Topic
Viral Hepatitis
Inflammation of the liver caused by the five hepatitis viruses (A to E): five very different agents that converge on one organ and one clinical syndrome. The shared acute picture and how to read it, the definitions of chronic and fulminant disease, the differential, and the serological markers that tell the viruses apart.
Viral hepatitis is the necro-inflammatory injury to the liver caused by one of the five hepatotropic viruses: hepatitis A, B, C, D and E (HAV, HBV, HCV, HDV, HEV). They share a single clinical syndrome but differ in almost everything else, from virus family and genome to route of spread and whether the infection can persist. The liver is also injured within wider systemic infections, by Epstein–Barr virus, cytomegalovirus, herpes simplex virus or yellow fever virus, but for those agents it is one target among many.
Two distinctions organise the whole topic. The first is the route of spread: the two enteric viruses (hepatitis A and E) travel by the faecal-oral route and cause acute, self-limited disease, while the three blood-borne viruses (hepatitis B, C and D) transmit parenterally and can persist. The second is chronicity, which drives the long-term burden: only the blood-borne viruses become chronic, and chronic infection is what leads to cirrhosis and hepatocellular carcinoma. The topic is treated across five virus profiles and one South African guidelines article.
→ See Hepatitis A virus for the enteric, self-limited infection, its age-dependent severity, and the inactivated vaccine.
→ See Hepatitis B virus for the DNA virus whose chronicity turns on age at infection, and the main vaccine-preventable cause of liver cancer.
→ See Hepatitis C virus for the blood-borne flavivirus now curable with direct-acting antivirals.
→ See Hepatitis D virus for the defective satellite that infects only alongside hepatitis B and worsens its course.
→ See Hepatitis E virus for the enteric, mostly self-limited virus that is dangerous in pregnancy and persistent in immunosuppression.
→ See South African Viral Hepatitis Guidelines for the national programme: who to screen, the targeted hepatitis B birth dose, antenatal management, and direct-acting antiviral access.
The five viruses at a glance
The single most useful contrast is between the enteric viruses spread by the faecal-oral route, which cause acute self-limited disease, and the blood-borne viruses, which can persist and drive cirrhosis and liver cancer.
| Feature | HAV | HBV | HCV | HDV | HEV |
|---|---|---|---|---|---|
| Family; genome | Picornaviridae; positive-sense RNA | Hepadnaviridae; DNA (reverse-transcribing) | Flaviviridae; positive-sense RNA | Kolmioviridae; negative-sense RNA (satellite) | Hepeviridae; positive-sense RNA |
| Incubation | 15 to 45 days | 45 to 160 days | 15 to 160 days | 30 to 60 days | 15 to 60 days |
| Chronicity | None | ~90% if perinatal, under 5% if adult | ~75% (55 to 85%) | High after superinfection | Only if immunosuppressed |
| Transmission | Faecal-oral | Blood, sexual, perinatal | Blood | Blood, sexual (needs hepatitis B) | Faecal-oral (water); zoonotic (food) |
| Acute liver failure | ~0.1% | ~0.1 to 1% | Rare | ~5 to 20% | ~1 to 2%; up to ~20 to 25% mortality in pregnancy (2nd and 3rd trimesters) |
| Vaccine | Yes | Yes | None | Hepatitis B vaccine protects | Licensed in China, Pakistan and India |
Chronicity in hepatitis B runs opposite to age at infection: infection acquired around birth becomes chronic in ~90% of cases, while infection acquired in adulthood becomes chronic in under 5%. This inverse relationship is the central reason infant vaccination matters. Hepatitis D cannot exist without hepatitis B, because it borrows the hepatitis B surface antigen (HBsAg) envelope, so hepatitis B vaccination is the only way to prevent hepatitis D. The enteric viruses do not become chronic in healthy people, the single exception being hepatitis E in the immunosuppressed.
