Stage Liver Disease Research Articles

Deciphering the complex links between inflammatory bowel diseases and NAFLD through advanced statistical and machine learning analysis

Background and Objective:Accurate classification of liver disease stages provides crucial insights into patient prognosis, aiding in the prediction of disease outcomes and influencing clinical decision-making. There is an urgent need for non-invasive methods to diagnose various stages of liver dysfunction and uncover hidden pattern based on individual disease characteristics. Method:One popular and effective approach is collecting serum biomarker samples. The study was conducted on collected serum biomaker samples of 81 patients with Inflammatory Bowel Disease (IBD) of Changhua Christian Hospital in China, including 36 with Crohn’s disease (CD) and 45 with Ulcerative Colitis (UC) using Latent Semantic Analysis(LSA) and machine learning (ML) techniques.Machine Learning algorithms Random Forest (RF), Logistic Regression (LR), XGBoost (XGB), and Support Vector Classifier (SVC), were utilized to predict liver risk associated with conditions including Hepatitis, Autoimmune Hepatitis (AIH), Alcoholic Liver Disease (ALD), and Non-Alcoholic Fatty Liver Disease (NAFLD). Models’ accuracy was assessed using K-Fold Cross-Validation (CV).Distinct pattern were identified using Latent Semantic Analysis(LSA). Furthermore, SHAP plots were utilized for enhanced interpretability, highlighting essential features for liver dysfunction levels. Results:The inflammatory profile, mixed disease profile, and healthy profile were the three distinct clusters were identified with LSA. The RF model achieved high accuracy of 0.94±0.06. Serum Glutamate Pyruvate Transaminase (GPT), Age at Diagnosis (AAD), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP) were found the most key important features in liver disease staging increment. Conclusion:The research significantly contributes to the fields of biomedical informatics and clinical decision-making. The developed model offers valuable decision-making tools for clinicians, enabling early and targeted interventions.

The AMPK-mTOR Pathway Is Inhibited by Chaihu Shugan Powder, Which Relieves Nonalcoholic Steatohepatitis by Suppressing Autophagic Ferroptosis.

Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine-choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR)-mediated autophagy and ferroptosis markers, such as p-AMPKα/AMPKα, p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH.

Key genes involved in nonalcoholic steatohepatitis improvement after bariatric surgery.

Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent chronic liver diseases. The effectiveness of bariatric surgery in treating NASH and preventing or even reversing liver fibrosis has been demonstrated in numerous clinical studies, but the underlying mechanisms and crucial variables remain unknown. Using the GSE135251 dataset, we examined the gene expression levels of NASH and healthy livers. Then, the differentially expressed genes (DEGs) of patients with NASH, at baseline and one year after bariatric surgery, were identified in GSE83452. We overlapped the hub genes performed by protein-protein interaction (PPI) networks and DEGs with different expression trends in both datasets to obtain key genes. Genomic enrichment analysis (GSEA) and genomic variation analysis (GSVA) were performed to search for signaling pathways of key genes. Meanwhile, key molecules that regulate the key genes are found through the construction of the ceRNA network. NASH mice were induced by a high-fat diet (HFD) and underwent sleeve gastrectomy (SG). We then cross-linked the DEGs in clinical and animal samples using quantitative polymerase chain reaction (qPCR) and validated the key genes. Seven key genes (FASN, SCD, CD68, HMGCS1, SQLE, CXCL10, IGF1) with different expression trends in GSE135251 and GSE83452 were obtained with the top 30 hub genes selected by PPI. The expression of seven key genes in mice after SG was validated by qPCR. Combined with the qPCR results from NASH mice, the four genes FASN, SCD, HMGCS1, and CXCL10 are consistent with the biological analysis. The GSEA results showed that the 'cholesterol homeostasis' pathway was enriched in the FASN, SCD, HMGCS1, and SQLE high-expression groups. The high-expression groups of CD68 and CXCL10 were extremely enriched in inflammation-related pathways. The construction of the ceRNA network obtained microRNAs and ceRNAs that can regulate seven key genes expression. In summary, this study contributes to our understanding of the mechanisms by which bariatric surgery improves NASH, and to the development of potential biomarkers for the treatment of NASH.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

Evaluating aspartate–platelet ratio index: A potential non-invasive tool for liver cirrhosis and esophageal varices detection

