Assessment of high-sensitivity C-reactive protein tests for the diagnosis of hepatocellular carcinoma in patients with hepatitis B-associated liver cirrhosis

Abstract

Abstract. Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, with high morbidity and mortality. Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma and the majority (~80%) of hepatocellular carcinoma patients in China exhibit co-morbidity with HBV-associated liver cirrhosis. The goal of reliable early diagnostic and prognostic techniques for HBV-associated HCC remains unrealized. The aim of the present study was to explore the efficacy of serum high-sensitivity C-reactive protein (hs-CRP) tests in the early diagnosis of HCC in patients with HBV-associated liver cirrhosis. A cohort of 493 patients with HBV-associated liver disease was divided into three groups: Chronic HBV (CHB) group; liver cirrhosis without HCC (LC) group; and liver cirrhosis with HCC (HCC) group. A further 47 healthy individuals comprised the healthy control (CN) group. Comparative analyses of clinical symptoms, histopathology, ultrasound imagery, computed tomography, magnetic resonance imaging, biochemistry [α-fetoprotein (AFP) and liver function enzymes], and hs-CRP tests were conducted across these four groups. Immunohistochemical analysis showed that CRP is strongly expressed in HCC tumor tissue, but is not expressed elsewhere. Analyses of the correlations between serum hs-CRP levels and HCC clinical parameters indicated that there was no correlation between serum hs-CRP levels, tumor Edmondson grade, tumor-node-metastasis stage and AFP status. Serum hs-CRP and AFP levels were found to be significantly elevated in the HCC group compared to those in the LC, CHB and CN groups (P<0.01). Receiver operator characteristic analysis showed that measurement of serum hs-CRP could differentiate HCC from HBV-associated liver cirrhosis, as well as increase the accuracy of HCC diagnoses. Additionally, measurement of hs-CRP and AFP together improved diagnostic accuracy for HCC compared with either test alone. Serum hs-CRP could have potential as an effective diagnostic tool to complement AFP in diagnosing HCC and improving the identification of AFP-negative HCC in patients with HBV-associated liver cirrhosis. The present findings may facilitate the earlier diagnosis of hepatocellular carcinoma, permitting more effective treatment and a broader spectrum of treatment modalities for patients with advanced hepatic disease.

IL-6 and NFE2L2: A putative role for the hepatoprotective effect of N. Sativa, P. Ginseng and C. Sempervirens in AFB-1 induced hepatocellular carcinoma in rats

“…Furthermore, N. Sativa reduction of hs-CRP reduction comes in agreement with, Alizadeh et al, 2016 who found that N. Sativa reduced hs-CRP in women with rheumatoid arthritis [46]. Along with reduction of IL-6 our results confirm anti-inflammatory effect for N. Sativa in HCC as well as the potential role for hs-CRP as an early diagnostic tool for HCC [47].…”

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

“…Ma et al (126) used a high-sensitivity CRP (hs-CRP) assay, which could be quantified as low as 0.04 mg/L of CRP and found that serum hs-CRP levels were significantly elevated in the HCC group compared with those in the non-HCC group and did not correlate with tumor Edmondson grade, TNM stage, or AFP status. Serum hs-CRP had a better performance than AFP (AUROC 0.903 vs. 0.824, sensitivity 84.2 vs. 74.4%, specificity 61.6 vs. 55.6%) for diagnosing HCC, and the diagnostic performance improved when the two indicators were combined (AUROC = 0.998, sensitivity = 94.1%), with similar positive rates between APHC and ANHC patients (86.9 vs. 84.6%) (126), indicating that serum hs-CRP level may be a useful diagnostic biomarker complementary to AFP for ANHC diagnosis. Another study also found that serum CRP-positive rate was significantly higher in the HCC than in the LC (64.15 vs. 37.97%) (127), and serum CRP levels were similar between ANHC and APHC patients.…”

“…C-reactive protein (CRP) is a non-specific acute-phase protein produced by the liver in response to acute and chronic inflammation, and elevated CRP expression has been detected in multiple tumors and is associated with poor prognosis ( 122 – 125 ). Ma et al ( 126 ) used a high-sensitivity CRP (hs-CRP) assay, which could be quantified as low as 0.04 mg/L of CRP and found that serum hs-CRP levels were significantly elevated in the HCC group compared with those in the non-HCC group and did not correlate with tumor Edmondson grade, TNM stage, or AFP status. Serum hs-CRP had a better performance than AFP (AUROC 0.903 vs. 0.824, sensitivity 84.2 vs. 74.4%, specificity 61.6 vs. 55.6%) for diagnosing HCC, and the diagnostic performance improved when the two indicators were combined (AUROC = 0.998, sensitivity = 94.1%), with similar positive rates between APHC and ANHC patients (86.9 vs. 84.6%) ( 126 ), indicating that serum hs-CRP level may be a useful diagnostic biomarker complementary to AFP for ANHC diagnosis.…”

The patient burden of opioidinduced bowel dysfunction

“…The Glasgow score, consisting only of the 2 parameters, CRP and albumin, has been found to be an important and independent prognosticator for several cancer types, including HCC [9-18]. Furthermore, there is evidence that CRP is produced not just by hepatocytes, but also by HCC cells [19]. However, the function, biological role and significance in determining HCC prognosis are still unclear.…”