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OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

Salvage liver transplantation (SLT) is the ideal treatment for patients with recurrent hepatocellular carcinoma (HCC) and liver cirrhosis. The optimal timing for offering SLT was controversial. This study aimed at investigating the impact of time to recurrence and other prognostic factors on survival outcome after SLT. Between May 2000 and April 2019, patients who had undergone hepatectomy or ablation for HCC and later received SLT in Queen Mary Hospital were included. Clinico-pathological data during primary treatment and SLT were retrospectively reviewed. Kaplan–Meier analysis and log-rank test were used to determine overall and disease-free survival after SLT. Prognostic factors affecting overall and disease-free survival were determined by multivariate analysis using Cox regression analysis. P-value of less than 0.05 was considered statistically significant. Fifty-three patients were identified within the specified period including 22 patients in early recurrence group (ER group, time to recurrence within 1 year) and 31 patients in late recurrence group (LR group, time to recurrence more than 1 year). The 1-, 5-, and 10-year overall survival after primary treatment was 100%, 76.6%, and 61.1% in the ER group and 100%, 90%, and 76.4% in the LR group (p = 0.59). There were no statistical differences in overall survival (p = 0.84) and disease-free survival (p = 0.85) after SLT between ER and LR group. Pre-transplant alpha-fetoprotein > = 400 ng/mL (p = 0.007) and macrovascular invasion in explant (p = 0.002) were independent risk factors for shorter overall survival after primary treatment. Time to recurrence after primary treatment of HCC did not affect survival outcome after SLT. With careful patient selection, SLT could be offered to patient with early or late tumor recurrence.

BACKGROUND AND AIMS There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU). APPROACH AND RESULTS Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time-to-progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P

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

Background An accurate prediction model of early recurrence of hepatocellular carcinoma (HCC) after hepatectomy is important to ascertain the postoperative adjuvant treatment and surveillance. Methods This is a retrospective cohort study including 1125 patients with HCC underwent curative hepatic resection. They were randomly divided into training (n = 562) and validation (n = 563) sets. Early intrahepatic recurrence within 18 months from surgery is the primary outcome. In the training set, a prediction scoring model (Recurrent Liver Cancer Score RLCS) was developed, which was legitimised in the validation set. Results RLCS was developed based on four clinicopathologic risk factors (serum alpha fetoprotein, tumor size, multiple tumors or satellite nodules, and microvascular invasion). Low-risk and high-risk groups had statistically significant differences in early recurrence rates (18% vs. 43.8%). The 5-year recurrence-free survival rates of low risk and high risk groups were 52.9% and 27.8%, respectively. This model showed good calibration and discriminatory ability in the validation set (c-index of 0.647). Conclusion RLCS is a user-friendly prediction scoring model which can accurately predict the occurrence of early intrahepatic recurrence of HCC. It establishes the basis of postoperative adjuvant treatment and surveillance in future studies.

