Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (50 page)

liver bx shows characteristic PAS
cytoplasmic inclusion bodies

• Treatment: standard Rx for cirrhosis/chronic liver dis.; ɑ
₁
-AT replacement for emphysema
Primary biliary cirrhosis (PBC)
(
Hepatology
2009;50:291;
Lancet
2011;377:1600)
• Autoimmune destruction of
intrahepatic
bile ducts; may be triggered by certain infxns or toxins; a/w X monosomy, variants in IL12ɑ & IL12 receptor genes (
NEJM
2009;360:2544) • Epi:
40–60 y/o; a/w Sjögren’s, Raynaud’s, scleroderma, celiac & thyroid disease • Sx (late): fatigue, pruritus, jaundice, steatorrhea, xanthelasma, autonomic & cog dysfxn • Ddx: PSC, autoimmune hepatitis (overlap syndrome), sarcoid, meds, idiopathic adult ductopenia, biliary stricture/cancer • Dx: ↑ AΦ, ↑ bili, ↑ IgM, ↑ chol,
antimitochondrial Ab (AMA) in 95%. If
AMA, liver bx not needed due to high Se & Sp. 0.5% gen pop
AMA & nl LFTs → 10% develop PBC at 6 y. If AMA
, liver bx (Pts often
ANA, smooth muscle Ab; same prognosis as
AMA).

•
Rx: ursodeoxycholic acid
(13–15 mg/kg/d) regardless of stage

~25% complete response, ↑ survival & ↓ histologic change & complications (eg, varices) (
Gastro
2005;128:297). Trials of colchicine, MTX, budesonide if refractory to urso.

Pruritus: cholestyramine (give 2–4 h after UDCA); if refractory sx: naltrexone, rifampin

Fat-soluble vitamins; screen/Rx osteoporosis (risk independent of vit Δ deficiency)

If ESLD: liver tx: ~20% recur but no impact on long-term survival

Primary sclerosing cholangitis (PSC)
(
Liver Transpl
2008;14:735)
• Diffuse inflammation of
intrahepatic and extrahepatic
bile ducts leading to fibrosis & stricturing of biliary system. A/w HLA-B8 and -DR3 or -DR4, frequent
autoantibodies but poor response to immunomodulator Rx suggesting nonautoimmune pathogenesis.

• Epi:
>
(20–50 y). ~70% of Pts w/ PSC have IBD (usually UC); only 1–4% w/ UC get PSC.

• Clinical sx: fatigue, pruritus, jaundice, fevers, RUQ pain, cholangioca., ↑ Tb, ↑ AΦ

• Ddx: extrahepatic obstruction, PBC, may also have overlap w/ AIH and similar presentation to IgG4 autoimmune cholangitis (steroid responsive) (
Gastro
2008;134:706) • Dx: MRCP ± ERCP →
multifocal beaded bile duct strictures
, but may miss dx if confined to small intrahepatic ducts (~2% “small duct PSC”: better prognosis,? different disease). Liver bx may show “onion-skin” fibrosis around bile ducts, but not necessary for dx, plays role in excluding autoimmune sclerosing cholangitis.

• Treatment: supportive care, fat-soluble vitamins; no meds have improved survival Ursodeoxycholic acid may ↓ colon CA risk in Pts w/ UC & improve LFTs in Pts w/o UC Dominant stricture: endoscopic dilation, short-term stenting or surgical resection Cholangiocarcinoma (20%): ? biannual surveillance w/ MRCP/RUQ U/S and CA19-9 Liver transplantation: ~30% recurrence, though if UC, colectomy may ↓ recurrence