Clinical
South African Viral Hepatitis Guidelines
Last reviewed 17 June 2026
A condensed, scannable companion to the 2019 National Department of Health (NDoH) viral hepatitis guideline, ordered as the guideline is, hepatitis A through E. The five virus profiles explain the biology and natural history; this page is the point-of-care tool. Viral hepatitis is a notifiable medical condition in South Africa.
Two anchors used throughout: the alanine aminotransferase (ALT) upper limit of normal (ULN) is 35 U/L in men and 25 U/L in women, and direct-acting antivirals for hepatitis C were registered by SAHPRA in 2022.
Hepatitis A
Faecal-oral, acute and self-limiting, with no chronic carrier state.
Diagnosis
Acute infection is anti-HAV IgM positive; past infection or vaccine immunity is anti-HAV IgG positive. ALT and AST are often 10 to 100 times the upper limit of normal. Add a liver profile and INR to gauge severity.
Post-exposure prophylaxis
| Exposed person | Within 14 days of exposure |
|---|---|
| Healthy, aged 1 to 40 years | Hepatitis A vaccine (non-inferior to immunoglobulin) |
| Under 2 years, over 40 years, or immunocompromised | Human normal immunoglobulin |
Vaccine is not licensed under 1 year. Many South African adults are already immune, so screening for anti-HAV before vaccinating healthcare workers is cost-effective. Exclude a case from work or school until 2 weeks after the onset of jaundice, provided AST and ALT are under 100 U/L.
Level of care
| Tier | Scope |
|---|---|
| Primary | Diagnosis (anti-HAV IgM and IgG, liver profile, INR); uncomplicated care |
| Secondary | Symptomatic jaundice, INR under 2, no encephalopathy |
| Tertiary | Acute liver failure (jaundice, encephalopathy, INR over 1.5), transplant access |
A cluster of cases is notified to the local outbreak response team, with safe water and sanitation the priority.
Hepatitis B
Acquired mostly in early childhood in South Africa; the dominant chronic hepatitis burden.
Interpreting serology
The marker pattern places a patient in a clinical state. (Anti-HBc is antibody to core antigen; HBsAg is surface antigen; HBeAg is e antigen.)
| Clinical state | Defining marker pattern | HBV DNA | ALT |
|---|---|---|---|
| Vaccinated, immune | anti-HBs positive (over 10 mIU/mL), all else negative | undetectable | normal |
| Past exposure, resolved | IgG anti-HBc positive, HBsAg negative, anti-HBs often positive | undetectable | normal |
| Acute HBV | HBsAg positive, HBeAg positive, IgM anti-HBc positive | detectable | high |
| Occult HBV | IgG anti-HBc positive, HBsAg negative, anti-HBs negative | under 200 IU/mL | normal |
| Chronic, HBeAg positive: immune tolerant | HBsAg positive, HBeAg positive | over 200,000 (often over 1M) | normal |
| Chronic, HBeAg positive: immune clearance | HBsAg positive, HBeAg positive | 20,000 or above | high |
| Chronic, HBeAg negative: immune control | HBsAg positive, anti-HBe positive | under 2,000 | normal |
| Chronic, HBeAg negative: immune escape | HBsAg positive, anti-HBe positive | 2,000 or above | high (fluctuating) |
Fulminant HBV may be HBsAg negative with IgM anti-HBc positive, HBV DNA detectable, and synthetic failure (INR over 1.5).
Treat or monitor
Treat regardless of ALT, HBV DNA or HBeAg if any of: cirrhosis (compensated or decompensated), APRI score over 2, acute liver failure, or impending immunosuppression, chemotherapy or rituximab. Pegylated interferon is contraindicated in decompensated cirrhosis.
Otherwise, in non-cirrhotic patients:
HBeAg positive
| HBV DNA (IU/mL) | ALT | Action |
|---|---|---|
| 20,000 or above | normal (immune tolerant) | Monitor. Treat if over 30 years with significant fibrosis or family history of HCC or cirrhosis |
| 20,000 or above | 1 to 2 times ULN | Exclude other causes. Treat if persistent or fibrosis F2 or worse |
| 20,000 or above | 2 times ULN or above (immune clearance) | Treat |
| 2,000 to 20,000 | 2 times ULN or above | Monitor viral load. Treat if it persists over 6 months or fibrosis F2 or worse |
HBeAg negative
| HBV DNA (IU/mL) | ALT | Action |
|---|---|---|
| under 2,000 | normal (immune control) | Monitor. Treat if close monitoring is not possible |
| 2,000 or above | normal | Monitor. Treat if ALT becomes persistently raised, or high-risk mutations with fibrosis |
| 2,000 or above | 1 to 2 times ULN | Exclude other causes. Treat if persistent or fibrosis F2 or worse |
| 2,000 or above | 2 times ULN or above (immune escape) | Treat (long-term nucleos(t)ide analogue) |
Fibrosis is staged with APRI (a score over 2 indicates cirrhosis), FIB-4, or transient elastography (F2 above roughly 7 to 8.5 kPa; F4 cirrhosis above roughly 11 to 14 kPa).
