Liver Transplantation最新文献

Donation after circulatory death (DCD) has increased hepatic graft supply but is plagued by complications that arise from hypoxic injury. There is a lack of understanding regarding donor physiology during DCD and how this contributes to hepatic dysfunction in transplantation. Herein, we outline the current DCD process and the concept of donor warm ischemic time. We then discuss physiologic mechanisms of hepatic blood flow and oxygenation, and how these are relevant to donor warm ischemic time and DCD. We discuss the pathophysiology of hepatic ischemia-reperfusion injury and relevant insights that can be derived from studies of other hepatic conditions. Lastly, we touch on emerging technologies such as machine perfusion. We hope that our review unites concepts of hepatic physiology with DCD practice and enlightens readers to envision novel areas of study in this field.

Portopulmonary hypertension (POPH), pulmonary arterial hypertension that develops in the setting of portal hypertension, has long been of significant interest to the pulmonary, cardiology, and hepatology communities. Optimal management of POPH has been challenging to define due to a lack of evidence from clinical trials regarding pulmonary arterial hypertension therapies and uncertainty regarding the role of liver transplantation (LT). Initially, the high risk of intraoperative and early post-transplant death in predominantly untreated patients with POPH tempered consideration of LT. More recently, the observation that POPH can improve, and sometimes even resolve, following LT, has led to reconsideration of the role of LT in selected patients. The first International Liver Transplantation Society (ILTS) POPH and hepatopulmonary syndrome practice guideline was a multidisciplinary consensus of expert opinions based on available evidence. Since that publication, hemodynamic definitions, management approaches, and POPH MELD exception criteria have evolved, and there have been new randomized controlled trials in POPH as well as studies regarding long-term outcomes. In order to ensure the guidelines remained current and reflected recent evidence, the original writing committee of the 2016 guidelines, leaders of the ILTS Cardiovascular Special Interest Group, and colleagues active in POPH research were invited to participate in the writing committee. In this document, approved for publication by the ILTS executive council, we provide an update to the prior guidelines with expert recommendations to guide and advance POPH management. Recommendations in these guidelines are based on expert opinion and available evidence and were agreed upon by consensus.

Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of HCC. However, their safety and efficacy in recipients of liver transplants with recurrent HCC remain unclear. This systematic review aims to evaluate the use of ICIs for recurrent HCC after liver transplantation (LT) and to identify potential predictive factors associated with graft rejection and treatment response. A comprehensive literature search was conducted using PubMed and Scopus databases to identify case reports and case series describing the use of ICIs for HCC recurrence after LT. Data on patient characteristics, treatment details, and outcomes were extracted and analyzed. Twenty-one case reports and case series involving 39 patients were included. The median time from LT to ICI initiation was 24 months. Nivolumab was the most commonly used ICI (59.0%). Among all cases, 25.6% demonstrated a positive response, including stable disease and partial or complete response, while 46.2% experienced progressive disease. Graft rejection occurred in 20.5% of patients, with 50% of these cases resulting in death. Although reported in only some of the cases (17 out of 39), positive programmed cell death ligand-1 expression was associated with a higher risk of graft rejection (66.7%) compared to negative expression (0%). calcineurin inhibitors-based immunosuppressive regimens appeared to have lower rejection rates (20%) compared to mammalian target of rapamycin inhibitor-based regimens (80%). ICIs show potential for treating recurrent HCC after LT, but the risk of graft rejection is significant. Careful patient selection, close monitoring, and individualized management of immunosuppression are crucial. Positive programmed cell death ligand-1 expression and the choice of immunosuppressive regimen appear to influence the risk of graft rejection; however, these findings are based on limited data. Prospective studies with larger sample sizes are needed to validate these findings and establish evidence-based guidelines for the use of ICIs in the posttransplant setting.

Malignancy has a crucial impact on long-term survival after liver transplantation. There have been enhanced early detection rates with refined cancer screening and improved prognosis for many cancer diagnoses in the general population with the advent of targeted anticancer therapies. Similar advancements have not occurred in the transplant population over this same timeframe. Individualized strategies to reduce the risk of cancer are needed in this high-risk population. Strict adherence to screening and surveillance specific to the transplant population is required. Lifestyle modifications and medication management (both immunosuppressive and non-immunosuppressive) that may impact cancer risk and outcome are highlighted here. As more effective anticancer therapies evolve, transplant recipients' access to these agents is paramount to truly impact cancer-related outcomes in this population. With adequate immunosuppression, rejection rates with immunotherapy are lower than previously purported. Prospective studies of immunosuppression modifications needed to minimize rejection and maximize cancer response are ongoing and will reduce the fear from oncology and transplant providers alike, allowing utilization of the most optimal therapy available to the individual. This review aims to assess current data to aid in clinical management and identify the need to facilitate further progress in this field.

The decision to initiate renal replacement therapy in patients who are ineligible for liver transplantation can be challenging. Careful patient selection is required to identify those who may benefit from early renal replacement therapy as a pathway toward liver recovery or as a palliative plan of care. Emerging literature suggests that the etiology of kidney injury should play less of a role in clinical decision-making. Decisions around renal replacement therapy are often influenced by medical, ethical, and end-of-life factors and should be made in conjunction with patients and their caregivers.

