Usefulness of PIVKA-II After Living-donor Liver Transplantation for Hepatocellular Carcinoma

Objective

Prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) is a useful tumor marker for hepatocellular carcinoma (HCC). However, the usefulness of post-transplantation surveillance with PIVKA-II is not clear. We evaluated the clinical value of PIVKA-II in monitoring HCC recurrence after living-donor liver transplantation (LDLT).

Expression Pattern Analysis of Hepatocellular Carcinoma Tumor Markers in Viral Hepatitis B and C Patients Undergoing Liver Transplantation and Resection

Background

This study was conducted to compare the expression patterns of serum alpha-fetoprotein (AFP) and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) and resection at a high-volume single institution.

Methods

First, 663 liver transplant recipients with HCC were selected. They were divided into hepatitis B virus (HBV) (n = 628) and hepatitis C virus (HCV) groups (n = 35). Their medical records were retrospectively reviewed. Second, another cohort of 2709 patients who underwent HCC resection included 2258 HBV, 143 HCV, and 308 non-HBV non-HCV (NBNC) patients.

Results

In the transplantation group, pretransplantation AFP level >20 ng/mL was observed in 42.5% of HBV patients and 60% of HCV patients (P = .042). PIVKA-II level >40 mAU/mL was observed in 30.6% of HBV patients and 42.9% of HCV patients (P = .127). In the resection group, a preoperative AFP level >20 ng/mL was observed in 51.7% of HBV patients and 43.3% of HCV patients (P = .052). PIVKA-II level >40 mAU/mL was observed in 59.7% of HBV patients and 56.6% of HCV patients (P = .47). Preoperative AFP level >20 ng/mL and PIVKA-II level >40 mAU/mL were observed in 35.7% and 61% of NBNC patients, respectively. Receiver-operator characteristic curve analyses revealed that the expression pattern of PIVKA-II in patients with elevated AFP level was not predictable and vice versa, regardless of background liver diseases.

Conclusions

This study indicates that serum AFP and PIVKA-II may be expressed variably regardless of the types of background liver disease. Further large-volume multicenter studies are needed to evaluate the possibility of the etiology-dependent expression of tumor markers.     

Liver transplantation for hepatocellular carcinoma: analysis of factors predicting outcome in 1074 patients in OPTN Region 5

Previous studies on loco‐regional therapy (LRT) and alpha‐fetoprotein (AFP) in predicting outcome after liver transplant (LT) for hepatocellular carcinoma (HCC) have shown inconsistent results. We analyzed the OPTN database in Region 5 from January 2004 to January 2009 and performed univariate and multivariate analysis of 11 pre‐transplant recipient and donor variables in 1074 patients with HCC meeting Milan criteria to detect association with post‐LT tumor recurrence or mortality. Mean waitlist time was 438 d. The 1‐ and 5‐yr post‐LT survival was 91.1% and 71.1%, respectively. In multivariate analysis, AFP before LT was the only predictor of HCC recurrence. The association between AFP and HCC recurrence was observed only in the subgroup receiving LRT but not in the subgroup without LRT. Predictors of mortality in multivariate analysis were HCC recurrence, Donor Risk Index, last AFP before LT, and MELD score. AFP before LT was the strongest predictor of post‐transplant HCC recurrence or death in multivariate analysis. In conclusion, in Region 5 with prolonged waitlist time, high AFP was the only pre‐transplant variable predicting post‐transplant tumor recurrence and mortality for HCC meeting Milan criteria. Our results also supported the importance of the effects of LRT on AFP in predicting prognosis.     

Significance of Tumor Necrosis for Outcome of Patients with Hepatocellular Carcinoma Receiving Locoregional Therapy Prior to Liver Transplantation

Background

Locoregional therapy has been advocated as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC), and the majority of patients with HCC receive locoregional therapy prior to liver transplantation (LT). We herein aim to determine the prognostic factors affecting the outcome in patients who receive pretransplantation therapy.

Methods

We conducted a retrospective study of the prospective data of patients who received locoregional therapy before undergoing LT for HCC. The clinicopathologic features of the patients were studied using univariate and multivariate analysis to determine prognostic factors.

