Predictors Of Steatosis Research Articles

Machine learning models predict liver steatosis but not liver fibrosis in a prospective cohort study

IntroductionScreening for liver fibrosis continues to rely on laboratory panels and non-invasive tests such as FIB-4-score and transient elastography. In this study, we evaluated the potential of machine learning (ML) methods to predict liver steatosis on abdominal ultrasound and liver fibrosis, namely the intermediate-high risk of advanced fibrosis, in individuals participating in a screening program for colorectal cancer. MethodsWe performed ultrasound on 5834 patients admitted between 2006 and 2020, and transient elastography on a subset of 1240 patients. Steatosis on ultrasound was diagnosed if liver areas showed a significantly increased echogenicity compared to the renal parenchyma. Liver fibrosis was defined as a liver stiffness measurement ≥8 kPa in transient elastography. We evaluated the performance of three algorithms, namely Extreme Gradient Boosting, Feed-Forward neural network and Logistic Regression, deriving the models using data from patients admitted from January 2007 up to January 2016 and prospectively evaluating on the data of patients admitted from January 2016 up to March 2020. We also performed a performance comparison with the standard clinical test based on Fibrosis-4 Index (FIB-4). ResultsThe mean age was 58±9 years with 3036 males (52%). Modelling laboratory parameters, clinical parameters, and data on eight food types/dietary patterns, we achieved high performance in predicting liver steatosis on ultrasound with AUC of 0.87 (95% CI [0.87–0.87]), and moderate performance in predicting liver fibrosis with AUC of 0.75 (95% CI [0.74–0.75]) using XGBoost machine learning algorithm. Patient-reported variables did not significantly improve predictive performance. Gender-specific analyses showed significantly higher performance in males with AUC of 0.74 (95% CI [0.73–0.74]) in comparison to female patients with AUC of 0.66 (95% CI [0.65–0.66]) in prediction of liver fibrosis. This difference was significantly smaller in prediction of steatosis with AUC of 0.85 (95% CI [0.83–0.87]) in female patients, in comparison to male patients with AUC of 0.82 (95% CI [0.80–0.84]). ConclusionML based on point-prevalence laboratory and clinical information predicts liver steatosis with high accuracy and liver fibrosis with moderate accuracy. The observed gender differences suggest the need to develop gender-specific models.

Serum Ferritin and NAFLD in Patients Undergoing Bariatric Surgery.

Non-alcoholic fatty liver disease (NAFLD) has become a challenge in public health, as the prevalence of obesity and overweight has been increasing. It has been observed that serum ferritin (SF) levels are commonly elevated in NAFLD patients. To assess the relationship between SF levels and NAFLD, exploring the role of SF as a non-invasive marker of NAFLD. Clinical, anthropometric, laboratory, and histological data of patients with obesity who underwent bariatric surgery in a reference center in Brazil were retrospectively evaluated. Data were collected in the preoperative period up to the first year postoperatively. A total of 431 patients were analyzed. The prevalence of hyperferritinemia was 18% in the preoperative period and 14% 1 year after the surgery. After multiple regression analysis, elevated SF was not an independent predictor of steatosis, non-alcoholic steatohepatitis (NASH), or liver fibrosis. Increased SF levels are common in patients with NAFLD; however, SF was not considered an independent predictor of steatosis, NASH, or fibrosis.

Non-invasive methods for diagnosis of non-alcoholic fatty liver disease in children and adolescents: literature review / Métodos não invasivos para diagnóstico da doença hepática gordurosa não alcoólica em crianças e adolescentes: revisão da literatura

With the significant increase in the prevalence of nonalcoholic fatty liver disease (NAFLD) in children and adolescents and knowing its association with other clinical conditions and its implications in adult life, noninvasive diagnostic methods may represent new paths for prevention, early diagnosis and follow-up of the evolution of the disease. Objective: To describe noninvasive methods for diagnosing NAFLD in children and adolescents. Methods: integrative review. The articles were searched in the PubMed, Lilacs, Medline, Embase and Google Scholar databases, from August to December 2021. The descriptors "non-alcoholic fatty liver disease", "non-invasive methods", "biomarkers", "child" and "adolescent" were used. Results: Several biomarkers have been associated with the diagnosis of NAFLD, and among the most recognized are the lipid and glucose profile, liver enzymes, anti-inflammatory profile and assessment of body fat reserves. Antioxidant profile, uric acid, genome, lipidomics and proteomics evaluations are also predictors of steatosis; however, it remains to be determined whether these markers should be used together or in isolation for better results. Conclusions: Noninvasive markers for the diagnosis of NAFLD in children and adolescents are promising and, when used in association with clinical data, can be useful in guiding and managing this population for the prevention and control of NAFLD.

