Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
, 7 (1), 11867

Differential Serum Cytokine Profiles in Patients With Chronic Hepatitis B, C, and Hepatocellular Carcinoma

Affiliations
Clinical Trial

Differential Serum Cytokine Profiles in Patients With Chronic Hepatitis B, C, and Hepatocellular Carcinoma

Jacqueline Estevez et al. Sci Rep.

Abstract

Cytokines play an important role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC), most cases of which are related to either hepatitis B virus (HBV) or hepatitis C virus (HCV). Prior studies have examined differences in individual cytokine levels in patients with chronic liver disease, but comprehensive cytokine profiling data across different clinical characteristics are lacking. We examined serum cytokine profiles of 411 patients with HCC (n = 102: 32% HBV, 54% HCV, 14% non-viral) and without HCC (n = 309: 39% HBV, 39% HCV, 22% non-viral). Multiplex analysis (Luminex 200 IS) was used to measure serum levels of 51 common cytokines. Random forest machine learning was used to obtain receiver operator characteristic curves and to determine individual cytokine importance using Z scores of mean fluorescence intensity for individual cytokines. Among HCC and non-HCC patients, cytokine profiles differed between HBV and HCV patients (area under curve (AUC) 0.82 for HCC, 0.90 for non-HCC). Cytokine profiles did not distinguish cirrhotic HBV patients with and without HCC (AUC 0.503) or HCV patients with and without HCC (AUC 0.63). In conclusion, patients with HBV or HCV infection, with or without HCC, have distinctly different cytokine profiles, suggesting potential differences in disease pathogenesis and/or disease characteristics.

Conflict of interest statement

Jacqueline Estevez, Vincent L. Chen, An Le, Philip Vutien, Ellen T. Chang, Yael Rosenberg-Hasson: none to disclose. Ondrej Podlaha, Biao Li, Zhaoshi Jiang, Stefan Pflanz, Dongliang Ge, Anuj Gaggar: Employees of Gilead Sciences Inc. and owners of Gilead stock. Mindie H. Nguyen: Research support: Bristol Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals. Advisory board or consultation honorarium: Janssen Pharmaceuticals, Gilead Sciences, Intercept Pharmaceuticals, Alynam Pharmaceuticals, Roche Laboratories, Dynavax Laboratories.

Figures

Figure 1
Figure 1
Liver disease etiology for patients without hepatocellular carcinoma.
Figure 2
Figure 2
Liver disease etiology for patients with hepatocellular carcinoma.
Figure 3
Figure 3
Serum cytokine and chemokine profile comparison of patients without hepatocellular carcinoma (non-HCC) with chronic hepatitis B vs. non-HCC patients with chronic hepatitis C. (a) Receiver operating characteristic (ROC) plot with area under the curve (AUC). (b) Levels of top predictive cytokines.
Figure 4
Figure 4
Multidimensional scaling plot comparing serum cytokine profiles of non-hepatocellular carcinoma (HCC) patients with chronic hepatitis B (red dots) vs. non-HCC patients with chronic hepatitis C (blue dots).
Figure 5
Figure 5
Serum cytokine and chemokine profile comparison of patients with chronic hepatitis B with hepatocellular carcinoma (HCC) vs. chronic hepatitis C with HCC. (a) Receiver operating characteristic (ROC) plot with area under the curve (AUC). (b) Levels of top predictive cytokines.
Figure 6
Figure 6
Serum cytokine levels of hepatocellular carcinoma (HCC) patients with chronic hepatitis B, C, or non-viral disease. Three-dimensional principal component analysis (PCA) plot comparing serum cytokine profiles of HCC patients with chronic hepatitis B (red dots) vs. C (green dots) vs. non-viral (blue dots).
Figure 7
Figure 7
Serum cytokine and chemokine profile comparison of chronic hepatitis B patients with vs. without hepatocellular carcinoma (HCC). (a) Receiver operating characteristic (ROC) plot with area under the curve (AUC). (b) Levels of top predictive cytokines.
Figure 8
Figure 8
Serum cytokine and chemokine profile comparison of patients with chronic hepatitis C with hepatocellular carcinoma (HCC) vs. without HCC. (a) Receiver operating characteristic (ROC) plot with area under the curve (AUC). (b) Levels of top predictive cytokines.

Similar articles

See all similar articles

Cited by 3 PubMed Central articles

References

    1. Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2015;61:191–199. doi: 10.1002/hep.27388. - DOI - PMC - PubMed
    1. Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. Journal of clinical gastroenterology. 2013;47(Suppl):S2–6. doi: 10.1097/MCG.0b013e3182872f29. - DOI - PMC - PubMed
    1. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet (London, England) 2015;386:1546–1555. doi: 10.1016/S0140-6736(15)61412-X. - DOI - PubMed
    1. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of hepatology. 2014;61:S45–57. doi: 10.1016/j.jhep.2014.07.027. - DOI - PubMed
    1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–1273 e1261. doi: 10.1053/j.gastro.2011.12.061. - DOI - PMC - PubMed

Publication types

Feedback