Steatosis In Donors Research Articles

Predicting of Hepatic Steatosis in Living Liver Donor via CT Liver Attenuation Index (LAI) and Fibroscan Controlled Attenuation Parameter (CAP) Correlation with Biopsy Result

Abstract Background The most prevalent persistent parenchymatous liver alterations in healthy individuals are thought to be hepatic steatosis. The liver biopsy is the most crucial procedure for the identification and measurement of hepatic steatosis. By identifying the liver attenuation index (LAI) at an unenhanced CT image, hepatic steatosis can be evaluated without the risk of liver resection. Objective Using liver biopsy histological analysis as a reference standard, to examine the precision of the CT liver attenuation index (LAI) and fibroscan controlled attenuation parameter (CAP) for quantitative evaluation of macro vesicular steatosis in living related liver donors. Methods In this study comparing CT liver attenuation index & fibroscan controlled attenuation parameter with liver pathology of steatosis in subject's candidate for liver living donors 50 subjects in each two study's correlation with biopsy results, conducted at Ain Shams Shams Specialized hospital and other Private hospitals over about 2 years. Results Our study reported that liver – spleen attenuation index of 9 is the cutoff value with sensitivity 100% and specificity 80% that make it a very good method to exclude donor to have steatosis ≥15%, which mean if donor had LS index < 9 we can safely do proceed do liver biopsy. Our study reported that CAP measurement had an AUROC OF 0.780, for detecting steatosis ≥ 15 %, with sensitivity is only 60% with specificity as CT LAI of 80%, which consider low compared to other study, that could be due to small number of donors in out study with steatosis ≥ 15 % (5 case from 50 donors) unlike the other studies. Conclusion When used to estimate the amount of liver fat in liver donors, the examined CAP and CT indices worked equally. But according to multivariate analysis, the only factor strongly linked with hepatic steatosis in alive donors was the CT L-S attenuation index. We contend that the combination of CT L-S attenuation index and CAP allows for the detection of the degree of hepatic steatosis and can be used as an option to liver biopsy, reserving liver biopsy for those with positive steatosis donors.

Donor Diabetes and Steatosis Affects Recipient Survival Following Liver Transplantation Based on Etiology of Liver Cirrhosis.

Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis. Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P < 0.001) but not other etiologies of cirrhosis. Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients.

Growing challenge of post-liver transplantation non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide, with an estimated prevalence of 25%. Post-liver transplantation (LT) recurrent or de novo hepatic steatosis is a common complication in recipients, irrespective of transplantation indication. Risk factors for graft steatosis mainly include obesity, immunosuppression, donor steatosis, and genetic factors. Liver transplant recipients are at high risk of developing insulin resistance, new-onset diabetes, and post-transplantation metabolic syndrome that is highly associated with immunosuppressive treatment. Post-LT NAFLD is often underdiagnosed due to the poor sensitivity of most routine imaging methods. The gold standard for the diagnosis of hepatic steatosis is liver biopsy, which is, however, limited to more complex cases due to its invasive nature. There is no approved pharmacotherapy in NAFLD. Lifestyle modification remains the cornerstone in NAFLD treatment. Other treatment strategies in post-LT NAFLD include lifestyle modifications, pharmacotherapy, bariatric surgery, and tailored immunosuppression. However, these approaches originate from recommendations in the general population, as there is scarce data regarding the safety and efficacy of current management strategies for NAFLD in liver transplant patients. Future prospective studies are required to achieve tailored treatment for these patients.

Characterization of hepatic steatosis using controlled attenuation parameter and MRI-derived proton density fat fraction in living donor liver transplantation.

