Chronic Non-alcoholic Liver Disease Research Articles

ZnR/GPR39 regulates hepatic insulin signaling, tunes liver bioenergetics and ROS production, and mitigates liver fibrosis and injury

Adequate supply of zinc is essential for hepatic function and its deficiency is associated with acute liver injury (ALI) and chronic nonalcoholic fatty liver disease (NAFLD). However, how zinc controls hepatic function is unknown. We found that the zinc sensitive ZnR/GPR39, a mediator of zinc signaling, enhances hepatic phosphorylation of ERK1/2, which is reduced in ZnR/GPR39 deficient livers. Surprisingly, livers from ZnR/GPR39 knockout (KO) mice exhibited elevated insulin receptor expression and downstream AKT activation. Moreover, ZnR/GPR39 KO mice had higher blood fasting glucose level, pronounced hepatic lipid accumulation, increased hepatocyte oxygen consumption rate (OCR) and reactive oxygen species (ROS) levels. These data suggest that ZnR/GPR39 modulates insulin receptor signaling, a major pathway in hepatic metabolism. Associated with the impaired signaling, ZnR/GPR39 KO livers exhibited increased tissue fibrosis, manifested by marked elevation of collagen expression, compared to wildtype (WT). Additionally, we found alteration of hepatocyte junctional proteins that was accompanied by increased macrophage infiltration and higher liver inflammation in ZnR/GPR39 KO mice. To determine the role of ZnR/GPR39 in ALI, we applied a mild LPS challenge that induced profound decrease in hepatic OCR, also leading to higher ROS generation in ZnR/GPR39 KO hepatocytes, but not in WT. We further found increased serum IL-2 and AST/ALT ratio only in ZnR/GPR39 KO mice. Our findings reveal a role of ZnR/GPR39 in controlling hepatic insulin receptor signaling and mitigating liver fibrosis and inflammation, thus underscoring the important role of ZnR/GPR39 in liver signaling and function.

Association between Chronic Kidney Disease and Non-Alcoholic Fatty Liver Disease: A Cross Sectional Study

Abstract Background The concept of chronic kidney disease (CKD) continues to evolve from a common pathway initiated by unrelated diseases into a number of complications and adaptations that affect the function of every organ. Non-alcoholic fatty liver disease (NAFLD) is a public health problem worldwide. Evidence linking NAFLD to the development and progression of CKD is emerging as a popular area of scientific interest. NAFLD and CKD are associated with poor outcomes and high costs; they have become major public health problems. Aim of the Work To assess the prevalence of NAFLD in CKD patients Patients and Methods This was a retrospective cross-sectional study that was conducted on patients with CKD at the National Institute of Urology and Nephrology, Cairo, Egypt. Results Our study revealed that, there was highly statistically significant increase among NAFLD Group than No NAFLD Group regarding CKD stages. Also, there was statistically significant increase among NAFLD Group than No NAFLD Group regarding Obesity and Hypertension, and there was highly statistically significant increase among NAFLD Group than No NAFLD Group regarding metabolic syndrome, and there was no statistically significant difference between the non NAFLD Group and NAFLD Group regarding Diabetes. Conclusion NAFLD and NAFLD with traditional comorbidities are associated with the risk of prevalence of CKD. It is recommended that patients with NAFLD, especially those with coexisting comorbidities, should be carefully accessed for the development of CKD. Future studies should focus on the mechanisms and therapeutic targets for both NAFLD and CKD in a comorbid setting.

Association between Chronic Kidney Disease and Non-Alcoholic Fatty Liver Disease: A Cross Sectional Study