Background: The global health challenge posed by liver cirrhosis, notably its progression to complications such as esophageal varices, necessitates advancements in diagnostic techniques. Aims and Objectives: This study probes the aspartate–platelet ratio index (APRI) capability, a non-invasive diagnostic approach, in effectively managing liver cirrhosis and foreseeing the development of esophageal varices. Materials and Methods: The research at MES Medical College in Perinthalmanna included a cohort of 114 ultrasonographically diagnosed liver cirrhosis patients. Utilizing established formulae, the APRI score was computed and juxtaposed with the incidence and gravity of esophageal varices, ascertained through endoscopic examinations. The analysis encompassed receiver operating characteristic (ROC) curve evaluation alongside descriptive and inferential statistical methodologies. Results: Within the participant group, the average age was 59.35 years, with males constituting 64.04% of the sample. Notably, 83.33% of the subjects were found to have esophageal varices varying in severity. The APRI score’s predictive capability was moderate (ROC curve area=0.655), indicating limitations in its sole use for diagnosing esophageal varices. Conclusion: While user-friendly and non-intrusive, the APRI score exhibits limited effectiveness in the specific diagnosis of liver cirrhosis and in forecasting the emergence of esophageal varices. Its utility, primarily in signaling liver fibrosis, does not extend robustly as an independent diagnostic tool in clinical scenarios. This study underscores an urgent need for extended research to affirm APRI’s accuracy in diverse liver disease stages and anticipate associated complications.

3D microscaffolds with triple-marker sensitive nanoprobes for studying fatty liver disease in vitro.

Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous condition that encompasses a wide range of liver diseases that progresses from simple hepatic steatosis to the life-threatening state of cirrhosis. However, due to the heterogeneity of this disease, comprehensive analysis of several physicochemical and biological factors that drive its progression is necessary. Therefore, an in vitro platform is required that would enable real-time monitoring of these changes to better understand the progression of these diseases. The earliest stage of NAFLD, i.e. hepatic steatosis, is characterised by triglyceride accumulation in the form of lipid vacuoles in the cytosol of hepatocytes. This fatty acid accumulation is usually accompanied by hepatic inflammation, leading to tissue acidification and dysregulated expression of certain proteases such as matrix metalloproteinases (MMPs). Taking cues from the biological parameters of the disease, we report here a 3D in vitro GelMA/alginate microscaffold platform encapsulating a triple-marker (pH, MMP-3 and MMP-9) sensitive fluorescent nanoprobe for monitoring, and hence, distinguishing the fatty liver disease (hepatic steatosis) from healthy livers on the basis of pH change and MMP expression. The nanoprobe consists of a carbon nanoparticle (CNP) core, which exhibits intrinsic pH-dependent fluorescence properties, decorated either with an MMP-3 (NpMMP3) or MMP-9 (NpMMP9) sensitive peptide substrate. These peptide substrates are flanked with a fluorophore-quencher pair that separates on enzymatic cleavage, resulting in fluorescence emission. The cocktail of these nanoprobes generated multiple fluorescence signals corresponding to slightly acidic pH (blue) and overexpression of MMP-3 (green) and MMP-9 (red) enzymes in a 3D in vitro fatty liver model, whereas no/negligible fluorescence signals were observed in a healthy liver model. Moreover, this platform enabled us to mimic fatty liver disease in a more realistic manner. Therefore, this 3D in vitro platform encapsulating triple-marker sensitive fluorescent nanoprobes would facilitate the monitoring of the changes in pH and MMP expression, thereby enabling us to distinguish a healthy liver from a diseased liver and to study liver disease stages on the basis of these markers.

B-Blockers in Liver Cirrhosis: A Wonder Drug for Every Stage of Portal Hypertension? A Narrative Review.

In cirrhotic patients, non-selective b-blockers (NSBBs) constitute the reference treatment of choice as monotherapy or combined with band ligation for the prevention of first variceal bleeding and rebleeding, respectively. Furthermore, the last Baveno VII guidelines recommended carvedilol, a b-blocker with additional anti-a1 receptor activity, in all compensated cirrhotics with clinically significant portal hypertension, to prevent liver decompensation. Interestingly enough, NSBBs have been reported to have a potentially positive impact on the short-term mortality of patients with acute-on-chronic liver failure. However, concerns remain about the use of b-blockers in the presence of severe complications, such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, or established cirrhotic cardiomyopathy. In addition, it has not been verified yet whether carvedilol supersedes all the other NSBBs in every stage of liver disease, even when severe complications have developed. Therefore, this review aims to illustrate recent data regarding the potential role of b-blockers across all stages of liver disease, beyond the primary and secondary prophylaxis of variceal bleeding, and address the authors' proposals on the use of NSBBs concerning the severity of liver disease and the patient's performance status.

