Article

Body Mass Index and Unenhanced CT as a Predictor of Hepatic Steatosis in Potential Liver Donors

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  • University of Health Sciences Istanbul Umraniye Training and Research Hospital
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Abstract

Background: In living-donor liver transplantation, donor hepatic steatosis is crucial for both the donor and the recipient. Body mass index (BMI) and the unenhanced computed tomography liver attenuation index (CT LAI) are noninvasive methods to predict hepatic steatosis in living-donor liver candidates. Aim: To analyze the diagnostic accuracy of CT LAI in conjunction with different BMI values for macrovesicular steatosis in living-donor liver candidates. Methods: A total of 264 potential liver donors were included. The diagnostic accuracy of 2 CT LAI cut-offs and 3 BMI cut-off values for the assessment of hepatic steatosis ≥15% and ≤5% was determined. Results: Using CT LAI, the area under the receiver operating characteristic curve was 0.97 (95% CI = 0.89-0.99) for hepatic steatosis ≥15% in donors with BMI <25 kg/m2. For detecting hepatic steatosis ≥15%, a CT LAI ≤0 had specificities of 100%, 76.2%, and 55.6% and positive predictive values of 100%, 95.5%, and 93.5% for patients with BMI values <25 kg/m2, 25 to 29.9 kg/m2, and ≥30 kg/m2, respectively. According to logistic regression analyses, only CT LAI ≤0 was found to be independently associated with hepatic steatosis ≥15%. Conclusions: In donors with BMI <30 kg/m2 and a CT LAI value >6, liver biopsy might be avoided. Biopsy may be reserved solely for donors with CT LAI value >0 and BMI ≥30 kg/m2 as the diagnostic accuracy of computed tomography for predicting hepatic steatosis decreases with increasing BMI.

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... Hepatic steatosis is associated with poor liver graft function and recipient outcome. Although liver biopsy is the gold standard for the estimation of steatosis, it is an invasive procedure and is associated with various complications [16]. So, non-invasive methods like BMI and LAI have been used for the assessment. ...
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Background Liver transplantation is the standard treatment for end-stage liver disease. Living donor liver transplantation is more commonly performed in Asian countries as compared to the Western due to the lack of organ donation. Donor safety is the key to sustaining a liver transplant program. Thus, we aimed to evaluate the overall safety of living donors and health-related quality of life using the 12-item Short Form Health Survey (SF-12) questionnaire at our institution. Methodology We analyzed the medical records of patients who underwent donor hepatectomy at Tribhuvan University Teaching Hospital, Kathmandu, from May 31, 2019, to April 18, 2023. Demography, postoperative complications, and quality of life were analyzed. Results The mean age of the 10 live liver donors was 27.9 years. Half of them were male. One of them had a post-hepatectomy bile leak and others did not have any post-operative complications. They have good physical and mental health status after liver donation as indicated by the average physical component summary and mental component summary scores of more than 50. Conclusion The case series highlights the safety and favorable outcomes of liver donors at a low-volume liver transplant center, where stringent preoperative assessments and careful surgical techniques were employed.
... Computed Tomography -Leaf Area Index (CT LAI) <0 had a reported specificity of 100% for identifying steatosis >15% in patients with BMI<25, dropping to 76.2% and 55.6% for 25<BMI<30 and BMI>30, respectively; Positive predictive value was adequate for all groups (100%, 95.5%, 93.5%). [30] The use of CT LAI is not appropriate to rule out hepatic steatosis in overweight/obese patients but can be considered a good screening imaging for liver biopsy. Magnetic resonance spectroscopy has established itself as a reference standard for quantification of liver steatosis. ...
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Living Donor Liver Transplantation (LDLT) is a valuable solution to the shortage of donor organs for patients with end-stage liver disease. However, the eligibility of obese donors for LDLT remains a subject of debate. This literature review explores global practices and perceptions of LDLT, identifies donor eligibility criteria, and discusses special considerations and ethical caveats. The review highlights the need for standardized guidelines for donor selection, considering the global distribution of Body mass index and variations in population-specific criteria. It also emphasizes the importance of non-invasive testing and pre-operative optimization of liver steatosis for select obese donors. Furthermore, the review examines the outcomes and complications associated with obese donors in LDLT. The findings of this review contribute to the ongoing discussion on the inclusion of obese donors in LDLT and provide insights for future research and guideline development.
