Fibrosis In Biopsies Research Articles

The Relationship of Vitamin D Level with Renal Prognosis in Focal Segmental Glomerulosclerosis Patients- A Retrospective Study

Introduction: The level of 25-hydroxyvitamin D3 is an independent predictor of disease progression and death in Chronic Kidney Disease (CKD) patients. However, there are insufficient data to evaluate the possible effects of plasma 25(OH)D3 levels on the prognosis of Focal Segmental Glomerulosclerosis (FSGS). Aim: To analyse the relationship between renal prognosis and serum 25(OH)D3 status in FSGS. Materials and Methods: The study was conducted on 56 patients, who were followed-up for at least one year and diagnosed with primary FSGS. Participants were grouped according to their baseline 25(OH)D3 levels (≤15 or >15 ng/mL) and treatment response at the end of one year (remission group or no remission group) was evaluated. Results: Mean age of the 56 participants was 44±13.92 years and 27 (48.2%) were male. Remission achievement in the first year was significantly higher and interstitial fibrosis was significantly lower for the group with a 25(OH)D3 above >15 ng/ mL (p<0.001, p=0.002, respectively). Basal serum 25(OH)D3 level was significantly lower and interstitial fibrosis and tubular atrophy percentages were higher for the ‘no remission’ group (p<0.001, p<0.001, p=0.005, respectively). Results of the binary logistic regression analysis revealed that low 25(OH)D3 level and higher interstitial fibrosis were independent predictive factors that increased the risk of no remission in the first year (p=0.036, p=0.004, respectively). Conclusion: In primary FSGS patients, low baseline 25(OH)D3 level at the time of biopsy and high interstitial fibrosis are independent predictors that reduce remission rates in the first year.

Factors Influencing Transient Elastography in Detecting Liver Stiffness

Transient elastography (TEE) is a method used for estimating liver fibrosis by measuring the liver stiffness (LSM). Aim of this study was to investigate whether TEE fibrosis scores and liver biopsy fibrosis scores are comparable. It was a Cross sectional study of patients undergoing liver biopsy because of high TEE with persistent transaminitis/normal TEE with persistent transaminitis/high TEE with normal transaminases. TEE fibrosis score of study population was compared to liver biopsy fibrosis scores, which is considered as gold standard, and patients with discordance of more than one fibrosis stage was analyzed with above mentioned variables which can affect TEE. Characteristics of the discordant population was analysed. After applying spearmanˊs correlation it was found that albumin, Total bilirubin and INR had a strong correlation with TEE values. Multiple regression analysis showed albumin and SGOT were independent predictors of Liver stiffness measurement. The discordant population was again analysed after classifying it into two groups i.e F 0-2 (minimal fibrosis) and F 3 (significant fibrosis based on biopsy). After analysis it was found that in F 0-2 group there were certain variables like SGPT, Albumin and INR which had strong correlation with TEE values. Total bilirubin and platelets had moderate correlation with TEE values. After analysing F3 group, age had strong positive correlation with TEE values. TEE was found to be better in detecting liver stiffness than liver biopsy in clinically suspected cirrhosis in this study.

I-IFTA and chronic active T cell-mediated rejection: A tale of 2 (DeKAF) cohorts.

Inflammation in areas of fibrosis (i-IFTA) in posttransplant biopsies is part of the diagnostic criteria for chronic active TCMR (CA TCMR -- i-IFTA ≥ 2, ti ≥ 2, t≥2). We evaluated i-IFTA and CA TCMR in the DeKAF indication biopsy cohorts: prospective (n=585, mean time to biopsy=1.7years); cross-sectional (n=458, mean time to biopsy=7.8years). Grouped by i-IFTA scores, the 3-year postbiopsy DC-GS is similar across cohorts. Although a previous acute rejection episode (AR) was more common in those with i-IFTA on biopsy, the majority of those with i-IFTA had not had previous AR. There was no association between type of previous AR (AMR, TCMR) and presence of i-IFTA. In both cohorts, i-IFTA was associated with markers of both cellular (increased Banff i, t, ti) and humoral (increased g, ptc, C4d, DSA) activity. Biopsies with i-IFTA=1 and i-IFTA≥2 with concurrent t≥2 and ti ≥ 2 had similar DC-GS. These results suggest that (a) i-IFTA≥1 should be considered a threshold for diagnoses incorporating i-IFTA, ti, and t; (b) given that i-IFTA ≥ 2,t≥2, ti ≥ 2 can occur in the absence of preceding TCMR and that the component histologic scores (i-IFTA,t,ti) each indicate an acute change (albeit i-IFTA on the nonspecific background of IFTA), the diagnostic category "CA TCMR" should be reconsidered.

