Homocysteine: A novel prognostic biomarker in liver transplantation for alpha-fetoprotein- negative hepatocellular carcinoma

2020 ◽  
Vol 29 (2) ◽  
pp. 197-206
Author(s):  
Modan Yang ◽  
Winyen Tan ◽  
Xinyu Yang ◽  
Jianyong Zhuo ◽  
Zuyuan Lin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Tumor Recurrence ◽  
Prognostic Biomarker ◽  
Milan Criteria ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Independent Risk Factors ◽  
Hcc Recurrence

BACKGROUND: Precise recipient selection optimizes the prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the most commonly used biomarker for diagnosis and prognosis of HCC in the clinical context. As a crucial molecule in methionine cycle, homocysteine (Hcy) level has been proved to be related to HCC progression and metastasis. OBJECTIVE: We aimed to explore the prognostic capacity of pre-transplant serum Hcy level in LT for HCC. METHODS: This study retrospectively enrolled 161 HCC patients who had underwent LT from donation after cardiac death (DCD) in the First Affiliated Hospital of Zhejiang University from 2015.01.01 to 2018.09.01. Pre-transplant serum Hcy level was incorporated into statistical analysis together with other clinical parameters and pathological features. RESULTS: From an overall perspective, significant difference was observed in Hcy level between recurrence (n= 61) and non-recurrence group (n= 100) though subsequent analysis showed unsatisfactory predicting performance. In the whole cohort, multivariate analysis showed that lnAFP (p= 0.010) and Milan criteria (MC, p< 0.001) were independent risk factors of HCC recurrence after LT. MA score based on MC and lnAFP performed well in predicting post-LT tumor recurrence with the AUROC at 0.836 (p< 0.001) and 3-year recurrence-free survival rate at 96.8% (p< 0.001) in the low risk group (n= 69). According to the clinical practice, serum concentration lower than 20 μg/L is considered as normal range of AFP. Elevated pre-transplant serum AFP (> 20 μg/L) predicts high HCC recurrence after LT. We further divided the 161 recipients into AFP- group (n= 77, AFP ⩽ 20 μg/L) and AFP+ group (n= 84, AFP > 20 μg/L). MA score was still well presented in the AFP+ group and the AUROC for tumor recurrence was 0.823 (p< 0.001), whereas the predicting accuracy was reduced in AFP- group (AUROC: 0.754, P< 0.001). After subsequent analysis, we found that elevated pre-transplant Hcy level (> 12.75 μmol/L) predicted increased tumor recurrence risk in AFP- group. The 3-year recurrence-free survival rates were 92.0% and 53.7% (p< 0.001) in low Hcy subgroup (n= 40) and high Hcy subgroup (n= 37) respectively. Multivariate analysis showed that Hcy (p= 0.040) and Milan criteria (p= 0.003) were independent risk factors for post-transplant tumor recurrence in AFP- group. Further combination of Hcy level and Milan criteria identified a subgroup of AFP- recipients with acceptable outcomes even though beyond Milan criteria (3-year recurrence-free survival rate: 77.7%, p< 0.001). CONCLUSION: As a classic predictor in HCC prognosis, AFP performed well in our study cohort when combined with Milan criteria. Homocysteine was an effective prognostic biomarker in LT for AFP- hepatocellular carcinoma. In recipients exceeding Milan criteria, acceptable post-transplant outcome could be seen in those with low Hcy and AFP level.

Impact of up-to-seven criteria and neutrophil-to-lymphocyte ratio in liver transplantation for patients who received pretreatment for hepatocellular carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14536-e14536
Author(s):  
Tomoharu Yoshizumi ◽  
Toru Ikegami ◽  
Shohei Yoshiya ◽  
Takashi Motomura ◽  
Yohei Mano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Multivariate Analysis ◽  
Tumor Recurrence ◽  
Survival Rates ◽  
Neutrophil To Lymphocyte Ratio ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Lymphocyte Ratio

