Satellite liver transplant centres significantly improve transplant assessment outcomes for patients with chronic liver disease but not hepatocellular carcinoma: a retrospective cohort study.

Introduction: Liver transplantation (LT) remains integral to the management of end-stage chronic liver disease (CLD). However, referral thresholds and assessment pathways remain poorly defined. Distance from LT centre has been demonstrated to impact negatively on patient outcomes resulting in the development of satellite LT centres (SLTCs). We aimed to evaluate the impact of SLTCs on LT assessment in patients with CLD and hepatocellular carcinoma (HCC). Methods: A retrospective cohort study was undertaken including all patients with CLD or HCC assessed for LT at King's College Hospital (KCH) between October 2014 and October 2019. Referral location, social, demographic, clinical and laboratory data were collected. Univariable and multivariable analyses (MVA) were performed to assess the impact of SLTCs on patients being accepted as LT candidates and contraindications being identified. Results: 1102 and 240 LT assessments were included for patients with CLD and HCC, respectively. MVA demonstrated significant associations with; patients living greater than 60 min from KCH/SLTCs and LT candidacy acceptance in CLD, and less deprived patients and LT candidacy acceptance in HCC. However, neither variable was associated with identification of LT contraindications. MVA demonstrated that referrals from SLTCs were more likely to result in acceptance of LT candidacy and less likely to result in a contraindication being identified in CLD. However, such associations were not demonstrated in HCC. Conclusion: SLTCs improve LT assessment outcomes in CLD but not HCC reflecting the standardised HCC referral pathway. Developing a formal regional LT assessment pathway across the UK would improve equity of access to transplantation.

The Liverpool alcohol-related liver disease algorithm identifies twice as many emergency admissions compared to standard methods when applied to Hospital Episode Statistics for England.

BACKGROUND: Emergency admissions in England for alcohol-related liver disease (ArLD) have increased steadily for decades. Statistics based on administrative data typically focus on the ArLD-specific code as the primary diagnosis and are therefore at risk of excluding ArLD admissions defined by other coding combinations. AIM: To deploy the Liverpool ArLD Algorithm (LAA), which accounts for alternative coding patterns (e.g., ArLD secondary diagnosis with alcohol/liver-related primary diagnosis), to national and local datasets in the context of studying trends in ArLD admissions before and during the COVID-19 pandemic. METHODS: We applied the standard approach and LAA to Hospital Episode Statistics for England (2013-21). The algorithm was also deployed at 28 hospitals to discharge coding for emergency admissions during a common 7-day period in 2019 and 2020, in which eligible patient records were reviewed manually to verify the diagnosis and extract data. RESULTS: Nationally, LAA identified approximately 100% more monthly emergency admissions from 2013 to 2021 than the standard method. The annual number of ArLD-specific admissions increased by 30.4%. Of 39,667 admissions in 2020/21, only 19,949 were identified with standard approach, an estimated admission cost of £70 million in under-recorded cases. Within 28 local hospital datasets, 233 admissions were identified using the standard approach and a further 250 locally verified cases using the LAA (107% uplift). There was an 18% absolute increase in ArLD admissions in the seven-day evaluation period in 2020 versus 2019. There were no differences in disease severity or mortality, or in the proportion of admissions with decompensation of cirrhosis or alcoholic hepatitis. CONCLUSIONS: The LAA can be applied successfully to local and national datasets. It consistently identifies approximately 100% more cases than the standard coding approach. The algorithm has revealed the true extent of ArLD admissions. The pandemic has compounded a long-term rise in ArLD admissions and mortality.

Intraductal fully covered self-expanding metal stents in the management of post-liver transplant anastomotic strictures: a UK wide experience.

