Severe Fatty Liver Research Articles

Association of Bariatric Surgery With Cardiovascular Outcomes in Adults With Severe Obesity and Nonalcoholic Fatty Liver Disease

There are no approved treatments for nonalcoholic fatty liver disease (NAFLD) despite its association with obesity and increased risk of cardiovascular disease (CVD). To examine the association between bariatric surgery and CVD risk in individuals with severe obesity and NAFLD. This large, population-based retrospective cohort study obtained data from the MarketScan Commercial Claims and Encounters database from January 1, 2007, to December 31, 2017. Participants included insured adults aged 18 to 64 years with NAFLD and severe obesity (body mass index ≥40) without a history of bariatric surgery or CVD before NAFLD diagnosis. Baseline characteristics were balanced between individuals who underwent surgery (surgical group) and those who did not (nonsurgical group) using inverse probability of treatment weighting. Data were analyzed from March 2020 to April 2021. Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy, and other bariatric procedures) vs nonsurgical care. The main outcome was the incidence of cardiovascular events (primary or secondary composite CVD outcomes). The primary composite outcome included myocardial infarction, heart failure, or ischemic stroke, and the secondary composite outcome included secondary ischemic heart events, transient ischemic attack, secondary cerebrovascular events, arterial embolism and thrombosis, or atherosclerosis. Cox proportional hazards regression models with inverse probability treatment weighting were used to examine the associations between bariatric surgery, modeled as time varying, and all outcomes. The study included 86 964 adults (mean [SD] age, 44.3 [10.9] years; 59 773 women [68.7%]). Of these individuals, 30 300 (34.8%) underwent bariatric surgery and 56 664 (65.2%) received nonsurgical care. All baseline covariates were balanced after applying inverse probability treatment weighting. In the surgical group, 1568 individuals experienced incident cardiovascular events compared with 7215 individuals in the nonsurgical group (incidence rate difference, 4.8 [95% CI, 4.5-5.0] per 100 person-years). At the end of the study, bariatric surgery was associated with a 49% lower risk of CVD (adjusted hazard ratio [aHR], 0.51; 95% CI, 0.48-0.54) compared with nonsurgical care. The risk of primary composite CVD outcomes was reduced by 47% (aHR, 0.53 [95% CI, 0.48-0.59), and the risk of secondary composite CVD outcomes decreased by 50% (aHR, 0.50; 95% CI, 0.46-0.53) in individuals with vs without surgery. Results of this study suggest that, compared with nonsurgical care, bariatric surgery was associated with significant reduction in CVD risk in individuals with severe obesity and NAFLD.

Predictors of hepatic steatosis in living liver donors

Fatty liver disease (steatosis) is considered a risk factor in donor liver transplantation (LT). Macrosteatosis (>50%) is associated with primary graft dysfunction and may reduce long-term recipient survival.Objective: to identify predictors of macrovesicular steatosis (>50%) by analyzing donor characteristics.Materials and methods. The retrospective study included 525 potential liver donors between January 1, 2019 and December 31, 2020. Clinical and morphological characteristics of donors were studied using logistic regression and receiver operating characteristic (ROC) analysis. Threshold values of parameters demonstrating statistical significance in multivariate analysis as predictors of >50% hepatic steatosis were obtained by ROC analysis based on calculation of the optimal cutoff point.Results. Diabetes mellitus (DM), cause of donor’s death (traumatic brain injury), alanine transaminase (ALT) >90 units/L and aspartate transaminase (AST) >110 units/L were predictors of >50% steatosis, revealed by time-zero biopsy in the donor. Almost identical sensitivity and specificity indicators were determined in ROC analysis for liver enzymes – ALT and AST – which were 69.1 and 80.6; 72.2 and 81.1, respectively. Given the obtained values, we can say that with elevated levels of liver enzymes in the donor’s blood, there is a high degree of probability of liver parenchymal damage, but low sensitivity indicates possible multifactoriality of liver damage, and fatty liver disease may be one of the factors, but there may also be no damage to the liver parenchyma. At the same time, the rather high specificity revealed in ROC analysis for liver enzymes is a reliable sign of the absence of fatty liver disease at enzyme values less than the threshold.Conclusion. The thresholds established for ALT and AST and their corresponding levels of sensitivity and specificity indicate that these parameters have a relatively low predictive level in the context of the presence of severe fatty liver disease in a donor. This allows, nevertheless, to use models built on their basis as screening models in the primary evaluation of liver donors.

