Early on-treatment predictions of clinical outcomes using alpha-fetoprotein and des-gamma-carboxy prothrombin responses in patients with advanced hepatocellular carcinoma

Background and Aim: The clinical utility of alpha‐fetoprotein (AFP) and des‐γ‐carboxy prothrombin (DCP) as a predictor of treatment outcome in patients with advanced hepatocellular carcinoma (HCC) receiving hepatic artery infusional chemotherapy (HAIC) or concurrent chemoradiation therapy (CCRT) has been poorly defined. Methods: Between January 2003 and December 2007, we enrolled 127 treatment‐naïve patients who received HAIC (n = 60) or CCRT (n = 67) as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 20% from the baseline level. Results: AFP responders showed significantly better overall survival (OS) than non‐responders among patients with HAIC (median 17.3 vs 6.4 months, P < 0.001) and with CCRT (median 17.6 vs 8.7 months, P = 0.014). DCP responders in the CCRT group also showed significantly better progression‐free survival (PFS) than non‐responders (median 9.2 vs 3.1 months, P < 0.001). Multivariate Cox regression analyses showed that AFP response was independently predictive of OS in both groups (P = 0.009 in HAIC and P = 0.008 in CCRT) whereas DCP only predicted PFS in patients with CCRT (P = 0.015). Conclusions: Early on‐treatment AFP response was predictive of OS in treatment‐naïve patients with advanced HCC receiving HAIC and CCRT as an initial treatment modality. Furthermore, DCP response was useful for predicting PFS in patients with CCRT.     

Clinical significance of half‐lives of tumor markers α‐fetoprotein and des‐γ‐carboxy prothrombin after hepatectomy for hepatocellular carcinoma

Aim

The prognostic significance of the half‐lives (HLs) of α‐fetoprotein (AFP) and des‐γ‐carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients.

Methods

This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post‐hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis.

Results

Three‐year recurrence‐free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five‐year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07).

Conclusion

Post‐hepatectomy HLs of AFP and DCP are predictors of long‐term outcome in patients with HCC.     

Significance of hepatic resection and adjuvant hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombus in the first branch of portal vein and the main portal trunk: a project study for hepatic surgery of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery

Background

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus in the major portal vein (PV) is extremely poor. The purpose of this study was to clarify the impact of hepatic resection for HCC with tumor thrombus in the major PV.

Patients

Four hundred patients undergoing macroscopic curative resection for HCC involving the first branch or trunk of the PV between 2001 and 2010 at the 22 institutions were enrolled. We examined the effect of adjuvant hepatic arterial infusion chemotherapy (HAIC) on prognosis and validated the prognostic index consisting of ascites, prothrombin activity, and maximal tumor diameter.

Results

Median survival time (MST) and 5‐year overall survival rate were 21.5 months and 25.7%. MST of HAIC group was longer than that of non‐HAIC group (28.1 months vs. 18.7 months, P = 0.0024). Significant prognostic factors for overall survival were PIVKA‐II, tumor diameter, and adjuvant HAIC. MST for patients with prognostic index 0, 1, 2, and 3 was 39.0, 21.1, 18.9, and 5.7 months, respectively (P = 0.005).

Conclusions

Macroscopic curative resection with adjuvant HAIC might provide better survival outcome. Furthermore, the prognostic index was useful to select adequate treatment modalities for patients with HCC with tumor thrombosis in the major PV.     

Differential Effects of Vitamin K1 on AFP and DCP Levels in Patients with Unresectable HCC and in HCC Cell Lines

Purpose  

DCP is a useful HCC tumor marker, which reflects a defect in vitamin K metabolism. We tested the hypothesis that vitamin K treatment of HCC patients might suppress this marker and possibly AFP also.     

Prognostic factors in patients with advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy

Background The prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor. We aimed to clarify the prognostic factors in patients with advanced HCC receiving hepatic arterial infusion chemotherapy (HAIC).Methods Forty-four HCC patients were treated with HAIC, using low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) with/without leucovorin (or isovorin). Of these 44 patients, 15 received low-dose CDDP and 5-FU, and 29 received low-dose CDDP, 5-FU, and leucovorin or isovorin. Prognostic factors were evaluated by univariate and multivariate analyses of patient and disease characteristics.Results Of all patients, 5 and 12 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, 38%). The response rate (48.3%) in the low-dose CDDP and 5-FU with leucovorin/isovorin group was significantly better than that (20%) in the low-dose CDDP and 5-FU group (P = 0.002). The 1-, 2-, 3-, and 5-year cumulative survival rates of the 44 patients were 39%, 18%, 12%, and 9%, respectively. The regimen using low-dose CDDP and 5-FU with leucovorin/isovorin tended to improve survival rates (P = 0.097). Univariate and multivariate analyses showed the same variables—the Child-Pugh score (P = 0.013, P = 0.018), -fetoprotein (AFP) level (P = 0.010, P = 0.009), and therapeutic effect after HAIC (P = 0.003, P = 0.01), respectively, to be significant prognostic factors.Conclusions Patients who had advanced HCC with favorable hepatic reserve capacity and a lower AFP level were suitable candidates for HAIC. Moreover, the regimen using low-dose CDDP and 5-FU with leucovorin/isovorin may be suitable for advanced HCC patients, because of the improvement in the response rate and survival compared with the low-dose CDDP and 5-FU regimen without leucovorin/isovorin.     

Diagnostic accuracy of des‐gamma‐carboxy prothrombin for hepatocellular carcinoma in a French cohort using the Lumipulse® G600 analyzer

The increasing incidence of hepatocellular carcinoma (HCC) in Western countries requests reliable tumour markers for preclinical diagnosis. We evaluated the diagnostic accuracy of des‐gamma‐carboxy prothrombin (DCP), in comparison with alpha‐fetoprotein (AFP) in a French cohort using a new analyser. One hundred and sixty‐two patients with virus‐related cirrhosis (46 HCC patients and 116 controls) were recruited in this retrospective proof‐of‐concept study. DCP was measured on new Lumipulse^® G600 analyzer and AFP on usual Cobas e602 analyzer in serum samples that were collected at the time of HCC diagnosis for HCC patients or during follow‐up for controls. DCP and AFP levels were higher in HCC patients. The area under receiver operating characteristic curve was larger for DCP than for AFP (0.89 vs 0.77, P=.03). At the cut‐off value of 128 mAU/mL, sensitivity and specificity for DCP were 74% and 92%. At the cut‐off value of 20 μg/L, sensitivity and specificity for AFP were 63% and 82%. NRI_>0 for the association of “AFP+DCP” were 101%, P<.0001, and 23%, P=.03, compared to “AFP” or “DCP” alone, respectively. We conclude that DCP outperformed AFP for the detection of HCC.     

Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma

Purpose  

Hepatic arterial infusion chemotherapy (HAIC) has often been used as a therapeutic option for patients with advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and safety of HAIC using cisplatin with or without 5-fluorouracil in patients with advanced HCC.     

AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC

Background

Alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxy prothrombin (DCP), and Golgi protein-73 (GP73) have been used or proposed as tumor markers for hepatocellular carcinoma (HCC).

Methods

They were measured in 96 patients undergoing hepatectomy for HCC to investigate their treatment response and association with variables linked with tumor invasiveness and/or prognosis. Values at 1 month post-surgery in the 77 patients without recurrence within 6 postoperative months were adopted as those after surgery.

Results

GP73 levels did not change after hepatectomy, but levels of other markers decreased and areas under receiver operating characteristic curves (95% CI) were: 0.64 (0.56–0.72), 0.63 (0.55–0.71), 0.79 (0.73–0.86), and 0.63 (0.55–0.71) for AFP, AFP-L3, DCP, and combination of AFP and AFP-L3, respectively. Cutoff points giving specificities of 96.1% (sensitivities at these points) were: 124 ng/mL (28.1%), 10% (21.9%), and 60 mAU/mL (52.1%), for AFP, AFP-L3, and DCP, respectively. The combination of AFP and AFP-L3 provided a sensitivity of 26.0% at a specificity of 96.1%. The increased DCP value was, or tended to be, associated with a larger tumor, vascular invasion, intrahepatic metastases, and a lower grade of tumor cell differentiation. Although similar associations were found between AFP and vascular invasion as well as a lower grade of tumor cell differentiation, no such relationship was found with AFP-L3.

Conclusions

DCP is a more effective tumor marker than AFP and AFP-L3. AFP-L3 showed comparable accuracy to AFP but no benefit was found in their combination. GP73 did not play a significant role in this context. Indices of tumor invasiveness were most closely associated with DCP.     

Predictive value of tumor markers for hepatocarcinogenesis in patients with hepatitis C virus

Background  

Increases in tumor markers are sometimes seen in patients with chronic liver disease without hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between the levels of three tumor markers [alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3%), and des-γ-carboxy prothrombin (DCP)] and hepatic carcinogenesis to identify hepatitis C virus (HCV) carriers at high risk for cancer development.     

