Acute Hepatitis (Viral)

1. History

• Key HPI questions: Onset and duration of symptoms; characterize the prodromal phase (fever, malaise, fatigue, anorexia, myalgias) followed by icteric phase (dark urine, jaundice, acholic stools, RUQ pain) [1-2]
• Symptom characterization: Nausea, vomiting, diarrhea (especially HAV/HEV), RUQ or epigastric pain, pruritus, arthralgias [1][3]
• Timing and triggers: Incubation periods vary — HAV ~28 days (15–50), HBV ~90 days (30–180), HCV ~45 days (14–180), HEV ~40 days (15–60) [3-5]
• Exposure history: Travel to endemic areas, contaminated food/water (HAV/HEV), sexual contacts (HAV/HBV), IV drug use (HBV/HCV/HDV), blood transfusions, needlestick injuries, tattoos, household contacts [6-7]
• Important negatives: Acetaminophen or other hepatotoxic drug use, alcohol intake, mushroom ingestion, recent hypotension/shock, herbal supplements, pregnancy

2. Alarm Features

• Fulminant hepatitis / acute liver failure (ALF): Encephalopathy (confusion, asterixis, somnolence), coagulopathy (INR >1.5), deep jaundice (bilirubin >10 mg/dL) [2][8]
• Signs of decompensation: Persistent vomiting with inability to tolerate PO, hypoglycemia, ascites, GI bleeding
• Hemodynamic instability: Hypotension and bradycardia have been reported as initial presentations of acute HAV [9]
• Protracted severe course: Jaundice and rising INR persisting >4 weeks in acute HBV warrants antiviral consideration [8]
• ALF from viral hepatitis carries only ~25% spontaneous survival — early transfer to a transplant center is critical [2]

3. Medications

• Medications to avoid/use with caution during acute hepatitis:
  • Acetaminophen — avoid or limit to <2 g/day; risk of compounding hepatic injury [10]
  • NSAIDs — avoid due to hepatotoxicity risk and potential GI bleeding with coagulopathy
  • Hepatically metabolized drugs — use with caution; dose-adjust or hold when possible [10-11]
  • Herbal/dietary supplements — discontinue; increasingly recognized as causes of liver injury [2][11]
• Treatments:
  • HAV/HEV: Supportive care only; no specific antiviral therapy [10][12]
  • HBV: Antivirals (entecavir, TDF, or TAF) reserved for severe/protracted hepatitis or ALF; interferon-α is contraindicated in acute HBV [8][13]
  • HCV: Direct-acting antivirals (DAAs) for confirmed acute HCV; spontaneous clearance occurs in ~25% so treatment may be deferred 12–16 weeks [11]
  • HDV: Treat underlying HBV; bulevirtide for chronic HDV

4. Diet

• No specific dietary restrictions are required for acute viral hepatitis [10]
• Hydration: Aggressive oral or IV rehydration if dehydrated from nausea/vomiting
• Avoid alcohol completely during acute illness and recovery
• Small, frequent meals may be better tolerated given anorexia and nausea
• HAV/HEV prevention: Avoid raw/undercooked shellfish, contaminated water; heat foods to >85°C (185°F) for ≥1 minute to inactivate HAV [7]

5. Review of Systems

• GI: Nausea, vomiting, diarrhea, anorexia, abdominal pain, acholic stools
• Dermatologic: Jaundice, pruritus, skin rash (less common), urticaria
• Musculoskeletal: Arthralgias, myalgias (serum sickness–like prodrome in HBV)
• Neurologic: Confusion, somnolence, asterixis (suggests encephalopathy — red flag)
• Hematologic: Easy bruising, bleeding (coagulopathy)
• Genitourinary: Dark (cola-colored) urine
• Constitutional: Fever, fatigue, malaise, weight loss

6. Collateral History and Family History

• Collateral: Confirm exposure sources — sick contacts, shared needles, sexual partners, food exposure history, recent travel
• Family history: Wilson disease, alpha-1-antitrypsin deficiency, hemochromatosis, autoimmune hepatitis (to exclude non-viral etiologies) [11]
• Social context: Injection drug use, homelessness, incarceration, MSM status, occupational exposure (healthcare workers) [14-15]
• Vaccination history: HAV and HBV vaccination status

