Risk Factors For Steatosis Research Articles

Lindera obtusiloba Blume Alleviates Non-Alcoholic Fatty Liver Disease Promoted by Nε-(carboxymethyl)lysine.

Non-alcoholic fatty liver disease (NAFLD) is a major issue because it is closely associated with metabolic diseases. Advanced glycation end products (AGEs) are implicated as risk factors for steatosis during NAFLD progression. AGEs influence NAFLD progression through a receptor-independent pathway involving AGE cross-link formation and a receptor-dependent pathway that binds to receptors like receptors for advanced glycation end products (RAGE). The objectives of this study are to examine the effect of Lindera obtusiloba Blume (LO) on NAFLD promoted by Nε-(carboxymethyl)lysine (CML), one of the most common dietary AGEs. The anti-glycation effects of LO were evaluated by inhibiting the AGEs formation and AGEs-collagen cross-links breaking. The efficacy of LO against NAFLD promoted by CML was assessed using both in vitro and in vivo models. NAFLD was induced in mice by feeding a high-fat diet and orally administering CML over a period of 12 weeks, and the effects of LO on lipid metabolism and its regulatory mechanisms were investigated. LO showed the effect of inhibited AGEs formation and breakage, and collagen cross-linking. Fed a high-fat diet with administered CML by gavage, LO administration resulted in a reduction in body weight, fat mass, serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. LO reduced hepatic CML accumulation and RAGE expression in mice fed a high-fat diet and orally administered CML. LO alleviated hepatic steatosis accompanied by lipid accumulation and histological damage by suppressing the expression of sterol regulatory element-binding protein 1c, carbohydrate response element binding protein, fatty acid synthase, stearoyl-CoA desaturase1, tumor necrosis factor-α, and interleukin-1β. LO alleviated the MAPK/NF-κB expression by attenuating CML and RAGE expression. Taken together, our results demonstrate that LO alleviates the progression of NAFLD by lowering the levels of AGEs by downregulating CML/RAGE expression.

Prevalence and risk factors for steatosis and liver fibrosis measured by magnetic resonance elastography in adults with cystic fibrosis-related diabetes

Prevalence and risk factors for steatosis and liver fibrosis measured by magnetic resonance elastography in adults with cystic fibrosis-related diabetes

Ultrasound attenuation imaging: a reproducible alternative for the noninvasive quantitative assessment of hepatic steatosis in children.

Pediatric hepatic steatosis is a global public health concern, as an increasing number of children are affected by this condition. Liver biopsy is the gold standard diagnostic method; however, this procedure is invasive. Magnetic resonance imaging (MRI)-derived proton density fat fraction has been accepted as an alternative to biopsy. However, this method is limited by cost and availability. Ultrasound (US) attenuation imaging is an upcoming tool for noninvasive quantitative assessment of hepatic steatosis in children. A limited number of publications have focused on US attenuation imaging and the stages of hepatic steatosis in children. To analyze the usefulness of ultrasound attenuation imaging for the diagnosis and quantification of hepatic steatosis in children. Between July and November 2021, 174 patients were included and divided into two groups: group 1, patients with risk factors for steatosis (n = 147), and group 2, patients without risk factors for steatosis (n = 27). In all cases, age, sex, weight, body mass index (BMI), and BMI percentile were determined. B-mode US (two observers) and US attenuation imaging with attenuation coefficient acquisition (two independent sessions, two different observers) were performed in both groups. Steatosis was classified into four grades (0: absent, 1: mild, 2: moderate and 3: severe) using B-mode US. Attenuation coefficient acquisition was correlated with steatosis score according to Spearman's correlation. Attenuation coefficient acquisition measurements' interobserver agreement was assessed using intraclass correlation coefficients (ICC). All attenuation coefficient acquisition measurements were satisfactory without technical failures. The median values for group 1 for the first session were 0.64 (0.57-0.69) dB/cm/MHz and 0.64 (0.60-0.70) dB/cm/MHz for the second session. The median values for group 2 for the first session were 0.54 (0.51-0.56) dB/cm/MHz and 0.54 (0.51-0.56) dB/cm/MHz for the second. The average attenuation coefficient acquisition was 0.65 (0.59-0.69) dB/cm/MHz for group 1 and 0.54 (0.52-0.56) dB/cm/MHz for group 2. There was excellent interobserver agreement at 0.94 (95% CI 0.92-0.96). There was substantial agreement between both observers (κ = 0.77, with a P < 0.001). There was a positive correlation between ultrasound attenuation imaging and B-mode scores for both observers (r = 0.87, P < 0.001 for observer 1; r = 0.86, P < 0.001 for observer 2). Attenuation coefficient acquisition median values were significantly different for each steatosis grade (P < 0.001). In the assessment of steatosis by B-mode US, the agreement between the two observers was moderate (κ = 0.49 and κ = 0.55, respectively, with a P < 0.001 in both cases). US attenuation imaging is a promising tool for the diagnosis and follow-up of pediatric steatosis, which provides a more repeatable form of classification, especially at low levels of steatosis detectable in B-mode US.

