An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population.
Hepatectomy could reactivate HBV replication during the perioperative period, especially in patients who did not receive any antiviral therapy. A close monitoring of HBV DNA during the perioperative period was necessary irrespective of the preoperative HBV DNA level. Once HBV was reactivated, antiviral therapy should be given.
The early diagnosis of hepatocellular carcinoma (HCC) is of great clinical desirable due to lack of specific and sensitive markers. Alterations in the sugar chains of glycoprotein synthesized by the liver contribute to the molecular basis of abnormalities in carcinogenesis. This study aims to construct and assess the diagnostic value of N-glycan based diagnostic model in HCC identification and follow-up. A total of 393 subjects including HBV-related HCC, liver fibrosis and healthy controls were recruited. Follow-up was carried out before and after surgical treatment in HCC. N-glycome of serum glycoprotein was profiled by DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Multiparameters diagnostic models were constructed based on N-glycan markers. The result found that 2 N-glycan structure abundances (NG1A2F, Peak 4; NA3Fb, Peak 9) were useful as N-glycan markers. The diagnostic efficacy of the log ratio [log(p9/4)] was similar to that of AFP in differentiating HCC from fibrosis. The accuracy and sensitivity of the diagnostic model combining AFP and N-glycan markers (Cscore B) were increased 7-10% compared with that of AFP. Log(p9/4) was more efficient in monitoring the progression of HCC with regarding to vascular invasion at improved specificity (16%) and accuracy (8%) compared with that of AFP. The N-glycan markers were found to be changed significantly after surgical resection in HCC follow-up. We conclude that the branching a (1,3)-fucosylated triantennary glycan and a biantennary glycan are promising as N-glycan markers. The diagnostic models based on the N-glycan markers and AFP improve the efficacy in HCC diagnosis and progression monitoring.Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are frequent causes of acute and chronic hepatitis worldwide and leading causes for hepatic cirrhosis and cancer. There is a distinct geographical variation in HBV and HCV infection incidence and prevalence in different regions. Chronic HBV infection is a serious health threat in the Asian-Pacific region. Of the estimated 50 million new cases of HBV infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these are in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. 1
Hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT) is associated with poor prognosis, early recurrence of HCC, and limited treatment options. Current guidelines do not have standardized diagnostic and treatment modalities, thus creating a need for a multidisciplinary treatment model for standardization of the treatment. Eastern Hepatobiliary Surgical Hospital (China) convened two working parties of experts from all the departments, to consolidate the current evidence, prevailing vision for the future, and experience of the practicing clinicians engaged in HCC management, so as to develop a consensus for PVTT diagnosis and treatment according to the GRADE system. Based on the quality of the existing evidence and the strength of recommendations, the consensus statements were categorized into 3 evidence levels (A/B/C) and 5 classes (I/II/IIa/IIb/III). The panel discussed and provided clarity on the management and research options in the field of HCC with PVTT. In addition, the panel also assessed the quality of the cited studies and assigned grades to the recommendation statements. Among the group of experts, there was excellent agreement with regard to effective diagnosis and treatment of HCC with PVTT. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective management of HCC with PVTT.
Immunoglubulin G (IgG) and its abnormal glycosylations are associated with carcinogenesis. The present study investigates the relationship between cancer-derived IgG and clinicopathological characteristics in hepatocellular carcinoma (HCC) and assesses the value of serum N-glycosylated IgG in diagnosing and monitoring hepatitis B virus (HBV)-related HCC. Tissue microarray analysis of 90 HCC tissues showed that HCC patients with IgG immunopositivity had higher levels of core-fucosylated a fetoprotein (AFP-L3), larger tumors, and a higher incidence of portal vein tumor thrombus. HCC-derived IgG stimulated the growth of liver cancer cells in vitro. HCC patients presented a significantly increased fraction of Lens culinaris agglutinin binding IgG (core-fucosylated IgG, IgG-L3) among total serum IgG. The clinical diagnostic performance of serum IgG-L3% was evaluated in 3 case-control studies (1 training set and 2 validation cohorts), including 293 patients with HCC, 131 with liver cirrhosis, 132 HBV carriers, and 151 healthy controls. IgG-L3% had better general diagnostic performance than AFP in the training set and validation cohort 1 (accuracy: 81.33-85.11% versus 63.33-78.61%). In validation cohort 2, where we aimed to assess the efficiency of IgG-L3% in patients with AFP-negative HCC, the diagnostic accuracy of IgG-L3% was 72.54-73.60%. Finally, a longitudinal evaluation based on 31 HCC patients demonstrated that IgG-L3% decreased in 24 patients after curative surgery. The remaining 7 patients showed elevated IgG-L3% and post-operative recurrence. HCC patients with higher IgG-L3% had poor survival during a 3-year follow up. We conclude that HCC-derived IgG is correlated with progressive behavior of HCC. Therefore, elevated core-fucosylated IgG is a new diagnostic and prognostic marker in HBV-related HCC.
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