The increasingly favorable outcomes of live donor liver transplantwarrant development of screening techniques to expand current donor pool. Transient elastography (TE) with controlled attenuation parameter (CAP) is accessible and has promising diagnostic performance in non-obese individuals. Here, we demonstrate its utility in grading donor steatosis for risk assessment in living liver donors (LLD). In a prospective study of LLD and recipients, accuracy was determined using MRI-derived proton density fat fraction (PDFF) as reference. One hundred and one LLD underwent TE, 95 of whom had available PDFF. Median CAP and MRI-PDFF were 233dB/m (206-270) and 2.9% (2.3-4.0), respectively. A CAP threshold of 270dB/m captured all steatosis which was present in 13 (13%) LLD (AUROC .942, 100% sensitivity and 83% specificity). Performance further improved when excluding obese LLD and limiting analysis to M-probe (AUROC .971 and .974, respectively, with 87% specificity). There was no difference in CAP and MRI-PDFF between LLD and nondonors (P=.26 and .21, respectively). Early allograft dysfunction was observed in one recipient (CAP 316, PDFF 9.5%), zero underwent retransplant, and one died from sepsis. The specific role of CAP in living liver donation warrants further study, beginning with its use as screening tool across peripheral clinics.

316.14: Impact of Donor Hepatic Steatosis on Kidney Transplant Recipient Outcomes

Introduction: Increasing evidence suggests an independent association of hepatic steatosis with chronic kidney disease, kidney function decline and risk of cardiovascular (CV) disease. Whether the presence or severity of an organ donor’s hepatic steatosis impacts on kidney transplant recipient (KTR) outcomes has not been studied. Methods: We performed a retrospective cohort study of deceased liver donors, matched to their KTR, in New South Wales (NSW), Australia from 2006-2020. We linked data from the Australian and New Zealand Dialysis and Transplantation (ANZDATA) and Organ Donation (ANZOD) registries with biopsy results of donor livers evaluated or utilised for transplantation at the NSW state-wide liver transplant unit. Donor hepatic steatosis was graded contemporaneously by histopathologists as S0 (<5%), S1 (5-33%), S2 (>33-66%) or S3 (>66%). Standard donor and recipient characteristics were collected. All-cause death, cardiovascular (CV) death, graft loss (death-censored), delayed graft function (DGF), graft function decline (assessed by eGFR) and post-transplant CV events (composite of coronary artery, peripheral vascular or cerebrovascular disease) were compared among recipients according to their presence and severity of hepatic steatosis. Results: 751 donors with liver biopsies were matched to 1,263 KTRs (8,043 person-years follow-up). Donor hepatic steatosis grades were: S0 453 (60%), S1 195 (26%), S2 71 (9%), S3 32 (4%). Donors with hepatic steatosis (S1-3) were significantly older (median age 53 vs 46 years) than those without steatosis and had worse metabolic profiles: higher body mass index (median 27 vs 25kg/m2), diabetes (9% vs 6%), hypertension (35% vs 25%). KTR of donors with and without hepatic steatosis had similar baseline characteristics. Presence of hepatic steatosis (vs no steatosis) and steatosis severity (S3 vs S0-2) did not impact on all-cause- or CV-death, graft loss, or DGF in the multivariable analysis. Univariable analysis suggested that decline in graft function was greater in recipients from donors with steatosis compared to recipients of donors without steatosis, but this no longer remained significant on multivariable analysis after adjusting for other variables. There was an increased risk of CV events on univariable (HR 1.42, 95%CI 1.00-2.02, p=0.05) and multivariable analysis (HR 1.47, 95%CI 1.03-2.10, p=0.04, Table 1) among recipients of donors with severe (S3) steatosis versus those with no/less donor steatosis. Conclusion: In this retrospective analysis, neither the presence nor severity of biopsy-proven donor hepatic steatosis appeared to impact kidney transplant recipient outcomes. Recipients from donors with severe hepatic steatosis may be at higher risk of cardiovascular events.

Use of steatotic donor livers for transplantation: Do they affect outcome?

