Viral Hepatitis (A, B, C, D, E) — Causes, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Viral hepatitis is inflammation of the liver caused by one of five distinct hepatitis viruses: hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV — requires HBV co-infection), and hepatitis E (HEV). These viruses differ dramatically in their transmission routes, chronicity, long-term complications, and treatment. Viral hepatitis is a major global public health problem — the WHO estimates that 296 million people live with chronic hepatitis B and 58 million with chronic hepatitis C worldwide; viral hepatitis causes approximately 1.1 million deaths annually, predominantly from cirrhosis and hepatocellular carcinoma (HCC) attributable to chronic hepatitis B and C. Acute viral hepatitis causes hepatocyte inflammation and necrosis, with the clinical spectrum ranging from asymptomatic infection (the majority) to acute liver failure. The critical clinical distinction is between self-limiting acute hepatitis (HAV, HEV, most HBV in immunocompetent adults) and chronic hepatitis (HBV in infants/immunocompromised — 90% chronicity; HCV — 75-85% chronicity). Chronic hepatitis drives progressive hepatic fibrosis over 10-30 years, leading to cirrhosis, liver failure, and a 15-20-fold increased risk of HCC. Hepatitis C is now curable with 8-12 week courses of oral direct-acting antivirals (DAAs) achieving above 95% sustained virological response (SVR — cure) rates; hepatitis B, by contrast, cannot currently be cured by available antivirals and requires lifelong antiviral suppression. Vaccination prevents hepatitis A and B; no vaccine exists for HCV.

Hepatitis A (HAV): RNA virus, faecal-oral transmission — contaminated food and water (shellfish, salads, raw produce), travel to endemic regions (South Asia, Sub-Saharan Africa, Central and South America), person-to-person contact (poor sanitation, overcrowding), and sexual transmission (oro-anal contact). Causes only acute self-limiting hepatitis (no chronicity). Hepatitis B (HBV): DNA virus (Hepadnaviridae), parenteral and sexual transmission — unprotected sexual intercourse (particularly anal sex — most common route in low-endemicity countries); sharing of needles, syringes, and drug paraphernalia (PWID — people who inject drugs); vertical transmission from mother to newborn at birth (the most important route in high-endemicity countries — Sub-Saharan Africa, East Asia; 90% chronicity rate when transmitted perinatally without prophylaxis vs. 5% in adults); unsafe medical/dental procedures and tattooing with unsterilised equipment. High-risk groups: men who have sex with men (MSM), PWID, healthcare workers. HBV is 50-100 times more infectious than HIV via the percutaneous route. Hepatitis C (HCV): RNA virus (Flaviviridae), predominantly parenteral transmission — sharing of needles and equipment for injecting drug use accounts for the majority of new HCV infections in high-income countries; blood transfusions and blood products (historical, before 1992 UK blood screening); sexual transmission (less efficient than HBV — low risk in heterosexual couples but significant in HIV-positive MSM); vertical transmission (approximately 5%); healthcare exposures (needlestick injuries, endoscopy). 75-85% of infected individuals develop chronic hepatitis C. Hepatitis D (HDV): RNA virus, requires HBV surface antigen (HBsAg) as its envelope — can only infect those with HBV; transmitted via the same routes as HBV; co-infection (simultaneous HBV and HDV) usually results in acute self-limited disease; superinfection (HDV in chronic HBV carrier) causes particularly severe and rapidly progressive liver disease with accelerated cirrhosis. Hepatitis E (HEV): RNA virus, faecal-oral transmission in developing countries (contaminated water — commonest cause of acute viral hepatitis in South Asia); in high-income countries, HEV genotype 3 is a zoonosis (pigs, deer, wild boar) transmitted through undercooked pork products (sausages, pork liver — particularly important in elderly immunocompromised patients where it can cause chronic hepatitis).

