Biomarker For Nonalcoholic Steatohepatitis Research Articles

Development and validation of a quantitative ultra performance LC® hydrophilic interaction liquid chromatography MS/MS method to measure fructose and sorbitol in human plasma.

Fructose and sorbitol are utilized as biomarkers for nonalcoholic steatohepatitis. Measurement of fructose and sorbitol levels helps understanding disease progression, drug response and underlying mechanism. Stable isotope-labeled fructose and sorbitol were used as surrogate standards and internal standards. Human plasma samples were processed and analyzed by ultra performance LC®-MS/MS via chromatographic separation on a hydrophilic interaction liquid chromatography analytical column without derivatization. Assay was validated with biomarker fit-for-purpose concept. A 12-min ultra performance LC®-MS/MS method was developed and validated to directly measure fructose and sorbitol in human plasma with acceptable intra- and inter-assay precision and accuracy. This sensitive, selective, and high-throughput assay with suitable dynamic ranges was successfully applied to clinical studies to provide reliable fructose and sorbitol biomarker data.

Drug-Induced Steatosis and Steatohepatitis: The Search for Novel Serum Biomarkers Among Potential Biomarkers for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

Drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH) are two of several types of drug-induced liver injury (DILI). They can be caused by various drugs and may present as acute, potentially lethal disorders or as chronic slowly progressive liver injury. Despite the fact that they are distinct disorders, the slow progressive forms of DIS and DISH are often confused with or misdiagnosed as non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), which are much more common and, by definition, not caused by drugs. Currently the only way to identify DIS is via imaging studies or a liver biopsy, while DISH can be identified only through liver biopsy. In addition, diagnosis of either DIS or DISH requires an exhaustive clinical evaluation and comprehensive causality assessment to rule out other possible causes and determine the association with the suspected drug. Furthermore, it is difficult, using existing methods, to monitor the progression of DIS and DISH and to determine the underlying mechanism. Therefore, there is a great unmet need for non-invasive biomarkers that will be able to identify the development of DIS or DISH during drug development and to monitor for progression or regression of the disorder during treatment or following drug discontinuation. Recent developments in the fields of NAFLD and NASH have introduced several novel biomarkers that show promise for the diagnosis, monitoring, and severity assessment of these common diseases. Given the significant overlap in possible underlying mechanisms and histological pattern between NAFLD/NASH and DIS/DISH, these postulated NAFLD and NASH biomarkers may have a potential application to DIS and DISH. This article reviews the existing medical literature and other publically available information pertaining to novel serum biomarkers for NAFLD and NASH, and explores the concurrent identification of these biomarkers for DIS and DISH.

Selenoprotein P levels discriminate the degree of hepatic steatosis and are related to the NAS score in patients with non-alcoholic fatty liver disease

Background: Alterations in glucose and lipid metabolism in the setting of insulin resistance (IR) play an important role in the progression from Non-alcoholic Fatty Liver (NAFL) to Non-alcoholic Steatohepatitis (NASH) via oxidative stress. Selenoprotein P (SeP) is a selenium carrier protein with antioxidant properties that is higher in obese and diabetic subjects but its potential role as biomarker of NASH is not fully elucidated yet.

Environmental Exposures to PCDDs, PCDFs, and PCBs and Mechanism of Steatohepatitis in the Anniston Community Health Survey II

