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Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon

Abstract

Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.

Keywords:
Hepatitis C; Genotype 4; Sustained viral response

INTRODUCTION

According to the World Health Organization (WHO), hepatitis C virus (HCV) affects millions of people worldwide; it is estimated that approximately 71 million people are chronically infected with HCV, causing a serious global public health problem11. World Health Organization (WHO). Hepatitis C. April 2017 - Updated October 2017. Available Available from: who.int/mediacentre/factsheets/fs164/en/ Access in Jun 7th, 2017.
from: who.int/mediacentre/factsheets/fs1...
.

There are seven HCV genotypes including 67 subtypes, which are geographically distributed throughout the world22. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014;59(1):318-27.. In Brazil, the genotype distribution pattern consists of genotype 1, followed by genotypes 3, 2, 4, and 533. Campiotto S, Pinho JR, Carrilho FJ, Da Silva LC, Souto FJ, Spinelli V, et al. Geographic distribution of hepatitis C virus genotypes in Brazil. Braz J Med Biol Res. 2005;38(1):41-9.-44. Lampe E, Espirito-Santo MP, Martins RM, Bello G. Epidemic history of Hepatitis C virus in Brazil. Infect Genet Evol. 2010;10(7):886-95..

The treatment recommended by the Brazilian Ministry of Health for chronic HCV infection involves oral combinations of direct-acting antivirals (DAAs); sofosbuvir in association with simeprevir or daclatasvir. These drug combinations are well tolerated and have been reported to increase sustained virological response (SVR) rates to approximately 90%55. Ministério da Saúde (MS). Secretaria de Vigilância e Saúde. Departamento de Vigilância, Prevenção e Controle das DST, do HIV/Aids e da Hepatites Virais. Protocolo Clínico e Diretrizes Terapêuticas para Hepatite C e Coinfecções. Brasília: MS; 2017. 143p.

6. Jiménez-Pérez M, González-Grande R, España Contreras P, Pinazo Martínez I, de la Cruz Lombardo J, Olmedo Martín R. Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance. World J Gastroenterol. 2016;22(29):6573-81.
-77. Welzel TM, Petersen J, Herzer K, Ferenci P, Gschwantler M, Wedemeyer H, et al. Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort. Gut. 2016;65(11):1861-70..

CASE REPORT

A 62-year-old woman was admitted to the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) in November 2015. Upon admission, the patient complained of a headache, nausea, and an extrahepatic manifestation of neurological motor impairment. The patient had received blood transfusion eight years prior in Alenquer, during an upper digestive endoscopy procedure. Follow-up tests prior to treatment are detailed in Table 1. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily); SVR was achieved and hepatic markers values returned to normal six months after the end of treatment (Table 1).

TABLE 1:
Patient laboratory test results.

DISCUSSION

Hepatitis C virus genotype 4 (HCV GT-4) represents approximately 15­18 million cases of the total global HCV infections. It is prevalent in lower income countries in Northern and Equatorial Africa, the Middle East, and Caribbean and Indian regions88. Abdel-ghaffar TY, Sira MM, El Naghi S. Hepatitis C genotype 4 : the past, present, and future. World J Hepatol. 2015;7(28): 2792-2810.,99. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology . 2015;61(1):77-87..

The frequency of the geographical distribution of the genotypes in the Amazon region is similar to the pattern in Brazil and other world regions; a higher prevalence of genotypes 1 (64.9%) and 3 (30.2%) and a lower prevalence of genotypes 2 (4.6%), 4 (0.2%), and 5 (0.1%)33. Campiotto S, Pinho JR, Carrilho FJ, Da Silva LC, Souto FJ, Spinelli V, et al. Geographic distribution of hepatitis C virus genotypes in Brazil. Braz J Med Biol Res. 2005;38(1):41-9.. However, genotype 4 is rarely reported in the State of Amazonas1010. Fonseca JCF, Brasil LM. Infecção pelo vírus da hepatite C na região Amazônica brasileira. Rev Soc Bras Med Trop. 2004;37(Suppl 2):1-8..

The current global distribution of HCV genotypes has undoubtedly been influenced by historical events and modified by contemporary human migration trends. Although genotype 1 has been established as the most prevalent genotype worldwide, including in the Amazon region, we must be aware of the introduction of other genotypes into the region.

In this case, the patient is a native of Tracuateua, a small City in Pará, in the Amazon region; however, she lives in Alenquer, another city in Pará closer to Manaus. Thus, this is not an autochthonous case as the patient temporarily moved to Manaus for HCV treatment. Migratory flow may contribute to the dissemination of genotype 4 originating from other states in the region into Amazonas via virus carriers prior to SVR.

