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.
Antiviral Therapy: The Basics | 19
Age. Younger patients (<40 years) have higher SVR rates with
SoC. Nonresponders tend to be on average 5 years older than
sustained responders (Hadziyannis 2004). Therapy is generally
deferred in elderly patients with comorbid conditions since
these may be exacerbated by combination therapy with
PegIFN/RBV. Despite all these observations, age alone should not
preclude antiviral therapy, and treatment decisions should be
made on a case by case basis.
The efficacy and safety of the PegIFN/RBVcombination is also
evaluated for pediatric patients. Only a limited number of
children with HCV infection cleared viremia spontaneously over
a decade of follow-up, and those who did were more likely to be
infected with G3. Persistent viral replication led to end-stage
liver disease in a small subgroup characterized by perinatal
exposure, maternal drug use, and infection with HCV G1a.
Children with such features should be considered for early
treatment. After treating children, SVR was attained in 65% of
the cases, genotype being the main predictor of response (G1:
53%; G2/3: 93%; G4: 80%). The rate of SVR was similar in younger
and older children. Baseline VL was the main predictor of
response in the G1 cohort. AEs were generally mild or moderate
in severity (Wirth 2010).
Race. Racial differences in the response to PegIFN/RBV therapy
have been signaled, with Hispanics and African-Americans less
likely to respond compared to Whites or Taiwanese patients
(Ghany 2009).
- 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.
Antiviral Therapy: The Basics | 19
Age. Younger patients (<40 years) have higher SVR rates with
SoC. Nonresponders tend to be on average 5 years older than
sustained responders (Hadziyannis 2004). Therapy is generally
deferred in elderly patients with comorbid conditions since
these may be exacerbated by combination therapy with
PegIFN/RBV. Despite all these observations, age alone should not
preclude antiviral therapy, and treatment decisions should be
made on a case by case basis.
The efficacy and safety of the PegIFN/RBVcombination is also
evaluated for pediatric patients. Only a limited number of
children with HCV infection cleared viremia spontaneously over
a decade of follow-up, and those who did were more likely to be
infected with G3. Persistent viral replication led to end-stage
liver disease in a small subgroup characterized by perinatal
exposure, maternal drug use, and infection with HCV G1a.
Children with such features should be considered for early
treatment. After treating children, SVR was attained in 65% of
the cases, genotype being the main predictor of response (G1:
53%; G2/3: 93%; G4: 80%). The rate of SVR was similar in younger
and older children. Baseline VL was the main predictor of
response in the G1 cohort. AEs were generally mild or moderate
in severity (Wirth 2010).
Race. Racial differences in the response to PegIFN/RBV therapy
have been signaled, with Hispanics and African-Americans less
likely to respond compared to Whites or Taiwanese patients
(Ghany 2009).
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