Serum vascular endothelial growth factor as a predictor of response and survival in patients with advanced hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy

Background

Hepatic arterial infusion chemotherapy (HAIC) has been recognized as a useful therapeutic modality for patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to investigate the association between serum vascular endothelial growth factor (VEGF) levels and the therapeutic effect of HAIC and the survival of patients undergoing HAIC.

Methods

Seventy-one patients with advanced HCC underwent HAIC through a subcutaneously implanted infusion port. One chemotherapy course consisted of low-dose cisplatin (10?mg/body on days 1–5) and 5-fluorouracil (250?mg/body on days 1–5), and 1 treatment cycle consisted of 2–3 courses of chemotherapy. Serum VEGF levels were measured with the Bio-Plex Suspension Array System (Bio-Rad Laboratories).

Results

The median survival time (MST) of all patients was 10.2?months, and the 1-, 2-, 3-, and 5-year survival rates were 46.5, 21.9, 12.8, and 3.7%, respectively. Of the 71 patients, 3 achieved a complete response (CR) and 22 achieved a partial response (PR) [response rate (CR?+?PR/71)?=?35%]. The serum VEGF level (≥100?pg/mL, P?=?0.026) was an independent predictor of therapeutic effect, and was positively correlated with the platelet count (r?=?0.569, P?r?=?0.543, P?P?=?0.046), serum VEGF level (P?=?0.004), and therapeutic effect (P?=?0.005) were identified by multivariate analysis as independent predictors of survival.

Conclusions

These results demonstrate that the serum VEGF level in patients with advanced HCC undergoing HAIC is an important predictive factor for therapeutic effect and survival.     

Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion

Background

The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients.

Methods

We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT).

Results

Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group (p < 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group (p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18 %, p < 0.01) and PVTT (45 vs. 18 %, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups (p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively).

Conclusions

CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT.

     

Early α‐fetoprotein response as a predictor for clinical outcome after localized concurrent chemoradiotherapy for advanced hepatocellular carcinoma

Backgrounds: There are limitations in using only radiological criteria to evaluate treatment outcomes in hepatocellular carcinoma (HCC). α‐fetoprotein (AFP) is regarded as an indicator of tumour activity in HCC. Aims: We present a novel correlation between AFP response and survival outcome in patients treated with localized concurrent chemoradiotherapy (CCRT). Materials: From 2005 to 2008, 187 locally advanced HCC patients underwent localized CCRT (external beam radiotherapy at 45 Gy over 5 weeks plus a concurrent hepatic arterial infusion of 5‐fluorouracil during the first/fifth week), followed by repetitive hepatic arterial infusional chemotherapy (HAIC) with 5‐fluorouracil and cisplatin. Among them, 149 with an elevated baseline AFP level (>20 ng/ml) were finally studied. AFP response was defined as >50% decrease from baseline, 1 month after the completion of localized CCRT. Results: Patients' characteristics were as follows: median age (52 years); Child–Pugh class A/B (n=137/12 respectively); and portal vein thrombosis (n=118). AFP responders (101 patients) had better objective responses than AFP non‐responders (48 patients) after CCRT (44.5 vs. 12.5%; P<0.001) and subsequent HAIC (51.5 vs. 16.7%; P<0.001). Both median progression‐free survival (PFS, 8.1 vs. 3.9 months; P<0.001) and overall survival (OS, 13.3 vs. 5.9 months; P<0.001) were longer in AFP responders than AFP non‐responders. In multivariate analysis, AFP response and objective response were independent factors affecting PFS and OS. Furthermore, AFP non‐responders were more likely to have extrahepatic metastasis within 6 months of treatments initiation than AFP responders (59.5 vs. 25.9%; P<0.001). Conclusions: Early AFP response may be useful not only in predicting prognosis and treatment response but also in establishing optimized treatment plans for HCC.     

