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In the realm of agriculture and natural resources, medicinal plants stand out as a valuable resource. In recent years, faced with challenges such as predicting climate changes, soil classification, land use, and identifying patterns, there is a growing need for optimal techniques with higher efficiency, particularly in the cultivation of medicinal plants. Therefore, this article introduces the application of data mining to analyze available data in the agriculture and natural resources areas, focusing specifically on the medicinal plant industry. The primary objective is to explore data mining techniques that can enhance various aspects of medicinal plant cultivation, addressing challenges related to climate predictions, soil classification, and optimizing production. The article concludes by presenting the most effective data analysis methods in this domain, accompanied by their corresponding algorithms. Additionally, the aforementioned research is a guide for those intending to investigate the applications of data mining methods are highlighted for increased productivity, encompassing areas such as predicting crop yield, forecasting weather conditions, rainfall patterns, seed and plant conditions, soil quality, and medicinal plant production. The summarization and analysis of the outcome indicated that implementing AI could improve the design and process engineering strategies in bioprocessing fields. [ABSTRACT FROM AUTHOR]

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The rose aphid, Macrosiphum rosae, is one of the most important pests on roses in the world and it causes economic damage. In this study, biology, seasonal population dynamics, and status of natural enemies of the rose aphid were studied. Seasonal population dynamics was studied by randomly sampling 10 shoots every week in two locations of Isfahan, Iran. Rose aphid with a high population density, both in spring (April and May) and in autumn (November), was observed on roses. The results showed that the rose aphid overwinters as parthenogenetic females and nymphs. This aphid migrates to a secondary host, Dipsacus fullonum (Dipsacaceae), in summer due to poor food quality of rose plants. Since sexual form and egg of the rose aphid were not observed in Isfahan, it is probably anholocyclic species with host alternation in this area. Natural enemies of the rose aphid include four species of Coccinellidae, three species of Syrphidae, two species of Chamaemyiidae, one species of Chrysopidae, a few species of Anthocoridae and Miridae, and one species of Cantharidae. One species of ectoparasite mite of Erythraeidae was also collected. In addition, four species of parasitoid wasps, Braconidae, were collected.

Background: Following a plant-based diet is associated with a wide range of health benefits. The current study aimed to investigate the association between plant-based diet indices, specifically the plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) and risk of mortality in cirrhotic patients., Methods: This cohort study included a total of 121 patients with cirrhosis, who were followed for four years. Plant-based diet indices were calculated based on a validated semi-quantitative food frequency questionnaire consisting of 168 items. The Hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were estimated using the Cox proportional risk models., Results: During 414 person-year of follow-up, 43 deaths (7 women, 36 men) were documented. After adjusting all confounders, it has been found that the PDI (HR T3 vs. T1 = 0.16, 95% CI = 0.03-0.89, P trend = 0.024) and hPDI (HR T3 vs. T1 = 0.04, 95% CI = 0.02-0.61, P trend = 0.020) were inversely associated with the risk of mortality. While uPDI was directly associated with a significant increase in mortality risk (HR T3 vs. T1 = 8.74, 95% CI = 0.33-17.14, P trend = 0.018). The 4-year survival rate among patients showed a significant relationship with all three indices., Conclusions: Our findings highlight that higher scores of PDI and hPDI can significantly reduce the risk of mortality in patients with cirrhosis, while a significant increase in mortality risk was found in those with higher uPDI. However, confirmation of these findings requires further studies., (© 2024. The Author(s).)

Portal vein thrombosis (PVT) is a common thrombotic complication of cirrhosis. It can lead to variceal bleeding and bowel ischemia and also complicate liver transplantation. Identifying the possible risk factors associated with PVT can aid in identifying patients at high risk, enabling their screening and potentially preventing PVT through the rational use of anticoagulants. This study focuses on examining the clinical characteristics of PVT in cirrhotic patients and identifying the clinical and biochemical factors that are linked to the development of PVT. Consecutive hospitalized cirrhotic patients between 2015 and 2023 were identified through the hospital's computerized medical records based on the Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding system and retrospectively analyzed. 928 individuals were included in this study; 783 (84.3%) without PVT and 145 (15.7%) with benign PVT. Hepatitis B virus (HBV) was significantly more common in the PVT group (P-value = .02), while alcohol and primary sclerosing cholangitis (PSC) were less common in this group (P-value = .01 and .02, respectively). Hepatocellular carcinoma (HCC) (P-value < .01), ascites (P-value = .01), and spontaneous bacterial peritonitis (SBP) (P-value = .02) were more common in the PVT group. Patients with PVT had a higher international normalized ratio (INR) level (P-value = .042) and lower plasma albumin (P-value = .01). No differences were identified in white blood cell, hemoglobin, platelet, and bilirubin levels. However, patients with PVT had higher model for end-stage liver disease (MELD) (P-value = .01) and Child-Pugh scores (P-value = .03). This study demonstrated a higher likelihood of PVT presence in cirrhotic patients with advanced age, HBV, and HCC, along with ascites, SBP, splenomegaly, hypoalbuminemia, elevated INR, and a higher MELD score. Nevertheless, additional research endeavors are necessary to accurately ascertain and validate supplementary risk factors within a broader demographic., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Dietary intake has an undeniable role in the development and progression as well as the prevention and treatment of cirrhosis. This study was conducted with the aim of investigating the association between dietary inflammatory indices and total mortality in patients with cirrhosis. A total of 166 outpatients with cirrhosis who were diagnosed within the last 6 months were followed up for 48 months in this cohort study. A 168-question valid food frequency questionnaire was used to evaluate dietary intake. Accordingly, the dietary inflammatory index (DII), empirical dietary inflammatory pattern (EDIP) and dietary inflammatory score (DIS) were calculated. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through cox proportional hazards regression models for an association of cirrhosis mortality and three dietary inflammatory indices. After full adjustment for confounders, the results showed that mortality risk increased significantly with increasing dietary inflammatory indices. Compared to the first tertile, the risk of mortality due to cirrhosis was associated with 4.8 times increase in the third tertile of DII (HR = 4.8, 95% CI = 1.1-19.8, p trend = 0.029), 3.3 times in the third tertile of EDIP (HR = 3.3, 95% CI = 1.3-8, p trend = 0.004), and 2.2 times increased in the third tertile of DIS (HR = 2.2, 95% CI = 1-4.7, p trend = 0.032). The results of the present study indicated a significant association between dietary inflammatory indices and total mortality among patients with cirrhosis. Additional research is necessary to confirm our findings., (© 2024. The Author(s).)