Results

Univariate and multivariate analysis of clinicopathologic features identified mean tumor necrosis (TN) ≥60% as the sole independent factor associated with lower HCC recurrence following LT. Further, the groups of patients with mean TN ≥60% who were within the University of California, San Francisco (UCSF) criteria and whose tumors beyond UCSF criteria were downstaged by TN following locoregional therapy had significantly better survival rates than the opposite groups. In-depth exploration of treatment modalities and pathological features indicated that HCC showed marked TN, while tumor nodules were well treated by locoregional therapy, and no viable tumors could be detected on radiological examination.

Conclusions

Mean TN ≥60% of tumor by locoregional therapy could offer better outcomes for patients with HCC undergoing LT. Therefore, locoregional therapy should be considered for patients with HCC awaiting LT or potential candidates for LT in order to induce TN as well as leading to diminished viable tumor burden and reducing the odds of HCC recurrence following LT.

     

Matrix Metalloproteinase 1 as a Novel Biomarker for Monitoring Hepatocellular Carcinoma in Liver Transplant Patients

Introduction

Orthotopic liver transplantation (LT) is considered to be one of the few curative treatments available for early stages of hepatocellular carcinoma (HCC). Alfa-fetoprotein (AFP) is the most-used biomarker for HCC despite low sensitivity and specificity. Matrix metalloproteinase 1 (MMP-1) has been considered to be involved in the process of vascular invasion of the malignant cells. The objective of this study was to assess the use of MMP-1 for the management of HCC patients for LT.

Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma waiting for liver transplantation

Lai Q, Avolio AW, Manzia TM, Sorge R, Agnes S, Tisone G, Berloco PB, Rossi M. Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma waiting for liver transplantation.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01572.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: In the last several years, there has been no agreement on how to possibly expand the Milan criteria (MC) in the selection of patients with hepatocellular carcinoma (HCC) for listing for liver transplant (LT). The aim of the study is to evaluate morphological and biological tumor parameters to identify new expanded criteria for the selection of patients with HCC as candidates for LT. Methods: We retrospectively analyzed 158 consecutive patients with HCC who underwent LT. Results: Twelve (7.6%) recurrences were observed. At multivariate analysis, alpha‐fetoprotein (AFP) >400 ng/mL (odds ratio [OR] 8.4, p < 0.01) and total tumor diameter (TTD) >8 cm (OR 7.4, p = 0.01) were the strongest predictors for recurrence. AFP‐TTD criteria resulted in a low five‐yr recurrence rate (4.9%) and an increased number of LT compared with the MC (22.2% increase). The five‐yr disease‐free survival rate was 74.4% in AFP‐TTD criteria in patients, with a higher effectiveness in stratifying the cohort with respect to the MC. Conclusions: Both AFP and TTD are good independent predictors of HCC recurrence. Their combination appears to obtain a better selection of candidates for LT without worsening patient survival and recurrence rates. This approach allows for an increase in the number of potentially transplantable patients.     

Soluble Interleukin-2 Receptor Levels in Hepatocellular Cancer: a More Sensitive Marker Than Alfa Fetoprotein

