Liver Disease Subjects Research Articles

The diagnostic performance of AFP and PIVKA-II models for non-B non-C hepatocellular carcinoma

ObjectiveThis study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC).ResultsA total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785–0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725–0.791) and 0.866 (95%CI: 0.836–0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients’ age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872–0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1–85.4) and 83.2% (95%CI: 78.9–86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.

Spliceosome component Usp39 contributes to hepatic lipid homeostasis through the regulation of autophagy

Regulation of alternative splicing (AS) enables a single transcript to yield multiple isoforms that increase transcriptome and proteome diversity. Here, we report that spliceosome component Usp39 plays a role in the regulation of hepatocyte lipid homeostasis. We demonstrate that Usp39 expression is downregulated in hepatic tissues of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) subjects. Hepatocyte-specific Usp39 deletion in mice leads to increased lipid accumulation, spontaneous steatosis and impaired autophagy. Combined analysis of RNA immunoprecipitation (RIP-seq) and bulk RNA sequencing (RNA-seq) data reveals that Usp39 regulates AS of several autophagy-related genes. In particular, deletion of Usp39 results in alternative 5’ splice site selection of exon 6 in Heat shock transcription factor 1 (Hsf1) and consequently its reduced expression. Importantly, overexpression of Hsf1 could attenuate lipid accumulation caused by Usp39 deficiency. Taken together, our findings indicate that Usp39-mediated AS is required for sustaining autophagy and lipid homeostasis in the liver.

Fatty liver index (FLI): more than a marker of hepatic steatosis.

Fatty liver index (FLI) was developed as a simple and accurate marker of hepatic steatosis. FLI is derived from an algorithm based on body mass index, waist circumference, and levels of triglycerides and gamma-glutamyltransferase, and it is widely used in clinical and epidemiological studies as a screening tool for discriminating between healthy and nonalcoholic fatty liver disease (NAFLD) subjects. However, a systematic review of the literature regarding FLI revealed that this index has more extensive relationships with biochemical and physiological parameters. FLI is associated with key parameters of lipid, protein and carbohydrate metabolism, hormones, vitamins and markers of inflammation, or oxidative stress. FLI can be a predictor or risk factor for a number of metabolic and nonmetabolic diseases and mortality. FLI is also used as an indicator for determining the effects of health-related prevention interventions, medications, and toxic substances on humans. Although in most cases, the exact mechanisms underlying these associations have not been fully elucidated, they are most often assumed to be mediated by insulin resistance, inflammation, and oxidative stress. Thus, FLI may be a promising marker of metabolic health due to its multiple associations with parameters of physiological and pathological processes. In this context, the present review summarizes the data from currently available literature on the associations between FLI and biochemical variables and physiological functions. We believe that this review will be of interest to researchers working in this area and can provide new perspectives and directions for future studies on FLI.

Does the Mediterranean Diet Have Any Effect on Lipid Profile, Central Obesity and Liver Enzymes in Non-Alcoholic Fatty Liver Disease (NAFLD) Subjects? A Systematic Review and Meta-Analysis of Randomized Control Trials.

The effectiveness of the Mediterranean diet (MD) in non-alcoholic fatty liver disease (NAFLD) subjects has been evaluated in several randomized controlled trials (RCTs). This systematic review and meta-analysis aimed to evaluate the overall effects of MD intervention in a cohort of NAFLD patients targeting specific markers such as central obesity, lipid profile, liver enzymes and fibrosis, and intrahepatic fat (IHF). Google Scholar, PubMed, and Scopus were explored to collect relevant studies from the last 10 years. RCTs with NAFLD subjects were included in this systematic review with a mean intervention duration from 6 weeks to 1 year, and different intervention strategies, mainly including energy restriction MD (normal or low glycaemic index), low-fat MD with increased monounsaturated and polyunsaturated fatty acids, and increased exercise expenditure. The outcomes measured in this meta-analysis were gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), total cholesterol (TC), waist circumference (WC), and liver fibrosis. Ten randomized controlled trials, which involved a total of 737 adults with NAFLD, were included. According to the results, the MD seems to decrease the liver stiffness (kPa) by -0.42 (CI95% -0.92, 0.09) (p = 0.10) and significantly reduce the TC by -0.46 mg/dl (CI95% -0.55, -0.38) (p = 0.001), while no significant findings were documented for liver enzymes and WC among patients with NAFLD. In conclusion, the MD might reduce indirect and direct outcomes linked with NAFLD severity, such as TC, liver fibrosis, and WC, although it is important to consider the variations across trials. Further RCTs are necessary to corroborate the findings obtained and provide further evidence on the role of the MD in the modulation of other disorders related to NAFLD.

