An estimated eight million individuals in the African region are living with HCV. Furthermore, ~172 000 new infections are reported in the African region annually. Importance of screening, testing and diagnosing HCV Between 15%-25 % of infected individuals naturally eliminate the virus within six months.¹  

However, the remaining 75%-85% will progress to chronic hep C. Among those with chronic infection, the risk of cirrhosis ranges from 15%-30% within 20 years, with an annual risk of hepatocellular carcinoma ranging from 1%-4%.²   

The authors of the South African National Department of Health’s Guidelines for the Management of Viral Hepatitis, stress that without proper diagnosis and treatment, ~30 % of individuals chronically infected with viral hepatitis will die as a result of severe liver conditions such as cirrhosis, liver failure, and hepatocellular carcinoma.²  

According to the World Health Organization (WHO) Global Hepatitis Report 2024, two major challenges in the effective management of hep C in the African region are the lack of diagnostics and access to curative treatment. Currently, only South Africa and Rwanda provide hep C diagnosis and treatment free of charge in the public sector, either fully or partly for specific subpopulations.¹ 

In the African region, only ~13% of individuals living with chronic HCV were diagnosed, and only ~3 % had access to treatment in 2022. Diagnostic coverage (24%) and access to treatment (19 %) were slightly better in South Africa compared to the rest of Africa.¹ 

Subpopulations at risk of HCV infection  

Subpopulations at high risk of HCV infection include individuals who inject drugs, men who have sex with men (particularly those living with HIV), patients living with HIV, and the incarcerated population.^3,4 

Findings from a South African study suggest that ~50 % of individuals who inject drugs, and between 3%-6% of men who have sex with men, especially if HIV positive, are re living with chronic Hep C virus infection.²  

Among South Africans who inject drugs, there is notable regional disparity in viraemic  prevalence, with the highest rates observed in Pretoria (~84%) and between 30%-40 % in Durban and Cape Town.² 

The prevalence of documented HIV/HCV co-infection in South Africa varies from 1% to 13.4%. This co-infection significantly alters the natural progression of HCV and is considered a priority for treatment with direct-acting antivirals (DAAs).² 

This is due to several factors, including accelerated fibrosis leading to cirrhosis, increased risk of hepatocellular carcinoma, increased HCV transmission risk (especially mother-to-child transmission), elevated susceptibility to liver injuries induced by antiretroviral therapy and tuberculosis medications, and reduced effectiveness of interferon-based therapy.²  

In sub-Saharan Africa, hep C transmission risk also arises in healthcare settings due to unsafe medical practices. In South Africa, unsafe medical practices account for 10% of cases.^3,4 

Additional risk groups include healthcare professionals (due to occupational hazards like needle stick injuries), and individuals undergoing chronic haemodialysis (~10%) or surgical procedures including dental or orthodontic procedures without adequate sterilisation. Furthermore, individuals involved in high-risk or traumatic sexual practices, intranasal cocaine users, or those who have tattoos or body piercings done, or opt for acupuncture procedures, are at increased risk. Traditional or cultural practices such as circumcision and scarification rituals also pose potential risks.²   

Despite a historically secure blood and blood products supply system, individuals living with haemophilia, and those who received blood or blood products before 1992 are at risk of infection. During acute hep C infection, individuals may experience symptoms such as malaise, nausea, and right upper quadrant pain, followed by dark urine and jaundice. These manifestations are clinically similar to those of other acute viral hepatitis cases.^4,5 

Chronically infected individuals typically remain asymptomatic. Symptoms, when present, are non-specific and may include fatigue, intermittent right upper quadrant pain, joint pain, and a general feeling of being unwell, leading to a reduced overall quality of life. However, attributing these symptoms solely to hep C is challenging, as there may also be a psychological component due to the awareness of having an underlying chronic disease.⁵ 

Prevalent hep C genotypes in SA and symptoms  

There are six clinically significant hep C genotypes and over 80 subtypes. The prevalence of genotypes varies depending on the geographic region and the route of acquisition. In South Africa, multiple genotypes, including 1 to 5, are observed, with genotypes 1 and 5 being the most common, and genotype 4 being increasingly detected.² 

