The Association between Preoperative Serum C-Reactive Protein and Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis B Virus (HBV) Infection—A Retrospective Study

<div><p>The prognosis of the patients with hepatocellular carcinoma (HCC) recurrence following curative hepatectomy is usually dismal. Whether preoperative serum C-reactive protein (CRP) can predict the recurrence of HCC in patients with chronic HBV infection is not clear. Total 232 patients with chronic HBV infection were included in this retrospective study. We investigated the association between detailed preoperative serum CRP levels and early (≤ 2 year) and late (> 2 year) HCC recurrence following curative hepatectomy. After adjusting for potential confounders, we found a saturation effect for preoperative serum CRP of 2.1 mg/dl existed for early HCC recurrence (ER). The incidence of ER increased with preoperative serum CRP less than 2.1 mg/dl (OR = 3.5, 95% CI 1.6–7.6, P = 0.001), and higher preoperative serum CRP (>2.1 mg/dl) did not increase the incidence of ER (OR = 0.8, 95% CI 0.2–2.7, P = 0.703). Whereas there is a linear relationship between preoperative serum CRP and late HCC recurrence (LR) (OR = 0.2, 95% CI, 0.1- 0.4) (OR = 1.8, 95% CI, 1.2–2.5, P = 0.002). In addition, the optimal cutoff point for serum CRP level was 1.5 mg/dl, instead of 1.0 mg/dl, in predicting both ER and LR. Patients with higher preoperative serum CRP level (>1.5 mg/dl) had lower recurrence free survival rates and overall survival rates (P<0.01). These results suggest that preoperative serum CRP played different roles on ER and LR following curative hepatectomy, thus further predictingthe prognosis in patients with chronic HBV infection.</p></div

Receiver-operating characteristic (ROC) of the optimal cutoff values for preoperative serum CRP in predicting ER and LR.

<p>(a) Preoperative serum CRP as indicator of ER with the area under the curve (AUC) of 0.65 (95% CI, 0.58–0.72) and the optimal cutoff point was 1.5 mg/dl with a sensitivity of 60.6% and a specificity of 69.4%. (b) Preoperative serum CRP as indicator of LR with the AUC of 0.63 (95% CI, 0.54–0.71). The optimal cutoff point was 1.5 mg/dl with a sensitivity of 56.2% and a specificity of 69.4%.</p

Patient characteristics and demographics between CRP negative and CRP positive groups.

<p>CRP: C-reactive protein; ALT: alanine aminotransferase; AST: aspartate aminotransferase.</p><p>^a Values shown are the mean±standard deviation.</p><p>Patient characteristics and demographics between CRP negative and CRP positive groups.</p

The recurrence-free survival curves and the overall survival curves in patients with serum CRP negative and positive.

<p>(a). The recurrence-free survival rates in the CRP negative group were significantly higher compared with those in the CRP positive group (P < 0.01). (b) The overall survival rates in the CRP negative group were significantly higher compared with those in the CRP positive group (P < 0.01).</p

Clinicopathological features of 232 patients who received curative hepatectomy.

<p>ER: early recurrence; LR: late recurrence; CRP: C-reactive protein; ALT: alanine aminotransferase; AST: aspartate aminotransferase.</p><p>^a Values shown are the mean±standard deviation</p><p>* Significant difference.</p><p>P¹ value: comparison between ER group and control group, P² value: comparison between LR group and control group.</p><p>Clinicopathological features of 232 patients who received curative hepatectomy.</p

The correlation between CRP and different clinicopathological features groups.

<p>(a) Distribution of CRP in both multiple tumors group and solitary tumor group. No significant difference of CRP level was found between the two groups (P = 0.229). (b) The correlation between preoperative serum CRP and the maximal tumor dimensions. This scatter plot showed that preoperative serum CRP levels were not positive correlation with the maximal tumor dimensions (P = 0.35, r = 0.062).</p

Effect of different clinicopathological features on association between CRP and HCC recurrence in exploratory subgroups.

<p>* Significant difference, association between CRP and HCC recurrence was significant different in subgroup analyzes</p><p>Effect of different clinicopathological features on association between CRP and HCC recurrence in exploratory subgroups.</p