Performance of Vibration-Controlled Transient Elastography and Clinical Prediction Models In Liver Transplant Recipients.

Hepatic fibrosis is a strong predictor of clinical outcomes following liver transplantation (LT).1 Despite the centrality of hepatic fibrosis in clinical outcomes, the published literature with noninvasive fibrosis assessment in LT recipients is limited and liver biopsy, despite its invasive nature, remains the reference standard. Vibration-controlled transient elastography (VCTE) and clinical prediction models (CPM) are point-of-care tests that can provide noninvasive assessment of hepatic fibrosis2-4; however, the data comparing the diagnostic performance of VCTE and CPM in LT recipients are lacking. The current study evaluated the diagnostic performance of VCTE and CPM in LT recipients using best practices in regulatory sciences for biomarker development.

Evaluation of liver stiffness measurement-based scores in liver transplantation recipients.

Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration-controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM-based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM-based fibrosis models (FibroScan-AST [FAST], AGILE-3+, and AGILE-4) were included ( n = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0-2 vs. 3-4) were determined by optimal cut-off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89-0.99), FAST was 0.65 (95% CI, 0.50-0.79), AGILE-3+ was 0.90 (95% CI, 0.83-0.97), and AGILE-4 was 0.90 (95% CI, 0.83-0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM-based scores. The false-positive rates for AGILE-3+ and AGILE-4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false-positive rates in LSM-based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM-based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.

Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease.

Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). METHODS: Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). RESULTS: The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. CONCLUSION: Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.

Diagnostic Performance of Vibration-Controlled Transient Elastography in Liver Transplant Recipients.

BACKGROUND & AIMS: Vibration-controlled transient elastography (VCTE) is a non-invasive tool for detecting hepatic steatosis and fibrosis in patients who have not received liver transplants. We aimed to evaluate the diagnostic performance of VCTE in detection of hepatic steatosis and fibrosis in patients who have undergone liver transplantation. METHODS: We performed a prospective study of 99 liver transplant recipients assessed by VCTE using a standard protocol. Controlled attenuation parameter cutoff values for pairwise steatosis grade and liver stiffness measurements (LSM) and cutoff values for pairwise fibrosis stage were determined using cross-validated area under the receiver operating characteristics (AUROC) curve analyses. We calculated sensitivity (fixed at 90%) and specificity (fixed at 90%) values. RESULTS: A controlled attenuation parameter cutoff value of 270 dB/m detected any hepatic steatosis with an AUROC of 0.88 (95% CI, 0.78-0.93). VCTE detected steatosis grades 2-3 vs 0-1 with an AUROC of 0.94 (95% CI, 0.89-0.99) and steatosis grade 3 vs 0-2 was similar and AUROC of 0.89 (95% CI, 0.83-0.96). When we used an LSM cutoff value of 10.5 kPa, VCTE identified patients with advanced fibrosis (fibrosis stages ≥ 3) with an AUROC of 0.94 (95% CI, 0.88-0.99). At fixed sensitivity, the cutoff LSM value of 10.5k Pa excluded advanced fibrosis with a negative predictive value of 0.99. At fixed specificity, the cutoff LSM value of 16.9 kPa detected advanced fibrosis with a sensitivity of 0.86, a positive predictive value (PPV) of 0.40, and a negative predictive value of 0.99. CONCLUSIONS: VCTE accurately detects hepatic steatosis and fibrosis in recipients of liver transplants. This non-invasive method might be used to identify patients in need of confirmatory liver biopsy analysis.

Evolution of robotic-assisted kidney transplant: successes and barriers to overcome.

