Hepatitis C virus pharmacogenomics in Latin American populations: implications in the era of direct-acting antivirals

Abstract

In recent years, great progress has been made in the field of new therapeutic options for hepatitis C virus (HCV) infection. The new direct-acting antiviral agents (DAAs) represent a great hope for millions of chronically infected individuals because their use may lead to excellent cure rates with fewer side effects. In Latin America, the high prevalence of HCV genotype 1 infection and the significant association of Native American ancestry with risk predictive single-nucleotide polymorphisms (SNPs) in IFNL4 and ITPA genes highlight the need to implement new treatment regimens in these populations. However, the universal accessibility to DAAs is still not a reality in the region as their high cost is one of the major, although not the only, limiting factors for their broad implementation. Therefore, under these circumstances, could the assessment of host genetic markers be a useful tool to prioritize DAA treatment until global access to these new drugs can be achieved? This review will summarize the scientific evidences and the potential implications of HCV pharmacogenomics in this rapidly evolving era of anti-HCV drug development.

Keywords: DAAs; Latin America; PEG-IFN/RBV; hepatitis C virus; pharmacogenomics.

Figure 1

Limiting factors for the global access to DAAs in Latin America. Abbreviations: DAAs, direct-acting antiviral agents; HCV, hepatitis C virus.

Figure 2

IFNL4 SNP rs12979860. Notes: Prevalence of the favorable (CC) and risk (CT/TT) genotypes of IFNL4 SNP rs12979860 in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.05 when comparing samples from the Central region of Argentina with those from the Northeastern and Northwestern regions, Peruvians and Paraguayans; ^bp<0.0001 when comparing samples from the Central region of Argentina with Bolivians. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554. Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish. Abbreviation: SNP, single-nucleotide polymorphism.

Figure 3

ITPA SNP rs1127354. Notes: Prevalence of the favorable (CA/AA) and risk (CC) genotypes of ITPA SNP rs1127354 in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.05 when comparing samples from the Central region of Argentina with Peruvians and Paraguayans; ^bp<0.001 when comparing samples from the Central region of Argentina with those from the Northwestern region; ^cp<0.0001 when comparing samples from the Central region of Argentina with Bolivians. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554. Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish. Abbreviations: ITPA, inosine triphosphatase; SNP, single-nucleotide polymorphism.

Figure 4

ITPA SNP rs7270101. Notes: Prevalence of the favorable (AC/CC) and risk (AA) genotypes of ITPA SNP rs7270101 in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.05 when comparing samples from the Central region of Argentina with those from the Northeastern region; ^bp<0.0001 when comparing samples from the Central region of Argentina with those from the Northwestern region, Bolivians, and Peruvians. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554. Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish. Abbreviations: ITPA, inosine triphosphatase; SNP, single-nucleotide polymorphism.

Figure 5

Maternal ancestry. Notes: Prevalence of the Native American and non-Native American mtDNA haplogroups in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.005 when comparing samples from the Central region of Argentina with those from the Western and Northeastern regions; ^bp<0.0001 when comparing samples from the Central region of Argentina with those from the Northwestern region, Bolivia, Peru, and Paraguay. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554. Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish. Abbreviation: mtDNA, mitochondrial DNA.

Figure 6

Paternal ancestry. Notes: Prevalence of the Native American and non-Native American Y-SNPs haplogroups in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.05 when comparing samples from the Central region of Argentina with those from the Southern and Western regions; ^bp<0.01 when comparing samples from the Central region of Argentina with those from Paraguay; and ^cp<0.0001 when comparing samples from the Central region of Argentina with those from the Northwestern region, Bolivia, and Peru. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554. Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish. Abbreviation: Y-SNPs, Y-chromosome single-nucleotide polymorphisms.