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

Abstract

BackgroundThe 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.MethodsIn 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.ResultsHepatocellular 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).ConclusionHBV 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.

Serum soluble DR5 predicts mortality risk in patients with HBV-related hepatocellular carcinoma

“…Although researchers and clinicians have been working hard to improve the screening rate and treatment of HCC, the incidence rate and mortality of HCC have not significantly decreased, suggesting that HCC is still a refractory disease ( 3 , 4 ). The evaluation of the prognosis of patients with HCC determines their follow-up frequency and treatment methods.…”

“…Primary liver cancer (PLC) is the sixth most commonly diagnosed cancer, the third leading cause of cancer death worldwide in 2020 ( 1 ), and the second leading cause of cancer death in mainland China ( 2 , 3 ). Hepatocellular carcinoma (HCC) is the major histotype of PLC, and hepatitis B-related HCC accounts for more than 84.4% of all hepatocellular carcinomas ( 4 ), imposing heavy economic and social burdens on the country. Current treatment methods for HCC include surgery, transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), chemotherapy, molecular targeted therapies, and immune checkpoint inhibitor therapies.…”

HBV preS Mutations Promote Hepatocarcinogenesis by Inducing Endoplasmic Reticulum Stress and Upregulating Inflammatory Signaling

“…In China, the first leading cause of cancer death in residents younger than 65 years is primary liver cancer [2]. Hepatocellular carcinoma (HCC) contributed 75-85% of primary liver cancer cases globally but 93.0% in China [3,4]. A total of 84.4% HCC in China are caused by Chronic Hepatitis B virus (HBV) infection [4].…”

“…Hepatocellular carcinoma (HCC) contributed 75-85% of primary liver cancer cases globally but 93.0% in China [3,4]. A total of 84.4% HCC in China are caused by Chronic Hepatitis B virus (HBV) infection [4]. Compared to other HCC-related etiological factors, chronic HBV infection is associated with a 10-year earlier onset and the more aggressive nature of HCC [4].…”

“…A total of 84.4% HCC in China are caused by Chronic Hepatitis B virus (HBV) infection [4]. Compared to other HCC-related etiological factors, chronic HBV infection is associated with a 10-year earlier onset and the more aggressive nature of HCC [4]. During HBV-induced hepatocarcinogenesis, HBV evolves gradually, which is partially induced by cytidine deaminases [5,6].…”