Liver Cirrhosis, defined as the final stage of chronic liver disease, may become more prevalent in the lower level of body defense against oxidation and inflammation. Therefore, we assessed the association of dietary total antioxidant capacity (DTAC) with the severity and mortality of cirrhosis in a cohort study. 120 newly diagnosed cirrhosis patients from Tehran, Iran, participated in this study. The patients' habitual diet was assessed using a 168-item validated food frequency questionnaire. Both ferric-reducing antioxidant potential (FRAP) and oxygen radical scavenging capacity (ORAC) methods were computed to achieve DTAC scores. The association between DTAC with disease severity and mortality was estimated by multivariate linear regression and cox proportional hazards regression models. Dietary total antioxidant capacity-ORAC had a significant inverse association with disease severity in both crude and adjusted models ( P for trend: <0.001 and 0.016 respectively). The risk of mortality in the first and second tertiles of ORAC was 5.56 (95 % CI: 2.25-13.75; P = 0.002) and 3.20 (95 % CI: 1.25-8.19; P = 0.015) higher than those in the third category, respectively. In conclusion, a higher antioxidant capacity of diet is associated with less disease severity and mortality risk in cirrhosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Purpose: The relationship between dietary patterns and cirrhosis is undeniable. The present study aimed to investigate the association between the Dietary Approaches to Stop Hypertension (DASH) diet and the risk of mortality in patients with cirrhosis prospectively., Methods: In this cohort study, 121 cirrhotic patients were enrolled and followed up annually for four years. Nutritional status and dietary intakes were assessed initially, and the DASH score was calculated accordingly. Crude and multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazard analyses., Results: DASH components including fruits, vegetables, legumes, nuts and seeds, and low-fat dairy products were significantly associated with lower mortality risk in cirrhotic patients. Also, a higher DASH score was significantly associated with a reduction in the risk of mortality in patients with cirrhosis, so that after adjusting for all confounders, the risk of mortality in the upper tertile was 89% lower than the first tertile (HR = 0.11, 95% CI: 0.03-0.42, P trend < 0.001). The 4-year survival rate among patients across tertiles of DASH was 32%, 37%, and 46%, respectively (P = 0.005)., Conclusion: It can be concluded that a higher DASH diet score may be associated with a reduced risk of mortality in cirrhotic patients. However, larger studies are needed to confirm the findings and determine their potential mechanisms., (© 2024. The Author(s).)

This study investigated batch-fed vermicomposting of cow manure, with a specific focus on assessing the effects of tylosin on the weight of earthworms and the overall quality of the resulting manure. Five reactors, including three concentrations of tylosin (50, 100, and 150 mg/kg) and two control reactors, were employed. Residual tylosin concentrations were measured using high-performance liquid chromatography (HPLC). Quality parameters such as pH, temperature, volatile solids (VS), organic carbon content (OCC), electrical conductivity (EC), ash content, C/N ratio, total Kjeldahl nitrogen (TKN), and microbial content were evaluated. The toxicity and maturity of vermicompost were assessed by determining the germination index (GI). The study also monitored variations in the earthworm's weight. The results demonstrated a decreasing trend in VS, OCC, C/N, and fecal coliforms, along with increased pH, EC, ash content, and TKN during the vermicomposting process. Furthermore, investigations revealed significant reductions in the reactors with tylosin concentrations of 50, 100, and 150 mg/kg, resulting in the removal of 98%, 90.48%, and 89.38% of the initial tylosin, respectively. This result confirms the faster removal of tylosin in reactors with lower concentrations. Degradation of tylosin also conforms to first-order kinetics. The findings showed a significant influence of tylosin on the weight of Eisenia fetida earthworms and the lowest antibiotic concentration led to the highest weight gain. Finally, the high percentage of germination index (90-100%) showed that the quality and maturity of vermicompost is by national and international standards., (© 2024. The Author(s).)

Background: Non-alcoholic fatty liver disease (NAFLD) accounts as a crucial health concern with a huge burden on health and economic systems. The aim of this study is to evaluate the effect of soy isoflavones supplementation on metabolic status in patients with NAFLD., Methods: In this randomized clinical trial, 50 patients with NAFLD were randomly allocated to either soy isoflavone or placebo groups for 12 weeks. The soy isoflavone group took 100 mg/d soy isoflavone and the placebo group took the similar tablets containing starch. Anthropometric indices, blood lipids, glycemic parameters and blood pressure were measured at the beginning and at the end of the study., Results: At the end of week 12 the level of serum triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TC) was significantly decreased only in soy isoflavone group compared to baseline (P < 0.05). Although waist circumference (WC) decreased significantly in both groups after 12 weeks of intervention (P < 0.05), hip circumference (HC) decreased significantly only in soy isoflavone group (P = 0.001). No significant changes observed regarding high density lipoprotein (HDL) and blood pressure in both groups. At the end of the study, serum glucose level was significantly decreased in the placebo group compared to baseline (P = 0.047). No significant changes demonstrated in the soy isoflavone group in regard to glycemic parameters (P > 0.05)., Conclusions: This study revealed that soy isoflavones could significantly reduce TG, LDL TC, WC and HC in NAFLD patients., Trial Registration: The Ethics committee of Ahvaz Jundishapur University of Medical Sciences approved the protocol of the present clinical research (IR.AJUMS.REC.1401.155). The study was in accordance with the Declaration of Helsinki. This study's registered number and date are IRCT20220801055597N1 and 20.09.2022, respectively at https://fa.irct.ir ., (© 2024. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases, affecting more than one-quarter of people worldwide. Hepatic steatosis can progress to more severe forms of NAFLD, including NASH and cirrhosis. It also may develop secondary diseases such as diabetes and cardiovascular disease. Genetic and environmental factors regulate NAFLD incidence and progression, making it a complex disease. The contribution of various environmental risk factors, such as type 2 diabetes, obesity, hyperlipidemia, diet, and sedentary lifestyle, to the exacerbation of liver injury is highly understood. Nevertheless, the underlying mechanisms of genetic variations in the NAFLD occurrence or its deterioration still need to be clarified. Hence, understanding the genetic susceptibility to NAFLD is essential for controlling the course of the disease. The current review discusses genetics' role in the pathological pathways of NAFLD, including lipid and glucose metabolism, insulin resistance, cellular stresses, and immune responses. Additionally, it explains the role of the genetic components in the induction and progression of NAFLD in lean individuals. Finally, it highlights the utility of genetic knowledge in precision medicine for the early diagnosis and treatment of NAFLD patients., (© 2024. The Author(s).)

