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Early detection saves lives: The critical role of screening and testing for hepatitis C

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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

A vector of a female doctor taking a biopsy of a liver to detect hepatitis C
Key populations that should be screened include people who inject drugs, people in prisons, and men who have sex with men, particularly those living with HIV. [Source: Shutterstock]

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

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