Impaired ketogenesis is associated with metabolic-associated fatty liver disease in subjects with type 2 diabetes.

The ketogenic pathway is an effective mechanism by which the liver disposes of fatty acids (FAs) to the peripheral tissues. Impaired ketogenesis is presumed to be related to the pathogenesis of metabolic-associated fatty liver disease (MAFLD), but the results of previous studies have been controversial. Therefore, we investigated the association between ketogenic capacity and MAFLD in subjects with type 2 diabetes (T2D). A total of 435 subjects with newly diagnosed T2D was recruited for the study. They were classified into two groups based on median serum β-hydroxybutyrate (β-HB) level: intact vs. impaired ketogenesis groups. The associations of baseline serum β-HB and MAFLD indices of hepatic steatosis index, NAFLD liver fat score (NLFS), Framingham Steatosis index (FSI), Zhejian University index, and Chinese NAFLD score were investigated. Compared to the impaired ketogenesis group, the intact ketogenesis group showed better insulin sensitivity, lower serum triglyceride level, and higher low-density lipoprotein-cholesterol and glycated hemoglobin levels. Serum levels of liver enzymes were not different between the two groups. Of the hepatic steatosis indices, NLFS (0.8 vs. 0.9, p=0.045) and FSI (39.4 vs. 47.0: p=0.041) were significantly lower in the intact ketogenesis group. Moreover, intact ketogenesis was significantly associated with lower risk of MAFLD as calculated by FSI after adjusting for potential confounders (adjusted odds ratio 0.48, 95% confidence interval 0.25-0.91, p=0.025). Our study suggests that intact ketogenesis might be associated with decreased risk of MAFLD in T2D.

Molecular Screening via Sanger Sequencing of the Genetic Variants in Non-Alcoholic Fatty Liver Disease Subjects in the Saudi Population: A Hospital-Based Study.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, along with steatosis and non-alcoholic steatohepatitis (NASH), and is associated with cirrhosis and hepatocellular carcinoma. Candidate gene and genome-wide association studies have validated the relationships between NAFLD, NASH, PNPLA3, TM6SF2, and HFE. The present study utilized five polymorphisms in three genes: PNPLA3 (I148M and K434E) TM6SF2 (E167K), and HFE (H63D and C282Y), based on undocumented case−control studies in the Saudi Arabian population. A total of 95 patients with NAFLD and 78 non-NAFLD subjects were recruited. Genomic DNA was isolated, and polymerase chain reaction and Sanger sequencing were performed using specific primers for the I148M, K434E, E167K, H63D, and C282Y. NAFLD subjects were older when compared to controls and showed the significant association (p = 0.0001). Non-significant association was found between gender (p = 0.26). However, both weight and BMI were found to be associated. Hardy−Weinberg equilibrium analysis confirmed that H63D, I148M, and K434E polymorphisms were associated. Genotype analysis showed only K434E variant was associated with NAFLD and non-NAFLD (OR-2.16; 95% CI: 1.08−4.31; p = 0.02). However, other polymorphisms performed with NAFLD and NASH were not associated (p > 0.05), and similar analysis was found when ANOVA was performed (p > 0.05). In conclusion, we confirmed that K434E polymorphism showed a positive association in the Saudi population.

Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients.

