STEPTRACKERGASTROINTESTINAL | PATHOLOGY + IMMUNOLOGY | HIGH-YIELD REVIEW

Cholestatic & Biliary Diseases

Diseases of the bile ducts themselves — autoimmune, inflammatory, congenital and malignant.

FOCUS ON
PBC: middle-aged women, small intrahepatic ducts, anti-mitochondrial antibody, pruritus, ↑ ALP, ursodiol. PSC: men with UC, intra- and extrahepatic ducts, beaded on cholangiography, "onion skin" fibrosis, cholangiocarcinoma risk. Biliary atresia: newborn with conjugated jaundice and acholic stool → Kasai.
DISORDER
MECHANISM
FEATURES
CLUE · TREATMENT
Primary biliary cholangitis
Autoimmune T-cell destruction of small intrahepatic bile ducts; granulomatous "florid duct lesion"
Middle-aged women; fatigue, pruritus, ↑ ALP, xanthelasma, hypercholesterolemia; later jaundice, cirrhosis
AMA ⁺, ↑ IgM · ursodiol, obeticholic acid
PBC — associations
Other autoimmune disease
Sjögren, Hashimoto, CREST/scleroderma, celiac; osteoporosis; fat-soluble vitamin deficiency
Steatorrhea from bile salt deficiency
Primary sclerosing cholangitis
Immune-mediated inflammation and concentric "onion skin" fibrosis of intra- and extrahepatic ducts
Men; often with ulcerative colitis; pruritus, jaundice, ↑ ALP; recurrent cholangitis
p-ANCA ⁺, ↑ IgM · beaded ducts on MRCP · transplant
PSC — complications
Chronic biliary injury
Secondary biliary cirrhosis, cholangiocarcinoma, gallbladder cancer, colorectal cancer (with UC)
Annual surveillance
Secondary biliary cirrhosis
Long-standing extrahepatic obstruction (stones, stricture, tumor) → ↑ pressure, injury, fibrosis
Jaundice, pruritus, recurrent cholangitis
Bile lakes and bile infarcts
Biliary atresia
Fibro-obliterative destruction of extrahepatic ducts in the first weeks of life
Jaundice > 2 weeks, acholic (pale) stools, dark urine, hepatomegaly; ↑ conjugated bilirubin, ↑ GGT
HIDA: no excretion into bowel · Kasai procedure · top cause of pediatric transplant
Alagille syndrome
JAG1 or NOTCH2 (AD) → paucity of intrahepatic bile ducts
Cholestasis, butterfly vertebrae, peripheral pulmonic stenosis, posterior embryotoxon, triangular face
Neonatal cholestasis + heart murmur
Choledochal cyst
Congenital cystic dilation of the bile duct
Abdominal pain, jaundice, RUQ mass; more in Asian girls
↑ cholangiocarcinoma → excise
Cholangiocarcinoma
Adenocarcinoma of bile ducts; PSC, liver flukes (Clonorchis, Opisthorchis), choledochal cysts, Caroli disease
Painless jaundice, weight loss, pruritus; hilar (Klatskin) tumor most common
CA 19-9 · desmoplastic glands
Intrahepatic cholestasis of pregnancy
Hormone-related bile transport defect
3rd trimester itching of palms and soles, no rash; ↑ serum bile acids
Risk of stillbirth · ursodiol, early delivery

Mechanism — cholestasis

Duct injury or block
→
Bile retained
→
Bile salts in bloodPruritus
Cholesterol ↑Xanthomas
No bile in gutPale stool, ADEK deficiency
Ongoing injury
→
Ductopenia, fibrosis
→
Biliary cirrhosis

PBC vs PSC

FEATURE
PBC
PSC
Who
Middle-aged women
Young-middle-aged men
Ducts
Small intrahepatic
Intra- + extrahepatic
Lesion
Granulomatous duct destruction
Onion-skin fibrosis, strictures
Antibody
AMA
p-ANCA
Association
Sjögren, thyroid, scleroderma
Ulcerative colitis
Cancer
HCC (with cirrhosis)
Cholangiocarcinoma

How it's tested

COMMON CONFUSIONPBC and PSC both raise ALP and cause itching. AMA in a woman = PBC; beaded ducts in a man with UC = PSC.
THE TRAPA newborn whose jaundice lasts beyond 2 weeks is not "physiologic" if the bilirubin is conjugated. Biliary atresia must be found early — Kasai works best before 2 months.
YOUR APPROACHCholestatic labs → age and sex → associated disease (UC, autoimmune, pregnancy) → antibody or imaging (MRCP, HIDA) → risk to watch.

If you see… think…

Middle-aged woman with itching, ↑ ALP, AMA⁺ → primary biliary cholangitis
PBC + xanthelasma → hypercholesterolemia of cholestasis
Man with UC, ↑ ALP, beaded bile ducts → primary sclerosing cholangitis
PSC patient with new jaundice and weight loss → cholangiocarcinoma
Concentric periductal "onion skin" fibrosis → PSC
6-week-old with jaundice, pale stools, dark urine → biliary atresia — Kasai
Neonatal cholestasis + butterfly vertebrae + pulmonic stenosis → Alagille syndrome
Pregnant woman with itchy palms and soles, ↑ bile acids → intrahepatic cholestasis of pregnancy
Southeast Asian with painless jaundice and a hilar mass → cholangiocarcinoma (liver fluke)
Child with RUQ mass, pain and jaundice → choledochal cyst