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a growing health problem that poses a significant burden as it is currently the most prevalent form of chronic liver disease, affecting an estimated 25% of the worldwide population. Aim of the Work to evaluate the role of plasma LCN2 levels in the diagnosis and prognosis of patients with non-alcoholic fatty liver disease. Patients and Methods Our case-control study was conducted on 102 Egyptian subjects between the ages of 18 and 70, recruited from the Internal Medicine and Hepatology Department and Clinics at Ain Shams University Hospital during the period from March 2023 to August 2023, and divided them into two groups. Group I: 51 Egyptian patients diagnosed with NAFLD (61% males; 39% females). Group II: 51 Egyptian healthy controls (51% males; 49% females) Results In this study, LCN2 levels were significantly higher in cases than in the control group (p < 0.001), with a mean of 1893.214 ±1002.852 in the cases and a mean of 466.020 ± 397.699 in the controls. This suggests the use of LCN2 as a possible diagnostic marker of NAFLD. The mean LCN2 levels in this study also significantly increased as the grade of fatty liver increased from I to III (p < 0.001). This in turn proposes the use of LCN2 as a prognostic marker for NAFLD progression. LCN2 also significantly correlated with the fatty liver index and NAFLD Fibrosis scoring systems, but not with Fib-4. It showed an excellent diagnostic performance in this study with an area under ROC of 0.906, an 84% sensitivity, a 90% specificity, 89.6% PPV and 85.2% NPV for the prediction of NAFLD patients. Conclusion Lipocalin-2 performs as a diagnostic marker for non-alcoholic liver disease, and a possible prognostic test that may be used to follow up the degree of steatosis. Other studies should be done on a larger size of participants to determine the prevalence of LCN2 in Egyptian population as well as other populations. Other studies should also be expanded to include NAFLD with degrees of fibrosis, and more quantitative imaging tools could be used to compare LCN2 levels with the NAFLD stage. The levels of LCN2 can be also measured in cohort studies before and after treatment of NAFLD to evaluate its sensitivity to the response of treatment.

Silymarin as an Antioxidant Therapy in Chronic Liver Diseases: A Comprehensive Review.

Chronic liver diseases (CLDs) such as chronic hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD) present significant global health challenges due to their high morbidity and mortality rates. Silymarin, a flavonoid complex derived from the seeds of the milk thistle plant (Silybum marianum), has been extensively studied for its hepatoprotective properties. This review aims to evaluate the role of silymarin as an antioxidant therapy in managing CLDs. We explore its efficacy, safety, and mechanisms of action through a comprehensive analysis of clinical trials and scientific studies. Silymarin offers protective effects on the liver and shows promise in improving liver function and histological outcomes in various chronic liver conditions. Despite the promising results, further research is needed to fully elucidate the optimal dosing regimens, long-term safety, and potential drug interactions of silymarin. This review underscores the therapeutic potential of silymarin in CLDs and provides a foundation for future studies aimed at enhancing its clinical application.

Multicolor Two-Photon Microscopy Imaging of Lipid Droplets and Liver Capsule Macrophages In Vivo.

Lipid droplets (LDs) store energy and supply fatty acids and cholesterol. LDs are a hallmark of chronic nonalcoholic fatty liver disease (NAFLD). Recently, studies have focused on the role of hepatic macrophages in NAFLD. Green fluorescent protein (GFP) is used for labeling the characteristic targets in bioimaging analysis. Cx3cr1-GFP mice are widely used in studying the liver macrophages such as the NAFLD model. Here, we have developed a tool for two-photon microscopic observation to study the interactions between LDs labeled with LD2 and liver capsule macrophages labeled with GFP in vivo. LD2, a small-molecule two-photon excitation fluorescent probe for LDs, exhibits deep-red (700 nm) fluorescence upon excitation at 880 nm, high cell staining ability and photostability, and low cytotoxicity. This probe can clearly observe LDs through two-photon microscopy (TPM) and enables the simultaneous imaging of GFP+ liver capsule macrophages (LCMs) in vivo in the liver capsule of Cx3cr1-GFP mice. In the NAFLD mouse model, Cx3cr1+ LCMs and LDs increased with the progress of fatty liver disease, and spatiotemporal changes in LCMs were observed through intravital 3D TPM images. LD2 will aid in studying the interactions and immunological roles of hepatic macrophages and LDs to better understand NAFLD.

Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis.

Evidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear. This study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets. We downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells. The WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells. We identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.

Pros and cons of live kidney donation in prediabetics: A critical review and way forward.

There is shortage of organs, including kidneys, worldwide. Along with deceased kidney transplantation, there is a significant rise in live kidney donation. The prevalence of prediabetes (PD), including impaired fasting glucose and impaired glucose tolerance, is on the rise across the globe. Transplant teams frequently come across prediabetic kidney donors for evaluation. Prediabetics are at risk of diabetes, chronic kidney disease, cardiovascular events, stroke, neuropathy, retinopathy, dementia, depression and nonalcoholic liver disease along with increased risk of all-cause mortality. Unfortunately, most of the studies done in prediabetic kidney donors are retrospective in nature and have a short follow up period. There is lack of prospective long-term studies to know about the real risk of complications after donation. Furthermore, there are variations in recommendations from various guidelines across the globe for donations in prediabetics, leading to more confusion among clinicians. This increases the responsibility of transplant teams to take appropriate decisions in the best interest of both donors and recipients. This review focuses on pathophysiological changes of PD in kidneys, potential complications of PD, other risk factors for development of type 2 diabetes, a review of guidelines for kidney donation, the potential role of diabetes risk score and calculator in kidney donors and the way forward for the evaluation and selection of prediabetic kidney donors.

