Page 18 - The Flying Publisher Guide to Hepatitis C Treatment

18 | Hepatitis C Treatment

virological responders. Greater sequence heterogeneity
generates diverse quasispecies, thereby providing a
reservoir of mutations that enable virus-escape from
antiviral therapy (Fan 2009).

Host factors
Variation in the IL28B gene region (that encodes IFN-lambda
- type III IFN) has been reported by several genome-wide
association studies as a major predictor of HCV treatment
response (Ge 2009, Tanaka 2009, Suppiah 2009) and of viral
kinetics during HCV therapy (Rauch 2010).
The presence of the CC inherited polymorphism in the IL 28B
gene (on chromosome 19 at SNP rs12979860) has been associated
with higher rates of therapeutic success, especially for
genotypes 1 and 4, compared with the presence of CT or TT
polymorhisms. The same is true for HCV co-infection with HIV
(Medrano 2010). Alleles frequencies differ between racial
groups, the favorable CC polymorphism being most frequently
encountered in Asians and least frequently in African-
Americans, explaining, at least partially, the differences in the
treatment response between races (Ge 2009, Thomas 2009). The
same polymorphism in the IL28B gene is a determinant of
natural HCV clearance (Thomas 2009) and is associated with
lower pretreatment levels of ISG (Thompson 2010). In
transplanted individuals, both donor and recipient IL28B
genotypes influence the response to HCV therapy (Fukuhara
2010).
Host immune response. The baseline pretreatment level of IP-
10 (CXCL10 – a chemochine active on lymphocytes) in plasma
and the intrahepatic IP-10 mRNA are elevated in patients
chronically infected with HCV genotypes 1/4 who do not achieve
SVR (Lagging 2011).
Other host-related negative predictors of response include
older age, male sex, black race, high body mass index (BMI) and
presence of co-morbitities.