Acute hepatitis (all types): the prodromal phase (1-2 weeks before jaundice) — malaise, fatigue, anorexia, nausea and vomiting, low-grade fever, right upper quadrant or epigastric discomfort (from hepatic capsule distension), arthralgias, and urticaria (serum sickness-like reaction in HBV — part of the prodrome). Icteric phase: jaundice (yellow discolouration of skin and sclera from bilirubin accumulation); dark urine (bilirubinuria — tea or cola-coloured); pale (acholic) stools (cholestasis); and pruritus (from bile salts). Liver tenderness on palpation (hepatomegaly); splenomegaly in some cases. Most acute hepatitis is mild or subclinical — jaundice is present in only 20-30% of HAV and less than 30% of HCV infections. Fulminant hepatic failure (rare but life-threatening): rapid progression of encephalopathy, coagulopathy (prolonged PT/INR), and jaundice — risk increased in HBV superinfection with HDV, HBV reactivation on immunosuppression, and HAV in patients with pre-existing liver disease; requires specialist liver centre management and possibly transplant. Chronic hepatitis B and C: the majority of patients with chronic viral hepatitis are asymptomatic for 10-30 years while progressive liver fibrosis develops — the silent disease period is why chronic viral hepatitis is often detected only at cirrhosis stage. Symptoms develop in advanced fibrosis and cirrhosis: fatigue and reduced exercise tolerance; anorexia and weight loss; pruritus; jaundice and scleral icterus; coagulopathy (bruising, bleeding tendency); hepatic decompensation manifestations: ascites (abdominal distension from portal hypertension and hypoalbuminaemia), oesophageal varices (haematemesis or malaena from rupture — the most acute life-threatening complication), hepatic encephalopathy (confusion, flapping tremor from ammonia accumulation), and spontaneous bacterial peritonitis. HCC symptoms: right upper quadrant mass, weight loss, pain, and deterioration in liver function tests in a patient with cirrhosis.

Liver function tests (LFTs): elevated ALT and AST (most sensitive markers of hepatocyte necrosis — peak in acute hepatitis at 1000-10,000 IU/L; in chronic hepatitis, ALT is the primary monitoring marker; normal ALT does not exclude significant liver fibrosis in chronic HCV); elevated bilirubin (conjugated hyperbilirubinaemia in icteric hepatitis); reduced albumin and elevated INR (prothrombin time) — markers of synthetic dysfunction indicating severity; raised ALP and GGT from cholestatic component. Serological diagnosis: Hepatitis A: anti-HAV IgM (acute infection); anti-HAV IgG (past infection or vaccination). Hepatitis B — four key markers: HBsAg (hepatitis B surface antigen — positive in acute and chronic HBV infection; defines the infectious state); anti-HBs (surface antibody — positive after resolution of infection or vaccination — indicates immunity); HBeAg (e antigen — marker of active viral replication and high infectivity; negative HBeAg with positive anti-HBe indicates low replication phase or pre-core mutation HBV — HBeAg-negative hepatitis B is common and can still cause progressive liver disease); anti-HBc IgM (indicates acute or recent HBV infection); anti-HBc IgG (indicates past or chronic HBV infection); HBV DNA (viral load by PCR — essential for quantifying replication and monitoring antiviral therapy response; target undetectable HBV DNA on treatment). Hepatitis C: anti-HCV antibody (screening test — positive 8-12 weeks after infection; does not distinguish active from cleared infection); HCV RNA (PCR — detects viraemia from approximately 1-2 weeks after exposure; required to confirm active HCV infection and to distinguish current from past infection — 20-25% of HCV infections self-clear with anti-HCV antibody remaining positive for life); HCV genotype (1a, 1b, 2, 3, 4, 5, 6 — guides selection of pan-genotypic DAA regimen, though modern pan-genotypic regimens cover all genotypes). Assessment of liver fibrosis (critical for management decisions): transient elastography (FibroScan — liver stiffness measurement by ultrasound-based technique; non-invasive; values above 7 kPa — F2 fibrosis; above 9.5 kPa — F3; above 12.5 kPa — cirrhosis); APRI and FIB-4 score (serological fibrosis indices); liver biopsy (Menghini or Tru-Cut needle — the gold standard for fibrosis staging but invasive; increasingly replaced by non-invasive methods). HCC surveillance: 6-monthly liver ultrasound ± AFP in all patients with cirrhosis and in HBV-infected patients at higher risk (African or Asian origin, family history of HCC).