e14536 Background: There is currently no consensus on how to manage patients with hepatocellular carcinoma (HCC) while awaiting liver transplantation (LT). The guideline published in UK states that locoregional therapy should be considered for all listed patients with HCC. Living donor LT (LDLT) is a choice for treating HCC patients in organ shortage era. The aim of the present study is to clarify the risk factors of tumor recurrence after LDLT in patients who had received pre-transplant treatments (pre-Tx) for HCC. Methods: One hundred two adult patients (39 females and 63 males) who had undergone LDLT due to end-stage liver disease with recurrent HCC after pre-Tx were enrolled. The primary end-point of this study was HCC recurrence after LDLT. Recurrence-free survival rates after LDLT were calculated. Risk factors of tumor recurrence were identified using univariate and multivariate analysis. Results: The 1-, 3-, and 5-year recurrence-free survival rates were 89.4%, 80.7%, and 78.8%, respectively. Seventy-four of 102 patients underwent pre-Tx more than twice. Moreover, the times of pre-Tx, the interval between the first treatment and LDLT, and the interval between the last treatment and LDLT did not affect the outcome of LDLT. On univariate analysis, the factors affecting recurrence-free survival were exceeding the up-to-seven criteria (p<0.0001), exceeding the Kyushu University criteria (p<0.0001), neutrophil-to-lymphocyte ratio (NLR) > 4 (p=0.0001), Alpha-fetoprotein > 400 ng/ml (p<0.0001), and bilobar tumor distribution (p=0.047). A multivariate analysis identified independent risk factors for post-LDLT tumor recurrence were exceeding the up-to-seven criteria (p=0.001) and NLR > 4 (p=0.002). The 1- and 3-year recurrence-free survival rates in the recipients with exceeding the up-to-seven criteria and NLR > 4 were 30.0% and 15.0%, respectively. Conclusions: The kind or duration of pre-Tx did not affect the outcome of LDLT, but LDLT should not be performed for the patients with exceeding the up-to-seven criteria and NLR more than 4 after pre-Tx for HCC to prevent tumor recurrence.

scholarly journals Extremes of Liver Transplantation for Hepatocellular Carcinoma

2019 ◽  
Vol 8 (6) ◽  
pp. 787 ◽  
Author(s):  
Michał Grąt ◽  
Maciej Krasnodębski ◽  
Marek Krawczyk ◽  
Jan Stypułkowski ◽  
Marcin Morawski ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Tumor Size ◽  
Tumor Recurrence ◽  
Significant Risk ◽  
Advanced Hepatocellular Carcinoma ◽  
Recurrence Free Survival ◽  
Donor Age ◽  
Free Survival

The aim of this retrospective observational study was to evaluate outcomes of patients with extremely advanced hepatocellular carcinoma (HCC) after liver transplantation. A total of 285 HCC patients after liver transplantation were screened for eligibility based on either intrahepatic dissemination (≥10 tumors) or macrovascular invasion. Tumor recurrence was the primary end-point. The study cohort comprised 26 patients. Median recurrence-free survival was 23.2 months with hepatitis B virus (HBV) infection (p = 0.038), higher AFP model score (p = 0.001), prolonged graft ischemia (p = 0.004), and younger donor age (p = 0.016) being significant risk factors. Median recurrence-free survival of HBV-negative and HBV-positive patients was 29.8 and 9.3 months, respectively (p = 0.053). In patients with macrovascular invasion, recurrence-free survival at 3 years was 46.3% with no specific predictors. Tumor size (p = 0.044), higher AFP model score (p = 0.019), prolonged graft ischemia (p = 0.016), and younger donor age (p = 0.041) were significant risk factors in patients with intrahepatic dissemination. Superior 3-year outcomes were observed in patients with intrahepatic dissemination and tumor size <3.5 cm (83.3%, p = 0.027) and HBV-negative patients with ischemia <9.7 h (85.7%, p = 0.028). In conclusion, patients with extremely advanced HCCs are remarkably heterogeneous with respect to their profile of tumor recurrence risk. This heterogeneity is largely driven by factors other than standard predictors of post-transplant HCC recurrence.

