Diagnosis Of Nonalcoholic Fatty Liver Research Articles

Deep Learning With Ultrasound Images Enhance the Diagnosis of Nonalcoholic Fatty Liver

ObjectiveThis research aimed to improve diagnosis of non-alcoholic fatty liver disease (NAFLD) by deep learning with ultrasound Images and reduce the impact of the professional competence and personal bias of the diagnostician. MethodThree convolutional neural network models were used to classify and identify the ultrasound images to obtain the best network. Then, the features in the ultrasound images were extracted and a new convolutional neural network was created based on the best network. Finally, the accuracy of several networks was compared and the best network was evaluated using AUC. ResultsModels of VGG16, ResNet50, and Inception-v3 were individually applied to classify and identify 710 ultrasound images containing NAFLD, demonstrating accuracies of 66.2%, 58.5%, and 59.2%, respectively. To further improve the classification accuracy, two features are presented: the ultrasound echo attenuation coefficient (θ), derived from fitting brightness values within sliding region of interest (ROIs), and the ratio of Doppler effect (ROD), identified through analyzing spots exhibiting the Doppler effect. Then, a multi-input deep learning network framework based on the VGG16 model is established, where the VGG16 model processes ultrasound image, while the fully connected layers handle θ and ROD. Ultimately, these components are combined to jointly generate predictions, demonstrating robust diagnostic capabilities for moderate to severe fatty liver (AUC = 0.95). Moreover, the average accuracy is increased from 64.8% to 77.5%, attributed to the introduction of two advanced features with domain knowledge. ConclusionThis research holds significant potential in aiding doctors for more precise and efficient diagnosis of ultrasound images related to NAFLD.

Polarity-sensitive fluorescent probe based on coumarin derivatives for imaging lipid droplets and diagnosis of non-alcoholic fatty liver

Aberrant alterations in the polarity of lipid droplets (LDs) are closely linked to disorders of lipid metabolism, which can result in LDs dysfunction and the onset of various diseases, including non-alcoholic fatty liver disease (NAFLD) and specific types of cancer. Therefore, it is imperative to comprehensively comprehend and accurately diagnose associated diseases by monitoring changes in LDs polarity in real time. In this paper, we designed and synthesized four novel fluorescent probes XOT1-XOT4 by using coumarin as a polarity-sensitive group and incorporate various triphenylamine derivatives as electron-donating groups, enabling specific targeting of LDs. All four probes possess high sensitivity towards minute polarity changes. Among them, XOT3 exhibited excellent photophysical properties and demonstrated a linear fluorescence change (R2 = 0.98596) within the polarity range of Δf = 0.023496 ∼ 0.047464. Moreover, probe XOT3 could be effectively utilized for visualizing intracellular LDs by precisely targeting them without requiring any washing steps. Importantly, probe XOT3 has been successfully utilized to monitor alterations in the polarity of LDs during apoptosis and ferroptosis as well as the quantity, size, and fluorescence intensity of LDs stimulated by oleic acid. Furthermore, probe XOT3 was capable of effectively visualizing LDs in tissues and organs in mouse models of non-alcoholic fatty liver disease (NAFLD), which provides a powerful tool for the early diagnosis of NAFLD.

Performance of ATT and UDFF in the diagnosis of non-alcoholic fatty liver: An animal experiment

ObjectiveTo establish a Bama minipigs model with Non-Alcoholic Fatty Liver (NAFL) induced by a high-fat diet and investigate the application of attenuation coefficient (ATT) and ultrasound-derived fat fraction (UDFF) in the diagnosis of NAFL. MethodsSix-month-old male Bama minipigs were randomly divided into normal control and high-fat groups (n = 3 pigs per group), and fed with a control diet and high-fat diet for 32 weeks. Weight and body length were measured every four weeks, followed by quantitative ultrasound imaging (ATT and UDFF), blood biochemical markers, and liver biopsies on the same day. Using the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) as a reference, we analyzed the correlation between ATT, UDFF, and their score results. ResultsCompared with the normal control group, the body weight, body mass index (BMI), and serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the High-fat group were significantly different at Week 12 (P < 0.05). Spearman correlation analysis showed that the ATT value was significantly correlated with NAS score (r = 0.76, P < 0.001), and the UDFF value was significantly correlated with NAS score (r = 0.80, P < 0.001). The optimal cut-off value of ATT and UDFF were 0.59 dB/cm/MHz and 5.5%, respectively. These values are optimal for diagnosis of NAFL in Bama minipig model. ConclusionATT and UDFF have a high correlation with steatosis, and can be used as a non-invasive method for early screening of hepatic steatosis, which can dynamically monitor the change of disease course.