... Standardization of the method allows this technique to diagnose the condition of the liver and facilitates decisions about treatment or participation of potential donors in transplantation. As reported by Adalı et al. [2019], liver biopsy could be avoided in donors with BMI <30 kg/m 2 and a computed tomography liver attenuation index > 6, but the diagnostic accuracy of computed tomography for predicting hepatic steatosis decreases with increasing BMI. Similarly, a combination of MR fat quantification and MR elastography can provide sufficient sensitivity to detect liver steatosis or fibrosis in candidates for liver donation [Yoon et al. 2015]. ...
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Noncontrast CT was a reliable method for detection of at least moderate hepatic steatosis (over 20%–33% fat at biopsy), with a pooled sensitivity and specificity of 82% and 94%, respectively.
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Article
Background: Donor BMI above 30 is generally considered contraindication for donor hepatectomy. We compared the donor outcomes based on BMI threshold and weight loss. Patients and methods: All potential donors were identified and data were collected retrospectively. Steatosis was assessed based on liver-spleen Hounsfield unit difference and absolute liver intensity values. We compared BMI≥30 (n = 53) and BMI<30 (n = 64) donor outcomes. Donors with weight loss (WL) prior to surgery were also analyzed separately. Complications were graded by Clavien-Dindo classification. Results: All donors underwent open right donor hepatectomy. There was no difference between BMI≥30 and <30 groups except female predominance in BMI≥30 group (p = 0.006). Both groups had similar rates of complication rates in all categories, similar remnant volume, operative time, length of stay and similar postoperative liver function recovery (all p>0.05). On the other hand, donors with WL were more commonly male, had smaller graft size, and higher biliary complications rates compared to no-WL donors (all p<0.05). Multivariate binary logistics regression analysis revealed no association between BMI or WL and outcomes. Conclusion: We demonstrate that donors with BMI≥30 have similar outcomes compared to BMI<30 donors with our defined selection criterion, therefore BMI≥30 is not an absolute contraindication to donate right liver, provided that there is no significant steatosis and remnant liver is satisfactory. For potential overweight donors, WL down to BMI<30 is a reasonable target. Higher biliary complication rates after WL should be investigated further. This article is protected by copyright. All rights reserved.
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To reduce waitlist mortality, living donor liver transplantation (LDLT) has increased over the past decade in US, however, not at a rate sufficient to completely mitigate organ shortage. As a result, there are ongoing efforts to expand the living liver donor pool. Simultaneously, the prevalence of Non‐alcoholic Fatty Liver Disease (NAFLD) in the general population has increased, which has significant implications on the pool of potential living liver donors. As such, a clinical assessment algorithm that exhaustively evaluates for NAFLD and fibrosis is critical to the safe expansion of LDLT. An ideal algorithm would employ safe and non‐invasive methods, relying on liver biopsy only when necessary. While exclusion of NAFLD and fibrosis by non‐invasive means is widely studied within the general population, there are no well‐accepted guidelines for evaluation of living donors using these modalities. Here we review the current literature regarding non‐invasive NALFD and fibrosis evaluation and propose a potential algorithm to apply these modalities for the selection of living liver donors.
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Fatty liver disease, including liver steatosis, is a major health problem worldwide. In liver transplantation, macrovesicular steatosis of donor livers is a major cause of graft failure and remains difficult to assess. On one hand, several imaging modalities can be used for the assessment of liver fat, but liver biopsy, which is still considered the gold standard, may be difficult to obtain in this context. On the other hand, computed tomography (CT) is commonly used by teams managing cadaveric donors to assess donors and to minimize the risk of complications in recipients. The purpose of our study was to validate the use of CT as a semi-quantitative method for assessing macrovesicular steatosis in cadaveric donors using liver biopsy as a reference standard. A total of 109 consecutive cadaveric donors were included between October 2009 and May 2011. Brain death was diagnosed according to French legislation. Liver biopsy and then CT were performed on the same day to determine the degree of macrovesicular steatosis. All liver biopsies and CT were analyzed double-blinded by a senior pathologist and a senior radiologist respectively. For CT, we used the liver-to-spleen (L/S) attenuation ratio which is a validated method to determine a 30% or greater steatosis in living liver donors. 14 out of 109 biopsies exhibited macrovesicular steatosis > 30% at histology. A ROC curve was generated for the L/S ratio to identify its ability to predict significant steatosis defined as > 30%. A cutoff value of 0.9 for CT L/S provided a sensitivity of 79% and a specificity of 97% to detect significant steatosis. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
