Liver Fibrosis Index Research Articles

Association Between Liver Fibrosis and Risk of Incident Stroke and Mortality: ALarge Prospective Cohort Study.

There is a well-established relationship between liver conditions and cardiovascular diseases. However, uncertainty persists regarding the contribution of liver fibrosis to major stroke types including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage at the population level. In this large prospective cohort study, participants without previous stroke or coronary heart disease at baseline from the UK Biobank were included. We identified participants at high probability of advanced liver fibrosis using the Fibrosis-4 index >2.67 or aspartate aminotransferase to platelet ratio index ≥1.0. Multivariable Cox proportional hazard regression analyses were conducted to estimate hazard ratios (HRs) for liver fibrosis with the incidence of major stroke types, stroke-related death, and all-cause death. Among 379 953 participants (mean age, 56.2 [SD, 8.1] years; 44.6% men), 7396 (1.9%) had a Fibrosis-4 index >2.67 at baseline. During a median follow-up of 12.75 (interquartile range, 12.03-13.48) years, 7143 (1.9%) incident stroke cases were documented. Advanced liver fibrosis assessed by the Fibrosis-4 index was associated with an increased risk of ischemic stroke (HR, 1.94 [95% CI, 1.70-2.22]), intracerebral hemorrhage (HR, 2.14 [95% CI, 1.63-2.81]), subarachnoid hemorrhage (HR, 1.90 [95% CI, 1.27-2.84), stroke-related death (HR, 2.20 [95% CI, 1.73-2.80]), and all-cause death (HR, 2.59 [95% CI, 2.46-2.73]). Using the aspartate aminotransferase to platelet ratio index as an alternative score, liver fibrosis was correlated with magnified risk of intracerebral hemorrhage (HR, 3.76 [95% CI, 2.38-5.93]) and subarachnoid hemorrhage (HR, 3.05 [95% CI, 1.51-6.13]) compared with ischemic stroke (HR, 1.58 [95% CI, 1.17-2.14]). Restricted cubic spline analysis showed nonlinear associations of the Fibrosis-4 index and aspartate aminotransferase to platelet ratio index with stroke incidence and all-cause death. Liver fibrosis is associated with increased risk of incident stroke and death among people without previous stroke or cardiovascular events, with particularly greater risk of intracerebral hemorrhage and subarachnoid hemorrhage. Noninvasive indices of liver fibrosis may serve as an easily accessible marker to detect individuals facing elevated risk of stroke and death in the primary prevention settings.

P0243 Evaluation of liver fibrosis and steatohepatitis associated with metabolic dysfunction (MASH) in patients with inflammatory bowel disease (IBD) and steatotic liver disease associated with metabolic dysfunction (MASLD)

Abstract Background Inflammatory bowel disease (IBD) is associated with a systemic inflammatory state and dysbiosis, which may increase the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). This occurs through intestinal bacterial translocation and the increased entry of lipopolysaccharides, free fatty acids, and other toxins into the liver via the portal circulation. One significant complication of MASLD is metabolic dysfunction-associated steatohepatitis (MASH), which can progress to cirrhosis. This study aimed to evaluate the prevalence of MASLD in IBD patients and assess the frequency of complications, such as MASH and liver fibrosis. Methods The presence of MASLD was based on the presence of NAFLD associated with the metabolic criterion in outpatients with IBD. The presence of NAFLD was confirmed using liver ultrasound. Noninvasive estimate of liver fibrosis (FIB-4) Index and NAFLD Fibrosis Score (NFS) were used as indirect scores of liver fibrosis. Patients with scores greater than NFS > 0.675 and/or FIB-4 > 2.67; and patients with indeterminate or discordant scores were indicated for liver biopsy to quantify liver fibrosis and evaluate MASH. Liver elastography was not performed due to unavailability in our center. Results A total of 179 patients underwent liver ultrasound, with 72 (40.2%) diagnosed with MASLD, including 33 with Crohn’s disease (CD) and 39 with ulcerative colitis (UC). Regarding disease activity, 36.11% were clinically active and 50% were endoscopically active. Biological therapy was used by 54.2% of patients. The degree of steatosis was mild (41.67%), moderate (44.4%) and intense (13.89%). According to the FIB-4 Index, patients were classified as low risk of fibrosis (72.22%), intermediate risk (26.32%) and high risk (1.39%). According to the NFS, the risks for fibrosis were low (53.52%), undetermined (38.08%) and high (8.45%). Sixteen (22.22%) patients underwent liver biopsy, and the presence of fibrosis was observed in 11 (68.75%) patients. The histological stage of fibrosis was F1 (n=6, 54.5%), F2 (n=3, 27,3%), F3 (n=1, 9.1%) and F4 (n=1, 9.1%) according to Kleiner's classification. 4 patients (25%) met criteria for MASH. Conclusion A high prevalence of MASLD was observed in patients with IBD. Among patients with MASLD, we must be aware of the risk of liver fibrosis and MASH. Routine monitoring of liver function and fibrosis, including liver biopsy or elastography when appropriate, is crucial for early detection and management of complications. Due to the lack of routine elastography in our center in Brazil, liver biopsy remains essential for accurate assessment in those patients.