The origin of the region of Tracuateua is linked to the construction of the Belém-Bragança railroad (completed in 1908), during which many African descent, Portuguese, and Spanish immigrants began to colonize the vicinity. Although this migratory phenomenon is not recent, it has been increasing; thus, new and unusual genotypes may be more prevalent than thought1111. Empresa Brasileira de Pesquisa Agropecuária (EMPRAPA). Prefeitura Municipal de Tracuateua. Tracuateua, PA: EMBRAPA; 2017. Access in Jun 7th, 2017 Disponível em: Disponível em: http://www.tracuateua.pa.gov.br/tracuateua/historia
http://www.tracuateua.pa.gov.br/tracuate...
.

Because of the low prevalence of HCV GT-4 in Brazil, this genotype has not been studied extensively in prospective trials evaluating treatment outcomes. The lack of genotype 4 in our samples indicates that it is absent or rarely present in our population. Because many people in Bahia are of African descent and Brazil is a country with continental proportions, it is possible that uncommon Brazilian HCV strains in other regions of Brazil may be the result of multiple introductions of genotype 41212. Lampe E, Lewis-Ximenez L, Espírito-Santo MP, Delvaux NM, Pereira SA, Peres-da-Silva A,et al. Genetic diversity of HCV in Brazil. Antivir Ther. 2013;18(3 Pt B):435-44..

Therefore, we believe that HCV patient numbers are inexact in some municipalities of the state of Amazonas, a poor region of the country affected by this endemic disease, where the only public access to advanced technology for diagnosis and treatment is at the FMT-HVD and Araújo Lima Ambulatory, the Federal University of Amazonas. In addition, the natural history of hepatitis C and the limited education of the population in some of these municipalities hinder patient notification and treatment.

This case report may contribute to demonstrate that there is HCV GT-4 in the North of Brazil and these individuals carrying this genotype have developed response to the DAAs.

Acknowledgments

We are greatly thankful to the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado and Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas for providing technical support for the development and implementation of this study.

REFERENCES

  • 1
    World Health Organization (WHO). Hepatitis C. April 2017 - Updated October 2017. Available Available from: who.int/mediacentre/factsheets/fs164/en/ Access in Jun 7th, 2017.
    » from: who.int/mediacentre/factsheets/fs164/en/
  • 2
    Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014;59(1):318-27.
  • 3
    Campiotto S, Pinho JR, Carrilho FJ, Da Silva LC, Souto FJ, Spinelli V, et al. Geographic distribution of hepatitis C virus genotypes in Brazil. Braz J Med Biol Res. 2005;38(1):41-9.
  • 4
    Lampe E, Espirito-Santo MP, Martins RM, Bello G. Epidemic history of Hepatitis C virus in Brazil. Infect Genet Evol. 2010;10(7):886-95.
  • 5
    Ministério da Saúde (MS). Secretaria de Vigilância e Saúde. Departamento de Vigilância, Prevenção e Controle das DST, do HIV/Aids e da Hepatites Virais. Protocolo Clínico e Diretrizes Terapêuticas para Hepatite C e Coinfecções. Brasília: MS; 2017. 143p.
  • 6
    Jiménez-Pérez M, González-Grande R, España Contreras P, Pinazo Martínez I, de la Cruz Lombardo J, Olmedo Martín R. Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance. World J Gastroenterol. 2016;22(29):6573-81.
  • 7
    Welzel TM, Petersen J, Herzer K, Ferenci P, Gschwantler M, Wedemeyer H, et al. Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort. Gut. 2016;65(11):1861-70.
  • 8
    Abdel-ghaffar TY, Sira MM, El Naghi S. Hepatitis C genotype 4 : the past, present, and future. World J Hepatol. 2015;7(28): 2792-2810.
  • 9
    Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology . 2015;61(1):77-87.
  • 10
    Fonseca JCF, Brasil LM. Infecção pelo vírus da hepatite C na região Amazônica brasileira. Rev Soc Bras Med Trop. 2004;37(Suppl 2):1-8.
  • 11
    Empresa Brasileira de Pesquisa Agropecuária (EMPRAPA). Prefeitura Municipal de Tracuateua. Tracuateua, PA: EMBRAPA; 2017. Access in Jun 7th, 2017 Disponível em: Disponível em: http://www.tracuateua.pa.gov.br/tracuateua/historia
    » http://www.tracuateua.pa.gov.br/tracuateua/historia
  • 12
    Lampe E, Lewis-Ximenez L, Espírito-Santo MP, Delvaux NM, Pereira SA, Peres-da-Silva A,et al. Genetic diversity of HCV in Brazil. Antivir Ther. 2013;18(3 Pt B):435-44.
  • Financial support: Fundação de Amparo à Pesquisa, Programa de Apoio a Núcleos emergentes de Pesquisa (PRONEN 009/2011).

Publication Dates

  • Publication in this collection
    Nov-Dec 2017

History

  • Received
    04 Apr 2017
  • Accepted
    09 Aug 2017
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