Prevalence of Elevated Liver Stiffness Among Potential Candidates for Bariatric Surgery in the United States

PurposeObesity represents a well-known risk factor for metabolic-dysfunction associated fatty liver disease (MAFLD) and its progression towards cirrhosis. The aim of this study is to estimate the proportion of potential candidates to a bariatric surgery intervention that has an elevated liver stiffness on vibration-controlled transient elastography (VCTE).Materials and MethodsThis is a cross-sectional study performed using data obtained during the 2017–2018 cycle of the National Health and Nutrition Examination Survey. Potential candidates for a bariatric surgery intervention from the general US population were identified by applying criteria from international guidelines. All included participants were evaluated by VCTE. A controlled attenuation parameter (CAP) value ≥ 288 dB/m was considered indicative of steatosis while liver stiffness measurement (LSM) was considered elevated if ≥ 9.7 kPa. Multivariable logistic regression models were fitted to identify independent predictors of both outcomes.ResultsA total of 434 participants were included (mean age 42.9 ± 0.6 years; 54.4% women). Among them, 76.7% (95% CI 71.7–81.0) had steatosis, while 23.1% (95% CI 17.8–29.3) had an elevated LSM. Male sex, older age, γ-glutamyltranspeptidase levels, and body mass index (BMI) were independent predictors of steatosis, while BMI was the only independent predictor of elevated LSM. Non-Hispanic black participants were protected from both outcomes, while other ethnicities were not.ConclusionThe prevalence of elevated LSM is high in potential candidates for a bariatric surgery intervention. Accurate screening for occult advanced liver disease might be indicated in this patient population.Graphical abstract

Viscoelasticity measured by shear wave elastography in a rat model of nonalcoholic fatty liver disease: comparison with dynamic mechanical analysis

BackgroundNonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common liver diseases. Ultrasound elastography has been used for the diagnosis of NAFLD. However, clinical research on steatosis by elastography technology has mainly focused on steatosis with fibrosis or non-alcoholic steatohepatitis (NASH), while steatosis without fibrosis has been poorly studied. Moreover, the relationship between liver viscoelasticity and steatosis grade is not clear. In this study, we evaluated the degree of liver steatosis in a simple steatosis rat model using shear wave elastography (SWE).ResultsThe viscoelasticity values of 69 rats with hepatic steatosis were measured quantitatively by SWE in vivo and validated by a dynamic mechanical analysis (DMA) test. Pathological sections were used to determine the steatosis grade for each rat. The results showed that the elasticity values µ obtained by the two methods followed the same trend, and µ is significantly correlated with liver steatosis. The Pearson’s correlation coefficients indicate that mu obtained by SWE is positively linear correlated with DMA (r = 0.628, p = 7.85 × 10–9). However, the viscosity values eta obtained by SWE were relatively independent of those obtained by DMA with a correlation coefficient of − 0.01. The combined Voigt elasticity measurements have high validity in the prediction of steatosis (S0 vs. S1–S4), with an AUROC of 0.755 (95% CI 0.6175–0.8925, p < 0.01) and the optimal cutoff value was 2.08 kPa with a sensitivity of 78% and specificity of 63%.ConclusionSWE might have the feasibility to be introduced as an auxiliary technique for NAFLD patients in clinical settings. However, the viscosity results measured by SWE and DMA are significantly different, because the two methods work in different frequency bands.

