Gastrointestinal · PANCE / PANRE

Viral Hepatitis (A, B, C)

Acute and chronic hepatocellular inflammation from hepatotropic viruses; transmission, course, and treatment differ by type.

Also known as: viral hepatitis, hepatitis A, hepatitis B, hepatitis C, HAV, HBV, HCV

Overview

Hepatocellular inflammation caused by hepatotropic viruses. Hepatitis A (HAV — picornavirus, fecal-oral, acute only); Hepatitis B (HBV — hepadnavirus, parenteral/sexual/perinatal, acute and chronic, DNA virus with reverse transcriptase); Hepatitis C (HCV — flavivirus, parenteral/sexual, predominantly chronic, RNA virus).

Epidemiology

HAV: outbreaks in food/water-contaminated settings; 6,500 cases/yr US (peaks with outbreaks). HBV: 1.5 million chronic carriers in US, 296 million worldwide. HCV: 2.4 million chronic infections in US; rising due to opioid epidemic and injection drug use; baby boomers (1945-1965) carry disproportionate burden.

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Risk factors

HAV: fecal-oral; travel to endemic areas, contaminated food/water (raw shellfish), MSM, homelessness, IV drug use, daycare outbreaks
HBV: parenteral (IV drug use, needlestick, transfusion before 1992), sexual contact, perinatal (vertical transmission — most important worldwide), MSM, dialysis, multiple partners
HCV: parenteral (IV/intranasal drug use — leading risk factor; transfusion before 1992; tattooing with unsterile equipment), perinatal (~5%), sexual (less efficient; higher in MSM/HIV), needlestick, dialysis
Birth cohort: HCV — born 1945-1965 (USPSTF universal screening)

Pathophysiology

HAV: cytopathic and immune-mediated; no chronic state. HBV: non-cytopathic; hepatocyte injury immune-mediated (CD8 T cells targeting infected hepatocytes); cccDNA in nucleus drives chronicity; viral DNA can integrate into host genome (HCC risk even without cirrhosis). HCV: high mutation rate (lacks proofreading) drives quasispecies and immune evasion; chronicity in 75-85%; cirrhosis develops over 20-30 yr.

Clinical presentation

Symptoms

Acute hepatitis (any type): malaise, fatigue, anorexia, nausea, vomiting, RUQ pain, low-grade fever, arthralgias, jaundice, dark urine, pale stools
Prodromal flu-like symptoms 1-2 weeks before jaundice
Asymptomatic in most acute HBV/HCV cases
Chronic infection: often asymptomatic; fatigue, intermittent RUQ discomfort; complications of cirrhosis (ascites, variceal bleed, encephalopathy)
Fulminant hepatic failure (<1% acute HAV/HBV): encephalopathy, coagulopathy, cerebral edema

Signs / physical exam

Jaundice, scleral icterus
Tender hepatomegaly
Splenomegaly possible
Stigmata of chronic liver disease (in chronic infection with cirrhosis): spider angiomata, palmar erythema, gynecomastia, caput medusae, ascites, asterixis
Extrahepatic manifestations of chronic HBV: polyarteritis nodosa, membranous nephropathy
Extrahepatic manifestations of chronic HCV: cryoglobulinemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, lichen planus, B-cell lymphoma

Classic findings

HAV: traveler to endemic area, raw shellfish, daycare exposure; acute illness, full recovery. HBV: 'serologic chase' (HBsAg, anti-HBs, anti-HBc IgM/IgG, HBeAg, anti-HBe). HCV: incidental detection of elevated ALT or positive antibody; new injection drug use.

Differential diagnosis

Alcoholic hepatitis — AST:ALT ratio >2:1, both <500; alcohol history; macrocytosis, GGT elevation
Autoimmune hepatitis — Female, elevated IgG, ANA/anti-smooth muscle (type 1) or anti-LKM1 (type 2); responds to steroids
Drug-induced liver injury (acetaminophen, INH, statins, amiodarone, methotrexate) — Medication exposure; RUCAM score; resolves with discontinuation
Hemochromatosis — Elevated ferritin and transferrin saturation; HFE mutation; arthropathy, bronze diabetes
Wilson disease — Young patient, neuropsychiatric symptoms, Kayser-Fleischer rings, low ceruloplasmin, elevated urinary copper
Alpha-1 antitrypsin deficiency — Low serum A1AT, MZ/ZZ phenotype, COPD in younger patients
Non-alcoholic steatohepatitis (MASH) — Metabolic syndrome features; ALT > AST; biopsy or imaging
Ischemic hepatitis ('shock liver') — ALT/AST in thousands rapidly after hypotensive event; resolves quickly
Hepatitis D, E, EBV, CMV, HSV — Specific serologies; HDV requires HBV co-infection
Biliary obstruction — Cholestatic LFT pattern; dilated ducts on imaging