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To evaluate the association of anthropometric indexes (body mass index and waist circumference) in patients with non-alcoholic fatty liver disease (NAFLD), and its association with insulin resistance (IR), metabolic syndrome (MS) and histological findings. From August 2003 to July 2004 a case series of 81 outpatients with clinic and/or histological diagnosis of NAFLD were selected at the Bahia University Gastro-Hepatology Clinic, Brazil. Liver function tests, lipid profile, glucose and insulin were performed in all patients. Body mass index (BMI) and waist circumference (WC) were determined according to WHO criteria. IR was measured by means of the homeostasis model assessment (HOMA) and IR was considered with HOMA > or =3. MS was defined according to the Adult Treatment Panel III (ATP III). Liver biopsy was performed in 37 cases. Body mass index > or = 30 kg m(-2) (obesity) was found in 39% of the cases and BMI > or = 25-29.9 kg m(-2) (overweight) in 53%. BMI was correlated with IR (r = 0.29; P = 0.02) and WC with ALT (r = 0.02; P = 0.03). Increased WC also was related to IR and to MS. The presence of steatohepatitis with fibrosis on liver biopsy was associated with overweight (68%) and increase of WC (41%). Body mass index and WC are frequent associated with MS, IR and histological findings (steatohepatitis and fibrosis) in patients with NAFLD.
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Over the past 2 decades, nonalcoholic fatty liver disease (NAFLD) has grown from a relatively unknown disease to the most common cause of CLD in the world. In fact, 25% of the world's population is currently thought to have NAFLD. Non‐alcoholic steatohepatitis (NASH) is the subtype of NAFLD that can progress to cirrhosis, hepatocellular carcinoma, and death. NAFLD and NASH are found in not only adults—there is a high prevalence in children and adolescents. Due to NAFLD's close association with type 2 diabetes (T2DM) and obesity, the latest models predict the prevalence of NAFLD and NASH will increase, causing a tremendous clinical and economic burden and poor patient‐reported outcomes. Nonetheless, there is no accurate non‐invasive method to detect NASH and treatment is limited to life style modifications. To examine the state of NAFLD among different regions and understand the global trajectory of this disease, an international group of experts came together during 2017 AASLD Global NAFLD Forum. We provide a summary of this forum and an assessment of the current state of NAFLD and NASH worldwide. This article is protected by copyright. All rights reserved.
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NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.
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Background: The accuracy of computed tomography (CT) for detecting donor hepatic steatosis (HS) before liver transplantation is not well established. Methods: A meta-analysis was performed to determine the accuracy of CT for HS detection in liver donor candidates. Pooled sensitivity, specificity, positive and negative likelihood ratios, hierarchical summary receiver operating characteristic (HSROC) curves, and the area under the curve (AUC) were estimated using HSROC and bivariate random-effects models. Results: Twelve studies involving 1782 subjects were eligible for this meta-analysis. For detecting significant HS (>10% to 30% steatosis in liver pathology) with CT in liver donors, the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 0.81 (95% confidence interval [CI]: 0.70-0.89), 0.94 (95%CI: 0.90-0.96), 13.7 (95%CI: 8.1-23.1), and 0.20 (95%CI: 0.12-0.33). The AUC was 0.95 (95%CI: 0.92-0.96). For detecting the presence of HS, these corresponding diagnostic estimates were 0.50 (95%CI: 0.36-0.64), 0.90 (95%CI: 0.83-0.95), 5.2 (95%CI: 3.1-8.9), 0.55 (95%CI: 0.42-0.72) and 0.80 (95%CI: 0.76-0.83). Moderate to high heterogeneity was detected. Conclusion: CT shows high accuracy in detecting significant HS while poor accuracy in detecting the presence of HS in liver donors. Donors estimated to have significant HS by CT may avoid unnecessary liver biopsy. This article is protected by copyright. All rights reserved.