MiRNAs and Hematological Markers in Non-Alcoholic Fatty Liver Disease-A New Diagnostic Path?

Background: Asymptomatic liver steatosis constitutes an emerging issue worldwide. Therefore, we decided to explore relationships between selected types of microRNAs (miRNAs), serological markers of liver fibrosis and hematological parameters in the course of non-alcoholic fatty liver disease (NAFLD). Methods: Two hundred and seven persons were included in the survey: 97 with NAFLD and 110 healthy controls. Serological concentrations of miR-126-3p, miR-197-3p, and miR-1-3p were measured in all participants. Direct indices of liver fibrosis [procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin] together with indirect markers (AAR, APRI, FIB-4 and GPR) were also evaluated. The assessment of hematological parameters concerned: mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), red blood cell distribution width (RDW), MPV to platelet (PLT) ratio (MPR), RDW to PLT ratio (RPR), neutrophil to lymphocyte (LYM) ratio (NLR), PLT to LYM ratio (PLR) and RDW to LYM ratio (RLR). Additionally, the NAFLD fibrosis score and BARD score were applied. Results: The concentration of miR-126-3p and miR-1-3p was higher, and miR-197-3p was lower in the NAFLD group (p < 0.0001). miR-197-3p correlated notably with hematological indices: negatively with PDW (p < 0.05) and positively with PLR (p < 0.05). Conclusions: Significant correlations between miRNA molecules and hematological markers in the course of NAFLD indicate inflammation as a potential background and create new possibilities for a diagnostic approach.

High-intensity interval aerobic exercise delays recovery from heart rate variability: a systematic review with meta-analysis.

The present review investigates the responses of heart rate variability indices following high-intensity interval aerobic exercise, comparing it with moderate-intensity continuous exercise in adults, with the aim of informing clinical practice. Searches were conducted in four databases until March 2023. Eligible studies included randomized controlled trials that assessed heart rate variability indices such as the standard deviation of normal-to-normal heartbeat intervals (SDNN), the root mean square of successive differences (RMSSD), the proportion of the number of pairs of successive normal-to-normal (NN or R-R) intervals that differ by more than 50 ms (NN50) divided by the total number of NN intervals (pNN50), power in high frequency range (HF), power in low frequency range (LF), and LF/HF before and after high-intensity interval and moderate-intensity continuous aerobic exercise. The risk of bias in included studies was evaluated using the RoB 2 tool. A total of 16 studies were included in the systematic review, while 9 were included in the meta-analysis. Overall, the majority of included individuals were healthy and young. Our meta-analysis indicated that individuals who performed high-intensity interval exercise showed a slower recovery to baseline levels for HF (standardized mean difference, SMD-0.98 [95% CI -1.52 to -0.44], p<0.001) and LF (SMD-0.42 [95% CI -0.81 to -0.02], p=0.04) within the first 10 min of recovery, which did not occur after 1 h. Among the 16 included studies, 10 had some concerns related to bias risk, while 6 were classified as high risk. High-intensity interval aerobic exercise results in delayed recovery of HF and LF indices within the first 10 min after the session. However, our review indicates that healthy individuals restore modulation of the autonomic nervous system to baseline levels after this time interval, regardless of exercise intensity.

