Transcript Cholestatic liver diseases:

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
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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.