The possible association between blood level of free cholesterol and the severity of steatosis in patients with nonalcoholic fatty liver disease

Background The global rising prevalence of nonalcoholic fatty liver disease (NAFLD) highlights the need to understand the risk factors related to its pathogenesis and its related complications. NAFLD is mediated by lipotoxicity that results from an imbalance in hepatic lipid metabolism. Emerging evidence suggests that lipotoxicity mediated by hepatic free cholesterol (FC) overload may result in steatohepatitis. Lipotoxicity is not only associated with the pathogenesis of NAFLD, but also related to increased risk of atherosclerosis and cardiovascular complications, the main leading causes of mortality in NAFLD. Aim The study tried to clarify the possible association between serum levels of FC and the severity of hepatic steatosis in NAFLD. Patients and methods This cross-sectional study included 120 participants, who proved to have different stages of hepatic steatosis using elastography with controlled attenuation parameter (CAP). The correlations between different lipid parameters as well as serum FC levels and CAP values of hepatic steatosis for all participants were assessed using multivariate linear regression analysis. Results The most independent significant lipid parameters associated with CAP values were FC, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P&lt;0.001 for all). Moreover, the discriminately performance of those parameters as risk factors for steatosis using receiver operating characteristics showed an area under the curve of 0.991, 0.957, and 0.861, respectively, with a significant performance (P&lt;0.001 for all). Conclusion We could conclude that increased serum levels of FC along with increased levels of low-density lipoprotein cholesterol and decreased levels of high-density lipoprotein cholesterol have significant correlations to the increased severity of hepatic steatosis in NAFLD.

Regression of Graft Steatosis After Liver Transplantation.

Introduction: Liver grafts with limited steatosis are currently used for liver transplantation, but the natural history of graft steatosis is not well known. Project Aims or Questions: This program evaluation aimed at assessing changes of steatosis after liver transplantation. Design: A retrospective chart review was performed assessing presence and severity of steatosis in the liver explant and in time zero donor graft biopsies carried out at the time-point of liver transplantation on histopathology and on imaging one year thereafter in 30 well characterized patients. Results: Ten patients (33%) showed steatosis on explant. Time zero biopsy revealed steatosis in 18 grafts (60%) and no steatosis in 12 (40%). One year after transplantation, 8 patients (27%) had steatosis and 22 patients (63%) had none. Fourteen patients (47%) showed changes in steatosis: 12 showed resolution and 2 showed de novo steatosis. Explant macrovesicular steatosis was associated with presence of steatosis 1 year after transplantation (binary logistic regression model, p = 0.014), but not macrovesicular steatosis in the donor graft at time-point of transplantation. Conclusion: Resolution of graft steatosis was frequent. Presence of steatosis in the recipient's liver, but not graft steatosis, was a risk factor for steatosis 1 year after transplantation. Factors related to the recipient seem to prevail over donor-related factors in determining the persistence or de novo appearance of steatosis after liver transplantation.

