Other Causes of Hepatitis or Hepatotoxicity Alcoholic hepatitis

• Aminotransferases usually 300-500 w AST ALT >2:1. in part b c concomitant B* defic.

• Treatment: discriminant function >32 or encephalopathy (w o GIB or infection)

discriminant function (4.6 • [PT-control]) - total bilirubin (mg dl) prednisolone or prednisone 40 mg PO qd x 1 mo then taper over 4-6 wks U mortality (NEJM 1992;326:507)

pentoxifylline 400 mg PO tid x 1 mo 1 mortality and HRS (Conn 2000,119:1637) Acetaminophen hepatotoxicity

• Normal metabolism via glucuronidation and sulfation — nontoxic metabolites

• Overdose (usually -10 g): CYP2E1 hydroxylation reactive electrophilic species

(NAPQI) that are scavenged by glutathione until reserves exhausted -* hepatotoxicity

• CYP2E1 induced by fasting and alcohol (allowing for "therapeutic misadventure" in malnourished alcoholics taking even low doses (2-6 g) of acetaminophen)

• Liver dysfunction may not be apparent for 2-6 d

• Treatment: NG lavage, activated charcoal if presenting w in 4 h

N-acetylcysteine: administer up to 36 h after ingestion if acetaminophen level above "no-risk" zone or if time of ingestion unknown or reliable hx of major poisoning (>10 g) should have low threshold for NAC (even if low or undetectable acetaminophen levels) PO NAC (preferred): 140 mg kg loading dose — 70 mg kg q4h >17 additional doses IV NAC: 150 mg kg load over 1h — 50 mg kg over 4 h — 100 mg kg over 16 h risk of anaphylaxis: use if unable to tolerate PO. GIB. preg.. fulminant hepatic failure

(Adapted Arc/wes 1981.141 382 & Guiddma for Management of Acute Acetaminophen Overdose McNeil. 1999.)

Other drugs and toxins that may cause hepatitis (NEJM 2006:354 731)

• Amiodarone. azoles. INH. methyldopa. phenytoin. PTU, rifampin, sulfonamides.

minocycline, chemotherapy drugs, herbal medications, statins (rare)

• Halothane. CCI«, solvents, toxic mushrooms (Amanita pholloides)

Ischemic hepatitis: "shock liver" w, AST & ALT >1000 ► Î1 LDH; 2° CHF. sepsis. HoTN

Nonalcoholic fatty liver disease (NAFLD) (Annoh 1997:126 137;)MM 2003:289 3000)

• Spectrum of fatty infiltration • inflammation • fibrosis in absence of EtOH abuse

• Prevalence 7-9%; metabolic syndrome (associated w DM. hyperinsulinemia, obesity.

hypertriglyceridemia). HAART. meds (tamoxifen, amiodarone)

• Clinical: usually asx 2-3 x t in ALT; 2 RUQ pain, fatigue; may — cirrhosis ( - 5%)

• Dx: exclusion of other causes of hepatitis or cirrhosis; US — hyperechoic liver, ® bx

• Rx: wt loss, glycemic lipid control; if IGT DM & bx-confirmed steatohepatitis thiazolidinediones i steatosis & aminotransferases (NE}M 2006:355 2297); ? ursodeoxycholic acid + vitamin E, ? metformin

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