Viral hepatitis Part 1: Understanding the Acute Inflammatory Liver Response 🦠

 Acute viral hepatitis refers to sudden-onset liver inflammation caused by one of the hepatitis viruses — most commonly Hepatitis A, B, C, D, or E. Each virus has distinct routes of transmission, clinical behaviour, and implications for public health — but they share overlapping patterns of hepatic injury.

In this post, we will explore:

• The pathophysiology of acute hepatitis
• Key clinical features
• Differences between the hepatitis viruses
• Diagnostic approach and natural history

There will be further posts to follow this regarding chronic hepatitis and on interpreting Hepatitis B serology - watch this space!

🦠 Acute Viral Hepatitis: A Detailed Look at the Viruses

Acute viral hepatitis is an inflammatory liver response triggered by a viral infection. In this post, we’ll break down what happens with each virus—from its transmission route and clinical picture to its pathophysiological mechanisms. Then, we’ll cap it off with a summary table for quick reference.

Hepatitis A

Transmission:

Spread via the faecal-oral route, commonly through contaminated food or water. Outbreaks are often linked to food handling in endemic areas, making it particularly relevant for travellers.

Incubation Period & Clinical Course:

Incubation usually ranges from 15 to 50 days. Hepatitis A tends to cause an acute, self-limiting illness.

• Symptoms: Fatigue, nausea, poor appetite, and sometimes diarrhoea.
• Jaundice: Gradually sets in, along with dark urine and pale stools.
• Lab Findings: Very high transaminases (ALT often > AST), reflecting significant hepatocyte injury.

Pathophysiology:

Once ingested, the virus enters the portal circulation and infects hepatocytes. The immune system, particularly through activated cytotoxic T cells and NK cells, rapidly clears the virus, which is why chronic infection does not occur.

Hepatitis B

Transmission:

Transmitted via blood and bodily fluids. Routes include sexual contact, percutaneous exposures (such as needlestick injuries), and perinatal transmission.

Incubation Period & Clinical Course:

The incubation period generally ranges from 45 to 180 days.

• Symptoms: Can be varied—from asymptomatic to severe acute illness with jaundice and RUQ pain.
• Lab Findings: Elevated ALT and AST; may also see high levels of bilirubin.
• Unique Aspects: Some cases can progress to fulminant hepatitis, and a fraction of adults (approximately 5–10%) may develop chronic infection.

Pathophysiology:

Hepatitis B infects hepatocytes and begins replicating while evading the innate immune response. The adaptive immune system, upon activation, leads to cytotoxic destruction of infected hepatocytes. The virus may integrate into the host genome, contributing to chronicity and long-term complications if not cleared.

Hepatitis C

Transmission:

Primarily spread through blood. High-risk groups include people who inject drugs (IVDU) and recipients of blood transfusions (especially before widespread screening).

Incubation Period & Clinical Course:

Incubation period ranges from 2 weeks to 6 months. While most acute HCV infections are subclinical or mildly symptomatic, about 75–85% of cases progress to chronic infection.

• Symptoms: Often subtle, but when present, may include fatigue and malaise.
• Lab Findings: Elevation in ALT/AST is usually observed; the virus is typically detected via anti-HCV antibodies and confirmed by HCV RNA levels.

Pathophysiology:

Hepatitis C is adept at evading the immune system through rapid mutation. The virus establishes persistence by impairing the host’s cellular immune response. Over time, chronic inflammation can lead to progressive liver fibrosis, cirrhosis, and an increased risk of hepatocellular carcinoma.

Hepatitis D

Transmission:

Hepatitis D virus (HDV) is a defective RNA virus that requires the presence of hepatitis B virus (HBV) for its replication. It is transmitted similarly to HBV—via blood and bodily fluids.

Incubation Period & Clinical Course:

The clinical course is generally more severe than HBV alone, particularly in cases of co-infection or superinfection.

