Nonalcoholic Liver Disease Research Articles

The Role of Interferon Receptors α/β/γ Ablation During Western Diet-Induced Obesity and Insulin Resistance in the Inflectional Model AG129 Mice Strain.

Diet-induced obesity triggers elevation of circulating pro-inflammatory cytokines and acute-phase proteins, including interferons (IFNs). IFNs strongly contribute to low-grade inflammation associated with obesity-related complications, such as nonalcoholic fat liver disease and diabetes. In this study, AG129 mice model (double-knockout strain for IFN α/β/γ receptors) was fed with a high-fat high-sucrose (HFHS) diet (Western diet) for 20 weeks aiming to understand the impact of IFN receptor ablation on diet-induced obesity, insulin resistance, and nonalcoholic fat liver disease. Mice were responsive to the diet, becoming obese after 20 weeks of HFHS diet which was accompanied by 2-fold increase of white adipose tissues. Moreover, animals developed glucose and insulin intolerance, as well as dysregulation of insulin signaling mediators such as Insulin Receptor Substrate 1 (IRS1), protein kinase B (AKT), and S6 ribosomal protein. Liver increased interstitial cells, and lipid accumulation was also found, presenting augmented fibrotic markers (transforming growth factor beta 1 [Tgfb1], Keratin 18 [Krt18], Vimentin [Vim]), yet lower expression on IFN receptor downstream proteins (Toll-like receptor [TLR] 4, nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB], and cAMP response element-binding protein [CREB]). Thus, IFN receptor ablation promoted effects on NFκB and CREB pathways, with no positive effects on systemic homeostasis in diet-induced obese mice. Therefore, we conclude that IFN receptor signaling is not essential for promoting the complications of diet-induced obesity and thus cannot be correlated with metabolic diseases in a noninfectious condition.

Effects of (20 R)-Panaxadiol on NAFLD using non‑targeted metabolomics in stool

Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by hepatocyte steatosis and adipose accumulation with the main lesion in the hepatic lobule, but without a history of excessive alcohol consumption. NAFLD ranges from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), and may further accumulate fibrosis leading to cirrhosis. Many studies have found that ginseng can treat NAFLD. (20 R)-Panaxadiol (PD) is a panax ginseng diol type compound, has been proved that can treat the obesity. This study wants to investigate the effect of PD on non-alcoholic liver disease. We used 20 ob/ob mice and 10 C57BL/6 J mice. C57BL/6 J mice as CONTROL group, ob/ob mice were divided into model group and PD group. In PD group, ob/ob mice were treated with PD for eight weeks(10 mg/kg, the CON and OB group was given the same amount of sodium carboxymethyl cellulose), detected the weight, food intake and serum index, observed the HE staining of liver and intestine, performed the 16 S rRNA and untargeted metabolomics analysis used mice feces, and verify the results by detect the expression of TNF-α, MDA and SOD. In vivo results, PD can improve abnormal glucose and lipid metabolism and liver function. In 16 S rRNA result, we found beneficial bacteria Muribaculaceae and Lactobacillus increased; in untargeted metabolomics analysis, inflammatory metabolites prostaglandin (PG) and lipopolysaccharide (LPS) decreased, antioxidant metabolites FAD and lipoic acid increased. Then, we proceeded the association analysis of gut microbiota and metabolites, the result showed gut microbiota have strongly associated with anti-inflammatory and antioxidant metabolites. In addition, PD improves intestinal wall integrity. Meanwhile, the expression of TNF-α、MDA and SOD were detected, it was verified that PD has the effect of antioxidant and anti-inflammation. Our study showed that PD, as an active ingredient of ginseng, can play an anti-inflammatory and antioxidant role by improving intestinal metabolites, thereby preventing and treating non-alcoholic fatty liver disease to a certain extent.

Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies.

Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease worldwide and a leading indication for liver transplantation in the United States. NAFLD encompasses a heterogeneous clinicopathologic spectrum, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis, and progressive fibrosis, which can lead to end-stage liver disease including cirrhosis and hepatocellular cancer. Predictive models suggest that over 100 million adults in the United States will have NAFLD by 2030, representing over a third of the population. In this manuscript, we provide an overview of NAFLD risk factors, natural history (including hepatic and extra-hepatic outcomes), diagnosis, and current management strategies.

