Comparison of Milan and UCSF criteria for liver transplantation to treat hepatocellular carcinoma

AIM:To assess the validity of the Milan and University of California San Francisco(UCSF) criteria and examine the long-term outcome of orthotopic liver transplantation(OLT) in patients with hepatocellular carcinoma(HCC) in a single-center study.METHODS:This study is a retrospective review of prospectively collected data.Between 1998 and 2009,56 of 356 OLTs were performed in patients with HCC.Based on pathological examination of liver explants,patients were retrospectively categorized into 3 groups:Milan +(n = 34),Milan-/UCSF +(n = 7) and UCSF-(n = 14).RESULTS:Median follow-up period was 39.5(1-124) mo.The 5-year overall survival rates in the Milan +,Milan-/UCSF + and UCSF-groups were 87.7%,53.6% and 33.3%,respectively(P < 0.000).Within these groups,tumor recurrence was determined in 5.8%,14.3% and 40% of patients,respectively(P < 0.011).Additionally,the presence of microvascular invasion within the explanted liver had a negative effect on the 5-year disease free survival(74.7% vs 46.7%,P < 0.044).CONCLUSION:The Milan criteria are reliable in the selection of suitable candidates for OLT for the treatment of HCC.For cases of OLT involving living donors,the UCSF criteria may be applied.

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.

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study

BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)metformin.During a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related mortality.Statin,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors:Where do we stand?

Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Although previously established criteria,such as Milan or UCSF,have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes,there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation.Immune checkpoint inhibitors(ICI)such as atezolizumab,pembrolizumab,or nivolumab have given hope to this group of patients.We completed a comprehensive literature review using PubMed,Google Scholar,reference citation analysis,and CrossRef.The search utilized keywords such as'liver transplant','HCC','hepatocellular carcinoma','immune checkpoint inhibitors','ICI','atezolizumab',and'nivolumab'.Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT,with acceptable early outcomes comparable to other criteria.Adverse effects of ICI have also been reported during the perioperative period.In such cases,a 1.5-month interval between ICI therapy and LT has been suggested.Overall,the results of downstaging using combination immunotherapy were encouraging and promising.Early reports suggested a potential ray of hope for patients with CLD and advanced HCC,especially those with multifocal HCC or branch portal venous tumor thrombosis.However,prospective studies and further experience will reveal the optimal dosage,duration,and timing prior to LT and evaluate both short-and long-term outcomes in terms of rejection,infection,recurrence rates,and survival.

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation

BACKGROUND Recurrence of hepatocellular carcinoma(HCC)following liver transplantation(LT)has a devastating influence on recipients’survival;however,the risk of recur-rence is not routinely stratified.Risk stratification is vital with a long LT waiting time,as that could influence the recurrence despite strict listing criteria.AIM This study aims to identify predictors of recurrence and develop a novel risk pre-diction score to forecast HCC recurrence following LT.METHODS A retrospective review of LT for HCC recipients at University Hospitals Bir-mingham between July 2011 and February 2020.Univariate and multivariate analyses were performed to identify recurrence predictors,based on which the novel SIMAP500(satellite nodules,increase in size,microvascular invasion,AFP>500,poor differentiation)risk score was proposed.RESULTS 234 LTs for HCC were performed with a median follow-up of 5.3 years.Recurrence developed in 25 patients(10.7%).On univariate analyses,RETREAT score>3,α-fetoprotein(AFP)at listing 100-500 and>500,bridging,increased tumour size between imaging at the listing time and explant histology,increase in the size of viable tumour between listing and explant,presence of satellite nodules,micro-and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence,based on which,the SIMAP500 risk score is proposed.The SIMAP500 demonstrated an excellent predictive ability(c-index=0.803)and outper-formed the RETREAT score(c-index=0.73).SIMAP500 is indicative of the time to disease recurrence.CONCLUSION SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence.Risk stratification allows patient-centric post-transplant surveillance programs.Further validation of the score is recommended.

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.

Combined Hangzhou criteria with neutrophillymphocyte ratio is superior to other criteria in selecting liver transplantation candidates with HBV-related hepatocellular carcinoma

BACKGROUND： The elevation of neutrophil-lymphocyte ratio （NLR） has adverse effects on the prognosis of patients with hepatocellular carcinoma （HCC） who have received liver transplantation （LT）. The Hangzhou criteria are set for selecting HCC patients for LT. The present study aimed to establish a set of new criteria combining the NLR and Hangzhou crite- ria for selecting HCC patients for LT.

Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation

AIM: To investigate that inflammatory markers can predict accurately the prognosis of hepatocelluar carcinoma (HCC) patients in living-donor liver transplantation (LDLT).

Milan criteria are useful predictors for favorable outcomes in hepatocellular carcinoma patients undergoing liver transplantation after transarterial chemoembolization

AIM: To evaluate whether the Milan criteria are useful in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before liver transplantation (LT). METHODS: Thirty-six HCC patients who fulfilled the Milan criteria after having received TACE and subsequently underwent LT were included (TACE + LT group) in the study. As controls, 21 patients who also met the Milan criteria and underwent LT without prior treatment were selected (LT group). Post-LT clinical outcomes, such as HCC recurrence, survival rate, and histologic features of explanted livers, were compared between the two groups. RESULTS: Baseline characteristics were not different between the two groups. Pre-LT maximal tumor diameter in TACE + LT group was similar to that of LT group (2.0 ± 0.6 cm vs 2.3 ± 0.9 cm; P = 0.10). Post-LT histologic findings also revealed similar maximal tumor diameter in the two groups (2.4 ± 1.4 cm vs 2.3 ± 0.9 cm; P = 0.70). Explanted livers showed similar incidence of unfavorable pathologic features. The morality within 60 d after transplantation was not different between the two groups (8.3% vs 9.5%; P = 0.99). Post-LT 5-year survival rate (57% vs 74%; P = 0.70) and cumulative recurrence rate (8.3% vs 4.8%; P = 0.90) were not significantly different between the two groups. CONCLUSION: The Milan criteria are still a useful selec- tion criteria showing favorable outcomes in HCC patientsreceiving TACE before LT.

Surgical resection versus liver transplantation for hepatocellular carcinoma within the Hangzhou criteria: a preoperative nomogram-guided treatment strategy

BACKGROUND: With the expansion of surgical criteria, the comparative efficacy between surgical resection (SR) and liver transplantation (LT) for hepatocellular carcinoma is inconclusive. This study aimed to develop a prognostic nomogram for predicting recurrence-free survival of hepatocellular carcinoma patients after resection and explored the possibility of using nomogram as treatment algorithm reference. METHODS: From 2003 to 2012, 310 hepatocellular carcinoma patients within Hangzhou criteria undergoing resection or liver transplantation were included. Total tumor volume, albumin level, HBV DNA copies and portal hypertension were included for constructing the nomogram. The resection patients were stratified into low- and high-risk groups by the median nomogram score of 116. Independent risk factors were identified and a visually orientated nomogram was constructed using a Cox proportional hazards model to predict the recurrence risk for SR patients. RESULTS: The low-risk SR group had better outcomes compared with the high-risk SR group (3-year recurrence-free survival rate, 71.1% vs 35.9%; 3-year overall survival rate, 89.8% vs 78.9%, both P<0.001). The high-risk SR group was associated with a worse recurrence-free survival rate but similar overall survival rate compared with the transplantation group (3-year recurrence-free survival rate, 35.9% vs 74.1%, P<0.001; 3-year overall survival rate, 78.9% vs 79.6%, P>0.05). CONCLUSIONS: This nomogram offers individualized recurrence risk evaluation for hepatocellular carcinoma patients within Hangzhou criteria receiving resection. Transplantation should be considered the first-line treatment for high risk patients.

Prognosis of Liver Transplantation for Hepatocellular Carcinoma in Terms of Different Criteria:A Single Center Experience

