Epidemiological Characteristics of Primary Liver Cancer in Mainland China From 2003 to 2020: A Representative Multicenter Study

Abstract

Background: The contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to primary liver cancer (PLC) and their association with cancer aggressiveness remains uncertain in China, a country with half of global PLC. We aimed to characterize this using data from four representative medical centers.

Methods: In total, 15,801 PLC patients were enrolled from the centers distributed in Easter5n, Southern, Northern, and Western China from 2003 to 2020. Of those, 7585 with curative surgery were involved in survival analysis. A nomogram was constructed using preoperative parameters to predict postoperative survival.

Results: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma accounted for 93.0%, 4.3%, and 1.6% in PLC, respectively. The seropositivities of HBV and HCV were 84.4% and 3.2% in HCC, respectively. The seropositivity of anti-HCV antibody was significantly higher in HBV-negative than in HBV-positive HCC patients (13.2% vs. 1.1%). Compared to HCV-positive HCC (HCV-HCC), HBV-positive HCC (HBV-HCC) was associated with 12-year earlier onset, higher proportions of males, high α-fetoprotein, large tumor size, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and vascular tumor thrombus. The proportions of HCC and HBV seropositivity increased, whereas that of anti-HCV decreased, from 2003 to 2020. Postoperative five-year survival rate was 73.5%, 64.1%, 34.9%, and 19.7% in HCC at BCLC stage 0, A, B, and C, respectively. The multivariate Cox regression analysis showed that HBV seropositivity, incomplete tumor capsule, vascular tumor thrombus, tumor diameter (≥3 cm), advanced BCLC stage (B+C), α-fetoprotein (≥20ng/ml), and direct bilirubin (>8µmol/L) contributed independently to shorter overall survival (OS); whereas post-operative radiofrequency ablation and second resection independently improved OS in HCC. HCV-HCC had a more favorable prognosis than did HBV-HCC (Log-rank test, P<0.001). A nomogram composed of age, gender, and the preoperative independent risk factors was accurate in predicting postoperative survival in HCC (C-index: 0.735; 95% confidence interval: 0.727-0.743).

Conclusion: HBV contributes to 84.4% of HCC in China, and actively promotes hepatocarcinogenesis and HCC progression. A favorable postoperative survival obtained in patients at the early BCLC stage highlights the importance of screening for early HCC in high-risk populations. Our preoperative prognosis prediction model is important in clinical decision-making.

Keywords: hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; primary liver cancer; prognosis.

Figure 1

The dynamic trend of clinical parameters of PLC patients from 2003 to 2020. (A) The proportions of HCC, HBV seropositivity, HCV seropositivity, and early BCLC stage in PLC. (B) The proportions of HBV seropositivity, HCV seropositivity, and early BCLC stage in HCC. (C) The dynamic trends of 1-year, 3-year, and 5-year survival rates. Linear trends were calculated by using Cochran-Armitage test. BCLC, Barcelona Clinic Liver Cancer; HBV, hepatitis B virus; HCV, hepatitis C virus; HCC, hepatocellular carcinoma.

Figure 2

Comparison of postoperative survival probability between HCC patients solely infected with HBV and HCC patients solely infected with HCV. (A) All the patients. (B) Patients following the 1:2 propensity score (PS) matching with age, gender, and BCLC stage. HBV, hepatitis B virus; HCV, hepatitis C virus; HCC, hepatocellular carcinoma. Kaplan–Meier curves were plotted to visualize the difference.

Figure 3

Preoperative nomogram for predicting postoperative survival in HCC. (A) The nomogram. To use this nomogram, a patient’s value is located on each variable axis, and a line represents the number of points received for each variable value. The sum of the score of each indicator is located on”Total Points” axis, and the total point represents the likelihood of postoperative survival of 1-, 3-, or 5-year shown on the survival axes. (B) AUC of time-dependent ROC curve for 1-, 3-, or 5-year survival in the training cohort. (C) AUC of time-dependent ROC curve for 1-, 3-, or 5-year survival in the validation cohort. (D) Comparison of OS probability between low- and high-risk groups according to total points from nomogram in the training cohort. (E) Comparison of overall survival probability between low- and high-risk group according to total points from nomogram in the validation cohort. AFP, α-fetoprotein; AUC, area under the curve; BCLC, Barcelona Clinic Liver Cancer; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; OS, overall survival; ROC, receiver operating characteristics.