South African Viral Hepatitis Guidelines — Questions

Impending immunosuppression is one of the situations in which the guideline says to treat regardless of ALT, HBV DNA or HBeAg. B cell depletion with rituximab, cytotoxic chemotherapy and transplant conditioning all carry a high risk of hepatitis B reactivation, which can be fulminant. Antiviral cover is started before the immunosuppression, not in response to a later flare.

The other triggers in this “treat regardless” group are cirrhosis (compensated or decompensated), an APRI score above 2, and acute liver failure.

Options A and B apply the ordinary viral-load and ALT thresholds, which are the wrong frame here: the point of prophylaxis is to act before reactivation, not to wait for it. Immunoglobulin (D) has no role in this setting, and the serology is unambiguous, so repeating it (E) only wastes time.

A non-responder cannot mount protective antibody quickly, so a high-risk exposure is covered with passive antibody twice. The guideline gives hepatitis B immunoglobulin now, re-immunises, and repeats the immunoglobulin at 1 month, bridging the worker through the window that a single dose would leave exposed.

A single immunoglobulin dose (A) or a booster alone (B) under-treats a proven non-responder facing an HBsAg-positive source. Starting only a vaccine course (C) is the response to a negative source, not a positive one. Dismissing the exposure (E) misjudges a needlestick from a known-positive source.

Unlike hepatitis B, hepatitis C has no post-exposure prophylaxis: there is no protective immunoglobulin and no vaccine. The exposed worker is instead monitored, with baseline and follow-up testing, and treated only if infection is established, where a short direct-acting antiviral course is curative.

Immunoglobulin (A) and a vaccine (D) do not exist for hepatitis C. Starting antivirals pre-emptively (B) is not prophylaxis and is not recommended for a mere exposure. Interferon (E) is obsolete for this indication.

A documented anti-HBs of 10 mIU/mL or above marks a known responder, who needs no post-exposure prophylaxis whatever the source status. Vaccine-induced immune memory protects even if the measured titre has since waned, so neither immunoglobulin nor a booster adds anything.

The immunoglobulin-containing options (C, D, E) belong to the non-responder or unvaccinated worker. A booster (B) is what you would consider for a worker of unknown response after checking the titre, not for a confirmed responder.

An immune-tolerant patient (HBeAg positive, very high viral load, normal ALT) is ordinarily monitored rather than treated. The guideline shifts to treatment when the patient is over 30 with significant fibrosis or a family history of hepatocellular carcinoma or cirrhosis. At 34 this patient already meets the age condition, so a family history of hepatocellular carcinoma is the factor that pushes towards treatment.

Being under 30 (B) would keep the patient in the monitored group. HBeAg positivity (C) and a normal ALT (D) simply describe the immune-tolerant state already given. Anti-HBs positivity (E) would point away from active disease altogether.

Maternal antiviral cover is the part of the perinatal pathway that targets the small group at highest transmission risk. When the HBV DNA is above 200,000 IU/mL, tenofovir disoproxil fumarate is started from 28 to 32 weeks and continued to 12 weeks postpartum, lowering the viral load before delivery so that the infant immunoprophylaxis has the best chance of working.

Treating every HBsAg-positive mother (A) is unnecessary, since below the threshold the birth-dose vaccine and immunoglobulin suffice. The 2,000 IU/mL figure in C is the chronic-hepatitis treatment threshold, not the perinatal one. Waiting until delivery (D) leaves no time to suppress the viral load, and the 36-week start in E is too late.

Both drugs are first-line, but TAF is preferred where the renal and bone toxicity of TDF is a concern: age over 60, a low estimated glomerular filtration rate, bone disease, and dialysis. The dialysis patient with reduced bone density in option E fits every part of that profile, and TAF is accessed through a Section 21 application.

A young adult with normal kidneys (A) has no reason to move off standard TDF. Pregnancy (B) favours TDF, which has the larger safety record in that setting. Paediatric use (C) is a separate licensing question, not a TDF-versus-TAF toxicity trade-off. In HIV co-infection (D) the tenofovir component is already supplied by the antiretroviral regimen.

Passive antibody has to be in place before the virus establishes infection, so timing is tight. Prophylaxis is regarded as ineffective if given more than 7 days after a needlestick or perinatal exposure. Immunoglobulin should therefore be given as soon as possible, ideally within 24 hours, not held pending source results.

