Patients with hepatocellular carcinoma (HCC) within the University of California, San Francisco down-staging (UCSF-DS) criteria (one lesion > 5 cm and ≤ 8 cm; two to three lesions each ≤ 5 cm; or four to five lesions each ≤ 3 cm with total tumor diameter ≤ 8 cm) who achieved successful down-staging (DS) to Milan criteria had similar outcomes after liver transplantation (LT) compared with HCC initially meeting the Milan criteria. Nevertheless, little is known about the outcome of DS in patients with initial tumor burden exceeding the UCSF-DS criteria, defined as "all-comers" (AC). We compared the intention-to-treat (ITT) outcomes of DS in 74 patients in the AC group and 133 patients in the UCSF-DS group. Successful DS to Milan was observed in 64.8% of the AC group versus 84.2% of the UCSF-DS group (P < 0.001). The sum of tumor number and largest tumor diameter was significantly associated with successful DS (hazard ratio [HR] 0.87, P < 0.05). The cumulative probability of dropout within 1 year and 3 years was 53.5% and 80.0%, respectively, for AC versus 25.0% and 36.1%, respectively, for UCSF-DS (P < 0.0001). Factors predicting dropout included sum of tumor number and largest tumor diameter greater than 8 (HR 1.79, P = 0.049) and Child class B and C (HR 2.54, P = 0.001). The AC group also had a significantly lower liver transplant (LT) rate (13.5% versus 59.0%, P < 0.001). ITT survival at 1 year and 5 years was 77.4% and 21.1%, respectively, in AC versus 85.5% and 56.0%, respectively, in UCSF-DS (P < 0.001). Three of 10 patients in the AC group who underwent LT developed HCC recurrence. Conclusion: We observed a significantly lower LT probability and inferior ITT survival with DS in the AC group versus the UCSF-DS group. Our results suggest that an upper limit in tumor burden exists beyond which successful LT after DS becomes an unrealistic goal. (Hepatology 2019;70:1185-1196). F or over two decades, the Milan criteria have been the gold standard for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). (1) Use of these restrictive criteria has ensured a low rate of HCC recurrence and an acceptable post-LT survival. (1-3) Nevertheless, with the rising incidence of HCC in the United States and the high mortality associated with the diagnosis, (4,5) the demand of LT as a potentially curative treatment for HCC has also increased. Multiple studies have proposed the use of local-regional therapy (LRT) for down-staging (DS) of HCC initially exceeding the

Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m 2 or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51-64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol-related liver disease; 68% developed ≥ stage 3 CKD at the end of follow-up. The 1-year, 3-year, and 5-year incidence rates of post-SLKT stage 4-5 CKD were 10%, 12%, and 16%, respectively. Pre-SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00-2.15), NASH (HR, 1.58; 95% CI, 1.01-2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10-2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22-0.89) reduced the risk. Women (β = −6.22 ± 2.16 mL/minute/1.73 m 2 ; P = 0.004), NASH (β = −7.27 ± 3.27 mL/ minute/1.73 m 2 ; P = 0.027), and delayed kidney graft function (β = −7.25 ± 2.26 mL/minute/1.73 m 2 ; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow-up. Stage 4-5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients.

The burden of early hospitalization (within 6 months) following simultaneous liver-kidney transplant (SLKT) is not known. We examined risk factors associated with early hospitalization after SLKT and their impact on patient mortality conditional on 6-month survival. We used data from the US Multicenter SLKT Consortium cohort study of all adult SLKT recipients between 2002 and 2017 who were discharged alive following SLKT. We used Poisson regression to model rates of early hospitalizations after SLKT. Cox regression was used to identify risk factors associated with mortality conditional on survival at 6 months after SLKT. Median age (N = 549) was 57.7 years (interquartile range [IQR], 50.6-63.9) with 63% males and 76% Whites; 33% had hepatitis C virus, 20% had non-alcohol-associated fatty liver disease, 23% alcoholassociated liver disease, and 24% other etiologies. Median body mass index (BMI) and Model for End-Stage Liver Disease-sodium scores were 27.2 kg/ m 2 (IQR, 23.6-32.2 kg/m 2 ) and 28 (IQR, 23-34), respectively. Two-thirds of the cohort had at least one hospitalization within the first 6 months of SLKT.Age, race, hospitalization at SLKT, diabetes mellitus, BMI, and discharge to subacute rehabilitation (SAR) facility after SLKT were independently associated with a high incidence rate ratio of early hospitalization. Number of hospitalizations within the first 6 months did not affect conditional survival. Early hospitalizations after SLKT were very common but did not affect conditional

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Background. Length of stay (LOS) during index solid organ transplant impacts morbidity and healthcare costs. To date, there are no studies evaluating characteristics and outcomes of simultaneous liver-kidney transplant (SLKT) index hospitalization. We examined factors associated with LOS and mortality during index SLKT admission. Methods. Adult SLKT recipients between 2002 and 2017 at 6 transplant centers across 6 UNOS regions were retrospectively enrolled in the US-Multicenter SLKT Consortium. Multivariable regression analyses assessed predictors of SLKT LOS and death during index admission. Results. Median age of cohort (N = 570) was 58 y (interquartile range: 51–64); 63% male, 75% White, 32.3% hepatitis C, 23.3% alcohol-related, 20.1% nonalcoholic steatohepatitis with median MELD-Na at SLKT 28 (23–34). Seventy-one percent were hospitalized at the time of SLKT with median LOS pretransplant of 10 d. Majority of patients were discharged alive (N = 549; 96%)‚ and 36% were discharged to subacute rehab facility. LOS for index SLKT was 19 d (Q1: 10, Q3: 34 d). Female sex ( P = 0.003), Black race ( P = 0.02), advanced age ( P = 0.007), ICU admission at time of SLKT ( P = 0.03), high MELD-Na ( P = 0.003), on cyclosporine during index hospitalization ( P = 0.03), pre-SLKT dialysis ( P < 0.001), and kidney delayed graft function ( P < 0.001) were the recipient factors associated with prolonged LOS during index SLKT hospitalization. Prolonged LOS also contributed to overall mortality (HR = 1.007; P = 0.03). Conclusions. Despite excellent survival, index SLKT admission was associated with high-resource utilization with more than half the patients with LOS >2 wk and affected overall patient survival. Further investigation is needed to optimize healthcare resources for these patients in a financially strained healthcare landscape.