Clinical Features, Outcomes, and Response to Corticosteroid Treatment of Acute Tubulointerstitial Nephritis: A Single-Centre Retrospective Cohort Study in the Czech Republic.

INTRODUCTION: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN. METHODS: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records. RESULTS: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) µmol/L in the conservatively managed group versus 374 (249-558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001). CONCLUSIONS: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.

Corrigendum: Delphi: A Democratic and Cost-Effective Method of Consensus Generation in Transplantation.

[This corrects the article DOI: 10.3389/ti.2023.11589.].

Corrigendum: Thrombotic Microangiopathy in the Renal Allograft: Results of the TMA Banff Working Group Consensus on Pathologic Diagnostic Criteria.

[This corrects the article DOI: 10.3389/ti.2023.11590.].

Delphi: A Democratic and Cost-Effective Method of Consensus Generation in Transplantation.

The Thrombotic Microangiopathy Banff Working Group (TMA-BWG) was formed in 2015 to survey current practices and develop minimum diagnostic criteria (MDC) for renal transplant TMA (Tx-TMA). To generate consensus among pathologists and nephrologists, the TMA BWG designed a 3-Phase study. Phase I of the study is presented here. Using the Delphi methodology, 23 panelists with >3 years of diagnostic experience with Tx-TMA pathology listed their MDC suggesting light, immunofluorescence, and electron microscopy lesions, clinical and laboratory information, and differential diagnoses. Nine rounds (R) of consensus resulted in MDC validated during two Rs using online evaluation of whole slide digital images of 37 biopsies (28 TMA, 9 non-TMA). Starting with 338 criteria the process resulted in 24 criteria and 8 differential diagnoses including 18 pathologic, 2 clinical, and 4 laboratory criteria. Results show that 3/4 of the panelists agreed on the diagnosis of 3/4 of cases. The process also allowed definition refinement for 4 light and 4 electron microscopy lesions. For the first time in Banff classification, the Delphi methodology was used to generate consensus. The study shows that Delphi is a democratic and cost-effective method allowing rapid consensus generation among numerous physicians dealing with large number of criteria in transplantation.

Thrombotic Microangiopathy in the Renal Allograft: Results of the TMA Banff Working Group Consensus on Pathologic Diagnostic Criteria.

The Banff community summoned the TMA Banff Working Group to develop minimum diagnostic criteria (MDC) and recommendations for renal transplant TMA (Tx-TMA) diagnosis, which currently lacks standardized criteria. Using the Delphi method for consensus generation, 23 nephropathologists (panelists) with >3 years of diagnostic experience with Tx-TMA were asked to list light, immunofluorescence, and electron microscopic, clinical and laboratory criteria and differential diagnoses for Tx-TMA. Delphi was modified to include 2 validations rounds with histological evaluation of whole slide images of 37 transplant biopsies (28 TMA and 9 non-TMA). Starting with 338 criteria in R1, MDC were narrowed down to 24 in R8 generating 18 pathological, 2 clinical, 4 laboratory criteria, and 8 differential diagnoses. The panelists reached a good level of agreement (70%) on 76% of the validated cases. For the first time in Banff classification, Delphi was used to reach consensus on MDC for Tx-TMA. Phase I of the study (pathology phase) will be used as a model for Phase II (nephrology phase) for consensus regarding clinical and laboratory criteria. Eventually in Phase III (consensus of the consensus groups) and the final MDC for Tx-TMA will be reported to the transplantation community.

A case report: Acute kidney injury with progression to chronicity in an eldery woman.

Acute renal failure in elderly patients can be caused by a wide spectrum of diseases that usually have a cause outside the kidney. The most common causes include renal impairment as part of ANCA vasculitis, another category includes clonal plasmatic cell disease with light chain cast nephropathy; and there also exists an increasing number of drug-induced tubulointerstial damage. We present a case of iatrogenic less common form of acute failure in a 73-year-old woman, who did not suffer from any serious disease until then. Although the biopsy helped to determine the cause of the failure and thus affect subsequent therapy, the function did not return to the previous state and the patient progressed to CKD G3bA1 with serum creatinine values of around 170-140 µmol/l.

