Journal of Liver Transplantation最新文献

Antibody-mediated rejection (AMR) following liver transplantation is a significant clinical challenge, with donor-specific antibodies (DSAs) playing a pivotal role. Understanding the mechanisms and impact of DSAs is crucial for improving transplant outcomes and patient care. This review provides an in-depth analysis of the pathogenesis, diagnosis, and management of AMR in liver transplantation, focusing on the role of DSAs. AMR in liver transplants, though less common than in other organ transplants, presents unique diagnostic and therapeutic challenges. The review explores the latest diagnostic criteria, including serum DSAs, C4d staining, and liver biopsy findings. It delves into the pathogenesis of AMR, emphasizing the role of both preformed and de novo DSAs in causing graft injury and rejection. The review also discusses current therapeutic strategies, such as the use of immunosuppressants, plasmapheresis, intravenous immunoglobulin, and proteasome inhibitors, highlighting their efficacy and limitations. Furthermore, it examines the unique aspects of liver immunology that contribute to the organ's relative resistance to DSA-mediated injury. Emerging research, particularly on gene expression changes in renal allografts during simultaneous liver-kidney transplantation, is also discussed, offering insights into future directions. This review is instrumental for clinicians and researchers in understanding the complexities of AMR in liver transplantation and in developing more effective management strategies.

Introduction

Non-alcoholic steatohepatitis (NASH) is a rising cause of liver transplantation and is linked to higher rates of cardiovascular complications. The aim of this study was to evaluate the risk of post-transplant cardiac events in patients with NASH that were exposed to sirolimus (SRL) vs. calcineurin-inhibitor (CNI) immunosuppression.

Methods

We retrospectively reviewed all adult liver transplant recipients at our institution between 2002 and 2020. Subjects were grouped based on immunosuppressive regimen. We also analyzed the subgroup of patients with NASH as the primary indication for transplant, as well as a non-NASH subpopulation. The primary outcome measure was risk of major adverse cardiovascular events (MACE) post-transplant. Comparisons between groups were conducted with chi-squared tests. Univariate Cox regression and multivariate time-dependent Cox regression models were used to analyze the relationship between immunosuppression and MACE risk.

Results

803 liver transplant patients met criteria for study inclusion. Of these, 169 patients had NASH as their primary indication for liver transplant. 18 % of the study population received SRL immunosuppression post-transplant, and the remainder received only CNI immunosuppression. Post-transplant MACE occurred in 32.65 % of patients on SRL compared to 10.27 % in patients on CNI immunosuppression (p =< 0.001). Without taking development of post-transplant CKD into account, our study showed a significantly higher risk of MACE with SRL immunosuppression in both the non-NASH cohort (HR 1.67, p = 0.036) and the NASH cohort (HR 2.48, p = 0.037. However, when accounting for post-transplant CKD, our analysis of the Non-NASH and NASH cohorts did not show a significantly greater risk of post-transplant MACE with SRL compared to CNI immunosuppression.

Conclusions

Our analysis shows that in both the NASH and non-NASH cohorts, liver transplant patients on sirolimus did not have a significantly higher risk of developing cardiovascular disease after transplant compared to immunosuppression with calcineurin inhibitors.

Thrombocytopenia in transplant period is nearly universal. Platelets are believed to have a significant role in the regeneration of hepatocytes and persistent thrombocytopenia can affect the graft function adversely. This current review discusses, in brief, the aetiology, implications, evaluation, and management of thrombocytopenia in post liver transplant period.

Background

While younger donors have better liver transplant (LT) outcomes, the median age of both the donor and recipient pools is rising. The impact of using donors ≥50 years on the LT outcomes of septuagenarians is unknown.

Methods

From 2011–2021, outcomes in septuagenarian LT recipients from donor livers <50 year-old (DON<50) and donor livers ≥50 year-old (DON≥50) were analyzed using the United Network for Organ Sharing database. Post-LT survival analysis was performed with the Kaplan-Meier method and multivariable Cox proportional-hazards model. A propensity score was utilized to conduct one-to-one matching using 14 recipient variables (1230-pairs).

Results

There were 2797 septuagenarian deceased-donor LT recipients during the study period. Of these, 1487 (53.2 %) were DON <50 with median age of 34 years and 1310 (46.8 %) were DON ≥50 with median age of 60 years. The number of LT for septuagenarians has increased over the last decade. The causes of donor and recipient deaths were different between two groups. Post-LT one-year survival (DON<50: 89.3 % vs. DON≥50: 88.3 %) and five-year survival (DON<50: 41.4 % vs DON≥50: 42.8 %) were comparable. Multivariable Cox proportional-hazards model showed that donor age ≥50 years is not associated with increased mortality after LT in the matched cohort (HR: 1.04, 95 % CI: 0.88–1.24, P = 0.63).

Conclusions

The utilization of carefully selected donor livers older than 50 years may be a viable option for septuagenarian LT candidates by lowering their waitlist time and can maximize the organ utilization without compromising the outcomes.

Solid organ transplant recipients (SOTRs) remain at high risk of progression to severe disease and hospitalization from Coronavirus disease 2019 (COVID-19). Regardless of vaccination status, burden of severe COVID-19 among SOTRs remains high and treatment of COVID-19 remains the main mitigating factor in preventing its progression. Oral antiviral therapies offer a convenient outpatient treatment option for mild-moderate COVID-19, and when used early may decrease the risk of progression of disease. Oral anti-viral therapies retain activity against all the currently known viral variants. Early diagnosis with prompt treatment and monitoring for drug-drug interactions is the key to optimal use of oral antiviral agents for COVID-19. Despite the promise to decrease morbidity and mortality from COVID-19, utilization of these medications among SOTRs remains low with existence of many barriers in their use.