The ABCs of PSC Jacqueline O’Leary, MD MPH Medical Director of Research, Baylor Simmons Transplant...
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Transcript of The ABCs of PSC Jacqueline O’Leary, MD MPH Medical Director of Research, Baylor Simmons Transplant...
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The ABCs of PSCThe ABCs of PSC
Jacqueline OJacqueline O’’Leary, MD MPHLeary, MD MPHMedical Director of Research, Baylor Simmons Transplant Medical Director of Research, Baylor Simmons Transplant
InstituteInstitute
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BiasBias
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Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis
• Primary = no known cause
• Sclerosing = Fibrosis and narrowing• Affects the large bile ducts of the liver = plumbing
• Cholangitis = infection that occurs in the bile ducts.
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisAffects Biliary SystemAffects Biliary System
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Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis
• What is the biliary system?
• Bile is made by the liver cells• Allows you to absorb your food
• Bile is toxic to the liver
• Bile is made – it is secreted into the plumbing of the liver (biliary system):• Stored in the gallbladder• Exits into the small intestine to help absorb food
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisAffects Biliary SystemAffects Biliary System
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Secondary Sclerosing CholangitisSecondary Sclerosing Cholangitis
• Secondary = known cause
• Some of the causes include:• Blockage of the bile ducts:
• Tumor – cancer or non-cancerous• Stones / Sludge• Abnormal anatomy• Parasites
• Inherited Disorder
• Toxin
• Lack of blood flow to bile ducts (ischemia)
• AIDS
• Surgery gone wrong
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisDiagnosisDiagnosis
• Abnormal Liver Tests:• Cholestatic profile (alk phos)
• 60% Men • Mean age 30 - 40 years
• Diagnosis is made by cholangiography• Operative Cholangiography• ERCP (Endoscopic Retrograde CholangioPancreatography)
• Scope
• Magnetic Resonance CholangioPancreatography• MRI
• Diagnosis is not made on liver biopsy
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Cholangiography in Normal and PSCCholangiography in Normal and PSC
Normal PSC
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PSCPSC
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Cholangiography in PSCCholangiography in PSC
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Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis
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Liver Biopsy in PSCLiver Biopsy in PSC
• Liver biopsy is used in PSC• 1) Cholangiogram is normal
• Small Duct PSC
• 2) Staging• 3) Rule out “over-lap” syndrome
• PSC with autoimmune hepatitis
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Liver Biopsy in PSCLiver Biopsy in PSC
Early Classic “onion skinning”
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisStages
• Fibrosis or scar is the final common pathway of all liver disease
• Stage of fibrosis is how much scar or permanent damage has been done.
• Several scoring systems• METAVIR 0-4• Ishak 0-6
• Higher score = more scar
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Stages of FibrosisStages of Fibrosis
Stage 1 Stage 2
Stage 3 Stage 4
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Regenerating nodules = CirrhosisRegenerating nodules = Cirrhosis
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisMeasure Fibrosis
• Gold standard is liver biopsy• Paired liver biopsy studies:
• 1/3 are different by 1 stage (scale of 0-4)• 2.4% are different by 2 stages
• Variability is more in diseases like PSC• Risks are: bleeding, bile leak, and pain
• Non – invasive measures have increased:• Fibrotest – blood test, in general inaccurate
• Not validated in PSC
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisMeasure Fibrosis
• Elastography:• Ultrasound
• No radiation• Reimbursed• Measures a small area of the liver but much bigger than a biopsy• Generally a good test when good images can be obtained.