Diagnostic workup

Diagnostic criteria

HAV: anti-HAV IgM positive. HBV acute: HBsAg + anti-HBc IgM. HBV chronic: HBsAg positive >6 months. HBV cleared: anti-HBs + anti-HBc IgG, HBsAg negative. HBV vaccine response: isolated anti-HBs (no anti-HBc). HCV active: anti-HCV + HCV RNA detectable.

Labs

ALT, AST — often in 1000s in acute viral hepatitis; AST < ALT typically
Bilirubin (total and direct), alk phos, GGT
INR, albumin (synthetic function — prognostic)
CBC (thrombocytopenia in chronic disease/cirrhosis)
Serologic panel based on clinical context:
HAV: anti-HAV IgM (acute), anti-HAV IgG (immunity)
HBV: HBsAg (active infection), anti-HBs (immunity from vaccine or recovery), anti-HBc IgM (acute), anti-HBc IgG (current or past), HBeAg (high infectivity), anti-HBe, HBV DNA (viral load)
HCV: anti-HCV antibody (screening); if positive → HCV RNA (confirms active infection); HCV genotype (less critical with pan-genotypic DAAs)
HIV testing in all suspected viral hepatitis
Hepatitis D antibody if HBsAg positive
Alpha-fetoprotein (chronic HBV/HCV — HCC surveillance)
Iron studies, ceruloplasmin, A1AT, autoimmune workup as indicated to exclude other causes

Imaging

Abdominal ultrasound — assess for cirrhosis, splenomegaly, ascites, HCC; first-line
Transient elastography (FibroScan) or MR elastography — non-invasive fibrosis assessment
FIB-4 and APRI scores — calculated from labs, useful for fibrosis staging
Liver biopsy rarely required for fibrosis staging in HBV/HCV with current non-invasive options
CT/MRI for evaluation of suspicious hepatic lesions

Diagnostic algorithm

HBV Serologic Pattern	HBsAg	Anti-HBs	Anti-HBc IgM	Anti-HBc IgG	Interpretation
Acute infection	+	-	+	+/-	Active acute hepatitis B
Window period	-	-	+	+/-	Acute, between HBsAg loss and anti-HBs
Chronic infection	+ (>6 mo)	-	-	+	Chronic hepatitis B
Resolved infection	-	+	-	+	Recovered, immune
Vaccine immunity	-	+	-	-	Vaccine response (no anti-HBc)
Isolated anti-HBc	-	-	-	+	Resolved, false positive, or occult HBV — check HBV DNA

Hepatitis B serologic interpretation chart.

Treatment

First-line

Supportive care for acute hepatitis A — most resolve spontaneously
Acute HBV — supportive care; antivirals (entecavir, tenofovir) only for fulminant or severe acute hepatitis
Chronic HBV — see by_subtype for treatment indications
Chronic HCV — direct-acting antiviral (DAA) therapy — see by_subtype
Universal precautions; partner testing and vaccination
Avoid alcohol, hepatotoxic medications, weight management
HCC surveillance with US ± AFP every 6 months in cirrhotic patients and high-risk HBV carriers

Hepatitis A — prevention and post-exposure

Vaccination: 2-dose series; recommended for travelers, MSM, IV drug users, chronic liver disease, occupational exposure, homeless persons, post-exposure prophylaxis within 2 weeks
Post-exposure prophylaxis: HAV vaccine for healthy persons 12 months-40 yr; immune globulin for <12 months, >40 yr, immunocompromised, or chronic liver disease
No specific antiviral therapy; supportive care

Chronic Hepatitis B — treatment indications (AASLD 2018)

