Viral Hepatitis, Acute

Acute viral hepatitis is inflammatory necrosis of the liver caused by 1 of 5 hepatotropic viruses — hepatitis A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV) — present for less than 6 months before either resolving or, for HBV and HCV, persisting into chronic infection. In Canadian practice, hepatitis A, B, and C account for almost every case, and this chapter covers their acute presentation and management: supportive care as the entire treatment for hepatitis A and for most acute hepatitis B, a defined severity threshold that triggers antiviral therapy in the minority of acute hepatitis B cases that need it, and a shift toward starting direct-acting antiviral therapy for acute hepatitis C as soon as the diagnosis is confirmed rather than waiting to see whether the infection clears on its own.^[1] Full direct-acting antiviral regimen selection for chronic hepatitis B and C is covered separately in Viral Hepatitis, Chronic. Two threats define the urgency of this chapter: fulminant hepatic failure — a rare but life-threatening complication of acute hepatitis from any cause that demands immediate transplant-centre referral^[2] — and acetaminophen-induced liver injury, a common and specifically treatable differential diagnosis for which N-acetylcysteine is a genuine antidote.

Typical presentation

Most acute viral hepatitis infections are asymptomatic. When symptoms occur, they look similar regardless of which virus is responsible, so the clinical picture alone cannot identify the causative virus — serologic testing is required (see Assessment & Diagnosis).

• Constitutional symptoms: fever, malaise, fatigue, myalgias, arthralgias, headache.
• Right upper quadrant abdominal pain and tender hepatomegaly.
• Jaundice, dark urine, and clay-coloured (pale) stools.
• Nausea, vomiting, and anorexia.

Laboratory pattern

An acute rise in serum aminotransferases with ALT greater than AST is the hallmark laboratory finding of acute viral hepatitis. Atypical lymphocytosis and an elevated immunoglobulin M (IgM) level may also be present. The degree of aminotransferase elevation does not reliably predict severity — synthetic function (INR, albumin) and bilirubin are what determine severity and urgency (see Red Flags & Refer).

Acute hepatitis C specifically

Acute HCV infection is usually asymptomatic and is typically recognized in 1 of 3 situations: documented seroconversion found on routine or repeat testing, a known parenteral exposure such as a needlestick injury, or, less commonly, acute clinical hepatitis with jaundice. Maintain a high index of suspicion after a known exposure — waiting for symptoms will miss most cases.

• Injection or non-injection illicit drug use, including shared drug-preparation equipment.
• High-risk sexual behaviour, multiple partners, or a partner with known viral hepatitis — particularly relevant for HBV; sexual transmission of HCV is uncommon outside of HIV co-infection or condomless anal intercourse.
• Travel to, or residence in, a region with endemic hepatitis A or E, or ingestion of potentially contaminated food or water.
• Eating undercooked pork, deer, or wild boar meat — hepatitis E is a zoonotic infection in high-income countries such as Canada.
• Household, daycare, or other close personal contact with a confirmed or suspected hepatitis A case.
• Occupational or household blood/body-fluid exposure, including a needlestick or other sharps injury.
• Receipt of blood products, hemodialysis, or a solid organ/stem cell transplant.
• Birth to a parent with chronic HBV infection, or birth in a region with high HBV/HCV endemicity.
• Men who have sex with men.
• Current or previous incarceration in a correctional facility.
• Pre-existing chronic liver disease of any cause, which increases the severity of a superimposed acute viral hepatitis.
• Immunocompromising conditions, which increase the risk of a complicated or prolonged course and, uniquely for hepatitis E, of chronic infection.

Differentiating the hepatitis viruses

Differential diagnosis — rule out non-viral causes

Consider these alongside, or instead of, viral hepatitis, especially when the presentation is severe or the serologic panel is negative:

• Drug-induced liver injury (DILI) — acetaminophen (paracetamol) overdose is the single most important cause to identify, since it has a specific antidote (N-acetylcysteine). Also review any other hepatotoxic drug started or increased recently.
• Herbal or natural health products with reported hepatotoxicity — buckthorn, chaparral, comfrey, germander, nutmeg, and valerian are specifically implicated.
• Autoimmune hepatitis — can present acutely and mimic viral hepatitis, particularly in children and young adults.
• Wilson disease — consider especially in children and young adults; can present as acute or fulminant hepatitis.
• Acute cholestatic (obstructive) injury — e.g., bile duct obstruction from gallstones.
• Vascular pathology — e.g., Budd-Chiari syndrome (hepatic venous outflow obstruction).

An abdominal Doppler ultrasound helps distinguish cholestatic obstruction and vascular causes from hepatocellular viral injury.

History

• Ask specifically about injection drug use, high-risk sexual behaviour, travel history, and daycare or household exposure.
• Review every medication, supplement, and herbal/natural health product taken in the preceding weeks, and characterize any acetaminophen exposure (dose, duration, and timing).
• Ask about alcohol use.

