High Sensitivity C-Reactive Protein (hs-CRP) Levels in HCC Patients and its Modulation During Locoregional Therapy

Abstract

Background: The levels of CRP increases in blood during inflammation. It is an acute phase protein (APP) synthesized in liver and this type I APP is induced by interleukin-1 like cytokines including IL-1α, IL-1β, TNF-α and TNF-β. Beside inflammation, it remains elevated during acute phase response to local or systemic infection, immunological disturbances and cancer. Recent studies have suggested that CRP may serve as prognostic biomarker for survival outcome in hepatocellular carcinoma (HCC) patients. However, modulation of hsCRP during locoregional therapy and association of its changes with therapeutic response is not studied well. For HCC patients, palliative locoregional therapy like percutaneous ablation and transarterial chemoembolisation (TACE) remains alternative to curative treatment. But in absence of suitable biomarker, imaging techniques like DPCT or MRI are only options for assessment of treatment response. In this study, we have evaluated hsCRP at baseline levels in HCC patients and its modulation during locoregional post therapy and association with therapeutic response. Methodology: The patients diagnosed as HCC are staged as per BCLC staging system. The patient receiving locoregional therapy was evaluated for therapeutic response by radiological imaging as per mRECIST criteria. Serum sample were collected at baseline and 1, 3 and 6 months post therapy. The CRP estimation was carried out by hsCRP ELISA kit and values were expressed in mg/L. Statistical significance between groups were determined by Student t test and association of CRP with therapeutic response by chi square test. Result: The mean hsCRP concentration at base line levels of HCC patient is 6.312 ± 8.268 mg/L (n = 78) and healthy subjects are 1.676 ± 1.401 mg/L (n = 10). The hsCRP level is <10 mg/L in majority of HCC patients (73%, n = 57) and the mean concentration is 2.174 ± 3.014 mg/L. Increased hsCRP (<10 mg/L) is observed in 27% of HCC patients. The mean hsCRP level is 17.54 ± 7.513 mg/L (n = 21). When HCC groups were compared with healthy subjects, hsCRP <10 mg/L group found statistically significant in unpair t test (P-value ≤ 0.0001) but not found significant hsCRP <10 mg/L (P = 0.616). During locoregional post therapy, hsCRP level increased at 1-month post therapy (mean hsCRP: 13.31 ± 11.8 mg/L) from baseline (mean hsCRP: 6.511 ± 7.851 mg/L, n = 47). Later it gets stabilized to mean hsCRP level 5.167 ± 4.563 mg/L at 3-month post therapy in HCC patients. Associations of hsCRP with final therapeutic response will be analyzed by Chi square test for hsCRP group of <5 mg/L and <5 mg/L with therapeutic response as responder and non-responder. Conclusion: Tumor induced inflammation from mild to moderate was observed HCC patients. The modulation of hs-CRP may be correlated with therapeutic response.