PCDDs, PCDFs, and some PCBs activate the aryl hydrocarbon receptor (AhR); but non-dioxin like (NDL) PCBs do not. We previously reported a high prevalence of suspected nonalcoholic steatohepatitis (NASH) associated with PCB exposures in the Anniston Community Health Survey (ACHS). Here, we determine if dioxins and NDL PCB exposures were associated with serologic biomarkers of NASH in the subgroup of ACHS-II participants with suspected liver disease. The total dioxin toxic equivalency (TEQ) was determined by summing the TEQs for serum PCBs, PCDDs, and PCDFs using WHO toxic equivalency factors. Disease biomarkers were measured by ELISA or Milliplex. Subjects were categorized as having suspected liver disease if serum cytokeratin 18 was elevated. Linear regression models examined associations between TEQ or ΣNDL PCBs with NASH biomarkers in the suspected liver disease subgroup. In 345 adult participants, the prevalence of suspected liver disease was 62%. These subjects were at risk for NASH due to a high prevalence of overweight/obesity and diabetes. Suspected liver disease was significantly associated with male sex, non-Hispanic White race/ethnicity, increased liver enzymes, and a trend towards increased diabetes. Both TEQ and ΣNDL PCBs were associated with altered intermediary metabolism biomarkers (increased LDL, VLDL, phospholipids; and decreased HOMA-IR). TEQ was also associated with decreased HOMA-B. TEQ was associated with increased TNFα, IL-12 and CXCL11; while ΣNDL PCBs was associated with increased IL-13. Both TEQ and ΣNDL PCBs were positively associated with TGFβ. Neither exposure biomarker was positively associated with either CK18 or transaminases. In ACHS-II participants with suspected liver disease we found associations with altered biomarkers of liver intermediary metabolism, inflammation, fibrosis, and synthetic function; but not cell death. The potential role of the AhR, dioxins, and NDL PCBs in NASH progression warrants further investigation.

ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P

Nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis (NASH) in response to elevated endoplasmic reticulum (ER) stress. Whereas the onset of simple steatosis requires elevated de novo lipogenesis, progression to NASH is triggered by accumulation of hepatocyte-free cholesterol. We now show that caspase-2, whose expression is ER-stress inducible and elevated in human and mouse NASH, controls the buildup of hepatic-free cholesterol and triglycerides by activating sterol regulatory element-binding proteins (SREBP) in a manner refractory to feedback inhibition. Caspase-2 colocalizes with site 1 protease (S1P) and cleaves it to generate a soluble active fragment that initiates SCAP-independent SREBP1/2 activation in the ER. Caspase-2 ablation or pharmacological inhibition prevents diet-induced steatosis and NASH progression in ER-stress-prone mice. Caspase-2 inhibition offers a specific and effective strategy for preventing or treating stress-driven fatty liver diseases, whereas caspase-2-generated S1P proteolytic fragments, which enter the secretory pathway, are potential NASH biomarkers.

Noninvasive biomarkers in NAFLD and NASH - current progress and future promise.

Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population and is the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is the active form of NAFLD, with hepatic necroinflammation and faster fibrosis progression. With an increasing number of patients developing NASH-related end-stage liver disease and pharmacological treatments on the horizon, there is a pressing need to develop NAFLD and NASH biomarkers for prognostication, selection of patients for treatment and monitoring. This requirement is particularly true as liver biopsy utility is limited by its invasive nature, poor patient acceptability and sampling variability. This article reviews current and potential biomarkers for different features of NAFLD, namely, steatosis, necroinflammation and fibrosis. For each biomarker, we evaluate its accuracy, reproducibility, responsiveness, feasibility and limitations. We cover biochemical, imaging and genetic biomarkers and discuss biomarker discovery in the omics era.

Blood-based novel biomarkers for nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease has become a social health challenge of global concern. The term nonalcoholic steatohepatitis (NASH) is a more severe condition than simple steatosis and distinguishing NASH from nonalcoholic fatty liver disease is particularly important. Liver biopsy remains a gold standard in diagnosing NASH. Meanwhile, radiological techniques such as ultrasonography and MRI are also applied widely. However, the invasive and expensive examination is not suitable for screening, and there is a great need for reliable and appropriate biomarkers to screen patients for NASH. Based on the current studies of blood-based novel biomarkers, we attempt to summarize the latest findings on biomarkers for NASH, including blood biomarkers encompassing proteins, lipids and miRNAs; the correlation between extracellular vesicles and NASH; and treatment strategies for NASH.

The Association of Hispanic Ethnicity with Nonalcoholic Fatty Liver Disease in Polycystic Ovary Syndrome

