Project description:Liver fibrosis is a common result of most chronic liver diseases, and advanced fibrosis often leads to cirrhosis. Currently, there is no effective treatment for liver cirrhosis except liver transplantation. Therefore, it is important to carry out antifibrosis treatment to reverse liver damage in the early stage of liver fibrosis. Mesenchymal stem cells (MSCs) are the most widely used stem cells in the field of regenerative medicine. The preclinical and clinical research results of MSCs in the treatment of liver fibrosis and cirrhosis show that MSC administration is a promising treatment for liver fibrosis and cirrhosis. MSCs reverse liver fibrosis and increase liver function mainly through differentiation into hepatocytes, immune regulation, secretion of cytokines and other nutritional factors, reduction of hepatocyte apoptosis, and promotion of hepatocyte regeneration. Recently, many studies provided a variety of new methods and strategies to improve the effect of MSCs in the treatment of liver fibrosis. In this review, we summarized the current effective methods and strategies and their potential mechanisms of MSCs in the treatment of liver fibrosis, as well as the current research progress in clinical practice. We expect to achieve complete reversal of liver injury with MSC-based therapy in the future.
Project description:Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression. To properly detect fibrosis, it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores, followed by a complementary imaging study (transient elastography, magnetic resonance elastography or acoustic radiation force impulse) and finally a liver biopsy, when needed. To help with the selection of the most appropriate method a Fagan's nomogram analysis is provided in this review, describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis. Finally, treatment should always include diet and exercise, as well as controlling the components of the metabolic syndrome, +/- vitamin E, considering the presence of sleep apnea, and when available, allocate those patients with advanced fibrosis or high risk of progression into clinical trials. The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD, aiming to decrease/stop its progression and improve their prognosis.
Project description:Technologies for digitizing tissues provide important quantitative data for liver histopathology investigation. We aimed to assess liver fibrosis degree with quantitative morphometric measurements of histopathological sections utilizing digital image analysis (DIA) and to further investigate if a correlation with histopathologic scoring (Scheuer staging) exists. A retrospective study of patients with at least two post-liver transplant biopsies having a Scheuer stage of ? 2 at baseline were gathered. Portal tract fibrotic percentage (%) and size (?m2) were measured by DIA, while clinical fibrosis score was measured by the Scheuer system. Correlations between DIA measurements and Scheuer scores were computed by Spearman correlation analysis. Differences between mean levels of fibrosis (score, size, and percentage) at baseline versus second visit were computed by Student's t-test. P values < 0.05 were considered significant. Of 22 patients who met the study criteria, 54 biopsies were included for analysis. Average levels ±standard error [S.E.] of portal tract fibrotic percentage (%) and size (?m2) progressed from 46.5 ± 3.6% at baseline to 61.8 ± 3.8% at the second visit (P = 0.005 by Student's t-test), and from 28,075 ± 3,232 ?m2 at base line to 67,146 ± 10,639 ?m2 at the second visit (P = 0.002 by Student's t-test), respectively. Average levels of Scheuer fibrosis scores progressed from 0.55±0.19 at baseline to 1.14±0.26 at the second visit (P = 0.02 by Student's t-test). Portal tract fibrotic percentage (%) and portal tract fibrotic size were directly correlated with clinical Scheuer fibrosis stage, with Spearman correlation coefficient and P value computed as r = 0.70, P < 0.0001 and r = 0.41, P = 0.002, respectively. Digital quantitative assessment of portal triad size and fibrosis percentage demonstrates a strong correlation with visually assessed histologic stage of liver fibrosis and complements the standard assessment for allograft monitoring, suggesting the utility of future WSI analysis.
Project description:Liver fibrosis is one of the risk factors for hepatocellular carcinoma (HCC) development. The staging of liver fibrosis can be evaluated only via a liver biopsy, which is an invasive procedure. Noninvasive methods for the diagnosis of liver fibrosis can be divided into morphological tests such as elastography and serum biochemical tests. Transient elastography is reported to have excellent performance in the diagnosis of liver fibrosis and has been accepted as a useful tool for the prediction of HCC development and other clinical outcomes. Two-dimensional shear wave elastography is a new technique and provides a real-time stiffness image. Serum fibrosis markers have been studied based on the mechanism of fibrogenesis and fibrolysis. In the healthy liver, homeostasis of the extracellular matrix is maintained directly by enzymes called matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). MMPs and TIMPs could be useful serum biomarkers for liver fibrosis and promising candidates for the treatment of liver fibrosis. Further studies are required to establish liver fibrosis-specific markers based on further clinical and molecular research. In this review, we summarize noninvasive fibrosis tests and molecular mechanism of liver fibrosis in current daily clinical practice.
Project description:Background and aimThe Gut and Obesity in Asia Workgroup recently reported that a two-step approach using fibrosis scores followed by liver stiffness measurement (LSM) could accurately detect patients with non-alcoholic fatty liver disease (NAFLD) having advanced fibrosis in low-risk fibrosis populations. This study aimed to validate the utility of this approach using a Japanese health checkup registry.MethodsThis cross-sectional study included subjects who underwent a health checkup from 2014 to 2019. Using estimated fibrosis stage measured by LSM as a standard, we calculated the percentage of misclassification from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score [FIB-4]) and LSM, alone or in combination.ResultsOf 630 subjects with NAFLD, 4 (0.8%) had advanced fibrosis. In the first-step evaluation, only 21.4-38.0% of subjects needed further testing. This approach was associated with a high specificity of approximately 100% and a negative predictive value of 99.7%. The percentage of misclassification based on NFS or FIB-4 values followed by LSM in all subjects and using LSM after NFS or FIB-4 determination only in subjects with indeterminate/high NFS or FIB-4 values (two-step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively. In addition, very few false negatives occurred for both NFS and FIB-4.ConclusionThe two-step approach helps to identify the subjects with NAFLD who have advanced fibrosis during a routine health checkup and is associated with only a few false negatives.