The 14-day figure in option D is the separate window for a sexual exposure, a common point of confusion. The occupational immunoglobulin dose itself is 0.06 mL/kg (about 500 IU) intramuscularly, given with the first vaccine dose at a different site.

Chronic hepatitis E occurs almost only in the immunosuppressed, typically genotype 3 in a transplant recipient. Management is stepwise: reduce immunosuppression first, which alone clears many cases, then give ribavirin (600 to 800 mg daily) if the virus persists.

Supportive care alone (A) is right for acute, self-limiting hepatitis E, not the chronic form. There is no licensed pan-genotypic direct-acting antiviral (B) or hepatitis E vaccine (D) in this setting, and interferon (C) is avoided in transplant recipients because it can precipitate graft rejection.

The guideline anchors its treat-versus-monitor decisions to a sex-specific ALT upper limit of normal: 35 U/L in men and 25 U/L in women. These thresholds are lower than the laboratory reference ranges printed on many result slips, so a “normal” ALT on the report can still be above the guideline limit and tip a patient into a treatment band.

Option C is the AASLD figure (30 in men, 19 in women), a plausible near-miss but not the value this guideline uses. Option D inverts the sexes. The 40 U/L cut-offs in A and E reflect older generic laboratory ranges rather than the guideline.

Impaired responders need both a larger antigen dose and an extra dose. Dialysis and immunocompromised adults receive four doses of 40 µg at 0, 1, 2 and 6 months, then annual anti-HBs monitoring with a booster if the titre falls under 10 mIU/mL.

Option A is the standard immunocompetent adult schedule (0, 1, 6 months at the ordinary dose), which under-immunises this group. The reduced or two-dose regimens in B, C and D would leave many of these patients unprotected.

Hepatitis D is defective and can only infect people who are already HBsAg positive, because it needs the hepatitis B surface antigen to assemble. Preventing hepatitis B therefore prevents hepatitis D, so hepatitis B vaccination is the only prophylaxis.

There is no hepatitis D-specific vaccine (B) or immunoglobulin (D). Interferon (C) is a treatment for established infection, not prophylaxis, and bulevirtide (E) is an entry inhibitor used therapeutically, not for pre-exposure prevention.

Treatment cures nearly everyone, so prioritisation is about who is harmed most by waiting. Significant fibrosis (F3 or cirrhosis) heads the priority order, followed by HIV or hepatitis B co-infection, extrahepatic disease, acute hepatitis C, transplant recipients, and people who inject drugs.

Patients with little or no fibrosis (B and C) can safely wait their turn. A person who is anti-HCV positive but HCV RNA negative (D) is not viraemic and needs no treatment at all. Declining harm reduction (E) is not a treatment-priority criterion; treatment is itself part of prevention.

Faecal shedding falls after the onset of jaundice, so exclusion is tied to that landmark: the guideline excludes a case until 2 weeks after the onset of jaundice, provided the AST and ALT are under 100 U/L.

Waiting for jaundice to resolve entirely (A) is unnecessarily long, and a fixed 7-day (C) or 6-week (E) rule ignores the jaundice landmark. Anti-HAV IgM (D) can persist for months after infectivity has passed, so it does not gauge when a case can return.

The guideline uses simple, widely available scores to stage fibrosis when biopsy and elastography are not to hand. An APRI (aspartate aminotransferase to platelet ratio index) above 2 indicates cirrhosis, which is itself a “treat regardless” trigger alongside decompensation, acute liver failure and impending immunosuppression.

For orientation on the elastography scale, significant fibrosis (F2) sits above roughly 7 to 8.5 kPa and cirrhosis (F4) above roughly 11 to 14 kPa. So the 6 kPa in option B is below the F2 threshold, and an APRI of 0.5 (option A) is reassuring. The isolated viral load in C and the mildly raised ALT in E are ordinary monitoring parameters, not markers of cirrhosis.

Now that regimens are pan-genotypic, genotype rarely changes the choice, and the decision turns on fibrosis and duration. Glecaprevir / pibrentasvir treats all genotypes in 8 weeks in a non-cirrhotic patient, the shortest option. Sofosbuvir / velpatasvir and sofosbuvir / daclatasvir are also pan-genotypic but run 12 weeks, so the 24-week figure in option A is wrong.