Treat: immune-active phase (HBeAg+ with HBV DNA >20,000 and elevated ALT, or HBeAg- with HBV DNA >2,000 and elevated ALT) OR cirrhosis with any detectable HBV DNA
Preferred first-line: entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) — high barrier to resistance
Pegylated interferon — alternative; finite duration; selected patients (young, no cirrhosis, high ALT, low HBV DNA, HBeAg+ genotype A or B)
Vaccinate household contacts and sexual partners (3-dose hepatitis B vaccine)
Post-exposure prophylaxis: HBIG + vaccine within 24 h for unvaccinated exposed individuals
Pregnancy: tenofovir for HBV DNA >200,000 IU/mL in 3rd trimester to prevent vertical transmission; HBIG + vaccine for infant at birth

Chronic Hepatitis C — direct-acting antivirals (AASLD 2023)

Universal treatment recommended — all patients with chronic HCV regardless of fibrosis stage
Pan-genotypic DAA regimens: sofosbuvir/velpatasvir (Epclusa) × 12 weeks OR glecaprevir/pibrentasvir (Mavyret) × 8 weeks (treatment-naive without cirrhosis)
Decompensated cirrhosis: sofosbuvir/velpatasvir + ribavirin × 12 weeks
Retreatment after DAA failure: sofosbuvir/velpatasvir/voxilaprevir (Vosevi)
Cure (SVR12) achieved in >95% of patients
HCC surveillance continues in cirrhotic patients despite SVR

Second-line / adjunct

Liver transplantation for fulminant hepatic failure or decompensated cirrhosis
Manage cirrhosis complications: ascites (sodium restriction, diuretics, paracentesis, TIPS), varices (beta-blockers, EVL), encephalopathy (lactulose, rifaximin), HCC (LI-RADS surveillance, locoregional or systemic therapy)
Treat extrahepatic manifestations: cryoglobulinemic vasculitis with rituximab + DAAs; HCV-associated MPGN responds to viral eradication

Complications

Acute: fulminant hepatic failure (<1% HAV/HBV; rare HCV); cholestatic hepatitis; relapsing hepatitis A
Chronic: cirrhosis, portal hypertension, ascites, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome
Hepatocellular carcinoma (HBV and HCV — even without cirrhosis in HBV; surveillance recommended)
Cryoglobulinemia, glomerulonephritis (HCV > HBV)
Polyarteritis nodosa (HBV)
Lymphoproliferative disorders (HCV)
Reactivation: HBV reactivation with immunosuppression (chemotherapy, anti-CD20, anti-TNF) — screen all patients receiving immunosuppression

PANCE pearls

HCV screening: USPSTF (2020) recommends one-time universal screening for all adults age 18-79 and repeat screening in those with ongoing risk (injection drug use, hemodialysis).
Universal HCV treatment with DAAs — all infected patients regardless of fibrosis stage. >95% cure with 8-12 week oral regimens.
HBV reactivation: screen ALL patients before immunosuppression (chemotherapy, rituximab, anti-TNF, transplant) — HBsAg, anti-HBc, anti-HBs. Prophylax with entecavir or tenofovir during and 6-12 months after immunosuppression.
Hepatitis B vaccine: 3-dose series; universal infant immunization since 1991; adults now universally recommended (ACIP 2022) for ages 19-59 and ≥60 with risk factors.
Hepatitis A vaccine: 2-dose series; consider for ALL patients with chronic liver disease, MSM, IV drug users, travelers, homeless.
AASLD HCC surveillance: every 6 months with ultrasound ± AFP in all cirrhotic patients and high-risk HBV carriers (Asian male >40, Asian female >50, African >20, family history HCC, cirrhotic).
HBeAg-negative chronic HBV is now the predominant form globally — precore mutations; HBV DNA is the key marker, not HBeAg.
Fulminant hepatic failure: INR ≥1.5 + encephalopathy in patient without prior liver disease — refer immediately to transplant center.
Avoid acetaminophen >2 g/day in chronic liver disease; AVOID NSAIDs in cirrhosis (renal failure, GI bleed risk).
Vaccinate HBV and HAV in patients with chronic HCV or chronic liver disease of any cause.

References

AASLD HBV 2018 — Terrault NA et al. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Hepatology 2018;67:1560-1599
AASLD/IDSA HCV — AASLD-IDSA HCV Guidance Panel. Recommendations for Testing, Managing, and Treating Hepatitis C. hcvguidelines.org (2023 update)
USPSTF HCV 2020 — US Preventive Services Task Force. Screening for Hepatitis C Virus Infection in Adolescents and Adults. JAMA 2020;323:970-975
ACIP HBV 2022 — Weng MK et al. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated ACIP Recommendations. MMWR 2022;71:477-483

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