The aim of this study was to evaluate ethnic differences in the prevalence and risk of NAFLD/NASH in women with PCOS. Among PCOS women followed in a large academic medical center the association of Hispanic ethnicity with elevated biomarkers of NASH, including plasma cytokeratin 18 (CK18) M30 fragments and/or ALT levels (n=303), was assessed. Prevalence of hepatic steatosis by Controlled Attenuation Parameter (CAP) imaging was also evaluated in a subset of PCOS women (n=35). The median cohort age (n=303) was 28 years (IQR 8), and 15.5% (n=47) were Hispanic, the majority of whom reported white race (94%). Most Hispanic women had hepatic steatosis on imaging, which was markedly higher than in non-Hispanics (83% vs 24%, p=0.005). Approximately 17% of PCOS women had elevated ALT or elevated CK18, which was more common in Hispanics than non-Hispanics, at 34% vs 14%, respectively, p=0.002. On univariate analysis, Hispanic ethnicity was associated with two-fold higher odds of NASH (OR 2.0, 95% CI 1.0-3.9, p=0.038), and the association persisted after adjustment for HOMA-IR and waist circumference (AOR 3.1, 95% CI 1.1-8.9, p=0.034). NAFLD/NASH is an important condition to be considered by PCOS providers and Hispanic women with PCOS are a particularly high-risk group that may warrant routine screening.

A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis

BackgroundNoninvasive biomarkers are urgently needed for patients with nonalcoholic steatohepatitis (NASH) to assist in diagnosis, monitoring disease progression and assessing treatment response. Recently several exploratory studies showed that circulating level of microRNA is associated with NASH and correlated with disease severity. Although these data were encouraging, the application of circulating microRNA as biomarkers for patient screening and stratification need to be further assessed under well-controlled conditions.ResultsThe expression of circulating microRNAs were profiled in diet-induced NASH progression and regression models to assess the diagnostic and prognostic values and the translatability between preclinical mouse model and men. Since these mice had same genetic background and were housed in the same conditions, there were minimal confounding factors. Histopathological lesions were analyzed at distinct disease progression stages along with microRNA measurement which allows longitudinal assessment of microRNA as NASH biomarkers. Next, differentially expressed microRNAs were identified and validated in an independent cohorts of animals. Thirdly, these microRNAs were examined in a NASH regression model to assess whether they would respond to NASH treatment.MicroRNA profiling in two independent cohorts of animals validated the up-regulation of 6 microRNAs (miR-122, miR-192, miR-21, miR-29a, miR-34a and miR-505) in NASH mice, which was designated as the circulating microRNA signature for NASH. The microRNA signature could accurately distinguish NASH mice from lean mice, and it responded to chow diet treatment in a NASH regression model. To further improve the performance of microRNA-based biomarker, a new composite biomarker was proposed, which consists of miR-192, miR-21, miR-505 and ALT. The new composite biomarker outperformed the microRNA signature in predicting NASH mice which had NAS > 3, and deserves further validations in large scale studies.ConclusionThe present study supported the translation of circulating microRNAs between preclinical models and humans in NASH pathogenesis and progression. The microRNA-based composite biomarker may be used for non-invasive diagnosis, clinical monitoring and assessing treatment response for NASH.