Hepatocellular carcinoma (HCC) is a severe complication of advanced alcoholic liver disease, which is modulated by genetic predisposition. Identifying new genetic loci might improve screening. Genetic variation of SAMM50 was linked to HCC. We aimed to validate this finding in a large cohort of patients with advanced alcoholic liver disease (ALD). A large, well-characterised cohort of patients with alcoholic cirrhosis without (n = 674) and with (n = 386) HCC, as well as controls with HCC due to viral hepatitis (n = 134), controls with heavy alcohol abuse without liver disease (n = 266) and healthy subjects (n = 237), were genotyped for SAMM50 rs3827385 and rs3761472 and for PNPLA3 rs738409. Genotype frequencies were compared between patients with alcohol-associated cirrhosis with and without HCC by uni- and multivariate analysis. Minor variants in both SAMM50 rs3827385 and rs3761472 were significantly more frequent in patients with alcoholic HCC versus alcoholic cirrhosis and versus the control cohorts. An even stronger association was noted for PNPLA3 rs738409. The univariate analysis resulted in an odds ratio (OR) of 1.8 for carriers of at least one minor variant of SAMM50 rs3827385 and rs3761472 (each p < 0.001), but this association was lost in multivariate analysis with age (OR 1.1/year), male sex (OR 3.2), diabetes (OR 1.9) and carriage of PNPLA3 148M (OR 2.1) remaining in the final model. Although minor variants of both SAMM50 loci are strongly associated with alcoholic HCC, this association is not independent of carriage of the well-known risk variant PNPLA3 148M.

Sex-specific differences in prevalence of nonalcoholic fatty liver disease in subjects with prediabetes and type 2 diabetes

AimsTo characterize the prevalence of NAFLD among subjects with NGT, prediabetes and type 2 diabetes (T2DM) by sex in adults with one or more cardio-metabolic risk factors, and to assess whether cardio-metabolic factors explained sex-related differences in NAFLD prevalence. MethodsThe study sample encompasses 742 individuals with NGT, 553 with prediabetes, and 431 with T2DM. ResultsWomen with prediabetes and T2DM exhibited greater relative differences in waist circumference, HOMA-IR, hsCRP, and lipid profile than prediabetic and diabetic men when compared with their NGT counterparts. Formal tests for glucose tolerance status × sex interaction were statistically significant for waist circumference (P = 0.008), HOMA-IR (P = 0.03), total cholesterol (P = 0.003), LDL (P = 0.001), HDL (P = 0.006), triglycerides (P < 0.0001), and hsCRP (P < 0.05). In a logistic regression analysis, prediabetic and diabetic women exhibited a higher OR for NAFLD than their male counterparts with test for glucose tolerance status × sex interaction being statistically significant. ConclusionsPrediabetic and diabetic women have higher OR of having NAFLD than men. Deterioration of glucose homeostasis in women is associated with a greater worsening in metabolic risk factors than men, which may explain the stronger impact of prediabetes and T2DM on NAFLD in women.

An Update on the Innovative Part of NLRP3 Inflammasome Regarding Newer Strategies for Treatment of Reproductive Conditions Possessing Greater Risk: A Systematic Review

Earlier we reviewed the role of NOD –like receptor protein (NLRP3) inflammasome in different patients presenting with various metabolic disorders is type 2 Diabetes mellitus obesity, Metabolic Syndrome (MetS), non-alcoholic fatty liver disease subjects NAFLD, non-alcoholic steatohepatitis (NASH). Thus Here we conducted a systematic review utilizing search engine PubMed, google scholar ;web of science; embase; Cochrane review library utilizing the MeSH terms like NLRP3 inflammasome; mode of action; recurrent spontaneous abortions (RSA); Gestational Diabetes mellitus(GDM); endometriosis; preterm birth; Polycystic ovary syndrome (PCOS); preeclampsia ;leaky gut;IL-1β;IL-18;caspase 1. We found a total of 150 articles out of which we selected 100 articles for this review. No meta-analysis was done. Here we have detailed the mechanism of action of NLRP3 inflammasome, their part in RSA, PCOS, GDM, PE, preterm birth, ovarian aging and newer non hormonal therapy for endometriosis&amp; other practical applications

Clinical Spectrum of Alcoholic Liver Disease in Subjects Attending Outpatient Department at a Tertiary Care Hospital