S3257 A Comparison of Non-Obese Non-Alcoholic Fatty Liver Disease (NAFLD) and Obese NAFLD Patients

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. The relationship between NAFLD and obesity is well-established. However, it is known that NAFLD can affect the non-obese as well, and less is understood about this population of NAFLD patients. Our study aimed to further investigate possible differences between obese and non-obese NAFLD to further our understanding of non-obese NAFLD. METHODS: An EMR search of appropriately coded patients was performed. Medical records were manually searched for pertinent variables. Non-obese NAFLD was determined those with biopsy-proven NAFLD and BMI ≤30. Of the NAFLD population identified, 64 patients were found to have non-obese NAFLD. Each patient was matched with an obese (BMI >30) NAFLD patient of the same gender and age-decade. A two-tailed students t-test based and chi-squared test were performed to determine differences. RESULTS: A total of 64 non-obese NAFLD (BMI ≤30) patients were identified. Each patient was matched with a >30 BMI patient of the same gender and age-decade; total study size 128 patients (N = 128). There were 27/64 males (42%) and 37/64 females (58%). Average age and BMI of the non-obese vs obese patients was 55 years and 25, and 54 years and 37, respectively. In non-obese vs obese patients, total number affected and means were calculated for a number of pertinent variables including diabetes, dyslipidemia, hemoglobin A1c, CKD stage (mean 0.4 vs 0.7), HDL, LDL, statin usage, HTN, steatosis grade, presence of steatohepatitis, fibrosis score, LDL/HDL ratio, transferrin saturation, ceruloplasmin, ferritin, AST, ALT, platelet count, MPV, APRI score, and Fib4 score. Analysis was then performed to determine any significant differences. This showed that Fib4 was significantly (P = 0.032), even though fibrosis scores between the two groups were not significantly different. A history of dyslipidemia was nearly significant (P = 0.051) as well, but did not meet established P-value cutoffs. CONCLUSION: Our study provides further data on characteristic of and differences between non-obese NAFLD and obese NAFLD populations. It showed significantly different Fib4 score results between the two populations, even though biopsy fibrosis scores were not significantly different. If replicated on further studies, this could suggest uncertainty interpreting Fib4 scores in the non-obese NAFLD population. The study is limited by small sample size. More research is needed to broaden understanding of non-obese NAFLD.Table 1.: Demographics: number of patients in each age/gender grouping in both categories, non-obese and obese NAFLDTable 2.: Comparisons of variables between non-obese (BMI ≤30) and obese (BMI >30) patient populations; x = mean, N = number affectedTable 3.: Statistical analysis between non-obese and obese NAFLD populations showing significantly different values of Fib4 scores between the two populations

Furosemide stress test and interstitial fibrosis in kidney biopsies in chronic kidney disease

BackgroundInterstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2 h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST.MethodsThis study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6 h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation.ResultsThe mean age of the participants was 38 years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p = 0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r = − 0.245, p = 0.02) was observed.ConclusionsOur findings indicate that interstitial fibrosis correlates with total urine output and FEM. Further studies are needed to determine if UO and FST could be a non-invasive tool to evaluate interstitial fibrosis.Trial registrationClinicalTrials.gov NCT02417883.