• Magnetic resonance:• No radiation• Not reimbursed• Picture of the entire liver• Best of diseases (like PSC) with more variability
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisMeasure Fibrosis
• Standard imaging studies do not evaluate fibrosis:• Ultrasound• CT scan• MRI
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PSCPSC
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisAfter CirrhosisAfter Cirrhosis
• After cirrhosis is diagnosed we no longer discuss stage:
• Symptoms:• Fluid in abdomen = ascites
• Fluid in legs = edema
• Mental confusion caused by liver disease = encephalopathy
• Internal Bleeding from big veins
• Skin manifestations:• Spider angioma
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisAfter CirrhosisAfter Cirrhosis
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisAfter CirrhosisAfter Cirrhosis
• Liver sickness score = MELD • Model for End-Stage Liver Disease• 3 lab tests:
• Bilirubin
• INR (clotting test)
• Creatinine (kidney function test)
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisIBDIBD
• Inflammatory Bowel Disease (IBD) – 75%• Autoimmune condition of the intestines
• Ulcerative Colitis (75%):• Colon
• Crohn’s Disease (25%):• Any part of the gastrointestinal track
• All patients with PSC need to have a colonoscopy:• At diagnosis
• If there are significant changes in bowel habits
• Progression of PSC is not related to symptoms of/problems with IBD
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisIBDIBD
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisEtiologyEtiology
• Unknown
• Associated with other autoimmune conditions
• Genetic predisposition• Permeability of the bowel
The Lancet, Volume 382, Issue 9904, 2013, 1587 - 1599
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisEtiologyEtiology
• Unknown• Alterations in the way immune
cells arrive at their destination:• Adhesion molecules
increases
The Lancet, Volume 382, Issue 9904, 2013, 1587 - 1599
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisEtiologyEtiology
• Unknown• Intestinal Bacteria
The Lancet, Volume 382, Issue 9904, 2013, 1587 - 1599
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisCourse of Disease
• Slowly Progressive• There is no currently approved therapy.• Infection in Bile ducts - Cholangitis
• Routine ERCP does not decrease this risk
• Bile Duct Cancer - Cholangiocarcinoma• 1% risk per year
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Primary Sclerosing CholangitisPrimary Sclerosing CholangitisTherapy
• No FDA approved therapy• Ursodiol is sometimes used:
• Low dose ursodiol (13-15 mg/kg divided 2x/day) improve the liver tests.
– Not been shown to improve survival• High dose ursodiol (>20 mg/kg divided 2x/day) is not
recommended.
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Pruritis (Itching)Pruritis (Itching)
• Common• Cause is unknown• Better in the summer—UV light• Treatment
• Cholestyramine 4 g po qd - qid• Take 1 hour before or 2 hours after other medications
• Ursodiol• Rifampin
• Liver injury 10%
• Antihistamines—only benefit is sedation
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Sertraline (Zoloft) for PruritisSertraline (Zoloft) for Pruritis
• Randomized placebo controlled trial with wash out and cross over.
• Highly effective• Takes 6 weeks to work• Higher dose works better
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Bone DiseaseBone Disease• Osteoporosis (thining of the bones) is common
• Vit D deficiency• Postmenopausal status
• Treatment • Ca• Vit D• Weight bearing exercise• Prescription medications
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Fat Soluble VitaminsFat Soluble Vitamins• Vitamin D—check 25OH
• Most common• Bone problems
• Vitamin A• Vision problems• Replete—carefully
• Vitamin K deficiency• Easy Bruising
• Vitamin E deficiency• Dementia
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Overlap Syndromes
• Autoimmune liver disease can be diagnosed alone or in combination:• Primary Sclerosing Cholangitis (PSC)• Autoimmune Hepatitis (AIH)• Primary Biliary Cirrhosis (PBC)
• When more than one is present it is called an “overlap syndrome”.• Both diseases require therapy
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Autoimmune Hepatitis (AIH)Autoimmune Hepatitis (AIH)
• AIH can occur alone or with PSC.• Previously called Lupoid Hepatitis• Strong Female predominance 3.6 : 1• Diagnosis is made with: • Requires a liver biopsy
• Liver tests look different from PSC• AST and ALT are elevated• Alkaline phosphatase is not elevated
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Treatments in DevelopmentTreatments in Development
• Intercept:• FXR agonist• Ombetacholic acid
• Takeda:• Humanized monoclonal antibody • Alpha4-beta7
• Vedolizumab
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SummarySummary
• PSC – liver disease of unknown cause that affects the large bile ducts.• Alone or as part of an overlap syndrome.• IBD is common in patients with PSC
• Fibrosis is the scar in the liver that results from inflammation. Final common pathway of all liver disease.
• No known effective treatment at this time, but an active area of research.