Long-Term Survival Outcome Between Living Donor and Deceased Donor Liver Transplant for Hepatocellular Carcinoma: Intention-to-Treat and Propensity Score Matching Analyses.

BACKGROUND: Previous studies comparing outcomes of hepatocellular carcinoma (HCC) patients after living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) showed conflicting results, and most studies measured survival outcomes from the time of liver transplantation (LT). METHOD: This retrospective study was aimed to evaluate the long-term outcomes of HCC patients listed for LT using intention-to-treat (ITT) and propensity score matching (PSM) analyses. Clinicopathological data were retrieved from a prospectively collected database. RESULTS: From 1995 to 2014, 375 HCC patients were listed for LT. ITT-LDLT group had 188 patients, whereas ITT-DDLT group had 187 patients. Twenty-seven patients (14.4%) and 122 patients (65.2%) were delisted from LDLT and DDLT waitlist, respectively. The 1-, 3- and 5-year overall survival rates were significantly better in ITT-LDLT group than ITT-DDLT group (94.1 vs. 77.5%, 81.4 vs. 48.7% and 75.9 vs. 40.8%). High alphafetoprotein (AFP) and ITT-DDLT treatment arm were independent poor prognostic factors affecting overall survival. LDLT group (n = 161) had more young patients, poorer liver function, higher AFP, more tumors outside Milan/UCSF criteria, when compared with DDLT group (n = 85). After PSM, the 1-, 3- and 5-year overall (95.4 vs. 98.5%, 80.0 vs. 92.3% and 73.4 vs. 84.4%) and recurrence-free (87.7% vs. 90.8%, 76.9% vs. 83.1% and 72.2% vs. 81.5%) survival rates were comparable between the matched LDLT and the matched DDLT group, respectively. CONCLUSION: Survival benefit of LDLT was observed for HCC patients with ITT analysis. Despite a more advanced tumor stage, overall and recurrence-free survival rates were comparable between LDLT and DDLT using PSM analysis.

Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors.

Liver grafts with macrovesicular steatosis of > 60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain-dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis > 60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis > 60%), and 354 patients had grafts with ≤ 60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End-Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30-day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1-year and 3-year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low-risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation.

Outcomes of hepatectomy for hepatocellular carcinoma with bile duct tumour thrombus.

BACKGROUND: Hepatocellular carcinoma (HCC) with bile duct tumour thrombus (BDTT) is rare. The aim of the present study was to determine the prognosis of HCC with BDTT after a hepatectomy. METHODS: A retrospective analysis was performed on all HCC patients with BDTT having a hepatectomy from 1989 to 2012. The outcomes in these patients were compared with those in the control patients matched on a 1:6 ratio. RESULTS: Thirty-seven HCC patients with BDTT having a hepatectomy (the BDTT group) were compared with 222 control patients. Patients in the BDTT group had poorer liver function (43.2% had Child-Pugh B disease). More patients in this group had a major hepatectomy (91.9% versus 27.5%, P = 0.001), portal vein resection (10.8% versus 1.4%, P = 0.006), en-bloc resection with adjacent structures (16.2% versus 5.4%, P = 0.041), hepaticojejunostomy (75.7% versus 1.6%, P < 0.001) and complications (51.4% versus 31.1%, P = 0.016). The two groups had similar hospital mortality (2.7% versus 5.0%, P = 0.856), 5-year overall survival (38.5% versus 34.6%, P = 0.59) and 5-year disease-free survival (21.1% versus 20.8%, P = 0.81). Multivariate analysis showed that lymphovascular permeation, tumour size and post-operative complication were significant predictors for worse survival whereas BDTT was not. DISCUSSION: A major hepatectomy, extrahepatic biliary resection and hepaticojejunostomy should be the standard for HCC with BDTT, and long-term survival is possible after radical surgery.

Hepatobiliary malignancies: lessons from Asia.