Prediction of Liver Histology Using Skin Autofluorescence Measurement in Patients Undergoing Liver Resection

Introduction: Skin autofluorescence (sAF) is an indirect measure of advanced glycation end-products (AGEs), which are associated with liver injury. The study aimed to assess the utility of sAF in preoperative prediction of non-tumoral liver status in patients undergoing liver resection. Methods: This prospective study comprised 120 patients undergoing liver resection in the Department of General, Transplant and Liver Surgery of the Medical University of Warsaw between September 2018 and November 2019. Liver fibrosis and steatosis was the primary and secondary end-point, respectively. Patients with cirrhosis were excluded from the study. sAF was assessed preoperatively in all patients using a device based on photodiodes (measurements were expressed in arbitrary units [AU]). Results: Liver fibrosis was found in 28.3% (34 of 120) and steatosis>10% in 29.2% (35 of 120) patients. There were no differences in sAF between obese or overweight patients and those with BMI< 25 (p=0.276). sAF≥2.4 AU was an independent predictor of liver fibrosis (odds ratio [OR] 2.94; 95% confidence interval [95% CI] 1.288 - 6.731; p=0.011) with positive (PPV) and negative (NPV) predictive values of 40.0% and 81.5%, respectively. The median sAF was higher in patients with liver steatosis>10% (p=0.024). The optimal cut-off for sAF in prediction of steatosis>10% was ≥2.5 AU (area under the curve 0.631, 95% CI 0.520-0.742; p=0.021), with PPV and NPV of 42.9.2% and 80.3%, respectively. Conclusion: Skin autofluorescence as non-invasive and clinically applicable test can potentially be used to initially predict the presence of hepatic fibrosis and steatosis in patients scheduled for liver resection.

Obese boys with low concentrations of high-density lipoprotein cholesterol are at greater risk of hepatosteatosis.

Non-alcoholic fatty liver disease (NAFLD) and associated morbidities have become a major public health problem, with a global three-fold increase in incidence among obese children over the last three decades. Although the gold standard for diagnosis of NAFLD is liver biopsy, it is not widely used in children. Imaging techniques, including magnetic resonance imaging (MRI) and ultrasound (US), can provide information on liver fat deposition, however, with variable sensitivity. A number of other predictors are therefore being investigated for pediatric screening and diagnostic purposes. The aim of this study was to assess easily measured parameters to prompt further investigation into NAFLD in obese children. Obese children/adolescents with a body mass index (BMI) percentile > 95 were enrolled in the study (n = 353). After a 12-hour fast, venous glucose, insulin, cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and uric acid were measured and a full blood count was performed in all subjects. TG/LDL ratio, AST/platelet ratio index (APRI score), and homeostatic model of assessment for insulin resistance (HOMA-IR) were calculated. All patients underwent an abdominal US examination to assess hepatosteatosis. Of 353 patients, median age 12.5 (range, 6-17.9) years, 210 patients (59%) had US-proven hepatosteatosis. Female gender reduced the risk of steatosis 2.08-fold (p = 0.005), a one-unit increase in HDL reduced the risk of steatosis 1.02-fold (p = 0.042), and a one-unit increase in BMI led to a 1.11-fold (p = 0.002) increase in the risk of steatosis. Gender, BMI, and HDL were found to be predictors of steatosis. Male patients with low HDL and high BMI are at greater risk of steatosis and should be carefully examined for the presence of NAFLD.

Association between PNPLA3[G]/I148M variant, steatosis and fibrosis stage in hepatitis C virus - genetic matters.

There is an established correlation between the PNPLA3 rs738409 C > G single nucleotide polymorphism (SNP) and hepatic steatosis and fibrosis in hepatitis C virus (HCV) infected patients. However not all data is convergent regarding the exact impact of this SNP on the pattern of disease progression in different clinical settings. In this study, we aimed to further bridge the knowledge gap on this topic by investigating the role of the G allele in promoting steatosis, fibrosis and disease progression in relation to other metabolic and anthropometric host factors. Two hundred and fifty consecutive patients, previously diagnosed with chronic hepatitis C (CHC) underwent liver biopsy. Histology was assessed using the Metavir scoring system. Transient elastography was used for follow-up. Ninety-eight patients were genotyped for PNPLA3 rs738409 and followed up for fibrosis progression. PNPLA3 rs738409[G] allele was significantly correlated with severe steatosis (P = 0.04), severe fibrosis at the time of enrollment (P = 0.0005) and fibrosis progression with an OR of 10.31 (95% CI 1.06 - 99.59, P = 0.04), after a mean follow-up time of 62.85 (95%CI: 52.21 - 76.15) months. Severe steatosis at the time of enrollment had an OR of 11.02 (95% CI 1.48 - 82.09, P = 0.01) for the association with fibrosis progression. The HOMA-IR index was also positively correlated with severe fibrosis (P = 0.03) and fibrosis progression on univariate analysis (P = 0.02). PNPLA3 rs738409[G] allele is a reliable predictor for steatosis and fibrosis in CHC. The presence of G allele, along with severe steatosis and insulin resistance are significant predictors for fibrosis progression.

