Acute Liver Injury / Acute Hepatitis

Acute hepatocellular injury with elevated transaminases ± jaundice — viral, DILI, or ischemic etiology drives management

Symptoms / Associated Sx

  • Fatigue, malaise, anorexia, nausea, vomiting, RUQ discomfort

  • Jaundice, dark urine, pale stools

  • Fever, myalgias, arthralgias (viral); rash, eosinophilia (DILI hypersensitivity)

  • Confusion, coagulopathy (acute liver failure — severe end)

Denies

  • Alcohol use (shifts away from alcoholic hepatitis)

  • Recent travel, shellfish, sick contacts (rules out HAV if absent)

  • New medications/supplements within 3 months (rules out DILI if absent)

  • Hypotension, cardiac event (rules out ischemic hepatitis if hemodynamically stable)

Social History (SHx)

IV drug use, high-risk sexual behavior (HBV/HCV/HDV), travel to endemic areas (HAV/HEV), recent medications or supplements, acetaminophen use, alcohol, recent hypotensive episode (ischemic hepatitis).

Main Etiology

  • Viral: HAV (fecal-oral, self-limited), HBV (acute or reactivation), HCV (rarely acute), HEV (travelers/pregnant), CMV, EBV

  • DILI: APAP (most common ALF in U.S.), isoniazid, statins, amoxicillin-clavulanate, NSAIDs, nitrofurantoin, herbals

  • Ischemic hepatitis: Shock liver — right heart failure, cardiogenic shock, hypotension; transaminases >1000–100,000 U/L

  • AIH: Young women; elevated IgG; ANA/ASMA; responds to steroids

  • Wilson's disease: Young patient; Kayser-Fleischer rings; hemolytic anemia; low ALP

Most Common DDx

  • Alcoholic hepatitis (AST:ALT >2:1; heavy alcohol use history; GGT markedly elevated; no ischemic precipitant)

  • Ischemic hepatitis / shock liver (transaminases dramatically elevated >1000–10,000; preceding hypotension or cardiac event; rapid normalization with resuscitation; echo often abnormal)

  • Acute cholecystitis / cholangitis (RUQ pain + fever; CBD dilation; elevated ALP/bilirubin > transaminases; imaging confirms biliary pathology)

  • Autoimmune hepatitis (young-middle aged women; ANA + ASMA + elevated IgG; liver biopsy confirms; responds to steroids)

  • Wilson's disease in young patient (low ALP — key clue; Coombs-negative hemolytic anemia; Kayser-Fleischer rings; ceruloplasmin low)

  • HELLP syndrome (pregnant/postpartum — thrombocytopenia + hemolysis + elevated LFTs; unique to pregnancy)

  • Budd-Chiari (hepatic vein thrombosis; painful hepatomegaly; ascites; Doppler shows no hepatic venous flow)

DATA

  • LFTs (AST/ALT/ALP/GGT/bilirubin direct vs. indirect), PT/INR, albumin, CBC, BMP

  • Viral serology: HAV IgM, HBsAg, HBcAb IgM, HCV Ab + RNA, HEV IgM, EBV/CMV PCR

  • ANA, ASMA, IgG (AIH); ceruloplasmin, serum copper (Wilson's); APAP level

  • Abdominal US with Doppler; echo if ischemic hepatitis suspected; liver biopsy if etiology unclear

Home Meds

  • All hepatotoxic medications — identify and hold offending agent

  • APAP (critical — assess total dose and timing); statins (hold until LFTs improve); herbal supplements (hold all)

Plan

  • Identify and remove causative agent; supportive care; avoid nephrotoxins; serial LFTs q24–48h

  • APAP overdose: NAC 150 mg/kg IV over 1h → 50 mg/kg over 4h → 100 mg/kg over 16h; Rumack-Matthew nomogram; poison control; transplant evaluation if ALF

  • Viral: HAV → supportive; acute HBV → tenofovir or entecavir if severe (INR >1.5 or jaundice); HBV reactivation → start antiviral urgently; HCV → defer 12 weeks (many clear spontaneously)

  • Ischemic hepatitis: Treat underlying cause; hemodynamic resuscitation; transaminases fall rapidly with perfusion restoration

  • AIH: Prednisone 40–60 mg daily ± azathioprine 50–100 mg daily; GI/hepatology + liver biopsy

  • ALF (INR >1.5 + HE within 26 weeks): ICU; NAC infusion; emergent transplant evaluation

  • Daily CBC, CMP, PT/INR, glucose; hepatology consult; toxicology if APAP/DILI; PT/OT when stabilized

  • Discharge: Avoid hepatotoxins (APAP <2 g/day; no alcohol; no herbals); LFTs recheck 2–4 weeks; hepatology follow-up for viral/AIH treatment; HAV/HBV vaccination if non-immune

Red Flags

  • INR >1.5 + any HE → acute liver failure → ICU + emergent transplant evaluation

  • Transaminases >10,000 → ischemic hepatitis or APAP toxicity → hemodynamic assessment immediately

  • APAP + INR rising despite NAC → ALF trajectory → transplant team now

  • HBV reactivation (immunosuppressed) → fulminant hepatitis → start antiviral immediately

  • Hy's Law in DILI (transaminases >3× ULN + bilirubin >2× ULN) → ~10% mortality → stop all drugs

Senior IM Resident Pearls

  • Ischemic hepatitis produces the most dramatically elevated transaminases (>10,000 common) — always ask about preceding hypotension or cardiac event

