Hepatitis
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Hepatitis - Comprehensive Overview
Definition
Hepatitis means inflammation of hepatic parenchyma. It can be acute or chronic, and arises from viral, toxic, autoimmune, metabolic, bacterial, or parasitic causes. - Textbook of Family Medicine 9e, p. 1132
Etiology
| Category | Examples |
|---|---|
| Viral | HAV, HBV, HCV, HDV, HEV, HGV; also EBV, CMV, toxoplasmosis |
| Toxic / Drug-induced | Acetaminophen overdose, isoniazid, statins, herbal supplements |
| Alcoholic | Chronic heavy alcohol use |
| Autoimmune | Autoimmune hepatitis (AIH) |
| Metabolic | Wilson disease, hemochromatosis, alpha-1 antitrypsin deficiency |
| Bacterial/Fungal/Parasitic | Leptospirosis, liver abscess, etc. |
Important: Acetaminophen overdose should be considered in all cases of acute non-viral hepatitis and treated immediately with N-acetylcysteine to prevent permanent hepatic damage and death. - Family Medicine 9e
The Five Hepatitis Viruses
Hepatitis A (HAV)
- Virus: RNA picornavirus (enterovirus)
- Transmission: Fecal-oral route (contaminated food/water, poor sanitation); blood transmission exceedingly rare
- Incubation: 15-45 days (typically ~30 days)
- Chronicity: Does NOT cause chronic infection or carrier state
- Epidemiology: Endemic worldwide; close to 50% of US urban adults are seropositive. Up to 100% of children seropositive in low-income countries. HAV vaccine approved in 1995 - widespread vaccination has shifted cases to adults
- Serology: Anti-HAV IgM = acute; Anti-HAV IgG = past infection/immunity
- High-risk groups: International travelers (most common risk in >15 yr), men who have sex with men, drug users
- ROSEN's Emergency Medicine
Hepatitis B (HBV)
- Virus: DNA hepadnavirus
- Transmission: Parenteral (blood products, shared needles), intimate contact/body fluids, vertical (mother to neonate). Very stable - survives outside body up to 7 days
- Incubation: Mean ~120 days; serologic markers appear within 1-3 weeks of exposure
- Chronicity: ~10% of acutely infected adults become chronic carriers. Up to 90% of perinatally infected neonates become chronic carriers (inversely age-related)
- Virion contains: DNA polymerase, HBsAg, HBcAg. HBeAg is secreted (not in virion) - marker of active replication
- Chronic HBV defined as: HBsAg in serum for >6 months
- Complications: Cirrhosis, hepatocellular carcinoma (HCC)
- Estimated US new cases: ~22,000/year
HBV Serologic Markers:
| Marker | Meaning |
|---|---|
| HBsAg | Surface antigen - active infection |
| Anti-HBs | Immunity (from vaccination or recovery) |
| HBcAg | Core antigen (not detectable in serum) |
| Anti-HBc IgM | Acute HBV infection |
| Anti-HBc IgG | Past infection |
| HBeAg | Active viral replication, high infectivity |
| Anti-HBe | Low/no viral replication |
| HBV DNA | Viral load - guides treatment |
"Window period": HBsAg has cleared but Anti-HBs not yet detectable - only Anti-HBc IgM is positive.