7. Risk Factors

• HAV: Travel to endemic areas, contaminated food/water, MSM, injection/non-injection drug use, homelessness, close contact with infected person [3][7][15]
• HBV: Unvaccinated status, sexual contact, perinatal transmission, IV drug use, healthcare exposure, immigration from endemic regions [4][16]
• HCV: IV drug use (primary risk), intranasal drug use, needlestick, MSM (especially with HIV), blood transfusion before 1992 [11]
• HDV: Only in HBV-infected individuals; same parenteral/sexual risk factors
• HEV: Travel to endemic areas, undercooked pork/game meat (genotype 3 in developed countries), organ transplant recipients [5-6]
• Risk factors for severe disease/ALF: Age >40 (HAV), pre-existing liver disease, immunosuppression, HBV-HDV coinfection, pregnancy (HEV — up to 25% mortality in third trimester) [2-4]

8. Differential Diagnosis

• Acetaminophen toxicity — most common cause of ALF in the US; check level and history [17-18]
• Ischemic hepatitis — rapid AST/ALT rise (often >1000) with rapid decline; history of hypotension, shock, heart failure [17][19]
• Drug-induced liver injury (DILI) — antimicrobials (amoxicillin-clavulanate, isoniazid), supplements, NSAIDs; clinical picture can mimic viral hepatitis exactly [19-20]
• Autoimmune hepatitis — check ANA, anti-smooth muscle antibody, IgG levels; may present acutely [17]
• Alcoholic hepatitis — AST:ALT ratio typically >2:1, AST usually <300, elevated GGT [19][21]
• Wilson disease — consider in patients <40 years; check ceruloplasmin, slit-lamp exam for Kayser-Fleischer rings [11][17]
• Biliary obstruction — may initially mimic hepatocellular injury; ultrasound to evaluate [17]
• Non-hepatotropic viral infections: EBV, CMV, HSV (especially immunocompromised), adenovirus — often with systemic features (lymphadenopathy, rash, atypical lymphocytes) [2][17]
• Tropical infections (in appropriate settings): Dengue, leptospirosis, scrub typhus, enteric fever — persistent fever after jaundice onset and thrombocytopenia favor these over AVH [22]

9. Past Medical History

• Pre-existing liver disease (NAFLD, cirrhosis, alcohol-related) — increases risk of fulminant course [3-4]
• Prior hepatitis episodes or known chronic HBV/HCV carrier status — acute flare vs. new infection
• Immunosuppression (transplant, HIV, chemotherapy) — higher risk for severe disease and atypical viral causes (HSV, CMV, adenovirus) [2]
• Autoimmune conditions — may predispose to autoimmune hepatitis overlap
• Surgical history: Prior liver transplant, biliary surgery

10. Physical Exam

• Vital signs: Fever (prodromal phase), hypotension and bradycardia (rare but reported with HAV); tachycardia if dehydrated [9]
• General: Ill-appearing, icteric sclerae, jaundiced skin
• Abdomen: RUQ tenderness, hepatomegaly (present in ~78% of HAV cases), splenomegaly (suggests chronic liver disease or EBV) [3][11]
• Skin: Jaundice, spider angiomata and palmar erythema (suggest chronic disease, not acute), excoriations from pruritus
• Neurologic: Mental status changes, asterixis — critical to assess; any encephalopathy = ALF until proven otherwise [2]
• Stigmata of chronic liver disease (ascites, caput medusae, gynecomastia) — suggest pre-existing cirrhosis with acute flare rather than de novo acute hepatitis [11]