  • Rumack-Matthew nomogram: APAP level vs. time post-ingestion; treatment line at 150 mcg/mL at 4h

  • Hy's Law for DILI: Transaminases >3× ULN + bilirubin >2× ULN + no other cause = ~10% fatal outcome

  • HBV reactivation critical in patients on rituximab, steroids, anti-TNF — screen all with HBsAg + HBcAb before immunosuppression

  • Wilson's disease pearl: Low ALP + hemolysis + hepatitis in young = Wilson's until proven otherwise

  • Common mistake: Permanently stopping statins after mild transaminase elevation — rechallenge is reasonable after normalization; severe hepatotoxicity is rare

orders

Labs

Admission Labs

  • CBC with diff

  • CMP

  • BMP

  • PT/INR

  • PTT

  • Albumin

  • Glucose

  • Magnesium

  • Phosphorus

Viral Hepatitis Workup

  • HAV IgM

  • HBsAg

  • HBcAb IgM

  • HBsAb

  • HCV Ab

  • HCV RNA

  • HEV IgM (if indicated)

  • CMV PCR

  • EBV PCR

DILI / Toxicology Workup

  • Acetaminophen level

  • Salicylate level (if concern)

  • Urine drug screen

  • Ethanol level

Autoimmune Hepatitis Workup

  • ANA

  • ASMA

  • IgG level

  • Anti-LKM antibodies (if indicated)

Wilson Disease Workup

  • Ceruloplasmin

  • Serum copper

  • 24-hour urine copper

Additional Labs

  • LDH (often very high in ischemic hepatitis)

  • Lactate

  • AFP

  • Pregnancy test if applicable

Trending Labs

  • CBC daily

  • CMP daily

  • PT/INR daily

  • Glucose q6–8 hr if severe disease

  • AST/ALT daily

  • Bilirubin daily

Imaging

Initial Imaging

RUQ Ultrasound with Doppler

  • Biliary obstruction

  • Portal vein thrombosis

  • Budd-Chiari

  • Liver morphology

Additional Imaging

CT Abdomen/Pelvis

If:

  • Malignancy concern

  • Unclear diagnosis

  • Vascular pathology

Echocardiogram

If:

  • Ischemic hepatitis

  • CHF

  • Cardiogenic shock

Specialty Imaging

MRCP

If:

  • Biliary obstruction suspected

  • Cholangitis concern

Procedures

Usually Not Needed Initially

Liver Biopsy

If:

  • Etiology unclear

  • Autoimmune hepatitis suspected

  • Persistent unexplained hepatitis

ICU Procedures

If ALF:

  • Central line

  • Arterial line

  • Frequent neuro checks

Medications

General Supportive Care

IV Fluids

  • LR or NS as indicated

  • Avoid volume overload

Avoid

  • Hepatotoxic medications

  • NSAIDs

  • Alcohol

  • Herbal supplements

Acetaminophen Toxicity

N-Acetylcysteine (NAC)

Loading

  • 150 mg/kg IV over 1 hr

Second Infusion

  • 50 mg/kg IV over 4 hr

Third Infusion

  • 100 mg/kg IV over 16 hr

Additional

  • Poison Control consult

  • Toxicology consult

Acute HBV

Severe Disease

(INR >1.5, severe jaundice, ALF)

Tenofovir

  • 300 mg PO daily

OR

Entecavir

  • 0.5 mg PO daily

HBV Reactivation

Immediate Treatment

  • Tenofovir 300 mg PO daily

OR

  • Entecavir 0.5 mg PO daily

Autoimmune Hepatitis

Prednisone

  • 40–60 mg PO daily

Steroid-Sparing

  • Azathioprine 50–100 mg PO daily

(Hepatology guided)

Ischemic Hepatitis

Treatment

  • Treat shock

  • Restore perfusion

  • Treat CHF

  • Treat sepsis

  • Optimize oxygen delivery

No specific liver-directed therapy.

Acute Liver Failure

Continue NAC

Even if non-APAP ALF

ICU Monitoring

  • Neuro checks

  • Glucose monitoring

  • Airway assessment

Early Transplant Evaluation

Hold Medications

Hold All Potential Hepatotoxins

  • Acetaminophen

  • Statins

  • Herbals/supplements

  • Amoxicillin-clavulanate

  • Nitrofurantoin

  • Isoniazid

  • Valproate

  • Methotrexate

Review Carefully

  • Anticoagulants

  • Sedatives

Consults

Hepatology (Most Patients)

  • Severe hepatitis

  • ALF

  • AIH

  • Viral hepatitis

Toxicology

  • Acetaminophen overdose

  • DILI

Poison Control

  • Any overdose concern

Transplant Team

If:

  • ALF

  • INR >1.5 + HE

  • Rapid deterioration

Critical Care

  • Acute liver failure

  • Shock

  • Encephalopathy

PT/OT

  • Deconditioning

Nursing Orders

Monitoring

  • Neuro checks q4 hr

  • Strict I&O

  • Daily weights

  • Fall precautions

Diet

  • Regular diet if tolerated

  • Avoid alcohol completely

Notify Physician

  • New confusion

  • Worsening jaundice

  • Hypoglycemia

  • Bleeding

  • INR rise

  • Worsening LFTs

Follow-Up Studies

Follow

  • Viral serologies

  • Autoimmune panel

  • Ceruloplasmin

  • Copper studies

  • APAP level

  • Ultrasound findings

Daily

  • AST

  • ALT

  • Bilirubin

  • INR

  • Creatinine