PURPOSE OF REVIEW: The aim of this study was to provide an updated review of robotic-assisted kidney transplant (RAKT) with an emphasis on advantages over the open kidney transplant (OKT), utility in special populations and resources available to overcome the learning curve of robotic surgery. RECENT FINDINGS: The majority of the reported studies showed that RAKT and OKT have similar functional outcomes including similar ischemia times and time to postoperative normalization of creatinine. However, RAKT results in fewer wound complications, decreased estimated blood loss and pain. Given these benefits, RAKT is a promising approach for obese patient across BMI subtypes and several studies showed decreased wound complications in this population compared with the open approach. Moreover, new 3D-print techniques are promising resources for robotic simulation, which may decrease the learning curve of robotic surgery. SUMMARY: Overall, RAKT is a feasible approach especially in obese patients. However, more data with long-term follow-up are needed to fully elucidate the advantages over OKT before universal implementation of this approach is possible.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants.

Impact of belatacept conversion on kidney transplant function, histology, and gene expression - a single-center study.

Prior studies on belatacept conversion from calcineurin inhibitor (CNI) have been limited by an absence of postconversion surveillance biopsies that could underestimate subclinical rejection, or a case-controlled design. A total of 53 adult patients with allograft dysfunction underwent belatacept conversion (median: 6 months) post-transplant. At a median follow-up = 2.5 years, patient survival was 94% with a death-censored graft survival of 85%. Seven (13%) patients had acute rejection (including 3 subclinical) at median 6 months postconversion. Overall, eGFR improved (P = <0.001) from baseline = 31±15 to 40.2 ± 17.6 ml/min/1.73m2 by 6 months postconversion, but then stayed stable. This improvement was also observed (P < 0.001) in comparison with a propensity matched control cohort on CNI, where eGFR stayed stable (mean ~ 32ml/min/1.72m2 ) over 2-year follow-up. Patients converted < 6 months post-transplant were more likely to have a long-term improvement in kidney function. Paired gene expression analysis of 30 (of 53) consecutive pre- and postconversion surveillance biopsies did not reveal changes in inflammation/acute injury; although atrophy-fibrosis score worsened (mean = 0.28 to 0.44; P = 0.005). Thus, improvement in renal function with belatacept conversion occurred early and then sustained in comparison with controls where renal function remained unchanged overtime. We were unable to show molecular signals that could be related to CNI administration and regressed after withdrawal.

Prevalence and Severity of Nonalcoholic Fatty Liver Disease Among Caregivers of Patients With Nonalcoholic Fatty Liver Disease Cirrhosis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting nearly 1 in 3 Americans.1 Nonalcoholic steatohepatitis (NASH), the clinically aggressive variant of NAFLD, has a propensity of fibrosis progression and increased risk of cirrhosis and hepatocellular carcinoma. NASH-related cirrhosis is now the most rapidly growing indication for liver transplantation (LT).2 Disease recurrence and progression to advanced fibrosis after LT are high3; however, the key contributors of these are unknown. We hypothesized that patients with NASH cirrhosis reside in a microenvironment conducive to not only development of NASH but also fibrosis progression, which likely persist after LT and contribute to disease recurrence. The hypothesis was tested by performing vibration-controlled transient elastography (VCTE) in primary caregivers and cohabitants of patients with decompensated cirrhosis awaiting LT.

The Abdominal Transplant Surgery Workforce: Current state and future trends.

Transplant surgical workforce concerns have arisen in the last 5 years as reflected in challenges securing job opportunities for new fellows. The present survey was designed by the ASTS Membership and Workforce Committee to describe the current practice characteristics of transplant centers in order to estimate changes in the workforce. The survey questionnaire requested information about the transplant programs, the transplant surgeons involved in the program, and the estimated changes in the staffing of the program over the next 3 years. Seventy-one transplant centers responded from a total of 235 identified and queried (30.2% response rate), with median responding centers per UNOS region of 7 (IQR 4.5-8.5). The recruitment outlook for the next 3 years forecasts a positive inflow of surgeons at a 2:1 rate (incoming:leaving). The new female transplant workforce within the responding cohort has increased from 3.7% in 1980 to 18.4% in 2010. Currently, 13.1% of practicing US transplant surgeons in this survey are female which is higher than many other surgical specialties. This report represents the most up-to-date view into the abdominal transplant surgical workforce. The positive job recruitment outlook for transplant surgeons and the narrowing gender gap are new findings from this study.

