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 &
survival.

4. 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.

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

14. 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.

15. 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.