Prevalence and risk factors of steatosis and advanced fibrosis using transient elastography in the United States' adolescent population.

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children and adolescents.AIMTo determine the prevalence and risk factors of steatosis and advanced fibrosis using transient elastography (TE) in the United States’ adolescent population.METHODSUsing the National Health and Nutrition Examination Survey 2017-2018, adolescent participants aged 13 to 17 years who underwent TE and controlled attenuation parameter (CAP) were included in this study. Forty-one factors associated with liver steatosis and fibrosis were collected. Univariate and multivariate linear regression analysis were used to identify statistically significant predictors.RESULTSSeven hundred and forty participants met inclusion criteria. Steatosis (S1-S3), based on CAP, and advanced fibrosis (F3-F4), based on TE, were present in 27% and 2.84% of the study population, respectively. Independent predictors of steatosis grade included log of alanine aminotransferase, insulin resistance, waist-to-height ratio, and body mass index. Independent predictors of fibrosis grade included steatosis grade, non-Hispanic black race, smoking history, and systolic blood pressure.CONCLUSIONThis study demonstrated a high prevalence of steatosis in the United States’ adolescent population. Almost 3% of United States’ adolescents had advanced fibrosis. These findings are concerning because a younger age of onset of NAFLD can lead to an earlier development of severe disease, including steatohepatitis, cirrhosis, and liver decompensation.

Psoriasis and Liver Damage in HIV-Infected Patients.

Background/objectives: Psoriasis is the most frequent skin disease in HIV-infected patients. Nonalcohol fatty liver disease (NAFLD) is more prevalent in patients with psoriasis. We report the prevalence of psoriasis and NAFLD and investigate risk factors of liver damage in HIV-infected patients with psoriasis. Methods: We performed a retrospective observational study. Steatosis was defined as indicative abdominal ultrasound findings, CAP (controlled attenuated parameter by transient elastography) > 238 dB/m, and/or triglyceride and glucose index (TyG) > 8.38. Significant (fibrosis ≥ 2) and advanced liver fibrosis (fibrosis ≤ F3) were studied by transient elastography (TE) and/or FIB-4 using standard cutoff points. FIB-4 (Fibrosis 4 score) results were adjusted for hepatitis C (HCV)-coinfected patients. Results: We identified 80 patients with psoriasis (prevalence, 1.5%; 95% CI, 1.1–1.8). Psoriasis was severe (PASI > 10 and/or psoriatic arthritis) in 27.5% of cases. The prevalence of steatosis was 72.5% (95% CI, 65–85). Severe psoriasis was an independent risk factor for steatosis (OR, 12; 95% CI, 1.2–120; p = 0.03). Significant liver fibrosis (p < 0.05) was associated with HCV coinfection (OR 3.4; 95% CI, 1.1–10.6), total CD4 (OR 0.99; 95% CI, 0.99–1), and time of efavirenz exposure (OR 1.2; 95% CI, 1.0–1.3). Conclusions: The prevalence of psoriasis in HIV-infected patients was similar to that of the general population. Steatosis is highly prevalent, and severe psoriasis is an independent risk factor for steatosis in HIV-infected patients.

Obstructive sleep apnea, chronic obstructive pulmonary disease and NAFLD: an individual participant data meta-analysis

