Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.

Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma

BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

BACKGROUND Liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established worldwide.The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience.The variations among the criteria are staggering,and the short-and long-term outcomes are controversial.AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future.METHODS We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were received.The centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was noted.RESULTS Of the 23 centers,35%were high volume center(>500 Liver transplants)while 52%were high-volume centers that performed more than 50 transplants/year.Approximately 39%of centers had performed>50 LT for HCC while the percent distribution for HCC in LT patients was 5%–15%in approximately 73%of the patients.Barring a few,most centers were divided equally between University of California,San Francisco(UCSF)and center-specific criteria when choosing patients with HCC for LT,and most(65%)did not have separate transplant criteria for deceased donor LT and living donor LT(LDLT).Most centers(56%)preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion.Positron-emission tomography-computed tomography(CT)was the modality of choice for metastatic workup in the majority of centers(74%).Downstaging was the preferred option for over 90%of the centers and included transarterial chemoembolization,transarterial radioembolization,stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications.The alphafetoprotein(AFP)cut-off was used by 74%of centers to decide on transplantation as well as to downstage tumors,even if they met the criteria.The criteria for successful downstaging varied,but most centers conformed to the UCSF or their center-specific criteria for LT,along with the AFP cutoff values.The wait time for LT from downstaging was at least 4–6 wk in all centers.Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52%of the centers.Approximately 65%of the centers preferred to start everolimus between 1 and 3 months post-LT.CONCLUSION The current predicted 5-year survival rate of HCC patients in India is less than 15%.The aim of transplantation is to achieve at least a 60%5-year disease free survival rate,which will provide relief to the prediction of an HCC surge over the next 20 years.The current worldwide criteria(Milan/UCSF)may have a higher 5-year survival(>70%);however,the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment,with much lower survival rates.To make predictions for 2040,we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome.With more advanced technology and better donor outcomes,LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.

Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the literature.AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT.METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACE or TAE.Some patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.RESULTS Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC.Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Analysis of the Effects of Preoperative Hepatic Artery Chemoembolization and Quality Nursing Intervention on the Perioperative Safety and Short-term Prognosis of Liver Transplantation in Patients with Hepatocellular Carcinoma

Objective: To investigate the effects of preoperative hepatic artery chemoembolization (TACE) and quality nursing interventions on the perioperative safety and short-term prognosis in patients with hepatocellular carcinoma undergoing liver transplantation. Methods: The study period spanned from January 2021 to December 2023, and 125 patients with hepatocellular carcinoma admitted to our hospital were selected, all of whom underwent liver transplantation. They were randomly divided into an observation group (n = 63) and a control group (n = 62). The patients in the control group did not undergo TACE before the operation, and the patients in the observation group underwent TACE and quality nursing intervention before the operation. The operation time, intraoperative blood loss, length of hospitalization, liver- free period, complication rate, short-term prognosis, and liver function indexes between the two groups were compared. Results: There was no significant difference in operation time, intraoperative blood loss, and length of hospitalization between the two groups (P < 0.05). The liver-free period of patients in the observation group was longer than that of the control group (P < 0.05). The two groups had no significant difference in the incidence of biliary complications, vascular complications, and postoperative infections (P > 0.05). The rate of immune reactive complications in the observation group was lower than that of the control group (P < 0.05). There was no significant difference in the perioperative mortality rate, 1-year postoperative survival rate, and 2-year postoperative survival rate (P > 0.05). The two groups had no significant difference in postoperative liver function indexes (P > 0.05). Conclusion: Preoperative TACE and high-quality nursing intervention in patients with hepatocellular carcinoma had no adverse effect on the perioperative safety and short-term prognosis, prolonged the liver-free time, and reduced the incidence of immune-reactive complications.

