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Background: Diabetes mellitus (DM) is said to adversely affect transplant outcomes. The aim of this study was to investigate the impact of pre-existing and new-onset DM on liver transplantation (LT) recipients., Methods: A single-center retrospective analysis of prospectively collected data of LT recipients (1990-2015) was undertaken., Results: Of the 2209 patients, 13% (n = 298) had Pre-DM, 16% (n = 362) developed post-transplant diabetes mellitus (PTDM), 5% (n = 118) developed transient hyperglycemia (t-HG) post-LT, and 65% (n = 1431) never developed DM (no DM). Baseline clinical characteristics of patients with PTDM were similar to that of patients with Pre-DM. Incidence of PTDM peaked during the first year (87%) and plateaued thereafter. On multivariate analysis (Bonferroni-corrected), nonalcoholic fatty liver disease and the use of tacrolimus and sirolimus were independently associated with PTDM development. Both Pre-DM and PTDM patients had satisfactory and comparable glycemic control throughout the follow-up period. Those who developed t-HG seem to have a unique characteristic compared with others. Overall, 9%, 5%, and 8% of patients developed end-stage renal disease (ESRD), major cardiovascular event (mCVE), and de novo cancer, respectively. Both Pre-DM and PTDM did not adversely affect patient survival, retransplantation, or de novo cancer. The risks of ESRD and mCVE were significantly higher in patients with Pre-DM followed by PTDM and no DM., Conclusions: In this largest nonregistry study, patients with Pre-DM and PTDM share similar baseline clinical characteristics. Pre-DM increases the risk of ESRD and mCVE; however, patient survival was comparable to those with PTDM and without diabetes. Understanding the impact of PTDM would need prolonged follow-up.

Background & Aims: Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy., Methods: We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged <70 years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2 cm vs. HCC >2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria., Results: We included 301 patients (167 HCC ≤2 cm and 134 HCC >2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC >2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2 cm group (p = 0.01). Tumor size >2 cm (hazard ratio 1.94; 95%CI 1.25-3.02) and alpha-fetoprotein levels at the time of ablation (100-1,000 ng/ml: hazard ratio 2.05; 95%CI 1.10-3.83) were found to be predictors of post-RFA recurrence outside Milan criteria., Conclusion: RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA., Lay Summary: Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: There are conflicting reports on the outcomes after live donor liver transplantation in patients with hepatocellular carcinoma (HCC). We aimed to compare the survival of patients with HCC, with a potential live donor (pLDLT) at listing vs. no potential donor (pDDLT), on an intention-to-treat basis., Methods: All patients with HCC listed for liver transplantation between 2000-2015 were included. The pLDLT group was comprised of recipients with a potential live donor identified at listing. Patients without a live donor were included in the pDDLT group. Survival was assessed by the Kaplan-Meier method. Multivariable Cox regression was applied to identify potential predictors of mortality., Results: A total of 219 patients were included in the pLDLT group and 632 patients in the pDDLT group. In the pLDLT group, 57 patients (26%) were beyond the UCSF criteria whereas 119 patients (19%) in the pDDLT group were beyond (p = 0.02). Time on the waiting list was shorter for the pLDLT than the pDDLT group (4.8 [2.9-8.5] months vs. 6.2 [3.0-12.0] months, respectively, p = 0.02). The dropout rate was 32/219 (14.6%) in the pLDLT and 174/632 (27.5%) in the pDDLT group, p <0.001. The 1-, 3- and 5-year intention-to-treat survival rates were 86%, 72% and 68% in the pLDLT vs. 82%, 63% and 57% in the pDDLT group, p = 0.02. Having a potential live donor was a protective factor for death (hazard ratio [HR] 0.67; 95% CI 0.53-0.86). Waiting times of 9-12 months (HR 1.53; 95% CI 1.02-2.31) and ≥12 months (HR 1.69; 95% CI 1.23-2.32) were predictors of death., Conclusion: Having a potential live donor at listing was associated with a significant decrease in the risk of death in patients with HCC in this intention-to-treat analysis. This benefit is related to a lower dropout rate and a shorter waiting period., Lay Summary: Liver transplantation (LT) offers the best chance of survival for patients with hepatocellular carcinoma and can be performed using grafts from deceased donors or live donors. In this work, we aimed to assess the differences in survival after live donor LT when compared to deceased donor LT. We studied 219 patients listed for live donor LT and 632 patients listed for deceased donor LT. Patients who had a potential live donor at the time of listing had a higher survival rate. Therefore, being listed for a live donor LT was a protective factor against death., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Liver resection (LR) and radiofrequency ablation (RFA) are curative-intent therapies for early stages of hepatocellular carcinoma (HCC). If HCC recurs, salvage liver transplant (SLT) may constitute a treatment option., Objective: We aimed to compare the outcomes of patients transplanted for recurrent HCC after curative-intent therapies with those transplanted as initial therapy., Methods: We conducted a matched-control (1:1) cohort study comparing patients with HCC treated with primary liver transplant (PLT) with SLT after HCC recurrence. Matching was performed according to the size and number of viable tumors at explant pathology following liver transplant., Results: Between November 1999 and December 2014, 687 patients with HCC were listed for transplant at our institution. A total of 559 patients were transplanted; 509 patients were treated with PLT and 50 patients were treated with SLT for HCC recurrence after primary treatment with LR (n = 25) or RFA (n = 25). The median length of follow-up from transplant was 64 months (0.5-195), and the median time from curative-intent treatment of HCC with RFA or LR to recurrence was 9.5 months (1-36) and 14.5 months (3-143), respectively (p = 0.04). The matched cohort was composed of 48 SLT patients (23 LR and 25 RFA) and 48 PLT patients. The 5-year risk of recurrence after LT was 22% in the PLT group versus 32% in the SLT group (p = 0.53), while the 5-year actuarial patient survival after PLT was 69% versus 70% in the SLT group (p = 1)., Conclusion: Liver transplant is an effective treatment for patients with HCC recurrence following RFA or LR. Outcomes are similar in both groups.