AbstractBackgroundThe exact effect of donor steatosis on post‐transplant outcome is not well established. The aims of this study were to evaluate the effect of different grades of deceased donor liver steatosis on recipient outcome and to validate performance of the MEAF score in conjunction with graft steatosis.MethodsAdult recipients of 228 livers were studied. Livers were divided into three groups according to grade of steatosis; S0, no steatosis (n = 152); S1, minimal to mild steatosis &lt;33% (n = 62); S2, moderate to severe steatosis 33%–66% (n = 14). Donor, recipient data and outcomes of transplantation were evaluated.ResultsModerate to severe steatosis (S2) was associated with older donors and higher donor BMI. Postoperative laboratory values were significantly higher in S2. Incidence of EAD did not differ significantly with no PNFs. MEAF score correlated well with EAD. S0 had a significant shorter ICU stay. Mortality did not differ significantly. Median MEAF score was higher for S2 than S0 and S1 (5.80 versus 4.73 and 4.49).ConclusionSteatosis was associated with older, more obese donors, but did not adversely affect the postoperative outcomes. Steatotic graft recipients had more renal impairment and longer ICU stay. MEAF score might be an accurate method for assessing the early graft function in conjunction with steatosis.

Identification of hepatic steatosis in living liver donors by machine learning models.

Selecting an optimal donor for living donor liver transplantation is crucial for the safety of both the donor and recipient, and hepatic steatosis is an important consideration. We aimed to build a prediction model with noninvasive variables to evaluate macrovesicular steatosis in potential donors by using various prediction models. The study population comprised potential living donors who had undergone donation workup, including percutaneous liver biopsy, in the Republic of Korea between 2016 and 2019. Meaningful macrovesicular hepatic steatosis was defined as >5%. Whole data were divided into training (70.5%) and test (29.5%) data sets based on the date of liver biopsy. Random forest, support vector machine, regularized discriminant analysis, mixture discriminant analysis, flexible discriminant analysis, and deep neural network machine learning methods as well as traditional logistic regression were employed. The mean patient age was 31.4 years, and 66.3% of the patients were men. Of the 1652 patients, 518 (31.4%) had >5% macrovesicular steatosis on the liver biopsy specimen. The logistic model had the best prediction power and prediction performances with an accuracy of 80.0% and 80.9% in the training and test data sets, respectively. A cut‐off value of 31.1% for the predicted risk of hepatic steatosis was selected with a sensitivity of 77.7% and specificity of 81.0%. We have provided our model on the website (https://hanseungbong.shinyapps.io/shiny_app_up/) under the name DONATION Model. Our algorithm to predict macrovesicular steatosis using routine parameters is beneficial for identifying optimal potential living donors by avoiding superfluous liver biopsy results.

Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation.

Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients. Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected. Liver biopsies were taken from the donor liver at transplant, and from recipients per protocol and for-cause (ie, abnormal transaminases and to rule out rejection) and were interpreted by a central pathologist. One hundred eighty-three paired donor/recipients liver biopsies at the time of transplant and posttransplant follow-up (median time 582 d; average time to last biopsies was 704 d [SD ± 402 d]) were analyzed. Donor steatosis did not influence recipient steatosis or fibrosis. Ten of 183 recipients had steatohepatitis on the last biopsy. Recipient body mass index at the time of liver biopsy was the most influential factor associated with posttransplant steatosis. Both donor and recipient metabolic syndrome features were not associated with graft steatosis. Untreated hepatitis C viral (HCV) infection was the most influential factor associated with the development of allograft fibrosis. In a large experience evaluating paired donor and recipient characteristics, recipient body mass index at the time of liver biopsy was most significantly associated with posttransplant steatosis. Untreated HCV etiology influenced graft fibrosis. Thus relative to untreated HCV, hepatic fibrosis in those with steatosis/steatohepatitis is less common though long-term follow-up is needed to determine the course of posttransplant fibrosis. Emphasis on recipient weight control is essential.

Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation

BackgroundOrthotropic liver transplantation (OLT) offers a therapeutic choice for hepatocellular carcinoma (HCC) patients. The poor outcome of liver transplantation is HCV recurrence. Several genome-wide associated studies (GWAS) have reported many genetic variants to be associated with HCV recurrence. Seven gene polymorphisms formed a cirrhosis risk score (CRS) signature that could be used to distinguish chronic HCV patients at high risk from those at low risk for cirrhosis in non-transplant patients. This study aims to examine the association of CRS score and other clinical parameters with the probability for HCC emergence and/or the rate of HCV recurrence following liver transplantation. ResultsSeven gene polymorphisms, forming the CRS, were genotyped by real-time PCR using allelic discrimination protocol in 199 end-stage liver disease patients (79 child A, 43 child B, and 77child C), comprising 106 patients who encountered liver transplantation. Recipient CRS scores were correlated with HCV recurrence (HCV-Rec) at the end of the third year after OLT. Around 81% (39) recipients with low steatosis (LS; < 3.5%) donor percentage revealed no HCV recurrence (non-Rec) (p<0.001). CRS score could distinguish between child A, child B, and child C only at the low-risk group. Among the HCV Rec group 27% (8/30), 40% (12/30), and 33% (10/30) fell into the high, moderate, and low CRS risk groups, respectively. Stepwise logistic regression evinced two features more likely to be seen in HCV-Rec patients: abnormal ALT [OR, 1.1; 95% CI, 1.02–1.2] and donor steatosis >3.5% [OR, 46.07; 95% CI, 1.5–1407.8]. ConclusionsAccordingly, the CRS score seems to be less useful to predict HCV recurrence after OLT. ALT and donor steatosis (exceed 3.5%) can significantly promote the HCV recurrence post-OLT. Moreover, the combination of MMF and CNI positively heightens HCV recurrence.

Non-invasive real-time assessment of hepatic macrovesicular steatosis in liver donors: Hypothesis, design and proof-of-concept study.

Macrovesicular Steatosis (MS) is an independent risk factor for adverse post-liver transplant (LT) outcomes. The degree of MS is intimately related to the viability of the liver graft, which in turn is crucial to the success of the operation. An ideal liver graft should have no MS and most centres would find it unacceptable to use a donor liver with severe MS for LT. While a formal liver biopsy is the gold-standard diagnostic test for MS, given the logistical and time constraints it is not universally feasible. Other tests like a frozen section biopsy are plagued by issues of fallibility with reporting and sampling bias making them inferior to a liver biopsy. Hence, the development of an accurate, non-invasive, easy-to-use, handheld, real-time device for quantification of MS would fill this lacuna in the deceased donor selection process. We present the hypothesis, design and proof-of-concept of a study, which aims to standardise and determine the feasibility and accuracy of a novel handheld device applying the principle of diffuse reflectance spectroscopy for real-time quantification of MS.

Nonalcoholic Fatty Liver Disease: Indian Perspective.

Nonalcoholic Fatty Liver Disease: Indian Perspective.

Contemporary strategies to assess and manage liver donor steatosis: a review.

Due to a persistent shortage of donor livers, attention has turned toward ways of utilizing marginal grafts, particularly those with steatosis, without incurring inferior outcomes. Here we review the evaluation and utilization of steatotic liver allografts, highlight recently published data, and discuss novel methods of graft rehabilitation. Although severe liver allograft (>60%) steatosis has been associated with inferior graft and recipient outcomes, mild (<30%) steatosis has not. There is ongoing debate regarding safe utilization of grafts with moderate (30-60%) steatosis. Presently, no established protocols for evaluating steatosis in donor candidates or utilizing such grafts exist. Liver biopsy is accepted as the gold standard technique, though noninvasive methods have shown promise in accurately predicting steatosis. More recently, machine perfusion has been shown to enhance ex situ liver function and reduce steatosis, emerging as a potential means of optimizing steatotic grafts prior to transplantation. Steatotic liver allografts constitute a large proportion of deceased donor organs. Further work is necessary to define safe upper limits for the acceptable degree of steatosis, develop standardized evaluation protocols, and establish utilization guidelines that prioritize safety. Machine perfusion has shown promise in rehabilitating steatotic grafts and offers the possibility of expanding the deceased donor pool.

Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is a viable alternative to liver biopsy for steatosis quantification in living liver donor transplantation.

