Viral, host and interferon‐related factors modulating the effect of interferon therapy for hepatitis C virus infection

Abstract

The estimated prevalence of hepatitis C virus infection in the US is approximately 1.8%. Although interferon monotherapy and combination therapy of interferon with ribavirin represent mainstay for treating HCV infection, the rate of sustained virologic response remains suboptimal. The growing evidence suggested that the clinical sequence and treatment response of chronic hepatitis C are determined by a dynamic, complex tripartite relationship among HCV infection, the host immune response, and the effect of different interferon regimens. The treatment response is associated with various viral factors including the pretreatment viral level, dynamic change of viral level during treatment, viral genotype quasispecies and nucleotide mutation in nonstructural protein 5A of hepatitis C virus. Host factors that may affect treatment response include age, gender, race, HLA alleles and the host immune responses. Interferon regimens, including type, dose, frequency and duration of treatment and combination of interferon with other anti-HCV agents also alter the therapeutic response. Understanding these complicated interaction may provide better insights into the mechanism(s) of interferon response, leading to more effective clinical application of interferon therapy.The response to both IFN monotherapy and combination therapy of IFN and ribavirin varies among different HCV genotypes [39,47±51]. The frequency of long-term normal-Ó

Hepatitis C virus load and expression of a unique subset of cellular genes in circulating lymphoid cells differentiate non‐responders from responders to pegylated interferon alpha–ribavirin treatment

“…Over the past number of years, a multitude of host and viral factors has been linked to success or failure of IFN‐based therapies [Hu et al, 2001; Navaneethan et al, 2009]. Aside from the classical parameters, such as HCV genotype, viral load, race, and age, a number of cellular genes has also been proposed to affect treatment outcomes.…”

Decreased IP-10 and Elevated TGFβ1 Levels are Associated with Viral Clearance Following Therapy in Patients with Hepatitis C Virus

“…HCV infection is treated with pegylated interferonα and ribavirin (pegIFNα/RBV). Factors associated with a favourable treatment outcome include younger age, low pre-treatment HCV viral load, minimal liver damage and HCV genotype 2 or 3 [10]. Histological assessment of a liver biopsy has been the "gold standard" to demonstrate fibrosis, but carries a risk of complications [24].…”

Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a

“…The massive genetic heterogeneity present in quasispecies has important biological consequences and enables HCV to escape immune clearance and to establish chronic infection [ 18 - 22 ]. Furthermore, the quasispecies distribution may influence the outcome of anti-viral therapy and be important in the development of resistance to anti-viral therapy [ 23 - 27 ]. It is well established that HCV genotype influences both response to therapy and disease severity as well as the viral-host interactions [ 19 , 28 - 30 ].…”

“…It is well established that HCV genotype influences both response to therapy and disease severity as well as the viral-host interactions [ 19 , 28 - 30 ]. Patients infected with HCV genotypes 2 or 3 respond more favourably than genotype 1 to pegylated α2a-Interferon and ribavirin anti-viral therapy [ 12 , 27 , 31 , 32 ].…”

“…In particular, the untranslated region at 5' and 3' ends of the genome exhibits areas of conservations, whereas the hypervariable region 1 (HVR1) located in the amino-terminus of the HCV envelope glycoprotein E2 is the most variable part of the HCV genome. There is strong evidence to suggest that the HVR1, encoding 27 amino acids (positions 1491 to 1571 on reference strain H77), is susceptible to immune pressure involving neutralising antibodies and allows the selection of escape mutants [ 27 , 31 , 33 - 36 ]. A considerable number of investigations into HCV quasispecies have focused on the analysis of the HVR1, given that a high degree of diversity increases the likelihood of distinguishing one viral species from another.…”