A mutation in the SAA1 promoter causes hereditary amyloid A amyloidosis.

Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys being the most commonly and earliest affected organ. Previously described amyloid A amyloidosis is linked to increased production and deposition of serum amyloid A proteins secondary to inflammatory conditions arising from infectious, metabolic, or genetic causes. Here we describe a family with primary amyloid A amyloidosis due to a chr11:18287683 T>C (human genome version19) mutation in the SAA1 promoter linked to the amyloidogenic SAA1.1 haplotype. This condition leads to a doubling of the basal SAA1 promoter activity and sustained elevation of serum amyloid A levels that segregated in an autosomal dominant pattern in 12 genetically affected and in none of six genetically unaffected relatives, yielding a statistically significant logarithm of odds (LOD) score over 5. Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed specifically of the SAA1.1 isoform. Tocilizumab (a monoclonal antibody against the interleukin-6 receptor) had a beneficial effect when prescribed early in the disease course. Idiopathic forms represent a significant and increasing proportion (15-20%) of all diagnosed cases of amyloid A amyloidosis. Thus, genetic screening of the SAA1 promoter should be pursued in individuals with amyloid A amyloidosis and no systemic inflammation, especially if there is a positive family history.

Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis.

BACKGROUND: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with immunoglobulin A nephropathy (IgAN) and patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the enzyme-linked immunosorbent assay PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores. RESULTS: S-ETP and U-ETP/Cr levels correlated with kidney function, increased CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort. CONCLUSIONS: We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys.

Renal involvement of a patient with Crohn´s disease: A case report.

Inflammatory bowel disease (IBD) is a group of chronic relapsing intestinal inflammatory processes primarily represented by ulcerative colitis (UC) and Crohn´s disease (CD). Nearly half of IBD cases are followed by extraintestinal complications and renal involvement can occur independatly or along with other complications and are described with the patients sufferring from UC or CD. Most frequent renal involvement is nephrolithiasis, tubulointerstinal nephritis, different kinds of glomerulonephritis and AA amyloidosis. We are presenting an unusal form of renal involvement of a young female patient with a severe form of Crohn´s disease treated with recombinant monoclonal antibodies.

Fabry disease with cardiovascular manifestation in a patient with end-stage renal disease.

Fabry disease is a rare X-linked hereditary storage disease caused by a mutation of the gene encoding alpha-galactosidase A. The clinical manifestation of the classical disease form is variable depending on the degree of individual organs involvement, including especially kidney, myocardium, central nervous system (CNS) and skin. We report a case of a 51-year-old man whose diagnostic manifestation was cardiac involvement leading to endomyocardial biopsy, which significantly contributed to the diagnosis. Although at that time he was already 9 years dependent on dialysis with terminal renal failure.

De novo HLA Class II antibodies are associated with the development of chronic but not acute antibody-mediated rejection after liver transplantation - a retrospective study.

Donor-specific antibodies (DSA) cause antibody-mediated rejection (AMR); however, their pathogenic role has not yet been adequately investigated after liver transplantation. The aim of our study was to analyse the clinical significance of DSA and complement-binding DSA for the prediction of AMR after liver transplantation. Our cohort included 120 liver recipients with assessed protocol biopsies one year post-transplant. All patients had defined HLA-specific and complement-binding (C1q + and C3d+) antibodies before and in regular intervals after transplantation. The incidence of DSA was evaluated in relation with clinical and histopathological data in the liver allografts. A higher occurrence of acute AMR was observed in recipients with preformed complement-binding DSA to HLA Class I antigens. Patients who developed chronic AMR had more frequently de novo-produced antibodies against HLA Class II antigens (P = 0.0002). A correlation was also found between de novo-formed C1q + and C3d+-binding antibodies to HLA Class II antigens and the development of chronic AMR (P = 0.043). Our study implies that preformed complement-binding DSA to HLA Class I antigens are related to increased risk of acute antibody-mediated rejection, while chronic AMR is more frequent in patients with de novo-produced antibodies to HLA Class II antigens after liver transplantation.