Different predictors of steatosis and fibrosis severity among lean, overweight and obese patients with nonalcoholic fatty liver disease

BackgroundsNon-obese nonalcoholic fatty liver disease (NAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but worse prognosis relative to obese NAFLD. AimTo compare predictors of disease severity in NAFLD with different body mass index (BMI) categories. MethodsAll 1509 consecutive NAFLD patients were classified as lean (20.2%), overweight (23.1%) and obese (56.7%). Liver fat content (LFC) and fibrosis were estimated with magnetic resonance imaging-based proton density fat fraction and shear wave elastography respectively. ResultsLipid profiles and uric acid (UA) were significantly increased in parallel with BMI categories (pairwise comparison P < 0.001), but insulin resistance (IR) was significantly different between the non-obese and obese groups. For LFC ≥ 10%, increased waist circumference (WC) was an independent predictor in all groups, while UA elevation (P = 0.02) was predictive in the overweight patients, but BMI ≥ 28 kg/m2 (P = 0.029) and IR (P = 0.026) were significant in the obese patients. For fibrosis, alanine aminotransferase (ALT) > 40 U/L (P = 0.031), increased WC (P = 0.012) and BMI ≥ 28 kg/m2 (P < 0.001) plus ALT > 40 U/L (P = 0.007) were predictors in the lean, overweight and obese patients, respectively. ConclusionsWC was strongly predictive of disease severity in all NAFLD, while UA and BMI plus IR were additional predictors in the overweight and obese NAFLD respectively. Individualized screening strategies should be established for NAFLD according to different BMIs.

Steatosis and steatohepatitis found in adults after death due to non-burn trauma

OBJECTIVE:With the increasing prevalence of steatosis, the number of steatotic liver grafts from deceased donors is also increasing. Thus, determining the prevalence and the population risk factors of steatosis may assist in risk stratification. The aim of this study was to evaluate the prevalence and predictors of steatosis and steatohepatitis among livers from adults who died due to non-burn trauma.METHODS:Specimens were collected from 224 adults undergoing autopsy at a regional autopsy referral center from September 2011 to April 2013. Histopathological examination was performed on six samples obtained from different lobes of each liver. The outcomes of interest were the presence of steatosis, steatohepatitis, NASH inflammation and NASH fibrosis. The main predictors were body mass index, abdominal circumference, liver weight and volume, presence of cholelithiasis, and siderosis. Our modeling strategy made use of a series of generalized linear models with a binomial family.RESULTS:Our sample had a mean age of 40 years; steatosis was diagnosed in 48.2% of cases, and steatohepatitis was diagnosed in 2.7%. The presence of a high proportion of fatty changes was more prevalent among males and older individuals, with the most affected age group being 41-60 years. When evaluating the crude odds ratio for steatosis, the factors significantly associated with an increased risk of steatosis were greater abdominal circumference, BMI, and liver weight and the presence of siderosis.CONCLUSION:Our study reinforces the role of older age, obesity and hepatomegaly as predictors of fatty liver disease. These variables should be considered in the assessment of fatty changes in the livers of potential liver donors.

Fractal Dimension of Tc-99m DTPA GSA Estimates Pathologic Liver Injury due to Chemotherapy in Liver Cancer Patients.

Chemotherapy-induced liver injury after potent chemotherapy is a considerable problem in patients undergoing liver resection. The aim of this study was to assess the relationship between the fractal dimension (FD) of Tc-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) and pathologic change of liver parenchyma in liver cancer patients who have undergone chemotherapy. We examined 34 patients (10 female and 24 male; mean age, 68.5 years) who underwent hepatectomy. Hepatic injury was defined as steatosis more than 30%, grade 2-3 sinusoidal dilation, and/or steatohepatitis Kleiner score ≥4. Fractal analysis was applied to all images of Tc-99m DTPA GSA using a plug-in tool on ImageJ software (NIH, Bethesda, MD). A differential box-counting method was applied, and FD was calculated as a heterogeneity parameter. Correlations between FD and clinicopathological variables were examined. FD values of patients with steatosis and steatohepatitis were significantly higher than those without (P>.001 and P>.001, respectively). There was no difference between the FD values of patients with and without sinusoidal dilatation (P=.357). Multivariate logistic regression showed FD as the only significant predictor for steatosis (P=.005; OR 36.5; 95% CI 3.0-446.3) and steatohepatitis (P=.012; OR, 29.1; 95% CI 2.1-400.1). FD of Tc-99m DTPA GSA was the significant predictor for fatty liver disease in patients who underwent chemotherapy. This new modality is able to differentiate steatohepatitis from steatosis; therefore, it may be useful for predicting chemotherapy-induced pathologic liver injury.