RationaleChronic intermittent hypoxia occurring in obstructive sleep apnea (OSA) is independently associated with nonalcoholic fatty liver disease (NAFLD). Chronic obstructive pulmonary disease (COPD) has also been suggested to be linked with liver disease. ObjectiveIn this individual participant data meta-analysis, we investigated the association between liver damage and OSA and COPD severity. Methods and measurementsPatients suspected of OSA underwent polysomnography (PSG) or home sleep apnea testing (HSAT). Non-invasive tests were used to evaluate liver steatosis (Hepatic Steatosis Index) and fibrosis (Fibrotest or FibroMeter). An individual participant data meta-analysis approach was used to determine if the severity of OSA/COPD affects the type and severity of liver disease. Results were confirmed by multivariate and causal mediation analysis. Sub-group analyses were performed to investigate specific populations. Main resultsAmong 2120 patients, 1584 had steatosis (75%). In multivariable analysis, risk factors for steatosis were an apnea-hypopnea index (AHI) > 5/h, body mass index (BMI) > 26 kg/m2, age, type 2 diabetes (all p-values <0.01) and male gender (p = 0.02). Concerning fibrosis, among 2218 patients 397 had fibrosis (18%). Risk factors associated with fibrosis were BMI>26 kg/m2, age, male gender, and type 2 diabetes (all p-values <0.01). AHI severity was not associated with fibrosis. A combination of AHI >30/h and COPD stage 1 was associated with an increased risk of steatosis. ConclusionThis meta-analysis confirms the strong association between steatosis and the severity of OSA. The relation between OSA and fibrosis is mainly due to BMI as shown by causal mediation analysis.

Evaluation of adjuvant chemotherapy-associated steatosis in colorectal cancer.

94 Background: Chemotherapy-associated steatosis (CAS) is poorly understood in context of colorectal cancer (CRC). It has been anecdotally observed that CRC patients undergoing chemotherapy appeared to develop steatosis at a higher rate than expected, and that statin therapy may have protective effects against CAS. Here, we sought to evaluate 1) the frequency of CAS in Stage II-III CRC patients; and 2) whether patients on statins throughout adjuvant chemotherapy develop CAS at a lower frequency. Methods: This study retrospectively examined medical records of 267 Stage II-III CRC patients who received adjuvant chemotherapy and were followed up at St. Michael’s Hospital, Toronto, Canada between January 1, 2006 and January 1, 2017. Patient information, relevant co-morbid conditions, statin use, and adjuvant chemotherapy were collected. Baseline and incident steatosis for up to one year from chemotherapy start date was assessed based on imaging reports (CT, ultrasound, MR). Results: Of 267 patients, 78 (29.2%) had steatosis at baseline radiology, prior to treatment with adjuvant chemotherapy. Of the remaining 189 cases, the incidence of steatosis within one year of adjuvant chemotherapy start date was significantly greater in patients who received adjuvant treatment (n = 132) compared to those who did not (n = 57), (39% vs. 23%, p = 0.03). Among patients who underwent chemotherapy, statin use for preexisting hyperlipidemia, a known risk factor for steatosis (n = 39), was associated with a lower incidence of steatosis compared to no statin administration (n = 93), although this result was not significant (31% vs. 42%, p = 0.243). Among statin users, 42.9% of patients treated using oxaliplatin-containing FOLFOX regimen (n = 21) developed steatosis, compared to 20% in patients on a capecitabine regimen (n = 15). There was a trend towards significance, with p = 0.151. Conclusions: Chemotherapeutic treatment of Stage II-III CRC is associated with an increased incidence of steatosis. Statins may protect against acute development of CAS within one year following chemotherapy, particularly with single agent capecitabine. Prospective clinical trials should be considered to assess protective use of statin in this curative patient population.

Alcoholic liver disease: the roles of genetic-epigenetic factors and the effect of abstinence