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Subjects were randomized to either receive two tablets of soy isoflavone (100 mg/day) or placebo. At week 12, the serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and controlled attenuation parameter (CAP) score were significantly decreased only in the soy isoflavone group (P < 0.05). A significant decline in the gamma glutamyl transferase (GGT) level was observed only in the placebo group (P = 0.017). A significant increase in the serum level of fetuin A was shown in both groups at the end of the trial with a significantly greater increment in the soy isoflavone group compared to the placebo group (P < 0.05). The changes in the serum level of FGF-21 were not significant in any of the two groups. Steatosis grade significantly improved only in the soy isoflavone group (P = 0.045). There was no significant change in the fibrosis grade in the groups. Soy isoflavone intake led to a decrease in ALT, AST, CAP score, steatosis grade and an increase in the level of fetuin A. However, no significant changes were observed in the fibrosis grade and serum levels of GGT and FGF-21., (© 2024. The Author(s).)

As a global health concern, cirrhosis contributes significantly to morbidity and mortality. This prospective cohort study aimed to investigate the association between dietary acid load (DAL) and cirrhosis-related mortality. Present study was conducted on 121 patients with newly diagnosed cirrhosis who were followed up for 48 months. Anthropometric measures, nutritional status and dietary intakes were assessed and DAL was estimated based on potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. Crude and multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazard analyses. Participants in the high PRAL and NEAP scores had significantly higher intakes of grains and lower intakes of fruits and vegetables. Also, the intake of dairy products and legumes, nuts and seeds decreased significantly with increasing NEAP score. After adjustment of all the confounders, the risk of mortality in the second and third tertiles of PRAL was 5.9 times and 10.97 higher than those in the first tertile, respectively (P trend: 0.006). Similarly, comparing the risk of mortality in the second and third tertiles with the first tertile of NEAP showed a 4.46-fold and 12.3-fold increased risk, respectively (P trend: 0.010). Our findings suggested that DAL was significantly associated with cirrhosis-related mortality and highlight the need for further research to understand the underlying mechanisms and establish optimal DAL levels in cirrhotic patients., (© 2024. The Author(s).)