This study aimed to investigate whether magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) can be a viable noninvasive alternative to liver biopsy for the quantification of living liver donor steatosis. Hepatic steatosis for 143 donors was graded by MRI-PDFF. Study endpoints included liver volume regeneration in donors, recipient outcomes including length of hospital stay, deaths, primary non-function (PNF), early allograft dysfunction (EAD), and small for size syndrome (SFSS). Correlation between MRI-PDFF determined donor steatosis and endpoints were analyzed. Donors had lower steatosis grade than non-donors. Donor remnant liver regenerated to an average of 82% of pre-donation volume by 101±24days with no complications. There was no correlation between percent liver regeneration and steatosis severity. Among recipients, 4 underwent redo-transplantation and 6 died, with no association with degree of steatosis. 52 recipients (36%) fulfilled criteria for EAD (driven by INR), with no difference in hepatic steatosis between groups. MRI-PDFF reliably predicted donor outcomes. Living donors with no or mild steatosis based on MRI-PDFF (ie, <20%) and meeting other criteria for donation can expect favorable post-surgical outcomes, including liver regeneration. Recipients had a low rate of death or retransplantation with no association between mild hepatic steatosis and EAD.

Pilot study of a noninvasive real-time optical backscatter probe in liver transplantation.

Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes. The probe is placed on the surface of the liver and emits red and near infrared light from the tip of the device and measures the amount of backscatter of light from liver tissue via two photodiodes. Measurement of optical backscatter (Mantel-Cox P<0.0001) and histopathological scoring of macrovesicular steatosis (Mantel-Cox P=0.046) were predictive of 5-year graft survival. Recipients with early allograft dysfunction defined according to both Olthoff (P=0.0067) and MEAF score (P=0.0097) had significantly higher backscatter levels from the donor organ. Backscatter was predictive of graft loss (AUC 0.75, P=0.0045). This study demonstrates the feasibility of real-time measurement of optical backscatter in donor livers. Early results indicate readings correlate with steatosis and may give insight to graft outcomes such as early allograft dysfunction and graft loss.

Comparing computerized tomography indices and liver biopsy in liver transplantation donors for hepatosteatosis

Background: Selecting the right donor to achieve a successful liver transplantation is very important; thus computerized tomography and liver biopsy are frequently applied in the diagnosis of steatosis in donors. Purpose: We sought to investigate the efficacy of computerized tomography in the evaluation of hepatosteatosis in living donor liver transplantation donors. Material and methods: The living donor liver transplantation cases between January 2015 and December 2017 were screened retrospectively. The study participants were divided into three groups according to the degree of steatosis determined during LB as follows: grade 0: less than 5%, grade 1: 6% to 20%, and grade 2: greater than 20%. Using computerized tomography scans, hepatic attenuation value (CTL), hepatic attenuation value and spleen attenuation value ratio (CTL/S), and the difference between hepatic attenuation value and splenic attenuation values (CTL−S) were determined and the correlations of these indices and the findings of LB were compared. Results: Of the 60 patients (42 males, mean age: 32.4±7.7 years), 43 had grade 0, 15 had grade 1, and two had grade 2 hepatosteatosis, respectively. The CTL, CTL/S, and CTL−S cutoff values were 48.3, 1.06, and 3.2, respectively, while the sensitivity and specificity results of these cutoff values were 64.7% and 88.3%, 64.7% and 86%, and 64.7% and 86% and the area under the curve values were determined to be 0.81, 0.79, and 0.80 (p< 0.001). Conclusion: The use of these noninvasive indices can reduce the need for liver biopsy, which is an invasive procedure, as well as lessen the associated complication and cost rates. Future prospective studies are needed on this subject.

Differential Impact of Extended Criteria Donors After Brain Death or Circulatory Death in Adult Liver Transplantation.

