Ethnicity and cytokine production gauge response of patients with hepatitis C to interferon‐α therapy

Abstract

Interferon is the primary treatment for hepatitis C virus (HCV). However, the long-term success rate is low particularly for African Americans relative to Caucasians and may be due to differential immune abilities. This study compared cytokine production from PHA-stimulated peripheral blood from 25 healthy and 40 HCV-infected African Americans and Caucasians. HCV patients were designated as IFN responders or nonresponders based on outcome after therapy. Ethnicity and genotype were associated with IFN response. IFN responders were 100% Caucasian, whereas nonresponders were 67% Caucasian and 33% African American (P = 0.01). Genotype 1 was present in 100% nonresponders and 50% responders (P < 0.05). Age, sex, liver histology, ALT, and viral titers were equivalent (ns). Cytokine production from healthy individuals showed ethnic variation in cytokine levels. Healthy African Americans produced greater amounts of IL-2 (P = 0.06), TNF-alpha (P = 0.06) and less IL-10 (P = 0.05) than healthy Caucasians. In contrast, IFN-gamma and TGF-beta levels were equivalent. Pretherapy cytokine production among HCV patients showed a similar pattern of ethnic variation. African American nonresponders produced more IL-2 (P = 0.06) and TNF-alpha (P = 0.02) than Caucasian nonresponders. Cytokine levels among Caucasian and African American nonresponders were equivalent (P = ns) to ethnically matched healthy individuals whereas Caucasian responders produced subnormal levels of IL-10 (P < 0.05) and TGF-beta (P < 0.05). Since all African Americans failed IFN therapy, cytokine production could not be compared with therapeutic outcome. However, comparison of cytokine production among Caucasians showed that responders produced less IL-10 (P < 0.001) and more TGF-beta (P = 0.06) than nonresponders and predicted Caucasian nonresponders with 83% sensitivity and 96% specificity. HCV genotype was not relevant to cytokine production (P = ns). Distribution of cytokine genetic polymorphisms (TNF-alpha, TNF-beta, IL-10, TGF-beta) was equivalent in all ethnic groups and did not predict clinical nonresponders. In summary, it appears that ethnicity may contribute to variable immune responses and therapeutic outcome. The cytokine profile among African Americans suggests a more robust immune response, which may complicate therapy with IFN. In contrast, the subnormal cytokine production among Caucasian responders may be more permissive to IFN therapy. Pretherapy cytokine production may allow prediction of drug resistance among Caucasians.

Monocyte Chemoattractant Protein-1 Promoter –2518 Polymorphism May Have an Influence on Clinical Heterogeneity of Bipolar I Disorder in the Korean Population

“…The Asian population showed more G allele frequency than Caucasians [19,26,27]. In line with those reports, interethnic variation has recently been reported in the production of cytokine and immune response between different ethnic origins [28]. Regarding the issue of sample size, although our sample with BID had a power of 0.80 to detect a small ES (w = 0.14), corresponding to a difference of 13% between the two alleles, in future study, the sample size should be increased in order to exclude type II error.…”

Polymorphisms near <b><i>Interleukin 28B</i></b> Gene Are Not Associated with Hepatitis B Virus Clearance, Hepatitis B e Antigen Clearance and Hepatocellular Carcinoma Occurrence

“…The causes of racial variation are still unclear. Some factors, like cytokine production and hepatic iron level, have been considered as the origin of inter-ethnic differences in prior investigations [41,42]. Since the strong associations of IL28B gene polymorphisms with HCV clearance have been demonstrated, SNPs near the IL28B gene are thought to be the leading cause of racial variation of HCV clinical outcomes [43].…”

Treatment responses in Asians and Caucasians with chronic hepatitis C infection

“…Further, viral kinetics studies have shown that African Americans exhibit significantly lower interferon effectiveness and achieve a lower reduction in HCV RNA in the first 24 h of treatment [29] . It was also noted that African Americans had different pretreatment cytokine profiles [30] . In addition, while they mounted a more robust HCV-specific CD4 Th1 proliferative response, it did not translate into a higher rate of IFN-gamma production, potentially secondary to their dysfunctional nature, which was associated with a failure of interferon therapy [31][32] .…”