雌性SDT fattyラットを用いた、血清中肝臓型脂肪酸結合蛋白（L-FABP）量の非アルコール性脂肪性肝炎(NASH)バイオマーカーとしての有用性に関する研究

雌性SDT fattyラットを用いた、血清中肝臓型脂肪酸結合蛋白（L-FABP）量の非アルコール性脂肪性肝炎(NASH)バイオマーカーとしての有用性に関する研究

Translational strategy in NASH diversity: learning from mouse models

Objectives Nonalcoholic steatohepatitis (NASH) is a histological definition that groups together defects in diverse biochemical processes causing hepatic fat accumulation, inflammation, necrosis and fibrosis. Increasing evidence points to different subtypes of nonalcoholic fatty liver disease (NAFLD) which progress to NASH and fibrosis at different rates and may respond differently to treatment. The identification of the types of mechanisms leading to NASH and the discovery of non-invasive biomarkers of NASH subtypes are central for the development of effective treatments and precise diagnosis. This study aims to capture the metabolic signature of different NASH subtypes through a translational research. Method We undertook metabolomic serum analysis in a mouse model that spontaneously develops NASH, methionine adenosyltransferase 1a knockout (Mat/a-KO), and compared with WT mice. Top fifty metabolites that more significantly differentiated between genotypes were selected and translated to a human cohort: 535 biopsied patients (353 steatosis, 182 NASH). For that, we performed a Silhouette cluster analysis and validate the process in 1000-fold repetition of a random partition (50/50) of samples into two cohorts with equal proportional representation of steatosis/NASH. The frequency distribution of NAFLD patients into subtypes and of metabolites that significantly differentiated between NASH and steatosis per subtype was calculated. Results Silhouette cluster analysis revealed that Mat/a-KO signature sub-classified the patients into two clusters, one showing a serum metabolic profile similar to that observed in Mat/a-KO mice (M-subtype) and other showing a different profile (non-M-subtype). Following the criteria based on 2:70% reproducibility of the frequency distribution, 262 patients were classified as M-subtype and 171 as non-M-subtype. The remaining 102 patients showed a reproducibility of less than 70%. A NASH biomarkers list per subtype was generated based on the frequency distribution (2:70% reproducibility) of the metabolites that significantly differentiated between NASH and steatosis: 54 and 6 metabolites for M- and non-M-subtypes, respectively. Conclusions We identified a serum specific metabolomic signature characteristic of Mat1a-KO mice and found that about half of NAFLD patients share it, suggesting that in these patients SAMe synthesis may be impaired. Interestingly, this phenotype was observed in patients with steatosis and NASH, which suggests that impaired SAMe synthesis may occur early in the development of NAFLD in a subgroup of patients. This translational strategy can be applied to different mouse models with diverse mechanisms leading to NASH. These results also indicate that the traditional, mainly pathology-driven classification of NAFLD/NASH, can be refined and perhaps represented by metabolomics classification.

Metabolite profiling identifies anandamide as a biomarker of nonalcoholic steatohepatitis.

The discovery of metabolite-phenotype associations may highlight candidate biomarkers and metabolic pathways altered in disease states. We sought to identify novel metabolites associated with obesity and one of its major complications, nonalcoholic fatty liver disease (NAFLD), using a liquid chromatography-tandem mass spectrometry method. In 997 individuals in Framingham Heart Study Generation 3 (FHS Gen 3), we identified an association between anandamide (AEA) and BMI. Further examination revealed that AEA was associated with radiographic hepatic steatosis. In a histologically defined NAFLD cohort, AEA was associated with NAFLD severity, the presence of nonalcoholic steatohepatitis, and fibrosis. These data highlight AEA as a marker linking cardiometabolic disease and NAFLD severity.

Cytokeratin-18 and uric acid predicts disease severity in Taiwanese nonalcoholic steatohepatitis patients.

Background & aimsIdentification of disease severity remains a challenge in the management of non-alcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18), is a recently developed non-invasive biomarker for NASH. We aimed to assess the performance of CK18 in disease severity prediction among Taiwanese NASH patients.MethodsA total of 76 biopsy-proven NASH patients (54 males, age = 41.0 ± 13.5 years) were consecutively recruited. The optimal cutoff values of CK18 for each stage of fibrosis were correlated with their histopathological manifestations.ResultsThere were 23 (30.3%) patients of Metavir fibrosis stage 0 (F0), 32 (42.1%) patients of F1, 14 (18.4%) patients of F2, and 7 (9.2%) patients of F3-4, respectively. The CK18 levels among those patients of F0, F1, F2, F3-4 were 86.7 ± 75.6 U/L, 122.4 ± 123.8 U/L, 160.7 ± 120.4 U/L, and 507.3 ± 343 U/L, respectively (trend for P<0.001). The adjusted optimal cutoff value for F2 prediction was 312.5 U/L, yielding the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of 96.4%, 28.6%, 77.9%, 75%, and 77.6%, respectively (P = 0.009). For the prediction of advanced fibrosis (F3-4), the adjusted optimal cutoff value was 374.5 U/L, yielding the sensitivity, specificity, PPV, NPV, and the accuracy of 97.1%, 54.1%, 95.7%, 66.7%, and 77.6%, respectively (P = 0.003). Among those patients without hyperuricemia, the PPV, NPV, and accuracy of CK18 reached 100%, 95.8%, and 96%, respectively (P<0.001).ConclusionsCK18 combined with uric acid measurement is a promising non-invasive biomarker for prediction of disease severity in NASH patients.Trial registrationClinicalTrials.gov NCT01068444.

Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging.