The role of endotoxin and nitric oxide in diagnosing of nonalcoholic fatty liver disease

S 21 ANNUAL CONFERENCE—2013 N o n -a co h o lic Fa ty Lver D iea se liver and severity of steatosis, inflammation and fibrosis (0.01-0.001). In conclusion, our results show decreased serum levels of hepcidin in patients with nonalcoholic and alcoholic fatty liver diseases, and chronic hepatitis C. The relationships between the parameters of iron metabolism and the severity of liver disease prove the importance of serum hepcidin as a surrogate marker for evaluation of iron overload in patients with chronic liver diseases. 40.74 ng/ ml) compared to the controls (99.14 Abstract Content: Chronic liver diseases, especially alcoholic fatty liver disease (AFLD), nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), are frequently associated with iron overload. Hepcidin is the iron-regulatory hormone, which is synthesized mainly in the liver and plays an important role in iron homeostasis. The aim of this study was to assess the serum levels of hepcidin and to evaluate its relationships with other parameters of iron metabolism in patients with various chronic liver diseases. Material and methods: A total of 186 patients with chronic liver disease (CLD), divided into six groups were studied (115male, 71 – female; mean age 50.41 12.85 y), and 60 healthy controls were studied. Laboratory parameters of liver function and indices of iron metabolism were evaluated. The presence of iron deposition and the histological grades of steatosis and inflammation, and stage of fibrosis were also evaluated in patients with CLD. The serum level of hepcidin was determined by ELISA test / DRG International Inc. (USA). Results: Hepcidin was significantly lower in the whole group of patients with CLD (82.9). Corresponding Author. Mariana Penkova. E-mail: mpenkovadoc@abv.bg HEPATIC STEATOSIS: CORRELATION OF BODY MASS INDEX AND CT FAT MEASUREMENT (LIVER ATTENUATION INDEX) Joy Varghese, R. L. Sunjay, Thomas Cherian, Srinivasa Mettu Reddy, Sunjay Vijaya, Venkataraman Jayanthi, Mohd Rela Department of Hepatology & Liver Transplantation, Global Hospitals & Health City, Chennai, India Introduction: Several studies have evaluated non-invasive methods of predicting the presence of fatty liver disease which utilizes complex imaging measures such as intra-abdominal mesenteric fat cross-sectional area measurements, magnetic resonance (MR) elastography, and MR spectroscopy.Most of themmay limit quick and practical clinical applications.Liver attenuation index (LAI) has beenwidelyused to predict steatosis in donor liver. More recently metabolic syndrome has also been used to predict hepatic steatosis. S30 Objective: To examine the relationship of bodymass index (BMI) with liver attenuation index (LAI), in predicting hepatic steatosis in donor liver. Methodology: All donors registered in the Liver Transplant Clinic had a detailed work up for fitness for donation. A retrospective study was done to compare the BMI of liver donors with the Liver Attenuation Index (LAI) noted at Contrast Enhanced Computed Tomography. The latter was considered as the gold standard for assessment of hepatic steatosis in this study. Liver Attenuation Index (LAI), was derived and defined as the difference between mean hepatic and mean splenic attenuation. The BMI standardized for south Asians (Western Pacific Region of WHO criteria pertaining to obesity (WPRO criteria, 2000) was used to categorise our patients. Normal BMI 18.5 to 22.9 kg/m2, underweight + 5, 0 to 5 as mild steatosis and less than 0 as severe steatosis. Only patients who had details of both BMI and LAI were included for the analysis.The Ethics Committee of the Institution approved the study. Statistical Analysis: The prediction value was determined using positive predictive value (PPV) and negative predictive value (NPV). Results: One hundred and forty donors were screened between Nov 2009 and April 2012 for 76 liver transplant recipients. There were 67 (47.8%) females. The median age of donors was 31 yrs (range 18 to 52 years). 101 donors had information on both BMI and LAI. There were 69 donors whose BMI was more than > 23; 21 of these donors had steatosis on LAI (PPV 30.4%). For 32 donors with BMI < 23 kg/m, only 2 (6.8%) had steatosis on LAI i.e. LAI was normal in 30 donors (NPV 93.8%). Conclusion: A normal BMI (18.5 to 22.9 kg/m 2) is a good predictor of steatosis and can be used as an initial screening parameter for screening patients for hepatic steatosis. However, this cannot be taken as the only parameter for predicting hepatic steatosis especially for donors with normal BMI. The study needs to be validated among larger number of donors. Corresponding Author. Joy Varghese. E-mail: joyvargese@gmail.com COMPARISON OF HISTOPATHOLOGICAL PROFILE BETWEEN YOUNG AND OLDER NAFLD PATIENTS Girish Kumar Pati, Shivaram Prasad Singh, Ayaskant Singh, BijayMisra, DebasisMisra, Pallavi Bhuyan, Niranjan Rout, Sanjib Kumar Kar, Manas Kumar Panigrahi, Chudamani Meher, Omprakash Agrawal