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma:A multicenter study

BACKGROUND Patients with combined hepatocellular carcinoma and cholangiocarcinoma(cHCC-CC)are not traditionally considered eligible for liver transplantation(LT)AIM To compare outcomes between living donor LT(LDLT)patients with hepatocellular carcinoma(HCC)and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients.METHODS Data for pathologically diagnosed cHCC-CC patients(n=111)who underwent LT from 2000 to 2018 were collected for a nine-center retrospective review.Patients(n=141)who received LDLT for HCC at Samsung Medical Center from January 2013 to March 2017 were selected as the control group.Seventy patients in two groups,respectively,were selected by 1:1 matching.RESULTS Cumulative disease-free survival(DFS)and overall survival(OS)in the cHCC-CC group were significantly worse than in the HCC group both before and after matching.Extrahepatic recurrence incidence in the cHCC-CC group was higher than that in the HCC group(75.5%vs 33.3%,P<0.001).Multivariate analysis demonstrated that the cHCC-CC group had significantly higher rates of tumor recurrence and death compared to the HCC group.In cHCC-CC subgroup analysis,frequency of locoregional therapies>3,tumor size>3 cm,and lymph node metastasis were predisposing factors for tumor recurrence in multivariate analysis.Only a maximum tumor size>3 cm was a predisposing factor for death.CONCLUSION The poor prognosis of patients diagnosed with cHCC-CC after LT can be predicted based on the explanted liver.Frequent regular surveillance for cHCC-CC patients should be required for early detection of tumor recurrence.

Liver Transplantation Outcomes of HBV-,HCV-,and Alcohol-induced Hepatocellular Carcinoma in the United States:Analysis of National Inpatient Samples

Objective Liver transplantation is a current treatment option for hepatocellular carcinoma(HCC).The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation,including locoregional recurrence,distant metastasis,and in-hospital mortality,in HCC patients with concurrent hepatitis B infection,hepatitis C infection,or alcoholic cirrhosis.Methods This retrospective cohort study included HCC patients(n=2391)from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection,co-infection with hepatitis B and C,or alcoholic cirrhosis of the liver between 2005 and 2014.Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models.Results Liver cirrhosis was due to alcohol in 10.5%of patients,hepatitis B in 6.6%,hepatitis C in 10.8%,and combined hepatitis B and C infection in 24.3%.Distant metastasis was found in 16.7%of patients infected with hepatitis B and 9%of hepatitis C patients.Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease.Conclusion After liver transplantation,patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis.Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.

Conversion therapy in liver transplantation for hepatocellular carcinoma:What's new in the era of molecular and immune therapy?

Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic treatments,fast development of targeted drugs,the success of immunotherapy,as well as the emergence of the therapeutic alliance,conversion therapy has recently become more well developed and an effective therapeutic strategy.This article aimed to review recent developments in conversion therapy in liver transplantation(LT)for HCC.Data sources:We searched for relevant publications on Pub Med before September 2022,using the terms“HCC”,“liver transplantation”,“downstaging”,“bridging treatment”and“conversion therapy.”Results:Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT.Although combining various local and systematic treatments in conversion therapy is still controversial,growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time,which ultimately increases the opportunities for LT.Moreover,the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors.Conclusions:In the era of targeted therapy and immunotherapy,applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients.With the expansion of conversion therapy concepts,further investigation and research is required to realize the full potential of conversion treatment strategies,including accurately selecting candidates,determining the timing of surgery,improving the conversion rate,and guaranteeing the safety and long-term efficacy of treatment.