Correlation of sarcopenia with progression of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease: a study from two cohorts in China and the United States

ObjectiveThe objective of this study was to investigate the association between sarcopenia and liver fibrosis in patients aged 18–59 years with metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential of sarcopenia as a risk factor for the progression of liver fibrosis.MethodsThe study included 821 patients with MASLD in the US cohort and 3,405 patients with MASLD in the Chinese cohort. Liver controlled attenuation parameters (CAP) and liver stiffness measurements (LSM) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the extent of hepatic steatosis and fibrosis. Sarcopenia was assessed by measuring appendicular skeletal muscle mass (ASM) and calculating ASMI. To analyze the relationship between sarcopenia, ASMI, and liver fibrosis, logistic regression models, multivariate-adjusted models, and restricted cubic spline (RCS) models were employed, with stratification and interaction analyses.ResultsThe results demonstrated that patients with sarcopenia exhibited a markedly elevated risk of significant liver fibrosis, advanced liver fibrosis, and cirrhosis compared to those without sarcopenia in both cohorts. After adjusting for confounding variables, sarcopenia was identified as an independent risk factor for the progression of liver fibrosis in patients with MASLD. A significant negative correlation was observed between ASMI and the severity of liver fibrosis, with a progressive reduction in the risk of liver fibrosis associated with increasing ASMI. Additionally, a non-linear feature was evident in some liver fibrosis indicators. Subgroup analysis further corroborated the finding that the harmful effect of sarcopenia on liver fibrosis was consistent across all identified subgroups.ConclusionSarcopenia may be associated with the progression of liver fibrosis in patients with MASLD. Monitoring ASMI may assist in identifying individuals at an elevated risk of liver fibrosis in MASLD patients.

Effects of the SGLT2 inhibitor ipragliflozin and metformin on hepatic steatosis and liver fibrosis: Sub-analysis of a randomized controlled study.

To compare the effects of ipragliflozin, a sodium-dependent glucose transporter-2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi-centre, open-label, blinded-endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis. In total, 103 Japanese patients with type-2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m2 and glycated haemoglobin level of 7%-10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. Various parameters, including hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS), liver fibrosis indices, AST to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index, were compared in the sub-analyses. The correlations between changes in each index and VFA were evaluated. At baseline, patients demonstrated moderate hepatic steatosis, with FLI scores of 52.9 ± 26.6 and 57.8 ± 29.0 in the ipragliflozin and metformin groups, respectively. At 24 weeks, compared with metformin, ipragliflozin showed improvements in hepatic steatosis indices: FLI (-9.24 ± 10.7 vs. -3.45 ± 11.8, p = 0.013), HSI (-1.45 ± 2.32 vs. -0.45 ± 1.87, p = 0.021), NAFLD-LFS (-0.70 ± 1.46 vs. -0.04 ± 0.98, p = 0.011) and liver fibrosis index: APRI (-0.110 ± 0.323 vs. 0.033 ± 0.181, p = 0.010). In the ipragliflozin group, changes in FLI and HSI were correlated with VFA reduction (r = 0.340, p = 0.024; r = 0.367, p = 0.011, respectively). Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early-stage liver disease associated with T2D.

A randomized clinical study to evaluate the possible antifibrotic effect of zinc sulfate in chronic HCV patient receiving direct-acting anti-viral therapy.