Association of radiologically defined hepatosteatosis and colorectal cancer liver metastases.

367 Background: Non alcoholic fatty liver disease (NAFLD) is common, with a prevalence estimated at 15-35%. NAFLD was found to be an independent risk factor for colorectal cancer (CRC). The relationship between CRC and metastasis to a fatty liver has not been well established. We performed a retrospective chart review to address the association of radiologic hepatosteatosis and liver metastases in patients with CRC. Methods: Medical records of 291 patients diagnosed with colorectal adenocarcinoma between 2006-2010 at MetroHealth Medical Center were reviewed. Patients with CRC and no abdominal imaging within 3 months of diagnosis were excluded. Demographic and tumor related data were collected. Presence of hepatic steatosis was defined by radiographic reports (CT, MRI, or US). Results: 6/38 (18.8%) patients with hepatosteatosis had liver metastases, compared to 60/253 (23.7%) with no steatosis. The difference did not reach statistical difference (p=0.40). Hepatosteatosis was noted in 27/280 (9.6%) contrasted CTs, 4/42 (9.5%) MRIs and 12/54 (22.2%) U/S. 66 (22.7%) patients had liver metastases. Patients with ≤3 metastases were less frequent in the non-fatty 22/59 (37.3%) vs fatty liver group 3/6 (50%), but this was not statistically significant (p=0.67). Fatty liver patients were more likely to have a stage ≤ II compared to non-fatty liver patients (OR 2.40, p=0.018). Patients with hepatosteatosis had a higher mean BMI (32.8 vs 27.6, p&lt;0.001). BMI was an independent predictor of steatosis. Alcohol consumption was not associated with BMI or steatosis. There was no statistically significant difference between racial groups and gender with respect to steatosis and liver metastases. Conclusions: This retrospective study suggests that liver metastases in CRC patients are less common in those with fatty livers compared to those with non-fatty livers. CRC patients with hepatosteatosis were also more likely to have earlier stage disease. Larger studies are needed to confirm these findings.

Serum FGF21 and RBP4 levels in patients with chronic hepatitis C

Introduction. Fibroblast growth factor-21 (FGF21) regulates glucose, lipid, and energy homeostasis. Retinol-binding protein-4 (RBP4) controls metabolic and proliferative cell functions. Aims and methods. Aims of the study were to assess (1) serum FGF21 and RBP4 levels in 75 non-obese chronic hepatitis C (CHC) patients and 41 healthy controls similar in age and BMI; (2) the relationship between their serum concentration and insulin resistance, liver histology, and biochemical parameters; (3) their effectiveness as diagnostic markers. Results. FGF21 levels increased significantly in CHC patients compared with controls (p = 0.04). CHC patients with steatosis had significantly higher FGF21 levels compared with those without steatosis (p = 0.01). FGF21 concentration was positively related to steatosis grade (r = 0.39, p = 0.007). RBP4 levels did not differ between CHC patients and controls, but were negatively associated with necro-inflammatory activity grade (r = (-0.34), p = 0.04), with significantly higher levels in patients with minimal inflammatory activity (G1 vs. G2/3, p < 0.001; G1 vs. G2, p = 0 < 001; G1 vs. G3, p = 0.01). After stepwise linear regression analysis adjusting for potential confounders, RBP4 levels retained their independent significance as a predictor of necro-inflammatory activity (β = -0.31; t = -2.15, p = 0.035) and FGF21 levels as a predictor of steatosis (β = 0.34; t = 2.31, p = 0.024). Serum FGF21 correlated with serum RBP4 levels (r = 0.32, p = 0.02). Conclusions. Serum FGF21 levels increased in CHC patients, especially in those with steatosis and were associated with steatosis grade. FGF21 seems to be a useful diagnostic marker in determining hepatic steatosis in CHC. A negative association between serum RBP4 and necro-inflammatory activity indicates that disease severity may determine RBP4 levels.