Background: Alcoholic liver disease is one of the primary medical complication of chronic ethanol abuse. It encloses a wide spectrum of diseases comprising of fatty liver, alcoholic hepatitis, alcoholic cirrhosis and hepatocellular carcinoma.&#x0D; Methodology: A prospective, observational study was done at AIG hospitals in the department of hepatology for a period of 6 months. A total of 200 patient’s diagnosed clinically and biochemically with various spectrum of ALD were recruited for the study.Non-invasive prognostic scores were calculated at the time of admission and correlated with severity of disease.&#x0D; Results: Among 200 study participants, 34.8% belongs to age group of 36-45 years. All were male patients with age group ranged from 25 to 73 years. We observed the high levels of alkaline phosphatese, aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, total bilirubin and international normalized ratio in Severe Alcoholic hepatitis patients. Non-invasive prognostic markers like child-turcotte-pugh score,model for end stage liver disease-sodium and maddrey’s discriminant factor were assessed for all patients.Prevalence of different stages of ethanol mediated liver disease were-12% of alcoholic fatty liver,17.5% of alcoholic hepatitis,6% of acute on chronic liver failure,32.5% of chronic liver disease,24% of decompensated chronic liver disease,6% of past decompensated chronic liver disease with current living donor liver transplant and 2% cases of hepatocellular carcinoma.&#x0D; Conclusion: Hazardous ethanol abuse is more typical in adult males especially among productive age group. The subjects were cautioned on their personal basis regarding fallout of alcoholic liver disease, and guided for latency of alcohol not immediately but definitely.

Effect of dietary chia supplementation on glucose metabolism and adipose tissue function markers in non-alcoholic fatty liver disease subjects.

Background: adipose tissue dysfunction is a key factor for diabetes and non-alcoholic fatty liver disease (NAFLD) development. Chia (Salvia hispanica) is an abundant source of omega-3 fatty acids, antioxidants, and fiber which could improve adipose tissue functionality. Aim: to analyze the effect of an isocaloric chia-supplemented diet on glucose metabolism, adipose tissue inflammation, and endothelial function markers in patients with NAFLD and early stages of diabetes. Methods: in 32 patients with previous NAFLD diagnosis, without known diabetes, the effect of a diet supplemented with ground chia (25 g/day/8 weeks) was evaluated. Visceral (VAF) and liver fat, plasma lipids, fatty acids, and cytokine profiles, oral glucose tolerance test (OGTT), insulinogenic index (IGI30), insulin disposition index (DIO), and endothelial progenitor cells (EPC) were analyzed. Before and after eight weeks of diet supplementation. Results: chia supplementation promoted increases in plasma alpha-linolenic acid (75 %) and fiber consumption (55 %), and a higher number of EPC (+126 %). Basal OGTT showed that nine patients had normal OGTT, 17 pre-diabetes, and six newly diagnosed diabetes. In patients with diabetes, chia favored a healthier adipose tissue (VAF -7 %, NAFLD -100 %, adiponectin +47 %, resistin -30 %, IL-6 -44 %, IL-1β -22 %) and upturn glucose metabolism through the improvement of beta-cell function (IGI30 +50 %, DIO +66 %). Conclusions: dietary supplementation with 25 g/day of ground chia may promote a healthier adipose tissue and improve pancreatic β-cell and endothelial function. Among patients with early metabolic abnormalities, phytochemical properties of chia may retard diabetes progression and advanced stages of liver damage.

New stem cell autophagy surrogate diagnostic biomarkers in early-stage hepatocellular carcinoma in Egypt: A pilot study.

BACKGROUNDStem cell autophagy disruption is responsible for the development of hepatocellular carcinoma (HCC). Many non-coding RNAs are linked to the activation and inhibition of certain genes. The SQSTM1 gene controls stem cell autophagy as shown in previous studies. The upregulation of SQSTM1 is associated with the inhibition of autophagy in cancerous stem cells in patients with HCC. AIMTo determine whether serum microRNA, hsa-miR-519d, is linked to SQSTM1 gene and whether they could be used as diagnostic biomarkers for early-stage HCC.METHODS In silico analysis was performed to determine the most correlated genes of autophagy with microRNAs. SQSTM1 and hsa-miR-519d were validated through this pilot clinical study. This study included 50 Egyptian participants, who were classified into three subgroups: Group 1 included 34 patients with early-stage HCC, Group 2 included 11 patients with chronic liver disease, and Group 3 (control) included 5 healthy subjects. All patients were subjected to full laboratory investigations, including viral markers and alpha-fetoprotein (AFP), abdominal ultrasound, and clinical assessment with the Child–Pugh score calculation. Besides, the patients with HCC underwent triphasic computed tomography with contrast to diagnose and determine the tumor site, size, and number. Quantitative real-time polymerase chain reaction was used to assess hsa-miR-519d-3p and SQSTM1 in the serum of all the study participants.RESULTSHsa-miR-519d-3p was significantly upregulated in patients with HCC compared with those with chronic liver disease and healthy subjects with an area under the curve (AUC) of 0.939, with cutoff value 8.34, sensitivity of 91.2%, and specificity of 81.8%. SQSTM1 was upregulated with an AUC of 0.995, with cutoff value 7.89, sensitivity of 97.1%, and specificity of 100%. AFP significantly increased in patients with HCC with an AUC of 0.794, with cutoff value 7.30 ng/mL, sensitivity of 76.5%, and specificity of 72.7%.CONCLUSIONThis study is the first to show a direct relation between SQSTM1 and hsa-miR-519d-3p; they are both upregulated in HCC. Thus, they could be used as surrogate diagnostic markers for stem cell autophagy disturbance in early-stage HCC.

