Interplay of Donor-Recipient Relationship and Donor Race in Living Liver Donation in the United States.

INTRODUCTION: Living liver donation improves survival of end-stage liver disease (ESLD) patients. Yet, it continues to represent a small proportion of United States (U.S.) liver transplantation with existing racial disparities. We investigated the interplay of donor-recipient relationship and donor race to understand donor subgroups with no significant increase. METHODS: We studied 4407 living liver donors in the U.S. from January 1, 2012, to December 31, 2022 (median age = 36 years, and 59% were biologically related to the recipient). We quantified the change in the number of donors per 3-year increment using negative binomial regression (incidence rate ratio [IRR]), stratified by donor-recipient relationship and race/ethnicity. RESULTS: Among biologically related donors, the observed annual number of White donors increased from 146 to 253, Hispanic donors from 18 to 53, and Black donors decreased from 11 to 10. Among unrelated donors, White donors increased from 65 to 221, Hispanic donors from 4 to 25, and Black donors from 3 to 11. For the IRR of biologically related donors aged <40 and ≥40 years, White donors increased by 18% and 22%; Hispanic donors increased by 25% and 54%; and Black donors did not change. Likewise, the IRR of unrelated donors aged <40 and ≥40 years, White donors increased by 48% and 55%; Hispanic donors increased by 52% and 65%; and Black donors did not change. CONCLUSIONS: While biologically related donors represent the majority of donors, unrelated donors have substantially risen in recent years, primarily driven by White donors. Although the rate of unrelated donations increased among Hispanic donors, the absolute number remains very small (≤25 donors/year). Interventions are needed to increase education among Hispanic and Black communities to grow unrelated living liver donations across race/ethnicity.

Recipient Survival among Living Donor vs. Deceased Donor Liver Transplants for Acute Liver Failure in the United States.

Objectives: Acute liver failure (ALF) is associated with high morbidity and mortality. Timely liver transplantation (LT) is the only universally accepted therapy for ALF that is non-responsive to medical therapy. Data regarding the use of living donor LT (LDLT) for this indication in the US is scarce. Materials and Methods: United Network of Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) data from January 2002 to December 2020 were reviewed. Adult and pediatric recipients listed as status 1 were included. Demographics, clinical and laboratory data, and post-LT survival rates were compared for LDLT vs. DDLT recipients. Results: There were 180 LDLT (3.6%) and 4779 DDLT (96.4%) recipients with a diagnosis of ALF. The majority of recipients in the LDLT group were pediatric (n = 164, 91%) compared to the DDLT group (n = 1455, 30%), p < 0.001. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients (p = 0.15). Five-year post-LT survival was higher for pediatric recipients compared to adults in the LDLT group (84.2% vs. 62.5%, respectively, p < 0.001) and the DDLT group (82.8% vs. 78.7%, respectively, p < 0.001). Adults had a higher hazard of death compared to pediatric recipients in the LDLT group (HR = 3.560, 95% CI 1.612-7.844, p = 0.002) and the DDLT group (HR = 1.472, 95% CI 1.290-1.679, p < 0.001). In multivariate analysis results, the type of LT and age group were not associated with higher post-LT mortality. Conclusions: In the US, LDLT constitutes 3.6% of LTs for ALF. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients. Overall, there were superior post-LT outcomes for pediatric recipients compared to adults for LDLT and DDLT.

Factors Associated With Serial Lipase Measurement in Hospitalized Patients With Acute Pancreatitis.

OBJECTIVES: To determine the factors associated with serial lipase measurement in patients with acute pancreatitis (AP). METHODS: Patients admitted to Johns Hopkins Health System between September 2019 and August 2020 with lipase ≥3 times upper limit normal were prospectively identified. Acute pancreatitis was defined using revised Atlanta criteria. Serial lipase measurement was defined as >2 lipase measurements on consecutive days within 7 days of presentation. RESULTS: There were 294 patients with AP with mean age 52.4 ± 16 years (SD), and 155 (52.7%) were male. A total of 227 (77.2%) were admitted to a medical service. There were 111 (37.7%) who underwent serial lipase measurements. There were 89 (30.8%), 36 (12.2%), 6 (1%), and 40 (13.6%) patients with systemic inflammatory response syndrome at time of initial lipase measurement, persistent organ failure, necrosis on admission, and intensive care unit admission. Serial lipase measurements were more likely to be obtained in patients admitted to surgical services (odds ratio, 4.3; 95% confidence interval, 1.4-13.2; P = 0.01) and nontertiary hospitals (odds ratio, 1.8; 95% confidence interval, 1.0-2.9; P = 0.04). CONCLUSION: More than one-third of AP patients undergo serial lipase measurements. This practice is more likely to occur on surgical services and in nontertiary hospitals.