An ER-targeted, Viscosity-sensitive Hemicyanine Dye for the Diagnosis of Nonalcoholic Fatty Liver and Photodynamic Cancer Therapy by Activating Pyroptosis Pathway.

The concept of molecular design, integrating diagnostic and therapeutic functions, aligns with the general trend of modern medical advancement. Herein, we rationally designed the smart molecule ER-ZS for endoplasmic reticulum (ER)-targeted diagnosis and treatment in cell and animal models by combining hemicyanine dyes with ER-targeted functional groups (p-toluenesulfonamide). Owing to its ability to target the ER with a highly specific response to viscosity, ER-ZS demonstrated substantial fluorescence turn-on only after binding to the ER, independent of other physiological environments. In addition, ER-ZS, being a small molecule, allows for the diagnosis of nonalcoholic fatty liver disease (NAFLD) via liver imaging based on high ER stress. Importantly, ER-ZS is a type I photosensitizer, producing O2 ⋅- and ⋅OH under light irradiation. Thus, after irradiating for a certain period, the photodynamic therapy inflicted severe oxidative damage to the ER of tumor cells in hypoxic (2 % O2 ) conditions and activated the unique pyroptosis pathway, demonstrating excellent antitumor capacity in xenograft tumor models. Hence, the proposed strategy will likely shed new light on integrating molecular optics for NAFLD diagnosis and cancer therapy.

An ER‐targeted, Viscosity‐sensitive Hemicyanine Dye for the Diagnosis of Nonalcoholic Fatty Liver and Photodynamic Cancer Therapy by Activating Pyroptosis Pathway

AbstractThe concept of molecular design, integrating diagnostic and therapeutic functions, aligns with the general trend of modern medical advancement. Herein, we rationally designed the smart molecule ER‐ZS for endoplasmic reticulum (ER)‐targeted diagnosis and treatment in cell and animal models by combining hemicyanine dyes with ER‐targeted functional groups (p‐toluenesulfonamide). Owing to its ability to target the ER with a highly specific response to viscosity, ER‐ZS demonstrated substantial fluorescence turn‐on only after binding to the ER, independent of other physiological environments. In addition, ER‐ZS, being a small molecule, allows for the diagnosis of nonalcoholic fatty liver disease (NAFLD) via liver imaging based on high ER stress. Importantly, ER‐ZS is a type I photosensitizer, producing O2⋅− and ⋅OH under light irradiation. Thus, after irradiating for a certain period, the photodynamic therapy inflicted severe oxidative damage to the ER of tumor cells in hypoxic (2 % O2) conditions and activated the unique pyroptosis pathway, demonstrating excellent antitumor capacity in xenograft tumor models. Hence, the proposed strategy will likely shed new light on integrating molecular optics for NAFLD diagnosis and cancer therapy.

Artificial intelligence and deep learning: New tools for histopathological diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is associated with metabolic syndrome and is rapidly increasing globally with the increased prevalence of obesity. Although noninvasive diagnosis of NAFLD/NASH has progressed, pathological evaluation of liver biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. However, the pathological diagnosis of NAFLD/NASH relies on the subjective judgment of the pathologist, resulting in non-negligible interobserver variations. Artificial intelligence (AI) is an emerging tool in pathology to assist diagnoses with high objectivity and accuracy. An increasing number of studies have reported the usefulness of AI in the pathological diagnosis of NAFLD/NASH, and our group has already used it in animal experiments. In this minireview, we first outline the histopathological characteristics of NAFLD/NASH and the basics of AI. Subsequently, we introduce previous research on AI-based pathological diagnosis of NAFLD/NASH.