Article
Background: metabolic risk factors should be important in addition to imaging for prediction of steatosis in prospective liver donors. Materials and methods: The study group included all prospective liver donors who had a liver biopsy during work-up. Risk factors of metabolic syndrome were analyzed and body mass index (BMI)≥25 Kg/M(2) was used in place of waist circumference.Three BMI cut-offs (25, 28 and 30 kg/m(2) ) and two CT measured liver attenuation index (LAI) cut-offs (<5 and ≤10) were used for steatosis assessmentof ≥5%, ≥10% and ≥20%. Results: Out of573 prospective donors (307 females), 282 (49.2%) donors had non-alcoholic fatty liver (NAFL). When donors with NAFL were compared with donorshaving normal histology; multivariate analysis showed BMI, ALT, triglycerides and LAI as significant predictors of NAFL. BMI ≥25 kg/m(2) and LAI <10 were better cut-offs. Presence of ≥2 metabolic risk factors had better sensitivity than CT-LAI for presence of NAFL and ≥20% steatosis (58% and 54% versus 47% and 22% respectively for CT LAI≤10). Presence of LAI>10 and <2 metabolic risk factors predicted <10% steatosis with 96% specificity and 92% positive predictive value. Conclusion: Presence of ≥2 metabolic risk factors improves sensitivity of CT-LAI for prediction of donor steatosis This article is protected by copyright. All rights reserved.
Article
Background: Hepatic steatosis threatens post-transplant graft survival therefore, pre-operative quantification of steatosis is crucial. Gold standard for evaluation is donor liver biopsy but it is invasive. An alternative non-invasive method is calculation of CT liver attenuation index. BMI can be an independent factor predicting grade of steatosis but it is necessary to re-define appropriate BMI cut-off points which are specific for Asians. Objective: To retrospectively analyze CT LAI and BMI for quantitative assessment of macro-vesicular steatosis in living related liver donors, using histological analysis as gold standard. Materials & methods: A radiologist blinded to histologic grading calculated mean CT hepatic attenuation in 48 potential living related liver donors. Results: CT derived LAI correctly predicted steatosis in all except 1 patient. Parametric analysis for CT LAI and BMI showed overall weak positive correlation. No significant association was found between BMI and biopsy findings. Conclusion: Liver biopsy remains a gold standard for evaluation of steatosis. CT LAI of ≤ 0 correlates well with significant hepatic steatosis and biopsy may be avoided in such cases. Biopsy may be reserved for patients with CT LAI between 1- 5. BMI alone is not a good predictor of hepatic steatosis in our study population. This article is protected by copyright. All rights reserved.
Article
Objectives: The role of liver biopsy in selecting optimal donors is an area of continuing controversy in living donor liver transplantation (LDLT). Our aim was to assess the potential implications of pre- and intraoperative biopsies in evaluating donor liver fat content. Methods: Of 3,859 consecutive subjects who underwent predonation needle biopsy from the right lobe, 1,766 actually donated their livers in LDLT and underwent intraoperative wedge biopsies from paired right and left lobes. The preoperative workup protocol also included abdominal ultrasonography (USG) and computed tomography (CT). Intersample agreement on steatosis grades (<5%; 5-15%; 15-30%; and ≥30%) was calculated, and clinico-metabolic factors related to sampling variability were evaluated. Results: For the 3,859 potential donors, USG and CT had sensitivities and specificities of 84.9% and 57.3%, and 76.3% and 92.7%, respectively, for detecting ≥30% steatosis, and positive and negative predictive values of 29.6% and 48.0%, and 97.7% and 94.8%, respectively. Analyses of the 1,766 actual donors showed that with respect to total steatosis grade in intraoperative right and left biopsies versus preoperative biopsy, 36.7% and 36.0% pairs, respectively, differed from the weighted κ values of 0.44 and 0.40. Similar agreement levels existed for the macrovesicular and microvesicular steatosis subtypes. The per-subject agreement rate for total steatosis grade between the intraoperative right and left biopsies was of 83.6%. According to a multivariate analysis, the independent factors affecting the variability of the total steatosis results obtained from preoperative biopsy and intraoperative biopsies (major features) were higher systolic blood pressure, body mass index and alanine aminotransferase and lower high-density lipoprotein cholesterol. Conclusions: Imaging may be insufficiently sensitive for evaluating donor hepatic steatosis. Preoperative and selective intraoperative liver biopsies are mandatory for assessing donor steatosis in LDLT, unless preoperative imaging demonstrates no fat. Liver Transpl , 2014. © 2014 AASLD.