End-stage of liver fibrosis as a precancerous state could lead to cirrhosis and hepatocellular carcinoma which liver transplantation is the only effective treatment. Previous studies have indicated that farnesoid X receptor (FXR) agonists, such as obeticholic acid (OCA) protect against hepatic injuries. However, free OCA administration results in side effects in clinical trials that could be alleviated by applying bio carriers such as MSC-derived exosomes (Exo) with the potential to mimic the biological regenerative effect of their parent cells, as proposed in this study. Loading OCA into the Exo was conducted via water bath sonication. Ex vivo bio distribution studies validated the Exo-loaded OCA more permanently accumulated in the liver. Using CCL4-induced liver fibrosis, we proposed whether Exo isolated from human Warton's Jelly mesenchymal stem cells loaded with a minimal dosage of OCA can facilitate liver recovery. Notably, Exo-loaded OCA exerted additive anti-fibrotic efficacy on histopathological features in CCL4-induced fibrotic mice. Compared to baseline, Exo-mediated delivery OCA results in marked improvements in the fibrotic-related indicators as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Accordingly, the synergistic impact of Exo-loaded OCA as a promising approach is associated with the inactivation of hepatic stellate cells (HSCs), extracellular matrix (ECM) remodeling, and Fxr-Cyp7a1 cascade on CCL4-induced liver fibrosis mice. In conclusion, our data confirmed the additive protective effects of Exo-loaded OCA in fibrotic mice, which suggests a valuable therapeutic strategy to combat liver fibrosis. Furthermore, the use of Exo for accurate drug delivery to the liver tissue can be inspiring., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Chronic liver diseases, especially cirrhosis, are associated with significant morbidity and mortality. Besides predisposing to chronic liver disease per se, diabetes, hypertension, and dyslipidemia worsen the prognosis of patients with cirrhosis induced by other causes. There is no standard of care in the management of these factors in patients with cirrhosis. Also, in particular, it is not known whether nutritional interventions in the modification of cardiometabolic factors can improve the course of cirrhosis or not. This narrative review aimed to investigate the clinical significance of diabetes, hypertension, and dyslipidemia and appropriate nutritional interventions in cirrhotic patients. A comprehensive literature search of the published data was performed in regard to the association of cirrhosis with cardiometabolic factors and the management of cirrhosis and its complications. There is limited evidence on the association of cirrhosis with cardiometabolic risk factors. Cirrhotic cardiometabolic abnormalities are associated with an increased risk of complications, such that the coexistence of diabetes, hypertension, and dyslipidemia increases the risk of clinical decompensation in cirrhosis. Dietary management of cirrhotic patients with risk factors such as diabetes, hypertension, or dyslipidemia does not seem to be considerably different from non-cirrhotic patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Gut microbiota dysbiosis is intimately associated with development of non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Nevertheless, the gut microbial community during the course of NAFLD and NASH is yet to be comprehensively profiled. This study evaluated alterations in fecal microbiota composition in Iranian patients with NAFLD and NASH compared with healthy individuals. This cross-sectional study enrolled 15 NAFLD, 15 NASH patients, and 20 healthy controls, and their clinical parameters were examined. The taxonomic composition of the fecal microbiota was determined by sequencing the V3-V4 region of 16S rRNA genes of stool samples. Compared to the healthy controls, NAFLD and NASH patients presented reduced bacterial diversity and richness. We noticed a reduction in the relative abundance of Bacteroidota and a promotion in the relative abundance of Proteobacteria in NAFLD and NASH patients. L-histidine degradation I pathway, pyridoxal 5'-phosphate biosynthesis I pathway, and superpathway of pyridoxal 5'-phosphate biosynthesis and salvage were more abundant in NAFLD patients than in healthy individuals. This study examined fecal microbiota dysbiosis in NAFLD and NASH patients and presented consistent results to European countries. These condition- and ethnicity-specific data could provide different diagnostic signatures and therapeutic targets., (© 2023. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) has recently emerged as a major public health concern worldwide due to its rapidly rising prevalence and its potential to progress into end-stage liver disease. While the precise pathophysiology underlying NAFLD remains incompletely understood, it is strongly associated with various environmental triggers and other metabolic disorders. Epigenetics examines changes in gene expression that are not caused by alterations in the DNA sequence itself. There is accumulating evidence that epigenetics plays a key role in linking environmental cues to the onset and progression of NAFLD. Our understanding of how epigenetic mechanisms contribute to NAFLD pathophysiology has expanded considerably in recent years as research on the epigenetics of NAFLD has developed. This review summarizes recent insights into major epigenetic processes that have been implicated in NAFLD pathogenesis including DNA methylation, histone acetylation, and microRNAs that have emerged as promising targets for further investigation. Elucidating epigenetic mechanisms in NAFLD may uncover novel diagnostic biomarkers and therapeutic targets for this disease. However, many questions have remained unanswered regarding how epigenetics promotes NAFLD onset and progression. Additional studies are needed to further characterize the epigenetic landscape of NAFLD and validate the potential of epigenetic markers as clinical tools. Nevertheless, an enhanced understanding of the epigenetic underpinnings of NAFLD promises to provide key insights into disease mechanisms and pave the way for novel prognostic and therapeutic approaches., Competing Interests: Declaration of Competing Interest All authors declare no potential competing interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objectives: Improving the oral health of the elderly is crucial to improving their general health and quality of life. To reach this goal, it is necessary to start with a comprehensive oral health assessment and a detailed treatment plan. The aim of this study was, therefore, to develop a comprehensive Oral Health Assessment Tool for the geriatric population., Material and Methods: Following a panel of experts' consultation, a clinical form and a self-assessment questionnaire were developed, encompassing eight domains: dental caries, periodontal diseases, partial and complete edentulism, oral soft tissue lesions, occlusion, xerostomia, temporomandibular joints, and oral or oral prostheses hygiene. Subsequently, a pilot study was conducted to appraise the clinical form and questionnaire involving 84 residents of an Iranian nursing home. After securing ethics approval, both the qualitative and quantitative aspects of the self-assessment questions' validity and reliability were assessed, and specificity and sensitivity were calculated., Results: The mean age of the participants was 69.8 (±4.1) years, and 86% had less than 12 years of education. The questions regarding the number of remaining teeth and the number of decayed teeth had the highest sensitivity (97% and 88%), respectively. Questions regarding the presence of periodontitis and gingivitis had the highest specificity (both 100%)., Conclusions: A Comprehensive Geriatric Oral Health Assessment Tool has been developed and its validity and reliability evaluated in a pilot study. It should now be further evaluated in larger studies., (© 2023 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Liver fibrosis is characterized by the excessive deposition and accumulation of extracellular matrix components, mainly collagens, and occurs in response to a broad spectrum of triggers with different etiologies. Under stress conditions, autophagy serves as a highly conserved homeostatic system for cell survival and is importantly involved in various biological processes. Transforming growth factor-β1 (TGF-β1) has emerged as a central cytokine in hepatic stellate cell (HSC) activation and is the main mediator of liver fibrosis. A growing body of evidence from preclinical and clinical studies suggests that TGF-β1 regulates autophagy, a process that affects various essential (patho)physiological aspects related to liver fibrosis. This review comprehensively highlights recent advances in our understanding of cellular and molecular mechanisms of autophagy, its regulation by TGF-β, and the implication of autophagy in the pathogenesis of progressive liver disorders. Moreover, we evaluated crosstalk between autophagy and TGF-β1 signalling and discussed whether simultaneous inhibition of these pathways could represent a novel approach to improve the efficacy of anti-fibrotic therapy in the treatment of liver fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Liver cirrhosis is a worldwide burden and is associated with poor clinical outcomes, including increased mortality. The beneficial effects of dietary modifications in reducing morbidity and mortality are inevitable., Aim: The current study aimed to evaluate the potential association of dietary protein intake with the cirrhosis-related mortality., Methods: In this cohort study, 121 ambulatory cirrhotic patients with at least 6 months of cirrhosis diagnosis were followed-up for 48 months. A 168-item validated food frequency questionnaire was used for dietary intake assessment. Total dietary protein was classified as dairy, vegetable and animal protein. We estimated crude and multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), applying Cox proportional hazard analyses., Results: After full adjustment for confounders, analyses showed that total (HR = 0.38, 95% CI = 0.2-1.1, p trend = 0.045) and dairy (HR = 0.38, 95% CI = 0.13-1.1, p trend = 0.046) protein intake was associated with a 62% lower risk of cirrhosis-related mortality. While a higher intake of animal protein was associated with a 3.8-fold increase in the risk of mortality in patients (HR = 3.8, 95% CI = 1.7-8.2, p trend = 0.035). Higher intake of vegetable protein was inversely but not significantly associated with mortality risk., Conclusion: A comprehensive evaluation of the associations of dietary protein intake with cirrhosis-related mortality indicated that a higher intakes of total and dairy protein and a lower intakes of animal protein are associated with a reduced risk of mortality in cirrhotic patients., (© 2023. The Author(s).)