Prevalence of High and Moderate Risk Nonalcoholic Fatty Liver Disease Among Adults in the United States, 1999–2016

Nonalcoholic fatty liver disease (NAFLD) subjects with fibrosis stage ≥2 are at high risk for mortality. We aimed to provide national estimates and temporal trends for NAFLD, based on different fibrosis severity. Data from the National Health and Nutrition Examination Survey (NHANES) (1999-2016) and NHANES III (1988-1994) were utilized. NAFLD was determined by ultrasound showing moderate to severe steatosis. For those without ultrasound, NAFLD was determined by the U.S. Fatty Liver Index score of ≥30. Hepatic fibrosis was assessed using Fibrosis-4 (FIB-4) score (FIB-4 <1.3= low risk; FIB-4 1.3-2.67= moderate risk; and FIB-4 >2.67= high risk). Annual percent change (APC) was calculated by using the joinpoint regression model. From NHANES III, 10,854 individuals were included (mean age 43.5 years; 47.5% male; 75.7% non-Hispanic White) and 37.7% had NAFLD. Among them, based on FIB-4, 80% had low-risk, 18.6% had moderate-risk, and 1.4% had high-risk NAFLD. NAFLD with moderate or high risk was more likely to have hypertension, hyperlipidemia, diabetes, cardiovascular disease, and metabolic syndrome than was low-risk NAFLD (all P < .02). NAFLD prevalence increased from 29.5% in 1999-2000 to 40.3% in 2015-2016 (APC, 2.78%; P < .02), moderate-risk NAFLD increased from 6.26% to 14.17% (APC, 5.34%; P < .02), and high-risk NAFLD increased from 0.49% to 1.15% (APC, 9.72%; P < .02). Independent predictors of advanced fibrosis were age (OR, 1.11; 95% CI, 1.06-1.17; P= .001) and diabetes (OR, 2.28; 95% CI, 1.03-5.05; P= .04). Compared with low-risk NAFLD, high-risk NAFLD was associated with significantly increased all-cause (HR, 1.53; 95% CI, 1.09-2.15; P= .01), cardiovascular disease-specific (HR, 1.99; 95% CI, 1.22-3.24, P < .01) and liver-specific (HR, 4.57; 95% CI, 1.03-28.79; P= .04) mortality. The prevalence of moderate- or high-risk NAFLD is increasing and is associated with increased all-cause, liver-related, and cardiovascular mortality.

Deep Learning Techniques for Fatty Liver Using Multi-View Ultrasound Images Scanned by Different Scanners: Development and Validation Study.

BackgroundFat fraction values obtained from magnetic resonance imaging (MRI) can be used to obtain an accurate diagnosis of fatty liver diseases. However, MRI is expensive and cannot be performed for everyone.ObjectiveIn this study, we aim to develop multi-view ultrasound image–based convolutional deep learning models to detect fatty liver disease and yield fat fraction values.MethodsWe extracted 90 ultrasound images of the right intercostal view and 90 ultrasound images of the right intercostal view containing the right renal cortex from 39 cases of fatty liver (MRI–proton density fat fraction [MRI–PDFF] ≥ 5%) and 51 normal subjects (MRI–PDFF < 5%), with MRI–PDFF values obtained from Good Gang-An Hospital. We obtained combined liver and kidney-liver (CLKL) images to train the deep learning models and developed classification and regression models based on the VGG19 model to classify fatty liver disease and yield fat fraction values. We employed the data augmentation techniques such as flip and rotation to prevent the deep learning model from overfitting. We determined the deep learning model with performance metrics such as accuracy, sensitivity, specificity, and coefficient of determination (R2).ResultsIn demographic information, all metrics such as age and sex were similar between the two groups—fatty liver disease and normal subjects. In classification, the model trained on CLKL images achieved 80.1% accuracy, 86.2% precision, and 80.5% specificity to detect fatty liver disease. In regression, the predicted fat fraction values of the regression model trained on CLKL images correlated with MRI–PDFF values (R2=0.633), indicating that the predicted fat fraction values were moderately estimated.ConclusionsWith deep learning techniques and multi-view ultrasound images, it is potentially possible to replace MRI–PDFF values with deep learning predictions for detecting fatty liver disease and estimating fat fraction values.

Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank.

BackgroundObesity is among the main determinants of nonalcoholic fatty liver disease progression towards severe liver disease (SLD). However, risk factors for SLD in individuals with obesity have not been examined.ObjectivesTo identify the independent risk factors for SLD among participants with obesity from the UK Biobank.MethodsA total of 80,224 UK Biobank participants with obesity (body mass index[BMI] > 30 kg/m2) and 242,822 without obesity, of European descent without clinical history of liver disease and liver cancer were prospectively followed for the onset of SLD, defined as a composite diagnosis of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation. Risk factors for incident SLD were assessed by Cox proportional hazards models. Different clinical phenotypes were derived by latent class analysis (LCA).ResultsObesity conferred a 2.6-fold increased risk for SLD that was abolished after the inclusion of waist circumference (WC) in the model. Among individuals with obesity, age (adjusted hazard ratio [aHR] 1.05, 95%CI 1.03–1.07, p = 3.9 * 10−7), type 2 diabetes (aHR 2.18, 95%CI 1.55–3.05, p = 6.2 * 10−6), PNPLA3 rs738409 (aHR 1.59, 95%CI 1.33–1.9, p = 3.1 * 10−7) and WC (aHR 1.04, 95%CI 1.02–1.06, p = 8.5 * 10−6) were independent predictors of SLD. BMI category-specific WC thresholds allowed a better risk stratification compared to traditional ones. By LCA, the clinical phenotype at highest risk for SLD was that with BMI < 35 kg/m2 and WC above BMI-category specific thresholds.ConclusionsAge, WC, type 2 diabetes, and the PNPLA3 variant are the main risk factors for SLD in individuals with obesity. WC is the principal mediator of SLD risk conveyed by increased BMI. BMI category-specific WC-thresholds may refine the SLD risk more accurately than traditional thresholds.

Spectroscopy-based multi-parametric quantification in subjects with liver iron overload at 1.5T and 3T.

To evaluate the precision profile (repeatability and reproducibility) of quantitative STEAM-MRS and to determine the relationships between multiple MR biomarkers of chronic liver disease in subjects with iron overload at both 1.5 Tesla (T) and 3T. MRS data were acquired in patients with known or suspected liver iron overload. Two STEAM-MRS sequences (multi-TE and multi-TE-TR) were acquired at both 1.5T and 3T (same day), including test-retest acquisition. Each acquisition enabled estimation of R1, R2, and FWHM (each separately for water and fat); and proton density fat fraction. The test-retest repeatability and reproducibility across acquisition modes (multi-TE vs. multi-TE-TR) of the estimates were evaluated using intraclass correlation coefficients, linear regression, and Bland-Altman analyses. Multi-parametric relationships between parameters at each field strength, across field strengths, and with liver iron concentration were also evaluated using linear and nonlinear regression. Fifty-six (n = 56) subjects (10 to 73 years, 37 males/19 females) were successfully recruited. Both STEAM-MRS sequences demonstrated good-to-excellent precision (intraclass correlation coefficient ≥ 0.81) for the quantification of R1water , R2water , FWHMwater , and proton density fat fraction at both 1.5T and 3T. Additionally, several moderate (R2 = 0.50 to 0.69) to high (R2 ≥ 0.70) correlations were observed between biomarkers, across field strengths, and with liver iron concentration. Over a broad range of liver iron concentration, STEAM-MRS enables rapid and precise measurement of multiple biomarkers of chronic liver disease. By evaluating the multi-parametric relationships between biomarkers, this work may advance the comprehensive MRS-based assessment of chronic liver disease and may help establish biomarkers of chronic liver disease.

Warfarin compared with non-vitamin K antagonist oral anticoagulants in subjects with liver disease and atrial fibrillation: A meta-analysis.