Background: Worldwide, the majority of cases of hepatocellular cancer (HCC) arise in individuals with chronic hepatitis B or C virus infections. Early detection of HCC in these patients provides the best chance for curative treatment, but serum alfa fetoprotein (AFP) levels are frequently normal in patients with small HCCs. The purpose of this study was to determine: (1) whether soluble interleukin-2 receptor (sIL-2R) levels are elevated more frequently than AFP levels in HCC patients and (2) whether sIL-2R levels are useful as a marker of successful treatment and recurrence of disease.Patients and Methods: We are performing a prospective screening program with high-risk, chronic hepatitis virus-infected patients to detect HCC. Patients are screened by using abdominal ultrasonography, serum AFP measurements, and serum sIL-2R measurements. Normal serum sIL-2R levels were established using results from 174 healthy volunteers with no evidence of hepatitis virus infection or HCC.Results: HCC has been diagnosed in 99 patients from a cohort of 1520 screened patients. Serum AFP levels were elevated in 79 patients (80%), whereas sIL-2R levels were elevated in 98 of the 99 patients (99%, P < .01, ² test). For 27 of the 99 patients (27%), HCC was diagnosed at an early stage and complete resection or ablation was performed. Serum sIL-2R levels returned to normal in all 27 patients after treatment, whereas AFP levels remained slightly elevated in 5 of the 27 (18%). Among the 16 patients in this group of 27 who developed recurrent HCC, sIL-2R levels became elevated in all 16, whereas AFP levels were elevated at diagnosis of recurrence for only 10 (P < .05).Conclusions: This study with chronic hepatitis B or C virus-infected patients indicates that (1) serum sIL-2R levels are abnormal in patients with HCC with a significantly greater frequency, compared with AFP levels, and (2) sIL-2R levels are a more sensitive marker of successful treatment and recurrence of HCC. Based on these findings, we now use serum sIL-2R measurements both to screen high-risk patients and to monitor treatment responses in patients with hepatitis who develop HCC.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 1998     

Expanded Criteria for Liver Transplantation in Patients with Hepatocellular Carcinoma

Liver transplantation (LT) is one of the few effective treatment options for hepatocellular carcinoma (HCC). Our aim in this study was to evaluate the risk factors for HCC recurrence and propose new criteria for LT based on pretransplantation findings. One hundred eighty patients who underwent LT for HCC between 2002 and 2008 were reviewed retrospectively. Outcome measures included maximal tumor size and number of tumors revealed by radiological studies before transplantation, demographics, and tumor recurrence. Maximal tumor size >6 cm, >7 tumors, and alpha-fetoprotein (AFP) levels >1000 ng/mL were identified as independent prognostic factors of HCC recurrence in univariate and multivariate analysis. Disease-free survival rate in patients with a maximal tumor size ≤6 cm, ≤7 tumors, and/or AFP levels ≤1000 ng/mL at 1, 3, and 5 years was 97.9%, 91.5%, and 90.0%, respectively, but the 1-, 3-, and 5-year disease-free survival rate of patients who had a maximal tumor size >6 cm, >7 tumors, and/or AFP levels >1000 ng/mL was 61.9%, 47.6%, and 47.6%, respectively (P < .001). In conclusion, LT can improve the survival of patients with advanced HCC if they have a maximal tumor size ≤6 cm, tumor number ≤7, and/or AFP levels ≤1000 ng/mL.     

Progression of Alphafetoprotein Before Liver Transplantation for Hepatocellular Carcinoma in Cirrhotic Patients: A Critical Factor

Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty‐three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, ‘progression’ of AFP was defined by >15 μg/L per month before LT. A total of 127 (83%) were transplanted under and 26(16%) over this threshold. After 45 months of follow‐up (median), 5‐year overall survival (OS) and recurrence free‐survival (RFS) were 72% and 69%, respectively. Five‐year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP >15 μg/L per month and preoperative nodules >3 were associated with decreased OS. Progression group and age >60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor >30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP >15 μg/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness.     

Liver transplantation for patients with hepatocellular carcinoma

BACKGROUND: Liver transplantation (LT) has been advocated as a salvage treatment for unresectable hepatocellular carcinoma (HCC). Selection criteria still need to be developed in Taiwan. OBJECTIVES: The purpose of our study was to assess the clinical findings and outcome of cirrhotic patients with HCC undergoing liver transplantation. METHODS: Our study consisted of 13 HCC patients who underwent liver transplantation during October 1996 to March 2003. The medical records and pathologic reports were analyzed retrospectively. RESULTS: Overall survival rates at 1 and 3 years were 86% and 61%, respectively. HCC recurrences occurred in three patients, one of whom is still alive with HCC recurrence 2 years after LT. The other two patients died of HCC recurrence 1 and 2 years after LT, respectively. Pretransplant alpha-fetoprotein (AFP) levels of >200 ng/mL were noted in all three patients with HCC recurrence. In contrast, only one of the ten patients without HCC recurrence had pretransplant AFP >200 ng/mL (P = .003). Four patients did not meet Milan criteria, two of whom had HCC recurrence. However, the other two patients with microscopic vascular invasion survived and were free of HCC. The only one patient, who had histologic grade 4 HCC, died of recurrence, although his tumor was AJCC stage 1. CONCLUSIONS: High AFP level is a risk factor for HCC recurrence after LT. In addition to Milan criteria, histologic tumor grading should be considered in patient selection. Microscopic vascular invasion may not affect the outcome of the patients with early HCC.     