Liver fibrosis is the excessive accumulation of extracellular matrix proteins. Due to the lack of an accurate test for an early diagnosis of liver fibrosis and the invasiveness of the liver biopsy procedure, there is an urgent need for effective non-invasive biomarkers for screening the patients. we aimed to evaluate the diagnostic performance of circulating miRNAs (miR-146b, -194, -214) and their related mechanisms in the pathogenesis of liver fibrosis. The expression levels of miR-146b, -194, and -214 were quantified in whole blood samples from NAFLD patients using real-time PCR. The competing endogenous RNA (ceRNA) network was constructed and a gene set enrichment analysis (GSEA) was performed for HSC activation-related genes. Also, the transcription factor (TF)-miR co-regulatory network and the survival plot for three miRNAs and core genes were illustrated. The qPCR results showed that the relative expression of miR-146b and miR-214 significantly increased in NAFLD patients, while miR-194 showed significant down-regulation. The ceRNA network analysis implicated NEAT1 and XIST as sponge candidates for these miRNAs. The GSEA results identified 15 core genes involved in HSC activation, primarily enriched in NF-κB activation and autophagy pathways. STAT3, TCF3, RELA, and RUNX1 were considered potential transcription factors connected to miRNAs in the TF-miR network. Our study elucidated three candidate circulating miRNAs differentially expressed in NAFLD that could serve as a promising non-invasive diagnostic tool for early detection strategies. Also, NF-κB activation, autophagy, and negative regulation of the apoptotic process are the main potential underlying mechanisms regulated by these miRNAs in liver fibrosis pathogenesis., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors.)

Liver fibrosis is a significant cause of morbidity and mortality without approved treatment. The therapeutic effects of Imatinib as a tyrosine kinase inhibitor on reversing liver fibrosis have already been shown. However, considering the conventional route of Imatinib administration, the amount of drug to be used is very high, and its side effects are raised. Therefore, we designed an efficient pH-sensitive polymer for the targeted delivery of Imatinib in treating a carbon tetrachloride (CCl4)-induced liver fibrosis. This nanotherapeutic system-based Vitamin A (VA)-modified Imatinib-loaded poly (lactic-co-glycolic acid)/Eudragit S100 (PLGA-ES100) has been successfully fabricated by adapting the solvent evaporation technique. The applying ES100 on the surface of our desired nanoparticles (NPs) protects drug release at the acidic pH of the gastric and guarantees the effective release of Imatinib at a higher pH of the intestine. Besides, VA-functionalized NPs could be an ideal efficient drug delivery system due to the high capacity of hepatic cell lines to absorb VA. For induction of liver fibrosis, CCL4 was intraperitoneally (IP) injected twice a week for six weeks in BALB/c mice. Oral administration of VA-targeted PLGA-ES100 NPs loaded with Rhodamine Red™ by live animal imaging showed a preferential accumulation of the selected NPs in the liver of mice. Besides, administrating targeted Imatinib-loaded NPs significantly decreased serum levels of ALT, and AST, and also reduced the expression of extracellular matrix components, including collagen I, collagen III, and α-SMA, considerably. Interestingly, histopathological evaluation of liver tissues through H&E and Masson's trichrome staining showed that oral administration of targeted Imatinib-loaded NPs reduced hepatic damage by enhancing hepatic structure condition. Also, the Sirius-red staining indicated a reduction in collagen expression during treatment with targeted NP containing Imatinib. The immunohistochemistry result on liver tissue shows a significant decrease in the expression of α-SMA in groups treated with targeted NP. In the meantime, administration of a very scarce dose of Imatinib via targeted NP caused a substantial decline in the expression of fibrosis marker genes (Collagen I, Collagen III, α-SMA). Our results confirmed that novel pH-sensitive VA-targeted PLGA-ES100 NPs could efficiently deliver Imatinib to the liver cells. Loading Imatinib in the PLGA-ES100/VA might overcome many challenges facing conventional Imatinib therapy, including gastrointestinal pH, the low concentration at the target region, and toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Liver fibrosis is a significant challenge to global health that results in organ failure through inflammation and the release of fibrotic biomarkers. Due to the lack of effective treatments for liver fibrosis, anti-fibrotic and anti-inflammatory therapies are being developed. Since there has been an association between aberrant expression of miR-124 and liver disease progression, we investigated whether delivery of miR-124 through human Wharton's jelly mesenchymal stem cells derived-exosomes (hWJMSC-Exo) can improve liver fibrosis., Methods: We established a 6-week carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis, then we administered hWJMSC-Exo and miR-124-3p-enriched exosomes (ExomiR-124) for three weeks. The extent of fibrosis and inflammation was assessed by histology, biochemistry, Real-time PCR, immunohistochemistry, and Enzyme-linked immunoassays (ELISA). The inflammatory status of the spleen was also investigated using flow cytometry., Results: Based on the gene and protein expression measurement of IL-6, IL-17, TGF-β, STAT3, α-SMA, and COL1, In vivo administration of Exo and ExomiR-124 effectively reduce collagen accumulation and inhibition of inflammation. Regarding histopathology findings, the therapeutic effect of ExomiR-124 against liver fibrosis was significantly greater than hWJMSC-Exo. In addition, we found that Exo and ExomiR-124 was capable of phenotype switching of splenic monocytes from inflammatory Ly6C hi to restorative Ly6C lo ., Conclusions: MSC-derived exosomes demonstrated anti-inflammatory effect via different aspects. Aside from the therapeutic approach, enrichment of exosomes as a nanocarrier by miR-124 revealed the down-regulation of STAT3, which plays a crucial role in liver fibrosis. The anti-inflammatory and anti-fibrotic properties of ExomiR-124 could be a promising option in liver fibrosis combination therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Non-Alcoholic fatty liver disease is characterized by the accumulation of excess fat in the liver, chronic inflammation, and cell death, ranging from simple steatosis to fibrosis, and finally leads to cirrhosis and hepatocellular carcinoma. The effect of Fibroblast growth factor 2 on apoptosis and ER stress inhibition has been investigated in many studies. In this study, we aimed to investigate the effect of FGF2 on the NAFLD in-vitro model in the HepG2 cell line., Methods: The in-vitro NAFLD model was first induced on the HepG2 cell line using oleic acid and palmitic acid for 24 h and evaluated by ORO staining and Real-time PCR. The cell line was then treated with various concentrations of fibroblast growth factor 2 for 24 h, total RNA was extracted and cDNA was consequently synthesized. Real-time PCR and flow cytometry was applied to evaluate gene expression and apoptosis rate, respectively., Results: It was shown that fibroblast growth factor 2 ameliorated apoptosis in the NAFLD in-vitro model by reducing the expression of genes involved in the intrinsic apoptosis pathway, including caspase 3 and 9. Moreover, endoplasmic reticulum stress was decreased following upregulating the protective ER-stress genes, including SOD1 and PPARα., Conclusions: FGF2 significantly reduced ER stress and intrinsic apoptosis pathway. Our data suggest that FGF2 treatment could be a potential therapeutic strategy for NAFLD., (© 2023. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)