SUN-316 Binding of β-catenin to TCF1 and FoxO1 controls TGF-beta fibrogenic signalling pathways and predicts adverse outcomes in transplanted kidneys

Chronic injury and maladptive fibrotic repair in kidney transplants remains the major cause of allograft loss. Transforming growth factor β (TGF-β) is a key cytokine causing fibrosis. Our recent work has demonstrated that β-catenin binding to Foxo or TCF determines the signaling direction of TGF-β, oscillating between profibrotic and anti-inflammatory pathways in murine models of kidney fibrosis. To explore the relevance of our findings to human disease, we examined β-catenin/FoxO1 and β-catenin/TCF1 in relation to the severity of kidney inflammation, fibrosis and dysfunction in biopsies of kidney transplant patients. Our aim was to examine control of fibrogenic pathways, and determine their prognostic value in clincially relevant outcomes in kidney transplantation. We simultaneously quantified binding of FoxO1 and TCF1 to β-catenin within tubular cells using a proximity ligation assay in 164 transplanted kidneys. eGFR and serum creatinine were measured on the day of biopsy and all biopsies were evaluated for fibrosis by renal pathologists according to the Banff classification. The ratio of β-catenin/TCF1 to β-catenin/FoxO1 binding (TF ratio) was calculated, and multivariable linear and logistic regression models were used for predictive analysis. Cox regression analysis was used to explore the relationship between TF ratio and chronic fibrosis. ROC curve was used for specificity and sensitivity analysis. The one month TF ratio correlated with reduced eGFR (r=-0.556, P<0.001) and increased serum creatinine (r=0.507, P<0.001), albuminuria (r=0.276, P=0.036) Banff ci (r=0.273, P=0.002) and ct scores (r=0.316, P<0.001) at 12 months in kidney transplant patients. Using multivariable linear regression, one year eGFR was only predictable by eGFR (β=0.548, p<0.001) and TF ratio (β=-5.905, p=0.002) at one month. Progression to 1-year moderate fibrosis (Banff ci≥2), was predicted by one month TF ratio (OR=3.221, 95%CI 1.610-6.444, P<0.001) adjusted for baseline pathology using logistic regression. Multivariable models confirmed TF ratio was a consistent and independent risk factor for progressive fibrosis, withstanding adjustment for multiple confounding clinical risk factors. The adjusted hazard ratio of one month TF was 1.773 (95%CI 1.416-2.221, P<0.001). The one month TF ratio predicted Banff ci≥1 fibrosis (AUC=0.717, 95%CI 0.522-0.712, P<0.001) or ci≥2 fibrosis (AUC=0.769, 95%CI 0.660-0.857, P<0.001) at 12-months. The predictive ability of one month TF ratio for 12 month functional impairment was impressive (AUC 0.817, 95%CI 0.746-0.887, P<0.001). The full model including TF ratio was optimal and highly predictive of late renal impairment (AUC 0.914, 95%CI 0.863-0.964, P<0.001). This study demonstrated that differences in binding of TCF1 or FoxO1 to β-catenin affects the direction of fibrogenic signalling and renal transplant outcomes, including intra-renal fibrogenesis and inflammation. The TF ratio at one month was associated with adverse renal fibrosis and clinical outcomes at one year. It may serve as a novel and powerful prognostic biomarker of progressive fibrosis, proteinuria and graft dysfunction. Altering the balance of β-catenin-associated transcriptional activity may be an interventional target for preventative anti-fibrotic therapy.

Advanced fibrosis is associated with incident cardiovascular disease in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy-proven NAFLD without pre-existing cardiovascular disease. From 2011 to 2018, adults with biopsy-proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow-up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. After a median follow-up time of 5.2years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3-4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36-6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non-invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. In adults with biopsy-proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.

High-Throughput, Machine Learning–Based Quantification of Steatosis, Inflammation, Ballooning, and Fibrosis in Biopsies From Patients With Nonalcoholic Fatty Liver Disease

