Risk Factors Affecting the Recurrence-Free Survival of Hepatocellular Carcinoma After Hepatectomy: a Meta-analysis

Author(s):  
Jisen Cao ◽  
Ruiqiang Zhang ◽  
Ye Zhang ◽  
Yijun Wang
BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
YiFeng Wu ◽  
ChaoYong Tu ◽  
ChuXiao Shao

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.


2020 ◽  
Vol 29 (2) ◽  
pp. 197-206
Author(s):  
Modan Yang ◽  
Winyen Tan ◽  
Xinyu Yang ◽  
Jianyong Zhuo ◽  
Zuyuan Lin ◽  
...  

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.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14536-e14536
Author(s):  
Tomoharu Yoshizumi ◽  
Toru Ikegami ◽  
Shohei Yoshiya ◽  
Takashi Motomura ◽  
Yohei Mano ◽  
...  

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.


2021 ◽  
Vol 36 (2) ◽  
pp. 172460082110326
Author(s):  
Wenfeng Liu ◽  
Keshu Hu ◽  
Feng Zhang ◽  
Shenxin Lu ◽  
Rongxin Chen ◽  
...  

Background Recently, microRNA-221 has been found to be abnormally expressed in hepatocellular carcinoma; however, its clinical value has not been summarised. This meta-analysis aimed to assess the prognostic significance of miR-221 in hepatocellular carcinoma. Material and Methods PubMed, Science Direct, Web of Science, Scopus, Ovid MEDLINE, EMbase, Google Scholar, the Cochrane Library, CNKI, CBM, VIP and Wanfang databases were searched for eligible articles. The endpoints included overall survival, progression-free survival, recurrence-free survival, metastasis-free survival, disease-free survival. Hazard ratios with 95% confidence intervals were used to explore the relationship between miR-221 expression and clinical survival results of liver cancer patients. Subgroup analysis and sensitivity analysis were performed. Begg’s test and Egger’s test were conducted to evaluate publication bias. Results A total of nine studies including 607 patients were recruited for this meta-analysis. The pooled hazard ratios displayed that high miR-221 expression was remarkably associated with poorer overall survival (hazard ratio = 1.91, 95% confidence interval: 1.53–2.38, p < 0.01) and unfavourable progression-free survival/recurrence-free survival/metastasis-free survival/disease-free survival (hazard ratio = 2.02, 95% confidence interval: 1.58–2.57, p < 0.01). The results of Begg’s test and Egger’s test did not exhibit obvious publication bias. Conclusions High expression of miR-221 can predict poor outcome of hepatocellular carcinoma. miR-221 can be used as a promising prognostic biomarker of hepatocellular carcinoma.


2018 ◽  
Vol 33 (3) ◽  
pp. 266-274 ◽  
Author(s):  
Dongjing Zhang ◽  
Zhihong Liu ◽  
Xueru Yin ◽  
Xiaolong Qi ◽  
Bingyun Lu ◽  
...  

Background: Several studies have been conducted to evaluate the prognostic value of prothrombin induced by vitamin K absence-II (PIVKA-II) overexpression in hepatocellular carcinoma patients treated with curative ablation. However, the results remain controversial. The purpose of this meta-analysis was to explore the correlation between PIVKA-II expression and survival outcomes in these patients. Methods: We performed a systematic literature search in PubMed, EMBASE, Medline, Cochrane Library, and Web of Science to identify the relevant articles investigating the prognostic value of PIVKA-II in patients with hepatocellular carcinoma. Combined hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival and recurrence-free survival were calculated as the analysis endpoints. Results: A total of 15 cohorts encompassing 5647 patients were included. The results indicated that elevated PIVKA-II was significantly associated with poorer overall survival (HR 1.59; 95% CI 1.40, 1.82; P < 0.001) and recurrence-free survival (HR 1.76; 95% CI 1.42, 2.17; P < 0.001). Similar results were observed in the subgroup analysis based on sample size, analytical method, treatment modality, and cut-off value. Conclusions: This meta-analysis suggests that elevated PIVKA-II is a predictor of unfavorable overall survival and recurrence-free survival in hepatocellular carcinoma patients receiving curative ablation. More rigorous studies are warranted to confirm the clinical utility of PIVKA-II in determining hepatocellular carcinoma prognosis.