The pathogenesis of alcoholic liver disease depends not only on the toxic effects of alcohol, but also on the complex interaction of host's and environmental factors. Thus, the genetic pre-disposition, co-morbidities and behavioral factors all play a role in the individual variations in the disease outcomes. On the other hand, the essential part of the therapeutic strategy is the complete withdrawal of the harmful etiological agent. The present paper is devoted to overview the genetics, the environmental factors and the effects of abstinence in alcoholic liver disease. Genetic variants in two enzymes involved in the metabolism of ethanol, alcohol-dehydrogenase ADH1B *2 and aldehyde-dehydrogenase ALDH2 *2 through increasing the blood level of acetaldehyde, may play a "protective" role against alcoholism. The P450 CYP2E1 *5 c2, an inducible microsomal oxidase, upregulated by ethanol and by formation of acetaldehyde and reactive oxygen species, increases liver toxicity. Three novel gene polymorphisms - such as the patatin-like phospholipase domain-containing 3 (PNPLA3 I148M C>G), the transmembrane 6 superfamily member 2 (TM6SF2 E167K), and the membrane-bound O-acyltransferase domain-containing 7 (MB0AT7 rs641738 C>T) - have been proven as risk factors of steatosis, fibrosis and even hepatocellular carcinoma in both alcoholic and non-alcoholic fatty liver disease patients. Alcohol-induced epigenetic effects, reversible but inheritable gene expression alterations - as histon modulations, DNA methylation and micro-RNA-s - are of importance in the pathogenesis as well, and in the future, they may serve as diagnostic markers and therapeutic targets. Women are at greater risk of developing alcoholic cirrhosis, furthermore, malnutrition, obesity, diabetes, smoking, and hepatitis virus infections are also risk factors. Alcoholic liver disease should be regarded as a preventable disease. Several clinical studies revealed that abstinence may result in the regression of steatohepatitis and fibrosis, compensation of cirrhosis, improving disease outcome and increasing survival even in patients with advanced stages. Early diagnosis and multidisciplinary interventions are highly required to achieve long-term abstinence and to prevent alcoholic cirrhosis. Orv Hetil. 2019; 160(14): 524-532.

Risk factors and prevalence of liver disease in review of 2557 routine liver biopsies performed during bariatric surgery

BackgroundObesity is a known risk factor for nonalcoholic fatty liver disease (NAFLD). However, among individuals undergoing bariatric surgery, the prevalence and risk factors for NAFLD, as well as distinct phenotypes of steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis remain incompletely understood. ObjectivesTo determine the prevalence and risk factors for steatosis, NASH, and fibrosis in individuals undergoing routine bariatric surgery. SettingAcademic medical center in the United States. MethodsLiver wedge biopsies were performed at the time of surgery between 2001 and 2017. Pathology reports were reviewed, and individuals were grouped by NAFLD phenotype. Covariates including demographic characteristics, co-morbidities, and preoperative laboratory values were compared between groups using Student’s t test, Pearson’s χ2, and logistic regression. ResultsLiver biopsies were obtained in 97.7% of first-time bariatric procedures, representing 2557 patients. Mean age was 45.6 years, mean body mass index was 46.7, and most were non-Hispanic white (76.1%) and female (71.6%). On histologic review 61.2% had steatosis and 30.9% NASH. Fibrosis was identified in 29.3% of individuals, and 7.8% had stage ≥2 fibrosis. On logistic regression, elevated aspartate aminotransferase (odds ratio [OR] 1.87; P < .001) and elevated alanine aminotransferase (OR 1.62; P < .001) were independently associated with fibrosis. Elevated hemoglobin A1C of 5.7% to 6.5% (OR 1.29; P < .01) and >6.5% (OR 3.23; P < .001) were also associated with fibrosis. A similar trend was seen for NASH. ConclusionsNASH and/or fibrosis is present in nearly one third of patients undergoing routine bariatric surgery. Risk factors include diabetes, elevated liver enzymes, and diabetes. Risk assessment and aggressive screening should be considered in patients undergoing bariatric surgery.

The diagnostic performance of a simplified blood test (SteatoTest-2) for the prediction of liver steatosis.

Serum biomarkers of steatosis such as the SteatoTest are recommended for large-scale screening studies, because imaging is less accessible and more expensive. The primary aim of this retrospective analysis of prospective studies was to construct a new SteatoTest-2 that was not inferior to the reference first-generation SteatoTest, but that did not include BMI or bilirubin, as these two components can increase test variability because of the assessment of weight and height and in case of Gilbert syndrome or hemolysis, respectively. Five different subsets of 2997 patients with biopsies were evaluated for test construction and validation, and four to assess the prevalence of steatosis in target populations with increasing risks of steatosis. The performance of the SteatoTest-2 was compared with the reference test, using the noninferiority test (0.10 margin) and the Lin concordance coefficient. Areas under the receiver operating characteristic curve of the SteatoTest-2 were noninferior to the reference test (P<0.001). Areas under the receiver operating characteristic curve varied in the SteatoTest-2 and the reference test according to subsets and the prevalence of steatosis, with 0.772 [95% confidence interval (CI): 0.713-0.820] versus 0.786 (95% CI: 0.729-0.832) in the 2997 cases with biopsy and 0.822 (95% CI: 0.810-0.834) versus 0.868 (95% CI: 0.858-0.878) in the 5776 cases including healthy individuals without risk factors of steatosis as controls, respectively. The Lin coefficient was highly concordant (P<0.001), from 0.74 (95% CI: 0.74-0.74) in presumed NAFLD to 0.91 (95% CI: 0.89-0.93) in the construction subset. The SteatoTest-2 is simpler and noninferior to the first-generation SteatoTest for the diagnosis of steatosis, without the limitations of BMI and bilirubin.