Clinicopathologic features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein-L3 and seronegative for des-gamma-carboxy prothrombin in comparison with those seropositive for des-gamma-carboxy prothrombin alone

BACKGROUND: There has been no study of the clinicopathologic features of patients with hepatocellular carcinoma (HCC) who are seropositive for lectin-reactive alpha-fetoprotein (AFP-L3) alone, or seropositive for AFP-L3 and seronegative for des-gamma-carboxy prothrombin (DCP) in comparison with those who are seropositive for DCP alone. Thus, the present comparative study was performed. METHODS: The clinicopathologic features of HCC patients with either one or two tumors who underwent a hepatectomy (n = 88) were compared among the following five groups according to the seropositivity of AFP, AFP-L3 and DCP: (i) group A, seropositive for AFP above 100 ng/mL, AFP-L3 above 15% and DCP above 100 mAU/mL; (ii) group B, seropositive for AFP-L3 and seronegative for DCP below 40 mAU/mL; (iii) group C, seronegative for AFP below 20 ng/mL, AFP-L3 below 15% and seropositive for DCP; (iv) group D, seropositive for AFP and seronegative for AFP-L3 and DCP; and (v) group E, seronegative for AFP, AFP-L3 and DCP. RESULTS: Group B patients showed a higher incidence of infiltrative-type HCC with an irregular margin (P < 0.05) and a higher frequency of poorly differentiated HCC (P < 0.01) compared with group C patients. Group A patients had larger tumors and more massive-type tumors than group B patients. Our HCC cases showed that advanced clinicopathologic features were demonstrated in the order of group B, group C and group D. Group A and B patients and group D and E patients showed similar characteristics. CONCLUSIONS: Hepatocellular carcinoma patients who were seropositive for AFP-L3 and seronegative for DCP demonstrated clinicopathologic features of more advanced HCC compared with those who were seropositive for DCP alone.     

Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: We conducted a prospective study to evaluate the significance of simultaneous measurement of 3 currently used tumor markers in the evaluation of tumor progression and prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), were measured in the same serum samples obtained from 685 patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL, AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition, tumor markers were measured after treatment of HCC. RESULTS: Of the 685 patients, 337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371 (54.2%) were positive for DCP. In a comparison of patients positive for only 1 tumor marker, patients positive for AFP-L3 alone had a greater number of tumors, whereas patients positive for DCP alone had larger tumors and a higher prevalence of portal vein invasion. When patients were compared according to the number of tumor markers present, the number of markers present clearly reflected the extent of HCC and patient outcomes. The number of markers present significantly decreased after treatment. CONCLUSIONS: Tumor markers AFP-L3 and DCP appear to represent different features of tumor progression in patients with HCC. The number of tumor markers present could be useful for the evaluation of tumor progression, prediction of patient outcome, and treatment efficacy.     

Clinicopathologic features of patients with primary malignant hepatic tumors seropositive for alpha-fetoprotein-L3 alone in comparison with other patients seropositive for alpha-fetoprotein-L3

BACKGROUND: Patients with hepatocellular carcinoma (HCC) seropositive for lectin-reactive alpha-fetoprotein (AFP-L3) have a poor prognosis. However, there have been no studies of the clinicopathologic features of patients seronegative for both AFP and des-gamma-carboxy prothrombin (DCP), and seropositive for AFP-L3 alone in comparison with other patients seropositive for AFP-L3. METHODS: Patients with primary malignant hepatic tumors seropositive for AFP-L3 who underwent hepatectomy (n = 84) were divided into four groups, and their clinicopathologic features were compared: (i) group A, seronegative for AFP <100 ng/mL and DCP <40 mAU/mL; (ii) group B, seropositive for AFP > or =100 ng/mL and seronegative for DCP; (iii) group C, seronegative for AFP and seropositive for DCP > or =40 mAU/mL; and (iv) group D, seropositive for AFP and DCP. RESULTS: Among the 14 group A patients seropositive for AFP-L3 alone with low AFP concentrations, three had intrahepatic cholangiocarcinoma (ICC), one had a cholangiolocellular carcinoma, one had combined HCC and ICC, and one had undifferentiated hepatic sarcoma. Group A had a higher incidence of non-HCC tumors (P < 0.001) and tumors derived from cholangiocytes (P < 0.001) than the other three groups. They also had a high frequency of poorly differentiated tumors and sarcomatous changes, and showed a poor prognosis. CONCLUSIONS: Patients with primary malignant hepatic tumors seropositive for AFP-L3 alone with low AFP concentrations have unique clinicopathologic features. Thus, we should be aware of these patients and should measure AFP-L3 levels, at least once, even in those seronegative for both AFP and DCP.     

ERS: A simple scoring system to predict early recurrence after surgical resection for hepatocellular carcinoma

Background

Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking.

Objectives

To develop and validate a simple scoring system to predict 2-year recurrence after SR for HCC.

Methods

2359 treatment-naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2-year recurrence in the DS and validated in the VS.

Results

Variables associated with 2-year recurrence in the DS were (with associated points) alpha-fetoprotein (<10 ng/mL:0; 10–100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2-year recurrence risk (Wolbers' C-indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C-indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post-operative model to predict time to early recurrence or recurrence-free survival.