Using grafts from extended criteria donors (ECDs) and donation after circulatory death (DCD) donors is a strategy to address organ shortage in liver transplantation (LT). We studied the characteristics and outcomes of ECD and DCD grafts. We retrospectively studied consecutive adults who underwent deceased donor LT between 2006 and 2019. ECD was defined using modified Eurotransplant criteria. Our primary outcomes were graft and patient survival. A total of 798 grafts were used for LT, of which 93.1% were donation after brain death (DBD; 59.9% were also ECD) and 6.9% were DCD grafts (49.1% were also ECD). Among DBD graft recipients, donors having >33% liver steatosis or 3 ECD criteria resulted in poorer graft survival. Otherwise ECD graft recipients had similar graft and patient survival compared with non-ECD graft recipients. DCD graft recipients also had similar patient survival compared with DBD recipients. However, DCD grafts from an ECD appeared to have worse outcomes. DCD graft recipients experienced higher rates of early allograft dysfunction (50.9% versus 24.7%; P<0.001) and ischemic biliopathy (16.4% versus 1.5%; P<0.001) compared with DBD graft recipients. Use of DBD grafts from ECDs did not impact outcomes unless there was significant donor steatosis or 3 Eurotransplant criteria were met. DCD graft recipients have similar patient survival compared with DBD graft recipients as long as the donor was not an ECD. We recommend that DBD donors with 3 or more ECD features or >33% steatosis and DCD donors with any ECD features be used with caution in adult LT.

VALUE OF CTGF IN ASSESSMENT OF LIVER GRAFT WITH NON-ALCOHOLIC FATTY LIVER DISEASE AFTER BRAIN DEATH

Background and Purpose: As the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing globally, an accurate evaluation of liver steatosis in potential donors is required for liver transplantation. Connective tissue growth factor (CTGF) plays an important role in the acute hepatic inflammation, chronic liver injury and liver fibrosis. In this study, intrahepatic and systemic CTGF expressions were measured from brain-dead donors (BDDs) with NAFLD, and evaluated as biomarker of NAFLD-induced graft injury. Methods: Liver and blood samples were obtained from brain-dead organ donors and patients with angiomas for RNA-sequencing and validation by RT-PCR, WB and IHC. The NAFLD rat model was established by feeding rats with the high fat diet, and thereafter brain death was developed by increasing intracranial pressure in healthy or NAFLD rats. The samples from NAFLD rats, brain-dead rats and the controls were used for further detection and analysis. Systemic CTGF levels from human and rats were measured by ELISA and analyzed the relation with the quantitative histopathological score in livers from NAFLD donors. Results: Through transcriptome analysis, CTGF was down-regulated in the healthy liver from BDDs with the fold change of 0.34 (P<0.05), which was further verified in the healthy livers from humans and rats by RT-PCR, WB and IHC (P<0.05). In parallel, CTGF protein was highly overexpressed in the fatty liver compared with the healthy liver after brain death by IHC (P<0.05). The correlation analysis indicated a linear correlation between serum levels and intrahepatic expression of CTGF in both humans and rats (P<0.05). CTGF concentration correlated with the severity of NAFLD-induced liver injury. Conclusion: After brain death, CTGF was down-regulated in the healthy liver and still over-expressed in the fatty liver from donor with NAFLD. Serum CTGF level from BDDs might be a predictor of steatosis severity for graft evaluation.

Macrosteatotic Allografts and Obese Recipients Have Nearly Equal Negative Impact on Liver Transplant Survival.

Our aim was to evaluate liver transplant outcomes involving donors with high macrosteatosis grafts in the obese modern liver transplant recipient population. A high-steatosis graft was defined as donor graft macrosteatosis ≥30% on biopsy. Recipient obesity was defined as body mass index (BMI) >35 adjusted for ascites. Raw and adjusted recipient liver transplant survival were evaluated and compared between 4 cohorts: (1) high-steatosis graft in high-BMI recipient; (2) low-steatosis graft in high-BMI recipient; (3) high-steatosis graft in normal-BMI recipient; and (4) low-steatosis graft in normal-BMI recipient. After adjustment for multiple factors, recipient high-BMI remained an independent predictor of posttransplant mortality at 30 days (P < 0.0001) and persisted at 1 year (P = 0.009). A high-steatosis graft was the strongest independent predictor of mortality at 30 days (hazard ratio 2.05, 1.66-2.53; P < 0.0001) and that effect was diminished but persistent at 1 year (1.27, 1.10-1.46; P = 0.001). Recipient high-BMI and a high-steatosis graft are both significant independent and equally powerful predictors of mortality after modern liver transplant. High-steatosis grafts transplanted into obese recipients have the highest mortality. The increase in mortality associated with a high-steatosis graft into a normal-BMI recipient is similar in magnitude to a low-steatosis graft placed into a high-BMI recipient.