Article
It is well known that implantation of donor livers with severe fatty infiltration (>60%) is frequently associated with early hepatic dysfunction and an increased incidence of primary nonfunction after liver transplantation. The outcome of donor livers with less fatty infiltration has not been well defined. We, therefore, studied the outcome of 59 liver transplantations in which donor livers with up to 30% fat were used. Patient outcome was compared to a time-matched control group of 57 patients. The two groups were similar in terms of age, gender, preservation time, primary diagnosis, and UNOS status. We compared both groups with regard to 4-month and 2-year patient and graft survival. We also assessed the incidence of ischemic type biliary strictures and hepatic artery thrombosis, and evaluated the causes of graft loss in both groups. We found that use of donor livers with up to 30% fatty infiltration was associated with a significant decrease in 4-month graft survival (76% vs. 89%, P<0.05) and in 2-year patient survival (77% vs. 91%, P<0.05). Primary nonfunction and primary dysfunction formed the main cause of graft loss and mortality. Multivariate analysis showed that fatty infiltration is an independent predictive factor for outcome after transplantation. We conclude that liver allografts with up to 30% fat lead to diminished outcome after liver transplantation. However, this diminished outcome should be viewed with respect to the increasing mortality on the national waiting list.
Article
The aim of the study was to evaluate the prevalence and risk factors of biopsy-proven non-alcoholic fatty liver disease (NAFLD) in potential living liver donors and to evaluate the efficacy of imaging techniques for the detection of steatosis in donors. We reviewed the results of liver biopsy, ultrasonography (USG) and computed tomography (CT) and biochemical data performed in 589 consecutive potential liver donors as a pretransplantation work up from July 2004 to September 2005 at Asan Medical Centre. Of 589 participants, 408 (69.3%) were men, with a mean age of 31.1+/-9.5 years. NAFLD (5% steatosis in biopsy) was diagnosed in 303 (51.4%); >30% steatosis in 61 (10.4%) and non-alcoholic steatohepatitis in 13 (2.2%). The independent risk factors for >30% steatosis were age over 30 (OR=2.223; p=0.014), obesity (OR=5.320; p<0.001) and hypertriglyceridemia (OR=2.253; p=0.019) by multivariate analysis. The sensitivity of USG and CT for detecting >30% steatosis was 92.3% and 64.1%, and positive predictive value was only 34.5% and 45.1%, respectively. NAFLD was highly prevalent in potential living liver donors. The independent risk factors for significant steatosis were older age, obesity and hypertriglyceridemia. USG and CT had limitations in detecting significant steatosis in liver donors.
Article
Despite increasing use of various imaging examinations for non-invasive assessment of hepatic steatosis (HS), their relative accuracy is unknown. The objective of this study is to prospectively compare the accuracy of computed tomography (CT), dual gradient echo magnetic resonance imaging (DGE-MRI), proton magnetic resonance spectroscopy ((1)H-MRS), and ultrasonography (US) for the diagnosis and quantitative estimation of HS. A total of 161 consecutive potential living liver donors underwent US (performed by two independent radiologists, US1 and US2), CT, DGE-MRI, (1)H-MRS, and liver biopsy on the same day. Using the histologic degree of HS as the reference standard, we compared the diagnostic performance of US1, US2, CT, DGE-MRI, and (1)H-MRS for diagnosing HS >or= 5% and HS >or= 30% and compared the accuracy of CT, DGE-MRI, and (1)H-MRS in the quantitative estimation of HS. DGE-MRI and (1)H-MRS significantly outperformed CT and US for the diagnosis of HS5%. DGE-MRI showed a tendency of higher accuracy than the other examinations for diagnosing HS >or= 30%. The cross-validated sensitivity and specificity of DGE-MRI at the optimal cut-off were 76.7% and 87.1%, respectively, for diagnosing HS >or= 5% and 90.9% and 94%, respectively, for diagnosing HS >or= 30%. The cross-validated Bland-Altman 95% limits of agreement between the estimated degree of HS on imaging examinations and the histologic degree of HS, were the narrowest with DGE-MRI, yielding -12.7% to 12.7%. Among CT, DGE-MRI, (1)H-MRS, and US, DGE-MRI is the most accurate method for the diagnosis and quantitative estimation of HS. Therefore, DGE-MRI may be the preferred imaging examination for the non-invasive assessment of HS.