Magnetic resonance imaging-derived measures of liver fat and volume are emerging as accurate, non-invasive imaging biomarkers in non-alcoholic steatohepatitis (NASH). Little is known about these measures in relation to histology longitudinally. To examine any relationship between MRI-derived proton-density fat-fraction (PDFF), total liver volume (TLV), total liver fat index (TLFI), vs. histology in a NASH trial. This is a secondary analysis of a 24-week randomised, double-blind, placebo-controlled trial of 50 patients with biopsy-proven NASH randomised to oral ezetimibe 10 mg daily (n = 25) vs. placebo (n = 25). Baseline and post-treatment anthropometrics, biochemical profiling, MRI and biopsies were obtained. Baseline mean PDFF correlated strongly with TLFI (Spearman's ρ = 0.94, n = 45, P < 0.0001) and had good correlation with TLV (ρ = 0.57, n = 45, P < 0.0001). Mean TLV correlated strongly with TLFI (ρ = 0.78, n = 45, P < 0.0001). After 24 weeks, PDFF remained strongly correlated with TLFI (ρ = 0.94, n = 45, P < 0.0001), maintaining good correlation with TLV (ρ = 0.51, n = 45, P = 0.0004). TLV remained strongly correlated with TLFI (ρ = 0.74, n = 45, P < 0.0001). Patients with Grade 1 vs. 3 steatosis had lower PDFF, TLV, and TLFI (P < 0.0001, P = 0.0003, P < 0.0001 respectively). Regression analysis of changes in MRI-PDFF vs. TLV indicates that 10% reduction in MRI-PDFF predicts 257 mL reduction in TLV. The MRI-PDFF and TLV strongly correlated with TLFI. Decreases in steatosis were associated with an improvement in hepatomegaly. Lower values of these measures reflect lower histologic steatosis grades. MRI-derived measures of liver fat and volume may be used as dynamic and more responsive imaging biomarkers in a NASH trial, than histology.

Poor Inter-test Reliability Between CK18 Kits as a Biomarker of NASH.

Nonalcoholic fatty liver disease (NAFLD) affects 15-40% of the general population; 10-20% of those patients have a more severe form of the disease known as nonalcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18), released during apoptosis and one of the most studied biomarkers in NASH, can be measured by a number of commercially available kits. We compared serum measurements of the CK18 M30 from two different kits using the same cohort to evaluate the reliability between two test kits. We measured serum levels of CK18 M30 from 185 patients with biopsy-proven NAFLD from a single center from 2009 to 2015, using two different ELISA kits, Test 1 (T1) and Test 2 (T2). Advanced fibrosis was defined as fibrosis stages 3-4 and NASH defined by NAS score ≥ 5. Mean age was 50.2 years (SD 12.6), 61.1% male and 87% White; 49.6% had NASH and 32.2% advanced fibrosis. There was no significant correlation between measurements from the two kits (p = 0.86, r = 0.01). While T2 predicted NASH and advanced fibrosis, T1 did not. The area under ROC curve for the prediction of NASH was 0.631 for T2 versus 0.500 for T1. Measurements from two different CK18 M30 test kits did not correlate with each other. One kit showed statistically significantly higher levels of CK18 M30 in patients with advanced fibrosis and NASH, while the other kit did not. With the increasing use of CK18 as a biomarker in NASH, it is important to standardize the different kits as it could greatly bias the results.

Nonalcoholic fatty liver disease: update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide affecting over one-third of the population in the U.S. It has been associated with obesity, type 2 diabetes, hyperlipidemia, and insulin resistance and is initiated by the accumulation of triglycerides in hepatocytes. Isolated hepatic steatosis (IHS) remains a benign process, while a subset develops superimposed inflammatory activity and progression to nonalcoholic steatohepatitis (NASH) with or without fibrosis. However, the molecular mechanisms underlying NAFLD progression are not completely understood. Liver biopsy is still required to differentiate IHS from NASH as easily accessible noninvasive biomarkers are lacking. In terms of treatments for NASH, pioglitazone, vitamin E, and obeticholic acid have shown some benefit. All of these agents have potential complications associated with long-term use. Nowadays, a complex hypothesis suggests that multiple parallel hits are involved in NASH development. However, the 'key switch' between IHS and NASH remains to be discovered. We have recently shown that knocking out enzymes involved in S-adenosylmethionine (SAMe) metabolism, the main biological methyl donor in humans that is abundant in the liver, will lead to NASH development in mice. This could be due to the fact that a normal SAMe level is required to establish the proper ratio of phosphatidylethanolamine to phosphatidylcholine that has been found to be important in NAFLD progression. New data from humans have also suggested that these enzymes play a role in the pathogenesis of NAFLD and that some of SAMe cycle metabolites may serve as noninvasive biomarkers of NASH. In this review, we discuss the evidence of the role of SAMe in animal models and humans with NAFLD and how studying this area may lead to the discovery of new noninvasive biomarkers and possibly personalized treatment for NASH.