Drugs
| Agent | Dose | When preferred or noted |
|---|---|---|
| Tenofovir disoproxil fumarate (TDF) | 300 mg daily | First line. Reduce in renal impairment |
| Tenofovir alafenamide (TAF) | 25 mg daily | Over 60 years, low eGFR, bone disease, dialysis (Section 21) |
| Entecavir | 0.5 mg daily (1 mg if lamivudine-experienced) | First line. Adjust for eGFR under 50 |
| Lamivudine | 100 mg daily (300 mg if HIV co-infected) | High resistance; not routine first line |
| Pegylated interferon alfa-2a | 180 µg weekly | Selected patients. Not in decompensated cirrhosis or pregnancy |
Most patients need lifelong nucleos(t)ide analogue therapy.
Monitoring
| Test | On treatment | Not on treatment |
|---|---|---|
| Liver profile, ALT | Baseline, week 4, then 3 to 6 monthly | With viral load |
| HBV DNA | Baseline, week 12, then 6 to 12 monthly | 3 monthly for 1 year, then 6 monthly |
| Creatinine, phosphate, urine protein | Baseline then at least annually (on TDF) | Not applicable |
| HBeAg or anti-HBe | Annually | Annually |
| HCC surveillance (alpha-fetoprotein + ultrasound) | 6 to 12 monthly | 6 to 12 monthly in at-risk groups |
Perinatal pathway
The highest-yield prevention activity. Three numbers to hold: viral load 200,000 IU/mL, gestation 28 to 32 weeks, neonatal window 12 to 24 hours.
| Step | Trigger | Action |
|---|---|---|
| 1. Screen | All pregnant women, first trimester | HBsAg (re-test at delivery if unknown and ongoing risk) |
| 2. Assess | HBsAg positive | Quantify HBV DNA |
| 3. Maternal antiviral | HBV DNA over 200,000 IU/mL | TDF from 28 to 32 weeks, continue to 12 weeks postpartum |
| 4. Neonate | Every baby of an HBsAg-positive mother | HBV monovalent birth dose plus HBIG, different sites, within 12 to 24 hours |
| 5. Infant series | 6, 10 and 14 weeks | Hepatitis B (hexavalent) |
| 6. Infant check | 9 to 18 months | HBsAg and anti-HBs (anti-HBs 10 or above is protected) |
The birth dose is targeted: given only to infants of HBsAg-positive or HBeAg-positive mothers. HBIG is recommended for the highest-risk neonates but is not currently available in the public sector. Caesarean section is not indicated; breastfeeding is safe if the mother is virally suppressed.
Occupational post-exposure prophylaxis
After percutaneous or mucosal exposure to a potentially HBsAg-positive source. HBIG dose is 0.06 mL/kg (about 500 IU) intramuscularly, given with the first vaccine dose at a different site.
| Exposed worker | Source HBsAg positive | Source HBsAg negative | Source unknown |
|---|---|---|---|
| Unvaccinated | HBIG + start vaccine course | Start vaccine course | HBIG + start vaccine course |
| Known responder (anti-HBs 10 or above) | None | None | None |
| Known non-responder (anti-HBs under 10) | HBIG + re-immunise + repeat HBIG at 1 month | Re-immunise | HBIG + re-immunise + repeat HBIG at 1 month |
| Response unknown | Test: if 10 or above none; if under 10, HBIG + booster, recheck at 1 month | Booster + recheck | Treat as non-responder if testing is delayed over 24 hours |
Prophylaxis is ineffective if given more than 7 days after a needlestick or perinatal exposure, or more than 14 days after a sexual exposure. There is no post-exposure prophylaxis for hepatitis C.
Vaccination schedules
| Group | Schedule | Notes |
|---|---|---|
| Infant (EPI) | Targeted birth dose if indicated, then 6, 10, 14 weeks | Hexavalent series |
| Standard adult | 0, 1, 6 months | Post-vaccine anti-HBs 10 or above is immune |
| Dialysis or immunocompromised | 4 doses of 40 µg at 0, 1, 2, 6 months | Annual anti-HBs, booster if under 10 |
Up to 10 per cent do not respond to a standard course. Priority groups include healthcare and laboratory workers, dialysis patients, people who inject drugs, men who have sex with men, and sexual or household contacts of HBsAg-positive people.