Triglyceride-glucose index is capable of identifying metabolically obese, normal-weight older individuals

BackgroundThe concept of metabolically obese, normal weight (MONW) has emerged to describe individuals with a normal body mass index (BMI) who are at a relatively high risk of chronic diseases. However, BMI itself is a suboptimal index for the assessment of the health risks associated with visceral fat. The triglyceride-glucose (TyG) index is considered to be a reliable and cost-effective marker of insulin resistance. Therefore, in the present study, we aimed to determine the TyG index cut-off values that could be used to define MONW in older people and to determine the usefulness of these values for the prediction of chronic diseases.MethodsA total of 4,721 participants in the Korea National Health and Nutritional Examination Survey who were ≥ 60 years of age and did not have underweight or obesity were included. MONW was defined using the criteria for metabolic syndrome (MS), and the TyG index was calculated on the basis of the fasting plasma triglyceride and glucose concentrations. Chronic diseases, including T2DM, hypertension, and non-alcoholic fatty liver disease (NAFLD), were diagnosed.ResultsThe prevalence of MS increased from the lowest to the highest TyG index tertile. The cut-off values of the TyG index for MONW were calculated as 8.88 and 8.80 for males and females, respectively. MONW, defined using these cut-off values, was associated with high odds ratios for NAFLD, T2DM, and hypertension in both males and females.ConclusionsThe TyG index cut-off values calculated in the present study can be used to discriminate individuals with MONW from other older individuals without obesity and to predict the risk of chronic diseases. These findings show that the TyG index is an effective and cost-efficient method of assessing the risk of chronic diseases in people with MONW.

A Mendelian randomization study between chronic periodontitis and non-alcoholic fatty liver disease.

Observational studies have suggested a potential association between non-alcoholic fatty liver disease (NAFLD) and chronic periodontitis (CP). However, these studies are prone to confounding factors. The aim of this study was to assess the causal relationship between NAFLD and CP using a two-sample bidirectional Mendelian randomization (MR) analysis method. Datasets of CP and NAFLD were retrieved from the European database, and instrumental variables (IVs) related to exposure were selected for the MR analysis. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the consistency of the selected IVs, following which the analysis results were visualized. Genetic variants associated with CP and NAFLD were identified as IVs, and the MR assessment was performed using the summary data (CP: 3046 cases and 195 395 controls; NAFLD: 894 cases and 217 898 controls). CP increased the risk of NAFLD (inverse variance weighted [IVW], b = 0.132 > 0, p = .006 < .05), whereas the reverse was not observed (IVW, b = -0.024 < 0, p = .081 > .05). The sensitivity analysis indicated no heterogeneity or horizontal pleiotropy. The MR analysis suggested that CP could increase the risk of NAFLD among European populations.

Assessment of the nutritional state of patients with chronic diffuse liver diseases

Chronic liver diseases present a serious problem of modern medicine. Quite often, patients with liver diseases suffer from a violation of the normal nutritional state. such as malnutrition against the background of deficiency or increased body weight, which can develop latently in the early stages of the liver pathology and lead to protein-energy malnutrition, the development of sarcopenia and its complications. Aim. Evaluation of the nutritional status of patients with chronic diffuse liver diseases using anthropometric and biochemical parameters. Materials and methods. There were examined 282 patients, men n=138(49%), women n=144(51%) with liver pathology, whom were divided into groups: 1 gr - with chronic hepatitis n=75 (27. 4%), 2 gr - with chronic fatty non-alcoholic liver disease n=96 (34. 2%), and 3 gr - with liver cirrhosis of various etiology n=111 (39. 4%). The average age is 54. 23. Anthropometric studies were carried out (chest circumference, waist circumference, circumference of the middle part of the shoulder, thigh circumference), body mass index was calculated. In all patients, we studied the indicators of protein metabolism - total protein and albumin levels in blood serum. Results. The study revealed the presenceof abdominal fat in all patients, characteristic of obesity sarcopenia and a decrease in protein metabolism: total protein and albumin in patients with liver cirrhosis. Conclusions. All patients have an android type of adipose tissue distribution and are at high risk of developing comorbid cardiovascular and endocrine dysfunction.