One-step metal affinity purification of recombinant hFGF19 without using tags

Human fibroblast growth factor 19 (hFGF19) belongs to the endocrine FGF19 superfamily and is considered a potential agent to treat severe or relapsing nonalcoholic fatty liver disease. Numerous studies have confirmed the beneficial effects of this hormone on the related symptoms of the disease and attempts at producing recombinant proteins in various hosts are steadily proliferating. Recently, we reported that authentic hFGF19 can be solubly expressed through combining synonymous codon substitutions and co-expression with disulfide-bond isomerase (DsbC) in Escherichia coli. However, during purification, hFGF19 without the His-tag occasionally co-eluted with His-tagged DsbC when using metal affinity chromatography, thereby requiring auxiliary purification steps to achieve apparent homogeneity. This phenomenon provides evidence that hFGF19 specifically interacts with immobilized Ni2+, which can thus be used as an alternative tool for the purification of hFGF19. Consequently, we could simply and reproducibly purify hFGF19 from cell lysates by using Ni2+-immobilized metal affinity chromatography and stepwise gradient elution with imidazole.

Nonalcoholic fatty liver disease and diabetes.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression. The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance; thus the association between diabetes and NAFLD is widely recognized in the literature. Since NAFLD is the hepatic manifestation of a metabolic disease, it is also associated with a higher cardio-vascular risk. Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis, although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients. Treatment of NAFLD patients depends on the disease severity, ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis. Abstinence from alcohol, a Mediterranean diet, and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events, as per all diabetic patients. In addition, weight loss induced by bariatric surgery seems to also be effective in improving liver features, together with the benefits for diabetes control or resolution, dyslipidemia, and hypertension. Finally, liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries. This review offers a comprehensive multidisciplinary approach to NAFLD, highlighting its connection with diabetes.

Multi-Channel Metabolomics Analysis Identifies Novel Metabolite Biomarkers for the Early Detection of Fatty Liver Disease in Dairy Cows.

Fatty liver disease, a type of metabolic disorder, frequently occurs in dairy cows during the parturition period, causing a high culling rate and, therefore, considerable economic losses in the dairy industry owing to the lack of effective diagnostic methods. Here, metabolite biomarkers were identified and validated for the diagnosis of metabolic disorders. A total of 58 participant cows, including severe fatty liver disease and normal control groups, in the discovery set (liver biopsy tested, n = 18), test set (suspected, n = 20) and verification set (liver biopsy tested, n = 20), were strictly recruited and a sample collected for their feces, urine, and serum. Non-targeted GC-MS-based metabolomics methods were used to characterize the metabolite profiles and to screen in the discovery set. Eventually, ten novel biomarkers involved in bile acid, amino acid, and fatty acid were identified and validated in the test set. Each of them had a higher diagnostic ability than the traditional serum biochemical indicators, with an average area under the receiver operating characteristic curve of 0.830 ± 0.0439 (n = 10) versus 0.377 ± 0.182 (n = 9). Especially, combined biomarker panels via different metabolic pipelines had much better diagnostic sensitivity and specificity than every single biomarker, suggesting their powerful utilization potentiality for the early detection of fatty liver disease. Intriguingly, the serum biomarkers were confirmed perfectly in the verification set. Moreover, common biological pathways were found to be underlying the pathogenesis of fatty liver syndrome in cattle via different metabolic pipelines. These newly-discovered and non-invasive metabolic biomarkers are meaningful in reducing the high culling rate of cows and, therefore, benefit the sustainable development of the dairy industry.