Background: Fully covered intraductal self-expanding metal stents (IDSEMS) have been well described in the management of post-liver transplant (LT) anastomotic strictures (ASs). Their antimigration waists and intraductal nature make them suited for deployment across the biliary anastomosis. Objectives: We conducted a multicentre study to analyse their use and efficacy in the management of AS. Design: This was a retrospective, multicentre observational study across nine tertiary centres in the United Kingdom. Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with IDSEMS insertion were analysed retrospectively. Recorded variables included patient demographics, procedural characteristics, response to therapy and follow-up data. Results: In all, 162 patients (100 males, 62%) underwent 176 episodes of IDSEMS insertion for AS. Aetiology of liver disease in this cohort included hepatocellular carcinoma (n = 35, 22%), followed by alcohol-related liver disease (n = 29, 18%), non-alcoholic steatohepatitis (n = 20, 12%), primary biliary cholangitis (n = 15, 9%), acute liver failure (n = 13, 8%), viral hepatitis (n = 13, 8%) and autoimmune hepatitis (n = 12, 7%). Early AS occurred in 25 (15%) cases, delayed in 32 (20%) cases and late in 95 (59%) cases. Age at transplant was 54 years (range, 12-74), and stent duration was 15 weeks (range, 3 days-78 weeks). In total, 131 (81%) had complete resolution of stricture at endoscopic re-evaluation. Stricture recurrence was observed in 13 (10%) cases, with a median of 19 weeks (range, 4-88 weeks) after stent removal. At removal, there were 21 (12%) adverse events, 5 (3%) episodes of cholangitis and 2 (1%) of pancreatitis. In 11 (6%) cases, the removal wires unravelled, and 3 (2%) stents migrated. All were removed endoscopically. Conclusion: IDSEMS appears to be safe and highly efficacious in the management of post-LT AS, with low rates of AS recurrence.

A UK survey on variation in the practice of management of choledocholithiasis and laparoscopic common bile duct exploration (ALiCE Survey).

BACKGROUND: The practice of managing suspected/confirmed common bile duct stones (CBDS) can vary significantly in the UK. We aimed to assess this variability in practice and challenges to form a basis for future consensus. METHODS: An electronic survey containing 40 questions on various aspects of management of CBDS was sent to surgeons who perform cholecystectomies via five surgical associations. RESULTS: A total of 132 surgeons responded to the survey. The speciality of surgeons includes upper gastro-intestinal (68%), general (18%), colorectal (12%), and others (2%). For patients with suspected CBD stones, 80% would choose magnetic resonance cholangio-pancreatography, and 14.4% would proceed to intra-operative imaging. Most surgeons preferred intra-operative cholangiogram over intra-operative ultrasound (83% vs 17%). For the treatment, 62.1% preferred a two-stage approach [endoscopic retrograde cholangio-pancreatography (ERCP) followed by laparoscopic cholecystectomy (LC)] and 33.4% chose a single-stage approach [LC + laparoscopic common bile duct exploration (LCBDE)]. Eighty (60.6%) responders performed LCBDE, and 19 (23.8%) of them performed > 10 LCBDEs in a year. Two third of surgeons (62.5%) preferred a trans-choledochal approach to CBDS. Half of the surgeons that perform LCBDE use a T-tube selectively and 1.6% routinely. The "availability of very good ERCP service" and "lack of formal training" were the two main reasons for surgeons not performing LCBDE. Both surgeons' speciality and whether they perform other complex laparoscopic surgery were significantly associated with choosing a two-stage approach over a one-stage approach (χ2 test, speciality p = 0.033, complex surgery p = 0.011). CONCLUSION: Our survey confirms the significant variability in the diagnosis and management of CBDS. The two-stage approach is still the most common way of managing CBDS in the UK. The main reasons for the low uptake of the single-stage approach are the availability of good ERCP service, lack of equipment and lack of formal training in the technique of LCBDE.

Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQß1.

Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQß1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQß1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQß1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQß1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQß1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

Real-World Outcomes of Direct-Acting Antiviral Treatment and Retreatment in United Kingdom-Based Patients Infected With Hepatitis C Virus Genotypes/Subtypes Endemic in Africa.

