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

BiasBias

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.

Primary Sclerosing CholangitisPrimary Sclerosing CholangitisAffects Biliary SystemAffects Biliary System

• 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

Primary Sclerosing CholangitisPrimary Sclerosing CholangitisAffects Biliary SystemAffects Biliary System

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

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

Cholangiography in Normal and PSCCholangiography in Normal and PSC

Normal PSC

PSCPSC

Cholangiography in PSCCholangiography in PSC

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

Liver Biopsy in PSCLiver Biopsy in PSC

Early Classic “onion skinning”

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

Stages of FibrosisStages of Fibrosis

Stage 1 Stage 2

Stage 3 Stage 4

Regenerating nodules = CirrhosisRegenerating nodules = Cirrhosis

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

• 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

• Standard imaging studies do not evaluate fibrosis:• Ultrasound• CT scan• MRI

PSCPSC

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

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)

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

Primary Sclerosing CholangitisPrimary Sclerosing CholangitisIBDIBD

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

• Unknown• Alterations in the way immune

cells arrive at their destination:• Adhesion molecules

increases

• Unknown• Intestinal Bacteria

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

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.

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

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

Bone DiseaseBone Disease• Osteoporosis (thining of the bones) is common

• Vit D deficiency• Postmenopausal status

• Treatment • Ca• Vit D• Weight bearing exercise• Prescription medications

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

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

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

Treatments in DevelopmentTreatments in Development

• Intercept:• FXR agonist• Ombetacholic acid

• Takeda:• Humanized monoclonal antibody • Alpha4-beta7

• Vedolizumab

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.

The ABCs of PSC Jacqueline O’Leary, MD MPH Medical Director of Research, Baylor Simmons Transplant...

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