- Henry's Clinical Diagnosis and Laboratory Methods; ROSEN's EM
Hepatitis C (HCV)
- Virus: RNA flavivirus (previously "non-A, non-B hepatitis")
- Transmission: Primarily bloodborne - IVDU is the strongest risk factor (53-75% prevalence among injection drug users). Transfusion risk now <1 in 2 million units screened
- Incubation: Mean ~50 days
- Chronicity: ~90% of HCV infections progress to chronic hepatitis - most common cause of cirrhosis in the US (>42% of chronic liver disease). Over 20-30 years, cirrhosis develops in 10-20%
- Cirrhosis carriers have elevated risk of HCC
- No vaccine available for HCV
- Worldwide prevalence: ~71 million cases (WHO 2020); US prevalence ~1.2-2.0%
- Treatment: Direct-acting antivirals (DAAs) - highly effective, >95% cure rates
- Coinfection with HIV leads to more aggressive disease course
Hepatitis D (HDV - Delta Hepatitis)
- Virus: Defective RNA virus - requires HBV to replicate (needs HBsAg as its envelope)
- Transmission: Same routes as HBV
- Two patterns:
- Coinfection (HDV + HBV simultaneously): more likely to cause fulminant hepatitis
- Superinfection (HDV in existing HBV carrier): range from self-limited to fulminant or chronic
- Key point: HDV worsens the disease course of HBV and leads to higher rates of fulminant hepatic failure
- Prevention: HBV vaccination protects against HDV (but does NOT protect HBV carriers from HDV superinfection)
Hepatitis E (HEV)
- Virus: RNA virus
- Transmission: Fecal-oral (like HAV)
- Incubation: 15-60 days
- Geography: Predominantly Asia, Africa, Russia
- Special risk: High mortality in pregnant women (up to 20-25% case fatality rate in third trimester)
- No chronic state in immunocompetent individuals (can be chronic in immunosuppressed)
Hepatitis G (HGV / GBV-C)
- RNA virus transmitted parenterally or by intimate contact
- Believed to be a "bystander virus" - disease manifestations largely attributable to coinfection with another hepatitis virus
- ROSEN's Emergency Medicine
Quick Comparison Table
| Feature | HAV | HBV | HCV | HDV | HEV |
|---|---|---|---|---|---|
| Virus type | RNA | DNA | RNA | RNA (defective) | RNA |
| Transmission | Fecal-oral | Parenteral/sexual/vertical | Parenteral (mainly IVDU) | Parenteral (needs HBV) | Fecal-oral |
| Incubation | 15-45 d | ~120 d | ~50 d | Same as HBV | 15-60 d |
| Chronic infection | No | Yes (10% adults, 90% neonates) | Yes (~90%) | Yes (superinfection) | No (except immunosuppressed) |
| Vaccine | Yes (1995) | Yes (1982) | No | Via HBV vaccine | Limited (China) |
| Cancer risk | No | Yes (HCC) | Yes (HCC) | Yes | No |
Clinical Features
The clinical presentation is highly variable, with many infections being asymptomatic (especially in children).
Prodromal/Constitutional symptoms:
- Malaise, fatigue, lethargy
- Low-grade fever, anorexia
- Nausea, vomiting, diarrhea
- RUQ abdominal pain
- Arthralgias and myalgias
- Dark (tea-colored) urine
- Pale/clay-colored stools
Icteric phase:
- Jaundice (scleral icterus appears when bilirubin >2.5 mg/dL)
- Hepatomegaly - smooth, tender
HBV-specific prodrome: Serum sickness-like illness with polyarticular arthralgia (small joints of hands/wrists), urticarial or macular/papular rash
Alarm signs of severe disease / fulminant hepatitis:
- Hepatic encephalopathy (altered mental status)
- Asterixis
- Ascites
- Prolonged PT/INR
- Spontaneous mucosal bleeding
Fulminant hepatitis most commonly seen with HBV + HDV coinfection; can occur with any hepatitis virus (1-2% of all cases).