• Symptoms: Patients often present with rapid onset of severe hepatitis, and the condition can quickly progress to fulminant hepatitis, especially in cases of superinfection in an HBV carrier.
• Lab Findings: Markedly elevated liver enzymes and features of acute liver failure may be seen.

Pathophysiology:

HDV invades hepatocytes only in the presence of HBV. 

It exacerbates liver inflammation through its own replication, leading to more aggressive hepatocyte destruction. This synergistic effect increases the risk of chronic liver disease and fulminant hepatitis.

Hepatitis E

Transmission:

Similar to Hep A, Hepatitis E is primarily transmitted via the faecal-oral route, usually from contaminated water or food. It is especially prevalent in regions with poor sanitation.

Incubation Period & Clinical Course:

The incubation period is typically 2 to 8 weeks.

• Symptoms: In most healthy adults, hepatitis E causes an acute self-limiting illness with symptoms similar to hepatitis A. Diarrhea can be common.
• Unique Consideration: In pregnant women, particularly in endemic regions, hepatitis E is associated with high maternal and foetal mortality.

Pathophysiology:

After ingestion, the virus infects hepatocytes and triggers a robust immune response. The viral clearance is usually effective, except in immunocompromised individuals or pregnant women, where the altered immune state can lead to severe outcomes.

Summary table: a quick comparison

Feature	Hep A	Hep B	Hep C	Hep D	Hep E
Virus Type	RNA	DNA	RNA	Defective RNA	RNA
Transmission	Faecal-oral (contaminated food/water)	Blood, bodily fluids (sexual, perinatal, percutaneous)	Blood (IVDU, transfusions)	Requires HBV co-infection; same as HBV route	Faecal-oral (often waterborne, contaminated food)
Incubation Period	15–50 days	45–180 days	2 weeks–6 months	Similar to HBV; often more severe	2–8 weeks
Acute vs. Chronic	Acute only	Mostly acute; 5–10% progress to chronic in adults	Frequently subclinical; 75–85% become chronic	Co-infection or superinfection with HBV; may lead to severe acute liver failure	Acute only (except in immunosuppressed)
Vaccine Availability	Yes	Yes	No	Indirect (preventable with HBV vaccination)	No (in Australia)
High risk groups	Travel, food	Health workers, MSM	IVDU, transfusion	HBV carriers	Pregnant women, travellers

🧬 What Happens in Acute Hepatitis? The Pathophysiology

Hepatitis viruses invade hepatocytes, triggering an immune-mediated inflammatory response that dictates both clinical symptoms and liver dysfunction.

🔬 Step-by-Step Breakdown of Hepatic Injury

1️⃣ Viral Entry & Replication

• HAV & HEV → Directly cytopathic (infect hepatocytes and trigger immune clearance).

• HBV, HCV, HDV → Evade early immune response, integrating into liver cells.

2️⃣ Innate Immune Response (First Defenders)

• NK cells & macrophages detect infected hepatocytes, initiating inflammatory cytokine release.

• Interferons suppress viral replication temporarily.

3️⃣ Adaptive Immune Response (Main Hepatocyte Destruction)

• CD8+ T cells attack infected hepatocytes, causing apoptosis & necrosis.

• Hepatocyte destruction releases intracellular enzymes (ALT > AST) into circulation.

4️⃣ Cholestasis & Jaundice

• Inflammation obstructs bile flow, leading to bilirubin accumulation → jaundice, dark urine, pale stools.

5️⃣ Resolution vs. Progression to Chronicity

• HAV & HEV → Cleared entirely; NO chronic infection.

• HBV & HCV → Risk of persistent infection due to immune evasion & viral integration.

⚠️ Clinical Features of Acute Hepatitis

Feature	Typical Presentation
Prodrome	Fatigue, nausea, anorexia, myalgia
Icteric Phase	Jaundice, dark urine, pale stools, RUQ pain
Systemic Signs	Low-grade fever, hepatomegaly, tender liver
Lab Findings	↑ ALT/AST (often >10× normal), ↑ bilirubin
Recovery Phase	Gradual symptom resolution over weeks

🚨 Red Flag: Fulminant Hepatitis (Acute Liver Failure)

• Hepatic encephalopathy (confusion, asterixis).
• Coagulopathy (elevated INR, spontaneous bleeding).
• Severe jaundice & rapid clinical deterioration.
• More common in HBV, HDV, or HEV in pregnancy.

