In our previous work, we found peripheral levels of CXCR3-associated chemokines, particularly CXCL10, to be significantly associated with liver fibrosis in primarily white chronic HCV-infected patients [8
]. CXCL10 in combination with CXCL9 had a strong potential to identify patients with advanced liver fibrosis. In this work, we analyzed the diagnostic abilities of CXCL9 and CXCL10 in a primarily African-American population. We found peripheral levels of CXCL10 to have potential to identify HCV-infected patients who are unlikely to have progressive liver fibrosis. CXCL9 levels were not associated with fibrosis stage on initial or later biopsy.
In contrast to our previous work [8
], this study found that CXCL9-10 expression was not significantly correlated with contemporaneous liver fibrosis in this patient population. However, several major differences in the 2 cohorts could explain the discrepancy in the results between these studies. For example, most patients described in this study were African-American (93.9%), whereas white patients (85%) made up most of our previous cohort. We have found CXCL10 expression levels to be considerably higher in African-American patients from this cohort in comparison with levels in white patients from the previous study (median ln(CXCL10) 6.27 [IQR 5.86–6.73] versus 5.56 [IQR 4.93–6.04], P
<.0001). Although the 2 studies did not use the same specimen type for chemokine measurements (plasma versus serum), significantly higher CXCL10 expression in African-Americans compared with white patients has been reported previously [13
]. Therefore, the capacity of CXCL10 to differentiate among HCV-infected patients with different levels of liver fibrosis might be, at least in part, race dependent. Secondly, whereas most (91%) of the patients from this cohort had insignificant or mild liver fibrosis on the first biopsy, only 38% of the patients from the previous cohort were in that category. We have previously reported that CXCL10 has the better potential to identify patients with advanced liver fibrosis compared with those with milder stages [8
]. Because none of the patients analyzed in this study had advanced fibrosis and only 9% had moderate fibrosis on the first biopsy, the discriminatory capacity of CXCL10 was consequently decreased in this cohort. Lack of advanced fibrosis in this cohort not only impacted the results reported here but also reduced the estimated performance of FibroSure and APRI for prediction of fibrosis [9
]. Finally, although our prior study used plasma samples, in this work chemokine expression was measured in serum. Although we did not expect to find significant differences in chemokine levels between serum and plasma, sample type might have at least partially contributed to the discrepant results obtained in these 2 studies.
The capacity of CXCR3-associated chemokines to predict fibrosis progression or future fibrosis in chronic HCV-infected patients has not been previously assessed. We have shown here that CXCL10 has reasonable ability to identify patients who are unlikely to develop advanced fibrosis in a 3–5 year interval. Although the calculated sensitivity of CXCL10 was suboptimal, patients with low chemokine levels were extremely unlikely to develop advanced fibrosis during the next several years. Therefore, observation of these individuals could be recommended instead of pursuing treatment using pegylated interferon and ribavirin combination therapy. Additionally, considering racial differences in CXCL10 expression, we would expect this chemokine to have higher capacity to predict future fibrosis among white patients.
In conclusion, although peripheral CXCL10 levels do have a potential to predict present and future fibrosis in patients with chronic hepatitis C, this ability is most likely dependent on the patients’ race. To determine if CXCL10 could be developed as a marker of fibrosis or fibrosis progression, additional analysis in larger, racially diverse populations is needed. Identification of race-specific CXCL10 cutoff values might be necessary to precisely identify HCV-infected patients most likely to have mild/moderate or advanced stages of fibrosis at the present or in the future. This information could be considered when making treatment decisions.