Clinical Practice Guidelines of the Russian Scientific Liver Society, Russian Gastroenterological Association, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians and National Society for Preventive Cardiology on Diagnosis and Treatment of Non-Alcoholic Liver Disease

Aim:present clinical guidelines, aimed at general practitioners, gastroenterologists, cardiologists, endocrinologists, comprise up-to-date methods of diagnosis and treatment of non-alcoholic fatty liver disease.Key points.Nonalcoholic fatty liver disease, the most wide-spread chronic liver disease, is characterized by accumulation of fat by more than 5 % of hepatocytes and presented by two histological forms: steatosis and nonalcoholic steatohepatitis. Clinical guidelines provide current views on pathogenesis of nonalcoholic fatty liver disease as a multisystem disease, methods of invasive and noninvasive diagnosis of steatosis and liver fibrosis, principles of nondrug treatment and pharmacotherapy of nonalcoholic fatty liver disease and associated conditions. Complications of nonalcoholic fatty liver disease include aggravation of cardiometabolic risks, development of hepatocellular cancer, progression of liver fibrosis to cirrhotic stage.Conclusion.Progression of liver disease can be avoided, cardiometabolic risks can be reduced and patients' prognosis — improved by the timely recognition of diagnosis of nonalcoholic fatty liver disease and associated comorbidities and competent multidisciplinary management of these patients.

Rational Design of a Near-Infrared Ratiometric Probe with a Large Stokes Shift: Visualization of Polarity Abnormalities in Non-Alcoholic Fatty Liver Model Mice.

Tracking liver polarity with noninvasive and dynamic imaging techniques is helpful to better understand the non-alcoholic fatty liver (NAFL). Herein, a novel near-infrared (NIR) fluorescent probe Cy-Mp is constructed using a "symmetry collapse" strategy. The structure modification leads to the conversion of locally excited state fluorescence to charge transfer state fluorescence. Cy-Mp emits at near-infrared (NIR) wavelengths with high photostability as well as a large Stokes shift. Cy-Mp exhibits a ratiometric response to polarity, providing more accurate analysis of intracellular polarity via the built-in internal reference correction. Most importantly, the in vivo studies indicate that Cy-Mp can accumulate in the liver and the decreased polarity in the liver of mice with NAFL is verified by the ratiometric imaging, implying the great potential of Cy-Mp in the diagnosis of NAFL.

Role of Thymosin Beta 4 in the diagnosis of Nonalcoholic Fatty Liver and its relation to Metabolic Syndrome in Egyptian patients

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic diseases linked to metabolic and cardiovascular disorders that impair quality of life and increase morbidity and mortality. There has been significant interest in replacing conventional diagnostic tools such as liver biopsy with non-invasive biomarkers for the diagnosis of NAFLD. Thymosin Beta 4 (Tβ4) is a G-actin sequestering peptide involved in many critical biological processes. This study aimed to evaluate the role of Tβ4 in the diagnosis of NAFLD, and its relation to metabolic syndrome. Eighty patients were enrolled in this study, divided into two equal groups of NAFLD cases (n=40) and a control group (n=40). The two groups were subjected to history taking, physical examination, measurement of waist circumference and body mass index (BMI). Laboratory workup included serum Tβ4, insulin resistance (HOMA-IR), fibrosis-4 score (FIB-4), fatty liver index (FLI) and NAFLD fibrosis score (NFL) were calculated for both groups. Serum Tβ4 was significantly lower in NAFLD patients (P < 0.001) and there was a significant positive correlation between serum Tβ4 and HDL (P = 0.034). On the other hand, there was a significant negative correlation between serum Tβ4 and waist circumference (P < 0.001), total cholesterol level (P < 0.001), insulin level (P < 0.001), HOMA-IR (P < 0.001), serum triglycerides (P= 0.025) and FLI (P = 0.004). Serum Tβ4 at a cut-off value of ≤900 ng/ml had 100 % sensitivity, 100 % specificity, 100% positive predictive value and 100% negative predictive value for the prediction of NAFLD. In conclusion, serum Tβ4 could be used as a biomarker for the diagnosis of NAFLD.

