Acute Hepatitis and Abnormal Liver Tests

Approach to Acute Liver Injury – Jacob Parnell


  • Acute liver injury (ALI) = elevated aminotransferases + INR >1.5 but NO hepatic encephalopathy (HE indicates acute liver failure; see below)
  • Alcoholic hepatitis (AH), though similar, is considered a separate process
  • The primary abnormality in congestive hepatopathy is hyperbilirubinemia, with mild elevations of AST/ALT or alkaline phosphatase though has a variable presentation
  • R-factor = (ALT/uln ALT) / (ALP/uln ALP);  Objectively differentiates patterns below
    • R > 5 = hepatocellular injury;   R<2 = cholestatic injury;   R 2-5 = mixed injury


Hepatocellular Injury: R factor > 5 (Primary elevation of AST/ALT)

Acute Viral Hepatitis

Hep A$, B*$, C*, D, E


Viral serologies; (Hep A panel, Hep B panel, Hep C Ig, EBV Ig, CMV PCR, IgM, IgG);  hx of tattoos, IVDU, piercings, blood transfusion prior to 1990s, intranasal cocaine use and mass vaccinations (in 3rd world countries)

Acetaminophen intoxication$


Acetaminophen lvl

Aspirin lvl

NASH – Non-alcoholic steatohepatitis*

Fatty infiltration of liver

ALT>AST; metabolic syndrome; rarely acute always <400

Autoimmune hepatitis*

Autoantibodies and high serum globulins 

Anti-smooth muscle (f-actin), ANA, ANCA, anti-liver/kidney microsomes soluble liver-pancreas IgG


Ethanol, cocaine, mushroom

UDS, ethanol level, Peth lvl,

AST>ALT in 2:1 ratio- suspect alcohol  (<400 or even 300 per ACG)

DILI – Drug Induced Liver Injury*$

Many drugs

Common: antibiotics (eg beta-lactams, quinolones, others), NSAIDs,

anti-epileptics, macrolides, isoniazid, SSRIs

*Query NIH Liver Tox database:

Ischemic Liver Injury (Shock Liver)$

hemorrhage, sepsis

AST > ALT, high LDH, history of hypotension

HELLP Syndrome, Acute Fatty Liver of Pregnancy


Pregnancy testing; urgent delivery

Wilson’s Disease*

Copper overload

Ceruloplasmin level (screening), 24h urine copper (confirmation), quantitative copper on liver biopsy


Iron overload

Ferritin, iron level; does not cause acute liver injury, usually mild to moderate chronic elevation. HFE testing for confirmation of main types

Alpha-1-antitrypsin deficiency*


AAT phenotype, only acute in children

Budd-Chiari Syndrome*

Hepatic vein obstruction

Ultrasound of abdomen w/ doppler, CT w/ contrast

Portal vein thrombosis*


Ultrasound of abdomen w/ doppler, CT w/ contrast, MRI

*May present as chronic liver injury as well     $ May present with AST/ALT >1000



Cholestatic Injury: R Factor < 2 (Primarily elevated Alkaline phosphatase)

Acute biliary obstruction


abdominal ultrasound, MRCP, ERCP

Primary Sclerosing Cholangitis*

Autoimmune, associated with IBD


Primary Biliary Cirrhosis*


Anti-mitochondrial antibody

DILI – Drug-induced liver injury*$

Many drugs, consult livertox website

Common: Augmentin, Bactrim, amiodarone, Imuran 


Pancreas, cholangiocarcinoma

CT abdomen, ERCP

*May present as chronic liver injury  $ May present with AST/ALT >1000


Isolated Hyperbilirubinemia: 

  • Differentiate direct vs indirect bilirubin
    • Direct bilirubin, refer to cholestatic
    • Indirect: Gilbert versus hemolysis (send LDH, haptoglobin, retic count, peripheral smear)

Consider non-hepatic causes of elevated liver chemistries

  • Thyroid disorder
  • Celiac disease
  • Tick-borne infection
  • Rhabdomyolysis, hemolysis (AST>>ALT)