- ROSEN's Emergency Medicine, p. 1239
Laboratory Investigations
- Elevated: AST, ALT (transaminases), ALP, serum bilirubin (conjugated and unconjugated)
- Specific values have poor prognostic value individually
- PT/INR prolongation - marker of hepatic synthetic failure (ominous sign)
- Serologic panel to identify virus type (see markers above)
- HBV DNA, HCV RNA (PCR) - viral load, guides treatment decisions
- Liver biopsy - for staging fibrosis in chronic disease
Treatment & Management
Acute Hepatitis
- Most cases resolve without complications - supportive/outpatient management
- Rest, hydration, adequate nutrition
- Avoid hepatotoxic drugs (alcohol, NSAIDs, acetaminophen)
- Proper isolation/contact precautions
Indications for admission:
- Uncertain diagnosis (rule out meningococcemia)
- Severe abdominal pain, intractable vomiting
- Coagulopathy, encephalopathy, ascites
- Compromised renal function
Chronic HBV Treatment
- Nucleoside/nucleotide analogues: tenofovir, entecavir (first-line)
- Pegylated interferon-alpha (in selected patients)
- Goal: sustained viral suppression, prevention of fibrosis progression
- Liver transplantation for end-stage disease
Chronic HCV Treatment
- Direct-acting antivirals (DAAs): sofosbuvir-based regimens, glecaprevir-pibrentasvir, ledipasvir-sofosbuvir
- Cure rates >95% across genotypes
- Treatment duration: typically 8-12 weeks
Post-Exposure Prophylaxis (HBV)
| Situation | Management |
|---|---|
| Unvaccinated, known HBsAg+ source | HBIG 0.06 mL/kg IM within 96h + start HBV vaccine series |
| Vaccinated - known responder (anti-HBs ≥10 mIU/mL) | No treatment needed |
| Non-responder after one series | HBIG x1 + repeat vaccine series |
| Non-responder after two series | HBIG x2 doses, 1 month apart |
HCV: No post-exposure prophylaxis - occupational health follow-up for baseline and serial testing.
- Washington Manual of Medical Therapeutics
Prevention & Vaccination
HAV Vaccine:
- Inactivated formalin-killed vaccine, licensed 1995 (US)
- Recommended: all children, international travelers, MSM, drug users
- Passive: IG within 1-2 weeks post-exposure (~90% protective)
HBV Vaccine:
- Recombinant DNA vaccine (yeast-derived HBsAg), available since 1982
- Universal infant vaccination, prenatal HBsAg screening, HBIG for neonates of HBsAg+ mothers
- Adolescent/adult catch-up vaccination for unvaccinated
- Immunosuppressed patients (dialysis, HIV, chemotherapy) respond less well
HDV: Prevented by HBV vaccination in non-carriers. No protection for existing HBV carriers.
HCV: No vaccine available. Prevention relies on harm reduction (clean needles, blood screening, safe sex).
- Jawetz Melnick & Adelberg's Medical Microbiology 28e
Recent Evidence (2024-2026)
- AGA 2025 Clinical Practice Guideline on HBV reactivation (PMID 39863345) - updated guidance on preventing and treating HBV reactivation in immunosuppressed patients (e.g., those on biologics/chemotherapy)
- BMJ 2025 review on advances in HBV management (PMID 40461178) - includes emerging therapies targeting HBV cccDNA
- Journal of Hepatology 2025 update on autoimmune hepatitis (PMID 39864459) - covers evolving diagnostic criteria and second-line immunosuppressants
Special Populations
- Neonates: 90% of HBV-infected neonates develop chronic infection - universal prenatal HBsAg screening and HBIG + vaccine at birth is standard of care
- Pregnant women: HEV carries up to 20-25% mortality in the third trimester; HBV screening is mandatory; tenofovir used to reduce vertical transmission in high-HBV-DNA mothers
- HIV coinfection: Accelerates HCV and HBV disease; shared antivirals (tenofovir) active against both HIV and HBV
- Immunosuppressed patients: Risk of HBV reactivation when starting immunosuppressive therapy (biologics, steroids, chemotherapy) - requires prophylactic antiviral coverage
Sources: ROSEN's Emergency Medicine, Textbook of Family Medicine 9e, Jawetz Melnick & Adelberg's Medical Microbiology 28e, The Washington Manual of Medical Therapeutics, Henry's Clinical Diagnosis and Management by Laboratory Methods
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