The Use of Donation After Cardiac Death Allografts Does Not Increase Recurrence of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) recurrence in patients undergoing liver transplantation (LT) with donation after brain death (DBD) and donation after cardiac death (DCD) allografts has not previously been investigated. Rates and patterns of HCC recurrences were investigated in patients undergoing DBD (N = 1633) and DCD (N = 243) LT between 2003 and 2012. LT for HCC was identified in 397 patients (340 DBD and 57 DCD). No difference in tumor number (p = 0.26), tumor volume (p = 0.34) and serum alphafetoprotein (AFP) (p = 0.47) was seen between the groups. HCC recurrence was identified in 41 (12.1%) patients in the DBD group and 7 (12.3%) patients in the DCD group. There was no difference in recurrence‐free survival (p = 0.29) or cumulative incidence of HCC recurrence (p = 0.91) between the groups. Liver allograft was the first site of recurrence in 22 (65%) patients in the DBD group and two (37%) patients in the DCD group (p = 0.39). LT for HCC with DBD and DCD allografts demonstrate no difference in the rate of HCC recurrence. Previously published differences in survival demonstrated between recipients with HCC receiving DBD and DCD allografts despite statistical adjustment can likely be explained by practice patterns not captured by variables contained in the SRTR database.     

Related Factors of Hepatocellular Carcinoma Recurrence Associated With Hyperglycemia After Liver Transplantation

BackgroundRecurrence of hepatocellular carcinoma (HCC) is the main factor affecting the prognosis of patients with HCC undergoing liver transplantation (LT). In this study, we investigated the influencing factors of tumor recurrence and survival after LT for HCC, especially the long-term correlation with elevated fasting blood glucose (FBG).MethodsClinical data from 165 patients with HCC after LT in the General Hospital of Southern Theater Command of PLA between January 2013 and December 2016 were retrospectively analyzed. Disease-free survival (DFS) and overall survival (OS) rates, demographic characteristics, tumor characteristics, and surgical and postoperative data were evaluated.ResultsAmong 165 patients, 144 completed over 60 months of follow-up; the median follow-up period was more than 36 months. DFS rates were 76.97%, 51.52%, and 34.73% for 1, 3, and 5 years, respectively. The OS rate for 5 years was 40.28%. Independent risk factors for 1-year DFS were maximum tumor diameter >5 cm, age <49 years, and platelet transfusion. Independent risk factors for 3- and 5-year DFS were maximum tumor diameter >5 cm, capsular invasion, and FBG ≥6.1 mmol/L. Independent risk factors for OS were maximum tumor diameter >5 cm, capsular invasion, and FBG ≥6.1 mmol/L.ConclusionElevated FBG after LT for HCC may promote medium- to long-term tumor recurrence and affect OS. Age <49 years, platelet transfusion, maximum tumor diameter, capsular invasion, and microvascular invasion in patients with HCC also impact survival and tumor recurrence after LT.     

Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression.

To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)-based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 +/- 86.4 ng/mL in recurrent vs. 169.9 +/- 33.3 in tumor-free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral- vs. non-viral-related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha-fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence-free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered.     