BACKGROUND: Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) in high-income countries where a restricted range of HCV genotypes/subtypes circulate. METHODS: We studied United Kingdom-resident patients born in Africa to examine DAA effectiveness in LMICs where there is far greater breadth of HCV genotypes/subtypes. Viral genome sequences were determined from 233 patients. RESULTS: Full-length viral genomic sequences for 26 known subtypes and 5 previously unidentified isolates covering 5 HCV genotypes were determined. From 149 patients who received DAA treatment/retreatment, the overall SVR was 93%. Treatment failure was associated primarily with 2 subtypes, gt1l and gt4r, using sofosbuvir/ledipasvir. These subtypes contain natural resistance-associated variants that likely contribute to poor efficacy with this drug combination. Treatment failure was also significantly associated with hepatocellular carcinoma. CONCLUSIONS: DAA combinations give high SVR rates despite the high HCV diversity across the African continent except for subtypes gt1l and gt4r, which respond poorly to sofosbuvir/ledipasvir. These subtypes are widely distributed across Western, Central, and Eastern Africa. Thus, in circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommended treatment option.

Mapping of population disparities in the cholangiocarcinoma urinary metabolome.

Phenotypic diversity in urinary metabolomes of different geographical populations has been recognized recently. In this study, urinary metabolic signatures from Western (United Kingdom) and South-East Asian (Thai) cholangiocarcinoma patients were characterized to understand spectral variability due to host carcinogenic processes and/or exogenous differences (nutritional, environmental and pharmaceutical). Urinary liquid chromatography mass spectroscopy (LC-MS) spectral profiles from Thai (healthy = 20 and cholangiocarcinoma = 14) and UK cohorts (healthy = 22 and cholangiocarcinoma = 10) were obtained and modelled using chemometric data analysis. Healthy metabolome disparities between the two distinct populations were primarily related to differences in dietary practices and body composition. Metabolites excreted due to drug treatment were dominant in urine specimens from cholangiocarcinoma patients, particularly in Western individuals. Urine from participants with sporadic (UK) cholangiocarcinoma contained greater levels of a nucleotide metabolite (uridine/pseudouridine). Higher relative concentrations of 7-methylguanine were observed in urine specimens from Thai cholangiocarcinoma patients. The urinary excretion of hippurate and methyladenine (gut microbial-host co-metabolites) showed a similar pattern of lower levels in patients with malignant biliary tumours from both countries. Intrinsic (body weight and body composition) and extrinsic (xenobiotic metabolism) factors were the main causes of disparities between the two populations. Regardless of the underlying aetiology, biological perturbations associated with cholangiocarcinoma urine metabolome signatures appeared to be influenced by gut microbial community metabolism. Dysregulation in nucleotide metabolism was associated with sporadic cholangiocarcinoma, possibly indicating differences in mitochondrial energy production pathways between cholangiocarcinoma tumour subtypes. Mapping population-specific metabolic disparities may aid in interpretation of disease processes and identification of candidate biomarkers.

A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.

BACKGROUND: Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors. METHODS: To identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group. RESULTS: A male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor. CONCLUSIONS: These novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection.

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10-04) and rs8099917 (P value = 5.5 × 10-04). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10-05). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10-04). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917.

Adult liver transplantation: A UK clinical guideline - part 1: pre-operation.

Liver transplantation is a highly successful treatment for all types of liver failure, some non-liver failure indications and liver cancer. Most referrals come from secondary care. This first part of a two-part guideline outlines who to refer, and how that referral should be made, including patient details and additional issues such as those relevant to alcohol and drug misuse. The process of liver transplant assessment involves the confirmation of the diagnosis and non-reversibility, an evaluation of comorbidities and exclusion of contraindications. Finally, those making it onto the waiting list require monitoring and optimising. Underpinning this process is a need for good communication between patient, their carers, secondary care and the liver transplant service, synchronised by the transplant coordinator. Managing expectation and balancing the uncertainty of organ availability against the inevitable progression of underlying liver disease requires sensitivity and honesty from all healthcare providers and the assessment of palliative care needs is an integral part of this process.

Adult liver transplantation: UK clinical guideline - part 2: surgery and post-operation.