Evaluation of the neutrophil-lymphocyte ratio as a predictor of survival after liver transplantation for hepatocellular carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 170-170 ◽  
Author(s):  
A. R. Limaye ◽  
R. Cabrera
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
Independent Predictor ◽  
Tumor Biology ◽  
Milan Criteria ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cumulative Survival ◽  
Neutrophil Lymphocyte Ratio

170 Background: The Milan criteria are utilized to predict outcomes in patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT). Though the survival of these patients has significantly improved since the adoption of these criteria, the risk of recurrence after LT is as high as 20 percent. One limitation of the Milan criteria is the lack of any estimation of tumor biology. The neutrophil-lymphocyte ratio (NLR) has been proposed as a peripheral surrogate for tumor biology. The predictive power of the NLR has been demonstrated for several solid tumors, and early evidence points to a role in HCC. We hypothesize that the NLR is predictive of overall survival and recurrence-free survival in patients with HCC who undergo LT. Methods: This is a retrospective analysis of adult patients undergoing LT for HCC between 2000 and 2008 at our institution. We defined an elevated NLR as a ratio of five or greater. Results: We identified 160 patients who underwent LT for HCC, 28 of whom had an elevated NLR. Seventeen subjects experienced recurrent HCC during the study period. The cumulative survival for subjects with an elevated NLR (1-year cumulative survival 70% ± 0.08, 3-year cumulative survival 48% ± 0.09, 5-year cumulative survival 38% ± 0.11) was significantly lower than for subjects with a normal NLR (1-year survival 80% ± 0.04, 3-year survival 75% ± 0.04, 5-year survival 68% ± 0.06). On univariate analysis, seven factors (including an elevated NLR) predicted decreased overall and recurrence-free survival. However, after multivariate analysis, only three factors (including elevated NLR) remained significant as predictors of overall survival. Additionally, multivariate analysis revealed that an elevated NLR was the only significant independent predictor of recurrence-free survival. Conclusions: Preoperative NLR is a powerful independent predictor of overall survival and recurrence-free survival in patients undergoing LT for HCC. Measurement of NLR could serve as a useful and easily obtained adjunct to the MELD score and Milan criteria when evaluating this patient population and determining which patients will gain the most survival benefit from transplant. No significant financial relationships to disclose.

scholarly journals Impact of Body Composition on the Risk of Hepatocellular Carcinoma Recurrence After Liver Transplantation

2019 ◽  
Vol 8 (10) ◽  
pp. 1672
Author(s):  
Karolina Grąt ◽  
Ryszard Pacho ◽  
Michał Grąt ◽  
Marek Krawczyk ◽  
Krzysztof Zieniewicz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Liver Transplantation ◽  
Body Composition ◽  
Adipose Tissue ◽  
Visceral Fat ◽  
Recurrence Free Survival ◽  
Muscle Area ◽  
Free Survival ◽  
Hcc Recurrence

Background: Body composition parameters are reported to influence the risk of hepatocellular carcinoma (HCC) recurrence after liver resection, yet data on patients undergoing liver transplantation are scarce. The aim of this study was to evaluate the impact of the amount of abdominal adipose tissue and skeletal muscles on the risk of HCC recurrence after liver transplantation. Methods: This was a retrospective observational study performed on 77 HCC patients after liver transplantation. Subcutaneous fat area (SFA), visceral fat area, psoas muscle area and total skeletal muscle area were assessed on computed tomography on the level of L3 vertebra and divided by square meters of patient height. The primary outcome measure was five-year recurrence-free survival. Results: Recurrence-free survival in the entire cohort was 95.7%, 90.8%, and 86.5% after one, three, and five years post-transplantation, respectively. SFA was significantly associated with the risk of HCC recurrence (p = 0.013), whereas no significant effects were found for visceral fat and skeletal muscle indices. The optimal cut-off for SFA for prediction of recurrence was 71.5 cm2/m2. Patients with SFA < 71.5 cm2/m2 and ≥71.5 cm2/m2 exhibited five-year recurrence-free survival of 96.0% and 55.4%, respectively (p = 0.001). Conclusions: Excessive amount of subcutaneous adipose tissue is a risk factor for HCC recurrence after liver transplantation and may be considered in patient selection process.

scholarly journals Survival Analysis after Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Single Center Cohort Study

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 446
Author(s):  
Byung-Gon Na ◽  
Seong-Hoon Kim ◽  
Sang-Jae Park
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Living Donor ◽  
Living Donor Liver Transplantation ◽  
Milan Criteria ◽  
Survival Outcomes ◽  
Donor Liver ◽  
Donor Liver Transplantation ◽  
Independent Risk Factors