Peroxisome Proliferator-Activated Receptor α Has a Protective Effect on Fatty Liver Caused by Excessive Sucrose Intake.

Sterol regulatory element binding protein (SREBP)-1c is a transcription factor that regulates lipid synthesis from glucose in the liver. It is activated by sucrose, which activates the fatty acid synthesis pathway. On the other hand, peroxisome proliferator-activated receptor (PPAR) α regulates the transcription of several genes encoding enzymes involved in fatty acid β-oxidation in the liver. To evaluate the beneficial effects of PPARα on fatty liver caused by excessive sucrose intake, we investigated the molecular mechanisms related to the development of fatty liver in PPARα-deficient mice that were fed a high-sucrose diet (Suc). The SREBP-1c target gene expression was increased by sucrose intake, leading to the development of fatty liver. Furthermore, PPARα−/− mice developed severe fatty liver. Male and female PPARα−/− mice fed Suc showed 3.7- and 3.1-fold higher liver fat content than Suc-fed male and female wild-type mice, respectively. Thus, PPARα may work to prevent the development of fatty liver caused by excessive sucrose intake. Liver TG accumulation differed between male and female PPARα−/− mice. A possible explanation is that male mice show the increased expression of Pparγ, which usually contributes to triglyceride synthesis in the liver, to compensate for Pparα deficiency. In contrast, female wild-type mice inherently have low Pparα levels. Thus, Pparα deficiency has less pronounced effects in female mice. A diet that activates PPARα may be effective for preventing the development of fatty liver due to excessive sucrose intake.

Rare ATG7 genetic variants predispose patients to severe fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants. We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n= 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level. In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio [OR] 5.26, 95% CI 2.1-12.6; p= 0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9; 95% CI 1.9-612; p= 0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30; 95% CI 1.1-7.5 and OR 12.30, 95% CI 2.6-36, respectively; p <0.001 for both). The low-frequency loss-of-function p.V471A variant (rs36117895 T>C) was also associated with severe NAFLD in the clinical cohort (OR 1.7; 95% CI 1.2-2.5; p= 0.003), predisposed to hepatocellular ballooning (p= 0.007) evolving to fibrosis in the Liver biopsy cohort (n= 2,268), and was associated with liver injury in the UK Biobank (aspartate aminotransferase levels, p <0.001), with a larger effect in severely obese individuals in whom it was linked to hepatocellular carcinoma (p= 0.009). ATG7 protein localized to periportal hepatocytes, particularly in the presence of ballooning. In the Liver Transcriptomic cohort (n= 125), ATG7 expression correlated with suppression of the TNFα pathway, which was conversely upregulated in p.V471A carriers. We identified rare and low-frequency ATG7 loss-of-function variants that promote NAFLD progression by impairing autophagy and facilitating ballooning and inflammation. We found that rare mutations in agene called autophagy-related 7 (ATG7) increase the risk of developing severe liver disease in individuals with dysmetabolism. These mutations cause an alteration in protein function and impairment of self-renewal of cellular content, leading to liver damage and inflammation.

Pathogenic effects of Desulfovibrio in the gut on fatty liver in diet-induced obese mice and children with obesity.