Over the last few decades, there have been tremendous advances in our understanding of the role of the gut microbiome in cirrhosis and the clinical sequelae that follow. Progressive dysbiosis and immune dysregulation occur in patients with cirrhosis. In fact, alterations in the gut microbiome occur long before a diagnosis of cirrhosis is made. Understandably, our attention has recently been diverted toward potential modulators of the gut microbiome and the gut-liver axis as targets for treatment. The goal of this review is to highlight the utility of manipulating the gut microbiome with a focus on fecal microbiome transplantation (FMT) in patients with cirrhosis. In addition, we will provide an overview of disease-specific microbial alterations and the resultant impact this has on cirrhosis-related complications.

Portal vein thrombosis (PVT) is a frequent event among patients with advanced liver disease, with a prevalence reaching up to 26% in those awaiting liver transplantation (LT). Extensive thrombosis affecting the mesenteric vein confluence correlates with increased morbidity and mortality post-LT, particularly when it impedes physiological anastomosis or contraindicates the LT. Current guidelines advocate for routine PVT screening in all potential liver transplant candidates and prompt treatment upon detection. The main objective of candidates for LT is to facilitate physiological portal-to-portal anastomosis. Anticoagulation serves as the first-line therapy, achieving recanalization rates between 33% and 75%. Discontinuation of anticoagulation significantly heightens the risk of rethrombosis in a substantial proportion of patients; therefore, it is recommended to continue anticoagulation until LT for those awaiting LT or potential candidates for LT. Nevertheless, 30%-60% of patients fail to respond to anticoagulation, with PVT progression occurring in up to 14% despite anticoagulation. In such cases, TIPS placement emerges as a viable alternative to maintain portal vein patency. While the feasibility of TIPS placement diminished with the presence of portal cavernoma or chronic PVT, the introduction of novel interventional radiological techniques to recanalize the portal venous axis through transplenic, transmesenteric, and/or transhepatic routes is revolutionizing this landscape. These advancements achieve TIPS placement and recanalization in 90%-100% of patients, warranting consideration in patients with cirrhosis with chronic PVT for whom LT would otherwise be contraindicated or when physiological anastomosis is not feasible.

Early liver transplant (ELT) is the practice of liver transplant for those with severe alcohol-associated hepatitis or acute on chronic alcohol-associated liver disease, without requiring any minimum pre-transplant abstinence period. It is an increasingly adopted practice for alcohol-associated liver disease (ALD) capable of providing excellent outcomes, but there are concerns regarding equity in access to ELT. Our objectives were (1) to quantify the association between social determinants of health (SDoH) and progression from referral to listing, and (2) to identify geographic disparities in referrals for ELT. We included 501 ELT candidates and a comparison population of 165 standard liver transplantation (SLT) candidates referred from 2017 to 2023. Multivariable regression quantified the association between individual-level and neighborhood-level SDoH and progression from referral to listing, adjusting for sociodemographic characteristics and MELD. Negative binomial regression quantified the association between neighborhood-level SDoH and the number of ELT referrals within 150 Nmi of our institution, adjusting for relevant geographic confounders. ELT candidates with Medicaid insurance were less likely to progress from referral to evaluation than candidates with private insurance (RR 0.69, 95% CI 0.56-0.85). ELT candidates from census tracts with a high Social Vulnerability Index (SVI) were less likely to progress from evaluation to listing than candidates from low SVI census tracts in Modified Poisson Regression (RR 0.64, 95% CI 0.46-0.88), but not in Cox regression (HR 0.67, 95% CI 0.41-1.09). These findings were not significant among SLT candidates. High SVI census tracts were less likely to have individuals referred for ALD compared to tracts with low SVI (incidence rate ratio [IRR] 0.53, 95% CI 0.42-0.66). Both individual-level and neighborhood-level SDoH are important factors that ultimately influence who is eligible for transplant.

Cardiovascular (CV) disease is a leading cause of postoperative mortality following liver transplantation (LT). The presence of abdominal aortic calcification (AAC) has been linked to CV events in the general population. We sought to investigate whether AAC on routine pre-transplant CT can improve the prediction of coronary artery disease, post-LT major adverse cardiovascular events (MACEs) or long-term mortality. Of 461 patients undergoing LT between 2010 and 2018, 318 were included in the analysis, among whom 81 had also undergone computed tomography coronary angiography. The extent of AAC was quantified with high AAC defined as a calcium score ≥500. High AAC was identified in 84/318 (26.4%) and demonstrated moderate correlation with coronary artery calcium score (CACS) ( r =0.52, p <0.001). Thirty-two MACE events occurred in 28 patients (8.8%) within 30 days. High AAC was a strong independent predictor of moderate-to-severe coronary disease on CT coronary angiography (OR 12.6, 95% CI 1.5-103.0, p =0.02). It was also associated with a significantly increased risk of 30-day MACE (OR 2.34, 95% CI 1.08-5.05, p =0.03) and long-term mortality (HR 2.45, 95% CI 1.18-5.06, p =0.02). Following multivariate analysis adjusting for pertinent CV risk factors, high AAC remained a strong independent predictor of MACE (OR 3.10, 95% CI 1.27-7.60, p =0.02). Addition of AAC to the Revised Cardiac Risk Index significantly improved model fit for predicting MACE outcomes ( p <0.01), while the absence of heavy AAC ruled out moderate-to-severe disease on CT coronary angiography with a negative predictive value of 97.0%. High AAC on routine CT scans was associated with a 3-fold increased risk of 30-day MACE post-LT and improved CV risk prediction compared to traditional indices. Quantification of AAC may offer a simple method of improving CV risk assessment in these patients.