Objective Patients undergoing liver transplantation for hepatocellular carcinoma(HCC)within the Milan criteria have an excellent outcome.We developed a program to analyze and prove that the Milan criteria can be expanded safely and effectively.Methods We retrospectively reviewed 117 HCC patients treated with liver transplantation between January 2013 and December 2017.Patients were grouped according to the Milan criteria,the University of California,San Francisco(UCSF)criteria,Up-to-seven criteria and Hangzhou criteria.Tumor-free and overall survival rates were investigated with a Kaplan-Meier analysis.Multivariable regression Cox models produced survival estimates for the patients that exceeded the Milan criteria.Results The 1-year,3-year and 5-year overall survival rates of patients fulfilling the Milan criteria(n=44)were 100%,87.5%and 78.9%,respectively.Compared with the Milan criteria,the UCSF criteria(n=50),Up-to-seven criteria(n=51)and Hangzhou criteria(n=86)provided an expansion of 13.6%,15.9%and 95.9%,respectively.The 1-year,3-year and 5-year overall survival rates of patients fulfilling UCSF criteria,Up-to-seven criteria and Hangzhou criteria were 96.0%,84.9%,76.9%;96.1%,85.2%,77.6%and 97.7%,83.9%,66.7%,respectively(P>0.05).Multifactor Cox regression showed that tumor diameter and microvascular invasion were independent risk factors for survival in patients that exceeded the Milan criteria.Conclusion Compared with the Milan criteria,the Hangzhou criteria can safely expand the scope of liver transplantation for HCC to a certain extent.By contrast,the UCSF criteria and Up-to-seven criteria result in a limited number of patients which need further expansion.Tumor diameter and microvascular invasion were the independent risk factors for survival in patients that exceeded the Milan criteria.

Criteria-specific long-term survival prediction model for hepatocellular carcinoma patients after liver transplantation

AIM: To establish a model to predict long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (MHCAT).

Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma:Report of an initial experience

AIM： To report a retrospective analysis of preliminary results of 36 patients who received sirolimus （SRL, Rapamune, rapamycin） in a consecutive cohort of 248 liver allograft recipients. METHODS： Thirty-six liver transplant patients with hepatocellular carcinoma （HCC） who were switched to SRL- based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation （OLT） were divided into group A （n = 11）, those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B （n = 18）, and those who developed renal insuffidency caused by caldneurin inhibitor （CNI） were assigned to group C （n = 7） after OLT. RESULTS： The patients were followed up for a median of 10.4 mo （range, 3.8-19.1 mo） after conversion to SRL therapy and 12.3 mo （range, 5.1-34.4 too） after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% （12/18） patients （2 with progressive tumor, 7 with stable tumor and 3 without tumor） were still alive due to conversing to SRL and/ or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia （n = 2）, anemia （n = 8）, and oral aphthous ulcers （n = 7） found in our cohort were easily manageable. CONCLUSION： The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.

Salvage liver transplantation in the treatment of hepatocellular carcinoma:A Meta-analysis

AIM:To evaluate survival and recurrence after salvage liver transplantation(SLT) for the treatment of hepatocellular carcinoma(HCC) compared with primary liver transplantation(PLT) using a meta-analysis.METHODS:Literature on SLT versus PLT for the treatment of HCC published between 1966 and July 2011 was retrieved.A meta-analysis was conducted to estimate pooled survival and disease-free rates.A fixed or random-effect model was established to collect the data.RESULTS:The differences in overall survival and disease-free survival rates at 1-year,3-year and 5-year survival rates were not statistically significant between SLT group and PLT group(P > 0.05).After stratifying the various studies by donor source and Milan criteria,we found that:(1) Living donor liver transplantation recipients had significantly higher 1-year survival rate,lower 3-year and 5-year survival rates compared with deceased-donor liver transplantation(DDLT) recipients.And in DDLT recipients they had better 1-year and 5-year disease-free survival rate in SLT group;and(2) No difference was seen in 1-year,3-year and 5-year survival rates between two groups who beyond Milan criteria at the time of liver transplantation.CONCLUSION:SLT can be effectively performed for patients with recurrence or deterioration of liver function after hepatectomy for HCC.It does not increase the perioperative mortality and has a similar long-term survival rates compared to PLT.

Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation

AIM: To evaluated patterns and outcomes of hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT).METHODS: From 2001 to 2014, 293 patients underwent LDLT for HCC at our transplant center. We retrospectively reviewed 54 (18.4%) patients with HCC recurrence after LDLT. We evaluated patterns and outcomes of HCC recurrence after LDLT, with particular attention to the Milan criteria at transplantation, treatments for HCC-recurrent patients, and factors related to survival after HCC recurrence. Furthermore, we evaluated the efficacy of combination treatment of sorafenib and an mTOR inhibitor.RESULTS: The 1-, 2-, and 3-year overall survival rates after HCC recurrence were 41.1%, 20.5%, and 15.4%, respectively. The median time interval between LDLT and HCC recurrence was 6.5 mo. Although recurrence rates according to the Milan criteria at LDLT were significantly different, HCC recurrence patterns and survival rates after HCC recurrence were not significantly different between the two groups. Time to recurrence &#x0003c; 12 mo (P = 0.048), multiple recurrences at HCC recurrence (P = 0.038), and palliative treatment for recurrent tumors (P = 0.003) were significant independent prognostic factors for poor survival after HCC recurrence in a multivariate analysis. The combination treatment of sorafenib and sirolimus showed survival benefits in the palliative treatment group (P = 0.005).CONCLUSION: Curative treatment for recurrent HCC after LDLT is the most important factor in survival rates after HCC recurrence and combination treatments of sorafenib and an mTOR inhibitor could have survival benefits in patients with HCC recurrence after LT in the palliative treatment group.

Strategies to improve outcome of patients with hepatocellular carcinoma receiving a liver transplantation

The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a 'difficult to treat' cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation(RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing.

A national report from China Liver Transplant Registry: steroid avoidance after liver transplantation for hepatocellular carcinoma

Objective：We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation（LT）for hepatocellular carcinoma（HCC）.Methods：We retrospectively analyzed HCC recipients without steroids after LT（SF group,n=368）based on the China Liver Transplant Registry（CLTR）database.These recipients were matched 1：2 with patients using steroids（S group,n=736）for the same period after LT for HCC,according to propensity scores.Results：Multivariate analysis indicates that recipients with younger age[odds ratio（OR）,1.053;P=0.011],preoperative hepatitis B virus（HBV）DNA≥1,000 copies/mL（OR,2.597;P=0.004）and beyond Milan criteria（OR,4.255;P〈0.001）were identified as the risk factors associated with tumor recurrence in steroid avoidance recipients after LT.The patients fulfilling the Milan criteria in the SF group presented higher overall and tumor-free survival rates than those in the S group（P〈0.05）.Multivariate analysis revealed that recipient beyond Milan criteria was an independent prognostic factor for overall survival（OR,1.690;P〈0.001）and tumor-free survival（OR,2.066;P〈0.001）.The incidences of new-onset diabetes mellitus（21.20% vs.33.29%,P〈0.001）,new-onset hypertension（10.05%vs.18.61%,P〈0.001）and hyperlipidemia（4.08% vs.7.20%,P=0.042）were significantly lower in the SF group.Conclusions：Steroid-free immunosuppression could be safe and feasible for HBV-related HCC patients in LT.Age,HBV DNA level and Milan criteria maybe risk factors associated with tumor recurrence in steroid avoidance recipients.Recipient beyond Milan criteria was an independent prognostic factor and recipient fulfilling Milan criteria can benefit the most from steroid-free immunosuppression.

Current strategies for preventing the recurrence of hepatocellular carcinoma after liver transplantation

BACKGROUND：Liver transplantation is the optimal treatment for a selected group of patients with moderate to severe cirrhosis and hepatocellular carcinoma（HCC）.Despite the strict selection of candidates,post-transplant recurrence often occurs and markedly reduces the long-term survival of patients with HCC.The present review focuses on the current strategies on preventing the recurrence of HCC after liver transplantation.DATA SOURCES： Relevant articles were identified by exten- sive searching of PubMed using the keywords ＂hepatocellular carcinoma＂, ＂recurrence＂ and ＂liver transplantation＂ between January 1996 and January 2014. Additional papers were searched manually from the references in key articles. RESULTS： The current theories of HCC recurrence after liver transplantation are： （i） the growth of pre-transplant occult metastases; （ii） the engraftment of circulating tumor cells released at the time of transplantation. Pre-transplant treatment aims to control local tumor by radiofrequency ablation, transarterial embolization and transarterial chemoembolization. The main objective during the operation is to prevent tumor cell dissemination. Post-transplant treatment includes systemic anticancer therapy, antiviral therapy, and most recently, immunotherapy. These strategies concentrate on the control of the tumor when the patients are waiting for transplant, to reduce the release of HCC cells during surgical procedures and to dear the occult HCC cells after transplantation.CONCLUSIONS： Much can be done to prevent HCC recurrence after liver transplantation. In future, effort is likely to be di- rected towards combining multidisciplinary approaches and various treatment modalities.