2019 ◽  
Vol 8 (6) ◽  
pp. 787 ◽  
Author(s):  
Michał Grąt ◽  
Maciej Krasnodębski ◽  
Marek Krawczyk ◽  
Jan Stypułkowski ◽  
Marcin Morawski ◽  
...  

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.


2018 ◽  
Vol Volume 11 ◽  
pp. 6555-6567 ◽  
Author(s):  
Andrea Casadei Gardini ◽  
Giorgia Marisi ◽  
Matteo Canale ◽  
Francesco Giuseppe Foschi ◽  
Gabriele Donati ◽  
...  

2020 ◽  
Author(s):  
Peng Liu ◽  
Yixiu Wang ◽  
Yuwei Xie ◽  
Luxun Zhang ◽  
Jinyu Pei ◽  
...  

Abstract BackgroundWe investigated the impact of elevated glucose levels on the early recurrence of hepatocellular carcinoma (HCC)after open radical hepatectomy.MethodsThis retrospective cohort study analyzed. The clinical data of 112 patients with hepatocellular carcinoma who underwent open radical hepatectomy from January 2013 to December 2014 at the Affiliated Hospital of Qingdao University. After radical resection of the hepatocellular carcinoma, 86 patients with an average fasting blood glucose(FBG) level of 3.9–6.1 mmol/L and 26 patients with an FBG level ≥ 6.1 mmol/L were divided into the normal group and hyperglycemic group, respectively. The recurrence rate of hepatocellular carcinoma was compared between the two groups 1 and 2 years after the operation.ResultsThe postoperative 1- and 2-year recurrence rates of HCC were 19.8% (17/86) and 33.7% (29/86), respectively, in the normal group and42.3% (11/26) and 61.5% (16/26), respectively, in the hyperglycemic group; there were significant differences between the two groups (χ2 = 6.719,P = 0.01;χ2 = 6.427༌P = 0.011). The univariate analysis showed that FBG, history of alcohol drinking, extent of hepatectomy, histopathological differentiation, maximal tumor diameter, satellite lesion, and the postoperative adjuvant treatment were risk factors affecting the tumor-free survival rate after open radical resection of hepatocellular carcinoma (P < .05).The results of the multivariate analysis showed that FBG levels ≥ 6.1 mmol/L, low histopathological differentiation, and no postoperative adjuvant treatment were independent risk factors affecting tumor-free survival rate after radical resection of hepatocellular carcinoma (P < .05).ConclusionAn elevated FBG level has a stimulating effect on the early recurrence of tumor after open radical resection of hepatocellular carcinoma. Therefore, postoperative monitoring and blood glucose control may facilitate a decrease in the early recurrence rate in patients with hepatocellular carcinoma.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
LingLing Zhuang ◽  
Liying Sun ◽  
Jianbing Wu

Abstract Background Sorafenib was reported as a useful adjuvant treatment in patients with hepatocellular carcinoma who underwent surgical resection. However, its therapeutic value remains controversial. This meta-analysis examined the available data regarding the efficacy and safety of sorafenib in patients with hepatocellular carcinoma after radical surgery. Methods The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in advance with PROSPERO (CRD42021233868). We searched PubMed, Embase, Cochrane Library, and Web of Science to identify eligible studies. Overall survival, recurrence-free survival, and recurrence rates were analyzed, and adverse events were reviewed. Hazard ratios or pooled risk ratios with 95% CIs were collected and analyzed using STATA version 12.0 in a fixed-effects or random-effects meta-analysis model. Results In total, 2655 patients from 13 studies were ultimately included in this meta-analysis. The combined results illustrated that sorafenib was associated with better overall survival than the control (hazard ratio = 0.71, 95% CI = 0.59–0.86; P < 0.001). Similarly, the drug also improved recurrence-free survival (hazard ratio = 0.68, 95% CI = 0.54–0.86, P = 0.001). Combined data revealed that patients treated with sorafenib after resection had a lower recurrence rate (pooled risk ratio = 0.78, 95% CI = 0.68–0.90, P < 0.001). The primary adverse events were hand-foot skin reaction, fatigue, and diarrhea of mild-to-moderate severity, whereas grade 4 adverse events were rare (< 1%). Conclusions This meta-analysis demonstrated that adjuvant sorafenib therapy after resection in patients with hepatocellular carcinoma could prolong overall survival and recurrence-free survival and reduce recurrence rates without intolerable side effects. However, more evidence is needed before reaching a definitive conclusion.


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