Background & AimsLiver biopsy is the reference standard for staging and grading nonalcoholic fatty liver disease (NAFLD), but histologic scoring systems are semiquantitative with marked interobserver and intraobserver variation. We used machine learning to develop fully automated software for quantification of steatosis, inflammation, ballooning, and fibrosis in biopsy specimens from patients with NAFLD and validated the technology in a separate group of patients.MethodsWe collected data from 246 consecutive patients with biopsy-proven NAFLD and followed up in London from January 2010 through December 2016. Biopsy specimens from the first 100 patients were used to derive the algorithm and biopsy specimens from the following 146 were used to validate it. Biopsy specimens were scored independently by pathologists using the Nonalcoholic Steatohepatitis Clinical Research Network criteria and digitalized. Areas of steatosis, inflammation, ballooning, and fibrosis were annotated on biopsy specimens by 2 hepatobiliary histopathologists to facilitate machine learning. Images of biopsies from the derivation and validation sets then were analyzed by the algorithm to compute percentages of fat, inflammation, ballooning, and fibrosis, as well as the collagen proportionate area, and compared with findings from pathologists’ manual annotations and conventional scoring systems.ResultsIn the derivation group, results from manual annotation and the software had an interclass correlation coefficient (ICC) of 0.97 for steatosis (95% CI, 0.95–0.99; P < .001); ICC of 0.96 for inflammation (95% CI, 0.9–0.98; P < .001); ICC of 0.94 for ballooning (95% CI, 0.87–0.98; P < .001); and ICC of 0.92 for fibrosis (95% CI, 0.88–0.96; P = .001). Percentages of fat, inflammation, ballooning, and the collagen proportionate area from the derivation group were confirmed in the validation cohort. The software identified histologic features of NAFLD with levels of interobserver and intraobserver agreement ranging from 0.95 to 0.99; this value was higher than that of semiquantitative scoring systems, which ranged from 0.58 to 0.88. In a subgroup of paired liver biopsy specimens, quantitative analysis was more sensitive in detecting differences compared with the nonalcoholic steatohepatitis Clinical Research Network scoring system.ConclusionsWe used machine learning to develop software to rapidly and objectively analyze liver biopsy specimens for histologic features of NAFLD. The results from the software correlate with those from histopathologists, with high levels of interobserver and intraobserver agreement. Findings were validated in a separate group of patients. This tool might be used for objective assessment of response to therapy for NAFLD in practice and clinical trials.

946 Factors Leading to Discordance Between Vibration-Controlled Transient Elastography and Liver Biopsy in Patients With Non-Alcoholic Fatty Liver Disease

INTRODUCTION: Vibration-Controlled Transient Elastography (VCTE) or Fibroscan® is used for the non-invasive assessment of liver fibrosis. However, liver biopsy remains the gold standard for diagnosis due to potential inaccuracies of VCTE including, the patient's body mass index and interobserver variance. Therefore, we examined simple lab parameters and patient related factors that might contribute to this discordance, in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). METHODS: Patients were identified using appropriate ICD 9 and 10 coding for NAFLD. We included patients 18 years and older who underwent a VCTE (both the M and XL probe) and liver biopsy within 6 months of each other. Electronic medical records were reviewed manually to extract data. Variables of interest included VCTE liver stiffness measurement (LSM), VCTE fibrosis score and biopsy fibrosis stage according to the NASH CRN Scoring System. Only valid VCTE results (IQR &lt; 30 and with 10 valid readings) were included. Discordance was defined a difference of more than 2 fibrosis stages between VCTE and biopsy results. Mann-Whitney U test was used to compare continuous variables, Fischer’s exact test to compare categorical variables and multivariate analysis for logistic regression. RESULTS: 109 patients with fatty liver on imaging and elevated transaminases without other types of liver disease underwent a Fibroscan and a subsequent biopsy. In 52% of patients (57/109) the Fibroscan overestimated fibrosis by 2 stages. In univariate analysis, discordance was associated with BMI (36 vs 32.9), ALT (45 vs 72), Fibroscan IQR (17.24 vs 13.5), FIB-4 Score (1.65 v/s 2.25), and NAFLD Activity Score (2.33 vs 3.36), (P value &lt; 0.05 for all). In multivariate analysis, BMI was the only factor independently associated with discordance (P &lt; 0.05). CONCLUSION: Although multiple factors may lead to discordant results for the stage of fibrosis between VCTE and liver biopsy, our results indicate that a higher BMI is the major factor for this discordance with the XL probe. These data also suggest that a stepwise approach combining a noninvasive scoring system and VCTE should be explored as an alternative approach to improve the accuracy of noninvasive methods and minimize the need for liver biopsy in NAFLD patients.

The JAK/STAT pathway is activated in systemic sclerosis and is effectively targeted by tofacitinib.