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

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

Steatosis Among Living Liver Donors Without Evidence of Fatty Liver on Ultrasonography

The degree of steatosis is an important factor that determines the graft function in the recipient and the recovery of the remnant liver in the living donor. To date, there is no consensus regarding how to assess steatosis among potential living liver donors. We evaluate the prevalence and risk factors for steatosis in living liver donors with normal serum aminotransferase levels and without fatty liver on ultrasonography (US-negative). The degree of steatosis was assessed for a total of 492 US-negative living liver donors with normal aminotransferase levels (age 30.1±9.9; male 301 [61.2%]). Total steatosis was defined by adding the degree of macrosteatosis and microsteatosis. No liver donor had a severe degree (≥60%) of macrosteatosis or microsteatosis. A moderate degree (30-59%) of macrosteatosis and microsteatosis was seen in 4 (0.8%) and 26 (5.3%) subjects, respectively. Severe and moderate degrees of total steatosis were seen in 3 (0.6%) and 53 (10.8%) subjects, respectively. Body mass index and serum triglyceride levels were independent factors associated with the moderate or greater degree of total steatosis. Noninvasive preoperative assessment for liver steatosis (US-negative with normal aminotransferase level) was sufficient to exclude severe macrosteatosis or microsteatosis and moderate macrosteatosis but not sufficient to exclude moderate microsteatosis or total steatosis in living liver donors.

Appraisal of donor steatosis in liver transplantation: a survey of current practice in Australia and New Zealand

Correspondence: Adam Bartlett New Zealand Liver Transplant Unit, Level 15, Support Building, Auckland City Hospital, 2 Park Road, Grafton, Auckland 1023, New Zealand Tel +64 21 241 4647 Fax +64 9 375 4345 Email a.bartlett@auckland.ac.nz Background: Hepatic steatosis is increasingly encountered among organ donors. Currently, there is no consensus guideline as to the type or degree of donor steatosis considered acceptable for liver transplantation (LT), and little is known about local practices in this area. The aim of this survey was to evaluate current clinical practices amongst liver transplant surgeons in Australia and New Zealand (ANZ) in the evaluation and use of steatotic donor livers in LT. Methods: An anonymous online twelve-question survey was emailed to all practicing LT surgeons in ANZ (n = 23) in January 2010. Results: The response rate was 83%. Estimated prevalence of steatosis in donor livers was between 40% and 60%. In determining suitability for LT, 90% of respondents reported rejecting organs with “severe” steatosis based on visual and palpation grounds alone. A total of 68% sought further histological assessment if the donor liver looked bad and there were risk factors for steatosis. The majority of respondents performed only one biopsy of the liver (79%), using hematoxylin and eosin staining for fat assessment (53%). There was wide variation in the upper limit of steatosis considered to be acceptable for LT (40%–80% steatosis). A total of 21% of respondents still considered microvesicular steatosis a risk factor for primary graft nonfunction. Conclusion: This survey highlights the significant variation in the appraisal and use of steatotic grafts by LT surgeons in ANZ. Accurate evaluation and judicious use of mild and moderately steatotic grafts is required if we are to utilize the available donor pool best.

