Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients

AIM:To clarify the utility of using des-γ-carboxy prothrombin(DCP)andα-fetoprotein(AFP)levels to predict the prognosis of hepatocellular carcinoma(HCC)in patients with hepatitis B virus(HBV)and the hepatitis C virus(HCV)infections.METHODS:A total of 205 patients with HCC(105patients with HBV infection 100 patients with HCV infection)who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively.Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy,and cutoff levels were calculated.Patients in the HBV and HCV groups were classified into three groups:a group with low AFP and DCP levels(LL group),a group in which one of the two parameters was high and the other was low(HL group),and a group with high AFP and DCP levels(HH group).Liver function parameters,the postoperative recurrence-free survival rate,and postoperative overall survival were compared between groups.The survival curves were compared by logrank test using the Kaplan-Meier method.Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis.RESULTS:The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/m L and 60 m AU/m L,respectively;for preoperative DCP levels,the cutoff levels were 21.0 ng/m L in the HBV group and 67 m AU/m L in the HCV group.The HBV group was significantly different from the other groups in terms of vascular invasion,major hepatectomy,volume of intraoperative blood loss,and surgical duration.Significant differences were found between the LL group,the HL group,and the HH group in terms of both mean disease-free survival time(MDFST)and mean overall survival time(MOST):64.81±7.47 vs 36.63±7.62 vs 18.98±6.17mo(P=0.001)and 85.30±6.55 vs 59.44±7.87 vs46.57±11.20 mo(P=0.018).In contrast,the HCV group exhibited a significant difference in tumor size,vascular invasion,volume of intraoperative blood loss,and surgical duration;however,no significant difference was observed between the three groups in liver function parameters except for albumin levels.In the LL group,the HL group,and the HH group,the MDFST was 50.09±5.90,31.01±7.21,and 14.81±3.08 mo(log-rank test,P<0.001),respectively,and the MOST was 79.45±8.30,58.82±7.56,and 32.87±6.31 mo(log-rank test,P<0.001),respectively.CONCLUSION:In the HBV group,the prognosis was poor when either AFP or DCP levels were high.In the HCV group,the prognosis was good when either or both levels were low;however,the prognosis was poor when both levels were high.High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups.The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.

Alpha-fetoprotein and des-gamma-carboxy-prothrombin at twenty-four weeks after interferon-based therapy predict hepatocellular carcinoma development

AIM: To investigate risk factors for development of hepatocellular carcinoma(HCC) in patients with hepatitis C virus-related liver cirrhosis(LC-C).METHODS: To evaluate the relationship between clinical factors including virological response and the development of HCC in patients with LC-C treated with interferon(IFN) and ribavirin, we conducted a multicenter, retrospective study in 14 hospitals in Japan. All patients had compensated LC-C with clinical or histological data available. HCC was diagnosed by the presence of typical hypervascular characteristics on computed tomography and/or magnetic resonance imaging.RESULTS: HCC was diagnosis in 50(21.6%) of 231 LC-C patients during a median observation period of 3.8 years after IFN and ribavirin therapy. Patients who developed HCC were older(P = 0.018) and had higher serum levels of pretreatment alpha-fetoprotein(AFP)(P = 0.038). Multivariate analysis revealed the following independent risk factors for HCC development: history of treatment for HCC [P < 0.001, odds ratio(OR) = 15.27, 95%CI: 4.98-59.51], AFP levels of ≥ 10 ng/m L(P = 0.009, OR = 3.89, 95%CI: 1.38-11.94), and des-γ-carboxy prothrombin(DCP) levels of ≥ 40 m AU/mL at 24 wk after the completion of IFN and ribavirin therapy(P < 0.001, OR = 24.43, 95%CI: 4.11-238.67).CONCLUSION: We suggested that the elevation of AFP and DCP levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.

The Number of Positive Tumor Marker Status Is Beneficial for the Selection of Therapeutic Modalities in Patients with Hepatocellular Carcinoma

Hepatic resection (HR) and radiofrequency ablation (RFA) are popular local therapies for early-stage hepatocellular carcinoma (HCC).Alpha-fetoprotein,Lens culinaris agglutininreactive fraction of alpha-fetoprotein,and des-c-carboxy prothrombin are well-known and useful tumor markers for HCC.The positive number status of these tumor markers has recently been demonstrated as beneficial for predicting outcome for HCC patients treated with local therapy.Although the normal ranges reported have differed by institution,the positivity of tumor markers is consistent and can easily be assessed.Kumamoto and Wakayama's group clearly demonstrated the following:1) Regardless of the degree of tumor stage,a triple-positive tumor marker profile can predict poor outcome in HCC patients undergoing HR;2) For RFA alone,HCC patients with double-and triple-positive status,having less than three lesions and lesions ≤3 cm in diameter show comparably insufficient outcomes;3) For HCC patients with lesions ≤5 cm in Child-Pugh grade A,HR is preferred over RFA;4) Microvascular invasion rates increased even in the double-positive patients,while poorly differentiated HCC was frequently observed only in the triple-positive patients;and 5) RFA with chemoembolization,anatomical liver resection,and postoperative adjuvant chemoembolization or hepatic arterial chemotherapy might improve the outcome for patients with highly malignant HCC with multiple positive tumor markers.However,the impacts of these therapies still need to be evaluated in prospective comparative studies.