Level of care
| Tier | Scope |
|---|---|
| Primary | Serology; TDF and lamivudine; follow-up of immune-tolerant and immune-control patients |
| Secondary | HBV DNA quantification, ultrasound; immune-clearance and immune-escape patients |
| Tertiary | Genotype and resistance; TAF, entecavir, interferon; cirrhosis, fulminant disease, co-infection |
Hepatitis C
Concentrated in key populations, above all people who inject drugs. Now curable with short oral courses.
Screen to cure
| Step | Result | Action |
|---|---|---|
| Anti-HCV antibody (EIA or rapid test) | Negative | Reassure. Retest in 6 to 12 months if a key population |
| Positive | Reflex quantitative HCV RNA (mandatory) | |
| HCV RNA | Negative | Not viraemic. Reassure; continue harm reduction |
| Positive | Test HIV and HBsAg; stage fibrosis (APRI, FIB-4 or elastography) | |
| Treat | Pan-genotypic DAA | See regimens below; address drug interactions |
| Confirm cure | HCV RNA 12 weeks after treatment ends | Undetectable is sustained virological response (cured) |
Treatment priority order: significant fibrosis (F3 or cirrhosis), HIV or HBV co-infection, extrahepatic disease, acute HCV, transplant recipients, and people who inject drugs.
DAA regimens
| Regimen | Genotypes | Non-cirrhotic | Compensated cirrhosis |
|---|---|---|---|
| Sofosbuvir / velpatasvir | All (1 to 6) | 12 weeks | 12 weeks |
| Glecaprevir / pibrentasvir | All (1 to 6) | 8 weeks | 8 weeks (12 to 16 weeks if genotype 3 and treatment-experienced) |
| Sofosbuvir / daclatasvir | All (1 to 6) | 12 weeks | 12 weeks (add ribavirin) |
Genotype rarely changes the choice now that regimens are pan-genotypic. Add weight-based ribavirin where a regimen specifies it for cirrhotic or treatment-experienced patients.
Level of care
| Tier | Scope |
|---|---|
| Primary | Anti-HCV and HCV PCR, including point-of-care testing |
| Secondary | RNA quantification, ultrasound, fibrosis staging |
| Tertiary | Genotype and resistance; DAA initiation; cirrhosis and co-infection |
Hepatitis D
Defective; occurs only in HBsAg-positive people. Hepatitis B vaccination is the only prophylaxis.
Which entity
| Entity | Serology | Outcome |
|---|---|---|
| Acute HBV and HDV co-infection | IgM anti-HDV positive, HDV RNA positive, HBsAg positive, IgM anti-HBc positive | Over 95 per cent clear both (higher fulminant risk) |
| HDV superinfection of chronic HBV | IgM anti-HDV positive, HDV RNA positive, HBsAg positive, IgM anti-HBc negative | Chronic in 70 to 90 per cent; rapid cirrhosis |
| Chronic HDV | IgG anti-HDV positive, HDV RNA positive, HBsAg positive | Progressive disease |
Treatment is pegylated interferon alfa for 48 weeks (HDV RNA clearance 17 to 47 per cent, relapse common). Refer all suspected cases to tertiary care.
Hepatitis E
Endemic in South Africa. Usually self-limiting, but dangerous in pregnancy and able to become chronic in the immunosuppressed.
Diagnosis
| Form | Markers | Setting |
|---|---|---|
| Acute | anti-HEV IgM and IgG positive | Usually self-limited |
| Chronic | anti-HEV IgG positive, HEV RNA over 6 months | Immunosuppressed (transplant, genotype 3) |
Severe disease occurs in pregnant women in the third trimester and in those with chronic liver disease. Acute disease is supportive; for chronic disease, reduce immunosuppression then give ribavirin 600 to 800 mg daily. Admit pregnant women and severe cases.
Level of care
| Tier | Scope |
|---|---|
| Primary | Anti-HEV IgM and IgG, liver profile, INR; uncomplicated care |
| Secondary | Symptomatic care |
| Tertiary | HEV RNA and genotype; acute liver failure, chronic HEV |
A cluster of cases is notified to the local outbreak response team; securing safe water and protecting pregnant women are the priorities.
References and recommended reading
- National Department of Health, South Africa. National Guidelines for the Management of Viral Hepatitis. First edition, December 2019. The primary source for every algorithm, table and threshold on this page.
- National Department of Health, South Africa (Knowledge Hub). Hepatitis B Vaccine: targeted birth dose [webinar]. 31 October 2023. The current detail of the targeted hepatitis B birth dose.
- Martinello M, Solomon SS, Terrault NA, Dore GJ. Hepatitis C. The Lancet 2023;402(10407):1085-1096. Current pan-genotypic direct-acting antiviral practice underpinning the hepatitis C pathway.