Project description:Liver fibrosis, is an urgent public health problem and is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of messenger RNA (mRNA) and long non-coding RNA (lncRNA) in different groups of liver tissues, and screened for differentially expressed genes, as well as performed gene co-expression analysis of the differential lncRNAs and mRNAs. The results showed that compared with the model group, the phloridzin treated groups showed a significant decrease in collagen deposition, and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell-substrate junctions, and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism and related changes in biomechanics.
Project description:Background & aimsCystic Fibrosis related liver disease (CFLD) is the 3rd largest cause of death in Cystic Fibrosis (CF). As advances in pulmonary therapies have increased life-expectancy, CFLD has become more prevalent. Current guidelines may underdiagnose liver fibrosis, particularly in its early stages. Newer modalities for the assessment of fibrosis may provide a more accurate assessment. FibroScan is validated in assessing fibrosis for several aetiologies including alcohol and fatty liver, the CFLD cohort have an entirely different phenotype so the cut off values are not transferrable. We appraised fibrosis assessment tools to improve diagnosis of CFLD.MethodsA prospective cohort (n = 114) of patients from the Manchester Adult Cystic Fibrosis Centre, UK were identified at annual assessment. Demographic data including co-morbidity, CFTR genotyping, biochemistry and imaging were used alongside current guidelines to group into CFLD and CF without evidence of liver disease. All patients underwent liver stiffness measurement (LSM) and assessment of serum-based fibrosis biomarker panels. A new diagnostic criterion was created and validated in a second, independent cohort.Results12 of 114 patient classified as CFLD according to the European Cystic Fibrosis Society best practice guidelines. No specific risk factors for development of CFLD were identified. Liver enzymes were elevated in patients with CFLD. Serum biomarker panels did not improve diagnostic criteria. LSM accurately predicted CFLD. A new diagnostic criterion was proposed and validated in a separate cohort, accurately predicating CFLD in 10 of 32 patients (31 %).ConclusionWe present a cohort of patients with CF assessed for the presence of liver fibrosis using blood biomarkers and LSM based platforms. We propose a new, simplified diagnostic criteria, capable of accurately predicting liver disease in patients with CF.Clinical trials number: NCT04277819.
Project description:ObjectivesTo assess the quality of the currently available clinical practice guidelines (CPGs) for hepatocellular carcinoma, and provide a reference for clinicians in selecting the best available clinical protocols.MethodsThe databases of PubMed, MEDLINE, Web of Science, Chinese Biomedical Literature database (CBM), China National Knowledge Infrastructure (CNKI), WanFang, and relevant CPGs websites were systematically searched through March 2014. CPGs quality was appraised using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument, and data analysis was performed using SPSS 13.0 software.ResultsA total of 20 evidence-based and 20 expert consensus-based guidelines were included. The mean percentage of the domain scores were: scope and purpose 83% (95% confidence interval (CI), 81% to 86%), clarity of presentation 79% (95% CI, 73% to 86%), stakeholder involvement 39% (95% CI, 30% to 49%), editorial independence 58% (95% CI, 52% to 64%), rigor of development 39% (95% CI, 31% to 46%), and applicability 16% (95% CI, 10% to 23%). Evidence-based guidelines were superior to those established by consensus for the domains of rigor of development (p<0.001), clarity of presentation (p?=?0.01) and applicability (p?=?0.021).ConclusionsThe overall methodological quality of CPGs for hepatocellular carcinoma and metastatic liver cancer is moderate, with poor applicability and potential conflict of interest issues. The evidence-based guidelines has become mainstream for high quality CPGs development; however, there is still need to further increase the transparency and quality of evidence rating, as well as the recommendation process, and to address potential conflict of interest.
Project description:Lifestyle modification comprising calorie restriction (CR) and increased physical activity enabling weight loss is the first-line of treatment for non-alcoholic fatty liver disease (NAFLD). However, CR alone is not optimal and evidence suggests that dietary pattern and composition are also critical in NAFLD management. Accordingly, high consumption of red and processed meat, saturated fat, added sugar, and sweetened beverages are associated with an increased risk of developing NAFLD and hepatocellular carcinoma, while other foods and compounds such as fish, olive oil, and polyphenols are, in contrast, beneficial for metabolic disorders. Therefore, several dietary interventions have been studied in order to determine which strategy would be the most beneficial for NAFLD. The evidence regarding the effectiveness of different dietary interventions such as low carbohydrate/low-fat diet, time-restricted eating diet, CR, and the well-studied Mediterranean diet is summarized.
Project description:IntroductionVaricoceles are abnormal dilatations of the pampiniform venous plexus. They are classified as primary or secondary, depending on their cause, and staged clinically on the basis of their extension and on the presence or the absence of spontaneous or induced reversal of blood flow.Materials and methodsWe examined 95 patients (age range: 3-77 years) using Color Doppler ultrasound with settings optimized for the study of slow flow. All patients found to have varicoceles underwent ultrasonographic assessment of the kidneys and retroperitoneum. Findings were classified with a simplified version of the Sarteschi system.Results41 (43.1%) of the patients were found to have varicoceles, which were classified as grade 1 in 11 cases, grade 2 in 13, grade 3 in 10, and grade 4 in 7 according to the simplified Sarteschi classification.DiscussionOur results are with those reported in the literature. They confirm that varicoceles are a frequent finding and ultrasonography is currently the best imaging technique for its diagnosis and also for the post-surgery follow-up.