🧪 Diagnostic Approach: How to Confirm the Cause?

Step 1: Laboratory Testing (Core Workup)

• Liver Function Tests (LFTs) → ALT > AST, bilirubin, ALP elevation (cholestasis).

• Coagulation Profile → Elevated INR in severe cases (liver dysfunction).

Step 2: Viral Serology & Molecular Testing

Virus	Key Tests
HAV	Anti-HAV IgM (acute infection)
HBV	HBsAg, anti-HBc IgM, HBeAg (active replication)
HCV	Anti-HCV antibodies, HCV RNA (confirm ongoing infection)
HDV	Anti-HDV, HDV RNA (only test if HBsAg positive)
HEV	Anti-HEV IgM (PCR in immunosuppressed)

🩺 Management Principles: What to Do Clinically?

✅ Supportive Care:

• Hydration, rest, nutrition, monitoring liver function.
• Avoid alcohol & hepatotoxic drugs.

✅ Monitor for Complications:

• Fulminant liver failure: Evaluate INR, encephalopathy, aggressive supportive care.
• Prolonged jaundice: Consider underlying cholestatic hepatitis.

✅ Public Health Considerations:

• Hepatitis A: Is an "urgent" notifiable condition, meaning it must be notified immediately, usually by phone, upon initial diagnosis. 
• All other viral hepatitis also notifiable, and reporting may occur through fax or online platforms, depending on the specific state or territory guidelines. 
• National Notifiable Diseases Surveillance System (NNDSS)
  

✅ Antivirals:

• Acute HBV → Consider treatment in severe cases.
• HCV → Not treated acutely, but chronic direct-acting antivirals (DAAs) are curative.

🧠 Special Situations

• Pregnancy: Hepatitis E has high maternal and fetal mortality. Avoid exposure in endemic regions.
• Superinfection with Hepatitis D: In HBV carriers, HDV can precipitate severe acute or fulminant hepatitis.
• Hepatitis C: While usually mild, 75–85% of cases become chronic. Direct-acting antivirals are curative in chronic disease

📉 Natural History: Does Acute Hepatitis Always Resolve?

Outcome	Typical Course
Complete Recovery	90–95% (especially HAV, HEV)
Chronic Infection	Common in HCV, some HBV cases
Fulminant Hepatitis	Rare (<1%) but critical to detect
Carrier State	HBV (e.g., perinatal transmission cases)

More on this topic in the next blog post! 

🧠 Case-Based Learning: Applying Concepts in Clinical Scenarios

 Case 1:  

Patient:

Alex, a 23-year-old university student who recently returned from a backpacking trip across Southeast Asia.

History of Present Illness:

Alex presents to the emergency department 10 days after returning to Australia with a 5-day history of increasing fatigue, nausea, and loss of appetite. Over the past 48 hours, he has noticed a yellowish discoloration of his skin and eyes, accompanied by dark urine and pale, clay-coloured stools. He denies any abdominal pain besides a vague discomfort in the right upper quadrant. Alex also reports mild fever and chills at the start of his symptoms. He recalls eating at several local street food vendors during his travels, although he did not note any overt gastrointestinal illness at the time.

Past Medical History:

No significant past medical history; no known drug allergies. Up-to-date with childhood immunisations, but he did not receive a Hepatitis A vaccine prior to his travel.

Social History:

• Recently returned from travel in Southeast Asia.
• Social alcohol consumption on weekends; no regular medications. No IVDU

Examination Findings

General:

• Alex appears slightly jaundiced, with noticeable yellowing of the sclera.