Hepatitis A and E: supportive management only — rest, adequate hydration, avoid alcohol and hepatotoxic medications; hospitalisation for severe jaundice, dehydration, or encephalopathy; fulminant hepatic failure requires liver transplant centre referral. Hepatitis B: NICE and EASL guidelines recommend antiviral treatment for: chronic HBV with HBV DNA above 2000 IU/mL with elevated ALT and/or fibrosis above F2; HBeAg-positive hepatitis with HBV DNA above 20,000 IU/mL even with normal ALT if age above 30; and compensated or decompensated cirrhosis at any viral load. First-line antivirals: tenofovir disoproxil fumarate (TDF — 245 mg daily; highly effective with minimal resistance; renally excreted — dose adjust for eGFR below 30); tenofovir alafenamide (TAF — 25 mg daily; equivalent efficacy with better renal and bone safety — preferred in renal impairment); entecavir 0.5 mg daily (equally effective alternative; 1 mg for lamivudine-resistant HBV). Treatment targets: in HBeAg-positive HBV — HBeAg seroconversion to anti-HBe and HBV DNA suppression (allows finite treatment if sustained); in HBeAg-negative HBV — HBsAg loss (functional cure — rare with current antivirals) or indefinite HBV DNA suppression. Treatment duration: typically lifelong in HBeAg-negative cirrhotic patients; finite (minimum 48-72 weeks post-HBeAg seroconversion) in selected HBeAg-positive non-cirrhotic patients. Interferon alpha or pegylated interferon (PEG-IFN): alternative finite treatment option (48-week course); subcutaneous injection with significant side effects (flu-like symptoms, depression, cytopenias); cure rate (HBsAg loss) approximately 10-15% — role diminishing with advent of oral antivirals. Hepatitis C — direct-acting antivirals (DAAs): current pan-genotypic regimens achieve above 95% SVR (sustained virological response = cure defined as undetectable HCV RNA 12 weeks after completing therapy): sofosbuvir/velpatasvir (Epclusa) 400/100 mg daily for 12 weeks — pan-genotypic; or glecaprevir/pibrentasvir (Mavyret) 300/120 mg daily for 8 weeks (non-cirrhotic) — pan-genotypic. Other regimens: sofosbuvir/ledipasvir (Harvoni — genotype 1, 4, 5, 6); sofosbuvir/daclatasvir (genotype 1-6); elbasvir/grazoprevir (genotype 1, 4 — avoid genotype 1a with NS5A polymorphisms without prior RAS testing). DAAs are generally very well-tolerated; main interactions: PPIs reduce ledipasvir absorption; rifampicin substantially reduces DAA efficacy; amiodarone — serious bradycardia with sofosbuvir combinations. Monitor for drug interactions carefully. Hepatitis D: bulevirtide (a novel entry inhibitor — European approved 2020) is the first treatment specifically for chronic hepatitis D; pegylated interferon alfa remains an option. Hepatitis B prevention of mother-to-child transmission: HBsAg-positive mothers with HBV DNA above 200,000 IU/mL should receive TDF from week 24-28 of pregnancy; all neonates of HBsAg-positive mothers should receive HBV vaccination plus HBV immunoglobulin (HBIG) within 12 hours of birth.

Acute liver failure (fulminant hepatitis): rare (0.1-0.4% of acute HBV) but life-threatening — coagulopathy (INR above 1.5), encephalopathy, and jaundice within 8 weeks of symptom onset; multiorgan failure; requires liver transplant centre referral and potentially emergency transplantation; HAV and HEV in patients with pre-existing chronic liver disease carry substantially higher risk of acute-on-chronic liver failure. Chronic liver disease complications from long-term hepatitis B and C: hepatic fibrosis progressing to cirrhosis (20-30% of untreated chronic HBV or HCV over 20-30 years); cirrhotic decompensation — ascites (abdominal distension; treated with diuretics — spironolactone 100-400 mg daily and furosemide 40-160 mg daily), oesophageal and gastric variceal haemorrhage (emergency endoscopic variceal banding plus terlipressin 2 mg IV plus ceftriaxone 1 g IV; TIPSS for refractory bleeding), spontaneous bacterial peritonitis (diagnostic paracentesis; cefotaxime IV; primary prophylaxis with norfloxacin 400 mg daily in patients with low ascitic protein below 15 g/L), and hepatic encephalopathy (lactulose, rifaximin 550 mg twice daily). Hepatocellular carcinoma (HCC): chronic HBV is the most common cause of HCC globally (accounting for 50-55% of all HCC cases); HCV is the most common HCC cause in Western countries. HCC risk is dramatically reduced but not eliminated by antiviral treatment — 6-monthly surveillance ultrasound ± AFP continues indefinitely in all patients who developed cirrhosis before achieving SVR. Extrahepatic manifestations of HCV: cryoglobulinaemia type II (monoclonal IgM RF complex — causes vasculitis, purpura, peripheral neuropathy, glomerulonephritis — type 2 membranoproliferative GN; resolves with HCV cure); lymphoma (2-fold increased NHL risk from chronic B-cell stimulation).

