According to the South African National Department of Health (NDoH), liver disease caused by chronic viral hepatitis infection is a silent and neglected contributor to morbidity and mortality in the country. This burden is exacerbated by insufficient screening, limited access to care and treatment, inadequate disease surveillance, and a lack of human and financial resources.³

Who should be screened and tested for hep C?

To eliminate hep C infection in South Africa, which is transmitted via parenteral and non-parenteral routes, it is essential to enhance seroprevalence surveillance and increase screening among high-risk groups, state the NDoH.³

The purpose of screening is to detect hep C viraemia. Key populations that should be screened include people who inject drugs (PWID), people in prisons, and men who have sex with men, particularly those living with HIV.^2,4

According to the NDoH, at risk groups also include:³

• Recipients of blood, blood products, and solid organ transplants in the country before 1992
• Individuals exposed to unsafe medical injection practices
• Healthcare workers with occupational exposure (e.g., needle stick injuries)
• Individuals undergoing chronic haemodialysis (up to 10% risk)
• Those involved in high-risk or traumatic sexual practices
• Users of intranasal cocaine
• Those undergoing tattooing, body piercing, acupuncture, or surgical procedures (including dental and orthodontic procedures without proper sterilisation)
• Individuals participating in traditional or cultural practices (e.g., circumcision, scarification rituals)

According to Sonderup et al, hep C screening should also form part of antenatal care, particularly for HIV-positive women, as well as for children born to hep C-positive mothers. Screening for the general population should leverage existing community-based or facility-based testing opportunities, such as those provided at antenatal clinics, HIV or tuberculosis clinics, and drug-treatment services.⁴

What are some of the signs and symptoms that should raise suspicion of possible hep C infection?

Recently acquired hep C infections are usually asymptomatic and rarely lead to symptomatic acute infection. Following infection, ~30% of infected individuals spontaneously clear the virus within six months without treatment, with a median time to clearance of 16.5 weeks.²

The remaining 70% of affected individuals will develop chronic hep C infection. Importantly, individuals who have cleared their infection, either spontaneously or through treatment, are not immune to the virus and can be reinfected if they have ongoing risk and exposure.²

Acute hep C infection may initially present with symptoms such as malaise, nausea, and right upper quadrant pain, followed by dark urine and jaundice, which clinically resemble other acute viral hepatitis cases.⁵

Chronically infected individuals often remain asymptomatic or may experience non-specific symptoms such as fatigue, intermittent right upper quadrant pain, joint pain, and a general feeling of unwellness that impacts their quality of life.⁵

In individuals with cirrhosis due to hep C infection, 10% to 20% may clinically decompensate within five years. This is characterised by the development of complications such as portal hypertension, oesophageal varices, ascites, coagulopathy, encephalopathy, or hepatocellular carcinoma.⁵

Physical examination at this stage may reveal signs typical of chronic liver disease, including caput medusae, spider angiomas, palmar erythema, asterixis, anasarca, and a fluid thrill. Additionally, patients may manifest signs of various extrahepatic manifestations such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, lichen planus, neurocognitive changes, insulin resistance, and B cell lymphoproliferative disorders.⁵

Who should be tested?

The WHO recommends offering hep C testing to all adults in settings where the prevalence of hep C viral antibodies in the general population >2%, and focused testing in all settings for the most affected populations. A 2015 meta-analysis suggests an overall hep C viral prevalence of 2.98% in sub-Saharan Africa.^2,6

Some countries also include other populations in their focused testing approach, such as migrants, homeless people and the children of parents with hep C.¹

The WHO emphasises that testing should be voluntary and should not contribute to further stigmatisation of populations at ongoing risk. Testing should be integrated with evidence-based primary prevention services that reduce transmission risks, and it should facilitate access to appropriate treatment and linkage to care.²

How to test and treat

The WHO summary algorithm for hep C testing and treatment follows a stepwise process:²

Step 1: Conduct anti-hep C antibody testing

• Use a rapid diagnostic test or laboratory-based immunoassay.

Step 2: If anti-hep C+ proceed to viral load testing

• Use lab-based hep C RNA (qualitative or quantitative) or hep C core antigen (cAg) assays, or point-of-care hep C RNA assays.

Step 3: Interpret results

• If RNA test or cAg is negative: No infection.
• If RNA test or cAg is positive: Hep c viraemic infection.

Step 4: Offer and start treatment

• Eligible Patients: Adults (≥18 years) and adolescents (12- to 17-years).
• Assessment prior to treatment initiation
  • Liver fibrosis: Assess using non-invasive tests (e.g., aspartate aminotransferase to platelet ratio index, Fibrosis-4) to determine if there is cirrhosis.
  • Other considerations: Evaluate comorbidities, pregnancy status, and potential drug-drug interactions.
• Treatment regimens
  • In South Africa, sofosbuvir/velpatasvir is indicated for the treatment of chronic hep C infection irrespective of genotype in treatment naïve or treatment experienced patients aged ≥12-years and weighing at least 30 kg:⁷
  • Without cirrhosis or with compensated cirrhosis
  • With decompensated cirrhosis in combination with ribavirin.

Step 5: Assess cure

• Sustained virological response (SVR): Evaluate at 12 weeks post-treatment using hep C RNA SVR, qualitative or quantitative nucleic acid test.
• Monitoring: For individuals with cirrhosis, detect hepatocellular carcinoma every six months using ultrasound or alfa-fetoprotein liver function test.

Conclusion

Early detection and treatment can greatly reduce hep C transmission and prevent complications like cirrhosis and liver cancer. Integrating hep C screening and testing into existing health services and ensuring voluntary, non-stigmatising practices will be vital steps toward achieving hep C elimination.

References

1. World Health Organization. Global hepatitis report 2024. Action for access in low- and middle-income countries. 2024. [Internet]. Available at: https://www.who.int/publications/i/item/9789240091672
2. World Health Organization. New recommendation on hepatitis C virus testing and treatment for people at ongoing risk of infection. Policy brief. 2023. [Internet]. Available at: https://www.who.int/publications/i/item/9789240071872
3. South African National Department of Health. National Guidelines for the Management of Viral Hepatitis. 2020. [Internet]. Available at: https://knowledgehub.health.gov.za/system/files/elibdownloads/2023-04/SA%2520NDOH_Viral%2520Hepatitis%2520guidelines%2520final.pdf
4. Sonderup MW, Afihene M, Ally R, et al. Hepatitis C in sub-Saharan Africa: the current status and recommendations for achieving elimination by 2030. Lancet Gastroenterology, 2017.
5. Basit H, Tyagi I, Koirala J. Hepatitis C. [Updated 2023 Mar 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430897/
6. Rao VB, Johari N, du Cros P, et al. Hepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Infectious Diseases, 2015.
7. Professional Information. Epclupsa. 2022. [Internet]. Available at: https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2022/04/Final-pi_epclusa_10-Mar2022.pdf