Impact of locoregional therapy and alpha‐fetoprotein on outcomes in transplantation for liver cancer: a UNOS Region 6 pooled analysis

Liver transplantation (LT) provides optimal long‐term disease‐free survival for hepatocellular carcinoma (HCC). High pre‐LT alpha‐fetoprotein (AFP) has been associated with HCC recurrence, but it is unclear whether a drop in AFP or locoregional therapy impacts survival/recurrence after LT. LT‐recipients transplanted for HCC in three centers (UNOS Region 6) were reviewed (2006–2009) for demographics, tumor characteristics, locoregional therapy, AFP, recurrence, and survival. Among 211 LT recipients (mean age 56.4 yr, 83% male, mean MELD 12.2), 94% met Milan criteria and 61% received locoregional therapy. Mean disease‐free survival (DFS) was 1549.7 d, and 84% are currently alive. Factors affecting DFS included recurrence (RR, 0.074; 95% CI, 0.038–0.14), normal peak AFP (29.6, 95% CI, 2.96–296.3), peak AFP >400 (RR, 0.15; 95% CI, 0.03–0.73) and AFP at LT >400 (RR, 15.5; 95% CI, 2.4–100.5). Twenty‐one patients had recurrence and were more likely beyond Milan criteria (5/23(21%) vs. 8/220 (4%), p = 0.0038), with peak AFP >400 and AFP at LT >400 (p = 0.001). Locoregional therapy did not affect mean DFS (1458.0 vs. 1603.8 d, p = 0.05) or recurrence (12.5% vs. 6%). Predictors of recurrence were similar to previous studies, including high AFP and tumor outside Milan criteria. While locoregional therapy itself did not affect DFS/recurrence, a decrease in AFP pre‐transplant appears to positively influence outcomes in those who received locoregional therapy.     

The Outcome of Salvage Liver Transplantation and Liver Resection for Recurrent Hepatocellular Carcinoma Using the 5-5-500 Rule,Japanese Extended Liver Transplantation Criteria for Hepatocellular Carcinoma

BackgroundLiver transplantation (LT) for hepatocellular carcinoma (HCC) is limited to Child-Pugh class C patients according to the Japanese HCC treatment algorithm. However, extended criteria of LT for HCC, known as the 5-5-500 rule, were published in 2019. Hepatocellular carcinoma reportedly has a high recurrence rate after primary treatment. We hypothesized that the outcome of recurrent HCC would be improved if the 5-5-500 rule were adopted for patients with recurrent HCC. We, therefore, analyzed the outcomes of surgical treatment (liver resection [LR] and LT) for recurrent HCC using the 5-5-500 rule in our institute.MethodsFifty-two patients younger than 70 years of age received surgical treatment for recurrent HCC using our institute's 5-5-500 rule from 2010 to 2019. We divided these patients into the LR and LT groups in the first study. The 10-year overall survival and re-recurrence-free survival were analyzed. The second study analyzed the risk factors of re-recurrence after surgical treatment for recurrent HCC.ResultsIn the first study, the background characteristics of the 2 groups (LR and LT) showed no significant difference, except for age and Child-Pugh classification. There was no significant difference in the overall survival between groups (P = .35), but the re-recurrence-free survival in the LR group was significantly shorter than that in the LT group (P < .01). In the second study, the male sex and LR were risk factors of re-recurrence after surgical treatment for recurrent HCC. Child-Pugh's class did not contribute to re-recurrence.ConclusionsTo improve the outcomes of recurrent HCC, LT is the better choice, regardless of the Child-Pugh class.     

Preoperative Alpha-Fetoprotein and Radiological Total Tumor Diameter as Predictors of Hepatocellular Carcinoma Recurrence After Liver Transplantation