Diagnostic role of transient elastography in patients with autoimmune liver diseases: A systematic review and meta-analysis.

Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying. To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD. The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis. A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80. Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

Exploring the Use of Diabetic Medications for Non-Diabetic Conditions: A Comprehensive Literature Review

Purpose: Currently, a significant portion of the US population has been impacted by diabetes, and alongside it, heart failure, chronic kidney disease (CKD), obesity, and non-alcoholic fatty liver disease (NAFLD) rates are on the rise. Recent research has highlighted the potential of antidiabetic medications to extend beyond diabetes management. This literature review is aimed at exploring the evolving roles of GLP-1 receptor agonists, SGLT2 inhibitors, and thiazolidinediones. It specifically investigates their applications in cardiovascular disease, chronic kidney disease (CKD), obesity, polycystic ovarian syndrome (PCOS), and NAFLD. As a novel therapeutic approach, their application could reshape treatment strategies for interconnected metabolic disorders, offering a new horizon in patient care.&#x0D; Methodology: We conducted a comprehensive search of PubMed and Google Scholar for English-language studies published in the United States and Canada between January 1st, 2013, and August 31st, 2023 focusing on trials involving GLP-1RA, SGLT-2i, and thiazolidinediones therapy. &#x0D; Findings: In our study, GLP-1 receptor agonists emerged as multifaceted pharmaceutical agents, showcasing improvements in cardiovascular disease outcomes, nephroprotective effects, substantial efficacy in obesity management, and promising prospects in addressing non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). Additionally, thiazolidinediones displayed effectiveness in the management of non-alcoholic steatohepatitis (NASH), while metformin exhibited notable benefits in PCOS management. Furthermore, Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors demonstrated remarkable advancements, particularly in terms of cardiovascular and renal benefits. Our findings emphasize the diverse and evolving applications of diabetic medications in addressing a wide range of chronic medical conditions, ultimately leading to enhanced patient care and improved outcomes.&#x0D; Recommendations: We recommend that healthcare practitioners carefully consider the expanded utility of these medications beyond their conventional diabetic indications and explore their integration into treatment strategies for the indicated medical conditions. This should be done while thoughtfully weighing the associated risks and benefits to ensure the most effective and safe patient care possible.

Study design for development of novel safety biomarkers of drug-induced liver injury by the translational safety biomarker pipeline (TransBioLine) consortium: a study protocol for a nested case–control study

A lack of biomarkers that detect drug-induced liver injury (DILI) accurately continues to hinder early- and late-stage drug development and remains a challenge in clinical practice. The Innovative Medicines Initiative’s TransBioLine consortium comprising academic and industry partners is developing a prospective repository of deeply phenotyped cases and controls with biological samples during liver injury progression to facilitate biomarker discovery, evaluation, validation and qualification.In a nested case–control design, patients who meet one of these criteria, alanine transaminase (ALT) ≥ 5 × the upper limit of normal (ULN), alkaline phosphatase ≥ 2 × ULN or ALT ≥ 3 ULN with total bilirubin > 2 × ULN, are enrolled. After completed clinical investigations, Roussel Uclaf Causality Assessment and expert panel review are used to adjudicate episodes as DILI or alternative liver diseases (acute non-DILI controls). Two blood samples are taken: at recruitment and follow-up. Sample size is as follows: 300 cases of DILI and 130 acute non-DILI controls. Additional cross-sectional cohorts (1 visit) are as follows: Healthy volunteers (n = 120), controls with chronic alcohol-related or non-alcoholic fatty liver disease (n = 100 each) and patients with psoriasis or rheumatoid arthritis (n = 100, 50 treated with methotrexate) are enrolled. Candidate biomarkers prioritised for evaluation include osteopontin, glutamate dehydrogenase, cytokeratin-18 (full length and caspase cleaved), macrophage-colony-stimulating factor 1 receptor and high mobility group protein B1 as well as bile acids, sphingolipids and microRNAs. The TransBioLine project is enabling biomarker discovery and validation that could improve detection, diagnostic accuracy and prognostication of DILI in premarketing clinical trials and for clinical healthcare application.

