Long-term outcome following liver transplantation of patients with ACLF grade 3.

BACKGROUND & AIMS: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included in a three-centre retrospective French study published in 2017. METHOD: All patients with ACLF-3 (n = 73), as well as their transplanted matched controls with ACLF-2 (n = 145), 1 (n = 119) and no ACLF (n = 292), who participated in the Princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survival rates, causes of death and their predictive factors. RESULTS: Median follow-up of patients with ACLF-3 was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patient survival rates were 72.6% vs. 69.7% vs. 76.4% vs. 77.0%, respectively (p = 0.31). Ten-year patient survival for ACLF-3 was 56.8% and was not different to other groups (p = 0.37). Leading causes of death in patients with ACLF-3 were infections (33.3%) and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and CLIF-C ACLF score were independently associated with 10-year patient survival. Long-term graft survival rates were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years. CONCLUSION: 5- and 10-year patient and graft survival rates were not different in patients with ACLF-3 compared to matched controls. 5-year patient survival is higher than the 50%-70% threshold defining the utility of a liver graft. Efforts should focus on candidate selection based on comorbidities, as well as the prevention of infection and cardiovascular events. IMPACT AND IMPLICATIONS: While short-term outcomes following liver transplantation in the most severely ill patients with cirrhosis (acute-on-chronic liver failure grade 3 [ACLF-3]) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favourable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in patients with ACLF-3 compared to matched patients with ACLF-2, ACLF-1, and no-ACLF. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidity evaluation, such as the age-adjusted Charlson comorbidity index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding whether to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and tightly managing cardiovascular risk over time.

99mTc-mebrofenin hepatobiliary scintigraphy and volume metrics before liver preparation: correlations and discrepancies in non-cirrhotic patients.

BACKGROUND: Accurate identification of insufficient future liver remnant (FLR) is required to select patients for liver preparation and limit the risk of post-hepatectomy liver failure (PHLF). The objective of this study was to investigate the correlations and discrepancies between the most-commonly used FLR volume metrics and 99mTc-mebrofenin hepatobiliary scintigraphy (HBS). METHODS: In 101 non-cirrhotic patients who underwent HBS before major hepatectomy, we retrospectively analyzed the correlations and discrepancies between FLR function and FLR volume metrics: actual percentage (FLRV%), standardized to body surface area (FLRV%BSA) and weight (FLRV%weight), and FLR to body weight ratio (FLRV-BWR). RESULTS: Among 67 patients with FLR function ≥2.69%/min/m2, PHLF was observed in none and 13 patients according to respectively 50-50 and ISGLS criteria. FLRV%, FLRV%BSA, FLRV%weight and FLRV-BWR significantly correlated with FLR function (P<0.001), with Spearman's correlation coefficients of 0.680, 0.704, 0.698, and 0.711, respectively. No difference was observed between the areas under the curve of FLRV%, FLRV%BSA, FLRV%weight and FLR-BWR (all P=ns). Overall, the percentages of patients misclassified by FLRV%, FLRV%BSA, FLRV%weight (thresholds: 30%) and FLR-BWR (threshold: 0.5) versus FLR function (threshold: 2.69%/min/m2) were 23.8% (95% CI: 15.9-33.3%), 18.8% (95% CI: 11.7-27.8%), 17.8% (95% CI: 11-26.7%), and 31.7% (95% CI: 22.8-41.7%), respectively. FLR volume metrics wrongly classified 1-13.9% of patients with sufficient FLR function (i.e., ≥2.69%/min/m2), and 9.9-30.7% of patients with insufficient FLR function. FLRV-BWR was the most and the least reliable measure to identify patients with sufficient and insufficient FLR function, respectively. CONCLUSIONS: Despite significant correlations, the discrepancy rates between FLR volume and function metrics speaks in favor of implementing 99mTc-mebrofenin HBS in the work-up before liver preparation.

Liver venous deprivation versus portal vein embolization before major hepatectomy: future liver remnant volumetric and functional changes.

BACKGROUND: We previously showed that embolization of portal inflow and hepatic vein (HV) outflow (liver venous deprivation, LVD) promotes future liver remnant (FLR) volume (FLR-V) and function (FLR-F) gain. Here, we compared FLR-V and FLR-F changes after portal vein embolization (PVE) and LVD. METHODS: This study included all patients referred for liver preparation before major hepatectomy over 26 months. Exclusion criteria were: unavailable baseline/follow-up imaging, cirrhosis, Klatskin tumor, two-stage hepatectomy. 99mTc-mebrofenin SPECT-CT was performed at baseline and at day 7, 14 and 21 after PVE or LVD. FLR-V and FLR-F variations were compared using multivariate generalized linear mixed models (joint modelling) with/without missing data imputation. RESULTS: Baseline FLR-F was lower in the LVD (n=29) than PVE group (n=22) (P<0.001). Technical success was 100% in both groups without any major complication. Changes in FLR-V at day 14 and 21 (+14.2% vs. +50%, P=0.002; and +18.6% vs. +52.6%, P=0.001), and in FLR-F at day 7, 14 and 21 (+23.1% vs. +54.3%, P=0.02; +17.6% vs. +56.1%, P=0.006; and +29.8% vs. +63.9%, P<0.001) differed between PVE and LVD group. LVD (P=0.009), age (P=0.027) and baseline FLR-V (P=0.001) independently predicted FLR-V variations, whereas only LVD (P=0.01) predicted FLR-F changes. After missing data handling, LVD remained an independent predictor of FLR-V and FLR-F variations. CONCLUSIONS: LVD is safe and provides greater FLR-V and FLR-F increase than PVE. These results are now evaluated in the HYPERLIV-01 multicenter randomized trial.

Liver transplantation in the most severely ill cirrhotic patients: A multicenter study in acute-on-chronic liver failure grade 3.

BACKGROUND & AIMS: Liver transplantation (LT) for the most severely ill patients with cirrhosis, with multiple organ dysfunction (accurately assessed by the acute-on-chronic liver failure [ACLF] classification) remains controversial. We aimed to report the results of LT in patients with ACLF grade 3 and to compare these patients to non-transplanted patients with cirrhosis and multiple organ dysfunction as well as to patients transplanted with lower ACLF grade. METHODS: All patients with ACLF-3 transplanted in three liver intensive care units (ICUs) were retrospectively included. Each patient with ACLF-3 was matched to a) non-transplanted patients hospitalized in the ICU with multiple organ dysfunction, or b) control patients transplanted with each of the lower ACLF grades (three groups). RESULTS: Seventy-three patients were included. These severely ill patients were transplanted following management to stabilize their condition with a median of nine days after admission (progression of mean organ failure from 4.03 to 3.67, p=0.009). One-year survival of transplanted patients with ACLF-3 was higher than that of non-transplanted controls: 83.9 vs. 7.9%, p<0.0001. This high survival rate was not different from that of matched control patients with no ACLF (90%), ACLF-1 (82.3%) or ACLF-2 (86.2%). However, a higher rate of complications was observed (100 vs. 51.2 vs. 76.5 vs. 74.3%, respectively), with a longer hospital stay. The notion of a "transplantation window" is discussed. CONCLUSIONS: LT strongly influences the survival of patients with cirrhosis and ACLF-3 with a 1-year survival similar to that of patients with a lower grade of ACLF. A rapid decision-making process is needed because of the short "transplantation window" suggesting that patients with ACLF-3 should be rapidly referred to a specific liver ICU. Lay summary: Liver transplantation improves survival of patients with very severe cirrhosis. These patients must be carefully monitored and managed in a specialized unit. The decision to transplant a patient must be quick to avoid a high risk of mortality.