Article
Evaluation of graft hepatic steatosis is important for the safety of the donor and the recipient in living donor liver transplantation. It is necessary to establish a noninvasive evaluation method to avoid performing a liver biopsy for donor safety. The aim of this study was to identify independent factors that correlated with hepatic steatosis to create a noninvasive method to evaluate hepatic steatosis. We retrospectively collected data from 105 living donors. No prisoners were used to obtain the grafts, all of which underwent postoperative histological evaluation for hepatic steatosis. Preoperative clinical and biochemical variables were examined with univariate analyses, and filtered variables further examined with ordinal regression analysis. Eighty (76.2%) donors showed no hepatic steatosis, 15 (14.3%), mild steatosis, and 10 (9.5%), moderate steatosis. In ordinal stepwise regression analysis, body mass index (BMI; P = .000) was the only independent factor that correlated with the grade of hepatic steatosis. Preoperative biochemical parameters were not significantly correlated with hepatic steatosis. A regression model based on BMI was created to evaluate hepatic steatosis grade. Furthermore, individuals with a BMI > 27.5 were most likely to show moderate steatosis, and those with BMI < 23 likely to display no or mild steatosis. BMI can help to identify the grade of hepatic steatosis among living donors. BMI is also useful to select living donors for a preoperative liver biopsy before liver transplantation.
Article
Liver biopsies detect silent donor disease in potential living liver donors and provide material for studies of subclinical non-alcoholic fatty liver disease (NAFLD). Our primary goal was to determine the contribution of biopsy findings to potential donor evaluation. Factors contributing to pre-clinical NAFLD and correlations between liver injury tests and histopathology have been also determined. Patient records, laboratory tests and results of the histopathologic examination and diagnoses of 284 patients from 2001 to 2005 were retrospectively extracted from the EDIT database. Hepatic histology was correlated with liver injury tests and with general demographic characteristics in an otherwise normal healthy population. A minority (n=119; 42%) of biopsies from this population of 143 males/141 females (average age=36.8years; mean BMI=26.6) were completely normal. The remainder showed steatosis (n=107; 37%), steatohepatitis (n=44; 15%), or unexplained low-grade/early stage chronic hepatitis, primary biliary cirrhosis, or nodular regenerative hyperplasia (n=16; 6%). Biopsy findings disqualified 29/56 donors. Independent risk factors for NAFLD by multivariate modeling, which differed by sex, included: BMI (p=0.0001), age (p=0.003), iron (p=0.01), and ALT (p=0.004). Liver biopsies provide valuable information about otherwise undetectable liver disease in potential liver donors. Obesity, age and iron, which are influenced by sex, contribute to NAFLD pathogenesis. Blood tests other than standard liver profiles are needed to detect early NAFLD.
Article
Methods of evaluating and comparing the performance of diagnostic tests are of increasing importance as new tests are developed and marketed. When a test is based on an observed variable that lies on a continuous or graded scale, an assessment of the overall value of the test can be made through the use of a receiver operating characteristic (ROC) curve. The curve is constructed by varying the cutpoint used to determine which values of the observed variable will be considered abnormal and then plotting the resulting sensitivities against the corresponding false positive rates. When two or more empirical curves are constructed based on tests performed on the same individuals, statistical analysis on differences between curves must take into account the correlated nature of the data. This paper presents a nonparametric approach to the analysis of areas under correlated ROC curves, by using the theory on generalized U-statistics to generate an estimated covariance matrix.
Article
Hepatic steatosis is a recognized risk factor for primary nonfunction of hepatic allografts, but the effect of steatosis on postoperative recovery after major liver resection is unknown. Our aim was to determine if hepatic steatosis is associated with increased perioperative morbidity and mortality in patients undergoing major resection. A retrospective review of medical records of 135 patients who had undergone major hepatic resection from 1990 to 1993 was performed. Histopathology of the hepatic parenchyma at the resection margin was reviewed for the presence of macro- or microvesicular steatosis. The extent of steatosis was graded as none (group 1), mild with less than 30% hepatocytes involved (group 2), or moderate-to-severe with 30% or more hepatocytes involved (group 3). Outcome of patients was correlated with extent of steatosis. Patients with moderate-to-severe steatosis were obese (body mass index = 25.8 +/- 0.5 vs. 26.5 +/- 1.0 vs. 33.4 +/- 2.9; P< 0.05 groups 1, 2, and 3, respectively) and had an increased serum bilirubin concentration preoperatively. Hepatectomy required a longer operative time for group 3 (290 +/- 9 minutes vs. 287 +/- 13 minutes vs. 355 +/- 24 minutes; P </=0.05 groups 1, 2 and 3, respectively). Likelihood of blood transfusion was 51% in group 1, 52% in group 2, and 71% in group 3. Mortality was 14% in group 3 vs. 3% in group 1, and 7% in group 2; and liver failure occurred in 14% of patients in group 3 compared to 4% and 9% in groups 1 and 2, respectively. Patients in group 3 also had increased postoperative bilirubin levels compared to preoperative values. Moderate-to-severe hepatic steatosis may be associated with increased perioperative morbidity and mortality, and preoperative identification of steatosis warrants caution prior to major resection.