Sonological grading of non-alcoholic fatty liver and comparison with liver enzymes

Background: Non-alcoholic fatty liver disease (NAFLD) is becoming more well acknowledged as a significant contributor to liver-related morbidity and mortality. Objectives: To assess the sonological grading of non-alcoholic fatty liver disease and comparison with liver enzymes. Methods: An analytical cross-sectional study was conducted from 2022 August to 2023 January among the patients referred to radiology unit for liver sonography with diagnosis of non-alcoholic liver disease. Ethical approval was obtained from the institutional review committee of Kathmandu Medical College (Ref. 12082022/06). A convenience sampling method was used. The sample size calculated was 107. Descriptive statistics (frequencies, means, and standard deviations) was used to describe the variables of interest. One-way analysis of variance was applied for comparison of serum liver enzymes in between various grades of NAFLD at 5% significance level. Results: Mean age of the patients was 37.9 ± 17.8 years, with 60% females. Most patients had grade I NAFLD (82, 76.6%), whereas 23 (21.5%) were of grade II. Levels of liver enzyme: Serum glutamic pyruvic transaminase (SGPT) with p-value 0.02 and serum glutamic oxaloacetic transaminase (SGOT) with p-value 0.03 were associated with fatty liver grade. Conclusion: Ultrasound-based grading of the severity of NAFLD was associated with abnormalities in the liver enzyme profile of patients. The SGPT and SGOT levels correlated with increasing severity of NAFLD based on ultrasound.

MiR-27b targets MAIP1 to mediate lipid accumulation in cultured human and mouse hepatic cells

Non-alcoholic liver disease (NAFLD) is a condition caused by excessive fat accumulation in the liver and developed via multiple pathways. miR-27b has been suggested to play crucial roles in the development of NAFLD, assuming via targeting genes involved in lipid catabolism and anabolism. However, other pathways regulated by miR-27b are largely unknown. Here we show that lipid accumulation was induced in miR-27b–transfected human and mouse hepatic cells and that knockdowns of three miR-27b–target genes, β-1,4-galactosyltransferase 3 (B4GALT3), matrix AAA peptidase interacting protein 1 (MAIP1) and PH domain and leucine rich repeat protein phosphatase 2 (PHLPP2), induced lipid accumulation. We also show that B4GALT3 and MAIP1 were direct targets of miR-27b and overexpression of MAIP1 ameliorated miR-27b−induced lipid accumulation. In addition, we show that hepatic Maip1 expression declined in mice fed a high-fat diet, suggesting the involvement of decreased Maip1 expression in the condition of fatty liver. Overall, we identified MAIP1/miR-27b axis as a mediator of hepatic lipid accumulation, a potential therapeutic target for NAFLD.

The Burden of Comorbidities in Obstructive Sleep Apnea and the Pathophysiologic Mechanisms and Effects of CPAP

Micro-arousals and the repeated desaturation of oxyhemoglobin, which are typical in obstructive sleep apnea syndrome (OSAS), have adverse effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction), cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), and neuropsychiatric complications as well as a wide range of malignancies. These, in turn, have multilateral effects on familial, occupational, and social life, as well as increasing the risks of road traffic accidents and accidents at the workplace. Awareness, timely screening, and the prevention of complications play important roles in diagnosing and treating comorbid conditions. This review focuses on comorbidities in OSAS and the effect of Continuous Positive Airway Pressure (CPAP) therapy on their prognoses.

Association of leisure sedentary behavior and physical activity with the risk of nonalcoholic fatty liver disease: a two-sample Mendelian randomization study.

Previous observational studies have demonstrated the relationship between leisure sedentary behavior, physical activity, and nonalcoholic liver disease (NAFLD). However, whether these associations are causal or confounding factors remains unclear. Pooled genetic data from the UK Biobank and other large genome-wide association studies (GWAS) were used to extract instrumental variables representing sedentary television watching, computer use, driving, vigorous physical activity (VPA), and moderate-to-vigorous physical activity (MVPA). The two-sample Mendelian randomization (MR) method was used to explain the causal relationship between them and NAFLD. The inverse variance of the weighted method was used as the main analysis method, and MR-Egger, weighted median, MR-PRESSO, and other supplementary methods were also used. A sensitivity analysis was also performed. Simultaneously, the common risk factors for NAFLD were further analyzed for potential mediating associations. We observed that sedentary television viewing (odds ratio (OR): 1.84; 95% confidence interval (CI): 1.09-3.10; p = 0.021) and genetically predicted VPA duration (OR: 0.0033; 95% CI: 0.000015-0.70; p = 0.036) were suggestively associated with the risk of NAFLD. Using a computer (OR: 1.51; 95% CI: 0.47-4.81; p = 0.484), driving (OR: 0.78; 95% CI: 0.05-11.94; p = 0.858), and MVPA time (OR: 0.168; 95% CI: 0.01-2.81; p = 0.214) were not significantly associated with NAFLD. The role of heterogeneity versus pleiotropy was limited in all the analyses. This study supports the association between sedentary television watching and an increased risk of NAFLD, along with vigorous physical activity as a possible protective factor for NAFLD.