Fibrosis leads to failure of the skin, lungs, and other organs in systemic sclerosis; accounts for substantial morbidity and mortality; and lacks effective therapy. Myofibroblast activation underlies organ fibrosis, but the key extracellular cues driving persistence of the process remain incompletely characterized. The objectives were to evaluate activation of the IL6/JAK/STAT axis associated with fibrosis in skin and lung biopsies from systemic sclerosis patients and effects of the Food and Drug Administration-approved JAK/STAT inhibitor, tofacitinib, on skin and lung fibrosis in animal models. Bioinformatic analysis showed that IL6/JAK/STAT3 and tofacitinib gene signatures were aberrant in biopsies from systemic sclerosis patients in four independent cohorts. The results were confirmed by JAK and STAT3 phosphorylation in both skin and lung biopsies from patients with systemic sclerosis. Furthermore, treatment of mice with the selective JAK inhibitor tofacitinib not only prevented bleomycin-induced skin and lung fibrosis but also reduced skin fibrosis in TSK1/+ mice. These findings implicate the JAK/STAT pathway in systemic sclerosis skin and lung fibrosis and identify tofacitinib as a potential antifibrotic agent for the treatment of systemic sclerosis and other fibrotic diseases.

IgA Nephropathy in Elderly Patients.

Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

SUN-129 The significance of β-catenin/Foxo in kidney transplantation

Transforming growth factor β (TGF-β) is the key cytokine causing fibrosis through cross-talk with major pro-fibrotic pathways. β-catenin is a common co-factor in different TGF-β signaling pathways. Our previous study demonstrated that by promotion of β-catenin binding to Foxo through inhibition of its binding to TCF, TGF-β signaling is redirected from profibrotic to anti-inflammatory and anti-fibrotic pathways in a murine model of kidney fibrosis. To explore the relevance to human disease, we examined β-catenin/Foxo1 and β-catenin/TCF1 in relation to the severity of kidney inflammation, fibrosis and dysfunction in biopsies of kidney transplant patients. We aimed to establish a prognostic value from kidney β-catenin/Foxo1 or β-catenin/TCF1 interactions for clinical outcomes of kidney transplantation. β-catenin/Foxo1 or β-catenin/TCF1 interactions in kidney biopsy samples were examined by proximity ligation assay (PLA). A data set of 33 kidney transplant patients were examined at different stages: pre-transplantation, 1, 3 and 12 months post-transplantation. Pearson correlation analysis was used for β-catenin/Foxo1 and β-catenin/TCF1 in relation to inflammation (i-FITA), fibrosis, and histologic (Banff ci & Banff ct) and functional consequences (eGFR). We found that the ratio of β-catenin/Foxo1 to β-catenin/TCF1 at each stage correlated positively with eGFR (P<0.05), while it correlated negatively with fibrosis score, Banff ci score, Banff ct score and i-FITA (P<0.05). Importantly, β-catenin/Foxo1 to β-catenin/TCF1 ratio pre-transplant correlated negatively with Banff ci score (r=0.921, P<0.05) and i-FITA (r=0.813, P<0.05) at 12 months post-transplant. β-catenin/Foxo1 to β-catenin/TCF1 ratio at 1 month post-transplant correlated positively with the eGFR at 12 months post-transplant (r=0.686, P<0.05), and negatively with Banff ci score (r=0.918, P<0.05), Banff ct score (r=0.688, P<0.05), and i-FITA (r=0.733, P<0.05) at 12 months post-transplant. The ratio of β-catenin/Foxo1 to β-catenin/TCF1 in early transplant biopsies correlates positively with eGFR, but negatively with histological injury, fibrosis and inflammation at one year after kidney transplantation. The ratio of β-catenin/Foxo1 to β-catenin/TCF may serve as a biological indicator of the progression of inflammation and fibrosis in kidney transplantation.

The histological assessment of liver fibrosis in grafts from extended criteria donors predicts the outcome after liver transplantation: A retrospective study