Many concerns were raised aboutthe outcome of non-vitamin K antagonist oral anticoagulants compared with warfarin in subjects with atrial fibrillation and liver disease. However, the reported relationship between their efficacy and safety was variable. This meta-analysis was performed to evaluate this relationship. A systematic literature search up to July 2020 was performed and six studies included 50074 subjects with atrial fibrillation and liver disease at the baseline with 32229 non-vitamin K antagonist oral anticoagulant consumers and 18920 warfarin consumers. They were reporting relationships between non-vitamin K antagonist oral anticoagulants and warfarin in subjects with atrial fibrillation and liver disease. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of the efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with warfarin in subjects with atrial fibrillation and liver disease subjects using the dichotomous method with a random or fixed-effect model. Non-vitamin K antagonist oral anticoagulants consumption was significantly related to lower all-cause mortality in subjects with atrial fibrillation and liver disease (OR, 0.90; 95% CI, 0.81-0.99, P=.03); lower intracranial haemorrhage (OR, 0.67; 95% CI, 0.55- 0.82, P<.001) and low stroke and system embolism (OR, 0.76; 95% CI, 0.68-0.86, P<.001) compared with warfarin consumption. However, non-vitamin K antagonist oral anticoagulants consumption was not significantly related to lower major bleeding in subjects with atrial fibrillation and liver disease (OR, 0.73; 95% CI, 0.52-1.02, P=.06); and gastrointestinal bleeding (OR, 0.93; 95% CI, 0.58-1.49, P=.77) compared with warfarin consumption. Based on this meta-analysis, non-vitamin K antagonist oral anticoagulant consumption may have an independent lower risk relationship with all-cause mortality, intracranial haemorrhage, and stroke and system embolism compared with warfarin consumption in subjects with atrial fibrillation and liver disease. This relationship forces us to recommend non-vitamin K antagonist oral anticoagulant use in subjects with atrial fibrillation and liver disease for better outcomes and to avoid any possible complications. Further studies are required.

Nutritional Status in patient with liver cirrhosis

Liver transplantation (OLT) is the treatment that provides long-term survival in liver disease patients (1). Malnutrition and sarcopenia are related to unfavorable post OLT outcomes (2). Characteristics of 26 liver disease subjects post-OLT or candidates to OLT are shown in Table 1. The risk of malnutrition was assessed using the GLIM criteria. Patients were also evaluated by bioimpedance analysis (BIA). Total muscle area was assessed for 10 patients by studying the transverse CAT scan (CT) image at L3 level and the Skeletal Muscle Index SMI (3). In Table 2 were summarized the conditions of the patients according to the GLIM criteria. For patients with CT was calculated SMI (Table 3). The evaluation of the condition of malnutrition by GLIM criteria and evaluations by BIA and CT in patients who were post OLT or candidates allows a better clinical outcome in subjects at high risk of sarcopenia and malnutrition. The most significant investigation for sarcopenia is the determination of the SMI by CT analysis. It is therefore desirable to have staff dedicated to the assessment of subjects at risk within the OLT team.

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects.

Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD). Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7±3.8years). Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P=.0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P<.0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P=.015). Death and decompensated cirrhosis were similar between these. The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.

NAFLD: Reporting Histologic Findings in Clinical Practice.

The role of liver biopsy in NASH has evolved along with the increased recognition of the significance of this disease, and the unmet medical need it presents. Drug development and clinical trials are rapidly growing, as are noninvasive tests for markers of steatosis, inflammation, injury, and fibrosis. Liver biopsy evaluation remains necessary for both drug development and clinical trials as the most specific means of diagnosis and patient identification for appropriate intervention. This White Paper, sponsored by the American Association for the Study of Liver Disease NASH Task Force, is a focused review of liver biopsy evaluation in fatty liver disease in subjects with presumed NAFLD for practicing clinical hepatologists and pathologists. The goal is to provide succinct and specific means for reporting the histopathologic elements of NASH, distinguishing NASH from nonalcoholic fatty liver without steatohepatitis, and from alcohol-associated steatohepatitis when possible. The discussion includes the special situations of NASH in advanced fibrosis or cirrhosis, and in the pediatric population. Finally, there is discussion of semiquantitative methods of evaluation of lesions of "disease activity" and fibrosis. Tables are presented for scoring and a suggested model for final reporting. Figures are presented to highlight the histopathologic elements of NASH.