Frequent guidewire passage into the pancreatic duct is an independent risk factor for postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among high-risk individuals: A post-hoc analysis of a randomized controlled trial data.

OBJECTIVES: To systematically evaluate the patient and procedural risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among patients receiving rectal indomethacin. METHODS: Data from a randomized controlled trial (RCT) of high-risk patients undergoing ERCP who received rectal indomethacin with or without topical epinephrine was evaluated. PEP was defined based on the consensus criteria. Pancreatic stenting was excluded to avoid confounding results with the role of epinephrine spray. Multivariable logistic regression analysis was used to identify patient and procedural risk factors for PEP. RESULTS: Among 960 patients enrolled in the RCT, the PEP incidence was 6.4%. An increased risk of PEP was seen with age <50 years and female gender (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.35-4.26), malignant biliary stricture(s) (OR 3.51, 95% CI 1.52-8.10), >2 guidewire passes into the pancreatic duct (PD) (OR 2.84, 95% CI 1.43-5.64), and pancreatic brush cytology (OR 6.37, 95% CI 1.10-36.90), whereas a decreased risk of PEP was seen with contrast- over guidewire-assisted cannulation (OR 0.14, 95% CI 0.02-0.99) and the use of lactated Ringer's (LR) over other fluid types (OR 0.52, 95% CI 0.27-0.98). There was a significant trend between the number of guidewire passes into the PD and PEP risk (P = 0.002). CONCLUSIONS: More than two guidewire passes into the PD and pancreatic brush cytology increased while the use of LR decreased the risk of PEP among high-risk patients receiving rectal indomethacin. Pancreatic stent placement and/or LR should be considered in patients with >2 guidewire passes into the PD.

Incidence, severity, and mortality of post-ERCP pancreatitis: an updated systematic review and meta-analysis of 145 randomized controlled trials.

BACKGROUND AND AIMS: The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs). METHODS: The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality. RESULTS: One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48). CONCLUSIONS: The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon.

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective.

Background and Aim: Prevention of hepatitis B virus (HBV) reinfection is important for long-term outcomes following liver transplantation (LT). Hepatitis B immunoglobulin (HBIG) is used among recipients who have (i) native HBV disease, (ii) hepatitis B core antibody positivity (HBcAb positivity), or (iii) received HBcAb positive organs. Nucleos(t)ide analogue (NA) monotherapy is emerging for treating patients in this setting. There is no generalized consensus on the ideal dosage of HBIG. The aim of this study was to evaluate the efficacy of low-dose HBIG (1560 international unit [IU]) for post-LT HBV prevention. Materials and Methods: HBcAb positive patients who received either HBcAb positive or hepatitis B core antibody negative (HBcAb negative) organs and HBcAb negative patients who received HBcAb positive organs between January 2016 and December 2020 were reviewed. Pre-LT HBV serologies were collected. HBV-prophylaxis strategy included NA with/without HBIG. HBV recurrence was defined as HBV deoxyribonucleic acid (DNA) positivity during the 1-year, post-LT follow-up. No HBV surface antibody titers were followed. Results: A total of 103 patients with a median age of 60 years participated in the study. Hepatitis C virus was the most common etiology. Thirty-seven HBcAb negative recipients and 11 HBcAb positive recipients with undetectable HBV DNA received HBcAb positive organs and underwent prophylaxis with 4 doses of low-dose HBIG and NA. None of the recipients in our cohort had a recurrence of HBV at 1 year. Conclusion: Low-dose HBIG (1560 IU) × 4 days and NA, for HBcAb positive recipients and HBcAb positive donors, appear to be effective in preventing HBV reinfection during the post-LT period. Further trials are needed to confirm this observation.

Liver transplantation in developing countries.

With the increasing incidence and prevalence of end-stage liver disease, demand for donor grafts continues to increase. Approaches on maximizing the potential donor grafts vary depending on the region. This review aims to summarize the current practice of liver transplantation with an emphasis on challenges encountered in developing countries.

Long-Term Outcomes of Living Donor Versus Deceased Donor Liver Transplant for Hepatocellular Carcinoma in the United States.