Notably, genotype 5a, initially discovered in South Africa, is unique to the region. This viral genotype significantly influences the response to interferon/ribavirin combination therapy, but not with the newer DAAs.²   

The DAA revolution  

DAAs have changed the trajectory of hep C management. DAA therapy boasts a high sustained viral response rate (SVR) at 12 weeks post-treatment completion and is linked with a decreased risk of mortality and hepatocellular carcinoma.⁶ 

According to the National Department of Health guidelines for the management of viral hepatitis, all patients with hep C must be offered therapy unless concomitant co-morbidities will result in short-term mortality.²  

The WHO recommends pan-genotypic DAA regimens for all adults, adolescents and children (≥3-years) living with chronic hep C, regardless of the stage of the disease.¹  

In South Africa, registered pan-genotypic DAA regimens are recommend for children >12-years. Pan-genotypic regimens include sofosbuvir/velpatasvir (SOF/VEL). Non-pangenotypic DAA regimens may be considered in settings where genotype 3 is minimal.^1,2   

How effective is sofosbuvir-velpatasvir?  

The fixed-dose combination (FDC) of SOF/VEL became available in South Africa in 2023. It is approved for treating chronic hep C infection, regardless of genotype, in both treatment-naïve and treatment-experienced patients aged ≥12-years, weighing at least 30kg, and without cirrhosis or with compensated cirrhosis. This regimen can also be used in combination with ribavirin for patients with decompensated cirrhosis.⁷  

SOF/VEL is the first pan-genotypic, pan-fibrotic, protease inhibitor-free, all-oral single-tablet regimen and can be used as a fixed 12-week treatment duration in all adult patients with chronic hep C.⁸  

FDC SOF/VEL is a once-daily single-tablet regimen that combines two pangenotypic antiviral agents with high potency, a high genetic barrier, and with favourable safety and tolerability profiles observed in a wide range of patients, including those with decompensated cirrhosis. SOF is a nucleotide analogue inhibitor targeting the HCV NS5B polymerase. VEL is a last generation, pangenotypic HCV NS5A inhibitor.⁹ 

In a comprehensive real-world analysis conducted by Mangia et al, the effectiveness of SOF/VEL without ribavirin in achieving SVR in individuals (n=5552) living with hep C was assessed across 12 clinical cohorts worldwide.⁸  

Some 13.3% of participants were treatment-experienced, 20.7% had liver cirrhosis, 30.2% were infected with genotype 1, 29.5% with genotype 2, 32.9% with genotype 3, and 4.7 % with genotype 4. Furthermore, 3.7% were living with HIV co-infection, 13.4 % were current/former intravenous drug users.⁸  

Overall, 98.9% of patients achieved SVRs with high rates observed across all genotypes, including genotype 3 (98.3%) and among those with compensated cirrhosis (97.9%). Compensated cirrhosis was identified as a significant risk factor for not achieving SVR. Non-virological reasons accounted for 6% of cases not achieving SVR, primarily due to loss to follow-up or early treatment discontinuation.⁸  

In the Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection (ASTRAL 1) study, Feld et al (2015) demonstrated that once-daily SOF/VEL for 12 weeks achieved high rates of SVR (99 %) among patients infected with hep C genotypes 1, 2, 4, 5, or 6, including those with compensated cirrhosis.¹⁰  

In the Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection (ASTRAL 2 and 3) study, Foster et al (2015) assessed the efficacy of SOF/VEL compared to SOF-ribavirin. Participants included some living with compensated cirrhosis. Among patients with genotype 2, the SOF/VEL group achieved a significantly higher SVR rate of 99% compared to 94% in the SOF-ribavirin group. Similarly, among patients with genotype 3, the SVR rate was notably higher in the SOF/VEL group at 95%, compared to 80% in the SOF-ribavirin group.¹¹   

