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Molecular characterization of hepatitis C virus in liver disease patients in Botswana: a retrospective
Lynnette Bhebhe1,2, Motswedi Anderson1, Sajini Souda3
1Botswana Harvard AIDS Institute Partnership, Research Laboratory, Gaborone, Botswana.
Insights
Hepatitis C virus (HCV) genotypes 5a and 4v are circulating in Botswana. Mutations found in genotype 5 may reduce the effectiveness of current interferon-based treatments, supporting a shift to direct-acting antivirals.
Area of Science:
- Hepatology
- Virology
- Genetics
Background:
- Hepatitis C virus (HCV) infection is a significant global cause of chronic liver disease.
- Current standard of care (SOC) in Botswana uses PEGylated interferon-α (IFN-α) with ribavirin, despite the availability of more effective direct-acting antivirals (DAAs).
- Interferon-based treatments can be hindered by specific HCV mutations conferring resistance.
Purpose of the Study:
- To determine the circulating Hepatitis C virus (HCV) genotypes in Botswana.
- To provide data for updating HCV treatment guidelines and understanding local HCV epidemiology.
- To inform the potential implementation of direct-acting antivirals (DAAs) as the new standard of care (SOC).
Main Methods:
- A retrospective cross-sectional pilot study was conducted.
- Plasma samples from 55 participants in Gaborone, Botswana, were analyzed.
- HCV genotypes were identified using phylogenetic analysis of the partial core region.
Main Results:
- HCV genotypes 5a (four sequences) and 4v (two sequences) were identified.
- Two mutations, K10Q and R70Q, were found in genotype 5a sequences.
- The R70Q mutation is associated with resistance to interferon-based treatments, and both mutations are linked to increased hepatocellular carcinoma (HCC) risk.
Conclusions:
- Hepatitis C virus (HCV) genotypes 5a and 4v are prevalent in Botswana.
- The identified mutations in genotype 5 suggest potential non-response to interferon-based regimens.
- Study findings, aligned with WHO recommendations, can guide policymakers in adopting DAAs as the new SOC for HCV in Botswana.
Background:
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease globally. Direct acting antivirals (DAAs) have proven effective in curing HCV. However, the current standard of care (SOC) in Botswana remains PEGylated interferon-α (IFN-α) with ribavirin. Several mutations have been reported to confer resistance to interferon-based treatments. Therefore, there is a need to determine HCV genotypes in Botswana, as these data will guide new treatment guidelines and understanding of HCV epidemiology in Botswana.
Methods:
This was a retrospective cross-sectional pilot study utilizing plasma obtained from 55 participants from Princess Marina Hospital in Gaborone, Botswana. The partial core region of HCV was amplified, and genotypes were determined using phylogenetic analysis.
Results:
Four genotype 5a and two genotype 4v sequences were identified. Two significant mutations - K10Q and R70Q - were observed in genotype 5a sequences and have been associated with increased risk of hepatocellular carcinoma (HCC), while R70Q confers resistance to interferon-based treatments.
Conclusion:
Genotypes 5a and 4v are circulating in Botswana. The presence of mutations in genotype 5 suggests that some patients may not respond to IFN-based regimens. The information obtained in this study, in addition to the World health organization (WHO) recommendations, can be utilized by policy makers to implement DAAs as the new SOC for HCV treatment in Botswana.