BackgroundLiver transplantation is a unique treatment opportunity for patients with chronic liver disease and hepatocellular carcinoma (HCC). Selection of HCC patients for transplantation was revolutionized by Milan-based criteria, but tumor recurrence and shortage of organs are still a major concern. Nowadays, additional preoperative tumor parameters can help to refine the graft allocation process. The objective of this study was to evaluate the prognostic value and cut-off points of pretransplant serum alpha-fetoprotein (AFP) levels and radiological tumor parameters on liver transplantation outcomes.MethodsThis is a single-team retrospective cohort of 162 consecutive deceased donor liver transplants (DDLT) with pathologically confirmed HCC. Pretransplant serum AFP levels and radiological tumor parameters were retrieved from a preoperative follow-up. Receiver-operating characteristics (ROC) curves were used to evaluate cut-off points for each outcome. Multivariate Cox regression model was used to assess the predictors of HCC relapse and recipient mortality.ResultsTwelve recipients (7.4%) had HCC recurrence after transplantation, with median survival time of 5.8 months. Pretransplant AFP ≥30 ng/mL (hazard ratio [HR]: 13.84, P = .003) and radiological total tumor diameter (TTD) ≥5 cm (HR: 12.89, P = .005) were independent predictors for HCC relapse. Moreover, pretransplant AFP ≥150 ng/mL was independently associated with recipient mortality (HR: 4.45, P = .003).ConclusionsPretransplant AFP levels and radiological TTD were independently associated with HCC relapse and recipient mortality after DDLT, with different cut-off points predicting different outcomes. These findings may contribute to improving decision-making in the context of liver transplantation for HCC patients.     

Protein Induced by Vitamin K Antagonist-II (PIVKA-II) Is a Reliable Prognostic Factor in Small Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) <2 cm in diameter has a favorable prognosis. Therefore surgical resection of small HCC is associated with good outcomes. However, the predisposing factors of prognosis following resection of HCC remain ill-defined. The aims of the present study were to identify the clinicopathologic characteristics and outcomes of patients with small HCC and analyze the predisposing factors for tumor recurrence after surgery.

Methods

We retrospectively reviewed 180 patients with small HCC who underwent hepatectomy between 2006 and 2010. Independent predictors of tumor recurrence were identified with Cox regression analysis.

Results

The 1-year, 3-year, and 5-year disease-free survival rates and overall survival rates were 83.7, 68.0, 65.3, and 98.9, 96.5, 92.7 %, respectively. Multivariate analysis reported that protein induced by the vitamin K antagonist-II (PIVKA-II) ≥200 mAU/mL, alkaline phosphatase (ALP) ≥80 IU/mL, and microvascular invasion were important predisposing factors for tumor recurrence. Elevated serum PIVKA-II level was associated with microvascular invasion in small HCC, which was a powerful predisposing factor.

Conclusions

Although small HCC is generally associated with a good prognosis, serum PIVKA-II level ≥200 mAU/mL, ALP ≥ 80 IU/L, and microvascular invasion were predisposing factors for tumor recurrence. These factors can be used to stratify patients with respect to recurrence after resection. Elevated PIVKA-II was closely associated with microvascular invasion in small HCC. These data emphasize the importance of PIVKA-II in small HCC.     

Combination of Morphologic Criteria and α-Fetoprotein in Selection of Patients With Hepatocellular Carcinoma for Liver Transplantation Minimizes the Problem of Posttransplant Tumor Recurrence

Background

Serum α-fetoprotein concentration (AFP) might be a useful addition to morphologic criteria for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). The aim of this study was to evaluate the role of AFP in selecting HCC patients at minimal risk of posttransplant tumor recurrence in the setting of existing criteria.

Methods

This retrospective cohort study was based on 121 HCC patients after LT performed at a single institution. AFP was evaluated as a predictor of posttransplant tumor recurrence with respect to fulfillment of the Milan, University of California, San Francisco (UCSF), and Up-to-7 criteria.

Results

There was a nearly linear association between AFP and the risk of HCC recurrence (p < 0.001 for linear effect; p = 0.434 for nonlinear effect). AFP predicted HCC recurrence in patients (1) beyond the Milan criteria (p < 0.001; optimal cutoff 200 ng/ml); (2) within the UCSF criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.015; optimal cutoff 200 ng/ml); and (3) within the Up-to-7 criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.023; optimal cutoff 100 ng/ml) but not in patients within the Milan criteria (p = 0.834). Patients within either UCSF and Up-to-7 criteria with AFP level <100 ng/ml exhibited superior (100 %) 5-year recurrence-free survival—significantly higher than those within UCSF (p = 0.005) or Up-to-7 (p = 0.001) criteria with AFP levels higher than the estimated cutoffs or beyond with AFP levels less than the estimated cutoffs.