Acute viral hepatitis
Acute viral hepatitis is the syndrome common to all five viruses. After the incubation period, a nonspecific prodrome of anorexia, nausea, fatigue, right-upper-quadrant discomfort and low-grade fever coincides with rising serum aminotransferases, typically one to two weeks before jaundice appears. The icteric phase brings jaundice, dark urine, pale stools, itch, and a tender, enlarged liver, and most patients recover clinically and biochemically within one to two months. Severity varies widely: subclinical or anicteric infection is common, especially in children, while a small minority progress to acute liver failure.
Fulminant hepatitis and acute liver failure
Fulminant viral hepatitis, or acute liver failure, is severe acute liver injury with hepatic encephalopathy and impaired synthetic function, conventionally a prolonged prothrombin time giving an international normalised ratio (INR) of 1.5 or above, in a patient without pre-existing cirrhosis. It may be complicated by multi-organ failure, disseminated intravascular coagulation, sepsis and cerebral oedema, and is managed in intensive care alongside a liver-transplant service. Viral hepatitis is a leading cause of acute liver failure in many lower-income countries. Per infection, the greatest risk is with hepatitis D, which causes the most severe acute and chronic liver disease of the five, and with hepatitis E in pregnancy, while the risk is lowest with hepatitis C. Absolute burden falls differently: hepatitis E causes the largest number of fulminant cases overall, through waterborne outbreaks in endemic regions, and where chronic hepatitis B is highly prevalent that virus has historically accounted for the greatest volume.
Chronic hepatitis
Chronic hepatitis is defined by persistence of infection beyond six months: hepatitis B surface antigen for hepatitis B, or detectable HCV RNA for hepatitis C. Hepatitis B, hepatitis C, and hepatitis D on a hepatitis B background are the causes of chronic viral hepatitis, and chronic infection drives the long-term burden of progressive fibrosis, cirrhosis and hepatocellular carcinoma (primary liver cancer). The enteric viruses do not contribute, apart from chronic hepatitis E in the immunosuppressed.
Reading the biochemistry
The laboratory picture of acute hepatitis follows a consistent pattern, and interpreting it correctly matters more than memorising numbers.
- Aminotransferases (alanine aminotransferase, ALT, and aspartate aminotransferase, AST) are released from injured hepatocytes and are often markedly raised. The height of the transaminases does not measure severity or predict outcome; a very high ALT simply confirms hepatocyte injury.
- Bilirubin rises in the icteric phase, producing jaundice, scleral icterus and dark urine.
- Synthetic function is the true severity marker. A rising prothrombin time and INR signal failing hepatic synthesis and warn of fulminant hepatitis; albumin falls in more sustained failure. These, not the transaminase level, decide how worried to be.
Hepatitis B has a characteristic extrahepatic prodrome worth recognising: a serum-sickness-like arthritis-dermatitis syndrome, with symmetrical small-joint arthritis and a variable rash, in the weeks before acute hepatitis, driven by immune complexes. The same mechanism underlies the polyarteritis nodosa and glomerulonephritis that can complicate chronic hepatitis B.
The clinical approach and differential diagnosis
A clinical and biochemical picture of acute hepatitis is not specific to viral hepatitis, and the differential must be kept in mind before anchoring on a virus. It includes other systemic viral infections, drugs and toxins (paracetamol, anti-tuberculosis drugs, alcohol and herbal remedies), ischaemic hepatitis, autoimmune hepatitis, Wilson’s disease, Budd–Chiari syndrome, and the pregnancy-related liver diseases. Because the syndrome looks the same whatever the cause, the diagnosis of viral hepatitis rests on serology and molecular testing, not on the clinical picture alone.
Serological markers by virus
Each virus is identified by a small, characteristic set of markers.
- Hepatitis A: IgM anti-HAV indicates acute infection; IgG anti-HAV indicates past infection or immunity.
- Hepatitis B: HBsAg is the first marker to appear and defines current infection, with persistence beyond six months defining chronic infection. Antibody to the surface antigen (anti-HBs) indicates recovery or vaccine immunity. IgM antibody to the core antigen (IgM anti-HBc) appears early and may be the only marker in the window period between HBsAg clearance and anti-HBs appearance. The e antigen (HBeAg) and HBV DNA report replication and guide prognosis and monitoring.
- Hepatitis C: anti-HCV antibody is the screening test and indicates exposure, but it stays positive after the virus is cleared, so active infection must be confirmed with HCV RNA.