SAT-433 - Assessing the role of organokines as biomarkers for diagnosing non-alcohol related liver disease

SAT-433 - Assessing the role of organokines as biomarkers for diagnosing non-alcohol related liver disease

Non-alcoholic faty liver disease and liver fibrosis score have an independent relationship with the presence of mitral annular calcification.

Non-alcoholic faty liver disease (NAFLD) and liver fibrosis score (FIB 4) are associated with increased mortality from cardiovascular causes. NAFLD and cardiac diseases are different manifestations of systemic metabolic syndrome. In this study, we aimed to reveal the relationship between NAFLD and FIB 4 liver fibrosis scores and mitral annular calcification (MAC). One hundred patients were included in the study. Blood samples and echocardiography measurements were obtained from each subject. The two groups were compared in terms of demographic and echocardiographic characteristics. Thirty-one men and 69 women with a mean age of 48.6 ± 13.1years were included in the analysis. The patients were divided into two groups as those with MAC (n = 26) and those without (n = 74). The baseline demographic and laboratory data for the two groups were compared. In the group with MAC (+) age, serum creatinine levels, FIB4 and NAFLD Scores; HL, DM rates, angiotensin converting enzyme (ACE) inhibitor and statin usage rates were higher, with statistical significance. NAFLD and FIB 4 liver fibrosis scores have an independent relationship with MAC.

Role of perfusion computed tomography for diagnostic intermediate stages of fibrosis in diffuse liver diseases: prospective study

INTRODUCTION: Despite the wide availability of the use of ultrasonic elastography to assess fibrosis in patients with diffuse liver diseases, this method didn’t have a high specificity for diagnosing intermediate stages of fibrosis.OBJECTIVE: To evaluate the diagnostic effectiveness of perfusion computed tomography (PCT) for detecting intermediate stages of fibrosis in patients with diffuse liver diseases.MATERIALS AND METHODS: PCT of the liver was performed in 73 patients (37 men, 36 women, mean age 47.2±4.4 years). All patients underwent a biochemical blood test, ultrasound elastography, PCT, based on the obtained biochemical blood test and instrumental data, the examined patients were divided into three groups depending on diffuse liver disease: hepatitis (n=25), cirrhosis (n=26), non-alcoholic inflammatory liver disease (n=22). Statistics: The results were processed using the Statistica 10.0 for Windows software package. Identification of the relationship between two quantitative variables that do not obey the normal distribution law was carried out using the Spearman rank correlation coefficient. To assess the diagnostic efficiency of perfusion parameters in patients with DLD, an ROC-analysis (Receiver Operating Characteristic Analysis) was performed. In all statistical analysis procedures, changes were considered statistically significant at a significance level of p<0.05. RESULTS: BV correlated in all three groups of diseases with the elastography in patients with viral hepatitis — (r=–0.5; p><0.04), in patients with alcoholic cirrhosis (r=0.66; p><0.02), in patients with non-alcoholic inflammatory liver disease (r=–0.55; p><0.02). In patients with alcoholic hepatitis — correlation between HAF and elastography index (r=0.98; p><0.001), with viral hepatitis — HAF and elastography index (r=0.66; p><0.01). MTT was statistically correlated with elastography index in patients in the alcoholic cirrhosis group (r=0.78; p><0.006). The BF had the highest diagnostic effectiveness for differentiating F1 and F2 fibrosis in patients with diffuse liver diseases (p><0.0001). DISCUSSION: PCT is able to differentiate between minimal and intermediate fibrosis, which accompany not only hepatitis, but also non-alcoholic fatty liver disease, whose diagnosis is very relevant, and the use of ultrasound elastography is limited. CONCLUSION: The BF promotes to the differentiation of intermediate stages of fibrosis, and in combination with ultrasonic elastography can provide a promising direction for the dynamic monitoring of the parenchyma in patients with diffuse liver diseases.> p<0.05.RESULTS: BV correlated in all three groups of diseases with the elastography in patients with viral hepatitis — (r=–0.5; p<0.04), in patients with alcoholic cirrhosis (r=0.66; p><0.02), in patients with non-alcoholic inflammatory liver disease (r=–0.55; p<0.02). ><0.02). In patients with alcoholic hepatitis — correlation between HAF and elastography index (r=0.98; p<0.001), with viral hepatitis — HAF and elastography index (r=0.66; p><0.01). MTT was statistically correlated with elastography index in patients in the alcoholic cirrhosis group (r=0.78; p<0.006). The BF had the highest diagnostic effectiveness for differentiating F1 and F2 fibrosis in patients with diffuse liver diseases (p><0.0001). >p<0.006). The BF had the highest diagnostic effectiveness for differentiating F1 and F2 fibrosis in patients with diffuse liver diseases (p<0.0001). ><0.0001).DISCUSSION: PCT is able to differentiate between minimal and intermediate fibrosis, which accompany not only hepatitis, but also non-alcoholic fatty liver disease, whose diagnosis is very relevant, and the use of ultrasound elastography is limited.CONCLUSION: The BF promotes to the differentiation of intermediate stages of fibrosis, and in combination with ultrasonic elastography can provide a promising direction for the dynamic monitoring of the parenchyma in patients with diffuse liver diseases.