Conclusions

ERS is a user-friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials.     

Decrease in alpha-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study

Background

Increasing evidence suggests the efficacy of interferon therapy for hepatitis C in reducing the risk of hepatocellular carcinoma (HCC). The aim of this study was to identify predictive markers for the risk of HCC incidence in chronic hepatitis C patients receiving interferon therapy.

Methods

A total of 382 patients were treated with standard interferon or pegylated interferon in combination with ribavirin for chronic hepatitis C in a single center and evaluated for variables predictive of HCC incidence.

Results

Incidence rates of HCC after interferon therapy were 6.6% at 5?years and 13.4% at 8?years. Non-sustained virological response (non-SVR) to antiviral therapy was an independent predictor for incidence of HCC in the total study population. Among 197 non-SVR patients, independent predictive factors were an average alpha-fetoprotein (AFP) integration value ≥10?ng/mL and male gender. Even in patients whose AFP levels before interferon therapy were ≥10?ng/mL, reduction of average AFP integration value to <10?ng/mL by treatment was strongly associated with a reduced incidence of HCC. This was significant compared to patients with average AFP integration values of ≥10?ng/mL (P?=?0.009).

Conclusions

Achieving sustained virological response (SVR) by interferon therapy reduces the incidence of HCC in hepatitis C patients treated with interferon. Among non-SVR patients, a decrease in the AFP integration value by interferon therapy closely correlates with reduced risk of HCC incidence after treatment.     

The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma

Background

Hepatocellular carcinoma (HCC) has a high mortality rate, and early detection of HCC improves patient survival. However, the molecular diagnostic markers for early HCC have not been fully elucidated. The aim of this study was to identify novel diagnostic markers for HCC.

Methods

Serum protein profiles of 45 hepatitis C virus infection (HCV)-related HCC patients (HCV-HCC) were compared to 42 HCV-related chronic liver disease patients without HCC (HCV-CLD) and 21 healthy volunteers using the ProteinChip SELDI system. One of the identified proteins was evaluated as a diagnostic marker for HCC in patients with HCV.

Results

Five protein peaks (4067, 4470, 7564, 7929, and 8130 m/z) had p-values less than 1 × 10^?7 and were significantly increased in the sera of HCV-HCC patients compared to HCV-CLD patients and healthy volunteers. Among these proteins, an 8130 m/z peak was the most differentially expressed and identified as the complement component 3a (C3a) fragment. For HCV-HCC and HCV-CLD, the relative intensity of this C3a fragment had the best area under the ROC curve [0.70], followed by des-γ-carboxy prothrombin (DCP) [0.68], lectin-bound alpha fetoprotein (AFP-L3) [0.58] and AFP [0.53] for HCC. A combined analysis of the C3a fragment, AFP and DCP led to a 98% positive identification rate. In addition, the measurable C3a fragment in some HCC patients was not only significantly higher in the year of HCC onset compared to the pre-onset year, but also decreased after treatment.

Conclusions

The 8130 m/z C3a fragment is a potential marker for the early detection of HCV-related HCC.     

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.     

Effects of loco regional treatments before living donor liver transplantation on overall survival and recurrence-free survival in South Korean patients with hepatocellular carcinoma

Background

We evaluated the effects of pre-transplant locoregional treatment on survival in living donor liver transplantation (LDLT), and the most accurate method for predicting survival after LDLT in patients who received pre-transplant locoregional treatment.

Methods

From December 2003 to December 2012, 234 patients underwent LDLT for hepatocellular carcinoma (HCC) at our transplant center. We retrospectively reviewed 86 patients newly diagnosed with HCC and who received pre-transplant locoregional treatments at our hospital.

Results

Of the 33 patients with HCC initially beyond the Milan criteria, 12 experienced successful down-staging after locoregional treatments, and the 5-year recurrence-free survival was 81.8%, which was comparable to those in patients with HCC initially within the Milan criteria. A bad responder according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) [HR, 4.874 (1.059–22.442), p = 0.042], and increased AFP levels [HR 4.002 (1.540–10.397), p = 0.004] during pre-transplant locoregional treatments were independent risk factors for HCC recurrence after LDLT in multivariate analysis.

Conclusions

Liver transplantation may be considered after successful down-staging in patients with HCC initially beyond the Milan criteria. The mRECIST and serum AFP level changes are better selection criteria for LDLT in patients who have received locoregional treatments.