Obesity does not significantly impact outcomes following simultaneous liver kidney transplantation: review of the UNOS database - a retrospective study.

Simultaneous liver kidney transplantation (SLK) is the only curative option for patients with combined end stage liver and kidney disease. With the global obesity epidemic, an increasing number of obese patients are in need of SLK. However, the impact of pre-transplant obesity on outcomes after SLK is unknown. An analysis of the United States OPTN registry (Oct 1987 - June 2016) identified 7205 SLK transplants. Of these, 1677 patients were overweight/obese (OW, BMI 30-39) and 183 were morbidly obese (MO, BMI ≥40). 29% of patients had NASH in the MO group versus 16.4% and 4.7% in the OW and normal weight (NW) groups, respectively. The 1, 3 and 5 year overall patient survival, kidney and liver graft survivals were comparable between the three groups. Numerically higher rates of acute kidney rejection were reported in the MO group at 1 year [12.73%, 8.59%, and 10.05% for MO, OW and NW, respectively (P = 0.22)]. Multivariate analysis identified diagnosis of hepatitis C, donor age, diabetes mellitus, and delayed kidney transplant function but not BMI as risk factors for poor patient and both liver and kidney graft survival. Based on these findings, obesity should not be a contraindication for SLK even for patients with BMIs ≥ 40.

Obtaining Optimal Long-Term Outcomes from Liver Transplantation for Hepatocellular Cancer.

Liver transplantation is the definitive treatment for patients with end-stage liver disease. Liver transplantation is also the optimal treatment for patients with hepatocellular carcinoma (HCC), especially in the setting of chronic liver disease. Unfortunately, due to the worldwide shortage of organs, this treatment is not available for all patients with HCC. Strict selection criteria have been developed in order to obtain optimal results. A surgical perspective of the preoperative selection, perioperative management, and postoperative care of patients is reviewed in depth and provides an overview for obtaining optimal long-term results from liver transplantation for HCC. With rigorous selection and patient management, excellent long-term outcomes can be obtained with liver transplantation for patients with HCC.

Outcomes of kidney transplants and risk of infection transmission from increased infectious risk donors.

Concern over transmission of viral infections has been reported to result in higher discard rates of high infectious risk kidneys (HIR) although data on actual viral transmission rates are lacking. At our center, we performed 89 HIR and 533 non-HIR kidney transplants (KTs) between 2004 and 2011. Follow-up screening labs in recipients of HIR kidneys tested for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus did not reveal any cases of viral transmission over median follow-up of 4.3 years. Patient and graft outcomes were similar at 5 years between HIR and non-HIR KTs. An updated analysis of the Organ Procurement and Transplant Network (OPTN) registry of deceased-donor kidney transplants between 2008 and 2012 included 57 526 transplants was performed. Retrospective calculation of KDRI (kidney donor risk index) differed (P<.001) between all groups with median KDRI of 0.99 for HIR kidneys, 1.07 for non-HIR standard criteria donor kidneys, and 1.81 for non-HIR expanded criteria donor (ECD) kidneys. This was reflected in the significantly improved 5-year graft survival for HIR KTs when compared with non-HIR ECD KTs (84% vs 78%; P<.001). Our data can guide counseling of KT candidates about the safety and benefits of HIR kidneys.

Hepatobiliary mucinous cystic neoplasms and mimics.

This review will provide an overview of hepatobiliary mucinous cystic neoplasms and their mimics such as complex appearing benign cysts, intraductal papillary neoplasm of bile ducts, choledochal cysts, infectious cysts, and other cystic neoplasms. Preoperative imaging, particularly abdominal MRI with MRCP, plays a key role in differentiating these entities which differ widely in management. Familiarity with the differentiating imaging features of mucinous cystic neoplasms and their mimics allows radiologists to provide management-guiding reports.

Radiologic findings of biliary complications post liver transplantation.