Effects of oleoylethanolamide supplementation on inflammatory biomarkers, oxidative stress and antioxidant parameters of obese patients with NAFLD on a calorie-restricted diet: A randomized controlled trial.

Background: Oxidative stress is considered a major factor in the pathophysiology of non-alcoholic liver disease (NAFLD). A growing body of evidence indicates that oleoylethanolamide (OEA), a bioactive lipid mediator, has anti-inflammatory and antioxidant properties. This trial investigated the effects of OEA administration on inflammatory markers, oxidative stress and antioxidant parameters of patients with NAFLD. Methods: The present randomized controlled trial was conducted on 60 obese patients with NAFLD. The patients were treated with OEA (250mg/day) or placebo along with a low-calorie diet for 12 weeks. Inflammatory markers and oxidative stress and antioxidant parameters were evaluated pre-and post-intervention. Results: At the end of the study, neither the between-group changes, nor the within-group differences were significant for serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1 beta (IL-1β), IL-6, IL-10, and tumor necrosis-factor α (TNF-α). Serum levels of total antioxidant capacity (TAC) and superoxide dismutase (SOD) significantly increased and serum concentrations of malondialdehyde (MDA) and oxidized-low density lipoprotein (ox-LDL) significantly decreased in the OEA group compared to placebo at study endpoint (p = 0.039, 0.018, 0.003 and 0.001, respectively). Although, no significant between-group alterations were found in glutathione peroxidase and catalase. There were significant correlations between percent of changes in serum oxidative stress and antioxidant parameters with percent of changes in some anthropometric indices in the intervention group. Conclusion: OEA supplementation could improve some oxidative stress/antioxidant biomarkers without any significant effect on inflammation in NAFLD patients. Further clinical trials with longer follow-up periods are demanded to verify profitable effects of OEA in these patients. Clinical Trial Registration: www.irct.ir, Iranian Registry of Clinical Trials IRCT20090609002017N32.

Activation of AMPK Entails the Protective Effect of Royal Jelly against High-Fat-Diet-Induced Hyperglycemia, Hyperlipidemia, and Non-Alcoholic Fatty Liver Disease in Rats.

This study examined the mechanism underlying the protective effect of royal jelly (RJ) against high-fat-diet (HFD)-mediated non-alcoholic liver disease (NAFLD) in rats. Adult male rats were divided into five groups (n = 8 each): control fed a standard diet, control + RJ (300 mg/kg), HFD, HFD + RJ (300 mg/kg), and HFD + RJ + CC (0.2 mg/kg). The treatment with RJ reduced weight gain, increased fat pads, and attenuated fasting hyperglycemia, hyperinsulinemia, and glucose tolerance in the HFD-fed rats. It also reduced the serum levels of liver function enzymes, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin but significantly increased the serum levels of adiponectin. In addition, and with no effect on lipid excretion in stool, RJ significantly decreased the hepatic mRNA expression of SREBP1, serum, hepatic cholesterol, and triglycerides but increased hepatic mRNA levels of PPARα. Furthermore, RJ reduced the hepatic levels of TNF-α, IL-6, and malondialdehyde (MDA) in the livers of these rats. Of note, with no effect on the mRNA levels of AMPK, RJ stimulated the phosphorylation of AMPK and increased the levels of superoxide dismutase (SOD) and total glutathione (GSH) in the livers of the control and HFD-fed rats. In conclusion, RJ attenuates NAFLD via its antioxidant potential and adiponectin-independent activation of liver AMPK.