OBJECTIVES: Although living donor liver transplant has become a vital treatment option in hepatocellular carcinoma, controversy remains on whether recurrence and survival rates are different versus deceased donor recipients. Here, we compared clinical characteristics and outcomes between recipients of living and deceased donor liver transplants for hepatocellular carcinoma in the United States. MATERIALS AND METHODS: Our comparisons used data from the United Network of Organ Sharing/Organ Procurement and Transplantation Network. RESULTS: There were 385 living donor and 25 274 deceased donor liver transplant recipients with diagnosis of hepatocellular carcinoma. Transplant list wait times of ≥6 months were more common in deceased donor(55.9%) versus living donor recipients (45.2%; P < .001). Both recipient groups were comparable with regard to alpha-fetoprotein level <200 ng/mL (P = .18). Only a small percentage in both groups had ≥3 total tumors (P = .73); both groups had similar low transplants outside of Milan criteria (P = .45). Overall, 1-, 5-, and 10-year overall survival rates for deceased versus living donor recipients were similar (91.2% vs 92%, 74% vs 76.4%, 58.9% vs 56.5%; P = .69). On multivariate analysis, Black/African American race/ethnicity was associated with worse outcomes than White race/ethnicity as reference (P < .001), whereas Hispanic and Asian race/ethnicity were more protected. Hepatitis C virus as liver disease etiology was associated with worse outcomes than other etiologies. Tumor characteristics, ≥3 lesions, tumor size, and higher alpha-fetoprotein levels were associated with worse outcomes. Living donor transplant was not associated with higher hazard of death. Among living donor recipients only, largest tumor size was associated with higher risk of death (P = .005). CONCLUSIONS: Survival was similarin between the living donor versus deceased donor recipients with hepatocellular carcinoma. With changes in Model for End-Stage Liver Disease exception policies for hepatocellular carcinoma in the United States, living donor transplant for hepatocellular carcinoma could expand the donor pool.

Impact of genetic testing and smoking on the distribution of risk factors in patients with recurrent acute and chronic pancreatitis.

OBJECTIVE: The aim of the present study is to assess the impact of smoking dose and duration on the distribution of risk factor(s) in patients with RAP and CP, and the impact of genetic testing on the distribution of risk factor(s) in patients with idiopathic RAP and CP. METHODS: All adult patients with RAP and CP referred to a multidisciplinary pancreatitis clinic between 2010 and 2017 were evaluated. Risk factors included alcohol and smoking, hypertriglyceridemia, biliary, and other etiologies. Genetic testing was only pursued in patients with idiopathic RAP or CP. RESULTS: Among the 1770 patients evaluated, 167 had RAP and 303 had CP. After genetic testing and smoking, the most common risk factors for RAP and CP were pathogenic variant(s) (23%) and the combination of alcohol and smoking (23%), respectively. Genetic testing and smoking assessment decreased the proportion of patients with alcoholic RAP from 17% to 5%, alcoholic CP from 33% to 10%, idiopathic RAP from 49% to 12%, and idiopathic CP from 54% to 14%. Pathogenic CFTR variants were the most common variant in patients with RAP (51%) and CP (43%). Among the 68 patients with pancreas divisum, other risk factor(s) were identified in 72%. CONCLUSION: Genetic testing and a detailed assessment of smoking dose and duration reduce the proportion of patients with alcoholic and idiopathic pancreatitis. Other risk factor(s) for pancreatitis are found in the majority of patients with pancreas divisum further questioning its role as an independent risk factor.1. What is the current knowledge?Approximately 30% of patients with pancreatitis have no clear risk factor(s) and are categorized as having an idiopathic etiology.Pathogenic variant(s) as well as smoking dose and duration are well-established risk factors for recurrent acute and chronic pancreatitis but are not widely recognized or incorporated into clinical practice.2. What is new here?Genetic testing and a detailed assessment of smoking dose and duration reduced the proportion of patients with alcoholic and idiopathic acute recurrent and chronic pancreatitis.Approximately three-fourths of patients with pancreas divisum have a risk factor for pancreatitis.

Hepatocellular Carcinoma and the Role of Liver Transplantation: A Review.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and liver transplantation (LT) is the only potentially curative treatment. Over the years, Milan criteria has been used for patient selection. There is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future treatment. Furthermore, newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant list. In addition, combination therapies for better outcome are under investigation. Interestingly, the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ pool. However, there is a conflict of opinion between different centers regarding its efficacy and data is scarce. The aim of this review article is to outline the various selection criteria for LT, discuss the outcomes of LT in HCC patients, and explore future directions of LT for HCC. Therefore, a comprehensive PubMed/MEDLINE review was conducted. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies, the authors independently reviewed them to identify the relevant studies. After careful evaluation 120 studies relevant to out topic are cited in the manuscript. Three tables and two figures are also included. In conclusion LT for HCC has evolved over the years. With the introduction of several expanded criteria beyond Milan, the introduction of bridging therapies, such as transcatheter arterial chemoembolization and radiofrequency ablation, and the approval of newer systemic therapies, it is evident that there will be more LT recipients in the future. It is promising to see ongoing trials and the continuous evolution of protocols. Prospective studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent, clarify the role of LDLT, and determine the optimal bridging therapies to LT.