Individualization of chronic hepatitis C treatment according to the host characteristics

Abstract

Hepatitis C virus (HCV) infection is a global health problem that affects more than 170 million people worldwide. It is a major cause of cirrhosis and hepatocellular carcinoma, making the virus the most common cause of liver failure and transplantation. The standard-of-care treatment for chronic hepatitis C (CHC) has been changed during the last decade and direct acting antiviral drugs have already been used. Besides, understanding of the pathogenesis of CHC has evolved rapidly during the last years and now several host factors are known to affect the natural history and response to treatment. Recent genome-wide association studies have shown the important role of interleukin-28B and inosine triphosphatase in HCV infection. The present review article attempts to summarize the current knowledge on the role of host factors towards individualization of HCV treatment.

Hepatitis C virus: Virology, diagnosis and treatment

“…The factors influencing the efficacy of anti-HCV treatments based on interferon are divided into two categories: viral-related and host-related factors [90,91] . The viral-related factors include the HCV genotype, baseline viral load, and virological response during treatment.…”

Pharmacogenomic Testing in the Era of Patient-Tailored HCV Treatment

“…HCV causes progressive liver injury in those patients, which in approximately 16% progress to liver cirrhosis and ultimately in 1-5%, within two decades from acute infection, to hepatocellular carcinoma. Therefore, HCV infection is one of the most common reasons for liver failure and an indication for liver transplantation procedures worldwide [5][6][7]. HCV has been classified into seven different genotype categories, having nucleotide differences of greater than 30% among genotypes (GT).…”

“…It has been noticed that many clinical factors, including pharmacogenetics, could influence the treatment response rate [9]. Both virological factors (such as HCV genotype, quasispecies diversity, and baseline viremia) and host factors (age, gender, race-ethnicity, fibrosis stage, obesity, hepatic steatosis, low-density lipoprotein cholesterol, insulin resistance, and genetic variances) played an important role in predicting the natural course of hepatitis C and IFN response to therapy [7,[55][56][57]. Pharmacogenetic testing could play very important role in optimizing HCV therapy by identifying variations in response to treatment, considering ethnic variations in response to therapy, enlightening the molecular mechanism of current and future therapies, and advancement of innovative genetic tools that will enable physicians to individualize drug therapy, adjust dosages, and reduce the possibility of adverse drug reactions and therapeutic costs ( Table 1) [54,58].…”

“…Over 40 genes have been linked to modulation of anti-HCV therapy affecting either adverse drug events or response to treatment [59,60]. [7]. Viral infection induces the corresponding cytokines and their antiviral activity is mediated by triggering JAK-STAT pathway [61][62][63].…”

Prevalência de marcadores sorológicos das hepatites A e B em pacientes com hepatite C crônica atendidos no ambulatório de hepatites do serviço de Gastroenterologia Clínica do Hospital das Clínicas da Faculdade de Medicina da Universidade

“…Vários estudos demonstram que a idade do indivíduo no momento da infecção (faixa etária > 40 anos demonstra uma pior evolução da doença), sexo masculino, a etnia (afro-americanos), coinfecção com outros vírus, entre eles o vírus da hepatite A (VHA), vírus da hepatite B (VHB) e o vírus da imunodeficiência humana (HIV), o etilismo, a obesidade, a presença de resistência insulínica, a imunossupressão e a presença de polimorfismo desfavorável do gene da interleucina 28B (o alelo T para o polimorfismo rs 12979860 e o alelo G para o polimorfismo rs 8099917 demonstram uma resistência maior ao tratamento com Interferon) influenciam na história natural da hepatite C crônica (GATSELIS N. K. et al, 2014;RE D. V. et al, 2014;FERREIRA C. S., 2013;CLARK P. J. et al, 2012;GOMEZ E. V. et al, 2012;MAASOUMY B.;WEDEMEYER H., 2012;DOYLE J. S. et al, 2012;RAO H.Y. et al, 2011;RAUCH A. et al, 2010;ASCIONE A. et al, 2007;MORGAN T. R., 2006;AFDHAL N. H., 2004;THOMAS D. L. et al, 2000).…”