Relationship Between Nonalcoholic Fatty Liver and Non High Density Lipoprotein to High Density Lipoprotein Ratio

Aim: The aim of this study was to investigate the relationship between non-alcoholic fatty liver and demographic characteristics, laboratory parameters and predictory non-high density lipoprotein to high density lipoprotein ratio. Material and Methods: Between February and September 2020, 329 patients with fatty liver prediagnosis were evaluated prospectively. Laboratory (whole blood counts, transaminases, lipid profiles, 25-oh vitamin d3 levels) and ultrasonography findings, body height, body weight and body mass index of patients were compared between fatty liver and control groups. Results: Fatty liver was diagnosed in 164 patients out of 329 participants. There were significant relationships between existence of fatty liver and age, body weight, body mass index, triglyceride levels, non-high density lipoprotein, non-high density lipoprotein to high density lipoprotein ratios. Also relationships between severity of fatty liver and body weight, alanine aminotransferase and body mass index were found to be significant. There were no relationship between existence of fatty liver and monocyte to high density lipoprotein ratio and vitamin D levels. Linear regression analysis for Non-HDL/ HDL ratio in diagnosis of nonalcoholic fatty liver, revealed a correlation coefficient as r=0.179. Positive and negative predictive values for Non-HDL/HDL ratio in diagnosis of nonalcoholic fatty liver were, 56.3% and 60.9%, respectively . Conclusion: There is a significant relationship between fatty liver and non-high density lipoprotein to high density lipoprotein ratio. This ratio may be a simple and readily available predictor in patients with fatty liver.

Study on the Correlation between Nonalcoholic Fatty Liver and Metabolic Syndrome Based on Magnetic Resonance Diffusion-Weighted Imaging

This paper explores the relationship between magnetic resonance diffusion-weighted imaging of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS), as well as the study of diffusion-weighted imaging, spectral imaging, and low density of nonalcoholic fatty liver correlation between serum concentration of lipoprotein cholesterol (LDL-C). This collection is from February 2018 to May 2018 in hospital as 39 cases of nonalcoholic fatty liver patients in the observation group and 39 patients in the control group with the same period of physical examination. All patients underwent magnetic resonance spectroscopy imaging, magnetic resonance diffusion-weighted imaging examination, and serum LDL-C test, compared the results of the two groups, and analysed the correlation between magnetic resonance spectroscopy imaging and magnetic resonance diffusion-weighted imaging examination results and LDL-C. The results showed that the prevalence of NAFLD was 12.33%, and the prevalence of NAFLD and MS was 3.47%. Magnetic resonance spectroscopy observation parameter group and the control group had statistically significant difference when compared ( P &lt; 0.05). Difference was statistically significant ( P &lt; 0.01). In conclusion, nonalcoholic fatty liver DWI and MR spectroscopy is closely related to LDL-C targets, quantitatively and noninvasively reflects the body’s fat metabolism, and can provide more extensive clinical diagnosis of nonalcoholic fatty liver. NAFLD is closely related to MS. The mutual aggravation and mutual promotion in the pathogenesis of the two should arouse enough attention and comprehensive prevention and treatment.

Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients.

Background: The present study aimed to assess the ability of serum bile acid profiles to predict the development of nonalcoholic fatty liver (NAFL) in type 2 diabetes mellitus (T2DM) patients. Methods: Using targeted ultraperformance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry (TQ/MS), we compared serum bile acid levels in T2DM patients with NAFL (n = 30) and age- and sex-matched T2DM patients without NAFL (n = 36) at the first time. Second, an independent cohort study of T2DM patients with NAFL (n = 17) and age- and sex-matched T2DM patients without NAFL (n = 20) was used to validate the results. The incremental benefits of serum biomarkers, clinical variables alone, or with biomarkers were then evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. The area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to evaluate the biomarker predictive abilities. Results: The serum bile acid profiles in T2DM patients with NAFL were significantly different from T2DM patients without NAFL, as characterized by the significant elevation of LCA, TLCA, TUDCA, CDCA-24G, and TCDCA, which may be potential biomarkers for the identification of NAFL in T2DM patients. Based on the improvement in AUC, IDI, and NRI, the addition of 5 bile acids to a model with clinical variables statistically improved its predictive value. Similar results were found in the validation cohort. Conclusions: These results highlight that the detected biomarkers may contribute to the progression of NAFL in T2DM patients, and these biomarkers particularly in combination may help in the diagnosis of NAFL and allow earlier intervention in T2DM patients.