11. Lab Studies

• Liver panel: AST, ALT (often markedly elevated, >10× ULN in acute viral hepatitis), total and direct bilirubin, alkaline phosphatase, GGT, albumin [11][23]
• Coagulation: PT/INR — INR >1.5 is a critical threshold suggesting possible ALF [2][24]
• CBC: Leukopenia or atypical lymphocytes (EBV/CMV); thrombocytopenia (suggests chronic disease or tropical infection) [22]
• BMP: Glucose (hypoglycemia in ALF), electrolytes, creatinine (hepatorenal syndrome)
• Serologic panel for etiology: [5][11][16][19]
  • HAV: Anti-HAV IgM (confirms acute infection)
  • HBV: HBsAg + anti-HBc IgM (confirms acute HBV); HBV DNA, HBeAg for further characterization
  • HCV: Anti-HCV antibody + HCV RNA (antibody may be negative early; RNA is essential)
  • HDV: Anti-HDV IgM/total (only if HBsAg positive)
  • HEV: Anti-HEV IgM ± HEV RNA (consider in travelers, older adults, unexplained hepatitis)
• Additional: Acetaminophen level, toxicology screen, ANA, anti-smooth muscle antibody, IgG levels, ceruloplasmin (if <40 years), lipase [17][19]

The following figure illustrates the temporal appearance of serologic and molecular markers in acute HBV and HCV infections, highlighting the diagnostic window period:

12. Imaging

• First-line: RUQ ultrasound with Doppler — to exclude biliary obstruction, assess hepatic vasculature (Budd-Chiari), evaluate for chronic liver disease features [21]
• Expected findings in acute viral hepatitis: Hepatomegaly, periportal edema, gallbladder wall thickening; generally nonspecific
• CT/MRI: Not routinely needed; consider if ultrasound is inconclusive or concern for malignancy, vascular pathology, or abscess
• Imaging is unnecessary to confirm the diagnosis of acute viral hepatitis — diagnosis is serologic [21]

13. Special Tests

• R-value calculation: (ALT/ULN) ÷ (ALP/ULN) — R >5 = hepatocellular pattern (typical of viral hepatitis); R <2 = cholestatic; 2–5 = mixed [17]
• MELD score: Useful for severity stratification and transplant listing
• King's College Criteria: For prognostication in ALF (non-acetaminophen: INR >6.5, or any 3 of: age <10 or >40, etiology unfavorable, jaundice >7 days before encephalopathy, INR >3.5, bilirubin >17.5 mg/dL)
• ALFSG Prognostic Index: Predicts spontaneous survival in ALF using encephalopathy grade, etiology, vasopressor use, bilirubin, and INR (AUROC 0.843) [26]
• Liver biopsy: Rarely needed in acute viral hepatitis; consider if diagnosis remains uncertain or autoimmune hepatitis is suspected [24]
• FibroScan/elastography: Not useful in the acute setting (inflammation falsely elevates stiffness)

14. ECG

• Not routinely indicated in uncomplicated acute viral hepatitis
• Indications for ECG: Bradycardia, hypotension, chest pain, or hemodynamic instability
• Reported findings: Sinus bradycardia and sinus arrest have been described as presenting features of acute HAV; cardiac autonomic dysregulation with increased vagal tone has been demonstrated in acute hepatitis [9][27]
• Consider myocarditis if persistent tachycardia, ST changes, or new arrhythmias in the setting of viral illness [28-29]

15. Assessment

• Typical presentation: Prodromal flu-like illness (1–2 weeks) → icteric phase with jaundice, dark urine, RUQ pain → convalescent phase (weeks to months) [1][3-4]
• Severity stratification:
  • Mild: Symptomatic with preserved synthetic function (normal INR, no encephalopathy)
  • Moderate: Significant jaundice (bilirubin >10), prolonged symptoms, dehydration
  • Severe/ALF: Coagulopathy (INR >1.5) ± encephalopathy — mortality without transplant is high [2]
• Atypical presentations: Anicteric (especially HCV — typically anicteric and asymptomatic), cholestatic (prolonged jaundice in HAV), relapsing (10–15% of HAV), biphasic course (HDV coinfection) [1][3][11]
• Complications: ALF (<1% HAV, 0.1–0.5% HBV), chronicity (HBV ~5% in adults, HCV ~55–85%), extrahepatic manifestations (reactive arthritis, GBS, pancreatitis with HAV; glomerulonephritis, polyarteritis nodosa with HBV) [3-4]