Survival rates for patients following liver transplantation exceed 90% at 12 months and approach 70% at 10 years. Part 1 of this guideline has dealt with all aspects of liver transplantation up to the point of placement on the waiting list. Part 2 explains the organ allocation process, organ donation and organ type and how this influences the choice of recipient. After organ allocation, the transplant surgery and the critical early post-operative period are, of necessity, confined to the liver transplant unit. However, patients will eventually return to their referring secondary care centre with a requirement for ongoing supervision. Part 2 of this guideline concerns three key areas of post liver transplantation care for the non-transplant specialist: (1) overseeing immunosuppression, including interactions and adherence; (2) the transplanted organ and how to initiate investigation of organ dysfunction; and (3) careful oversight of other organ systems, including optimising renal function, cardiovascular health and the psychosocial impact. The crucial significance of this holistic approach becomes more obvious as time passes from the transplant, when patients should expect the responsibility for managing the increasing number of non-liver consequences to lie with primary and secondary care.

Effect of zinc treatment on clinical outcomes in patients with liver cirrhosis: A systematic review and meta-analysis.

BACKGROUND: Zinc is an essential trace element integral to many cellular and immune functions. Zinc deficiency is highly prevalent in patients with cirrhosis and related to disease severity. AIM: To evaluate whether zinc supplementation improves clinical outcomes (disease severity and mortality) in patients with cirrhosis. METHODS: This prospectively registered systematic review (PROSPERO reference: CRD42018118219) included all studies in Medline, Embase or Cochrane database with inclusion criteria of adult human studies, comparing zinc supplementation of at least 28 d with standard care or placebo in patients with cirrhosis. Mortality and clinical severity score data were extracted. Random effects meta-analyses compared mortality at 6 mo and 2 years. Risk of bias was assessed using the National Institutes of Health quality assessment tool. RESULTS: Seven hundred and twelve articles were identified of which four were eligible. Zinc formulations and doses varied (elemental zinc 3.4-214 mg daily) for different intervention periods in patients with differing etiology and severity of cirrhosis. Two studies were considered to be at high risk of bias. There was no significant difference in 6-mo mortality between patients treated with zinc versus controls [risk ratio 0.98 (0.90-1.05)]. Changes in severity scores were not reported in any study. CONCLUSION: Zinc supplementation is not associated with reduced mortality in patients with cirrhosis. Findings are limited by the small number of eligible studies and significant heterogeneity in intervention and patient population.

Trace element deficiency is highly prevalent and associated with infection and mortality in patients with alcoholic hepatitis.

BACKGROUND: Malnutrition is common in patients with alcohol-related liver disease and is associated with outcome in patients with alcoholic hepatitis. Trace elements (cobalt, copper, iron, selenium and zinc) are micronutrients essential for many cellular processes including antioxidant pathways. The prevalence and relevance of trace element deficiency is unknown in alcoholic hepatitis. AIM: To determine the prevalence of trace element deficiency and its association with clinical outcomes in patients with alcoholic hepatitis. METHODS: Serum was obtained from patients with alcoholic hepatitis, alcohol-related cirrhosis and healthy volunteers as part of clinical trials, cohort studies and a biobank. Trace element concentration was measured by inductively coupled plasma mass spectrometry. Association of trace element levels with development of infection within 90 days and mortality within 28 and 90 days was evaluated by multivariate logistic regression. RESULTS: Sera from 302 patients with alcoholic hepatitis, 46 with alcohol-related cirrhosis and 15 healthy controls were analysed for trace element concentration. The prevalence of zinc deficiency (85%) and selenium deficiency (67%) in alcoholic hepatitis was higher than in alcohol-related cirrhosis (72% [p=0.04] and 37% [p<0.001], respectively). Zinc, selenium, copper and chromium were significantly different between groups. Iron deficiency was a predictor of development of infection within 90 days. Zinc deficiency was a predictor of mortality within 28 and 90 days. CONCLUSION: Trace element deficiency in patients with alcoholic hepatitis is highly prevalent and associated with infection and mortality. Supplementation with selected trace elements may improve clinical outcomes in this patient group but further insight is required of their biological and clinical effects.

Risk-adjusted survival in liver transplant patients assessed and managed by a non-transplanting centre: South West Liver Unit experience.