Estimation of Hepatic Proton-Density Fat Fraction by Using MR Imaging at 3.0 T

To compare the accuracy of several magnetic resonance (MR) imaging-based methods for hepatic proton-density fat fraction (FF) estimation at 3.0 T, with spectroscopy as the reference technique. This prospective study was institutional review board approved and HIPAA compliant. Informed consent was obtained. One hundred sixty-three subjects (39 with known hepatic steatosis, 110 with steatosis risk factors, 14 without risk factors) underwent proton MR spectroscopy and non-T1-weighted gradient-echo MR imaging of the liver. At spectroscopy, the reference FF was determined from frequency-selective measurements of fat and water proton densities. At imaging, FF was calculated by using two-, three-, or six-echo methods, with single-frequency and multifrequency fat signal modeling. The three- and six-echo methods corrected for T2*; the two-echo methods did not. For each imaging method, the fat estimation accuracy was assessed by using linear regression between the imaging FF and spectroscopic FF. Binary classification accuracy of imaging was assessed at four reference spectroscopic thresholds (0.04, 0.06, 0.08, and 0.10 FF). Regression intercept of two-, three-, and six-echo methods were -0.0211, 0.0087, and -0.0062 (P <.001 for all three) without multifrequency modeling and -0.0237 (P <.001), 0.0022, and -0.0007 with multifrequency modeling, respectively. Regression slope of two-, three-, and six-echo methods were 0.8522, 0.8528, and 0.7544 (P <.001 for all three) without multifrequency modeling and 0.9994, 0.9775, and 0.9821 with multifrequency modeling, respectively. Significant deviation of intercept and slope from 0 and 1, respectively, indicated systematic error. Classification accuracy was 82.2%-90.1%, 93.9%-96.3%, and 83.4%-89.6% for two-, three-, and six-echo methods without multifrequency modeling and 88.3%-92.0%, 95.1%-96.3%, and 94.5%-96.3% with multifrequency modeling, respectively, depending on the FF threshold. T2*-corrected (three- and six-echo) multifrequency imaging methods had the overall highest FF estimation and classification accuracy. Among methods without multifrequency modeling, the T2-corrected three-echo method had the highest accuracy. Non-T1-weighted MR imaging with T2 correction and multifrequency modeling helps accurately estimate hepatic proton-density FF at 3.0 T.

Risk factors for chemotherapy-associated liver injuries: A multivariate analysis of a group of 146 patients with colorectal metastases

Chemotherapy for colorectal liver metastases (CLM) may be associated with pathologic changes to the liver parenchyma, possibly increasing the risk of surgery. The aim of this study was to determine the risk factors for chemotherapy-associated liver injuries (CALI). From 1998 to 2006, 146 patients underwent a liver resection for CLM within 3 months of preoperative chemotherapy. CALI were defined as follows: steatosis > or =30%, or steatohepatitis, or moderate or severe sinusoidal lesions. Univariate and multivariate analysis were used to examine the relationship between CALI and 36 other preoperative factors. Pathologic examination showed CALI in 74/146 patients (51%), including sinusoidal lesions (n = 50), steatosis > or = 30% (n = 32), and steatohepatitis (n = 15). Twenty-three patients had overlapping CALI. In multivariate analysis, BMI > 27 (P = .002), hyperglycemia > 7 mmol/l (P = .006), and an interval between chemotherapy and surgery < 4 weeks (P = .011) were independent risk factors for CALI, whereas aspirin intake was associated with reduced risk of CALI (P = .002). In multivariate analysis, synchronous metastases (P = .015), unresectable liver metastases at diagnosis (P = .034), GGT plasma level > 1.5N (P = .028), and oxaliplatin-based chemotherapy (P < .01) were risk factors for sinusoidal lesions. Aspirin intake was associated with reduced risk for sinusoidal lesions (P = .03). In multivariate analysis, BMI > 27 (P = .026) was the only risk factor for steatosis or steatohepatitis. In patients with CLM, there are few preoperative risk factors for CALI. In patients treated by oxaliplatin-based chemotherapy, aspirin intake appears to be associated with a reduced risk of sinusoidal lesions and should be tested in a randomized phase II study.

