Citations

Background. Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant. Methods. A total of 717 MASH cirrhosis patients who had LT (1997–2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30–≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined. Results. Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a “reset point,” signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups ( P < 0.0001). Conclusions. The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.

Posttransplant diabetes mellitus (PTDM) is associated with significant morbidity and mortality in liver transplant recipients (LTRs). We used the Organ Procurement and Transplantation Network (OPTN) database to compare the incidence of developing PTDM across the United States and develop a risk prediction model for new-onset PTDM using OPTN region as well as donor-related, recipient-related, and transplant-related factors. All US adult, primary, deceased donor, LTRs between January 1, 2007, and December 31, 2016, with no prior history of diabetes noted, were identified. Kaplan-Meier estimators were used to calculate the cumulative incidence of PTDM, stratified by OPTN region. Multivariable Cox proportional hazards models were fitted to estimate hazards of PTDM in each OPTN region and build a risk prediction model, through backward selection. Cumulative incidence of PTDM at 1 year, 3 years, and 5 years after transplant was 12.0%, 16.1%, and 18.9%, respectively. Region 3, followed by regions 8, 2, and 9, had the highest adjusted hazards of developing PTDM. Inclusion of OPTN region in a risk prediction model for PTDM in LTRs (including recipient age, sex, race, education, insurance coverage, body mass index, primary liver disease, cold ischemia time, and donor history of diabetes) modestly improved performance (C-statistic = 0.60). In patients without pre-existing, confirmed diabetes mellitus, the incidence of PTDM in LTRs varied across OPTN regions, with the highest hazards in region 3, followed by regions 8, 2, and 9. The performance of a novel risk prediction model for PTDM in LTRs has improved performance with the inclusion of the OPTN region. Vigilance is recommended to centers in high-risk regions to identify PTDM and mitigate its development.

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.

ABSTRACTBackgroundIntraductal papillary mucinous neoplasms (IPMNs) are the most commonly identified pancreatic cystic neoplasms. Incidentally detected IPMNs are common among liver transplant recipients. The risk of IPMN progression to pancreatic cancer in transplant recipients and the impact of immunosuppression on the risk of malignant transformation of IPMN are unclear.MethodsIn this retrospective study of consecutive liver transplant recipients across Mayo Clinic over a 13‐year period, patients were assessed for possible IPMN by automated chart review. Pancreatic cystic lesions were characterized as suspected IPMNs based on imaging criteria. Cox proportional hazards models were used to determine the association between IPMN progression (the development of cancer or worrisome features) and clinical and immunosuppression regimen characteristics.ResultsOf 146 patients with suspected IPMNs, progression occurred in 7 patients (2 cases of IPMN‐associated cancer and 5 cases of worrisome features) over an average follow‐up of 66.6 months. Immunosuppression type, medication number, and tacrolimus trough levels were not associated with IPMN progression (p > 0.05). Combined kidney and liver transplantation (p = 0.005) and pretransplant cholangiocarcinoma (p = 0.012) were associated with IPMN progression.ConclusionIPMN progression is rare after liver transplantation even over an extended follow‐up period. The findings were notable for the absence of an association between IPMN progression and immunosuppression regimen. Larger studies are needed given the low incidence.

ObjectivesMetabolic dysfunction‐associated steatotic liver disease (MASLD) is the most prevalent liver disorder in Western countries, with approximately 20%–30% of the MASLD patients progressing to severe stages. There is an urgent need for noninvasive, cost‐effective, widely accessible, and precise biomarkers to evaluate liver steatosis. This study aims to assess and compare the diagnostic performance of a novel reference frequency method‐based ultrasound attenuation coefficient estimation (ACE) in both fundamental (RFM‐ACE‐FI) and harmonic (RFM‐ACE‐HI) imaging for detecting and grading liver steatosis.MethodsAn Institutional Review Board‐approved prospective study was carried out between December 2018 and October 2022. A total number of 130 subjects were enrolled in the study. The correlation between RFM‐ACE‐HI values and magnetic resonance imaging proton density fat fraction (MRI‐PDFF), as well as between RFM‐ACE‐FI values and MRI‐PDFF were calculated. The diagnostic performance of RFM‐ACE‐FI and RFM‐ACE‐HI was evaluated using receiver operating characteristic (ROC) curve analysis, as compared to MRI‐PDFF. The reproducibility of RFM‐ACE‐HI was assessed by interobserver agreement between two sonographers.ResultsA strong correlation was observed between RFM‐ACE‐HI and MRI‐PDFF, with R = 0.88 (95% confidence interval [CI]: 0.83–0.92; P < .001), while the correlation between RFM‐ACE‐FI and MRI‐PDFF was R = 0.65 (95% CI: 0.50–0.76; P < .001). The area under the ROC (AUROC) curve for RFM‐ACE‐HI in staging liver steatosis grades of S ≥ 1 and S ≥ 2 was 0.97 (95% CI: 0.91–0.99; P < .001) and 0.98 (95% CI: 0.93–1.00; P < .001), respectively, and 0.76 (95% CI: 0.65–0.85) and 0.80 (95% CI: 0.70–0.88) for RFM‐ACE‐FI, respectively. Great reproducibility was achieved for RFM‐ACE‐HI, with an interobserver agreement of R = 0.97 (95% CI: 0.94–0.99; P < .001).ConclusionsThe novel RFM‐ACE‐HI method offered high liver steatosis diagnostic accuracy and reproducibility, which has important clinical implications for early disease intervention and treatment evaluation.