Background: Living-donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) has been used as a curative treatment option for hepatocellular carcinoma (HCC) because of a shortage of deceased donors. This study aimed to investigate survival outcomes after LDLT for HCC. Method: This study included 359 patients undergoing LDLT for HCC. We analyzed overall survival (OS) and recurrence-free survival (RFS) and the prognostic factors related to them. Results: The 5-year OS and RFS rates of patients within the Milan criteria (WM) were better than those of patients beyond the Milan criteria (BM) (87.3% vs. 64.1% and 87.6% vs. 57.8%, respectively, both p < 0.05). Alpha-fetoprotein level (AFP) > 400 ng/mL (hazard ratio (HR), 2.07; 95% CI, 1.28–3.36; p < 0.05) and HCC of BM (HR, 2.61; 95% CI, 1.60–4.26; p < 0.05) at immediate pretransplant were independent risk factors of OS. AFP > 400 ng/mL (HR, 2.16; 95% CI, 1.34–3.49; p < 0.05) and HCC of BM (HR, 3.01; 95% CI, 1.81–5.01; p < 0.05) were also independent risk factors of RFS. In pathologic findings of explanted liver, tumor size, Edmondson–Steiner grade III–IV, and microvascular invasion were independent risk factors of both OS and RFS (p < 0.05). Conclusions: BM and AFP > 400 ng/mL at immediate pretransplant are unfavorable predictors of survival outcomes after LDLT for HCC.

scholarly journals Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Christin Bürger ◽  
Miriam Maschmeier ◽  
Anna Hüsing-Kabar ◽  
Christian Wilms ◽  
Michael Köhler ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Complete Remission ◽  
Tumor Recurrence ◽  
Significant Risk ◽  
Treatment Modalities ◽  
Special Focus ◽  
The Impact ◽  
Hcc Recurrence

Background. Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. Methods. All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. Results. A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). Conclusion. Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied.

scholarly journals Inflammatory indexes in preoperative blood routine to predict early recurrence of hepatocellular carcinoma after curative hepatectomy

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
YiFeng Wu ◽  
ChaoYong Tu ◽  
ChuXiao Shao
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Tumour Size ◽  
Area Under The Curve ◽  
Early Recurrence ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Lymphocyte Ratio ◽  
Inflammatory Index ◽  
Curative Hepatectomy

Abstract Background The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence. Methods The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival. Results The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse. Conclusion The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.

scholarly journals Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mamatha Bhat ◽  
Sergi Clotet-Freixas ◽  
Cristina Baciu ◽  
Elisa Pasini ◽  
Ahmed Hammad ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Protein Expression ◽  
Univariate Analysis ◽  
Milan Criteria ◽  
Post Transplant ◽  
Gene And Protein Expression ◽  
Galectin 3 ◽  
Transcriptomic Signature ◽  
Hcc Recurrence

Abstract Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Results Seventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p < 0.05). Univariate survival analysis identified Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) gene (HR = 0.084, 95%CI 0.01–0.68, p = 0.0152), ALDH1A1 protein (HR = 0.039, 95%CI 0.16–0.91, p = 0.03), Galectin 3 Binding Protein (LGALS3BP) gene (HR = 7.14, 95%CI 1.20–432.96, p = 0.03), LGALS3BP protein (HR = 2.6, 95%CI 1.1–6.1, p = 0.036), Galectin 3 (LGALS3) gene (HR = 2.89, 95%CI 1.01–8.3, p = 0.049) and LGALS3 protein (HR = 2.6, 95%CI 1.2–5.5, p = 0.015) as key dysregulated analytes in recurrent HCC. In concordance with our proteome findings, HCC recurrence was linked to decreased ALDH1A1 and increased LGALS3 protein expression by Western Blot. LGALS3BP protein expression was validated in 29 independent HCC samples. Conclusions Significantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance.

scholarly journals Homeostatic Model Assessment of Insulin Resistance for Predicting the Recurrence of Hepatocellular Carcinoma after Curative Treatment

2019 ◽  
Vol 20 (3) ◽  
pp. 605 ◽  
Author(s):  
Kenji Imai ◽  
Koji Takai ◽  
Tatsunori Hanai ◽  
Atsushi Suetsugu ◽  
Makoto Shiraki ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Curative Treatment ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
The Impact ◽  
Hcc Recurrence

Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan–Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM (p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 μU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM (p = 0.009), and there was no significant difference between those groups with DM (p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment.

Sign in / Sign up

Export Citation Format

Share Document