Initial and confirmatory investigations

• Liver aminotransferases (ALT, AST) to confirm hepatocellular injury.
• Liver synthetic function — total and direct bilirubin, serum albumin, and INR. Any elevation in INR or bilirubin warrants urgent hepatology referral, not routine outpatient follow-up.
• Abdominal Doppler ultrasound when cholestatic obstruction or vascular pathology is suspected.
• Acetaminophen level, plotted against a validated nomogram when the ingestion time is known, whenever acetaminophen exposure is a possibility.

Serologic diagnosis

In immunocompromised patients with suspected HEV, combine serology with HEV RNA testing, since the antibody response can be blunted or delayed. Screen high-risk individuals for HCV annually with anti-HCV; anyone previously treated or who spontaneously cleared a prior infection needs HCV RNA rather than anti-HCV for re-screening, since anti-HCV remains positive for life.

• Prevent transmission to others during the infectious period.
• Limit hepatocellular injury and support recovery of liver function.
• Identify and treat a specifically treatable cause promptly — most importantly, start N-acetylcysteine without delay for acetaminophen-induced injury.
• Recognize fulminant hepatic failure early and arrange transplant-centre referral before deterioration becomes irreversible.
• Start antiviral therapy for the subset of acute hepatitis B that meets severity criteria, to prevent death and reduce the chance of needing transplantation.
• Start direct-acting antiviral therapy for confirmed acute hepatitis C as soon as the diagnosis is confirmed, to prevent progression to chronic infection.
• Complete post-exposure prophylaxis for hepatitis A and B contacts within the window where it remains effective.
• Support symptom control and quality of life through recovery.

• Avoid alcohol completely until full clinical and biochemical recovery (aminotransferases normalized).
• Stop all non-essential hepatotoxic medications for the duration of acute hepatitis, and specifically ask about — and stop — hepatotoxic herbal or natural health products: buckthorn, chaparral, comfrey, germander, nutmeg, and valerian have all been implicated.
• No dietary restriction is required, and there is no role for vitamin supplementation.
• No restriction of physical activity is needed — let fatigue guide activity rather than imposing bed rest.
• Counsel on transmission-prevention measures appropriate to the virus: strict hand hygiene and safe food/water handling for hepatitis A and E; safer-sex practices and avoiding shared injection or personal-care equipment (razors, toothbrushes) for hepatitis B and C.
• Identify household, sexual, and other close contacts and offer them testing and/or post-exposure prophylaxis as appropriate to the virus (see Choose Initial Treatment).

Pregnancy — hepatitis A

Acute hepatitis A in pregnancy is uncommon. No birth defects have been reported. Management is the same as in non-pregnant patients — supportive care — though clinicians should counsel about an increased risk of miscarriage or preterm labour. Breastfeeding can continue.

Pregnancy — hepatitis B

Acute hepatitis B is not teratogenic and is managed the same as in non-pregnant patients — supportive care unless the severity criteria above are met, in which case tenofovir disoproxil fumarate is the preferred antiviral given the most pregnancy safety experience; avoid entecavir in pregnancy. Hospitalize if there is coagulopathy, encephalopathy, or severe debilitation. Antenatal antiviral prophylaxis to reduce vertical transmission in a pregnant patient with chronic HBV and a high viral load is a distinct, chronic-HBV-specific intervention covered in Viral Hepatitis, Chronic — it does not apply to true acute infection. Every infant born to an HBsAg-positive parent still needs HBIG plus vaccine within 12 hours of birth, regardless of any antenatal antiviral therapy the parent received.

Pregnancy — hepatitis C

Universal hepatitis C screening — anti-HCV, with reflex or follow-up HCV RNA if positive — is now recommended in every pregnancy, in the first trimester or at the first antenatal visit, replacing the older approach of testing only patients with identified risk factors.^[8] Vertical transmission is not reduced by mode of delivery (vaginal vs. cesarean). Antiviral treatment is generally deferred to the postpartum period; patients of childbearing age with known HCV who are planning a pregnancy should be treated beforehand when feasible.

Breastfeeding

Hepatitis A: continue breastfeeding. Hepatitis B: not contraindicated once the infant has received birth-dose HBIG and vaccine; breastfeeding can continue even during maternal antiviral therapy, and should only be paused if the nipples are cracked or bleeding, resuming once healed. Hepatitis C: not shown to transmit through breastfeeding; pause only for cracked or bleeding nipples until healed.

Pediatrics

Hepatitis A in young children is frequently mild or asymptomatic but still infectious, which matters for daycare/household transmission control. Vaccine dosing is age- and product-specific (see Drug Tables). Pediatric antiviral therapy for acute hepatitis B meeting severity criteria should be directed by a pediatric hepatologist, since dosing and safety data are less established than in adults.

Renal impairment

Tenofovir disoproxil fumarate, tenofovir alafenamide, and entecavir all require dose or interval adjustment in renal impairment — confirm current renal dosing before prescribing. Hepatitis B vaccine dosing is unaffected by renal function except in dialysis patients, who need a higher-antigen formulation and annual anti-HBs titre monitoring with booster doses as needed.