Association of Non-Alcoholic Fatty Liver Disease with Chronic Obstructive Lung Disease Patients: An Egyptian Study

Abstract Background Chronic Obstructive Pulmonary Disease (COPD) and Non-Alcholic Fatty Liver Disease (NAFLD) share common risk factors, such as reduced physical activity, and pathophysiological mechanisms including oxidative stress, low grade inflammation, and metabolic syndrome. COPD severity is also recognized as an independent risk factor of NAFLD. Interestingly, the literature reports a higher prevalence of all-cause liver disease in patients with COPD, but only a small number of patients with NAFLD. Therefore, the specific links between NAFLD and COPD need to be confirmed and further evaluated. Aim of the Work The aim of the study is to determine the possible association between Chronic Obstructive Lung Disease and Non-Alcoholic Fatty Liver Disease. Patients and Methods This cross-sectional study was conducted at outpatient clinics at Ain Shams Hospital during a Period 1 year. This study was performed on 60 Egyptian Patients divided into two groups as follow: Group 1:40 Patients diagnosed with COPD (Patients diagnosed by history of disease, smoking history and A ration of post bronchodilator FEV1 10 FVC of less than 70% of the predicted value). Group2: 20 Normal Healthy People (Control Group) Results There was no statistically significant difference with p-value &amp;gt;0.05 between both groups as regards age and sex, which indicated proper matching between groups. The present study showed that there was a statistically significant difference with p-value &amp;lt;0.05 between study groups as regards obstructive sleep apnea with high percentage of obstructive sleep apnea among cases. On the other hands, there was no statistically significant difference with p-value &amp;gt;0.05 between both groups as regards smoking and hypertension. The current study showed that there was no statistically significant difference with p-value &amp;gt;0.05 between study groups as regards systolic blood pressure, weight, height, waist circumference and BMI. On the other hand, there was a statistical significance difference with p-value &amp;lt;0.05 with higher mean of diastolic blood pressure among cases. Conclusion This study showed that NAFLD is associated with COPD. Physicians should be aware of possible liver comorbidities in COPD patients and that extrahepatic disease in NAFLD patients may vary more than previously thought. Further studies concerning the biochemical and metabolic mechanisms of NAFLD and COPD are required.

Chronic kidney disease and non-alcoholic fatty liver disease - new pathogenetic links

This article discusses the association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). There is ample evidence of an increased risk of CKD in patients with NAFLD. Most researchers attribute to the common risk factors for these two conditions. Currently, in addition to traditional factors associated with CKD and NAFLD, such as components of the metabolic syndrome, the influence of new pathogenetic factors, i. e. endothelial dysfunction, metabolic disorders of fibroblast growth factor-21, pathological activation of the renin-angiotensin system and influence of adiponectin level change are considered. Further examination of these mechanisms will open up new therapeutic options for the treatment of CKD and NAFLD.

Valuable effects of lactobacillus and citicoline on steatohepatitis: role of Nrf2/HO-1 and gut microbiota

Non-alcoholic steatohepatitis (NASH) is a more dangerous form of chronic non-alcoholic fatty liver disease (NAFLD). In the current investigation, the influence of citicoline on high-fat diet (HFD)-induced NASH was examined, both alone and in combination with Lactobacillus (probiotic). NASH was induced by feeding HFD (10% sugar, 10% lard stearin, 2% cholesterol, and 0.5% cholic acid) to rats for 13 weeks and received single i.p. injection of streptozotocin (STZ, 30 mg/kg) after 4 weeks. Citicoline was given at two dose levels (250 mg and 500 mg, i.p.) at the beginning of the sixth week, and in combination with an oral suspension of Lactobacillus every day for eight weeks until the study’s conclusion. HFD/STZ induced steatohepatitis as shown by histopathological changes, elevated serum liver enzymes, serum hyperlipidemia and hepatic fat accumulation. Moreover, HFD convinced oxidative stress by increased lipid peroxidation marker (MDA) and decreased antioxidant enzymes (GSH and TAC). Upregulation of TLR4/NF-kB and the downstream inflammatory cascade (TNF-α, and IL-6) as well as Pentaraxin, fetuin-B and apoptotic markers (caspase-3 and Bax) were observed. NASH rats also had massive increase in Bacteroides spp., Fusobacterium spp., E. coli, Clostridium spp., Providencia spp., Prevotella interrmedia, and P. gingivalis while remarkable drop in Bifidobacteria spp. and Lactobacillus spp. Co-treatment with citicoline alone and with Lactobacillus improve histopathological NASH outcomes and reversed all of these molecular pathological alterations linked to NASH via upregulating the expression of Nrf2/HO-1 and downregulating TLR4/NF-kB signaling pathways. These results suggest that citicoline and lactobacillus may represent new hepatoprotective strategies against NASH progression.