16. Treatment Plan

• Initial stabilization:
  • IV fluids for dehydration; correct electrolyte abnormalities and hypoglycemia
  • Antiemetics (ondansetron) for nausea/vomiting
  • Avoid hepatotoxic medications — hold acetaminophen, NSAIDs, statins, and unnecessary drugs [10-11]
• Virus-specific management:
  • HAV: Supportive care only; self-limited in >99% [3][10]
  • HBV: Supportive in most cases (>95% spontaneous recovery in adults); start entecavir, TDF, or TAF if severe hepatitis (INR >1.6, bilirubin >10, encephalopathy) or ALF; interferon-α is contraindicated [8][16]
  • HCV: DAA therapy (e.g., sofosbuvir/velpatasvir); may observe 12–16 weeks for spontaneous clearance before initiating [11]
  • HDV: Treat underlying HBV; bulevirtide for chronic HDV
  • HEV: Supportive; ribavirin for severe or chronic HEV in immunocompromised [12]
• ALF management: ICU admission, N-acetylcysteine (IV NAC improves transplant-free survival even in non-acetaminophen ALF with early coma grades), early transplant center consultation, intracranial pressure monitoring if grade III–IV encephalopathy [2]
• Post-exposure prophylaxis:
  • HAV: Vaccine ± immune globulin within 2 weeks of exposure for contacts
  • HBV: HBIG + vaccine series for unvaccinated contacts/neonates

17. Disposition

• Discharge criteria (outpatient management):
  • Tolerating oral intake, adequate hydration
  • Normal mental status, no encephalopathy
  • INR <1.5, stable or improving transaminases
  • Reliable follow-up and return precautions understood
• Admission criteria: [1-2][10]
  • Intractable vomiting/dehydration requiring IV fluids
  • INR >1.5 or any coagulopathy
  • Any encephalopathy (even subtle — confusion, sleep-wake reversal)
  • Bilirubin >10 mg/dL with worsening trajectory
  • Hypoglycemia, renal insufficiency
  • Significant comorbidities (pre-existing liver disease, immunosuppression, pregnancy)
• Transfer to transplant center: Any patient meeting ALF criteria (coagulopathy + encephalopathy) — spontaneous survival in viral ALF is only ~25% [2]
• Specialist consultation: Gastroenterology/hepatology for all confirmed cases; infectious disease if atypical presentation or immunocompromised host

18. Follow Up / Return Precautions

• Follow-up timing: Recheck liver enzymes and INR within 1–2 weeks of discharge; repeat at 4–6 weeks to confirm resolution
• HBV: Recheck HBsAg at 6 months to confirm clearance vs. chronic infection [16][30]
• HCV: Recheck HCV RNA at 12–16 weeks; if persistent, initiate DAA therapy [11]
• Return precautions — instruct patients to return immediately for:
  • Worsening jaundice, dark urine, or pale stools
  • Confusion, excessive drowsiness, or personality changes (encephalopathy)
  • Inability to keep fluids down
  • Easy bruising or bleeding
  • Abdominal swelling
• Patient counseling:
  • Avoid alcohol until full recovery (and indefinitely if chronic HBV/HCV)
  • Avoid hepatotoxic medications including OTC supplements
  • Practice hand hygiene (HAV/HEV); use barrier protection during sex (HBV); avoid sharing needles or personal items that may contact blood [6][10]
  • HAV: Considered noninfectious ~1 week after jaundice onset [3]
• Expected recovery: Most HAV cases resolve within 2 months; 10–15% may have prolonged or relapsing symptoms up to 6 months. HBV recovery typically within 6–12 months in adults [3-4][7][30]
• Public health reporting: Acute viral hepatitis (A, B, C) is reportable in all US states

References

1. Viral Hepatitis in Pregnancy: ACOG Clinical Practice Guideline No. 6. — Committee on Clinical Practice Guidelines–Obstetrics Obstetrics and Gynecology. 2023.

2. Acute Liver Failure Guidelines. — Shingina A, Mukhtar N, Wakim-Fleming J, et al. The American Journal of Gastroenterology. 2023.

3. Hepatitis A. — Langan RC, Goodbred AJ. American Family Physician. 2021.

4. Hepatitis B. — Wen-Juei Jeng, MD, PhD, Terry Cheuk-Fung Yip, PhD, Anna S. Lok, MD JAMA. 2026.

5. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.