With the higher incidences of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in the East compared with the West, Asian centers have made significant contributions to the management of these malignancies. The major risk factor for HCC is hepatitis B infection in Asia in contrast to hepatitis C in Western populations. Barcelona Clinic for Liver Cancer (BCLC) staging that guides the treatment of patients with HCC in the West is considered too conservative by many Asian centers. In Asia, liver resection is widely offered to patients with multifocal, bilobar tumor or tumor invasion to the portal vein. The criteria for liver transplantation for HCC are also often more extended in Asian centers. Asian surgeons pioneered the development of living donor liver transplantation, which plays a major role in the management of early HCC associated with severe cirrhosis in Asia due to shortage of deceased donor graft. Asian centers have also made significant contributions to the modern management of CCA. A more aggressive surgical approach is generally adopted in Asia, including radical lymphadenectomy for intrahepatic CCA and simultaneous hepatic artery and portal vein resection with hepatectomy for hilar CCA. Eastern and Western centers should collaborate in further studies to establish the optimal treatment strategies for hepatobiliary malignancies.

Prevention of recurrent hepatitis B infection after liver transplantation.

BACKGROUND: Recurrence of hepatitis B virus (HBV) infection after liver transplantation can lead to graft loss and a reduction in long-term survival. The purpose of this review is to summarize the current therapeutic options for preventing HBV recurrence in liver transplant recipients. DATA SOURCES: Up to January 2013, studies that were published in MEDLINE and EMBASE on prevention of HBV recurrence after liver transplantation were reviewed. RESULTS: There have been remarkable advancements in the past two decades on the prevention of HBV recurrence after liver transplantation, from the discovery of hepatitis B immune globulin (HBIG) and lamivudine monotherapy to the combination therapy using HBIG and lamivudine. With the development of newer and stronger antiviral agents, the need for life-long HBIG is doubtful. With their low resistance profile, oral antiviral prophylaxis using these new agents alone is sufficient and is associated with excellent outcome. CONCLUSIONS: Restoration of host HBV immunity with adoptive immunity transfer and vaccination may represent the ultimate strategy to withdraw prophylactic treatment and to achieve a drug free regimen against HBV recurrence after liver transplantation.

Comparison of clinical outcome between stereotactic body radiotherapy and radiofrequency ablation for unresectable hepatocellular carcinoma.

ABSTRACT: Stereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for unresectable hepatocellular carcinoma (HCC). Whether its efficacy is comparable to radiofrequency ablation (RFA), a recommended therapy for unresectable HCC, is unknown. The present study aims to compare the clinical outcome between SBRT and RFA for patients with unresectable HCC.The clinical data of 60 patients with unresectable HCC from January 2018 to January 2021 were retrospectively reviewed. There were 22 cases treated by SBRT and 38 cases by RFA. The short-term and long-term clinical outcomes were compared.There was no significant difference in the baseline demographic characteristics between two groups. The complete remission rate at 3 months was comparable between SBRT group (81.8%) and RFA group (89.4%). Local tumor control rate was also similar between two groups (90.9% vs. 94.7%). There was no severe complication (grade IIIa or above) in both groups. The 1-year and 2-year overall survival rates were 88.2% and 85.7% in SBRT group and 100% and 75% in RFA group, respectively. There was no statistical significant difference between groups (P = .576).SBRT can achieve similar short and long-term clinical outcome as RFA for unresectable HCC. Future prospective clinical study is needed to justify its role in patients with HCC.

A comparison of angiographic embolization with surgery after failed endoscopic hemostasis to bleeding peptic ulcers.