Increased soluble leptin receptor levels in morbidly obese patients with insulin resistance and nonalcoholic fatty liver disease.

The adipocyte hormone, leptin has been demonstrated to have profibrogenic actions in vitro and in animal models. However, no correlation was found between plasma leptin levels and fibrosis stage in humans. Thus, our aim was to study whether soluble leptin receptor (SLR) or free leptin index (FLI; calculated as the ratio of leptin to SLR), may correlate better with the features of metabolic syndrome and with the histological grade and stage of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). We studied a population (n = 104) of morbidly obese patients undergoing bariatric surgery. Data including BMI, type 2 diabetes mellitus, hypertension, and hyperlipidemia were obtained. Plasma fasting leptin and SLR, fasting glucose and insulin were measured, and homeostasis model of assessment insulin resistance (HOMA(IR)) index and FLI were calculated. All patients had intraoperative liver biopsies. Leptin levels correlated with the BMI. The multiple regression analysis indicated that increasing HOMA and decreasing FLI were predictors of steatosis in the liver (P < 0.0003). SLR levels were positively correlated with the presence of diabetes mellitus and the stage of fibrosis. In conclusion, increased SLR levels in morbidly obese patients with diabetes are correlated with the stage of liver fibrosis, and may reflect progressive liver disease.

Prevalence and Predictors of Steatosis in Patients with Chronic Hepatitis C (HCV) Infection

Prevalence and Predictors of Steatosis in Patients with Chronic Hepatitis C (HCV) Infection

Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infection.

Hepatic steatosis is common in hepatitis C, but the relative importance of host and viral factors is controversial. In the present prospective study, we examined metabolic factors associated with non-alcoholic fatty liver and viral genotype as predictors of steatosis and fibrosis in chronic hepatitis C infection. In 124 chronic hepatitis C patients, the association between liver histology and the following was investigated: demographic and anthropometric data, alcohol intake, alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglyceride, transferrin saturation, ferritin, insulin, c-peptide, glucose and insulin resistance (homeostasis model). By multivariate analysis, genotype 3 was associated with increased steatosis grade (P = 0.02). There were significant pairwise interactions between genotype 3 status and total cholesterol (P = 0.01), current alcohol intake (P = 0.04) and serum ALT (P = 0.01). This showed that the etiology of steatosis was different in patients with genotype 3 and those with non-genotype 3 chronic hepatitis C infection. In genotype 3 patients, the degree of steatosis was inversely associated with serum cholesterol (P = 0.005) and positively associated with serum triglyceride (P = 0.02). There was no association between body mass index (BMI) and the extent of steatosis. Among patients with other genotypes, the steatosis grade was strongly influenced by BMI (P < 0.0001) and serum ALT (P < 0.01). Independent predictors of fibrosis were age (P = 0.001), past alcohol intake (P = 0.04), ALT (P = 0.002), serum insulin (P = 0.001) and portal inflammation (P < 0.001). Hepatitis C genotype 3 may interfere with pathways of hepatic lipid metabolism, whereas increased BMI appears to be a more important pathogenic factor in other genotypes. Although steatosis and BMI were not associated with hepatic fibrosis, their relationship with serum insulin suggests that metabolic factors related to insulin action could influence fibrogenesis in hepatitis C.

Predictors for steatosis and fibrosis in chronic hepatitis C

Predictors for steatosis and fibrosis in chronic hepatitis C

Predictors for steatosis and fibrosis in chronic hepatitis C

Predictors for steatosis and fibrosis in chronic hepatitis C