What is the appropriate diagnostic work‑up and management plan for a patient presenting with acute hepatitis, including evaluation of viral and toxic etiologies, severity assessment, and treatment recommendations?

Acute Hepatitis: Diagnostic Work-Up and Management

Immediate Risk Stratification

The first priority is to identify acute liver failure by checking prothrombin time/INR and mental status—if INR ≥1.5 with any mental status change, immediately transfer to ICU and contact a liver transplant center. 1, 2

• Acute liver failure is defined as coagulopathy (INR ≥1.5) plus any degree of mental alteration in a patient without preexisting cirrhosis 1
• This represents a medical emergency with potential progression to cerebral edema and multiorgan failure within days 3
• Do not delay transfer to a transplant center while awaiting complete laboratory results 1, 3

Essential Diagnostic Laboratory Work-Up

Initial Core Panel

• Prothrombin time/INR – the single most critical test; INR ≥1.5 defines coagulopathy requiring urgent action 1, 3
• Hepatic panel (AST, ALT, alkaline phosphatase, GGT, total and conjugated bilirubin, albumin) 1, 3
• Complete blood count with platelets – essential for detecting hemolytic anemia (Wilson disease) and bleeding risk 3
• Comprehensive metabolic panel including electrolytes, glucose, creatinine, BUN 1, 3
• Arterial blood gas and lactate – rising lactate predicts poor prognosis 3
• Arterial ammonia level – correlates with encephalopathy severity 3

Etiologic Work-Up

• Viral hepatitis serologies: anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV, HCV RNA if acute HCV suspected 1, 3
• Acetaminophen level – mandatory in every case as acetaminophen is the leading cause of acute liver failure in North America and Europe 1, 3
• Comprehensive toxicology screen 1, 3
• Autoimmune markers (ANA, anti-smooth muscle antibody, immunoglobulin levels) – but note that ANA is absent in 29-39% of acute severe autoimmune hepatitis cases and IgG is normal in 25-39%, so negative results do not exclude the diagnosis 3
• Ceruloplasmin and 24-hour urinary copper in patients <40 years to screen for Wilson disease 3
• Pregnancy test in all females of childbearing age 1, 3

Detailed Medication History

• Obtain comprehensive history of all prescription drugs, over-the-counter medications, herbal supplements, and dietary products taken over the past year 1, 2
• Determine ingredients of non-prescription medications whenever possible 1

Etiology-Specific Management

Acute Viral Hepatitis A and E

Provide supportive care only—no antiviral therapy has proven effective, and over 95% of immunocompetent patients recover spontaneously. 1, 2, 4

• Mandate complete abstinence from alcohol and avoidance of all hepatotoxic medications, particularly acetaminophen 1, 2
• Monitor hepatic panels (ALT, AST, bilirubin, INR) every 2-4 weeks until resolution 1, 2
• Watch for signs of progression: rising bilirubin, prolonging INR, mental status changes 1, 2
• Approximately 10-15% may experience relapsing illness within the first 6 months 1

Acute Hepatitis B

For uncomplicated acute hepatitis B, do not initiate antiviral therapy—treatment may interfere with protective immunity, and over 95% of adults clear infection spontaneously. 1, 2

• However, initiate oral nucleoside analogs (entecavir or tenofovir preferred) if persistent severe hepatitis or acute liver failure develops 1
• Provide supportive care and monitor as with hepatitis A 1

Acute Hepatitis C

Initiate direct-acting antiviral (DAA) therapy immediately upon diagnosis with detectable HCV RNA—do not wait for spontaneous clearance. 1, 2

• Use the same DAA regimens recommended for chronic HCV infection 1, 2
• This approach reduces HCV transmission and prevents loss to follow-up 1
• Counsel patients to avoid sharing injection equipment and consider barrier precautions during sex, even in monogamous relationships during the acute phase 1, 2
• Refer patients with injection drug use history to addiction medicine specialists 1, 2

Herpes Simplex Virus Hepatitis

Initiate acyclovir treatment immediately in suspected cases—HSV hepatitis has a lethality rate of approximately 75% without treatment. 1, 5

• HSV hepatitis typically presents as anicteric hepatitis and accounts for only 1% of acute liver failure cases 5
• Because of low incidence and lack of dermal manifestations, begin empiric acyclovir in any acute liver failure of unknown origin 1, 5
• List for transplantation as this is often the only lifesaving option 1
• Pregnancy (especially third trimester) increases risk of HSV-induced acute liver failure 1

Autoimmune Hepatitis

Treat with corticosteroids (prednisone 40-60 mg/day) and list for transplantation if severe. 1

• Consider liver biopsy to establish diagnosis when suspected 1
• Do not delay corticosteroid treatment while awaiting biopsy or antibody results 1, 3
• Remember that negative ANA or normal IgG does not exclude the diagnosis 3