Background & Aims The impact of hepatitis B core antibody (anti-HBc) positive liver grafts on survival and the risk of de novo hepatitis B virus (HBV) infection after liver transplantation (LT) remain controversial. Therefore, we aimed to analyze this risk and the associated outcomes in a large cohort of patients. Methods This was a retrospective study that included all adults who underwent LT at Queen Mary Hospital, Hong Kong, between 2000 and 2015. Data were retrieved from a prospectively collected database. Antiviral monotherapy prophylaxis was given for patients receiving grafts from anti-HBc positive donors. Results A total of 964 LTs were performed during the study period, with 416 (43.2%) anti-HBc positive and 548 (56.8%) anti-HBc negative donors. The median follow-up time was 7.8 years. Perioperative outcomes (hospital mortality, complications, primary nonfunction and delayed graft function) were similar between the 2 groups. The 1-, 5- and 10-year graft survival rates were comparable in anti-HBc positive (93.3%, 85.3% and 76.8%) and anti-HBc negative groups (92.5%, 82.9% and 78.4%, p = 0.944). The 1-, 5- and 10-year patient survival rates in anti-HBc positive group were 94.2%, 87% and 79% and were similar to the anti-HBc negative group (93.5%, 84% and 79.7%, p = 0.712). One-hundred and eight HBsAg negative recipients received anti-HBc positive grafts, of whom 64 received lamivudine and 44 entecavir monotherapy prophylaxis. The risk of de novo HBV was 3/108 (2.8%) and all occurred in the lamivudine era. There were 659 HBsAg-positive patients and 308 (46.7%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between the 2 groups. Donor anti-HBc status did not impact on long-term patient and graft survival, or the risk of hepatocellular carcinoma recurrence after LT. Conclusions De novo HBV was exceedingly rare especially with entecavir prophylaxis. Anti-HBc positive grafts did not impact on perioperative and long-term outcomes after transplant. Lay summary The risk of de novo hepatitis B infection after liver transplantation was rare when using hepatitis B core positive liver grafts with entecavir monotherapy prophylaxis. Hepatitis B core antibody status did not impact on perioperative and long-term outcomes after liver transplantation. This provides support for the clinical use of hepatitis B core positive liver grafts when required.

Summary: 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 ηg/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. Keywords: Primary transplantation, Salvage transplantation, Hepatocellular carcinoma, Propensity score matching

OBJECTIVE The aim of this study was to determine the outcomes of living donor liver transplantation (LDLT) according to various graft-to-recipient weight ratio (GRWR). BACKGROUND The standard GRWR in LDLT is >0.8%. Our center accepted predicted GRWR ≥0.6% in selected patients. METHODS Data from patients who underwent LDLT from 2001 to 2017 were included. Patients were stratified according to actual GRWR (Group 1:GRWR ≤0.6%; Group 2: 0.6% 0.8%). RESULTS There were 545 LDLT (group 1 = 39; group 2 = 159; group 3 = 347) performed. Pretransplant predicted GRWR showed good correlation to actual GRWR (R2 = 0.834) and these figures differed within a ± 10%margin (P = 0.034) using an equivalence test. There were more left lobe grafts in group 1 (33.3%) than group 2 (10.7%) and 3 (2.9%). Median donor age was 10% was rare.There was no difference in postoperative complication, vascular and biliary complication rate between groups. Over one-fifth (20.5%) of group 1 patients required portal flow modulation (PFM) and was higher than group 2 (3.1%) and group 3 (4%) (P = 0.001). Twenty-six patients developed small-for-size syndrome (SFSS): 5 of 39 (12.8%) in group 1 and 21 of 159 (13.2%) in group 2 and none in group 3 (P < 0.001). There were 2 hospital mortalities; otherwise, the remaining patients [24/26 (92.3%)] survive with a functional liver graft. The 5-year graft survival rates were 85.4% versus 87.8% versus 84.7% for group 1, 2, and 3, respectively (P = 0.718). GRWR did not predict worse survivals in multivariable analysis. CONCLUSIONS Graft size in LDLT can be lowered to 0.6% after careful recipient selection, with low incidence of SFSS and excellent outcomes. Accurate graft weight prediction, donor-recipient matching, meticulous surgical techniques, appropriate use of PFM, and vigilant perioperative care is important to the success of such approach.

