Circulating IL-6, IL-17 and vitamin D in hepatocellular carcinoma: Potential biomarkers for a more favorable prognosis?

Abstract

Hepatitis C virus (HCV) infects primarily hepatocytes, leads to development of fibrosis and/or cirrhosis of the liver and is a significant factor for developing hepatocellular carcinoma (HCC). Evidence indicates that liver fibrosis contains uncontrolled inflammation as a part of its etiology. Normal cell-mediated immunity plays a central role in the mechanisms involved in viral clearance/persistence in the liver. In this context, cytokines modulate the immune system and exert direct anti-viral activity. To this end, this study investigated potential associations of serum IL-17 and IL-6 with exacerbation of hepatic damage in chronic HCV patients to determine their utility as prognostic markers for potential development of HCC. Chronic HCV-patients were recruited, divided into groups according to degree of liver damage, i.e. patients with perihepatic fibrosis, hepatic cirrhosis, or HCC, and had their blood collected for analysis of liver function and serum IL-6 and IL-17 levels. Interestingly, increases in serum IL-17 levels in the study groups were associated with aggravation of the clinical state from HCV to cirrhosis and then to HCC. Serum IL-6 levels followed a similar pattern. The association of both cytokines with progressive exacerbation of the initial HCV-induced liver damage was further confirmed by correlation analysis that revealed positive correlations between HCV RNA titer and IL-17 (þ0.951, p50.05) and IL-6 (þ0.85, p50.05). A receiver operating characteristics (ROC) analysis revealed their beneficial addition as promising biomarkers for a better prognostic profile of HCC. Interestingly, a significant progressive decline in the active vitamin D status was noted in all three clinical states, and these too were associated with progressive liver disease. This study confirms the necessity of adding screening for IL-6 and IL-17 and vitamin D to that of the classic marker AFP for patients with HCV and cirrhosis to hopefully permit clinicians to initiate measures that ultimately might mitigate/delay development of HCC in these infected patients.

Postoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio predicts the outcomes of hepatocellular carcinoma

“…We believe that these treatments may also impact the outcomes. Moreover, the neutrophil, lymphocyte, and platelet levels can be impacted by some cytokines, such as IL-6 and 17 [17,28,29]. In other words, a high NLR or PLR may not directly impact a patient's outcome but rather reflect an unfavorable systemic inflammatory state.…”

Vitamin D and Chronic Diseases

“…Deficiency in VDBP also affects the function of Vitamin D. For example, studies have demonstrated that low level of VDBP is related to a variety of malignant tumors, including breast, prostate and colorectal [20, 37-41]. Both prospective and retrospective epidemiologic studies indicate that levels of 25OHD below 20 ng/ml are associated with a 30 to 50% increased risk of incident colon, prostate, and breast cancer, along with higher mortality from these cancers [42-46].…”

Low serum interleukin-6 levels as a predictive marker of recurrence in patients with hepatitis B virus related hepatocellular carcinoma who underwent curative treatment

“…Jang et al reported that a higher serum IL-6 level was an independent cytokine-related factor for predicting shorter survival in patients with unresectable HCC who underwent transarterial chemoembolization [7]. Furthermore, Hammad et al [33] reported similar results in patients with hepatitis C virus-related HCC. However, these studies included advanced-stage HCC patients.…”