Circulating Soluble Fas and Fas Ligand Levels Are Elevated in Children with Nonalcoholic Steatohepatitis.

There is an urgent need to develop alternatives to liver biopsy in children to diagnose nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease (NAFLD). Increased hepatocyte apoptosis plays a central role in the development of NASH. To evaluate the plasma levels of two markers of apoptosis, soluble Fas (sFas) and soluble Fas ligand (sFasL), in children with NAFLD and assess their utility as biomarkers of disease severity. Children with biopsy-proven NAFLD were included, and blood samples were collected. Patients were divided into NASH and "not NASH." We measured plasma sFas and sFasL using specific ELISA immunoassays. One hundred and seventeen children with NAFLD were recruited. Average age was 12.2±2.9years, 67% were male, and 58% had NASH. Patients with NASH had significantly higher levels of sFas and sFasL than patients in the "not NASH" group (686.0±186.5pg/mL versus 594.2±244.9, p=0.023 for sFas and 324.9±146.5pg/mL versus 221.4±134.0, p<0.001 for sFasL). sFasL was found to have higher accuracy for predicting the presence of NASH on liver biopsy with an AUC (95% CI) of 0.714 (0.618, 0.810). A prediction model, the NASH apoptosis score, was generated consisting of plasma sFasL, age, ferritin, transferrin, and triglyceride levels. The area under receiver operating characteristic curve was 0.78 (95% CI 0.0.69, 0.87). Markers of the extrinsic pathway of hepatocyte apoptosis are elevated in children with NASH. sFasL and the NASH apoptosis score are potential novel biomarkers for NASH.

Volatile Organic Compounds in the Exhaled Breath as Biomarkers of Nonalcoholic Steatohepatitis in Obese Children

Volatile Organic Compounds in the Exhaled Breath as Biomarkers of Nonalcoholic Steatohepatitis in Obese Children

Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis

Background:Non alcoholic steatohepatitis (NASH), severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD). It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease.Objective:To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH).Materials and Methods:Male Wister rats were divided into 8 groups. The activities of alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and γ-Glutamyl Transferase (GGT) were assayed in serum. The levels of various other biochemical parameters such as serum albumin, total bilirubin, creatinine, urea, uric acid and glucose were also estimated in experimental NASH.Results:The NASH group produced severe liver injury by significantly increasing the serum levels of ALT, AST, GGT and LDH compared with that of the control. However, the experimental NASH rats treated with pioglitazone, with quercetin and with hydroxy citric acid showed an obvious decrease in ALT, AST, GGT and LDH levels when compared with that of NASH induced group. A significant increase in the levels of albumin, creatinine, urea, uric acid, glucose and total bilirubin was noticed in experimentally induced NASH group (group 2) when compared to rats in control group (group 1).Conclusion:It could be inferred from this study that, pioglitazone, quercetin and hydroxy citric acid may afford protection to the liver against NASH, as evidenced by the results of this study on the levels of various biochemical parameters such as glucose, urea, uric acid, creatinine and bilirubin. Whereas from the results of hepatic marker enzymes, it is evident that optimal protection was observed after quercetin treatment against experimental NASH whereas pioglitazone and hydroxy citric acid also confers protection to some extent against NASH.

Science to Practice: Can We Diagnose Nonalcoholic Steatohepatitis with Intravoxel Incoherent Motion Diffusion-weighted MR Imaging?

By showing that intravoxel incoherent motion parameters at diffusion-weighted magnetic resonance (MR) imaging may be indicators of the microcirculatory changes in patients with nonalcoholic steatohepatitis and fatty liver disease, Joo et al have taken a step forward in the validation of quantitative MR imaging parameters as biomarkers of nonalcoholic steatohepatitis and fatty liver disease. Further steps, including standardization, validation, and multiparametric imaging, must be taken before these parameters can be used as biomarkers in clinical practice.