BackgroundThe use of extended criteria donors (ECD) in liver transplantation is increasing due to the organ shortage. Histological evaluation of the liver graft in the context of procurement is an important tool for extending the donor pool without affecting the quality of the transplanted organs. Macrovesicular steatosis is widely accepted as predictor of early allograft dysfunction (EAD), while other features, such as portal fibrosis, are poorly studied. AimTo identify morphological features, other than macrovesicular steatosis, that may affect recipients’ outcome. MethodsBetween 2014 and 2016, 132 donors with extended criteria underwent pre-transplant liver biopsy during procurement. Histological variables of the graft, donors’/recipients’ clinical data, EAD and patient/graft survival were registered. ResultsThe recipients who received a graft with histological-proven portal fibrosis had a significant lower patient and graft survival in comparison to patients without fibrosis (P = 0.044 and P = 0.039, respectively). Donors’ dyslipidemia was significantly associated with the occurrence of EAD (P = 0.021). When dyslipidemia was combined with histological liver fibrosis a 54.5% incidence of EAD was observed (P = 0.012). ConclusionsThe histological assessment of liver fibrosis in pre-transplant biopsy of ECD grafts, together with donor’s clinical data, provides important information on recipients’ outcome.

ARE PATIENTS WITH DIABETIC NEPHROPATHY DIFFERENT REGARDING RENAL ULTRASOUND PARAMETERS AND DOPPLER SONOGRAPHY FINDINGS COMPARED WITH RENAL HISTOPATHOLOGY?

Ultrasonography (US) findings and Doppler sonography of renal vessels can provide useful information on the structural and vascular supply of patients suffering from chronic kidney disease (CKD). The purpose of this study was to compare the US findings of patients with diabetic nephropathy with the pathologic findings of their renal biopsy. In this descriptive study, US parameters including resistivity index (RI), renal size and volume and cortical and medullary echogenicity, and histopathological findings of renal biopsy (fibrosis, inflammation and chronicity) of 60 patients (27 women and 33 men) with diabetic nephropathy admitted in Hasheminejad kidney center (HKC) of Tehran were extracted and analyzed. Of 60 patients, interstitial fibrosis (IF) in 47 patients, interstitial inflammation (II) in 50 patients and signs of chronicity in 43 patients in pathology report were observed. Patients with IF had larger renal length, higher sinus volume, coarse echogenicity, and abnormal medullary echogenicity, significantly. The presence of II was associated with larger renal length, higher renal and sinus volume, higher cortical echogenicity, and more patients with coarse echogenicity and abnormal medullary echogenicity. The observation of chronicity was significantly correlated with higher sinus volume and more patients with irregular renal rim. According to the findings of this study, renal length and volume, renal sinus volume, and the presence of coarse echogenicity and abnormal medullar echogenicity strongly correlate with renal histopathologic findings in patients with diabetic nephropathy. RI is not a suitable marker for identifying tubulointerstitial changes in these patients.

Characteristics and risk factors for recurrence of nonalcoholic steatohepatitis following liver transplantation

Objectives: Nonalcoholic steatohepatitis (NASH), which is a common and increasing indication for liver transplantation (LT), is known to recur after LT. Since the recurrence of NASH can lead to graft failure, the identification of predictive factors is needed and preventive strategies should be implemented.Methods: We retrospectively examined 95 patients who had undergone LT for NASH or alcoholic liver disease (ALD) as a primary indication. We evaluated peritransplant characteristics and histological findings 1-year post LT among liver transplant patients due to NASH or ALD.Results: Pre-LT body mass index (BMI) was higher and pre-LT diabetes was more prevalent in NASH patients than in ALD patients (p < .01). The difference of BMI persisted at 3 months and 1 year after LT. There were no differences between the groups regarding histopathological findings including the degree of steatosis and fibrosis in 1-year biopsy. In multivariate analysis, recipient age and 1-year BMI were independent risk factors for post-LT fatty liver disease development. Regarding predictive factors of NASH recurrence, the prevalence of pre-LT insulin-dependent diabetes was significantly higher in patients who developed NASH recurrence than those who did not. The increase of HbA1c at 1-year post-LT checkup was higher in patients who developed recurrence than those who did not, although the difference did not reach statistical significance.Conclusions: The results of this study suggest that insulin-dependent diabetes has detrimental effects on NASH recurrence following LT. Optimal glycemic control should be recommended, but studies are needed to prove its preventive effect on NASH recurrence.