Article
Evaluation of the living donor for liver transplantation is a complex process involving such invasive studies as liver biopsy and angiography. It is important to establish the likelihood and extent of hepatic steatosis in living donors by clinical, imaging, and biochemical parameters to avoid performing a liver biopsy, if possible. In this study, the predictive value of body mass index (BMI), liver chemistry tests, and imaging studies was compared with liver histological examination in 33 potential living donors. Patients were grouped and compared based on their BMI (<25, 25 to 28, >28). No patient with a BMI less than 25 had hepatic steatosis. Of patients with a BMI of 25 to 28, steatosis was found on biopsy in 3 of 9 patients. Thirteen of 17 patients (76%) with a BMI greater than 28 had hepatic steatosis on liver biopsy. There was a significant correlation between BMI and overall grade of steatosis (R = 0.49). All subjects with steatosis detected on magnetic resonance imaging (MRI) or computed tomography (CT) had steatosis on biopsy, and all but 2 such patients had greater than 10% steatosis on biopsy. Conversely, 30% of patients in the MRI group and 24% of patients in the CT group failed to show hepatic steatosis when it was present on biopsy. Thus, it appears that liver biopsy could be avoided in subjects with a normal BMI and absence of risk factors. Individuals with a high BMI should undergo liver biopsy because biochemical and imaging data are currently inadequate to determine the extent of steatosis. Future studies should aim at improving the sensitivity of imaging techniques in the diagnosis of steatosis.
Article
Living donor liver transplantation allows an increasing number of patients with end-stage liver disease the opportunity for effective treatment in the face of a critical shortage of cadaveric organs. Hepatic steatosis decreases functional graft mass and may contribute to graft dysfunction. Screening liver biopsy allows accurate quantitation of hepatic fat, but is an invasive procedure that is not universally employed in the evaluation of living donors. We studied 100 consecutive prospective right lobe living donors, all evaluated with liver biopsy, imaging studies, and various clinical parameters. The accuracy and predictive value of body mass index (BMI) and imaging were compared with biopsy in determining the amount of hepatic fat. There were no complications to biopsy, with 33% showing some degree of steatosis. BMI correlated only weakly with biopsy, with 73% of overweight (BMI > 25) donors having little or no hepatic fat. Imaging was only 12% sensitive to small amounts (5% to 10%) of fat, with increasing sensitivity to more severe steatosis. Imaging diagnosed steatosis in 2 donors without hepatic fat and failed to identify a candidate denied with biopsy-proven 30% steatosis. Conversely, 9% of candidates with BMIs of 25 or less had 10% or greater steatosis. Moreover, three candidates were denied surgery because biopsy detected occult liver disease. Accurate quantification of hepatic fat is not afforded by BMI and imaging studies alone. Screening liver biopsy has a low complication rate and may serve to increase donor safety. Biopsy is essential in identifying donor grafts at risk for poor recipient outcome while maximizing the donor pool.
Article
Steatosis of the donor liver is known to impact on patient and allograft outcome after orthotopic liver transplantation (OLT). The aim of this study is to evaluate the effect of increasing grades of cadaveric donor liver steatosis on recipient outcome. Between January, 1986 and December, 2000, 120 OLTs were performed with 72 mild, 25 moderate, and 23 severe steatotic donor livers. Donors of steatotic livers were more likely to be older (P =.001) and have died of intracerebral haemorrhage than donors of nonsteatotic livers. Initial poor graft function (IPF) was more common in donor livers with either moderate or severe steatosis than in donor livers with mild steatosis (P =.03). Primary graft nonfunction (PNF) occurred in only 1 donor liver with severe steatosis. PGE1 (PGE1) usage was higher in recipients of donor livers with moderate or severe steatosis versus donor livers with mild steatosis (P =.001). Allograft loss was greater at 1 year both in the moderate and severe (P =.03) steatotic liver groups. Patient survival at 3 months and overall allograft survival both were impacted negatively by increasing grades of donor liver steatosis (P =.02, P =.03). Three-month allograft survival was reduced in the steatotic donor livers if the donor was 50+ years old (P =.033). Recipient status at OLT (P =.001) and donor steatosis (P =.046) impacted on 30 day allograft survival (multivariate analysis). In conclusion, increasing grades of donor liver steatosis were associated with worse IPF and increased PGE1 usage. There was a negative impact of steatosis on both recipient and early allograft survival.