BACKGROUND: In patients with bleeding peptic ulcers in whom endoscopic hemostasis fails, surgery usually follows. Transarterial embolization (TAE) has been proposed as an alternative. OBJECTIVE: To compare the outcomes of TAE and salvage surgery for patients with peptic ulcers in whom endoscopic hemostasis failed. DESIGN: Retrospective study. SETTING: A university hospital. PATIENTS: Patients with peptic ulcer bleeding in whom endoscopic hemostasis failed. INTERVENTIONS: TAE and surgery as salvage of peptic ulcer bleeding. MAIN OUTCOMES MEASUREMENTS: All-cause mortality, rebleeding, reintervention, and complication rate. RESULTS: Thirty-two patients underwent TAE and 56 underwent surgery. In those who underwent TAE, the bleeding vessels were gastroduodenal artery (25 patients), left gastric artery (4 patients), right gastric artery (2 patients), and splenic artery (1 patient). Active extravasation was seen in 15 patients (46.9%). Embolization was attempted in 26 patients, and angiographic coiling was successful in 23 patients (88.5%). Bleeding recurred in 11 patients (34.4%) in the TAE group and in 7 patients (12.5%) in the surgery group (P=.01). More complications were observed in patients who underwent surgery (40.6% vs 67.9%, P=.01). There was no difference in 30-day mortality (25% vs 30.4%, P=.77), mean length of hospital stay (17.3 vs 21.6 days, P=.09), and need for transfusion (15.6 vs 14.2 units, P=.60) between the TAE and surgery groups. LIMITATIONS: Retrospective study. CONCLUSIONS: In patients with ulcer bleeding after failed endoscopic hemostasis, TAE reduces the need for surgery without increasing the overall mortality and is associated with fewer complications.

Evaluation of the Intention-to-Treat Benefit of Living Donation in Patients With Hepatocellular Carcinoma Awaiting a Liver Transplant.

Importance: Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC). Objective: To investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription. Design, Setting, and Participants: This multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020. Main Outcomes and Measures: Intention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created. Results: A total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated. Conclusions and Relevance: This study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.

Long-term survival comparison between primary transplant and upfront curative treatment with salvage transplant for early stage hepatocellular carcinoma.

BACKGROUND: Whether primary liver transplantation (PLT) or upfront curative treatment with salvage liver transplantation (SLT) is a better treatment option for early hepatocellular carcinoma (HCC) is controversial. This study aims to compare the long-term survival starting from the time of primary treatment between the two approaches for early HCC using propensity score matching (PSM) analysis. METHODS: From 1995 to 2014, 175 patients with early HCC undergoing either PLT (n = 149) or SLT (n = 26) were retrospectively reviewed in a prospectively collected database. Patients' demographic data, tumor characteristics, short-term and long-term outcome were compared between two groups after PSM. RESULTS: After matching, the baseline characteristics were comparable between mPLT group (n = 45) and mSLT group (n = 25). The tumor recurrence rate after transplant was significantly higher in mSLT group than mPLT group (28% vs. 15.6%). Calculating from the time of primary treatment, the 1, 3, and 5-year overall survival rates were comparable between mPLT group (97.8%, 91.1% and 86.3%) and mSLT group (100%, 95% and 85%). However, the 1, 3, and 5-year recurrence-free survival rates were significantly better in mPLT group than mSLT group (95.6% vs. 90%, 86.6% vs. 80% and 84.3% vs. 70%). SLT approach and high pre-treatment serum alpha-fetoprotein level (>200 Î·g/mL) were poor prognostic factors for recurrence-free survival after transplant. CONCLUSIONS: PLT may be a better treatment option for early HCC, whereas SLT approach for HCC should be cautiously considered under the circumstance of organ shortage.

Impact of intraoperative blood transfusion on long-term outcomes of liver transplantation for hepatocellular carcinoma.