Drug-Induced Hepatotoxicity

Discontinue all non-essential medications immediately. 1, 2

• Determine ingredients of all non-prescription medications 1
• Provide supportive care and monitor closely 1

Wilson Disease (patients <40 years)

• Consider liver transplantation urgently 1
• Use albumin dialysis, continuous hemofiltration, or plasma exchange to lower serum copper 1
• Characteristic pattern: Coombs-negative hemolytic anemia, modest aminotransferase elevations (<2,000 IU/L), markedly low alkaline phosphatase (<40 IU/L), and alkaline phosphatase-to-bilirubin ratio <2 3

Mushroom Poisoning

• Administer penicillin G and silymarin (30-40 mg/kg/day for 3-4 days) 1
• List for transplantation as this is often the only lifesaving option 1

Management of Acute Liver Failure

Immediate Actions

• Transfer to ICU immediately 1, 3, 2
• Contact liver transplant center without delay—fulminant hepatic failure patients receive status 1 priority for deceased-donor organs 3
• Administer N-acetylcysteine regardless of suspected etiology 1, 2

Neurologic Management

• Monitor encephalopathy frequently and maintain serum sodium between 140-145 mmol/L to reduce cerebral edema risk 1, 3
• Perform tracheal intubation and sedation when Glasgow Coma Scale falls below 8 1, 3
• Avoid benzodiazepines and other psychotropic agents (e.g., metoclopramide) as they aggravate encephalopathy 1, 3

Hemodynamic and Respiratory Support

• Evaluate volume status, cardiac output, and ventricular function 3
• Use crystalloid solutions as first-line fluid; norepinephrine for refractory hypotension 3
• Apply lung-protective ventilation; avoid high PEEP (>10 cm H₂O) to prevent hepatic congestion 3

Coagulation Management

Do not routinely correct coagulopathy with fresh frozen plasma or clotting factors unless active bleeding is present—this obscures disease monitoring. 1, 3

• Bleeding complications occur in approximately 10% of patients, most commonly from upper GI tract 3

Infection Management

• Initiate empiric broad-spectrum antibiotics in patients with worsening encephalopathy or signs of systemic inflammatory response syndrome 1, 3
• Infection markedly worsens prognosis 3

Renal Support

• Follow acute kidney injury guidelines; continuous dialysis modalities are preferred 3
• Avoid nephrotoxic agents including NSAIDs 1, 3

Monitoring Parameters

• Check arterial lactate, arterial ammonia, and bedside blood glucose at least every 2 hours 3
• Monitor hepatic panels frequently 1, 2

Special Populations

Pregnant Patients

• For acute fatty liver of pregnancy or HELLP syndrome, consult obstetrical services and expedite delivery 1, 2
• Pregnancy increases risk of severe hepatitis E and HSV hepatitis 1, 2
• For acute hepatitis A: routine cesarean delivery is not recommended unless obstetric indication exists; breastfeeding should be encouraged; neonatal immunization is not routinely advised 2

Active Substance Users

• Treatment decisions should be made on an individual basis with addiction specialists 1
• Patients on stable maintenance substitution therapy can be safely treated with only slightly reduced response rates 1

Post-Exposure Prophylaxis for Hepatitis A Contacts

• Administer hepatitis A immune globulin (IG) to unvaccinated contacts within 14 days of exposure—provides >85% protection 1
• Target household members, co-habitants, sexual partners, and persons with ongoing close personal contact 1
• Do not delay IG administration while awaiting anti-HAV testing 1

Critical Pitfalls to Avoid

• Delaying transfer to a transplant center for patients with acute liver failure 1, 3
• Failing to identify specific etiologies that might influence treatment 1
• Using benzodiazepines for sedation in patients with liver failure 1, 3
• Administering nephrotoxic agents 1, 3
• Routinely correcting coagulation abnormalities without active bleeding 1, 3
• Delaying corticosteroid treatment in suspected autoimmune hepatitis 1
• Waiting for spontaneous clearance in acute hepatitis C—treat immediately 1, 2
• Using acetaminophen or alcohol during acute hepatitis 1, 2
• Relying on negative ANA or normal IgG to rule out autoimmune hepatitis 3
• Underestimating severity based on modest aminotransferase elevations, especially in Wilson disease 3

Prognostic Indicators

Poor Prognosis

• Age >50 years 3
• Idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, or indeterminate cause 1
• Persistent arterial lactate elevation 3
• Factor V level <50% 3
• Underlying chronic liver disease (hepatitis B or C) 3

Good Prognosis

• Post-transplant survival rates for acute liver failure are 80-90% 1, 3
• Spontaneous recovery occurs in approximately 30-60% of fulminant hepatitis A cases 3