liver transplantation is considered for patients with intractable pruritus or complications from cirrhosis. • Long-term outcomes tend be better than outcomes achieved for other indications for transplantation.

10. PSC: Epidemiology • A chronic cholestatic liver disease of unknown cause characterized by progressive bile duct destruction& may lead to secondary biliary cirrhosis. • The disease develops more often in men than in women (3:1), generally occurs in patients 20-30 years. • Up to 80% have an IBD (most often ulcerative colitis), but < 5% with UC develop PSC.

11. PSC: Features • The most common presenting symptoms are pruritus, jaundice, abdominal pain, fatigue, although almost 50% of patients are asymptomatic at initial diagnosis. • Patients with more advanced disease may present with cirrhosis & related complications. • Other associated disorders include bacterial cholangitis, pigmented bile stones, steatorrhea, malabsorption, metabolic bone disease.

12. PSC: Diagnosis • Lab findings include a cholestatic liver profile, with SAP *3-5> normal& mild hyperbilirubinemia. • The diagnosis is confirmed by ERCP or MRCP that shows findings of multifocal strictures / dilatation of the intra& extrahepatic bile ducts, resembling beads on a string. • Liver biopsy is usually done for staging rather than for diagnosis may show histologic findings ranging from portal hepatitis to biliary cirrhosis. • The classic histologic lesion, termed periductal (“onionskin”) fibrosis, is seen in only 10% of biopsy specimens.

13. Primary Sclerosing Cholangitis: DD • Include bile duct surgical injury, infectious cholangitis (including AIDS cholangiopathy) &malignancy.

14. PSC: Complications • Patients are at risk for developing cholangiocarcinoma (lifetime prevalence of 10-30%). • Detecting this malignancy at an early stage is difficult despite the availability of studies for the tumor markers CA 19-9/ CEA ( alone or in combination), cytologic sampling&advanced imagings. • Patients with advanced disease& cirrhosis are also at risk for developing HCC& patients with both PSC& UC have an increased risk of developing CRC. • An aggressive surveillance program for neoplasia should begin immediately in patients diagnosed with both diseases.

15. PSC: Management • Includes assessment of dominant strictures • treatment of superimposed bacterial cholangitis • symptomatic therapy. • Only liver transplantation appears to improve overall survival & quality of life. • Although multiple medical therapies have been studied, to date none has provided the long-term benefits of transplantation. • Median survival from the time of diagnosis is 12 years.