Vital Signs:

• Temperature: 37.8°C (Normal: 36.5–37.5°C)
• Heart Rate: 88 beats per minute (Normal: 60–100 bpm)
• Blood Pressure: 118/76 mmHg (Within normal ranges)
• Respiratory Rate: 16 breaths per minute (Normal: 12–20 breaths/min)
• Saturation: 98% on room air

Abdominal Examination:

• Mild tenderness in the right upper quadrant with a palpable, slightly enlarged liver (hepatomegaly).
• No rebound tenderness, guarding, or signs of ascites.

Other Systems:

• Cardiovascular and respiratory examinations are unremarkable

Laboratory Investigations

Test	Result	Normal Range
White Cell Count	6.8 x 10⁹/L	4.0 – 11.0 x 10⁹/L
Haemoglobin	14.0 g/dL	13.5 – 17.5 g/dL
Platelets	240 x 10⁹/L	150 – 400 x 10⁹/L
ALT	980 U/L	< 40 U/L
AST	720 U/L	< 40 U/L
Bilirubin (Total)	65 µmol/L	< 20 µmol/L
ALP	180 U/L	30 – 130 U/L
GGT	75 U/L	10 – 71 U/L
INR	1.1	0.8 – 1.2

Viral Serology:

• Anti-HAV IgM: Positive (indicative of recent acute Hepatitis A infection)
• HAV RNA (if available): Positive (confirmatory in some cases

Management Plan

1. Supportive Care:

• Advise rest, adequate hydration, and a balanced diet.
• Recommend avoiding alcohol and unnecessary medications that could further injure the liver.

2. Monitoring:

• Serial liver function tests to track improvement or detect any worsening.
• Observe for signs of acute liver failure (e.g., deteriorating mental state, worsening coagulopathy).

3. Infection Control & Public Health:

• Advise Alex on the importance of hand hygiene and isolation (when needed) to prevent viral spread.
• Notify public health authorities as Hepatitis A is a notifiable disease in Australia
• Provide education on preventing future exposure, especially prior to travel.

4. Follow-Up:

• Schedule a follow-up appointment within 1–2 weeks to review clinical progress and laboratory trends.
• Provide information on vaccination for Hepatitis A for future travel.

Summary

This case of Alex, a young traveller with acute hepatitis A, illustrates a typical presentation with prodromal symptoms, jaundice, and significant transaminase elevation. The clinical picture, combined with a positive anti-HAV IgM test, confirms the diagnosis. Supportive management, public health notification, and careful follow-up are key in managing such acute viral hepatitis cases

Case 2:

Patient:

Jordan, a 30-year-old registered nurse working in a busy hospital unit.

History of Present Illness:

Jordan presents with a 7-day history of increasing fatigue, right upper quadrant (RUQ) abdominal pain, and low-grade fever. Two weeks ago, while on duty, Jordan experienced a needlestick injury while handling a patient known to be HBV-positive. Despite the hospital protocol, he did not notify anyone at the time. Although initially asymptomatic, the nurse began noticing malaise and mild nausea a few days later, which progressed to the current symptoms including mild jaundice and discomfort in the upper right abdomen.

Past Medical History:

• No significant past illnesses.
• Up-to-date with immunizations, including routine childhood vaccines.
• Uncertain HBV vaccination status; last documented HBV vaccine was over a decade ago.

Social History:

• Non-smoker, minimal alcohol use, no IVDU
• Works in the healthcare setting with regular potential exposures.

Examination Findings

General Appearance:

• Jordan appears alert but slightly fatigued; mild jaundice is noted in the sclera.

Vital Signs:

• Temperature: 38.0°C
• Heart Rate: 90 beats per minute
• Blood Pressure: 120/78 mmHg
• Respiratory Rate: 16 breaths per minute
• Oxygen Saturation: 99% on room air

Abdominal Examination:

• Mild tenderness on palpation of the RUQ without guarding or rebound tenderness.
• A slightly enlarged, tender liver is palpable on deep inspiration.

Other Systems:

• Cardiovascular and respiratory exams are within normal limits.