BACKGROUND: Liver transplant services remain a scarce resource not reflective of geography or burden of liver disease within the UK. To address geographical concerns in the South West (SW), a devolved network model of care for liver transplantation was established in 2004 between the SW Liver Unit (SWLU) at Derriford Hospital, Plymouth and King's College Hospital, London. The SWLU has evolved to deliver both pre-transplant and post-transplant care for patients across the SW Peninsula. We determined whether risk-adjusted survival in patients assessed and managed at the SWLU compared with existing UK transplant centres. DESIGN: Retrospective analysis of records at National Health Service Blood and Transplant (NHSBT) for patients ≥18 years listed or undergoing first liver only deceased donor transplantation from 1 January 2006 to 31 December 2017. Data collected and used were in accordance with standard NHSBT outcome measures. RESULTS: We identified 8492 patients registered for first liver only transplant and 6140 patients who subsequently underwent transplantation. Of these, 215 patients listed and 172 patients transplanted were registered at the SWLU. The 1-year, 5-year and 10-year risk-adjusted post-listing survival for patients registered at the SWLU were 86%, 75% and 67%, respectively, with 1-year and 5-year risk-adjusted post-transplant survival 94.9% and 84.4%, respectively. CONCLUSIONS: Risk-adjusted post-listing 1-year, 5-year and 10-year survival outcomes and risk-adjusted 1-year and 5-year post-transplant survival outcomes at the SWLU are good and comparable with the seven UK transplant centres. These outcomes provide assurance that care delivered by our regional programme is equivalent to well-established liver transplant programmes.

Characterisation of the Serum Metabolic Signature of Cholangiocarcinoma in a United Kingdom Cohort.

BACKGROUND: A distinct serum metabonomic pattern has been previously revealed to be associated with various forms of liver disease. Here, we aimed to apply mass spectrometry to obtain serum metabolomic profiles from individuals with cholangiocarcinoma and benign hepatobiliary diseases to gain an insight into pathogenesis and search for potential early-disease biomarkers. METHODS: Serum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer. A total of 47 serum specimens from 8 cholangiocarcinoma cases, 20 healthy controls, 8 benign disease controls (bile duct strictures) and 11 patients with hepatocellular carcinoma (as malignant disease controls) were included. Data analysis was performed using univariate and multivariate statistics. RESULTS: The serum metabolome disparities between the metabolite profiles from healthy controls and patients with hepatobiliary disease were predominantly related to changes in lipid and lipid-derived compounds (phospholipids, bile acids and steroids) and amino acid metabolites (phenylalanine). A metabolic pattern indicative of inflammatory response due to cirrhosis and cholestasis was associated with the disease groups. The abundance of phospholipid metabolites was altered in individuals with liver disease, particularly cholangiocarcinoma, but no significant difference was seen between profiles from patients with benign biliary strictures and cholangiocarcinoma. CONCLUSION: The serum metabolome in cholangiocarcinoma exhibited changes in metabolites related to inflammation, altered energy production and phospholipid metabolism. This study serves to highlight future avenues for biomarker research in large-scale studies.

Sequential Cohort Analysis After Liver Transplantation Shows de Novo Extended Release Tacrolimus Is Safe, Efficacious, and Minimizes Renal Dysfunction.

The use of once-daily extended-release tacrolimus (ERT) is associated with improved long-term graft and patient survival when compared with twice-daily tacrolimus (BDT), but the underlying reasons for differential survival are unclear. The aim of the study was to compare clinical outcomes known to impact on posttransplant survival for de novo BDT and ERT in liver transplantation (LT) recipients. METHODS: We conducted a single-center, prospective sequential cohort analysis of adult patients undergoing LT during a change in protocol from de novo BDT to ERT, with a 6-month post-LT follow-up. RESULTS: A total of 160 transplanted patients were evaluated; 82 were in the BDT group and 78 were in the ERT group. The cohorts were matched for standard variables and a similar proportion in each group received induction interleukin-2 receptor antibody (36% and 31%). There were no significant differences in the measured outcomes of patient and graft survival, biopsy-proven acute rejection episodes, post LT diabetes, and toxicity. A significantly lower number of patients developed chronic kidney disease Stage3-4 in the ERT cohort compared with BDT cohort. In patients with pre-LT renal dysfunction who received antibody induction, estimated glomerular filtration rate decreased significantly in the BDT but not the ERT group. CONCLUSIONS: We show that once-daily ERT is as safe and efficacious as BDT in de novo LT but optimally conserves renal function post-LT.