The activation of hepatic stellate cells is the primary function of facilitating liver fibrosis. Interfering with the coordinators of different signaling pathways in activated hepatic stellate cells (aHSCs) could be a potential approach in ameliorating liver fibrosis. Regarding the illustrated anti-fibrotic effect of imatinib in liver fibrosis, we investigated the imatinib's potential role in inhibiting HSC activation through miR-124 and its interference with the STAT3/hepatic leukemia factor (HLF)/IL-6 circuit. The anti-fibrotic effect of imatinib was investigated in the LX-2 cell line and carbon tetrachloride (CCl 4 )-induced Sprague-Dawley rat. The expression of IL-6, STAT3, HLF, miR-124, and α-smooth muscle actin (α-SMA) were quantified by quantitative real-time PCR (qRT-PCR) and the protein level of α-SMA and STAT3 was measured by western blot analysis both in vitro and in vivo. The LX-2 cells were subjected to immunocytochemistry (ICC) for α-SMA expression. After administering imatinib in the liver fibrosis model, histopathological examinations were done, and hepatic function serum markers were checked. Imatinib administration alleviated mentioned liver fibrosis markers. The expression of miR-124 was downregulated, while IL-6/HLF/STAT3 circuit agents were upregulated in vitro and in vivo. Notably, imatinib intervention decreased the expression of IL-6, STAT3, and HLF. Elevated expression of miR-124 suppressed the expression of STAT3 and further inhibited HSCs activation. Our results demonstrated that imatinib not only ameliorated hepatic fibrosis through tyrosine kinase inhibitor (TKI) activity but also interfered with the miR-124 and STAT3/HLF/IL-6 pathway. Considering the important role of miR-124 in regulating liver fibrosis and HSCs activation, imatinib may exert its anti-fibrotic activity through miR-124., (© 2023 International Federation for Cell Biology.)

Introduction: Liver cirrhosis is a chronic condition caused by different conditions including viral infection, alcoholism, and autoimmune disorders. Malnutrition is one of the complications of liver cirrhosis that is associated with poor outcomes. This study aimed to determine the association of malnutrition with mortality in liver cirrhosis patients., Methods: This prospective cross-sectional study was conducted on liver cirrhosis patients who were referred to two referral centers for liver disease in Tehran, Iran. Patients' information including demographics (age, gender, etiology of cirrhosis, alcohol and smoking history) in addition to triceps skinfold (TSF), mid-arm circumference (MAC), Child-Pugh score and Model for End-Stage Liver Disease (MELD) score were recorded in all patients. Patients were classified into A, B, and C categories based on the Subjective Global Assessment (SGA) questionnaire., Results: Among 121 participants (68.6%) were males and the mean age was 54.78. Viral infections were the most common etiology and 65 patients (56.2%) were in the classification A of Child-Pugh Score. TSF (P = 0.001) and MAC (P = 0.003) were significantly lower in SGA class C. The survival rate in SGA class C was significantly lower than other groups (P < 0.001; log-rank test). The risk of mortality in patients with SGA class A and B was 85% (HR value: 0.15; 95% CI: 0.02-0.87; P = 0.03) and 76% (HR value: 0.24; 95% CI: 0.06-0.83; P = 0.02) lower than those with SGA class C., Conclusion: Anthropometric and SGA measure are two easy and accessible methods for assessing malnutrition and mortality in liver cirrhosis patients., Competing Interests: Declaration of competing interest No conflict of interest was declared by the authors., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Non-alcoholic steatohepatitis (NASH) is associated with intrahepatic lipid accumulation, inflammation, and hepatocyte death. Several studies have indicated that high-fat diets increase ceramide synthases-6 (CerS-6) expression and a concomitant elevation of C16-ceramides, which can modulate endoplasmic reticulum (ER) stress and further contribute to the progression of NASH. Ceramide levels have reportedly been impacted by basic fibroblast growth factor (bFGF) in various diseases. This study looked into the role of bFGF on CerS6/C16-ceramide and ER stress-related pathways in a mouse model of NASH. Male C57BL/6J mice were fed a western diet (WD) combined with carbon tetrachloride (CCl4) for eight weeks. Next, bFGF was injected into the NASH mice for seven days of continuous treatment. The effects of bFGF on NASH endpoints (including steatosis, inflammation, ballooning, and fibrosis), ceramide levels and ER-stress-induced inflammation, reactive oxygen species (ROS) production, and apoptosis were evaluated. Treatment with bFGF significantly reduced CerS-6/C16-ceramide. Further, the inflammatory condition was alleviated with reduction of nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) gene expression. ROS level was also reduced. ER stress-related cell death diminished by reducing C/EBP homologous protein (CHOP) mRNA expression and caspase 3 activity. Furthermore, activation of the hepatic stellate cells was inhibited in the bFGF-treated mice by lowering the amount of alpha-smooth muscle actin (α-SMA) at the mRNA and protein level. According to our findings, CerS-6/C16-ceramide alteration impacts ER stress-mediated inflammation, oxidative stress, and apoptosis. The bFGF treatment effectively attenuated the development of NASH by downregulating CerS-6/C16-ceramide and subsequent ER stress-related pathways., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease which is associated with Inflammatory Bowel Disease (IBD) in 70% of cases. It seems PSC/IBD is a distinct phenotype that is different from PSC, and IBD alone. Hence, we review the epidemiology, pathogenesis, natural course and management of PSC/IBD before and after LT for PSC. Extensive colitis, rectal sparing, backwash ileitis, and mild symptoms are the characteristics of IBD coexisting with PSC. Moreover, PSC patients with concurrent IBD have higher risk of cholangiocarcinoma, and colorectal neoplasia predominantly in right colon and at younger age. Therefore, it is essential to monitor these individuals continuously. It is interesting to note that the course of IBD (ulcerative colitis) after liver transplantation (LT) for PSC varies greatly, and some patients may develop worsening colitis after LT despite immunosuppressive regimens. As well, management of these patients was discussed in this review., Competing Interests: There is no conflict of interest for authors of this article., (© 2023, Gastroenterology and Hepatology From Bed to Bench (GHFBB).)