OBJECTIVE: To investigate the impact of intraoperative blood transfusion on the long-term outcomes of liver transplantation for hepatocellular carcinoma. METHOD: Adult patients who had non-salvage liver transplantation at our centre between January 2005 and December 2012 for hepatocellular carcinomas that were within the University of California, San Francisco criteria and could not be resected or ablated were divided into groups with and without intraoperative blood transfusion. Comparisons were made between groups. RESULTS: Ninety-nine patients were included in the study. Sixty-two (62.6%) patients received intraoperative blood transfusion. Patients without transfusion were younger (54 versus 56 years; P = 0.04) and had a lower Model for End-stage Liver Disease score (11 versus 14; P < 0.001). Most of them had stage-I tumours (64.9 versus 37.1%; P = 0.007) and fewer of them had postoperative complications of grade IIIA or above in the Clavien-Dindo classification (21.6 versus 48.4%; P = 0.008). The groups were comparable in hospital mortality (3.2 versus 2.7%; P = 1.00), 5-year overall survival (90.8 versus 89.2%; P = 0.611) and 5-year disease-free survival (90.5 versus 89.2%; P = 0.835). On multivariate analysis, postoperative complications of grade IIIA or above were associated with worse survival (hazard ratio, 7.108; 95% confidence interval, 1.455-34.712; P = 0.015). CONCLUSION: Intraoperative blood transfusion was shown to have no significant impact on the long-term outcomes of liver transplantation for hepatocellular carcinoma, whereas postoperative complications of grade IIIA or above were associated with worse recipient survival.

Survival outcomes of hepatocellular carcinoma resection with postoperative complications - a propensity-score-matched analysis.

Curative resection remains the only hope of cure for hepatocellular carcinoma (HCC), but postoperative complications can have a significant impact on long-term survival. However, only scarce data on such impact can be found in the literature.This retrospective study reviewed the prospectively collected data of patients who underwent primary liver resection for HCC at our hospital during the period from December 1989 to December 2014. Patients with and without postoperative complications were compared. A 1:1 propensity score matching was adopted by matching age, comorbidity, Model of End-stage Liver Disease score, tumor stage, and extent of resection.Totally 1710 patients were eligible for the study. Four hundred and sixty-one (27.0%) of them developed postoperative complications while 1249 (73.0%) did not. After propensity score matching, 922 patients were compared in a 1:1 ratio (461 with postoperative complications and 461 without). Patients who developed postoperative complications were demographically similar to patients who did not, but had more intraoperative blood loss and transfusion (both P < 0.001), longer hospital stay (17 vs 9 days; P < 0.001), worse hospital mortality (12.1% vs 0%; P < 0.001), and shorter overall survival (P < 0.001). On multivariate analysis, factors that might have affected overall survival were cancer stage (HR 1.22, P < 0.001), tumor size (HR 1.02, P = 0.005), tumor number (HR 1.08, P < 0.001), venous invasion (HR 1.38, P = 0.003), extent of resection (HR 1.19, P = 0.045), intraoperative blood loss (HR 1.11, P < 0.001), postoperative complication (HR 1.37, P < 0.001), and era effect (HR 1.27, P = 0.01).Patients should be monitored closely after HCC resection. Prompt treatment of postoperative complications may be salvational.

Retransplantation using living-donor right-liver grafts.

BACKGROUND: This study reviews the outcomes of retransplantation using living-donor right-liver grafts. METHODS: A retrospective study of liver retransplants performed between 1996 and 2013 was conducted. The retransplants were divided into the DD group (with deceased donors) and the LD group (with living donors). Survival outcomes were analyzed. RESULTS: The DD group contained 23 patients and 27 retransplants using whole-liver grafts and the LD group contained 11 patients and 11 retransplants using right-liver grafts. Vascular and biliary complications were the main indications for retransplantation in both groups. The LD group had significantly younger donors, lighter grafts, shorter cold ischemia and longer operations. The two groups were comparable in age, preoperative liver function, warm ischemia, blood loss, transfusion, intensive care unit stay, hospital stay, hospital mortality, complication and graft loss. The 1-year, 3-year and 5-year patient survival rates were 78.3%, 73.7% and 63.8%, respectively, in the DD group. The LD group had the corresponding rates all at 90.9% (P = 0.246). The 1-year, 3-year and 5-year graft survival rates were 74.1%, 65.8% and 61.5%, respectively, in the DD group. The LD group had the corresponding rates all at 90.9% (P = 0.132). CONCLUSION: Excellent long-term survival after retransplantation using living-donor right-liver grafts can be achieved.