Study of Correlation between Fibroscan and Resistin Level in Non-Alcoholic Fatty Liver Disease Patient

Background: Hormone resistin is linked to the development of insulin resistance, but direct evidence of resistin levels in humans with nonalcoholic fatty liver disease (NAFLD) is lacking. Objective: To study the role of fibroscan and resistin level in diagnosis of nonalcoholic fatty liver patients. Methods: This study was conducted on60 NAFLD patients, 27 patients with nonalcoholic steatohepatitis (NASH), and 33 patients with simple steatosis, who were admitted to Tropical Medicine Department in Shebin El-Kom Fever Hospital and 30 healthy subjects as control. Patients were subjected to meticulous history taking, clinical examination, routine laboratory investigations, abdominal ultrasound, fibroscan, and measurement of serum resistin level. Results: Serum resistin can be used to discriminate between simple steatosis group and NASH group at a cutoff level of > 10.5, with 53.3% sensitivity, 83.3% specificity, 76.1% PPV and 64.1% NPV (AUC = 0.73 and p-value = 0.002). Also, there was a significant difference in fibroscan score in comparison between groups, NASH group represented the highest score. There was a significant relation between serum resistin level and fibroscan score in both NASH and simple steatosis groups. Conclusion: Fibroscan and serum resistin level can be used for diagnosis of nonalcoholic fatty liver and for discrimination between simple steatosis and NASH patients.

Accuracy of Multi-echo Dixon Sequence in Quantification of Hepatic Steatosis.

ObjectiveToday, a biopsy is the gold standard in the diagnosis of non-alcoholic fatty liver. However, a biopsy is an invasive technique, limited to the sample taken, and it may lead to misdiagnosis. Therefore, novel noninvasive options are needed. The objective of this study was to investigate the accuracy of magnetic resonance (MR) Dixon sequence and elastography using magnetic resonance spectroscopy (MRS) as a reference in the quantification of hepatic steatosis.MethodsA total of 60 patients were included in the study. All patients underwent magnetic resonance imaging (MRI), MRS, and elastography in order to quantify hepatosteatosis. MRI and MRS imaging studies were performed using MR Dixon and high-speed T2-corrected multiple-echo 1H-MRS sequence (HISTO) sequences, respectively, in order to calculate proton density fat fraction (PDFF) values.ResultsThe mean MRI-PDFF value with the MRS region of interest (ROI) was found as 9.4% ± 12.1%. The mean MRS-PDFF was found as 8.9% ± 11.3%. No statistically significant difference was found between MRS-PDFF and MRI-PDFF values measured in ROI (p < 0.005). The correlation between MRS-PDFF and MRI-PDFF was examined with Spearman’s correlation analysis. Accordingly, there was an excellent correlation between MRS and MRI values measured in ROI (r ≥ 0.8, p < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated as 96%, 100%, 89.5%, and 92.6%, respectively, for MRI-PDFF in predicting hepatic steatosis for the same ROI localization with MRS. The optimum cut-off value of MRS-PDFF in predicting hepatic steatosis was found as 5.3% using the same ROI localization with MRS.ConclusionThe results of this study indicated an excellent correlation between MRI-PDFF and MRS-PDFF. The multi-echo Dixon MRI technique seems a promising alternative method in the detection of non-alcoholic fatty liver disease.

A Study of Ultrasonography Diagnosis of Non-Alcoholic Fatty Liver and Its Correlation with Obesity, Diabetes and Other Risk Factors