ABSTRACT Introduction Hepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients. Methods We conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Conventional recombinant hepatitis B vaccine (Recombivax HB) was used before 2020, and Heplisav‐B was preferred after 2020. HBV seroprotection was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L. Furthermore, we compared characteristics between recipients who maintained HBV seroprotection and those who lost HBV seroprotection (HBsAb < 10 IU/L) at 30 days posttransplantation (D30). Results Among 922 candidates who were eligible for HBV vaccination, 430 (47%) completed the HBV vaccine series. Patients receiving Heplisav‐B were more likely to complete the series than Recombivax HB (81% vs. 60%, p < 0.001) and Heplisav‐B had a higher seroprotection rate than Recombivax HB (75% vs. 64%, p = 0.023). Multivariate logistic regression analysis identified receiving Heplisav‐B as an independent predictor for HBV seroprotection (adjusted odds ratio [aOR] 1.723; 95% confidence interval [CI] 1.056–2.810; p = 0.029). A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. Loss of HBV seroprotection occurred in 38 (26%) patients at D30. Multivariate logistic regression analysis identified two predictors for HBV seroprotection loss at D30: age ≥ 60 years (aOR, 2.503; 95% CI 1.026–6.107; p = 0.044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI 5.211–66.209; p < 0.001). Conclusions Although less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav‐B provided a higher vaccine completion rate and seroprotection than the 3‐dose Recombivax HB. Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L. Assessment of seroprotection after HBV vaccination should be prioritized during the pretransplant period.

ABSTRACTIntroductionHepatitis B virus reactivation (HBVr) can occur in solid organ transplant (SOT) recipients with previously inactive hepatitis B virus (HBV) infection. Previous studies have reported that HBVr is generally less than 10% in nonliver SOT recipients with past HBV infection.MethodsWe conducted a retrospective study from January 2018 to August 2023 at Mayo Clinic sites in Arizona, Florida, and Minnesota. We examined the antiviral prophylaxis strategy used and the characteristics of HBVr in hepatitis B core antibody‐positive (HBcAb +) nonliver SOT adult recipients. Past HBV infection was defined as HBcAb + / hepatitis B surface antigen (HBsAg) –. Chronic HBV infection was defined as HBcAb + / HBsAg +.ResultsA total of 180 nonliver SOT recipients were identified during the study period. Indefinite antiviral prophylaxis was utilized in 77 recipients, and none developed HBVr after transplantation. In 103 recipients without antiviral prophylaxis, the incidence of HBVr was 12% (12/97) and 33% (2/6) in those with past HBV infection and chronic HBV infection. The incidence of HBVr in patients with past HBV infection is 16% (8/50), 15% (3/20), and 5% (1/22) in kidney, heart, and lungs, respectively. HBVr was more frequent in those who received alemtuzumab. Among 14 recipients with HBVr, none had HBV‐associated liver failure or death.ConclusionsOur study observed a higher rate of HBVr (12%) in nonliver SOT recipients with past HBV infection compared to the previous studies. Further studies are needed to identify predictors of HBVr in nonliver SOT recipients and optimize antiviral prophylaxis guidance.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

Abstract Background Visceral fat represents a metabolically active entity linked to adverse metabolic sequelae of obesity. We aimed to determine if celiac artery mesenteric fat thickness can be reliably measured during endoscopic ultrasound (EUS), and if these measurements correlate with metabolic disease burden. Methods This was a retrospective analysis of patients who underwent celiac artery mesenteric fat measurement with endosonography (CAMEUS) measurement at a tertiary referral center, and a validation prospective trial of patients with obesity and nonalcoholic steatohepatitis who received paired EUS exams with CAMEUS measurement before and after six months of treatment with an intragastric balloon. Results CAMEUS was measured in 154 patients [56.5% females, mean age 56.5 ± 18.0 years, body mass index (BMI) 29.8 ± 8.0 kg/m2] and was estimated at 14.7 ± 6.5 mm. CAMEUS better correlated with the presence of non-alcoholic fatty liver disease (NAFLD) (R2 = 0.248, P &lt; 0.001) than BMI (R2 = 0.153, P &lt; 0.001), and significantly correlated with metabolic parameters and diseases. After six months of intragastric balloon placement, the prospective cohort experienced 11.7% total body weight loss, 1.3 points improvement in hemoglobin A1c (P = 0.001), and a 29.4% average decrease in CAMEUS (−6.4 ± 5.2 mm, P &lt; 0.001). CAMEUS correlated with improvements in weight (R2 = 0.368), aspartate aminotransferase to platelet ratio index (R2 = 0.138), and NAFLD activity score (R2 = 0.156) (all P &lt; 0.05). Conclusions CAMEUS is a novel measure that is significantly correlated with critical metabolic indices and can be easily captured during routine EUS to risk-stratify susceptible patients. This station could allow for EUS access to sampling and therapeutics of this metabolic region.