Interferon (D) and ribavirin monotherapy (E) belong to the pre-DAA era and have no place as first-line hepatitis C treatment. Weight-based ribavirin is added only where a regimen specifies it for cirrhotic or treatment-experienced patients.

The discriminator is the marker of recent hepatitis B infection. In acute co-infection both viruses are caught together, so IgM anti-HBc is positive; in superinfection the hepatitis B is long-standing, so IgM anti-HBc is negative. This distinction matters: co-infection usually clears both viruses (over 95%), whereas superinfection becomes chronic in 70 to 90% and drives rapid cirrhosis.

HBsAg (A), HDV RNA (B) and IgM anti-HDV (D) are positive in both scenarios, so none separates them. Anti-HBs (E) would not be present during active surface-antigenaemia.

Post-exposure prophylaxis is stratified by who mounts a reliable vaccine response. The hepatitis A vaccine (non-inferior to immunoglobulin) is used for healthy people aged 1 to 40, while immunoglobulin is reserved for those under 2, over 40, or immunocompromised. The 18-month-old in option D falls in the under-2 group, and the vaccine is in any case not licensed below 1 year.

All the other contacts are healthy adults aged 1 to 40, so each receives the vaccine within the 14-day window. Because many South African adults are already immune, screening for anti-HAV before vaccinating healthcare workers is cost-effective.

A positive antibody marks exposure, not current infection, so the pathway runs from confirming viraemia to proving cure.

a. Confirm viraemia. The antibody-positive result triggers a mandatory reflex quantitative HCV RNA. A positive RNA confirms active (viraemic) infection; a negative RNA means past or cleared infection, needing only reassurance and continued harm reduction.

b. Work up before treatment. Test for HIV and HBsAg (co-infection changes management and carries a reactivation risk), and stage fibrosis with APRI, FIB-4 or elastography.

c. Treat. Give a pan-genotypic direct-acting antiviral regimen, checking for and managing drug interactions, which matter in this population.

d. Confirm cure. Measure HCV RNA 12 weeks after treatment ends; an undetectable result is a sustained virological response, which equals cure.

Ongoing harm reduction continues throughout, and reinfection is possible, so retesting is offered if exposure continues.

The perinatal pathway is the highest-yield prevention activity in hepatitis B, built around three numbers: a viral load of 200,000 IU/mL, a gestational window of 28 to 32 weeks, and a neonatal window of 12 to 24 hours.

a. Assess the mother. Quantify the HBV DNA. Maternal antiviral treatment is indicated when the viral load is above 200,000 IU/mL, which identifies the pregnancies at highest transmission risk.

b. Maternal antiviral. Give tenofovir disoproxil fumarate from 28 to 32 weeks, continued to 12 weeks postpartum, to suppress the viral load before delivery.

c. Immunise the neonate. Every baby of an HBsAg-positive mother receives the monovalent hepatitis B birth dose plus hepatitis B immunoglobulin (HBIG), at different sites, within 12 to 24 hours of birth. (HBIG is recommended for the highest-risk neonates but is not currently available in the public sector.)

d. Complete and confirm. Give the routine hexavalent infant series at 6, 10 and 14 weeks, then check HBsAg and anti-HBs at 9 to 18 months; an anti-HBs of 10 mIU/mL or above confirms protection.

Caesarean section is not indicated, and breastfeeding is safe once the mother is virally suppressed.

TDF can cause a proximal renal tubulopathy, so the annual review is built around renal safety.

• Serum creatinine (or estimated glomerular filtration rate): tracks falling renal function, which also prompts a dose reduction or a switch to tenofovir alafenamide.
• Serum phosphate: hypophosphataemia is an early marker of the proximal tubular injury TDF causes.
• Urine protein: tubular proteinuria signals the same nephrotoxicity before creatinine rises.
• Rationale: together these detect TDF-associated nephrotoxicity early, allowing a change of agent before lasting renal or bone harm.

Acute liver failure is the point at which acute hepatitis becomes an emergency needing tertiary care and transplant assessment. The defining features are:

• Hepatic encephalopathy: altered mental state signalling loss of hepatic function.
• Coagulopathy with an INR over 1.5: synthetic failure, the key laboratory marker.
• Deepening jaundice: rising bilirubin marking severe hepatocellular injury.

Any of these in a patient with acute hepatitis warrants referral to a centre with transplant access.