Conclusions

Combining the UCSF and Up-to-7 criteria with an AFP level <100 ng/ml is associated with minimal risk of tumor recurrence. Hence, this combination might be useful for selecting HCC patients for LT.     

Impact of body mass index on hepatocellular carcinoma recurrence after liver transplantation through long-term follow-up

BackgroundObesity is associated with increased oncological risk and outcomes but the evidence surrounding the effect of body mass index (BMI) on increased risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is still questionable. The purpose of this retrospective study of a large cohort of adult patients transplanted for HCC was to investigate the effect of BMI on the incidence of HCC recurrence and outcome.MethodsData from 427 adult recipients transplanted for HCC between 2000 and 2017 were collected. Patients were classified at time of LT according to the World Health Organization BMI classification into 3 groups; group 1: BMI <25 (n=166), group 2: BMI 25–29.9 (n=150) and group 3: BMI ≥30 (n=111).ResultsThere were no significant changes of mean BMI overtime 26.8±5.0 kg/m2 at time of LT and 28.8±23.1 at 5 years. The recurrence rates of HCC after LT in the three groups were 19%, 16% and 17% respectively. The 5, 10 and 15-year recurrence free survival (RFS) rates were respectively 68.6%, 47.3% and 40.8% in group 1, 73.3%, 66.2% and 49.5% in group 2 and 68.8%, 57.5% and 47.7% in group 3 (log rank P=0.47).ConclusionsRecipient BMI at time of transplant and during follow-up didn’t impact the incidence of HCC recurrence nor long-term patient survival, irrespective to the status of the patients and their tumor characteristic at time of LT. The present study clearly confirms that obesity should not be considered, when selecting patients with HCC to LT, as a predictive factor of recurrence.     

Hepatocellular carcinoma: Can it be considered a controversial indication for liver transplantation in centers with high rates of hepatitis C?

Hepatocellular carcinoma (HCC) is still considered a controversial indication for liver transplantation (LT), mainly because of long waiting times and underlying viral cirrhosis. The goal was to evaluate the outcome of LT in 104 patients with HCC and cirrhosis, mainly hepatitis C virus (HCV)–related, in a center with a short waiting time (median, 105 days). Four groups were formed according to the HCC and HCV status: HCV positive with HCC (group 1, n = 81), HCV negative with HCC (group 2, n = 23), HCV positive without HCC (group 3, n = 200), and HCV negative without HCC (group 4, n = 207). Predictive factors of tumor recurrence were demographics, tumor related (size or number of nodules, capsule, bilobar involvement, vascular or lymphatic invasion, clinical and pathologic TNM staging, pre-LT percutaneous ultrasound-guided ethanol injection or transarterial chemoembolization, α-fetoprotein levels), donor and surgery related, and year of transplantation. The same variables and “tumor recurrence (yes/no)” were applied to evaluate the effect on survival. The median follow up was 29 months (range, 0 to 104 months). Patient survival was 70% at 1 year and 59% at 5 years for group 1, 87% at 1 year and 77% at 5 years for group 2, 81% at 1 year and 64% at 5 years for group 3, and 88% at 1 year and 77% at 5 years for group 4 (P = .013). Survival was significantly lower in patients with HCC than in those without (74% and 63% versus 85% and 70%, at 1 and 5 years, respectively; P = .05). The causes of death in those with and without HCC were tumor recurrence (24%) and recurrent HCV (8%) versus sepsis (34%) and recurrent HCV (14%). HCC recurrence occurred in 12 patients (11.5%) at a median of 14 months (range, 3 to 60 months) with a probability increasing from 8% at 1 year to 16% at 5 years. In patients with HCC, tumor recurrence was associated with vascular invasion (P = .0004) by multivariate analysis; variables predictive of survival were donor old age (P = .01), viral-related etiology (P = .02), and tumor recurrence (P = .001). Although LT still remains an adequate indication for HCC in centers with high prevalence of HCV infection and short waiting times, both tumor and HCV-related recurrent diseases hamper significantly the outcomes of these patients. (Liver Transpl 2002;8:1020-1027.)