Detection of serum large and middle hepatitis B virus surface proteins: A novel potential diagnostic and prognostic biomarker for chronic hepatitis B

BackgroundThe significance of large (LHB) and middle (MHB) HBV surface proteins in chronic hepatitis B (CHB) remains uncertain. This study investigates the role of LHB and MHB in different infection phases and liver diseases. MethodsSerum samples from 217 patients with HBV chronic infection, CHB, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) were subjected to quantification of LHB and MHB using ELISA. ResultsPositive correlations were observed among LHB, MHB, and LHB/HBsAg, with HBV serum markers including HBsAg, HBeAg, and HBV DNA. (P < 0.0001). In HBeAg-positive chronic infection, LHB and MHB were higher than in HBeAg-positive CHB (P < 0.01). In HBeAg-negative chronic infection, LHB and MHB were lower than in HBeAg-negative CHB (P < 0.01). ROC analysis identified LHB and MHB as potential discriminators of CHB and chronic infection. LC and HCC exhibited lower LHB, MHB, and MHB/HBsAg than CHB (P < 0.05). Multivariate analysis found that age and the MHB/HBsAg serve as independent factors for the progression of CHB to end stage of liver disease. ConclusionsLHB and MHB emerge as novel biomarkers distinguishing chronic infection and CHB. MHB/HBsAg shows promise as a predictor for CHB progression.

A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol

BackgroundLiver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.MethodsIn this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.DiscussionThe anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.Trial registrationClinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic.clinicaltrials.gov/ct2/show/NCT05502198.

Parental History of Type 2 Diabetes Mellitus and PNPLA3 Polymorphism Increase the Risk of Severe Stages of Nonalcoholic Fatty Liver Disease.

In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis. This was a case-control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan® (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs. 161 T2D offspring and 78 controls, 10-46years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09-72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93-34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11-16.61, p = 0.034). The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.

The Role of Bifidobacterium in Liver Diseases: A Systematic Review of Next-Generation Sequencing Studies.

The physiopathology of liver diseases is complex and can be caused by various factors. Bifidobacterium is a bacterial genus commonly found in the human gut microbiome and has been shown to influence the development of different stages of liver diseases significantly. This study investigated the relationship between the Bifidobacterium genus and liver injury. In this work, we performed a systematic review in major databases using the key terms "Bifidobacterium", "ALD", "NAFLD", "NASH", "cirrhosis", and "HCC" to achieve our purpose. In total, 31 articles were selected for analysis. In particular, we focused on studies that used next-generation sequencing (NGS) technologies. The studies focused on assessing Bifidobacterium levels in the diseases and interventional aimed at examining the therapeutic potential of Bifidobacterium in the mentioned conditions. Overall, the abundance of Bifidobacterium was reduced in hepatic pathologies. Low levels of Bifidobacterium were associated with harmful biochemical and physiological parameters, as well as an adverse clinical outcome. However, interventional studies using different drugs and treatments were able to increase the abundance of the genus and improve clinical outcomes. These results strongly support the hypothesis that changes in the abundance of Bifidobacterium significantly influence both the pathophysiology of hepatic diseases and the related clinical outcomes. In addition, our critical assessment of the NGS methods and related statistical analyses employed in each study highlights concerns with the methods used to define the differential abundance of Bifidobacterium, including potential biases and the omission of relevant information.

Liver segmentation using Mnet for cirrhosis

Liver biopsies for diagnosing cirrhosis, the last stage of chronic liver disease was analysed using imaging and it could able to determine the severity level of the disease. Liver lesions can be segmented for evaluation of tumor burden, therapeutic strategy, prognosis, and follow-up on the efficacy of therapy. Automatic technologies for malignancy identification and segmentation are preferable because manual segmentation is a laborious process that is prone to error. We thus propose an M-Net approach to cirrhosis of the liver segmentation. The liver datasets are collected initially as raw data, which, due to the existence of noise, must be normalized before the investigation can begin. With the help of the Bilateral Filter and the Wavelet Transform, we can get rid of the noise and improve the de-noised image. The Gabor Filter is used for feature extraction. Hybrid Genetic Algorithm (HGA) is used to pick the best feature subsets for classification. Ensemble Deep Convolutional Neural Network (EDCNN) method is applied to the classification process. MATLAB, a simulation program, is used to conduct the entire inquiry. In terms of accuracy, our system has outperformed the most sophisticated automatic techniques.