Objective: Non-Alcoholic Fatty Liver Disease (NAFLD) is a major hepatic problem in a modern –day, which, refer to a group of conditions where there is accumulation of steatosis in the liver of nonalcoholic people. It is a very common disorder which often asymptomatic. And may associated with many risk factors such as diabetes obesity and other factors. Therefore this study was conducted to determine the correlation between NAFLD and above mentioned condition using ultrasonography investigation, because that the relation of non-alcoholic fatty liver disease to these factors are not fully understood. Methods: A total of 250 Sudanese participants screening by abdominal ultrasound were used as the population of this cross-sectional prospective study, 50 out of them diagnosed with NAFLD represented the study sample. The data of the study were obtained in Sudan –Khartoum city in period from July to September 2018. Results data was analyzed to find out the correlation between NAFLD with diabetes, obesity and some other risk factors such as hypertension, elevation of cholesterol level and patient physical activities and participants were included if they didn’t have alcohol intake and their age is 20 years old and above. Statistical descriptive analysis using (SPSS) statistical package for the social sciences program was used to determine the frequency distribution of demographic variables in tables and graphs. Results: The total prevalence result of NAFLD among study population sample achieved 20% percentage and in comparing results of the total number of male and female, the gender distribution reflect that the higher percentage of fatty liver presence in male with (56.00%) percentage more than female with (44.00%) of the study sample, corresponded to maximum age range (40-49) years of group aging in the general sample of the study. Regarding to histologic and/or clinical markers of the study samples, incidence of diabetes, were (40%) with NAFLD and in correlate with patient gender, most of the diabetics are female with (22%) detection. Results for correlation of NAFLD and obesity achieved 78% detection of total study samples. Others Ultrasound results, found that there are correlation with NAFLD and many other risk factors including hypertension, elevation of cholesterol level and patient physical activity. Conclusion: Association with Nonalcoholic fatty liver disease (NAFLD) with obesity, diabetes in addition to hypertension, elevation of cholesterol level and type of patient activities as have been detected in the recent study, these findings should be taken into consideration when patient counseling and monitoring.

Which Method is Superior in the Diagnosis of Nonalcoholic Fatty Liver and Steatohepatatis in Children?

Context: Nonalcoholic fatty liver disease (NAFLD) is increasing with the increased rate of obesity and reduced physical activity in children worldwide. Despite high prevalence of the disease, a standard and acceptable diagnostic method is not available. The current study aimed at collecting all related articles and evaluating the challenges. Methods: The current study searched Scopus, Web of Science, and PubMed. Articles and guidelines in English in the field of invasive and noninvasive diagnostic methods for NAFLD and nonalcoholic steatohepatitis (NASH) in children and adolescents up to Oct 2016 were used. It was tried to evaluate all laboratory and radiologic methods, biomarkers, and scores in addition to mention the challenges. Results: Ultrasonography and laboratory evaluation, which were routine methods in early diagnosis, did not have enough accuracy in this field. Diagnosis of steatosis and fibrosis and determining the severity of disease were achieved by fibro scan and controlled attenuation parameter (CAP) without the challenges of computed tomography (CT) scan and magnetic resonance imaging (MRI). Fatty liver can be predicted with high accuracy by body analyzer, anthropometric, and DEXA methods. Conclusions: Diagnosis and prediction of fatty liver should be done in all children with obesity aged > 3 years, and physician should seek the genetic and metabolic causes in children aged < 3 years and/or without overweight.

Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

It is estimated that 30% of the adult population in Japan is affected by nonalcoholic fatty liver disease (NAFLD). Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography (US) and computed tomography (CT), but the sensitivity of these imaging techniques is low in cases of mild steatosis. Alanine aminotransferase levels may be normal in some of these patients, warranting the necessity to establish a set of parameters useful for detecting NAFLD, and the more severe form of the disease, nonalcoholic steatohepatitis (NASH). Although liver biopsy is currently the gold standard for diagnosing progressive NASH, it has many drawbacks, such as sampling error, cost, and risk of complications. Furthermore, it is not realistic to perform liver biopsies on all NAFLD patients. Diagnosis of NASH using various biomarkers, scoring systems and imaging methods, such as elastography, has recently been attempted. The NAFIC score, calculated from the levels of ferritin, fasting insulin, and type IV collagen 7S, is useful for the diagnosis of NASH, while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis. This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.