How to improve the histopathological diagnosis of systemic vasculitides in daily practice?

The most common group of systemic vasculitides in adulthood are anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). AAV represent autoimmune systemic vasculitides and include 3 clinical phenotypes: Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis), Microscopic polyangiitis (MPA) and Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). Histological features are similar to each other in all affected locations, and there are represented by necrotizing vascular inflammation of small and medium calibers, often venules, capillaries or arteriols, typically with fibrinoid vessel wall necrosis. The consequences of this condition are bleeding, as well as compromise of the lumen which may result in downstream tissue ischemia and necrosis. Typically affected locations in biopsy practice are: ENT, lung, skin, GIT, and kidney. The aim of this review is to provide a comprehensive overview of the important histopathological findings. ANCA positive vasculitis is a serious life-threatening disease and therefore requires a rapid diagnosis and appropriate therapy.

Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort.

BACKGROUND: The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. RESULTS: All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). CONCLUSION: We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.

Mutational screening of inverted formin 2 in adult-onset focal segmental glomerulosclerosis or minimal change patients from the Czech Republic.

BACKGROUND: Mutations in INF2 are frequently responsible for focal segmental glomerulosclerosis (FSGS), which is a common cause of end stage renal disease (ESRD); additionally, they are also connected with Charcot-Marie-Tooth neuropathy. INF2 encodes for inverted formin 2. This protein participates in regulation of the dynamics of the actin cytoskeleton, involving not only the polymerisation, but also the depolymerisation of filaments. The present study is the first mutational analysis of INF2 done in the Czech Republic. METHODS: Mutational analysis of INF2 was performed on 109 patients (mean age at onset 41.44 ± 18.91 years) with FSGS or minimal change disease (MCD); and also in 6 patients without renal biopsy who had already developed chronic kidney disease (CKD)/ESRD at the time of diagnosis. We used high resolution melting method (HRM), with subsequent Sanger sequencing, in suspect samples from HRM analysis. The HRM method is an effective method for the screening of large cohorts of patients. RESULTS: Two pathogenic mutations (p.Arg214His and p.Arg218Gln) were detected in INF2. The first (p.Arg214His) was identified in the FSGS patient with a positive family history. The second mutation (p.Arg218Gln) was found in two brothers with ESRD of unknown etiology. The most frequent sequence change was the substitution p.P35P, the incidence of which corresponded with the frequencies available in the ExAC Browser and gnomAD Browser databases. This analysis also detected different exonic and intronic changes that probably did not influence the phenotype of the included patients. CONCLUSIONS: The INF2 mutational screening is useful in familial FSGS cases as well as in patients with an unknown cause for their ESRD, but with a positive family history. INF2 seems to be not only the cause of FSGS, but also of ESRD of unknown etiology. Our study has confirmed that the HRM analysis is a very useful method for the identification of single nucleotide substitutions.

Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis.

BACKGROUND: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. METHODS: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. RESULTS: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15-34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9-19) mL/min/1.73 m2. Over a median (IQR) follow-up of 33.5 (17-82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). CONCLUSIONS: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

Early isolated V-lesion may not truly represent rejection of the kidney allograft.

Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n=6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n=4) and non-rejection histologic findings (n=8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n=12) and TCMRV (n=8) samples. The transcriptome of early IV (< 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.

Isolated v-lesion represents a benign phenotype of vascular rejection of the kidney allograft - a retrospective study.

