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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.