Immunocompromised patients

Hepatitis E can become chronic in immunocompromised patients — use combined serology and HEV RNA testing, and involve hepatology. Vaccine responses to hepatitis A and B are often blunted; consider a higher-antigen formulation, an extra dose, or confirmatory anti-HBs titre testing after the series.

• Repeat ALT, AST, total and direct bilirubin, albumin, and INR at intervals guided by initial severity — more frequently (e.g., every 1-3 days) if any value is trending toward the red-flag thresholds, less frequently once clearly improving.
• For acute hepatitis B, retest HBsAg (and anti-HBs) at 6 months; persistence beyond 6-12 months means the infection has become chronic and management should transition to the chronic hepatitis B pathway.
• For acute hepatitis C, confirm a negative HCV RNA with a repeat test before concluding spontaneous clearance in the rare untreated patient; for patients treated with direct-acting antivirals, follow the same on-treatment and post-treatment (sustained virologic response) monitoring used for chronic hepatitis C.
• Confirm completion of the full vaccine series (and, where indicated, HBIG) in every post-exposure prophylaxis patient, and confirm household/sexual contacts have themselves been tested and offered prophylaxis.
• Check anti-HBs titre 1-2 months after completing the hepatitis B vaccine series in health care workers, dialysis patients, and other patients where confirming a protective response changes management.
• For acetaminophen-induced injury, continue N-acetylcysteine and monitoring until acetaminophen is undetectable, INR is below 2, and ALT/AST are normal or clearly improving from peak.
• Reinforce alcohol avoidance and hepatotoxic-drug avoidance at every follow-up until aminotransferases have normalized.

1. Acute hepatitis B with HBsAg still positive after 6-12 months — this is now chronic infection; transition management to the chronic hepatitis B pathway (see Viral Hepatitis, Chronic) rather than continuing to manage it as acute.
2. Acute hepatitis C with a confirmed positive repeat HCV RNA — proceed to direct-acting antiviral therapy using standard chronic-HCV dosing without further delay, rather than continuing to await spontaneous clearance.^[1]
3. Worsening INR, bilirubin, or new encephalopathy at any point during outpatient monitoring — escalate immediately to urgent hepatology assessment and transplant-centre referral rather than continuing outpatient follow-up.
4. No anti-HBs response after a completed hepatitis A or B vaccine series — revaccinate with a single booster dose, a complete repeat series, or a higher-antigen formulation depending on the clinical context, and consider testing for undiagnosed immunocompromise if nonresponse persists.
5. Rising transaminases or worsening synthetic function despite N-acetylcysteine for acetaminophen-induced injury — continue or extend the infusion beyond the standard protocol and escalate to a transplant centre rather than stopping at the protocol's scheduled end time.^[2]

• Waiting for a fully elevated transaminase level to "confirm" acetaminophen toxicity before starting N-acetylcysteine — start based on ingestion history and nomogram threshold; do not wait for liver injury to become biochemically obvious.
• Starting peginterferon-alfa for acute hepatitis B — it is contraindicated in this setting.
• Treating every case of acute hepatitis B with antivirals by default — most immunocompetent adults clear the infection spontaneously and need monitoring only; reserve antivirals for the defined severity criteria.
• Waiting for spontaneous clearance before treating confirmed acute hepatitis C — current guidance is to treat immediately upon diagnosis.
• Using an abbreviated/shortened direct-acting antiviral course for acute hepatitis C — this produces inferior response rates; use the same standard-duration regimen used for chronic infection.
• Concluding that a single negative HCV RNA test proves viral clearance in a patient with acute hepatitis C — repeat the test before concluding clearance.
• Giving hepatitis B immune globulin for a routine community-acquired needlestick injury with an unknown source — this is not an indication; reserve HBIG for the defined higher-risk exposures.
• Delaying the first hepatitis B vaccine dose while awaiting the exposed person's serology results — a first dose can be given while results are pending.
• Treating a persistently elevated INR with vitamin K alone and assuming this has "fixed" the coagulopathy — an INR that fails to correct with vitamin K reflects true synthetic liver failure and is a red flag for urgent referral, not a dosing problem.
• Missing drug-induced liver injury, autoimmune hepatitis, Wilson disease, cholestatic obstruction, or vascular pathology as the actual cause in a patient assumed to have viral hepatitis.
• Allowing a patient with acute hepatitis to continue a hepatotoxic medication or herbal product because it is "not contraindicated" — stop all non-essential hepatotoxic agents for the duration of the acute illness.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Antidote for acetaminophen-induced liver injury

Coagulopathy management

Antiviral therapy for acute hepatitis B meeting severity criteria

Reserved for acute liver failure or a protracted, severe course — total bilirubin >3 mg/dL (51 micromol/L) or direct bilirubin >1.5 mg/dL (26 micromol/L), INR >1.5, encephalopathy, or ascites. Peginterferon-alfa is contraindicated in acute hepatitis B.

Hepatitis A immunizing agents

Hepatitis B immunizing agents

Combined vaccine

Hepatitis E — severe or neurologic disease