Laboratory Investigations

 

Test	Result	Normal Range
White Cell Count	7.2 x 10⁹/L	4.0 – 11.0 x 10⁹/L
Haemoglobin	13.8 g/dL	13.5 – 17.5 g/dL
Platelets	230 x 10⁹/L	150 – 400 x 10⁹/L
ALT	550 U/L	< 40 U/L
AST	470 U/L	< 40 U/L
Total Bilirubin	40 µmol/L	< 20 µmol/L
ALP	150 U/L	30 – 130 U/L
HBsAg	Positive	Negative
Anti-HBc IgM	Positive	Negative
HBeAg	Positive	Negative
HBV DNA (viral load)	> 10^7 IU/mL (High level)	Undetectable / Low level
INR	1.1	0.8 – 1.2

Don't worry, we will do a whole post on Hep B serology - its not as tricky as it looks !

Management Plan

1. Monitoring & Evaluation:

• Observation: In acute HBV, many patients will clear the virus spontaneously.
• Serial Testing: Regular monitoring of liver function tests (LFTs) and HBV serology (including HBV DNA) to assess for viral clearance versus progression to chronic infection.
• Clinical Assessment: Monitor for any signs of deterioration, such as worsening jaundice, coagulopathy, or hepatic encephalopathy.

2. Treatment Considerations:

• Antivirals: HBV antiviral therapy is not routinely initiated in uncomplicated acute hep B.
• Initiation of antiviral medication (e.g., entecavir or tenofovir) is reserved for cases where there are signs of severe hepatic injury or fulminant hepatitis.
• Supportive Care:
• Encourage rest, adequate hydration, and a balanced diet.
• Advise avoidance of alcohol and hepatotoxic medications.

3. Infection Control & Occupational Health:

• Exposure Protocol: The needlestick injury must be documented and reported through occupational health channels.
• Post-Exposure Prophylaxis (PEP): Although Jordan has developed acute hepatitis, this case highlights the importance of reviewing HBV vaccination status and considering HBIG/antiviral prophylaxis immediately after exposure in future incidents.
• Counselling and Education: Provide education on HBV transmission prevention and the potential implications of chronicity.
• Notification: Acute hepatitis B is a notifiable condition. Public health authorities must be informed to facilitate contact tracing and to implement necessary control measures.

4. Follow-Up:

• Schedule follow-up visits in 1-2 weeks and then monthly until resolution or confirmation of chronic infection.
• Reassess HBV markers (HBsAg, anti-HBc, HBeAg, and HBV DNA) as well as LFTs.
• Discuss long-term monitoring if the infection persists beyond 6 months, as this indicates chronic HBV.

Summary

This case of Jordan—a 30-year-old nurse with acute hepatitis B following a needlestick injury—illustrates the typical progression of the disease, characterized by RUQ pain, fatigue, mild fever, and evidence of hepatocellular injury with high viral load. The management plan highlights the importance of monitoring for spontaneous viral clearance versus progression, judicious use of antivirals, and calls for both occupational health and public health notification to ensure proper follow-up and prevention of further exposure.

Case 3:

Patient:

Liam, a 35-year-old man with a history of intravenous drug use.

History of Present Illness:

Liam presents for routine screening at a community health clinic focused on harm reduction. He reports feeling generally well, with only occasional fatigue that he attributes to his lifestyle. There are no significant complaints of jaundice, abdominal pain, or nausea. However, given his high-risk behaviour with needle sharing, he agreed to comprehensive hepatitis screening.

Past Medical History:

• History of intravenous drug use, occasional minor skin infections.
• No known chronic illnesses; no prior diagnosis of liver disease.

Social History:

• Lives in shared accommodation.
• Occasionally consumes alcohol.
• Actively using harm reduction services and needle exchange programs.

Examination Findings

General Appearance:

• Liam appears healthy and well, without overt signs of jaundice.
• He is alert and oriented.