Hepatitis A vaccination: two-dose inactivated HAV vaccine (Havrix, Avaxim, Vaqta — dose 0 and 6-12 months) provides over 95% seroprotection after the first dose and near-lifetime immunity after 2 doses; recommended for all travellers to endemic areas, MSM, chronic liver disease patients, PWID, and workers in sewage and food handling. Hepatitis B vaccination: three-dose recombinant HBsAg vaccine (Engerix B, HBvaxPRO — 0, 1, 6 months) achieves above 95% protective antibody response (anti-HBs above 10 IU/L); universal infant vaccination programmes (UK schedule — birth, 2, 3, 4 months — combined with 5-in-1 Infanrix Hexa vaccine); vaccination of high-risk adults: MSM, PWID, household and sexual contacts of HBV carriers, healthcare workers, and travellers to high-endemic areas. Post-exposure prophylaxis (PEP) for HBV: HBV-susceptible individuals exposed to HBsAg-positive source — HBIG 500 IU IM within 48 hours plus initiation of HBV vaccination course. Harm reduction for HCV (no vaccine exists): needle and syringe programmes (NSP) providing sterile injecting equipment are the most effective public health intervention for reducing new HCV infections among PWID — reduce transmission by approximately 50%; opioid substitution therapy (methadone, buprenorphine); sexual risk reduction (condom use in HIV-positive MSM is particularly important). Blood supply safety: mandatory HBV and HCV screening of all donated blood since 1991 (UK) has virtually eliminated transfusion-transmitted hepatitis. Universal precautions in healthcare settings prevent healthcare-associated transmission. Test-and-treat strategy for HCV: the WHO 2030 hepatitis elimination target (90% reduction in new infections, 65% reduction in mortality) requires systematic population screening — NICE recommends one-time HCV antibody testing for all adults (anti-HCV ELISA with reflex RNA PCR testing if positive) to identify and treat the estimated 90,000 people in England currently undiagnosed with chronic HCV. NHS community HCV testing programmes (pharmacies, drug services, prisons) have significantly increased diagnosis rates.

Go to A&E immediately for: jaundice with confusion, agitation, or drowsiness (possible acute liver failure — hepatic encephalopathy), which is a life-threatening emergency requiring immediate hospital admission; vomiting blood or passing black tarry stools in a patient with known chronic viral hepatitis or cirrhosis (oesophageal or gastric variceal haemorrhage — mortality up to 20% per episode without emergency endoscopy and vasoconstrictor treatment); severe right upper quadrant pain with fever and jaundice (cholangitis or liver abscess); and signs of sepsis in a patient with ascites (spontaneous bacterial peritonitis — requires emergency paracentesis and IV antibiotics). See a GP within 1-2 weeks for: new onset jaundice in an adult — requires urgent investigation to exclude viral hepatitis, biliary obstruction, or haemolysis; known or suspected risk factors for blood-borne viral hepatitis (ever injected drugs, MSM, sexual partner from high-endemic country, previous needlestick injury, blood transfusion before 1991) — request hepatitis B and C serology; any abnormal liver function tests — particularly elevated ALT above twice the upper limit of normal — to exclude viral hepatitis and other liver disease. Seek sexual health clinic testing: annual hepatitis B and C testing is recommended for sexually active MSM and PWID. All pregnant women should have HBsAg testing at the first antenatal appointment — to allow timely neonatal prophylaxis. If diagnosed with hepatitis B or C, referral to hepatology for specialist management, antiviral therapy assessment, and monitoring is essential.