Liver Transplantation最新文献

Cirrhosis constitutes a significant global health burden with decompensation characterized by ascites, hepatic encephalopathy, as well as variceal hemorrhage. These decompensation features are independent predictors of mortality. Liver transplantation remains the definitive treatment for patients with cirrhosis. However, given that this is a limited resource, thus its allocation, using the MELD score, has to be judicious despite decompensation features affecting the patient's quality of life. Patients with grade 3 ascites or overt hepatic encephalopathy have significant mortality; therefore, in some instances, these decompensation features should be considered indications for liver transplantation despite low MELD. The majority of patients listed for liver transplantation have low MELD scores (≤15 points); and approximately half will die due to liver-related complications. Current evidence demonstrates a mortality reduction of ~40% with LT in those patients with a low MELD. Furthermore, new scores have been developed, such as the MELD 3.0, which incorporates female sex, albumin, and all the MELD-Na components (bilirubin, creatinine, international normalized ratio, and sodium), and the Gender-Equity Model for Liver Allocation, that includes bilirubin, international normalized ratio, and the Royal Free Hospital glomerular filtration rate, which have demonstrated improved discrimination. Lastly, to address the limited resource, living donor liver transplant has demonstrated a significant survival benefit in patients even at MELD-Na scores as low as 11, suggesting that life-years gained are similar to deceased-donor transplant. In this review, our goal is to present the frequency of patients listed for transplant with low MELD, and the limitation of using MELD in patients for liver transplantation. We will provide practical guidance on the management of common complications of cirrhosis and early consideration for liver transplant referral in patients with clinical decompensation and low MELD.

Donor safety is of paramount importance in live donor hepatectomy, and acute pain is the most frequent complaint reported by donors. There are various approaches to managing perioperative and postoperative pain following live donor hepatectomy. These include the administration of opioid and nonopioid analgesics and neuraxial, regional, and local anesthesia. However, there is limited data on the practice patterns of pain management for live donor hepatectomy, particularly when comparing left and right lobe hepatectomies. A national electronic survey was administered to active living donor liver transplant centers in the United States, identified via the Organ Procurement and Transplantation Network directory. The survey focused on demographics, perioperative and postoperative pain management strategies, and differences in pain management practices based on left versus right lobe hepatectomies and surgical approach. We received responses from 37 centers (86%). The majority of centers (67.6%) performed both right and left live donor hepatectomies. Most centers had protocolized perioperative (78.4%) and postoperative (83.8%) pain management guidelines. Perioperatively, most centers utilized a multimodal approach, based on intravenous fentanyl and/or hydromorphone combined with nonopioid adjuncts. Acetaminophen was the most common postoperative analgesic for both right (75.7%) and left (80%) lobe donors. Transversus abdominis plane blocks were the most frequently used regional anesthesia technique for both right (43.2%) and left (48%) lobe donors. Epidural catheters were placed more frequently in left (40%) than in right (32.4%) lobe donors. We observed a significant variation in perioperative and postoperative pain management strategies after live donor hepatectomy between centers. Some centers adapt analgesic techniques based on the surgical technique (eg, open vs. laparoscopic/robotic, and right vs. left lobe hepatectomy).

