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 &

survival.

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

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 • Bile duct surgical injury.• Infectious cholangitis (including AIDS cholangiopathy) • Malignancy.

PSC: Complications • Cholangiocarcinoma CC ( 10-30%). • Detecting CC at an early stage is difficult.• Tumor markers CA 19-9+/- CEA• Cytologic sampling • Advanced imagings with cholangioscopic biopsy. • Patients with advanced disease& cirrhosis are at risk for HCC.• Patients with both PSC& UC have an increased risk of CRC&

aggressive surveillance needed.

PSC: Management • Includes assessment & management of dominant strictures• Treatment of superimposed bacterial cholangitis• Symptomatic therapy. • Only liver transplantation appimprove overall survival & quality

of life. • Up to date no TRT has provided the long-term benefits of

transplantation. • Median survival from the time of diagnosis is 12 years.