Effect of low-calorie diet on psoriasis severity index, triglycerides, liver enzymes, and quality of life in psoriatic patients with non-alcoholic fatty liver disease.

Chronic-plaque psoriasis is a chronic inflammatory dermatological disease. Obesity comorbidities, including non-alcoholic fatty liver disease, are highly prevalent in patients with chronic-plaque psoriasis. Recently, weight loss has been a highly recommended intervention to improve the severity of psoriatic symptoms, psoriasis-induced chronic systemic inflammation, psoriasis-associated cardiovascular risk factors, quality of life, and the efficacy of anti-psoriatic drugs. This study was designed to assess the effect of a 12-week low-calorie-diet intervention on aspartate transaminase, psoriasis severity (assessed via Psoriasis Area and Severity Index - PASI), alanine transaminase, quality of life (assessed via Dermatology Life Quality Index - DLQI), triglycerides, waist circumference (WC), and body mass index (BMI) in class I obese men with chronic-plaque and non-alcoholic fatty liver disease. Sixty men with age ≥ 18 years with class I obesity and with chronic plaque psoriasis and non-alcoholic fatty liver disease were included in the study. All participants were randomly assigned to one of two groups: the first group as the low-calorie-diet group (30 men received immunosuppressive drugs, followed a low-calorie diet, and increased their energy expenditure through a daily 15,000-step outdoor walking program for 12 weeks) and the second as the control group (30 men received immunosuppressive drugs only). The primary outcome consisted of the results of the area and severity index. Weight, BMI, WC, laboratory results such as triglycerides, liver enzymes (alanine transaminase and aspartate transaminase) as well as DLQI were considered as secondary outcomes. While no significant improvements were achieved in the measured variables of the control group, the low-calorie-diet group demonstrated significant improvement in all the measured variables. The results of the present study confirmed that 12-week low-calorie-diet intervention controls BMI, increases the response of psoriasis to pharmacological agents and improves the quality of life. Diet interventions significantly control the elevated hepatic enzymes (aspartate and alanine transaminases) and triglycerides in male patients with chronic-plaque psoriasis and non-alcoholic fatty liver disease.

Hepatitis C mortality trends in Mexico from 2001 to 2017

Introduction and ObjectivesWe aimed to analyze the trends of total and sex-stratified mortality from hepatitis C virus (HCV) and to estimate the proportion of non-alcoholic liver disease deaths in Mexico attributable to HCV from 2001-2017. Materials and MethodsUsing the mortality multiple-cause dataset, we selected the codes for acute HCV and chronic HCV to analyze trends from 2001 to 2017. We then estimated the proportion of HCV-related deaths out of non-alcoholic chronic liver disease deaths, by including in the denominator: other acute and chronic viral hepatitis, malignant neoplasm of the liver, liver failure, chronic hepatitis, fibrosis, and cirrhosis of the liver, and other inflammatory diseases of the liver. Average percent change (APC) for trends, overall and by sex, were estimated using Joinpoint regression. ResultsThe trend in crude mortality rate significantly increased from 2001-2005 (APC 18.4%; 95%CI=12.5, 24.5; p value<0.001), and then significantly decreased from 2013-2017 (APC -6.5%; 95%CI=-10.1, -2.9; p value<0.001). Stratified by sex women experienced a more rapid decline in the 2014-2017 period than men. ConclusionsHCV mortality seems to have started to decrease, but much remains to be done in terms of prevention, diagnosis, and timely access to treatment.

COVID-19 and the liver: Are footprints still there?

The coronavirus disease 2019 (COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionally, liver function abnormalities were noted in patients with severe COVID-19. Profound cytokine storm, direct viral infection, drugs and reactivation of viral infections were causes of deranged liver functions. Here, we discuss the relation between COVID-19 and chronic liver disease, specifically cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease (NAFLD), as well as the liver manifestations of COVID-19. The metabolic syndrome, obesity, diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide. Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19. Recently, COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis. The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.

Minimal Risk of Drug-Induced Liver Injury With Molnupiravir and Ritonavir-Boosted Nirmatrelvir

Minimal Risk of Drug-Induced Liver Injury With Molnupiravir and Ritonavir-Boosted Nirmatrelvir