Updated: 6/1/2019

Primary Sclerosing Cholangitis

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Snapshot
  • A 34-year-old man presents to his gastroenterologist's office complaining of worsening fatigue, jaundice, and pruritis over the last 2 months. He was diagnosed with ulcerative colitis 8 years ago. The physician ordered labs which came back with an elevated ALP, GGT, and bilirubin.  She then scheduled the patient for magnetic resonance cholangiography and pancreatography which revealed multifocal stricturing of both the intrahepatic and extrahepatic biliary system. He is prescribed ursodeoxycholic acid.
Introduction
  • Clinical definition
    • primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disorder characterized by multifocal biliary strictures and progressive liver disease
  • Epidemiology
    • demographics
      • young to middle-aged men
        • mean age of 30-40
    • risk factors
      • inflammatory bowel disease (IBD)
        • primarily ulcerative colitis
        • up to 2/3 of PSC patients may have IBD
  • Pathogenesis
    • inflammation leads to multifocal fibrosis, sclerosis, and eventual stricturing and occlusion of both the extra- and intrahepatic bile ducts
      • the etiology of the inflammation is unknown
      • theorized to be caused by inflammatory mediators brought from the GI tract through the portal circulation
  • Genetics
    • significant genetic component but multifactorial
      • siblings at ↑ risk
  • Associated conditions
    • ulcerative colitis
Presentation
  • Symptoms
    • usually insidious onset, presenting with
      • cholestatic symptoms
        • fatigue
        • jaundice
        • pruritis
      • +/- IBD symptoms
    • later, symptoms resulting from chronic bile stasis
      • steatorrhea
      • symptoms of fat-soluble vitamin deficiencies
      • episodes of cholangitis (RUQ pain and fever)
  • Physical exam
    • jaundice
    • signs of fat soluble vitamin deficiencies
    • in late disease
      • signs of cirrhosis and/or liver failure
        • e.g. ascites
Studies
  • Diagnostic testing
    • diagnostic approach
      • requires a radiological diagnosis with exclusion of causes of secondary sclerosing cholangitis
    • imaging
      • magnetic resonance cholangiography/pancreatography (MRCP)
        • first-line modality for diagnosis
        • shows segmental stricturing and dilation of the bile duct resulting in a "bead-like" appearance
      • endoscopic retrograde cholangiography/pancreatography (ERCP)
        • gold standard
        • similar appearance as on MRCP
    • studies
      • cholestatic liver labs
        • ↑ alkaline phosphatase (ALP) and ↑ GGT
        • +/- ↑ bilirubin
        • ALT and AST may be normal
      • p-ANCA
        • not specific nor required for diagnosis
      • liver biopsy
        • shows concentric periductal sclerosis (AKA "onion-skinning")
Differential
  • Primary biliary cirrhosis
    • commonly confused
    • distinguishing factors
      • typically no extrahepatic disease
      • typically female
      • positive anti-mitochondrial antibody (AMA)
  • Secondary cirrhosis
    • history of causative disease (e.g. alcohol use, hepatitis, etc.)
  • Primary cholangiocarcinoma
    • typically older
    • presence of mass without duct strictures on imaging
Treatment
  • Management approach
    • symptomatic treatment until liver transplant
    • no level 1 evidence of disease-altering treatments
  • First-line
    • ursodeoxycholic acid (cholestyramine)
      • relief of cholestatic symptoms (e.g., pruritus)
    • liver transplant
      • the only definitive/curative treatment
      • may recur even after transplant
  • Other treatments
    • endoscopic balloon dilatation and/or stenting
      • relieves symptoms via bile duct dilatation and improved bile flow
    • antibiotics
      • during episodes of ascending cholangitis
    • vitamin supplementation
Complications
  • Cirrhosis and end-stage liver disease
    • inevitable in the majority of patients
  • GI and hepatobiliary Mmalignancy
    • risk for cholangiocarcinoma
      • up to ~400x normal or around 10% of PSC patients
    • ↑ risk for colorectal cancer
      • ~5x risk
    • ↑ risk for several others including liver and gallbladder cancers
  • Ascending cholangitis
    • increased susceptibility because of bile stasis
  • Fat-soluble vitamin deficiencies 
    • from the inability to release bile acid
 

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Questions (1)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.GI.73) A 32-year-old male presents to his primary care physician because of a one month history of generalized itching, fatigue, and a recent 5 lb unintended weight loss. He is a tax accountant, with no occupational exposures, drinks alcohol occasionally on weekends, and has never smoked. His past medical history is notable for ulcerative colitis, for which he is on mesalamine therapy. On physical exam, vital signs are within normal limits. The patient is tired appearing, with no notable abnormalities; abdominal exam elicits mild tenderness to palpation in the right upper quadrant, Murphy's sign is not present. Laboratory studies show an elevated alkaline phosphatase, gamma-glutamyl-transpeptidase (GGT), and mild transaminitis. The patient is referred for endoscopic retrograde cholangiopancreatography (ERCP), which is shown in Figure A. Which of the following findings are likely present in this patient? Review Topic

QID: 106582
FIGURES:
1

Computed tomography will demonstrate extensive calcification of the gall bladder

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Serum anti-mitochondrial antibody titers will be elevated

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Biopsy will demonstrate obliteration of intra and extrahepatic bile ducts

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Serum anti-smooth muscle antibody titers will be elevated

33%

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5

Biopsy will demonstrate granulomatous inflammation of intrahepatic bile ducts

33%

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M2

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