Although we know the key role of gut dysbiosis in nonalcoholic fatty liver disease (NAFLD), it remains unclear what microbe(s) are responsible. This study aims to identify the microbes that cause NAFLD. C57BL/6JNarl male mice fed a high-fat diet (HFD) were orally administered Lactobacillus reuteri (L. reuteri) or Lactobacillus rhamnosus GG plus Bifidobacterium animalis subsp. lactis BB12 (LGG plus BB12). Their fecal microbiomes identified by 16S rRNA sequencing were correlated with the severity of fatty liver. We then used a human cohort to confirm the role of the microbe(s). The HFD-fed mice were administrated with the identified bacterium, Desulfovibrio. The histopathological changes in the liver and ileum were analyzed. Lactobacillus and Bifidobacterium improved hepatic steatosis and fibrosis in HFD-fed mice, which was related to the decreased abundance of Desulfovibrio in feces. Further human study confirmed the amount of D. piger in the fecal microbiota of obese children with NAFLD was increased. We then administered D. piger and found aggravated hepatic steatosis and fibrosis in HFD-fed mice. Hepatic expression of CD36 was significantly increased in HFD-fed mice gavaged with D. piger. In HepG2 cells, overexpression of CD36 increased lipid droplets, whereas knockdown of CD36 decreased lipid droplets. HFD-fed mice gavaged with D. piger had a decrease in the villus length, crypt depth, and zonula occludens-1 density in the ileum tissue. Our findings provide novel insights into the role of Desulfovibrio dysregulation in NAFLD. Modulation of Desulfovibrio may be a potential target for the treatment of NAFLD.

Curcumin Offers No Additional Benefit to Lifestyle Intervention on Cardiometabolic Status in Patients with Non-Alcoholic Fatty Liver Disease

Cardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Curcumin has been shown to exert glucose-lowering and anti-atherosclerotic effects in type 2 diabetes. Hence, we investigated curcumin’s effects on atherogenesis markers, fatty liver, insulin resistance, and adipose tissue-related indicators in patients with NAFLD. In this secondary analysis of a 12-week randomized controlled trial, fifty-two patients with NAFLD received lifestyle modification. In addition, they were randomly allocated to either the curcumin group (1.5 g/day) or the matching placebo. Outcome variables (assessed before and after the study) were: the fatty liver index (FLI), hepatic steatosis index (HSI), fatty liver score (FLS), BMI, age, ALT, TG score (BAAT), triglyceride glucose (TyG) index, Castelli risk index-I (CRI-I), Castelli risk index-II (CRI-II), TG/HDL–C ratio, atherogenic coefficient (AC), atherogenic index of plasma (AIP), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), lipid accumulation product (LAP), body adiposity index (BAI), visceral adiposity index (VAI), metabolic score for visceral fat (METS-VF), visceral adipose tissue (VAT), and waist-to-height ratio (WHtR) values. The TyG index decreased in the curcumin group and increased in the placebo group, with a significant difference between the groups (p = 0.029). However, a between-group change was not significant after adjustment for multiple testing. Other indices were not significantly different between the groups either before or after multiple test correction. After the intervention, there was a lower number of patients with severe fatty liver (FLI ≥ 60) and metabolic syndrome in the curcumin group compared to the placebo (p = 0.021 and p = 0.012, respectively). In conclusion, curcumin offers no additional cardiometabolic benefits to lifestyle intervention in patients with NAFLD.

Artificial intelligence in liver ultrasound.

Artificial intelligence (AI) is playing an increasingly important role in medicine, especially in the field of medical imaging. It can be used to diagnose diseases and predict certain statuses and possible events that may happen. Recently, more and more studies have confirmed the value of AI based on ultrasound in the evaluation of diffuse liver diseases and focal liver lesions. It can assess the severity of liver fibrosis and nonalcoholic fatty liver, differentially diagnose benign and malignant liver lesions, distinguish primary from secondary liver cancers, predict the curative effect of liver cancer treatment and recurrence after treatment, and predict microvascular invasion in hepatocellular carcinoma. The findings from these studies have great clinical application potential in the near future. The purpose of this review is to comprehensively introduce the current status and future perspectives of AI in liver ultrasound.

Feasibility of Ultrasound Attenuation Imaging for Assessing Pediatric Hepatic Steatosis.