Article
A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with NAFLD and normal ALT were identified and compared with 50 consecutive subjects with NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained hepatomegaly (n = 21) and evaluation as a potential donor for living donor liver transplantation (n = 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the metabolic syndrome, the major risk factor for NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of NAFLD. A total of 12 subjects with normal ALT levels had bridging fibrosis, whereas 6 had cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced fibrosis (bridging fibrosis or cirrhosis) by multivariate analysis (relative risk: 2.3, P <.01). The mean steatosis (1.6 vs. 2.16, P <.04) and perisinusoidal fibrosis scores (0.35 vs. 0.9, P <.049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying steatohepatitis with advanced fibrosis.
Article
The role of liver biopsy (LB) in donor selection for adult living donor liver transplantation remains controversial, since the procedure is associated with additional potential risks for the donor. From April 1998 to August 2004, 730 potential living donors for 337 adult recipients underwent our multistep evaluation program. In 144 candidates, LB was performed. LB was obtained in a percutaneous ultrasound-guided fashion by means of Menghini needle (32 cases) or Tru-cut needle (112 cases). The biopsy specimen was preserved in 5% formalin and processed with hematoxylin & eosin-stained sections. Thirty-one (21%) of 144 candidates who underwent an LB had a positive finding at histological examination that induced their exclusion from donation, of whom 21 had liver steatosis of varying kind and grade (10%-80%) and 10 had a nonsteatotic hepatopathy (non-A-D hepatitis in 6 cases, diffuse granulomatosis in 2, schistosomiasis in 1, fibrosis in 1). The only observed major complications related to LB were 2 intraparenchymal haematomas, both of which resolved spontaneously within a few months. In conclusion, based on these findings, we believe that preoperative LB in the donor selection for adult LDLT is necessary, once the initial donor screening and noninvasive evaluation is complete. Because other screening modalities can be unreliable, without preoperative LB a fraction of potential donors will be operated on inappropriately, risking both donor and recipient. The main objective of LB should be to ensure the donor's safety more than the preservation of the graft function.
Article
To determine prospectively the diagnostic performance of unenhanced computed tomography (CT) in the assessment of macrovesicular steatosis in potential donors for living donor liver transplantation by using same-day biopsy as a reference standard. Institutional review board approval and informed consent were obtained. A total of 154 candidates, including 104 men (mean age, 30.2 years +/- 10.3 [standard deviation]) and 50 women (mean age, 31.8 years +/- 11.2), underwent same-day unenhanced CT and ultrasonography-guided liver biopsy. Histologic degree of macrovesicular steatosis was determined. Three liver attenuation indices were derived: liver-to-spleen attenuation ratio (CT(L)(/S)), difference between hepatic and splenic attenuation (CT(L)(-S)), and blood-free hepatic parenchymal attenuation (CT(LP)). Regression equations were used to quantitatively estimate the degree of macrovesicular steatosis. Limits of agreement between estimated macrovesicular steatosis and the reference standard were calculated. Receiver operating characteristic analyses were used to determine the performance of each index for qualitative diagnosis of macrovesicular steatosis of 30% or greater. The cutoff value that provided a balance between sensitivity and specificity and the highest cutoff value that yielded 100% specificity were determined. Limits of agreement were -14% to 14% for CT(L)(/S) and CT(L)(-S) and -13% to 13% for CT(LP). Performance in diagnosing macrovesicular steatosis of 30% or greater was not significantly different among indices (P > .05). Cutoff values of 0.9, -7, and 58 were determined for CT(L)(/S), CT(L)(-S), and CT(LP), respectively, and provided a balance between sensitivity and specificity. Cutoff values of 0.8, -9, and 42 were determined for CT(L)(/S), CT(L)(-S), and CT(LP), respectively, and yielded 100% specificity for all indices, with corresponding sensitivities of 82%, 82%, and 73% for CT(L)(/S), CT(L)(-S), and CT(LP), respectively. Diagnostic performance of unenhanced CT for quantitative assessment of macrovesicular steatosis is not clinically acceptable. Unenhanced CT, however, provides high performance in qualitative diagnosis of macrovesicular steatosis of 30% or greater.