Background and Aims Previous recommendations suggested living donor liver transplantation (LDLT) should not be considered for patients with Model for End‐Stage Liver Disease (MELD) > 25 and hepatorenal syndrome (HRS). Approach and Results Patients who were listed with MELD > 25 from 2008 to 2017 were analyzed with intention‐to‐treat (ITT) basis retrospectively. Patients who had a potential live donor were analyzed as ITT‐LDLT, whereas those who had none belonged to ITT‐deceased donor liver transplantation (DDLT) group. ITT‐overall survival (OS) was analyzed from the time of listing. Three hundred twenty‐five patients were listed (ITT‐LDLT n = 212, ITT‐DDLT n = 113). The risk of delist/death was lower in the ITT‐LDLT group (43.4% vs. 19.8%, P 25 and patients with both MELD > 25 and HRS (56% vs. 33.8%, P 25 (88% vs. 85.4%, P = 0.279) and patients with both MELD > 25 and HRS (77% vs. 76.4%, P = 0.701) after LDLT and DDLT, respectively. The LDLT group has a higher rate of renal recovery by 1 month (77.4% vs. 59.1%, P = 0.003) and 3 months (86.1% vs, 74.5%, P = 0.029), whereas the long‐term estimated glomerular filtration rate (eGFR) was similar between the 2 groups. ITT‐LDLT reduced the hazard of mortality (hazard ratio = 0.387‐0.552) across all MELD strata. Conclusions The ITT‐LDLT reduced waitlist mortality and allowed an earlier access to transplant. LDLT in patients with high MELD/HRS was feasible, and they had similar perioperative outcomes and better renal recovery, whereas the long‐term survival and eGFR were comparable with DDLT. LDLT should be considered for patients with high MELD/HRS, and the application of LDLT should not be restricted with a MELD cutoff.

Since the introduction of Milan Criteria, all scoring models describing the prognosis of hepatocellular cancer (HCC) after liver transplantation (LT) have been exclusively based on characteristics available at surgery, therefore neglecting the intention-to-treat principles. This study aimed at developing an intention-to-treat model through a competing-risk analysis. Using data available at first referral, an upper limit of tumor burden for downstaging was identified beyond which successful LT becomes an unrealistic goal. Twelve centers in Europe, United States, and Asia (Brussels, Sapienza Rome, Padua, Columbia University New York, Innsbruck, Medanta-The Medicity Dehli, Hong Kong, Kyoto, Kaohsiung Taiwan, Mainz, Fukuoka, Shulan Hospital Hangzhou) created a Derivation (n = 2318) and a Validation Set (n = 773) of HCC patients listed for LT between January2000&ndash, March 2017. In the Derivation Set, the competing-risk analysis identified two independent covariables predicting post-transplant HCC-related death: combined HCC number and diameter (SHR = 1.15, p &lt, 0.001) and alpha-fetoprotein (AFP) (SHR = 1.80, 0.001). WE-DS Model showed good diagnostic performances at internal and external validation. The identified upper limit of tumor burden for downstaging was AFP &le, 20 ng/mL and up-to-twelve as sum of HCC number and diameter, AFP = 21&ndash, 200 and up-to-ten, AFP = 201&ndash, 500 and up-to-seven, AFP = 501&ndash, 1000 and up-to-five. The WE-DS Model proposed here, based on morphologic and biologic data obtained at first referral in a large international cohort of HCC patients listed for LT, allowed identifying an upper limit of tumor burden for downstaging beyond which successful LT, following downstaging, results in a futile transplantation.

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.

BACKGROUND AND AIMS The prognosis in severe acute flares of chronic hepatitis B (AFOCHB) is often unclear. The current study aimed to establish the predictive value using the Model for End-Stage Liver Disease (MELD) score for short-term mortality for severe AFOCHB. APPROACH AND RESULTS Patients with severe AFOCHB with bilirubin > 50 µmol/L, alanine aminotransferase > 10× upper limit of normal, and international normalized ratio > 1.5 were included. All patients were commenced on entecavir and/or tenofovir. Laboratory results and MELD scores were pooled to calculate mortality at four time points (days 7, 14, 21, and 28). A total of 240 patients were included. Median hepatitis B virus DNA was 7.77 log IU/mL (range, 4.11-10.06), and 49 (20.4%) were hepatitis B e antigen-positive. The 7, 14, 21, and 28-day survival was 96.7%, 88.5%, 79.5%, and 72.8%, respectively. Using pooled results derived from 4,201 blood samples, the area under the receiver operating curve for the MELD score to predict day 7, 14, 21, and 28 mortality was 0.909, 0.892, 0.883, and 0.871, respectively. For MELD ≤ 28, mortality at day 28 was low ( 50% mortality for MELD ≥ 32. For MELD = 28-32, higher day-28 mortality was observed for four criteria: age ≥52 years, alanine aminotransferase > 217 U/L, platelets < 127, and abnormal baseline imaging (all P

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

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). 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. 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. 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.