Steroid therapy in drug induced acute interstitial nephritis- Retrospective analysis of 83 cases

Drug-induced acute interstitial nephritis (DIAIN) is a common cause of acute deterioration of renal function. Early diagnosis and discontinuation of the offending drug usually lead to recovery of renal function. Steroid administration further hastens the recovery. However, the outcome of steroid-treated DIAIN is not well studied in the Indian scenario. We aimed to study the clinical profile and one-year renal outcome of DIAIN patients treated with steroids. We performed a retrospective study in biopsy-proven acute interstitial nephritis (AIN) and presumptive DIAIN patients who did not respond to discontinuation of the offending drug after five days of the diagnosis of AIN. Eighty-three DIAIN patients were included who were treated with 500 mg of methylprednisolone for three consecutive days followed by prednisolone of 0.5-1 mg/kg tapered over four to six weeks. We evaluated clinical profile, serum creatinine (SCr), and need of renal replacement therapy at the end of one year. We divided the patients into two groups: 1st as complete responders group (CR) when SCr is <1.5 mg/dL at the end of one year and 2nd as incomplete responders (IR) when it is ≥1.5 mg/dL and evaluated the outcome between two groups. In total, there were 39 (47%) CR and 44 (53%) were IR. Diabetes mellitus, present in a significant number of cases 27 (33%) was associated with poor response to steroids. Most common offending agents recognized were antibiotics (34%), nonsteroidal anti-inflammatory drugs (25%), herbal medications (13%), proton pump inhibitors (10%), and miscellaneous drugs (18%). There was no correlation between drug category and response to steroids. Interstitial fibrosis in renal biopsy was associated with poor response to steroids (4 cases in CR and 35 cases in IR, P ≤0.0001). Neutrophilic predominance in biopsy was associated with favorable response to steroids. Initial SCr and initial the requirement of dialysis support was not helpful in predicting the response to steroids and final recovery.

Characteristics and risk factors of fatty liver disease development and nonalcoholic steatohepatitis recurrence after liver transplantation

Introduction: Nonalcoholic steatohepatitis (NASH), which is a common and increasing indication for liver transplantation (LT), is known to recur after LT. Since the recurrence of NASH can lead to graft failure, the identification of predictive factors and preventive strategies need to be implemented. Method: We retrospectively identified 694 consecutive patients who had undergone LT at Karolinska University Hospital between June 2007 and February 2017. Of these, 95 patients who received LT for NASH or alcoholic liver disease (ALD) as a primary indication were included. Peritransplant characteristics and histological findings 1 year post-LT among NASH patients were evaluated in comparison with ALD patients. Risk factors of post-LT fatty liver disease development and NASH recurrence were assessed. Result: Among 27 NASH patients, pre-LT body mass index (BMI) was higher (31.3 vs. 28.6, p=0.0095) and pre-LT diabetes was more prevalent than in ALD patients (p<0.0001). The difference of BMI persisted at 3 months and 1 year after LT. There were no differences between the groups regarding histopathological findings including the degree of steatosis and fibrosis in 1-year biopsy. In multivariate analysis, recipient age and 1-year BMI were independent risk factors for post-LT fatty liver disease development. Regarding predictive factors of NASH recurrence, the prevalence of pre-LT insulin dependent diabetes was significantly higher in patients who developed NASH recurrence than those who did not. The increase of HbA1c at 1-year post-LT check-up was higher in patients who developed recurrence than those who did not, although the difference did not reach statistical significance (Δ 15 vs. 5 mmol/mol, p=0.051). Conclusion: The results of this study suggests that insulin dependent diabetes has detrimental effects on NASH recurrence following LT. Optimal glycemic control should be recommended, but studies are needed to prove its preventive effect on NASH recurrence.

Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss.

The individual course of CKD may vary, and improved methods for identifying which patients will experience short-term eGFR loss are needed. Assessing urinary Dickkopf-3 (DKK3), a stress-induced tubular epithelia-derived profibrotic glycoprotein, may provide information about ongoing tubulointerstitial fibrosis and short-term eGFR loss. To investigate urinary DKK3's potential as a biomarker of short-term eGFR loss (over 12 months), we prospectively assessed eGFR and urinary DKK3 levels in patients with CKD of various etiologies at baseline and annual follow-ups. We also measured urinary DKK3 in a general population sample and patients with diagnostic kidney biopsies or IgA nephropathy under treatment. Median urinary DKK3-to-creatinine concentration at baseline was significantly higher in patients with CKD than the general population sample (431 versus 33 pg/mg). In the CKD cohort, having a urinary DKK3-to-creatinine level >4000 pg/mg was independently and significantly associated after multiple adjustments with mean annual decline in eGFR of 7.6% over 12 months. Urinary DKK3 significantly improved prediction of kidney function decline compared with eGFR or albuminuria alone. Urinary DKK3-to-creatinine levels were related to the extent of tubulointerstitial fibrosis in kidney biopsies. In patients with IgA nephropathy, a rise in urinary DKK3 was associated with significant eGFR decline within 6 months, whereas stable or decreasing urinary DKK3 indicated a more favorable course. Urinary DKK3 levels identify patients at high risk for eGFR decline over the next 12 months regardless of the cause of kidney injury and beyond established biomarkers, potentially providing a tool to monitor CKD progression and assess effects of interventions.