Links between donor macrosteatosis, interleukin-33 and complement after liver transplantation.

BACKGROUNDAs prevalence of nonalcoholic fatty liver disease increases in the population, livers with steatosis will continue to infiltrate the donor pool. Safe utilization of these extended criteria grafts is paramount given the increased risk associated with their use in transplantation. Prognostic factors that can predict liver dysfunction immediately after transplantation with macrosteatotic grafts are lacking.AIMTo understand the relationship between interleukin-33 (IL-33) and complement in recipients immediately following liver reperfusion as a marker of liver dysfunction.METHODSCohort consisted of patients who received a liver transplant from September 2016–September 2019 at our institution. Clinical variables were retrospectively extracted from the electronic medical record. Back-table donor biopsies were obtained with donor steatosis percentage retrospectively determined by a board-certified pathologist. Blood samples were available immediately following liver transplantation. Quantification of plasma IL-33 and complement proteins, C3a and C5a, were determined by enzyme-linked immunosorbent assay. For mRNA expression, RNA was extracted from donor biopsies and used against a 780 gene panel.RESULTSCohort consisted of 99 donor and recipients. Donor median age was 45 years and 55% male. Recipients had a median age of 59 years with 62% male. The main etiologies were alcoholic hepatitis, nonalcoholic steatohepatitis, and hepatocellular carcinoma. Median MELD-Na at transplant was 21. Donors were grouped based on moderate macrosteatosis (≥ 30%). Recipients implanted with moderate macrosteatotic grafts had significantly higher peak alanine aminotransferase/aspartate aminotransferase (P < 0.001 and P < 0.004), and increased incidence of early allograft dysfunction (60% compared to 18%). Circulating IL-33 levels were significantly elevated in recipients of ≥ 30% macrosteatotic grafts (P < 0.05). Recipients with detectable levels of circulating IL-33 immediately following reperfusion had significantly higher alanine aminotransferase/aspartate aminotransferase (P < 0.05 and P < 0.01). Activated complement (C3a and C5a) were elevated in recipients implanted with moderate macrosteatotic grafts. RNA expression analysis of donor biopsies revealed moderate steatotic grafts upregulated genes inflammatory processes while downregulated hepatocyte-produced complement factors.CONCLUSIONCirculating IL-33 and activated complement levels immediately following liver reperfusion in recipients of moderate macrosteatotic grafts may identify which patients are at risk of early allograft dysfunction.

Liver Steatosis in Brain-Dead Donors: Progression Pattern and Affecting Factors

ObjectivesNo study has investigated the short-term effect of acute insulin resistance on liver steatosis in critically ill condition. We analyzed the effects of critically ill conditions of brain-dead donors (BDDs) on the development and progression of liver steatosis to investigate the influencing factors. MethodsThis study was conducted retrospectively between January 2003 and December 2017. BDDs were for organ procurement. BDDs with body mass indexes (BMIs) < 18.5 kg/m2 and ≥ 30 kg/m2 were excluded. Liver steatosis was defined as ≥5% of the fat vacuole. The serum glucose level (SGL) was used to reflect insulin resistance. ResultsOf the 179 BDDs, 87 (48.6%) had liver steatosis. BMI (r = 0.176, P = .019) and SGL (r = 0.267, P < .001) were correlated with steatosis. The length of the predonation period (LPDP) was negatively correlated with steatosis (r = -0.379, P < .001). BMI (odds ratio 1.266, P = .002), SGL ≥180 mg/dL (odds ratio 2.825, P = .003), and LPDP (odds ratio 0.885, P = .001) were independent risk factors for liver steatosis. ConclusionLiver steatosis is related to the SGL and BMI. Liver steatosis develops acutely in the early phase of critical illness and patients recover gradually.