Background: Since the introduction of the Milan Criteria (MC), all systems, which describe post-transplant prognosis of patients with hepatocellular cancer (HCC), are exclusively based on characteristics available at surgery, and neglect the intention-to-treat principles. This study, based on a large international HCC patient cohort, aimed to develop comprehensive intention-to-treat models through a competing-risk analysis. We used data available at first referral to predict the risk of delisting and HCC-related death after liver transplantation (LT). Methods: Twelve centres in the United States, Europe and Asia created a Derivation Set (n=2,318) and an external Validation Set (n=773) of HCC patients listed for LT between January 2000-March 2017. The study was registered at http://www.ClinicalTrials.gov (ID:NCT03595345). Findings: In the Derivation Set, the competing-risk analysis identified three independent covariates predicting delisting (Model#1): age (sub-hazard ratio, SHR=1·049; p=0·001), MELD (SHR=1·033; p=0·002) and living donation availability (SHR=0·422; p-value=0·001), all evaluated at first referral. The risk of post-transplant HCC-related death (Model#2) was predicted by the combination of Metroticket2.0 (SHR=1·724; p=0·001) and MELD (SHR=0·970; p=0·045), both evaluated at first referral. In the external validation, Model#1 was compared with MELD, deMELD, MELDeq, and HCC-MELD, and Model#2 with the AFP French Model and the TRAIN score. Both exhibited the highest diagnostic performances (c-statistic=63·3% and 67·7%, respectively). The identified upper limit of post-transplant HCC-related death was 13%, corresponding to the different combinations of alpha-fetoprotein (AFP) and morphological indicators: AFP≤20 ng/mL and up-to-twelve as sum of diameter/number of lesions; AFP=21-200 and up-to-ten; AFP=201-500 and up-to-seven; AFP=501-1,000 and up-to-five. Interpretation: This study presents a scoring system based on a large international cohort of HCC patients awaiting LT. A freely accessible web calculator has been created to estimate the individual risks of delisting and HCC-related death after LT. Furthermore, a risk "recalculation" after neo-adjuvant treatments can improve patient selection and indications. Funding: None in relation to the here presented work. Declaration of Interest: The authors have no conflicts of interest to declare in relation to the present study. Ethical Approval: The Institutional Ethical and Scientific Review board of the coordinating centre approved the study, registered at http://www.ClinicalTrials.gov (ID: NCT03595345).

With improvements in survival, liver transplant recipients now suffer more morbidity from long-term immunosuppression. Considerations were given to develop individualized immunosuppression based on their risk of rejection.We retrospectively analyzed the data of 788 liver transplants performed during the period from October 1991 to December 2011 to study the relationship between acute cellular rejection (ACR) and various clinical factors.Multivariate analysis showed that older age (P=0.04, OR=0.982), chronic hepatitis B virus infection (P=0.005, OR= 0.574), living donor liver transplantation (P=0.02, OR=0.648) and use of interleukin-2 receptor antagonist on induction (P0.001, OR=0.401) were associated with fewer ACRs. Patients with fulminant liver failure (P=0.004, OR=4.05) were more likely to develop moderate to severe grade ACR.Liver transplant recipients with older age, chronic hepatitis B virus infection, living donor liver transplantation and use of interleukin-2 receptor antagonist on induction have fewer ACR. Patients transplanted for fulminant liver failure are at higher risk of moderate to severe grade ACR. These results provide theoretical framework for developing individualized immunosuppression.

