Performance of pre-transplant criteria in prediction of hepatocellular carcinoma progression and waitlist dropout.

BACKGROUND & AIM: Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout because of tumour progression. The aim of this study was to compare the alpha-foetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. METHODS: A multicentre cohort study was conducted in 20 Latin American transplant centres, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumour characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics. RESULTS: HCC dropout rate was significantly higher in patients beyond (24% [95% CI 16-28]) compared to those within Milan criteria (8% [95% IC 5%-12%]; p < .0001), with a SHR of 3.01 [95% CI 2.03-4.47]), adjusted for waiting list time and bridging therapies (c-index 0.63 [95% CI 0.57; 0.69). HCC dropout rates were higher in patients with AFP scores >2 (adjusted SHR of 3.17 [CI 2.13-4.71]), c-index of 0.71 (95% CI 0.65-0.77; p = .09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout (SHR 1.68 [95% CI 1.08-2.61]). CONCLUSIONS: Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.

Liver transplantation for hepatocellular carcinoma: impact of expansion criteria in a multicenter cohort study from a high waitlist mortality region.

This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).

Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort.

BACKGROUND & AIM: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.

Direct-Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait-List Progression or Posttransplant Recurrence.

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre- or post-LT DAA effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alpha-fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre- or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT.

Evaluación de los resultados del trasplante hepático con hígados que nadie quiere / Result evaluation of liver transplantation with livers that nobody wants

INTRODUCCIÓN: La escasez de donantes para suplir la demanda de trasplantes es un problema Mundial. "Hígados que nadie quiere" (HNQ) define injertos que fueron rechazados numerosas veces por varios centros antes de su aceptación. OBJETIVO: evaluar los resultados en la utilización de "HNQ" en nuestro centro. Fuente de datos CRESI-SINTRA y una base prospectiva, Periodo 2013-2016. MÉTODOS: Estudio retrospectivo, dos grupos pre-determinados: 1. Pacientes que recibieron un órgano más allá del percentilo 75 de mediana de rechazos 2. Resto de los receptores. RESULTADOS: Se realizaron 1325 trasplantes a nivel nacional, con una mediana de rechazos previos al implante de 5 (IQR3-11). 153 fueron realizados en el HEC y la mediana de rechazos fue de 7 (IQR3-18); 55/36% de esos injertos mas allá de p75, ninguno fue usado para falla fulminante. Comparando 1 vs 2 (55 vs 72), no hubo diferencias estadísticamente significativas en la edad (51 años IQR45-60 vs 50 años IQR39-59 p=0.53), incidencia de falla primaria del injerto (RR 0.65 IC95%0.33-1.32 p=0.19), extubacion temprana (RR 1.16 IC95%0.43-3.16p=0.78),o diálisis (RR 1.36 IC95%0.84-2.21 p=0.26); tampoco en la duración de estadía en UTI (4 días IQR3-6 vs 5 días IQR 3-9 p=0.12) u hospitalaria (8 días IQR 6-14 vs 1.5 días IQR 8-17.5 p=0.06), sobrevida del injerto (p=0.51) y del paciente (p=0.59). El MELD del receptor fue la única diferencia (24 IQR22-25 vs 28 IQR25-33 p<0.05: Un tercio de la población de nuestro centro recibió "HNQ" (injertos rechazados previamente 12 veces), con similares resultados. Futuras investigaciones deberían determinar la causa de esos rechazos.

INTRODUCTION: Donor scarcity to supply the demand for transplants is a global problem. "Livers that nobody wants" (LNW) are those grafts that were refused by several centers multiple times before being accepted. OBJECTIVE: to evaluate the results in the use of "LNW" in our center. Data source: CRESI-SINTRA and a prospective database, period 2013-2016. METHODS: Retrospective study in two predetermined groups: 1. Patients who received an organ beyond the 75th percentile of median rejections 2. The rest of recipients. RESULTS: At national level, 1325 transplantations were made, its median refusals prior to implantation being 5 (IQR3-11), of which 153 were made in the HEC and the median refusals were 7 (IQR3-18); out of 55/36% of these grafts beyond the 75th p, none were used in fulminant hepatic failure. In comparing 1 vs 2 groups (55 vs 72), there were no statistically significant differences in age (51 years IQR45-60 vs 50 years IQR39-59 p=0.53), incidence ofdraft primary failure (RR 0.65 IC95%0.33-1.32 p=0.19), early extubation (RR 1.16 IC95%0.43- 3.16p=0.78),or dialysis requirement (RR 1.36 IC95%0.84-2.21 p=0.26); there were no differences either in the ICU stay (4 days IQR3-6 vs 5 days IQR 3-9 p=0.12) or in hospital stay(8 days IQR 6-14 vs 1.5 days IQR 8-17.5 p=0.06), draft survival (p=0.51) and patient survival (p=0.59). The only difference was in the MELD score of the receptor (24 IQR22-25 vs 28 IQR25-33 p<0.05:). A third of the population in our center received LNW (drafts previously refused 12 times) and showed similar results. The cause of these refusals should be determined by future research.