Valor pronóstico de la fibrosis hepática valorada por el índice FIB4 en pacientes ingresados por síndrome coronario agudo

Introduction and objectivesLiver fibrosis is present in nonalcoholic liver disease (NAFLD) and both precede liver failure. Subclinical forms of liver fibrosis might increase the risk of cardiovascular events. The objective of this study was to describe the prognostic value of the FIB-4 index on in-hospital mortality and postdischarge outcomes in patients with acute coronary syndrome (ACS). MethodsRetrospective study including all consecutive patients admitted for ACS between 2009 and 2019. According to the FIB-4 index, patients were categorized as <1.30, 1.30-2.67 or> 2.67. Heart failure (HF) and major bleeding (MB) were assessed taking all-cause mortality as a competing event and subhazard ratios (sHR) are presented. Recurrent events were evaluated by the incidence rate ratio (IRR). ResultsWe included 3106 patients and 6.66% had a FIB-4 index ≥ 1.3. A multivariate analysis verified a higher risk of in-hospital mortality associated with the FIB-4 index (OR, 1.24; P=.016). Patients with a FIB-4 index> 2.67 had a 2-fold higher in-hospital mortality risk (OR, 2.35; P=.038). After discharge (median follow-up 1112 days), the FIB-4 index had no prognostic value for mortality. In contrast, patients with FIB-4 index ≥ 1.3 had a higher risk of first (sHR, 1.61; P=.04) or recurrent (IRR, 1.70; P=.001) HF readmission. Similarly, FIB-4 index ≥ 1.30 was associated with a higher MB risk (sHR, 1.62; P=.030). ConclusionsThe assessment of liver fibrosis by the FIB-4 index identifies ACS patients not only at higher risk of in-hospital mortality but also at higher risk of HF and MB after discharge.Full English text available from:www.revespcardiol.org/en

Ferroptosis in non-alcoholic liver disease: Molecular mechanisms and therapeutic implications.

Ferroptosis refers to a novel modality of regulated cell death characterized by excessive iron accumulation and overwhelming lipid peroxidation, which takes an important part in multiple pathological processes associated with cell death. Considering the crucial roles of the liver in iron and lipid metabolism and its predisposition to oxidative insults, more and more studies have been conducted to explore the relationship between ferroptosis and various liver disorders, including non-alcoholic fatty liver disease (NAFLD). With increased morbidity and high mortality rates, NAFLD has currently emerged as a global public health issue. However, the etiology of NAFLD is not fully understood. In recent years, an accumulating body of evidence have suggested that ferroptosis plays a pivotal role in the pathogenesis of NAFLD, but the precise mechanisms underlying how ferroptosis affects NAFLD still remain obscure. Here, we summarize the molecular mechanisms of ferroptosis and its complicated regulation systems, delineate the different effects that ferroptosis exerts in different stages of NAFLD, and discuss some potential effective therapies targeting ferroptosis for NAFLD treatment, which putatively points out a novel direction for NAFLD treatment.

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.

Hepatic genomic assessment of dietary ingestion of 2-aminoanthracene in Sprague Dawley rats

This research aims to investigate the effects of 2-aminoanthracene (2-AA), a polycyclic aromatic hydrocarbon (PAH), on the liver. PAH is a by-product of the incomplete combustion of fossil fuels. Specifically, the impact of 2-AA on different body tissues in animals has been reported. The liver is an organ central to the metabolism of PAHs, including 2-AA. Sprague Dawley rats ingested a well-defined dose of 2-AA in their diet (0, 50, and 100 mg/kg 2-AA) for 12 weeks. Hepatic global gene expression using Affymetrix Rat Genome 230 2.0 microarray was performed. Overall, more than 17,000 genes were expressed. Approximately 70 genes were upregulated, while 65 were downregulated when control rats were compared with low-dose animals. Similarly, 103 genes were upregulated and 49 downregulated when the high-concentration 2-AA group was compared with the control group rats. This result suggests that the magnitude of gene expression fold change depends on the dose of 2-AA ingested. Several differentially expressed genes are involved in biological processes such as gene transcription, cell cycle, and immune system function, indicating that the ingestion of 2-AA could impact these processes. The over-expression of genes related to liver inflammation, nonalcoholic liver disease, hepatic glucose processing, and PAH metabolism were noted.

Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes.

Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.

Once a week consumption of Western diet over twelve weeks promotes sustained insulin resistance and non-alcoholic fat liver disease in C57BL/6 J mice

The Western diet (high in fat and sucrose) consumption is a highly prevalent feature in the whole world, mainly due to the increasing consumption of ultra-processed foods (UPF), which are cheaper and easier-to-eat, as compared to fresh and highly nutritive meals. Epidemiological studies have associated UPF consumption with development of obesity, non-alcoholic fat liver disease (NAFLD) and insulin resistance. For molecular studies, mice fed with Western diets have been used to characterize signaling pathways involved in these diet-induced pathologies. However, these studies fed mice continuously with the diets, which is not compatible with what occurs in real life, when consumption is occasional. Here, we fed mice once-a-week with a high fat, high sucrose (HFHS) diet and compared these animals with those fed continuously with HFHS diet or with a standard diet. Our results show that after a single day of consuming HFHS, animals presented impaired oral glucose tolerance test (oGTT) as compared to control group. Although this impairment was reversed after 24 h consuming regular diet, repetition of HFHS consumption once-a-week aggravated the picture such as after 12-weeks, oGTT impairment was not reversed after 6 days under control diet. Liver steatosis, inflammation, impaired insulin signaling pathway and endoplasmic reticulum stress are similar comparing animals that consumed HFHS once-a-week with those that continuously consumed HFHS, though weekly-fed animals did not gain as much weight. Therefore, we conclude that regimen of one day HFHS plus 6 days normal diet over 12 weeks is sufficient to induce insulin resistance and NAFLD in mice.

Liver Targeting Novel Trends In Therapies

Background: In this review Novel strategies for site-specific delivery of active pharmaceutical ingredients to different types of liver cells like Hepatic stellate cells [HSCs], active Kupffer cells, sinusoidal endothelial cells etc. have been discussed. The most prevalent liver ailments are hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic venous-occlusive disease, liver fibrosis, and cirrhosis. Method: Literature was searched through various online resources for the recent advances in liver-targeted site-specific delivery using various approaches. We focused on the use of novel targeted delivery to improve Drug efficacy, dose reduction and Rapid onset of action. Results: Novel medicines aim to minimize unfavorable side effects by either sustaining drug action at a set rate or delivering the drug at a suitable time in the body. Therapeutic nanocarriers and their surface modification with particular ligands including carbohydrates, peptides, proteins, and antibodies are two main strategies that have been suggested to optimize the transport of various medications to the liver and hepatocytes. It subsequently lowers the toxicity and prolongs the drug's time in the systemic circulation. Conclusion: The current review provides information on various liver illnesses as well as the targeting techniques used to concern hepatic anatomy and disease etiologies.

High fat diet is protective against kidney injury in hypertensive-diabetic mice, but leads to liver injury.

Chronic kidney disease (CKD) is a worldwide health burden with increases risk of end-stage renal function if left untreated. CKD induced in the context of metabolic syndrome (MS) increases risks of hypertension, hyperglycemia, excess body fat and dyslipidemia. To test if combining a high-fat diet (HFD) regimen onto the hypertensive/ diabetic phenotype would mimic features of MS induced-CKD in mice, hyperglycemia was induced in genetically hypertensive mice (Lin), followed by HFD regimen. For that, 8-week-old male were subjected to streptozotocin (STZ) intraperitoneal (i.p.) injections (50 mg/kg, 5 days consecutive). LinSTZ were fed a 60% kCal HFD for 8 weeks. Lin mice treated with STZ developed polydipsia, became hypertensive and hyperglycemic. HFD induced weight gain, protected against glomerular hypertrophy, scarring, and albuminuria at endpoint compared to regular diet fed LinSTZ. On the other hand, HFD induced steatosis, liver fibrosis, inflammation, and increase in AST/ALT ratio, characteristics of non-alcoholic liver disease. Taken together, our results show that LinSTZ mice fed a HFD did not lead to a more robust model of MS-induced CKD, protected against kidney injury, but inducing liver damage. More studies are necessary to understand the kidney protective mechanisms of HFD when superimposed with hypertension and type 1 diabetes.