While the detrimental impact of the humoral acute vascular rejection (AVR) phenotype is recognized, the prognostic significance of isolated v-lesion (IV) remains unclear. In this retrospective single-centre study, AVR was found in 98 of 1015 patients (9.7%) who had undergone kidney transplantation in 2010-2014, with donor-specific antibodies (DSA) evaluated in all of them. The outcome of four AVR phenotypes was evaluated during median follow-up of 59 months; in 25 patients with IV, 18 with T-cell-mediated vascular rejection (TCMVR), 19 with antibody-mediated vascular rejection (AMVR) and 36 with suspected antibody-mediated rejection (sAMVR). AVR was diagnosed mainly by for-cause biopsy (81%) early after transplantation (median 19 POD) and appeared as mild-grade intimal arteritis. IV occurred in low-sensitized patients after the first transplantation (96%) in the absence of DSA. IV responded satisfactorily to treatment (88%), showed no persistence of rejection in surveillance biopsy, and had stable graft function, minimal proteinuria and excellent DCGS (96%). Contrary to that, Kaplan-Meier estimate of 3-year DCGS of AMVR was 66% (log-rank = 0.0004). Early IV represents a benign phenotype of AVR with a favourable outcome. This study prompts further research to evaluate the nature of IV before considering any change in the classification and management.

Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort.

BACKGROUND: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. METHODS: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. RESULTS: In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ≥0.4 g/day/1.73 m2 and an eGFR of <90 ml/min/1.73 m2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m2) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. CONCLUSION: This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

[Intestinal transplantation in Czech Republic]. / Transplantace tenkého streva v Ceské republice.

Intestinal transplantation represents a suitable treatment for patients with intestinal failure who then develop life-threatening complications of total parenteral nutrition and for some patients with complex abdominal disorders not suitable for conventional treatment. METHODS: prior to launch of the clinical program, preparation started in 2006 initially with extensive experimentation carried out on pigs. The clinical phase involved a specialized, multidisciplinary team who examined 23 patients being considered for transplantation. Seven patients were put on a waiting list and one female, due to the improvement of her medical status, was unlisted. The first ever intestinal transplantation was done in 2014. RESULTS: three out of six transplanted patients are alive with 380 days of actual survival; median 131 days (63-763). Two patients are on a full oral diet and nutritionally independent with an excellent quality of life. One female is nutritionally independent but with the need for partial supplemental parenteral rehydration due to the stomal output. CONCLUSION: intestinal transplantation is a suitable treatment for highly selected patients with intestinal failure who meet specific listing criteria.

Prevalence and risk factors of steatosis after liver transplantation and patient outcomes.

Steatosis occurs frequently after liver transplantation (LT). We aimed to determine the prevalence of steatosis in adult LT recipients, to determine the effects of significant (>33%; grades 2-3) steatosis on patient survival, and to identify risk factors for the development of significant steatosis and its effect on fibrosis progression. We retrospectively examined 2360 posttransplant biopsies of 548 LT recipients. Survival was compared between patients with significant steatosis and those with grades 0-1 steatosis. Patients with significant steatosis were compared to controls without steatosis (grade 0) for clinical and laboratory factors and fibrosis progression. Steatosis was found in 309 (56.4%) patients, including 93 (17.0%) patients with significant steatosis. Steatohepatitis (nonalcoholic fatty liver disease activity score ≥ 5) was diagnosed in 57 (10.4%) patients. The prevalence of steatosis increased from 30.3% at 1 year to 47.6% at 10 years after LT (P < 0.001). Survival times did not differ between groups (P = 0.29). On multivariate analysis of pretransplant factors and initial immunosuppression (IS), alcohol-induced cirrhosis (P < 0.001) and high body mass index (BMI; P = 0.002) were associated with the development of significant steatosis, whereas increased levels of alkaline phosphatase (P = 0.01) and mycophenolate mofetil given initially (P = 0.009) appeared to protect against significant steatosis. On multivariate analysis of posttransplant factors, high BMI (P < 0.001), serum triglycerides (P < 0.001), alcohol consumption (P = 0.005), and type 2 diabetes mellitus (P = 0.048) were associated with significant steatosis, whereas high creatinine (P = 0.02) appeared to protect against significant steatosis. Significant steatosis was not associated with a higher fibrosis stage (P = 0.62). Posttransplant steatosis affects 56.4% of LT recipients, and the prevalence increases with time after LT. Recipient factors and types of IS affect the risk for significant steatosis, which is not associated with a higher fibrosis stage or worse patient survival. Liver Transplantation 22 644-655 2016 AASLD.