This study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy. This randomized controlled study included 50 chronic HCV-infected patients with fibrosis stage (F1 & F2). Participants were randomly assigned to two groups: Group 1 (Control group, n = 25) received standard direct-acting antiviral therapy for 3months, while Group 2 (Zinc group, n = 25) received 50mg/day of zinc sulfate in addition to the standard direct-acting antiviral therapy for the same duration. Baseline and 3-month post-intervention assessments included evaluating serum levels of hyaluronic acid, transforming growth factor beta-1, and fibronectin. Furthermore, indices of liver fibrosis, such as the Fibrosis Index based on the 4 factors (FIB-4) and the Aspartate Transaminase-to-Platelet-Ratio Index (APRI), were calculated during these assessments. At baseline, the two studied groups had no statistical difference in demographic and laboratory data. After treatment, serum zinc levels significantly increased in the zinc-treated group compared to the control group. Additionally, serum fibronectin and hyaluronic acid levels were significantly reduced in group 2 (zinc group) compared to group 1 (control group). Moreover, zinc group showed lower APRI scores than the control group after a 3-month follow-up period, but there was non-significant difference in FIB-4 scores between the two groups after treatment. Furthermore, total bilirubin levels were reduced after zinc therapy for 3months. Administering zinc sulfate could potentially serve as a safe and efficient therapeutic strategy for the management of hepatic fibrosis in individuals with chronic hepatitis C virus. ClinicalTrials.gov identifier: NCT05465434, On 19/7/2022.

Effect of elexacaftor-tezacaftor-ivacaftor on liver transient elastography, fibrosis indices and blood tests in children with cystic fibrosis.

Elexacaftor-tezacaftor-ivacaftor (ETI) has significantly improved the clinical course of people with cystic fibrosis (pwCF) and eligible CFTR variants. In this study, we prospectively evaluated liver elastography, liver fibrosis indices and liver tests in children with CF aged 6-12 years started on ETI therapy. Body mass index, sweat test, percent predicted forced expiratory volume in one second, serum markers of liver injury or portal hypertension, liver fibrosis indices, controlled attenuation parameter and liver stiffness were assessed before starting ETI and three and twelve months post-ETI, according to new international guidelines. 27 children with CF were enrolled, 14 with liver involvement and 13 without liver involvement at baseline. A significant improvement in sweat chloride after ETI was observed in all subjects. In those with liver involvement, liver stiffness significantly decreased at 12 months of ETI, with all individuals achieving normalization or near-normalization of liver stiffness. The majority of individuals with abnormal AST, ALT, GGT, or liver fibrosis indices at baseline experienced normalization by 12 months of ETI (AST: 67%, ALT: 100%, GGT: 50%, APRI: 100%, GPR: 100%). In the no liver involvement group, the only significant change in liver health metrics at 12 months was a significant reduction in platelets (P<0.05) that remained within the normal range. ETI is associated with improvement in liver stiffness, liver function tests and fibrosis indices in pwCF and liver involvement. ETI may reduce the development of advanced CF liver disease, but longer observations with larger cohorts are needed.

Efficacy of imeglimin in patients with type 2 diabetes mellitus complicated by metabolic dysfunction-associated steatotic liver disease: A multicentre study.

This study aimed to evaluate the effectiveness of imeglimin in improving liver function and fibrosis in patients with type 2 diabetes (T2D) complicated by metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a multicentre study involving 80 patients with T2D and MASLD who were treated with or without imeglimin for 24 weeks. We assessed the changes in diabetes-related parameters, including HbA1c, fasting blood glucose, glycoalbumin and C-peptide index. Liver function was monitored using AST, ALT, γ-GTP and liver fibrosis indicators such as Fib-4 index and FibroScan-AST (FAST) score. Liver fat content and stiffness were measured using controlled attenuation parameter and vibration-controlled transient elastography, which were measured using FibroScan. Compared with the control group, imeglimin treatment led to a significant reduction in HbA1c levels, fasting blood glucose and liver-related parameters, including AST, ALT and γ-GTP. Additionally, the Fib-4 index and FAST score, which reflect liver fibrosis and inflammation, were significantly lower in the imeglimin group. Liver fat content and stiffness remained unchanged during the study period. Imeglimin efficaciously improved liver inflammation and fibrosis in patients with T2D and MASLD, with no significant changes in liver fat content or stiffness. These findings suggest that imeglimin is a promising therapeutic drug for the management of MASLD in the context of T2D, warranting further research on its long-term efficacy and mechanisms of action.