22. Factors influencing detection of liver stiffness by transient elastography

Background and Aims: Transient elastography (TEE) is a useful, noninvasive, quantitative method for evaluating liver fibrosis by measuring the liver stiffness (LSM). This study investigated factors affecting detection of liver fibrosis by TEE, in cases where there is a discordance of more than one fibrosis stage between TEE and liver biopsy. Methods: Cross sectional study of patients undergoing liver biopsy because of high TEE with persistent transaminitis/normal TEE with persistent transaminitis/high TEE with normal transaminases. Gender, Age, BMI, CBC, RFT, LFT, Etiology, TEE fibrosis score (within 3 months of liver biopsy), Liver biopsy fibrosis score (Metavir). TEE fibrosis score of study population was compared to liver biopsy fibrosis scores, which is considered as gold standard, and patients with discordance of more than one fibrosis stage was analyzed with above mentioned variables which can affect TEE. Results: 54 patients, 35 male and 19 female were included in the study. Mean age of population was 42.2 years. 32 (59%) had NASH, 14 (25.9%) had Chronic hepatitis B, 6 (11.1%) had Chronic hepatitis C and 2 (3.7%) had Autoimmune hepatitis. After applying Spearman's correlation, INR had moderate strength of positive correlation (rs) value of 0.421 and P value of 0.029. A weak positive correlation was found between Age (0.208), Total bilirubin (0.397), Direct bilirubin (0.286), ALP (0.302), RBS (0.247), HDL (0.279) and LSM. A weak negative correlation was found between Albumin (−0.313), Urea (−0.208), Creatinine (−0.325), Ceruloplasmin (−0.221) and LSM. Conclusions: Age, Bilirubin, ALP, Albumin, RFT, RBS, HDL, Ceruloplasmin, INR, affects the LSM detection by TEE and should be taken into account while interpreting TEE scores. There was no correlation of transaminases with TEE score. The authors have none to declare.

48. Factors influencing transient elastography in detecting liver stiffness

Background and Aims: Liver stiffness, which correlates well with liver fibrosis stage, can be measured noninvasively by transient elastography, also known as Fibroscan. The present study aimed to determine the independent factors influencing Fibroscan detection. Methods: Liver stiffness measurement (LSM) was detected by Fibroscan. Clinical information, routine biochemical tests and liver biopsy were also done. Correlation was analyzed by Spearman's correlation, and multiple regression analysis was performed to analyze the independent influencing factors. Results: In this study 79 patients, 50 males and 29 females, were enrolled out of which 45 (56%) had NASH, 19 (24%) had Chronic hepatitis B, 11 (13%) had Chronic hepatitis C and 4 (5%) had Autoimmune hepatitis. 55 patients had TEE score discordant with liver biopsy fibrosis score. 2 patients had TEE fibrosis score less than liver biopsy fibrosis score and rest of the patients had a TEE fibrosis score > 1 liver biopsy fibrosis score. Conclusions: Age, BMI, INR, albumin affected the LSM detection by TEE. The authors have none to declare. Table 1Tabled 1MeanAge43.18BMI23.81TEE score12.18Hemoglobin13.21Total count7847.46Platelet count (lakhs/mm3)2.21Total bilirubin2.13Direct bilirubin1.5SGOT73.33SGPT104.44Alkaline Phosphatase132.5Total protein7.28Albumin3.89INR1.1Creatinine1.36RBS134.31 Open table in a new tab Table 2 Correlation analysis between liver stiffness measurement and various indexes.