When immunotherapy meets liver transplantation for hepatocellular carcinoma: A bumpy but promising road

Liver transplantation(LT)is a highly curative therapy for patients with hepatocellular carcinoma(HCC).However,due to the shortage of donor livers and rapid progression of HCC,a majority of patients are dropped out from the waitlist.Recently,immunotherapy has shown great promise in the treatment of advanced HCC.However,the use of immunotherapy is limited in LT mainly due to the potentially increasing risk of graft rejection.One of the main challenges for researchers is the protection of donor graft from an immunotherapy-boosted immune response mounted by the host.Besides,the safety,availability,and costs of immunotherapy are other challenges that need to be addressed.Here,we reviewed the literature involving patients who received immunotherapy prior to transplant to avoid waitlist dropouts and following transplantation to prevent the progression of tumor recurrence and metastasis.Statistically,the incidence of rejection was 25.0%pre-transplant and 18.5%post-transplant.Based on the review of these clinical studies,we can conclude that conducting clinical trials on the safety and efficacy of currently available immunotherapy drugs and identifying novel immunotherapy targets through extensive research may be promising for patients who do not meet the selection criteria for LT and who experience post-transplant recurrence.To date,the clinical experience on the use of immunotherapy before or after LT comes from individual case studies.Although some of the reported results are promising,they are not sufficient to support the standardized use of immunotherapy in clinical practice.

Global trends in hepatitis C-related hepatocellular carcinoma mortality:A public database analysis(1999-2019)

BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and mortality rates of HCC across different geographical regions.With the advent of new widely available treatment modalities,such as direct-acting antivirals,it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C.Furthermore,gender disparities in HCC mortality related to Hepatitis C are a crucial,yet underexplored aspect that adds to the disease's global impact.While some studies shed light on gender-specific trends,there is a lack of comprehensive data on global and regional mortality rates,particularly those highlighting gender disparities.This gap in knowledge hinders the development of targeted interventions and resource allocation strategies.DISCUSSION The results of our study show an overall decline in the mortality rates of patients with hepatitis C-related HCC over the last two decades.Notably,females exhibited a remarkable decrease in mortality compared to males.Regionally,East Asia and the Pacific displayed a significant decline in mortality,while Europe and Central Asia witnessed an upward trend.Latin America and the Caribbean also experienced an increase in mortality rates.However,no significant difference was observed in the Middle East and North Africa.North America exhibited a notable upward trend.South Asia and Sub-Saharan Africa significantly declined throughout the study period.This raises the hope of identifying areas for implementing more targeted resources.Despite some progress,multiple challenges remain in meeting the WHO 2030 goal of eliminating viral hepatitis[24].

Prognostic implication of early posttransplant hypercholesterolemia in liver transplantation for patients with hepatocellular carcinoma

Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.

Prognostic Factors of Liver Transplantation for Hepatocellular Carcinoma: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis

Objective We aimed to identify new,more accurate risk factors of liver transplantation for liver cancer through using the Surveillance,Epidemiology,and End Results(SEER)database.Methods Using the SEER database,we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma(HCC)and subsequent liver transplantation between 2010 and 2017.Overall survival(OS)was estimated using Kaplan-Meier plotter.Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease[presented as adjusted hazard ratios(HR)with 95%CIs].Results Totally,1530 eligible patients were included in the analysis.There were significant differences in ethnicity(P=0.04),cancer stage(P<0.001),vascular invasion(P<0.001)and gall bladder involvement(P<0.001)between the groups that survived,died due to cancer,or died due to other causes.In the Cox regression model,there were no significant differences in OS at 5 years with different operative strategies(autotransplantation versus allotransplantation),nor at survival at 1 year with neoadjuvant radiotherapy.However,neoadjuvant radiotherapy did appear to improve survival at both 3 years(HR:0.540,95%CI:0.326–0.896,P=0.017)and 5 years(HR:0.338,95%CI:0.153–0.747,P=0.007)from diagnosis.Conclusion This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC.These criteria can be used to inform patient selection and consent in this setting.Preoperative radiotherapy may improve long-term survival post-transplantation.