Focus

Focus

Letter: FibroTest for staging fibrosis in non‐alcoholic fatty liver disease

We read with interest the review of non-invasive methods for the diagnosis of non-alcoholic fatty liver in liver disease (NAFLD) by Festi et al.1 We agree with several of their conclusions, but not on their ranking of biomarkers’ performance, stated in the summary, results and discussion. Several methodological errors, lead to misleading conclusions concerning the biomarkers’ comparisons. First, the authors used standard area under the receiver operating-characteristics curve (AUROC) to indirectly compare the performance between biomarkers, without taking into account the spectrum effect. If the spectrum effect is not taken into account, the AUROC for bridging fibrosis (or cirrhosis) can vary significantly according to stages’ prevalence from 0.67 to 0.98 for the same biomarker.2 Second, this review is not exhaustive. Several large studies of FibroTest have not been included. In a meta-analysis of three studies (two independent of the FibroTest inventor group) in 494 obese patients, FibroTest had a highly significant performance for fibrosis staging, with the appropriate method taking into account the spectrum effect: Obuchowski measure = 0.85 (95% CI: 0.83–0.87; P < 0.0001).3, 4 Another independent study, only partially published in the cited meta-analysis (reference 41), assessed the performance of FibroTest in 242 NAFLD patients, and found similar AUROCs to those of Hepascore and FIB4 for advanced fibrosis or cirrhosis.5 Third, several fibrosis tests, such as Fibrometer, FIB4 and NAFLD fibrosis score, are at higher risk of false positive/negative as they included ALT or AST in their components. The presence of these sensitive biomarkers of the necrotico-inflammatory histological activity in a composite fibrosis biomarker systematically increases the risk of false positive prediction before treatment and the risk of overestimating the impact of treatment on fibrosis after treatment. It took more than 20 years to separate in biopsy scoring systems (such as METAVIR) the estimate of fibrosis (stage) vs. necrosis/inflammation (activity). It is hazardous to ‘regress’ in the non-invasive biomarkers discovery by mixing fibrosis markers and inflammation/necrosis markers. Fourth, biomarkers reaching more than 90% of AUROC, such as Fibrometer, are suspect of false positive results. It is mathematically impossible to obtain such performance using a 25 mm biopsy due to its own variability.6 Fifth, the concept of grey zone used by the authors for their algorithm is another artefact due to the spectrum effect and the higher variability in biopsy staging between intermediate stages.7 Due to these methodological errors, the following authors’ statement is unfair: ‘the most accurate estimating methods are FibroMeter, FIB-4 and NAFLD fibrosis score and transient elastography’. Using evidence based published data, FibroTest does not have lower performance than these biomarkers. Even more, FibroTest has the advantages of being less corrupted by necro-inflammatory activity than biomarkers including ALT, validated by more appropriate methods and with higher applicability than transient elastography.8, 9 Declaration of personal interests: Thierry Poynard is the inventor of FibroTest with a capital interest in BioPredictive, the company marketing the FibroTest. Patents belong to the public Organization Assistance Publique Hôpitaux de Paris. Mona Munteanu is a full employee of BioPredictive. Declaration of funding interests: None.

A Paradigm Shift in the Outpatient Approach to Liver Function Tests

The American Gastroenterological Association (2002), Canadian Medical Association (2005), and the Centers for Disease Control and Prevention (2006) released guidelines to screen patients with mild elevations of liver enzymes for hepatitis B and hepatitis C. Mildly elevated liver enzymes were defined as less than five times the upper limit of normal, but above the normal reference range. The rationale for this recommendation was based on many factors including cost effectiveness, lab variation, and ultimately, for better patient care.Chronic hepatitis B and C have values of transaminases that fluctuate between normal and mildly abnormal. Screening patients with even mild elevations of transaminases allows many chronic hepatitis patients to be diagnosed early in the course of their disease. Diagnosing these patients early in their disease course leads to better treatment response, decreased progression to cirrhosis, lower viral loads leading to decreased incidence of extrahepatic manifestations, prevention of hepatocellular carcinoma, and decreased likelihood of liver transplantation.There are organizations which recommend discontinuing hepatotoxic medications such as acetaminophen or nonsteroidal anti-inflammatory drugs and reevaluating the patient in three months. However, this recommendation misses a number of hepatitis patients for the reasons aforementioned. The obesity epidemic has clouded the diagnosis of hepatitis B/C as patients that have obesity, diabetes mellitus, and metabolic syndrome are not being screened due the presumptive diagnosis of nonalcoholic fatty liver disease.Not screening patients in the setting of obesity is not cost-effective and also leads to increased morbidity, as we will discuss in this manuscript. Additionally, it has been proven in the literature that it is more cost-effective to screen for hepatitis B/C in high-prevalence areas, than to reassess the patient months later, and potentially miss a diagnosis of hepatitis B/C. The overall goal of this study is to increase screening awareness of patients with mild transaminitis elevations through publication in order to diagnose patients with hepatitis B and C prior to the development of chronic liver disease.