Liver transplantation is a potentially curative treatment for patients with acute liver failure, end-stage liver disease, and primary hepatic malignancy. Despite tremendous advancements in surgical techniques and immunosuppressive management, there remains a high rate of post-transplant complications, with one of the main complications being biliary complications. In addition to anastomotic leak and stricture, numerous additional biliary complications are encountered, including ischemic cholangiopathy due to the sole arterial supply of the bile ducts, recurrence of primary biliary disease, infections, biliary obstruction from stones, cast, or hemobilia, and less commonly cystic duct remnant mucocele, vanishing duct syndrome, duct discrepancy and kinking, post-transplant lymphoproliferative disorder, retained stent, and ampullary dysfunction. This article presents an overview of biliary anatomy and surgical techniques in liver transplantation, followed by a detailed review of post-transplant biliary complications with their corresponding imaging findings on multiple modalities with emphasis on magnetic resonance imaging and MR cholangiopancreatography.

Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871.

Web-based image transmission: a novel approach to aid communication in split liver transplantation.

BACKGROUND: Split liver transplantation (SLT) is technically demanding and requires good communication between transplant centers. The recipient surgeon receiving a shipped split liver needs detailed information on allocation of inflow and outflow vessels. We describe the first use of an image transmission system to facilitate SLT. METHODS: Twenty cadaver livers undergoing ex situ splitting were studied. Fifteen were shared between the geographically separate Birmingham adult and pediatric centers and five were shared with other UK centers. RESULTS: A total of six to eight images of each split graft were taken with a camera at standardized settings using the National Organ Retrieval Imaging System (NORIS), showing details of appearance, size, and anatomy of allocated inflow and outflow vessels. These were uploaded using a personal digital assistant to a secure website (http://www.noris.org.uk). The remote recipient surgeon then viewed these images by logging onto the password-protected website. Minimum time interval between division of the hilar vessels and completion of the split procedure was two h, allowing remote surgeon to view their allocated "shipped" graft in advance of commencing surgery. CONCLUSION: This advanced yet simple image transmission system has the potential for routine application in transplant surgery, not only for splitting but also for reporting injuries and graft steatosis.

Acute liver failure due to primary angiosarcoma: a case report and review of literature.

BACKGROUND: Hepatic angiosarcoma is a primary sarcoma of the liver, accounting for only 2% of all primary hepatic malignancies. Acute liver failure is an extremely rare presentation of a primary liver tumour. CASE PRESENTATION: We report a case of a seventy year-old man who presented with a very short period of jaundice leading to fulminant hepatic failure (FHF). On further investigation he was found to have primary angiosarcoma of liver. CONCLUSION: The treatment outcomes for hepatic angiosarcoma are poor, we discuss the options available and the need for prompt investigation and establishment of a diagnosis.

Application of Portsmouth modification of physiological and operative severity scoring system for enumeration of morbidity and mortality (P-POSSUM) in pancreatic surgery.

BACKGROUND: Pancreatoduodenectomy (PD) is associated with high incidence of morbidity and mortality. We have applied P-POSSUM in predicting the incidence of outcome after PD to identify those who are at the highest risk of developing complications. METHOD: A prospective database of 241 consecutive patients who had PD from January 2002 to September 2005 was retrospectively updated and analysed. P-POSSUM score was calculated for each patient and correlated with observed morbidity and mortality. RESULTS: 30 days mortality was 7.8% and morbidity was 44.8%. Mean physiological score was 16.07 +/- 3.30. Mean operative score was 13.67 +/- 3.42. Mean operative score rose to 20.28 +/- 2.52 for the complex major operation (p < 0.001) with 2 fold increase in morbidity and 3.5 fold increase in mortality. For groups of patients with a physiological score of (less than or equal to) 18, the O:P (observed to Predicted) morbidity ratio was 1.3-1.4 and, with a physiological score of >18, the O:P ratio was nearer to 1. Physiological score and white cell count were significant in a multivariate model. CONCLUSION: P-POSSUM underestimated the mortality rate. While P-POSSUM analysis gave a truer prediction of morbidity, underestimation of morbidity and potential for systematic inaccuracy in prediction of complications at lower risk levels is a significant issue for pancreatic surgery.