Albumin, an interesting and functionally diverse protein, varies from ‘native’ to ‘effective’ (Review)

Albumin, an interesting and functionally diverse protein, varies from ‘native’ to ‘effective’ (Review)

SREBP Regulation of Lipid Metabolism in Liver Disease, and Therapeutic Strategies.

Sterol regulatory element-binding proteins (SREBPs) are master transcription factors that play a crucial role in regulating genes involved in the biogenesis of cholesterol, fatty acids, and triglycerides. As such, they are implicated in several serious liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). SREBPs are subject to regulation by multiple cofactors and critical signaling pathways, making them an important target for therapeutic interventions. In this review, we first introduce the structure and activation of SREBPs, before focusing on their function in liver disease. We examine the mechanisms by which SREBPs regulate lipogenesis, explore how alterations in these processes are associated with liver disease, and evaluate potential therapeutic strategies using small molecules, natural products, or herb extracts that target these pathways. Through this analysis, we provide new insights into the versatility and multitargets of SREBPs as factors in the modulation of different physiological stages of liver disease, highlighting their potential targets for therapeutic treatment.

Diagnosis and Treatment of Liver Disease: Current Trends and Future Directions.

This narrative review delves into the intricate landscape of liver diseases, providing a comprehensive background of the diverse conditions that afflict this vital organ. Liver diseases, ranging from viral hepatitis and non-alcoholic fatty liver disease (NAFLD) to cirrhosis and hepatocellular carcinoma (HCC), pose significant global health challenges. Understanding these diseases' multifaceted origins and progression is pivotal for developing effective diagnostic and therapeutic strategies. The epidemiology and etiology of liver diseases emphasize the global impact of viral hepatitis, with hepatitis B and C as significant contributors. Concurrently, the rising prevalence of NAFLD, linked to lifestyle factors and metabolic syndrome, underscores the intricate relationship between modern living and liver health. Chronic liver diseases often evolve insidiously, progressing from inflammation to fibrosis and, ultimately, to cirrhosis - a stage characterized by irreversible scarring and compromised function. The heightened risk of HCC in advanced liver disease stages further underscores the urgency of effective diagnostic and therapeutic interventions. The evolving landscape of non-invasive diagnostic tools is explored for their role in enabling early detection and accurate staging of liver diseases. In the realm of treatment, there is a continuous transition toward personalized medicine, customized to suit the unique profiles of individual patients. This shift encompasses a broad spectrum, ranging from personalized pharmacological interventions to lifestyle modifications and surgical options. Delving into innovative therapies, such as gene editing and immunomodulation, offers a glimpse into the promising future directions that have the potential to redefine the landscape of liver disease diagnosis and treatment.

Survival in Patients with Liver Cirrhosis: A Prospective Study.

Introduction: The differences in the survival time of cirrhotic patients reported by different studies are probably caused by the influence of many contributing factors. The aim of the study was to evaluate the survival over a one-year period, to register the occurrence of acute decompensation (AD) and to determine the most frequent causes of death. Material and methods: Out of 71 patients enrolled in the study, 63 completed the prospective one-year follow-up. During the follow-up, we evaluated the occurrence of AD, the causes of death, and we registered three-month, six-month and one-year survival regarding the AD status at presentation. Results: Of the 63 patients, 24 (38.09%) died before the end of the study (14 patients before the end of three months, 6 before the end of six months and 4 patients before the end of one year). The overall survival was 38.09% and the mean survival time was 108 ± 98.53 days. The most prevalent cause of death was bleeding from esophageal varices (5 patients, 20.83%). AD patients had a significantly shorter survival than patients without AD (97±90.54 vs. 229±138.59) and 78.57% of them died during the follow-up. The estimated six-month and one-year median survival time were 272.8 [95% CI (238.4-307.2)] and 267.1 [95% CI (232.9-301.2)] days, respectively. The six-month and one-year survival were significantly shorter in AD patients (p<0.0001). Conclusion: The etiology, stage of liver disease and the presence of AD are important factors that influence on the survival in cirrhotic patients.