Vital Signs:

• Temperature: 36.8°C
• Heart Rate: 80 beats per minute
• Blood Pressure: 122/78 mmHg
• Respiratory Rate: 16 breaths per minute
• Oxygen Saturation: 98% on room air

Abdominal Examination:

• The abdominal exam is essentially unremarkable—no tenderness, hepatomegaly, or organomegaly detected.

Other Systems:

• Cardiovascular, respiratory, and neurological examinations are normal.

Laboratory Investigations

Test	Result	Normal Range
White Cell Count	6.8 x 10⁹/L	4.0 – 11.0 x 10⁹/L
Haemoglobin	14.2 g/dL	13.5 – 17.5 g/dL
Platelets	220 x 10⁹/L	150 – 400 x 10⁹/L
ALT	110 U/L	< 40 U/L
AST	95 U/L	< 40 U/L
Total Bilirubin	18 µmol/L	< 20 µmol/L
ALP	120 U/L	30 – 130 U/L
Anti-HCV Antibody	Positive	Negative
HCV RNA (viral load)	5.0 x 10⁶ IU/mL (High)	Undetectable/very low
INR	1.0	0.8 – 1.2

Note: While the liver enzymes are only mildly elevated compared to the dramatic picture seen in symptomatic cases, they still suggest hepatocellular injury. The combination of a positive anti-HCV antibody and high HCV RNA confirms an acute HCV infection, even in the absence of overt clinical symptoms.

Management Plan

1. Monitoring and Evaluation:

• Observation: Recognize that most acute HCV cases are subclinical; however, regular monitoring is needed. Despite minimal symptoms, there is a high risk (approximately 75–85%) of progression to chronic infection.
• Serial Testing: Schedule repeat testing for liver enzymes (ALT, AST) and HCV RNA at 1- and 3-month intervals to assess trends.

2. Counselling and Harm Reduction:

• Education: Counsel Liam about HCV transmission, the risk of chronic infection, and the critical importance of maintaining safe injection practices.
• Referral: Connect him with harm reduction services and support groups focusing on sustainable lifestyle changes.

3. Infection Control & Public Health Notification

• Although acute hepatitis C is often subclinical, many jurisdictions—Australia included—classify it as a notifiable condition.
• Liam’s case should be promptly reported to public health authorities as per local legislation so that appropriate surveillance and contact tracing measures can be enacted.

4. Treatment Considerations:

• Antiviral Therapy: While immediate treatment during the acute phase is typically deferred in asymptomatic individuals, early antiviral intervention with direct-acting agents may be considered if laboratory trends suggest significant progression.
• Lifestyle Recommendations: Advise avoidance of alcohol and other hepatotoxins to minimize liver injury.

5. Follow-Up:

• Schedule regular follow-up appointments to monitor liver function and viral dynamics.
• Discuss potential treatment options if HCV persists beyond the acute phase (6 months), indicating a transition to chronic infection.

Summary

This case exemplifies the more common, subclinical nature of acute hepatitis C in high-risk populations. Despite minimal symptoms, the laboratory findings—especially the presence of HCV RNA—are critical in establishing the diagnosis. Management in this scenario centres on vigilant monitoring, harm reduction, public health notification, and patient education, with a view toward early intervention if necessary.

🏁 Key Takeaways: Understanding Acute Hepatitis

✅ Viruses behave differently—some resolve, some persist chronically.

✅ Pathophysiology matters—knowing HOW & WHY hepatocyte damage occurs aids diagnosis.

✅ Serology guides decisions—don’t rely only on LFTs; always confirm viral cause.

✅ Public health plays a role—remember notification and contact tracing

🧾 Summary

Acute viral hepatitis presents as a spectrum — from subclinical infection to fulminant liver failure. A strong understanding of virology, immune response, and clinical red flags helps in early diagnosis, safe management, and public health prevention.

Want to keep learning?

• 📝 Complete the quiz on this topic →
• 📝 All posts on the gastrointestinal system →
• 📝 Structure and function of the liver →
• 📝 Signs of liver dysfunction →
• 📝 Chronic viral hepatitis and hepatocellular carcinoma→