Liver fibrosis is a disorder in which inflammatory reactions play an important role, and central to the progression and pathogenesis of this disease are the immune-specific cells known as macrophages. Macrophage types are distinguished from each other by the expression of a series of surface markers. STAT6 and Arg1 play an important role in the polarization of macrophages, so these two factors are downstream of interleukin 4 (IL-4) and IL-13 cytokines and cause to differentiate M2. Therefore, this study aimed to compare the independent effects of imatinib and mesenchymal cell treatment on the polarization of macrophages in rat models of liver fibrosis. The liver fibrosis was induced by the injection of CCL4 for 6 weeks in Sprague-Dawley rats. Then, rats were divided into four different groups, and the effects of imatinib and mesenchymal cells on the expression of Arg1, Ly6c, and STAT6 were evaluated. Histopathology experiments considered the amelioration effect of treatments. Our results showed that Arg1 expression was significantly increased in the groups treated with mesenchymal cells and imatinib compared to the control group. On the other hand, expression of STAT6 was significantly increased in the imatinib-treated mice compared to mesenchymal and control groups. Moreover, the expression of LY6C significantly decreased in imatinib and mesenchymal treated groups compared to the control group. Therefore, our data showed that mesenchymal stem cells and imatinib significantly modulate the fibrotic process in rat models of fibrosis, probably by polarizing macrophages towards an anti-inflammatory profile and increasing the frequency of these cells in liver tissue., (© 2022 International Federation for Cell Biology.)

Aim: To evaluate the effects of N-acetylcysteine (NAC) supplementation in cirrhotic patients., Background: Chronic hepatic inflammation leads to fibrosis and cirrhosis through various mechanisms such as oxidative stress. NAC is one of the intracellular precursors of glutathione that can degrade most reactive oxygen species. Recently, the beneficial effects of NAC in animal and human studies on preventing liver injury progression and improving liver function have been examined. However, more studies on human subjects are still required., Methods: Well-known cirrhotic patients with a specific etiology and aged 18 to 70 years who referred to the gastrointestinal clinic of Ayatollah Taleghani Hospital from December 2018 to December 2019 were enrolled in the present randomized double-blind controlled trial. Patients in the intervention group received NAC tablets at a dose of 600 mg daily, and the control group received a placebo. Demographic data, medical characteristics, and Child-Pugh and MELD scores evaluated at baseline and after 6 months., Results: Totally, 60 patients completed the present study (30 patients in the intervention group, and 30 patients in the control group). Hematological and biochemical parameters were normal in both groups with no significant differences at baseline and 6 months after intervention values. Moreover, the renal function indicators including serum creatinine (Cr) and urea (BUN) decreased significantly after intervention. Hepatic parameters also decreased significantly 6 months after intervention. Decreases in the renal and hepatic parameters 6 months after baseline in the control group were not statistically significant., Conclusion: The results of this study showed that NAC improved hepatic and renal function by decreasing serum urea and creatinine levels but had no significant effect on hematological and biochemical parameters. Furthermore, NAC significantly improved hepatic profiles by decreasing ALT, AST, and ALP in the liver enzymes between the intervention and control groups. Moreover, NAC caused a significant decrease in Child-Pugh and MELD scores., Competing Interests: The authors declare that they have no conflict of interest., (© 2023, Gastroenterology and Hepatology From Bed to Bench (GHFBB).)

Since conducting a long-term randomised clinical trial is not logical and feasible to find the optimum dosage of salt intake in patients with cirrhosis, cohort studies are the best design to assess the long-term effects of dietary salt on the survival of cirrhotic patients. This cohort study aimed to evaluate the association between dietary intake of salt and mortality risk in cirrhotic patients. The present study was designed as a cohort in three referral hospitals in Iran in 2018. One hundred and twenty-one patients aged between 20 and 70 years with established cirrhosis were recruited. Dietary intakes, demographic data and disease severity were evaluated at the baseline. Participants were followed up annually. Crude survival was greater in patients with low-to-moderate salt consumption rather than in those with high consumption, and in non-consumers [34⋅26 (95 % CI 33⋅04, 35⋅49) v . 30⋅41 (95 % CI 27⋅13, 33⋅69) v . 32⋅72 (95 % CI 30⋅63, 34⋅80), P = 0⋅028; log-rank test]. Using the Cox proportional hazard model, it was shown that the risk of mortality in the high-salt consumption category was approximately 126 % higher than that of the reference category (non-consumers) [HR value 2⋅26, (95 % CI 0⋅91, 5⋅63)], while this risk for the low-to-moderate consumption group was about 28 % lower than the reference category [HR value 0⋅72, (95 % CI 0⋅26, 1⋅99), P -trend = 0⋅04]. In conclusion, a high daily dietary intake of salt might increase the rate of mortality and moderate salt restriction (instead of elimination of salt) decreases the risk of death., (© The Author(s) 2022.)