Peculiarities of Metabolism and Cardiac Electrical Activity in Patients with Chronic Obstructive Pulmonary Disease and Coronary Heart Disease in the Presence of Metabolically-Associated Liver Steatosis

While the development of specific steatohepatitis-associated cardiomyopathy (SHACMP) in the context of fatty liver disease has been documented, it remains unclear whether any cardiac changes occur during the initial stage of fatty liver disease, known as metabolic-associated liver steatosis (LS). Objective — to evaluate the characteristics of metabolism and electrical activity of the heart in patients with chronic obstructive pulmonary disease and chronic forms of coronary heart disease and concomitant liver steatosis. Materials and methods. 35 patients with chronic obstructive pulmonary disease, respiratory insufficiency stages I and II, coronary heart disease, atherosclerotic cardiosclerosis, and heart failure functional classes I and II, were examined. Their diagnosis and treatment were conducted in accordance with established protocols and international recommendations. Depending on the occurrence of LS, patients, matched for age, gender and lung function parameters, were divided into two groups: those suffering from it (n = 26) or not suffering from it (n = 9). Additionally, leptin level was determined, body mass index (BMI), leptin to BMI ratio, De Ritis ratio, hepatic steatosis index, glomerular filtration rate (according to MDRD) were calculated, and automatic ECG test was run. The results were processed statistically; the significance assumed at р &lt; 0.05. Results and discussion. It was established that LS was diagnosed in patients with a higher BMI and was accompanied by clear metabolic changes — higher values of leptin, leptin-to-BMI ratio, fasting blood glucose and total cholesterol levels. The criteria of LS are not only an increase in echogenicity and size of the liver, but also higher values of ALT, De Ritis ratio and hepatic steatosis index. According to the correlation analysis, the deterioration of the liver condition was accompanied by changes in the heart — tachycardia and a decrease in the angle of the QRS complex, which can be considered as signs of the development of SHACMP, characteri­zed by a prolongation of the PQ interval (р = 0.07) and a significant deviation of the angle of the QRS complex. Inflammation and endogenous intoxication are the leading mechanisms of progression of both LS and SHACMP. Conclusions. Patients with chronic obstructive pulmonary disease and chronic forms of coronary heart disease, alongside with liver steatosis, exhibit signs of steatohepatitis-associated cardiomyopathy caused by metabolic changes, inflammation and endogenous intoxication.

Сhanges in the composition of gut microbiota in patients with chronic hepatitis С, non-alcoholic fatty liver disease at different stages of liver disease: a review

INTRODUCTION. The human gut microbiota is a set of microorganisms that are in symbiosis with the host organism. The predominance of bacteria of Bacteroidetes, Firmicutes, Actinobacteria types is a characteristic feature of human gut microbiota. However, the composition of the gut microbiota is subject to change under the influence of a number of factors. The influence of the gut-liver axis on the pathogenesis of many chronic liver diseases of various etiologies, both infectious and metabolic, has been proven. At the same time, in the analyzed literature, the data on the relationship between the nature of GM changes and the stage of liver damage are quite controversial.&#x0D; OBJECTIVE. Updating and systematization of ideas about the nature of changes in the composition of intestinal microbiota in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) at different stages of the disease.&#x0D; MATERIALS AND METHODS. We analyzed the scientific literature on GM changes in chronic liver diseases with regard to their etiology and disease stage, in particular in chronic viral hepatitis C and NAFLD. The search was conducted in PubMed, Google Scholar, and eLIBRARY databases for 2000-2023 using the following keywords: gut microbiota; microbiota in hepatitis C; microbiota in NAFLD; microbiota in liver fibrosis; liver fibrosis progression. Sixty scientific articles were analyzed and 42 sources were selected, of which more than 60% were published within the last five years.&#x0D; RESULTS. This review presents the results of original studies describing the main taxonomic differences between the microbiomes of healthy individuals and patients with CHC complicated by the formation of liver cirrhosis and hepatocellular carcinoma (HCC). Thus, patients with viral cirrhosis showed impoverishment of intestinal commensals Lachnospiraceae and Ruminococcaceae and significant enrichment of Streptococcaceae, Lactobacillaceae and Enterobacteriaceae. In patients with non-alcoholic steatohepatitis (NASH) and FII, enrichment of GM Phylum Bacteroides and Proteobacteria, Families Lachnospiraceae and Enterobacteriaceae, Genera Blautia and Escherichia, with a concomitant decrease of Prevotella was detected.&#x0D; DISCUSSION. The analysis of GM taxonomic units in the previously described studies did not reveal significant differences depending on the etiology of the underlying disease. However, a decrease in the representative of the phylum Firmicutes - Ruminococcaceae was observed in CHC in contrast to NAFLD. A more distinct relationship can be observed in the changes of intestinal microbiota in F(III-IV) irrespective of etiology. Thus, in advanced liver fibrosis and cirrhosis of both CHC and NAFLD etiologies, enrichment of GM has been described due to an increase in phylum Proteobacteria, in particular the genus Escherichia and phylum Firmicutes (Blautia, Veillonellaceae). In the studies analyzed, at F(III-IV), an enrichment of the microbiota is observed due to an increase in the phylum Bacteroidetes. Regarding the genus Prevotella, contradictory results were found. In addition, there are ambiguous data regarding the genera Lactobacillus, Ruminococcaceae and Bifidobacteria.&#x0D; CONCLUSION. Based on the results of the literature review, we obtained contradictory data on GM composition in patients with CHC and NAFLD. This may be due to the size of samples, heterogeneity of initial data during the selection of patients in the study. The relationship between the composition of microbiota and persistent inflammatory process, expressed liver fibrosis is observed. GM reflects not only functional disorders in chronic liver diseases of various etiologies, but can also serve as a diagnostic indicator of their progression.

Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis.

Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.

Liver fibrosis is associated with left ventricular remodeling: insights into the liver-heart axis

Abstract Background Non-alcoholic fatty liver disease (NAFLD), common in type 2 diabetes, has emerged as an important and independent risk factor for adverse cardiac remodeling. Fibrosis in the liver could be a key factor in this relationship. Despite the fact that NAFLD is a long-term progressive disease, imaging studies on this topic are mainly limited to selected patients from tertiary centres. Purpose To investigate the relationship between liver fat, liver fibrosis and cardiac remodeling in the general population. We also sought to explore biomarkers of cardiovascular inflammation and fibrosis, for possible mechanistic pathways in these relationships. Methods We included 46 participants with type 2 diabetes and 46 age and sex-matched controls (overall 35%/65% F/M, mean age 59.5 ± 4.6), all randomly sampled from the general population. Participants underwent careful clinical phenotyping, including blood sampling, echocardiography, and magnetic resonance imaging (MRI) at 1.5 T. The MRI protocol included sequences for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography at 56 Hz), left ventricular (LV) structure, function, and tissue characteristics (native T1 mapping). We also analyzed ∼290 circulating cardiovascular biomarkers. A Bayesian statistical approach (‘Stochastic Search Variable Selection’) was used to identify the biomarkers most strongly associated with cardiac remodeling. Results For liver stiffness, the mean value was 2.1 ± 0.4 kPa and the highest value was 2.9 kPa. The median liver fat value was 5.7% (IQR 9.9%) and 53 participants (58%) displayed hepatic steatosis (liver fat &amp;gt; 5%). LV concentricity increased across quartiles of liver stiffness (P=0.0014 for ANOVA), while LV concentricity and diastolic dysfunction increased across quartiles of liver fat (P=0.0023 and P=0.030 for ANOVA, respectively). Myocardial T1 displayed no relationships to neither liver fat nor liver stiffness. In a multiple linear regression, liver stiffness was positively associated with LV concentricity (Beta=0.26, P=0.0053), independently of diabetes and liver fat. This association was attenuated (Beta=0.17, P=0.077) when adjusting for circulating levels of IL-1 receptor type 2, the biomarker with the strongest association to LV concentricity in the Bayesian statistical analysis. Conclusion In our well-characterized subjects from the general population, we found that a majority had hepatic steatosis but overall rather low liver stiffness values. Despite this, liver stiffness was related to increased LV concentricity independently of liver fat and diabetes. This association was attenuated when also adjusting for IL-1 receptor type 2. Our results suggest a link between liver fibrosis and cardiac remodeling also in the early stages of fatty liver disease, possibly involving the IL-1 signaling pathway. Future studies are needed to further establish causality and potential mechanisms.Multiple linear regression analysesLiver magnetic resonance elastogram