Furthermore, Curry et al (2015) highlighted the increasing prevalence of decompensated cirrhosis among HCV-infected individuals. In the Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis (ASTRAL 4), SVR rates of 83% were reported in individuals living with decompensated cirrhosis who received 12 weeks of SOF/VEL, 94% among those who received 12 weeks SOF/VEL plus ribavirin, and 86% among those who received 24 weeks of SOF/VEL.¹²  

Wyles et al (2017) assessed the efficacy of SOF/VEL in patients coinfected with HCV and HIV-1 in the Sofosbuvir and Velpatasvir for the Treatment of Hepatitis C Virus in Patients Coinfected with Human Immunodeficiency Virus Type 1 (ASTRAL 5) study, demonstrating favourable SVR rates and safety profiles.¹³  

In addition, the AIDS Clinical Trials Group A5360 Minimal Monitoring trial explored simplified monitoring strategies for hep C treatment, emphasising the use of SOF/VEL. The trial revealed high SVR rates (95%) and safety outcomes (4% of the study population experienced adverse effects) with minimal monitoring, suggesting the potential for this approach to enhance treatment accessibility and contribute to global hep C elimination efforts.¹⁴  

Conclusion  

Hep C infection remains a significant global healthcare challenge, with millions of individuals affected. The introduction of pan-genotypic effective treatments like SOF/VEL represents a crucial advancement in hep C management, offering high cure rates across diverse patient populations, including those with compensated cirrhosis.  

Real-world analyses have demonstrated the effectiveness of SOF/VEL in achieving SVR rates >98 % across various genotypes and patient cohorts. Importantly, SOF/VEL's once-daily single-tablet regimen and predictable safety profile make it an option for simplifying treatment and improving adherence. However, challenges persist, including limited diagnostic coverage and treatment access, especially in resource-constrained settings. Efforts to expand screening, testing, and treatment initiatives are crucial for maximising the impact of SOF/VEL and moving closer to the goal of hep C elimination by 2030.  

References 

1. World Health Organization. Global Hepatitis Report. 2024. [Internet]. Accessed 11 April 2024. Available at: https://www.who.int/publications/i/item/9789240091672 
2. South African National Department of Health. National Guidelines for the Management of Viral Hepatitis. 2023. [Internet]. Accessed 12 April 2024. https://knowledgehub.health.gov.za/system/files/elibdownloads/2023- 04/SA%2520NDOH_Viral%2520Hepatitis%2520guidelines%2520final.pdf 
3. Saayman E, Hechter V, Kayuni N, et al. A simplified point-of-service model for hepatitis C in people who inject drugs in South Africa. Harm Reduct J, 2023. 
4. Sonderup MW, Gogela N, Nordien R, et al. Direct-acting antiviral therapy for hepatitis C: The initial experience of the University of Cape Town/ Groote Schuur Hospital Liver Clinic, South Africa. SAMJ, 2020. 
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. Ichikawa T, Miyaaki H, Miuma S, et al. Direct-acting Antivirals Improved the Quality of Life, Ameliorated Disease-related Symptoms, and Augmented Muscle Volume Three Years Later in Patients with Hepatitis C Virus. Intern Med, 2020. 
7. Professional information. Epclusa. https://www.gilead.com/-/media/ files/pdfs/medicines/liver-disease/epclusa/ epclusa_pi.pdf 
8. Mangia A, Milligan S, Khalili M, et al. Global real-world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: Analysis of 5552 patients from 12 cohorts. Liver Int, 2020. 
9. Zignego AL, Monti M, Gragnani L. Sofosbuvir/Velpatasvir for the treatment of Hepatitis C Virus infection. Acta Biomed, 2018. 
10. Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med, 2015. 
11. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med, 2015. 
12. Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med, 2015. 
13. Wyles D, Bräu N, Kottilil S, et al. Sofosbuvir and Velpatasvir for the Treatment of Hepatitis C Virus in Patients Coinfected with Human Immunodeficiency Virus Type 1: An Open-Label, Phase 3 Study. Clin Infect Dis, 2017.