Simple SummaryHepatic steatosis is associated with cardiovascular disease, diabetes mellitus, and liver cirrhosis. The increasing prevalence of hepatic steatosis among children has become a public health concern. Although liver biopsy is the gold standard for the diagnosis of hepatic steatosis, it has limited value because of invasiveness. Among imaging studies, ultrasonography is readily accessible and can be used to exclude other pathology, but its accuracy is limited by low sensitivity and specificity. Although magnetic resonance imaging is highly accurate for liver steatosis and fibrosis, its application is curbed in children as it requires sedation and longer scan time. Recently, attenuation imaging (ATI) has emerged as a new modality for quantifying fat deposition in the liver in real time. However, investigations of ATI for pediatric hepatic steatosis are still in their preliminary stages. Thus, we investigated the feasibility of ultrasound attenuation imaging (ATI) for assessing pediatric hepatic steatosis. This study demonstrated that ATI can differentiate fatty liver from normal liver as well as moderate to severe fatty liver from mild fatty liver. Thus, ATI may be useful for identifying children who require liver biopsy and early treatment.We investigated the feasibility of ultrasound attenuation imaging (ATI) for assessing pediatric hepatic steatosis. A total of 111 children and adolescents who underwent liver ultrasonography with ATI for suspected hepatic steatosis were included. Participants were classified into the normal, mild, or moderate–severe fatty liver group according to grayscale US findings. Associations between clinical factors, magnetic resonance imaging proton density fat fraction, steatosis stage and ATI values were evaluated. To determine the cutoff values of ATI for staging hepatic steatosis, areas under the curve (AUCs) were analyzed. Factors that could cause measurement failure with ATI were assessed. Of 111 participants, 88 had successful measurement results. Median ATI values were significantly increased according to steatosis stage (p < 0.001). Body mass index (BMI) was a significant factor for increased ATI values (p = 0.047). To differentiate fatty liver from normal liver, a cutoff value of 0.59 dB/cm/MHz could be used with an AUC value of 0.853. To differentiate moderate to severe fatty liver from mild fatty liver, a cutoff value of 0.69 dB/cm/MHz could be used with an AUC value up to 0.91. ATI can be used in children as an effective ultrasonography technique for quantifying and staging pediatric hepatic steatosis.

Correlation of Cytokeratin-18 as a Marker of Cardiovascular Risk Assessment in Nonalcoholic Fatty Liver Disease in Nonobese and Nondiabetic Patients

Background: The evidence of nonalcoholic fatty liver disease (NAFLD) in absence of obesity and diabetes is not fairly adequate; furthermore, there is not much data on the markers of NAFLD for this patient population, especially in Indian patients. We aimed to evaluate the severity of NAFLD in nonobese and nondiabetic patients and determine the correlation of its severity with cytokeratin-18 (CK-18). We also aimed to analyze the data for correlation between the conventional marker alanine aminotransferase (ALT), cardiovascular surrogate markers carotid intima-media thickness (CIMT), and CK-18 in adults with NAFLD. Materials and Methods This prospective, single-center, and noninterventional study enrolled 200 nonobese, nondiabetic adults with ultrasonography-confirmed NAFLD (presence of any two of the features – increased liver echogenicity with a clear contrast between kidney and liver, clouding of vessels, or deep weakening of the ultrasound signal) and 100 healthy controls and was conducted in the Department of Gastroenterology at Sher-i-Kashmir Institute of Medical Sciences, Kashmir, India. Results The CK-18 levels progressively increased with the severity of fatty liver, 68.54 (Grade 1), 167.5 (Grade 2), and 324.44 (Grade 3). In patients with Grade 2 and 3 NAFLD, the levels of CK-18 were significantly higher compared to controls as well as Grade 1 (P = 0.00). The correlation between ALT, CIMT (right and left), and CK-18 levels using Pearson's correlation coefficient showed that CIMT had a significant (P ≤ 0.0001) and positive correlation with both ALT and CK-18. The CIMT and ALT are highly correlated, whereas the CIMT and CK-18 are moderately correlated. Conclusion Apart from ALT, elevated CK-18 in patients with NAFLD appears to be promising as a signal for cardiovascular risk evaluation even in nonobese, nondiabetic adults.

