IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection

Abstract

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-␣-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) > 25 kg/m 2 (P ‫؍‬ .004) and with baseline viral load > 2 million IU/mL (P ‫؍‬ .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P ‫؍‬ .0002), including those having higher BMI (P < .05), higher viral load (P ‫؍‬ .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention. (HEPATOLOGY 2006;44:1617-1625

The long way toward understanding host and viral determinants of therapeutic success in HCV infection

“…The results reported here are therefore noteworthy in the context of host protection against HCV, host/virus synergy, and further development of therapeutics. These data are concordant with other reports indicating that (1) a lower Th1/Th2 ratio before treatment predicts a long-term virological response in patients with chronic HCV infection [13], and (2) the therapy seems to be more effective in HCV-infected patients with a predominant Th2 profile or with low levels of IP-10 [19]. Nevertheless, some points need substantial clarification and several conclusions need to be taken with caution.…”

Coinfection with Hepatitis C Virus among HIV-1-Infected Individuals Increases Proinflammatory Cytokines and HIV-1 Disease Severity

“…During HCV infection, hepatocytes produce IP-10 and circulating levels of IP-10 are known to be measurable during chronic HCV infection [37]. High levels of IP-10 levels are known to be associated with reduced rates of sustained virological response during treatment of HCV with pegylated (PEG)-IFN/ribavirin (RBV) [37,[47][48][49] HIV-1/HCV coinfection [38,50] and reduced spontaneous clearance to acute infection [51]. Further, high IP-10 levels have been associated with greater inflammation and liver fibrosis [48,49] even in a cohort of African-American injection drug users with chronic HCV [52].…”

“…High levels of IP-10 levels are known to be associated with reduced rates of sustained virological response during treatment of HCV with pegylated (PEG)-IFN/ribavirin (RBV) [37,[47][48][49] HIV-1/HCV coinfection [38,50] and reduced spontaneous clearance to acute infection [51]. Further, high IP-10 levels have been associated with greater inflammation and liver fibrosis [48,49] even in a cohort of African-American injection drug users with chronic HCV [52]. Thus, these increased levels of IP-10 within the HIV-1/HCV co-infected individuals in the CARES Cohort could likely be a marker of reduced response to therapy, immunologic dysfunction ultimately leading to an accelerated progression of disease.…”

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

“…Levels of IP-10 at onset of therapy are reportedly elevated in patients infected with HCV of genotypes 1 or 4 who do not achieve SVR [110]. In difficult-to-treat genotype-1-infected HCV patients, cut-off levels of IP-10 in plasma of 150 pg/mL (approximately equal to 2 standard deviations above the mean IP-10 level of HCV seronegative blood donors) and 600 pg/mL have yielded positive and negative predictive values for SVR of 71% and 100%, respectively [111]. IP-10 in plasma is mirrored by intrahepatic IP-10 mRNA and strongly predicts the HCV RNA decline during the first days ("first phase decline") during IFN/RBV therapy for all HCV genotypes [112].…”