This study was presented at the 11th World IHPBA Congress, 22–27 March 2014, Seoul., 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. © 2014 International Hepato-Pancreato-Biliary Association., link_to_OA_fulltext

Long-term antiviral prophylaxis is required to prevent hepatitis B recurrence for patients with chronic hepatitis B after liver transplantation. We determined the long-term outcome of 265 consecutive chronic hepatitis B liver transplant recipients treated with entecavir monotherapy without hepatitis B immune globulin. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. The median duration of follow-up was 59 months. The cumulative rates of hepatitis B surface antigen (HBsAg) seroclearance were 90% and 95% at 1 and 5 years, respectively. At 1, 3, 5, and 8 years, 85%, 88%, 87.0%, and 92% were negative for HBsAg, respectively, and 95%, 99%, 100%, and 100% had undetectable hepatitis B virus (HBV) DNA, respectively. Fourteen patients remained persistently positive for HBsAg, all of whom had undetectable HBV DNA. There was no significant difference in liver stiffness for those who remained HBsAg-positive compared to those who achieved HBsAg seroclearance (5.5 versus 5.2 kPa, respectively; P = 0.52). The overall 9-year survival was 85%. There were 37 deaths during the follow-up period, of which none were due to hepatitis B recurrence. Conclusion: Long-term entecavir monotherapy is highly effective at preventing HBV reactivation after liver transplantation for chronic hepatitis B, with a durable HBsAg seroclearance rate of 92%, an undetectable HBV DNA rate of 100% at 8 years, and excellent long-term survival of 85% at 9 years. (Hepatology 2017;66:1036-1044).

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.

Patients with hepatocellular carcinoma have a very short life expectancy if they receive no surgical intervention. A relatively new surgical technique termed “Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy” (ALPPS) has been employed for inducing rapid hypertrophy of the future liver remnant for patients waiting for hepatectomy. As portal vein embolization may not result in satisfactory hypertrophy before tumor progression occurs, ALPPS can be an alternative for patients with advanced hepatocellular carcinoma. Herein we describe an ALPPS procedure with tumor thrombectomy for a patient who had a small left liver lobe and a large hepatocellular carcinoma involving the whole right liver lobe and the middle hepatic vein and extending into the inferior vena cava. In the first-stage operation, the right portal vein was controlled and divided with a Hemolock. The right hepatic artery was well protected. Hepatic transection was performed with a 1-cm margin from the tumor. The middle hepatic vein trunk was preserved. Ten days afterwards, there was significant hypertrophy of the left lateral section of the liver, and the second-stage operation was conducted. Extended right hepatectomy and tumor thrombectomy were performed under sternotomy and total vascular exclusion. The patient had good recovery and was free of disease 10 months after the operation. ALPPS may be a good treatment option even for patients with advanced disease if carried out at high-volume centers.

Session SF231: Transplantation and Tissue Engineering II. Track: General Surgery (GEN), Basic / Translational Research (BTR)

Our aim was to study the long-term outcomes of living donor liver transplantation using small-for-size (SFS) grafts. From July 2002 to July 2009, 233 patients received a right liver graft with a middle hepatic vein from a living donor in our center. Recipients were stratified according to the graft weight to recipient standard liver volume (GW/SLV) ratio into 4 groups: >50% (n = 89), >40% to 50% (n = 85), >35% to 40% (n = 38), and ≤ 35% (n = 21). They were compared in terms of graft survivals, biliary stricture rates, renal function in terms of estimated glomerular filtration rate (eGFR), platelet counts, and graft function in terms of serum bilirubin and international normalized ratio (INR). The 5-year graft survivals for patients with GW/SLV of >50%, >40% to 50%, >35% to 40% and ≤ 35% were 88.8%, 88.2%, 81.5%, and 81.0%, respectively. Transplantation for hepatocellular carcinoma affected graft survivals (P = 0.02), but graft size did not (P = 0.66). There were no differences in frequency of biliary stricture (21.3% versus 17.1% versus 21.1% versus 28.6%; P = 0.75). At each year after transplant, their platelet counts (P = 0.12-0.65), eGFR (P = 0.49-0.91), bilirubin (P = 0.14-0.51), and INR (P = 0.20-0.98) remained comparable. SFS grafts with GW/SLV ≤ 35% and >35% to 40% had comparable long-term outcomes with larger liver grafts. Graft size did not affect long-term graft survivals.