TNFα-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafishs-adenosylhomocysteine hydrolase

Hepatic steatosis and liver degeneration are prominent features of the zebrafish ducttrip (dtp) mutant phenotype. Positional cloning identified a causative mutation in the gene encoding S-adenosylhomocysteine hydrolase (Ahcy). Reduced Ahcy activity in dtp mutants led to elevated levels of S-adenosylhomocysteine (SAH) and, to a lesser degree, of its metabolic precursor S-adenosylmethionine (SAM). Elevated SAH in dtp larvae was associated with mitochondrial defects and increased expression of tnfa and pparg, an ortholog of the mammalian lipogenic gene. Antisense knockdown of tnfa rescued hepatic steatosis and liver degeneration in dtp larvae, whereas the overexpression of tnfa and the hepatic phenotype were unchanged in dtp larvae reared under germ-free conditions. These data identify an essential role for tnfa in the mutant phenotype and suggest a direct link between SAH-induced methylation defects and TNF expression in human liver disorders associated with elevated TNFalpha. Although heterozygous dtp larvae had no discernible phenotype, hepatic steatosis was present in heterozygous adult dtp fish and in wild-type adult fish treated with an Ahcy inhibitor. These data argue that AHCY polymorphisms and AHCY inhibitors, which have shown promise in treating autoimmunity and other disorders, may be a risk factor for steatosis, particularly in patients with diabetes, obesity and liver disorders such as hepatitis C infection. Supporting this idea, hepatic injury and steatosis have been noted in patients with recently discovered AHCY mutations.

Hyperferritinemia is a risk factor for steatosis in chronic liver disease

To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. Mean level of ferritin was 881 +/- 77 ng/mL in men and 549 +/- 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and gamma-glutamyltransferase were independent predictors of steatosis. Ferritin levels were significantly related to low platelet count, steatosis and hepatitis C virus infection. In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.

Correlation of serum adiponectin levels and hepatic steatosis in hepatitis c virus genotype 1 infection

Steatosis is an important cofactor in hepatitis C virus (HCV) because it is associated with fibrosis and reduces early and sustained virologic response. Recent studies suggest that HCV genotype 1 is not steatogenic if additional risk factors are not present. Because hypoadiponectinemia was found to be a feature of nonalcoholic steatohepatitis (NASH) independent of insulin resistance, its level in patients with hepatitis C genotype can reveal the optimal therapeutic strategy. This study was conducted to determine the role of the relationship between steatosis and serum adiponectin levels in the progression of liver damage in HCV genotype 1 without known risk factors for NASH. Patients (n=50) with biopsy-proven chronic hepatitis C (CHC), positive HCV RNA, and raised alanine aminotransferase were enrolled. They were carefully selected to rule out possible confounding factors for the presence of steatosis and additional systemic or liver disease. Associations between serum adiponectin levels and grade of steatosis, histologic activity index (HAI), fibrosis grade of liver biopsies, patient age, HCV viral load, and serum transaminase activities were studied. Also, adiponectin levels were compared with those of a control group of 30 healthy volunteers with normal ultrasound findings of the upper abdomen who had no known NASH risk factors. The investigators found that adiponectin levels in patients with CHC genotype 1 were similar to those in healthy subjects. No significant association was found between adiponectin levels and severity of steatosis, HCV RNA levels, HAI, transaminases, and fibrosis. Steatosis was present in 41 patients (82%) with CHC. Multivariate analysis of data on 50 patients revealed that severity of steatosis was independently related to age alone (P=.03). A correlation between HCV RNA load and HAI was observed (P=.02; r=0.712). HAI also was associated with stage of fibrosis (P=.00; r= 0.612). In cases of chronic HCV genotype 1 hepatitis, steatosis is a common histologic feature, although no risk factors are known. Results presented here cannot establish an association between adiponectin and severity of steatosis when risk factors for steatosis are unknown. Additional studies are needed to discover a metabolic treatment that would seek to improve the progression of hepatic steatosis in CHC infection.