SAT021 - Increased burden of inherited IRF3 rare genetic variants in Europeans with severe Non-alcoholic fatty liver diease

SAT021 - Increased burden of inherited IRF3 rare genetic variants in Europeans with severe Non-alcoholic fatty liver diease

A retrospective study to find out the correlation between NAFLD, diabetes, and obesity in Indian patients.

Nonalcoholic fatty liver disease (NAFLD) is present in the body with metabolic disorders such as Type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease. However, no significant evidence has been found till date exhibiting their association epidemiologically in Indian patients. To assess the association among NAFLD, T2DM, and obesity, and to validate the scoring system with grades of fatty liver (severity of liver disease) estimated by ultrasound vs. NAFLD fibrosis score, BARD score, and aspartate aminotransferase to platelet ratio index (APRI) score. A retrospective, observational study was conducted out in patients with NAFLD (n = 316) where diagnosis and grades of fatty liver were established via ultrasound reports. The patients were divided into two groups, Group A (n = 114, NAFLD with T2DM) and Group B (n = 202, NAFLD without T2DM). R 4.0.0 was used for statistical analysis. The mean age (in years) of the patients was 54.08 ± 10.78 in Group A and 48.10 ± 15.36 in Group B. The mean BMI in Group A was found to be slightly higher as compared to Group B, 27.49 ± 4.94 and 26.56 ± 4.68, respectively, and the difference was found to be statistically significant (p-value <0.05). The overall predictive ability of the NAFLD scoring system matched that to ultrasonography liver grading fibrosis report for approximately 53% of patients. The BARD scoring system was found to be matched with ultrasonography reported Grade 1 fatty liver (198/316). In the case of the APRI scoring system, the association was not observed with ultrasonography reports in any grades of fatty liver. Body mass index might be an independent risk factor for NAFLD. NAFLD fibrosis score appears to be a reliable non-invasive tool to determine the severity of liver fibrosis in NAFLD patients. BARD score may predict Grade 1 liver fibrosis. However, APRI scores do not correlate with imaging evidence of fibrosis like NAFLD and BARD scores.

Quantification of liver fat deposition in obese and diabetic patients: A pilot study on the correlation with myocardium and periapical fat content

Backgroud and aimNon-alcoholic fatty liver disease (NAFLD) is a worldwide health problem, which associated with systemic health problems and causes a higher risk of all-cause mortality. The leading causes of death in NAFLD patients are cardiac complications followed by NAFLD-related liver complications. This study aimed to quantitatively measure the contents of liver and cardiac fat with varying degrees of NAFLD in an obese group and a type 2 diabetes mellitus (T2DM) group to explore differences and correlations. Materials and methodsThis study included 170 patients who underwent echo asymmetry and least square estimation-iron quantification sequencing at 3.0 T magnetic resonance imaging. Fat fraction values were quantitatively measured in regions of interest of the liver, myocardium, and periapical adipose tissue. ResultsIn both the obese and T2DM groups, cardiac fat content was correlated with liver fat content using linear regression (P < 0.01). For both the obese and T2DM groups, myocardial fat was higher in the T2DM group than that in the obese group (ventricular septum, 3.33% ± 1.40% vs. 2.51% ± 0.88%; the left ventricle, 3.38% ± 1.43% vs. 2.26% ± 0.87%). For the T2DM group, the different myocardial fat contents and myocardial enzymes were positively correlated with fatty liver severity by multiple comparisons of different degrees of NAFLD (P < 0.05). Periapical fat was statistically significant only between mild fatty and normal liver (obese group, P < 0.01; T2DM group, P = 0.01). ConclusionT2DM patients with fatty liver had higher myocardial fat content than obese patients with fatty liver, and both had a linear relationship. Periapical fat is an index for liver fat deposition in patients. The myocardial fat contents in T2DM patients with an increase in the liver fat content, which would influence cardiac function, should be given more attention in clinic.

Pro-Neurotensin as a Potential Novel Diagnostic Biomarker for Detection of Nonalcoholic Fatty Liver Disease.