6. Viral Hepatitis: Milestones, Unresolved Issues, and Future Goals. — Torre P, Aglitti A, Masarone M, Persico M. World Journal of Gastroenterology. 2021.

7. Hepatitis A. — Megan G. Hofmeister and Mark K. Weng CDC Yellow Book. 2025.

8. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. — Terrault NA, Lok ASF, McMahon BJ, et al. Hepatology. 2018.

9. Acute Type a Hepatitis Presenting With Hypotension, Bradycardia, and Sinus Arrest. — Gordon SC, Patel AS, Veneri RJ, Keskey KA, Korotkin SM. Journal of Medical Virology. 1989.

10. Sexually Transmitted Infections Treatment Guidelines, 2021. — Workowski KA, Bachmann LH, Chan PA, et al. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2021.

11. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. — Kwo PY, Cohen SM, Lim JK. The American Journal of Gastroenterology. 2017.

12. Treatment Options for Hepatitis a and E: A Non-Systematic Review. — Gabrielli F, Alberti F, Russo C, et al. Viruses. 2023.

13. Pharmacological Interventions for Acute Hepatitis B Infection: An Attempted Network Meta-Analysis. — Mantzoukis K, Rodríguez-Perálvarez M, Buzzetti E, et al. The Cochrane Database of Systematic Reviews. 2017.

14. Hepatitis Panel. — National Library of Medicine (MedlinePlus) 2022.

15. Widespread Community Transmission of Hepatitis a Virus Following an Outbreak at a Local Restaurant - Virginia, September 2021-September 2022. — Helmick MJ, Morrow CB, White JH, Bordwine P. MMWR. Morbidity and Mortality Weekly Report. 2023.

16. Hepatitis B. — Jeng WJ, Papatheodoridis GV, Lok ASF. Lancet. 2023.

17. ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. — Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR. The American Journal of Gastroenterology. 2021.

18. A Multicenter Study Into Causes of Severe Acute Liver Injury. — Breu AC, Patwardhan VR, Nayor J, et al. Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association. 2019.

19. AASLD Practice Guidance on Drug, Herbal, and Dietary Supplement-Induced Liver Injury. — Fontana RJ, Liou I, Reuben A, et al. Hepatology. 2023.

20. Drug-Induced Liver Injury — Types and Phenotypes. — Hoofnagle JH, Björnsson ES. The New England Journal of Medicine. 2019.

21. ACR Appropriateness Criteria® Abnormal Liver Function Tests. — Expert Panel on Gastrointestinal Imaging, Arif-Tiwari H, Porter KK, et al. Journal of the American College of Radiology : JACR. 2023.

22. Persistent Fever in Acute Hepatitis: Think Beyond Acute Viral Hepatitis. — Samanta A, Poddar U, Sen Sarma M, et al. Infectious Diseases. 2024.

23. Etiologies and Features of Acute Viral Hepatitis in Spain. — Llaneras J, Riveiro-Barciela M, Rando-Segura A, et al. Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association. 2021.

24. Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause. — Kelgeri C, Couper M, Gupte GL, et al. The New England Journal of Medicine. 2022.

25. Advances in Rapid Nucleic Acid Diagnostics for Hepatitis B and C Viruses: A Comprehensive Review. — Ho HY, Dai CY, Feng IJ, et al. Reviews in Medical Virology. 2026.

26. Acute liver failure. — William M. Lee Yamada's Textbook of Gastroenterology 7e. 2022.

27. Cardiac Autonomic Dysregulation in Patients With Acute Hepatitis. — Chen KY, Chen CL, Yang CC, Kuo TB. The American Journal of the Medical Sciences. 2006.

28. Cardiac Effects of Common Viral Illnesses. — Montague TJ, Marrie TJ, Bewick DJ, et al. Chest. 1988.

29. ECG Findings in Comparison to Cardiovascular MR Imaging in Viral Myocarditis. — Deluigi CC, Ong P, Hill S, et al. International Journal of Cardiology. 2013.

30. Hepatitis B: Part II. Updates on Diagnosis and Therapy. — Moore Ii R, Porter CL, Darling JM. American Family Physician. 2026.