The AGH score is a predictor of disease-free survival and targeted therapy efficacy after liver transplantation in patients with hepatocellular carcinoma

Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy.The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population,and to evaluate whether these patients are suitable for adjuvant targeted therapy.Methods:Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed.Results:A total of 201 patients were included in the study.The multivariate Cox analysis suggested that preoperative alpha-fetoprotein(AFP)>200μg/L(HR=2.666,95%CI:1.515-4.690;P=0.001),glutamyl transferase(GGT)>96 U/L(HR=1.807,95%CI:1.012-3.224;P=0.045),and exceeding the Hangzhou criteria(HR=2.129,95%CI:1.158-3.914;P=0.015)were independent risk factors for poor disease-free survival(DFS)in patients with HCC who underwent LT.We established an AFP-GGT-Hangzhou(AGH)scoring system based on these factors,and divided cases into high-,moderate-,and low-risk groups.The differences in overall survival(OS)and disease-free survival(DFS)rates among the three groups were significant(P<0.05).The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria,UCSF criteria,Milan criteria,and TNM stage.Only in the high-risk group,we found that lenvatinib significantly improved prognosis compared with that of the control group(P<0.05).Conclusions:The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China.Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.

The “No-touch” technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial

Background:Liver transplantation(LT)is the best treatment for patients with hepatocellular carcinoma(HCC).However,the surgical technique needs to be improved.The present study aimed to evaluate the“no-touch”technique in LT.Methods:From January 2018 to December 2019,we performed a prospective randomized controlled trial on HCC patients who underwent LT.The patients were randomized into two groups:a no-touch technique LT group(NT group,n=38)and a conventional LT technique group(CT group,n=46).Operative outcomes and survival in the two groups were analyzed.Results:The perioperative parameters were comparable between the two groups(P>0.05).There was no significant difference between the two groups in disease-free survival(DFS)(P=0.732)or overall survival(OS)(P=0.891).Of 36 patients who were beyond the Hangzhou criteria for LT,the DFS of the patients in the NT group was significantly longer than that in the CT group(median 402 vs.126 days,P=0.025).In 31 patients who had portal vein tumor thrombosis(PVTT),DFS and OS in the NT group were significantly better than those in the CT group(median DFS 420 vs.167 days,P=0.022;2-year OS rate 93.8%vs.66.7%,P=0.043).In 14 patients who had diffuse-type HCCs,DFS and OS were significantly better in the NT group than those in the CT group(median DFS 141 vs.56 days,P=0.008;2-year OS rate 75.0%vs.33.3%,P=0.034).Multivariate analysis showed that for patients with PVTT and diffusetype HCCs,the no-touch technique was an independent favorable factor for OS(PVTT:HR=0.018,95%CI:0.001-0.408,P=0.012;diffuse-type HCCs:HR=0.034,95%CI:0.002-0.634,P=0.024).Conclusions:The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique.The no-touch technique may provide a new and effective LT technique for advanced HCCs.

Patients with hepatocellular carcinoma that die during the first year of liver transplantation have high blood sFasL concentrations

BACKGROUND Fas ligand(FasL)is one ligand that activates extrinsic apoptosis pathway.High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation(LT).No high blood concentrations of soluble FasL(sFasL)have been found in patients with acute LT rejection;however,the samples size of those studies was small.AIM To determine whether patients with hepatocellular carcinoma(HCC)that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample size.METHODS Patients underwent LT due to HCC were included in this retrospective study.Serum sFasL levels prior to LT were measured and one-year LT mortality was registered.RESULTS Non-surviving patients(n=14)showed higher serum sFasL levels[477(269-496)vs 85(44-382)pg/mL;P<0.001]than surviving patients(n=113).Serum sFasL levels(pg/mL)were associated with mortality(OR=1.006;95%CI=1.003-1.010;P=0.001)independently of age of LT donor in the logistic regression analysis.CONCLUSION We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.

Gut Microbiota Modulation:A Viable Strategy to Address Medical Needs in Hepatocellular Carcinoma and Liver Transplantation

Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its effectiveness.In recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related disciplines.Gut microbiota,an emerging field of research,also plays a crucial role.Through the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as LT.This review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in HCC.In addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were discussed.In the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.

Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation

BACKGROUND Clinical factors predicting graft survival(GS)after ABO-incompatible(ABOi)liver transplantation(LT),and differences between recipients with and without hepatocellular carcinoma(HCC)are unclear.AIM To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without(HCC)in ABOi living-donor liver transplantation(LDLT).METHODS We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT,including 47 patients with HCC.RESULTS The 1-,3-,5-,and 10-year GS rates were 85.9%,73.3%,71.4%,and 71.4%,respectively,and there were no significant differences between HCC and non-HCC recipients.In multivariate Coxregression analyses,tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT,in addition to the antibody-mediated rejection(AMR)were associated with poor-graft outcomes.In HCC patients,AMR[hazard ratio(HR)=63.20,P<0.01]and HCC recurrence(HR=20.72,P=0.01)were significantly associated with poor graft outcomes.HCCs outside Milan criteria,and tacrolimus concentrations at 4 wk post-LT>7.3 ng/mL were significant predictive factors for HCC recurrence.After propensity score matching,patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival.CONCLUSION Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence.Therefore,careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States

BACKGROUND Early in the coronavirus disease 2019(COVID-19)pandemic,there was a significant impact on routine medical care in the United States,including in fields of transplantation and oncology.AIM To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation(LT)for hepatocellular carcinoma(HCC)in the United States.METHODS WHO declared COVID-19 as a pandemic on March 11,2020.We retrospectively analyzed data from the United Network for Organ Sharing(UNOS)database regarding adult LT with confirmed HCC on explant in 2019 and 2020.We defined pre-COVID period from March 11 to September 11,2019,and early-COVID period as from March 11 to September 11,2020.RESULTS Overall,23.5%fewer LT for HCC were performed during the COVID period(518 vs 675,P<0.05).This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020.Among LT recipients for HCC,concurrent diagnosis of non-alcoholic steatohepatitis significantly increased(23 vs 16%)and alcoholic liver disease(ALD)significantly decreased(18 vs 22%)during the COVID period.Recipient age,gender,BMI,and MELD score were statistically similar between two groups,while waiting list time decreased during the COVID period(279 days vs 300 days,P=0.041).Among pathological characteristics of HCC,vascular invasion was more prominent during COVID period(P<0.01),while other features were the same.While the donor age and other characteristics remained same,the distance between donor and recipient hospitals was significantly increased(P<0.01)and donor risk index was significantly higher(1.68 vs 1.59,P<0.01)during COVID period.Among outcomes,90-day overall and graft survival were the same,but 180-day overall and graft were significantly inferior during COVID period(94.7 vs 97.0%,P=0.048).On multivariable Coxhazard regression analysis,COVID period emerged as a significant risk factor of post-transplant mortality(Hazard ratio 1.85;95%CI:1.28-2.68,P=0.001).CONCLUSION During COVID period,there was a significant decrease in LTs performed for HCC.While early postoperative outcomes of LT for HCC were same,the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Recent advances in recurrent hepatocellular carcinoma therapy

Hepatocellular carcinoma(HCC)is the most prevalent form of primary liver cancer,accounting for 75%-85%of cases.Although treatments are given to cure early-stage HCC,up to 50%-70%of individuals may experience a relapse of the illness in the liver after 5 years.Research on the fundamental treatment modalities for recurrent HCC is moving significantly further.The precise selection of individuals for therapy strategies with established survival advantages is crucial to ensuring better outcomes.These strategies aim to minimize substantial morbidity,support good life quality,and enhance survival for patients with recurrent HCC.For individuals with recurring HCC after curative treatment,no approved therapeutic regimen is currently available.A recent study presented novel approaches,like immunotherapy and antiviral medication,to improve the prognosis of patients with recurring HCC with the apparent lack of data to guide the clinical treatment.The data supporting several neoadjuvant and adjuvant therapies for patients with recurring HCC are outlined in this review.We also discuss the potential for future clinical and translational investigations.