Refractory ascites often requires therapeutic paracentesis, which is associated with potential risks and diminished quality of life. Terlipressin is a vasopressin analog that is indicated for i.v. bolus injection for hepatorenal syndrome, with the potential to reduce large-volume ascites and its complications. Continuous infusion of terlipressin is associated with fewer adverse effects than bolus dosing. The efficacy and safety of continuous infusion of a novel liquid formulation of terlipressin acetate (BIV201) were evaluated in this open-label phase 2 study. Patients with cirrhosis and refractory ascites were randomly assigned (2:1) to receive two 28-day cycles of continuous infusion BIV201 plus standard of care (SOC) separated by a ≤56-day washout (n=10), or SOC alone (n=5). Data analysis was limited by the small sample size and confounded by a potential interaction with gabapentinoids in the BIV201+SOC group. Nonetheless, there were differences in favor of BIV201+SOC versus SOC in the coprimary efficacy endpoints and several quality of life assessments. The beneficial effects of BIV201 on liver complications (mean: 90% CI; BIV201-completers=2.87: 1.51; 5.46 vs. SOC=2.38: 1.20; 4.73) and the change in cumulative ascites (mean: 90% CI; BIV201-completers=-10.76: -26.51; 5.00 vs. SOC=-4.99: -21.95; 11.97) were more pronounced versus SOC in the 5 BIV201+SOC patients who completed both treatment cycles. There were also greater improvements in exploratory quality of life assessments and the percent change in therapeutic paracenteses with BIV201+SOC (-27.94±41.80) versus SOC (-16.67±45.64). Despite the high rate of hyponatremia in the BIV201+SOC group (4/10 patients), the safety profile suggested that continuous BIV201 infusion was well tolerated. These findings support further development of BIV201 in confirmatory trials.

Increases in deaths from drug intoxication in the United States could be contributing to more liver donations. This study investigates regional variation in liver donation following death by drug intoxication over a decade. The number of drug intoxication-related deaths in the continental United States (2011-2020) was collected from CDC WONDER. Reports from UNOS provided the number of liver donors who died of drug intoxication over the decade. County-level ratios of liver donors after drug intoxication to the total number of drug intoxication-related deaths were calculated. Missed donation opportunities were quantified by comparing the actual number of donors to the hypothetical number if all counties achieved the efficiency of counties in the 90th and 50th percentiles. Regression analysis was used to assess the relationship between missed opportunities for liver donation per drug intoxication-related death and county-level variables. County-level proportions of liver donors after drug intoxication to all eligible drug intoxications ranged from 0 to 0.600. If every county matched the efficiency of the 90th and 50th percentile county, the liver donor pool could grow by 7572 or 1550 donors over the decade, respectively. The national rate of missed opportunities for a liver donation per death by drug intoxication was 0.114 or 0.022, depending on whether the 90th or 50th percentile donation ratio was used in the calculation. The number of missed donations per drug intoxication increased with higher social vulnerability, distance from a trauma center, and rural county status. Conversely, it decreased as the rate of deaths by drug intoxication rose. Assessing liver donation following drug intoxication allows for targeted efforts to increase donations in regions with the greatest potential for improvement.

In living donor liver transplant, graft hyperperfusion can lead to early allograft dysfunction, graft loss, and even mortality. Portal inflow modulation is advocated to prevent hyperperfusion injury. We implemented intraoperative distal splenic artery ligation (SAL) since January 2021 in recipients with one or more of the indications: graft to recipient weight ratio <0.8, graft to spleen volume ratio ≤1, high post-reperfusion portal venous flow (≥250 mL/min/100 g of graft weight), low hepatic artery peak systolic velocity (≤20 cm/s), and/or high post-reperfusion portal venous pressure (≥15 mm Hg). This group was compared with a retrospective splenic artery ligation-not done (non-SAL) group, during July 2019-December 2020, who met any one or more of the above criteria, but had not undergone SAL. Out of 426 patients who underwent living donor liver transplant during the study period, 90 and 42 right lobe adult recipients were included in the SAL and non-SAL groups, respectively. The SAL group had a significant reduction in post-reperfusion portal flow and pressure and also improved hepatic arterial peak systolic velocity compared to the non-SAL group ( p <0.01). Significant reduction in serum total bilirubin and ascitic fluid was observed on post-operative days 1, 3, 5, 7, and 14 in the SAL group ( p <0.01). There was a significant reduction in the incidence of early allograft dysfunction in the SAL group compared to the non-SAL group (8.8% vs. 26.2%, p <0.01). There was a decreased incidence of small for size syndrome (SFSS) ( p <0.05) with no incidence of grade-C SFSS and lower 90-day mortality in the SAL group ( p <0.01). Intraoperative distal SAL significantly reduces portal hyperperfusion, thereby reducing early allograft dysfunction, small for size syndrome, morbidity, and improving 1-year survival.