The outcomes of hepatitis B virus (HBV)-related hepatitis after liver transplantation (LT) without hepatitis B immune globulin (HBIG) is not well documented. This study aims to determine the outcomes of chronic hepatitis B (CHB) patients using an HBIG-free regimen. All biopsies performed 3 months or more after LT in consecutive CHB patients transplanted from 2003 to 2012 were reviewed. None of the patients received HBIG. Results of all liver histologies were reviewed to determine the cause of graft dysfunction. Of the 435 patients transplanted during this period, 263 liver biopsies were performed in 144 patients. Thirty-six patients were positive for hepatitis B surface antigen (HBsAg) with undetectable HBV DNA at the time of biopsy, and none had histological evidence of HBV infection. Of the 263 biopsies, 44 (17%) had evidence of fibrosis. There was a significantly higher rate of fibrosis in those with large duct obstruction compared to those without (51% versus 9%, respectively; P

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.

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

Improved outcomes have been shown in liver transplantation (LT) with portal vein thrombosis (PVT). However, PVT is still discovered incidentally during surgery despite careful preoperative imaging. Data are limited comparing the outcomes of incidental PVT with PVT diagnosed via preoperative imaging before LT. This study aims to compare the overall outcomes of patients with PVT. From 2008 to 2012, 369 patients had LT, and 58 patients with PVT were identified. They were divided into those with non-PVT (group 0; n = 311), preoperatively identified PVT (group 1; n = 28), and incidental PVT (group 2; n = 30). The demographics, characteristics, preoperative assessment, and postoperative outcomes were compared. A survival analysis was also performed. Baseline characteristics and preoperative evaluations of all 3 groups were comparable (P > 0.05) except for Model for End-Stage Liver Disease score, tumor status, platelet levels, and serum bilirubin. A multivariate analysis only showed a high serum bilirubin level to be a predictor of PVT (P = 0.004; odds ratio, 3.395; 95% confidence interval, 1.467-7.861). Postoperative outcomes were also comparable (P > 0.05). Compared to group 2, group 1 had more patients with a Yerdel classification of 3 or 4 with more extensive surgical intervention required (P = 0.02). The survival analysis in all 3 groups was comparable with 5-year survival rate of 87.4%, 84.6%, and 91.8% in group 0, 1, and 2, respectively (P = 0.66). In conclusion, recipients with PVT undergoing LT can have similar outcomes as the non-PVT patients even if PVTs were discovered incidentally. Discovery of incidental PVT only requires thrombectomy with no substantial change of treatment strategy, and the outcome is not adversely affected because most incidental PVTs are of a lower Yerdel grade. Preoperative imaging is useful to identify those with a higher Yerdel grade to allow planning of surgical strategy during transplantation. Liver Transpl 21:944-952, 2015. © 2015 AASLD.

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.

Liver resection is the treatment of choice and standard of care in patients with hepatocellular carcinoma (HCC). The ultimate goal of liver resection in HCC patients is to resect primary tumor with an adequate margin while preserving as much functional liver parenchyma as possible. Tremendous improvements in perioperative outcomes after liver resection have been achieved in the past three decades. The overall and disease-free survival rates have also improved. Liver resection is feasible and safe even in cirrhotic patients. This is a result of more accurate preoperative evaluation of liver function, the ability to manipulate future liver remnant volume, the use of anatomical resection and an anterior approach, meticulous surgical techniques to achieve bloodless liver resection, and better perioperative care. The purpose of this review is to highlight the importance of different resection strategies for HCC that in turn have contributed to the safety and improvement in long-term outcomes after liver resection.

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.