Liver cirrhosis is a chronic and relatively common disease without a definitive cure in most cases. Few studies have investigated affected individuals perceptions of the disease. This qualitative study aimed to describe the perceptions of individuals ( n = 27) with liver cirrhosis toward their disease. Interview data was analyzed using conventional content analysis. Data analysis revealed two main themes: the first theme was "perceived sensitivity to the cirrhosis," which was characterized by concerns about disease transmission to others, concerns about seeing symptoms as a reason in referring to medical centers, hiding disease from others, feeling remorse or guilt in having disease, and personal beliefs about cause of disease. The second theme was the "perceived severity of the cirrhosis," which was characterized by feelings of disease exacerbation due to tension and stress, discomfort due to continuation of annoying symptoms, discomfort due to ascites, and fear and hope while waiting for liver transplantation. The findings indicate a perceived threat from liver cirrhosis. Such perceived threats and their characteristics could help nurses and other healthcare providers to be aware of this perception in their care of individuals living with liver cirrhosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Society of Gastroenterology Nurses and Associates.)

Objectives: All patients with cirrhosis should be periodically examined for esophageal varices (EV), however, a large percentage of patients undergoing screening, do not have EV or have only mild EV and do not have high-risk characteristics. Therefore, developing a non-invasive method to predict the occurrence of EV in patients with liver cirrhosis as a non-invasive method with high accuracy seems useful. In the present research, we compared the performance of several machine learning (ML) methods to predict EV on laboratory and clinical data to choose the best model., Methods: Four-hundred-and-ninety data from the Liver and Gastroenterology Research Center of Shahid Beheshti University of Medical Sciences in the period 2014-2021, were analyzed applying models including random forest (RF), artificial neural network (ANN), support vector machine (SVM), and logistic regression., Results: RF and SVM had the best results in general for all grades of EV. RF showed remarkably better results and the highest area under the curve (AUC). After that, SVM and ANN had the AUC of 98%, for grade 3, the SVM algorithm had the highest AUC after RF (89%)., Conclusions: The findings may help to better predict EV with high precision and accuracy and also can help reduce the burden of frequent visits to endoscopic centers. It can also help practitioners to manage cirrhosis by predicting EV with lower costs., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with no medical treatment proven to improve survival and postpone liver transplantation. Previous studies have shown the effectiveness of fibrates in primary biliary cholangitis. The current study prospectively evaluated the effect of fenofibrate on PSC patients. We administered 200 mg of fenofibrate to PSC patients in the intervention arm and a placebo in the control arm once per day for 6 months and evaluated liver biochemistries (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin) and the Mayo Risk Score at the start and end of the study. The primary endpoint was defined as a reduction greater than 50% or normalization of ALP levels. Secondary endpoints were an improvement in the Mayo Risk Score and serum bilirubin levels. Thirty patients were included (19 female, 11 male, 40.2 ± 9.2 years old), all under treatment with Ursodeoxycholic acid prior to this study. ALP and ALT levels significantly decreased in the fenofibrate group, by 64.7% (mean difference = 557, p = 0.004, 95% CI = 208.72, 905.27) and 52.78%, (p = 0.006), respectively. The primary endpoint was achieved in 66.7% of patients (10 in 15) in the fenofibrate group versus 20% of patients (3 in 15) in the placebo group (p = 0.009). Other endpoints were not met. As studies have demonstrated lower levels of ALP may improve outcomes for PSC, our study resulted in significantly lower levels of ALP in the fenofibrate group, which could translate into better disease prognosis in PSC., (© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objectives: The present study was conducted to improve the performance of predictive methods by introducing the most important factors which have the highest effects on the prediction of esophageal varices (EV) grades among patients with cirrhosis., Methods: In the present study, the ensemble learning methods, including Catboost and XGB classifier, were used to choose the most potent predictors of EV grades solely based on routine laboratory and clinical data, a dataset of 490 patients with cirrhosis gathered. To increase the validity of the results, a five-fold cross-validation method was applied. The model was conducted using python language, Anaconda open-source platform. TRIPOD checklist for prediction model development was completed., Results: The Catboost model predicted all the targets correctly with 100% precision. However, the XGB classifier had the best performance for predicting grades 0 and 1, and totally the accuracy was 91.02%. The most significant variables, according to the best performing model, which was CatBoost, were child score, white blood cell (WBC), vitalism K (K), and international normalized ratio (INR)., Conclusions: Using machine learning models, especially ensemble learning models, can remarkably increase the prediction performance. The models allow practitioners to predict EV risk at any clinical visit and decrease unneeded esophagogastroduodenoscopy (EGD) and consequently reduce morbidity, mortality, and cost of the long-term follow-ups for patients with cirrhosis., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Although the role of a diet rich in fructose and saccharose in development of nonalcoholic fatty liver disease (NAFLD) is well known, the effects of a low free sugar diet in the management of the disease have not yet been investigated in adult patients with NAFLD. We aimed, therefore, to analyze the effects of a low-free sugar diet on NAFLD main features., Methods: Participants with FibroScan-proven NAFLD were randomized to a 12-week dietary intervention (low free sugar diet or usual diet). The primary outcome was change in hepatic steatosis measurement between baseline and 12 weeks. The secondary outcomes included changes in anthropometric measurements, lipid profile, glycemic indices, liver enzymes, and inflammatory factors., Results: Forty-three subjects completed the 12-week intervention. Low free sugar diet compared with the usual diet significantly decreased the concentrations of ALT (43.00 ± 27.54 to 27.95 ± 20.77 U/L), TG (172.86 ± 83.04 to 144.19 ± 65.55), TC (155.54 ± 37.55 to 139.86 ± 33.63 mg/dL), FBS (103.95 ± 15.42 to 91.00 ± 14.36 mg/dL), insulin (14.37 ± 5.79 to 8.92 ± 5.43 mU/L), HOMA-IR (3.81 ± 1.80 to 2.06 ± 1.29), hs-CRP (3.80 ± 1.09 to 2.88 ± 0.52 mg/L), TNF-α (4.60 ± 1.54 to 3.41 ± 0.69 pg/mL), NF-kb (3.89 ± 1.34 to 3.35 ± 1.33), as well as resulted in reduced fibrosis score and steatosis score, with increased QUICKI (P < 0.05). The differences in AST, GGT, HDL-C and LDL-C were not significant (P > 0.05)., Conclusion: Low free sugar diet in overweight/obese NAFLD patients may reduce hepatic steatosis and fibrosis while improving glycemic indices, decreasing the concentrations of biomarkers of inflammation, TG, and TC levels., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)