Background and AimsCurrently, liver biopsy is the gold standard method for diagnosis of non-alcoholic fatty liver severity. It is critical to develop non-invasive diagnostic method to diagnose nonalcoholic fatty liver rather than invasive techniques. Our case–control study was to address the value of circulating miRNA-122 and serum pro-neurotensin as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases.MethodsClinical assessment, laboratory investigations, and anthropometric measurements were reported for 157 patients with proven NAFLD. Apparently, healthy participants (n=100) were enrolled as a control group. Serum samples were tested for micro-RNAs−122 and pro-neurotensin.ResultsCompared with the control subjects, both mi-RNA-122 and serum proneurotensin levels were increased in NAFLD (p<0.001) and at a cut-off ≥6.83, mi-RNA-122 had 51.0% sensitivity, 70.0% specificity to differentiate NAFLD from healthy controls, while serum proneurotensin had 80.0% sensitivity and 80.0% specificity at a cutoff ≥108.ConclusionThe circulating pro-neurotensin might be used as a novel biomarker for diagnosis of patients with NAFLD, wherefore the integration of a circulating mi-RNA-122 and serum pro-neurotensin could be beneficial to diagnose NAFLD cases. Large-scale studies are needed to investigate the possible role of mi-RNA-122 and pro-neurotensin in the development, progression, and prognosis of NAFLD and NASH.

Distinct Cytokine Profiles in Severe COVID-19 and Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is identified as a risk factor for developing severe COVID-19. While NAFLD is associated with chronic low-grade inflammation, mechanisms leading to immune system hyperactivation remain unclear. The aim of this prospective observational study is to analyze cytokine profiles in patients with severe COVID-19 and NAFLD. A total of 94 patients with severe COVID-19 were included. Upon admission, clinical and laboratory data were collected, a liver ultrasound was performed to determine the presence of steatosis, and subsequently, 51 were diagnosed with NAFLD according to the current guidelines. There were no differences in age, sex, comorbidities, and baseline disease severity between the groups. Serum cytokine concentrations were analyzed using a multiplex bead-based assay by flow cytometry. Upon admission, the NAFLD group had higher C-reactive protein, procalcitonin, alanine aminotransferase, lactate dehydrogenase, and fibrinogen. Interleukins-6, -8, and -10 and CXCL10 were significantly higher, while IFN-γ was lower in NAFLD patients. Patients with NAFLD who progressed to critical illness had higher concentrations of IL-6, -8, -10, and IFN-β, and IL-8 and IL-10 appear to be effective prognostic biomarkers associated with time to recovery. In conclusion, NAFLD is associated with distinct cytokine profiles in COVID-19, possibly associated with disease severity and adverse outcomes.

Opisthorchis viverrini infection induces metabolic disturbances in hamsters fed with high fat/high fructose diets: Implications for liver and kidney pathologies

A combination of Opisthorchis viverrini infection and high fat/high fructose diets (HFa/HFr) intake is likely to enhance fatty liver and kidney pathologies. Here we investigated the combined effects of chronic O. viverrini infection and HFa/HFr intake on liver and kidney pathologies, metabolism, and gut microbiome in hamsters. Animals were infected with O. viverrini and fed with either standard chow (OV group) or HFa/HFr diet (OH group) and non–infected hamsters were fed with either standard chow (NC) or HFa/HFr diet (HF) for 8 months. The OH group exhibited dyslipidemia and the highest severity of fatty liver. Tubular damage, inflammatory cell infiltration, and tubular fibrosis were the most prominently observed in this group, supported by increased expression of KIM-1, HMGB-1, and MCP-1. Urinary 1H NMR metabolic profiles revealed that tauro-β-muricholic acid level was increased in the OV and OH groups, whereas metabolites involved in the TCA cycle and gut microbiota-associated metabolites (phenylacetylglycine, trimethylamine, and trimethylamine-N-oxide) were lower in OV, HF and OH groups compared to the NC group. Gut microbial profiles of the OH group were also different from other groups. In conclusion, O. viverrini infection and HFa/HFr diet-induced disturbance of metabolites and gut microbiota associated with concurrent liver and kidney pathologies in hamsters.