- Hepatitis D: test only in a person who is HBsAg positive, since the virus cannot exist without hepatitis B; anti-HDV antibody screens and HDV RNA confirms active infection.
- Hepatitis E: IgM anti-HEV indicates recent infection and IgG persists afterwards, but in immunosuppressed patients antibody may be absent, so HEV RNA is the reliable marker.
Screening and staging
Because hepatitis B and hepatitis C are common, often silent, and treatable, risk-based screening targets them in people who inject drugs, those with a tattoo or piercing history, people in custodial settings, sex workers, sexual and household contacts of infected people, children of infected mothers, pregnant women, and recipients of blood products or organs from the era before reliable donor screening.
Once chronic infection is confirmed, the stage of liver fibrosis determines prognosis and the need for cancer surveillance. Non-invasive methods, transient elastography and serum fibrosis scores, have largely replaced liver biopsy, which is now reserved for diagnostic doubt or where the result would change management.
Key terms
The vocabulary that recurs across the topic, grouped by theme.
Serological and virological markers:
| Marker | What it indicates |
|---|---|
| HBsAg (hepatitis B surface antigen) | Current hepatitis B infection; persistence beyond six months defines chronic infection. |
| Anti-HBs (antibody to surface antigen) | Recovery or vaccine-induced immunity. |
| HBeAg (hepatitis B e antigen) | Active replication and higher infectivity. |
| Anti-HBc IgM (IgM antibody to core antigen) | Recent or acute hepatitis B; the sole marker in the window period. |
| Anti-HBc IgG (IgG antibody to core antigen) | Past exposure; persists for life. |
| Anti-HDV (antibody to hepatitis D) | Hepatitis D exposure; test only when HBsAg positive. |
| HEV RNA | Active hepatitis E, and the reliable marker when antibody is absent in immunosuppression. |
Disease course:
| Term | Meaning |
|---|---|
| Acute hepatitis | The self-limited necro-inflammatory illness common to all five viruses, resolving within weeks to a few months. |
| Chronic hepatitis | Persistence of infection beyond six months (HBsAg for hepatitis B, HCV RNA for hepatitis C); the driver of cirrhosis and liver cancer. |
| Fulminant hepatitis (acute liver failure) | Severe acute injury with encephalopathy and coagulopathy (INR of 1.5 or above) in a previously non-cirrhotic liver. |
| Occult hepatitis B | Detectable HBV DNA with undetectable HBsAg; can reactivate under immunosuppression. |
Treatment and staging:
| Term | Meaning |
|---|---|
| Nucleos(t)ide analogue | Oral hepatitis B agent (tenofovir, entecavir) that suppresses replication long-term without clearing the virus. |
| Pan-genotypic DAA (direct-acting antiviral) | Hepatitis C regimen active across all genotypes, curing most in eight to twelve weeks. |
| SVR (sustained virological response) | Undetectable HCV RNA twelve weeks after treatment; taken as cure. |
| APRI (AST-to-platelet ratio index) | A simple blood-test score that estimates liver fibrosis. |
| Transient elastography | An ultrasound-based measure of liver stiffness used to stage fibrosis non-invasively. |
| Fibrosis stage (F0 to F4) | Histological scale from no fibrosis (F0) to cirrhosis (F4). |
References and recommended reading
- Valaydon ZS, Locarnini SA, Thompson AJV. Viral Hepatitis. In: Richman DD, Whitley RJ, Hayden FG, editors. Clinical Virology, 4th edition, Chapter 5. Washington: ASM Press; 2016. The overview source for the cross-virus comparison, the acute and chronic syndrome definitions, and the clinical and biochemical approach.
- Spearman CWN, Sonderup MW, et al. National Guidelines for the Management of Viral Hepatitis, first edition. National Department of Health, South Africa, with WHO South Africa support; 2019. The national reference for screening, antenatal management and treatment access.
- World Health Organization. Global health sector strategies on HIV, viral hepatitis and sexually transmitted infections, 2022 to 2030. Geneva: WHO; 2022. The global elimination framework and its 2030 targets.