Whether and when recovery beyond the need for transplant may occur in patients listed for decompensation remains unclear. This study aimed to investigate the characteristics of patients delisted following recompensation. Seventy-seven patients who were listed between 2005 and 2015 for decompensation, but later delisted following recompensation were included. Alcohol-related liver disease (ALD) was the underlying etiology in the majority (n = 47, 61%). Listing characteristics of these patients were compared with those of decompensated ALD patients who either underwent deceased donor liver transplantation or died on the waiting list. The model for end-stage liver disease (MELD) score <20 and serum albumin ≥32 g/l at listing were the only independent predictors of recompensation/delisting in ALD. The probability of recompensation was 70% when both factors were present at listing. Interestingly, about a tenth of decompensated ALD patients who died on the waiting list (median duration on waiting list 11 months) and a quarter of decompensated ALD patients who underwent living donor liver transplantation (median duration on waiting list 2 months) also had both factors at listing. In conclusion, ALD seems to be the most favorable etiology for recompensation beyond the need for transplantation. Both MELD and serum albumin at listing independently predict recompensation/delisting in ALD. It seems advisable to implement a period of observation for ALD patients with both favorable factors, before embarking on living donor liver transplantation., (© 2017 Steunstichting ESOT.)

Background: Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT)., Methods: All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival., Results: Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p = 0.02) and tumor burden (p < 0.001). The majority of those listed underwent LT (n = 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599-15.464; p = 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660-12.768; p = 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (n = 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p = 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%., Conclusion: Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.

Because of a persistent discrepancy between the demand for liver transplantation (LT) and the supply of deceased donor organs, there is an interest in increasing living donation rates at centers trained in this method of transplantation. We examined a large socioeconomically heterogeneous cohort of patients listed for LT to identify recipient factors associated with living donation. We retrospectively reviewed 491 consecutive patients who were listed for LT at our center over a 24-month period. Demographic, medical, and socioeconomic data were extracted from electronic records and compared between those who had a potential living donor (LD) volunteer for assessment and those who did not; 245 patients (50%) had at least 1 potential LD volunteer for assessment. Multivariate logistic regression analysis identified that patients with a LD were more likely to have Child-Pugh C disease (odds ratio [OR], 2.44; P = 0.02), and less likely to be older (OR, 0.96; P = 0.002), single (OR, 0.34; P = 0.006), divorced (OR, 0.53; P = 0.03), immigrants (OR, 0.38; P = 0.049), or from the lowest income quintile (OR, 0.44; P = 0.02). In conclusion, this analysis has identified several factors associated with access to living donation. More research is warranted to define and overcome barriers to living donor liver transplantation through targeted interventions in underrepresented populations., (© 2015 American Association for the Study of Liver Diseases.)