The impact of pylorus preservation on the development of nonalcoholic fatty liver disease after pancreaticoduodenectomy: A historical cohort study.

The pathophysiology and associated factors of nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) remain elusive. We aimed to investigate these factors, including the operation type, for NAFLD development after PD. This historical cohort study included 786 consecutive patients treated with either classic Whipple operation or pylorus-preserving pancreaticoduodenectomy (PPPD) in Korea between 2012 and 2018. De novo NAFLD was determined based on hepatic attenuation in nonenhanced computed tomography during follow-up. Of the 786 patients, 216 (27.5%) had a newly developed NAFLD at 2 years after PD. The incidences of newly developed NAFLD at 0.5, 1, 1.5, and 2 years were 13 (1.7%), 41 (5.2%), 48 (6.1%), and 114 (14.5%), respectively. The Whipple group showed a significantly higher incidence of NAFLD than the PPPD group (40.3% vs 24.5%, P < .001). Seventeen patients (2.2%) had severe fatty liver with abnormal liver enzymes. Multivariable analysis revealed that Whipple operation (vs PPPD; adjusted odds ratio [AOR]: 1.92, P < .001) and high preoperative body mass index (vs normal; AOR: 1.71, P=.001) were independently associated with a higher risk of NAFLD. The incidence of NAFLD was 27.5% at 2 years after PD. Undergoing Whipple operation and high preoperative body mass index were significantly associated with de novo NAFLD development.

Is Fatty Liver Associated with Increased Mortality and Morbidity in Coronavirus Disease 2019 (COVID-19) Pneumonia?

BackgroundFatty liver has been shown to be associated with severe COVID-19 disease without any impact on mortality. This is based on heterogenous criteria for defining both fatty liver as well as the severity parameters. This study aimed to study the impact of fatty liver on the mortality and severity of disease in patients with COVID-19 pneumonia.MethodsIn a case control study design, patients with COVID-19 pneumonia (COVID-19 computed tomography severity index [CTSI] on high-resolution computed tomography chest of ≥1) with fatty liver (defined as liver to spleen attenuation index ≤5 on noncontrast computed tomography cuts of upper abdomen) were compared with those without fatty liver. The primary outcome measure was in-hospital mortality, and the secondary outcome measures were CTSI score, need for intensive care unit (ICU) care, need for ventilatory support, duration of ICU stay, and duration of hospital stay.ResultsOf 446 patients with COVID-19 pneumonia, 289 (64.7%)admitted to Max Hospital, Saket, India, between January 1, 2021, and October 30, 2021, had fatty liver. Fifty-nine of 446 patients died during the index admission. In-hospital mortality was not different between patients with fatty liver (38 [13.24%]) or without fatty liver (21 [13.81%]). COVID-19 CTSI score was found to be significantly higher among patients who had fatty liver (13.40 [5.16] vs 11.81 [5.50]; P = 0.003). There was no difference in the requirement of ICU (94 [32%] vs 62 [39.49%]; P = 0.752), requirement of ventilatory support (27 [9.34%] vs 14 [8.91%]; P = 0.385), duration of ICU stay (8.29 [6.87] vs 7.07 [5.71] days; P = 0.208), and duration of hospital stay (10.10 [7.14] vs 10.69 [8.13] days; P = 0.430) between the groups with fatty liver or no fatty liver. Similarly, no difference was found in primary or secondary outcomes measure between the group with severe fatty liver vs mild/moderate or no fatty liver. High total leucocyte count and Fibrosis-4 (FIB-4) index were independently associated with mortality.ConclusionsFatty liver may not be associated with increased mortality or clinical morbidity in patients who have COVID-19 pneumonia.