Meta-analysis of the efficacy of the Fuzheng Huayu formula in the treatment of hepatitis B-associated liver fibrosis or cirrhosis

Objective: To systematically evaluate the efficacy of Fuzheng Huayu (FZHY) tablets/capsules on hepatitis B-associated liver fibrosis or cirrhosis based on randomized controlled trials (RCTs) in order to provide more accurate evidence-based medicine for clinical rational drug use. Methods: Randomized controlled clinical trial research reports related to the treatment of hepatitis B-associated liver fibrosis or cirrhosis with FZHY published in SCI and statistical source core journals were retrieved from databases such as PubMed, Cochrane Library, and China National Knowledge Infrastructure (CNKI). RevMan 5.3 and Stata18.0 software were used to conduct a meta-analysis of the improvement rate of liver tissue inflammatory activity (HAI) and Ishak stage of liver fibrosis, the decrease value of liver stiffness measurement (LSM), hyaluronic acid (HA), laminin (LN), type Ⅲ procollagen (PC-Ⅲ), type Ⅳ collagen (IV-C), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (Alb). The Q test was used for the heterogeneity test, with a random-effect model selected for large heterogeneity and a fixed-effect model for less heterogeneity. Results: A total of 852 articles were retrieved. Duplicate articles, non-RCT articles, non-SCI/statistical source/core journal articles, and other articles that did not meet the inclusion criteria were sequentially excluded. Finally, a total of 2 746 cases (1 382 cases in the FZHY group and 1 364 cases in the control group) were included from 25 studies. The results of statistical analysis showed that the improvement rates of HAI grade of liver inflammation were 75.56% (68/90) and 42.22% (38/90, P<0.001) in the FZHY group and the control group at 24-48 weeks of treatment, while the improvement rates of Ishak stage of liver fibrosis were 67.90% (110/162) and 40.91% (63/154, P=0.005), respectively. Compared with the control group (95%CI -5.10-1.77, P<0.001) the mean △LSM of the FZHY group decreased by 3.43 kPa (P<0.001)and 0.30 kPa (P=0.93) at 48 and 72 weeks of treatment. The standardized mean differences (SMDs) of △HA, △LN, △PC-Ⅲ and △Ⅳ-C were -1.12, -1.00, -0.89 and -1.10 (P<0.001) after 24 weeks of treatment between the FZHY group and the control group. The SMDs of △HA, △IV-C, △LN and △PC-Ⅲ were -1.13 (P=0.01), -1.51 (P<0.001), -0.53 (P=0.14) and -0.42 (P=0.19) after 48 weeks of treatment between the two groups. The △TBil, △ALT, △AST, and △ALB was -12.99 μmol/L (P=0.007), -36.91 U/L (P<0.001), -22.05 U/L (P=0.12), and 6.09 g/L (P=0.05) after 24 weeks of treatment between the two groups. The observation on indicators such as aspartate aminotransferase and platelet ratio index, fibrosis-4 index, and hepatocellular carcinoma incidence in current RCT studies remained deficient. Conclusion: FZHY can significantly improve the degree of histologic liver inflammation and fibrosis, LSM values, reduce serum liver fibrosis indexes, and serum bilirubin and transaminase levels in patients with hepatitis B-associated liver fibrosis or cirrhosis. Therefore, it is necessary to further explore the optimal course of FZHY and its long-term effects on the risk of complications of cirrhosis such as hepatocellular carcinoma, ascites, and esophageal varicose bleeding, through prospective large-sample multicenter real-world cohort studies.

The Fibrosis-4 index for advanced liver fibrosis in NAFLD with T2DM: Half a loaf is better than no bread.

The Fibrosis-4 index for advanced liver fibrosis in NAFLD with T2DM: Half a loaf is better than no bread.

Effect of Dendrobium nobile powder combined with conventional therapy on mild to moderate fatty liver.

Nonalcoholic fatty liver disease (NAFLD) encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol. Recently, traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver, among which Dendrobium nobile Lindl. powder has been affirmed by many doctors and patients to be effective. However, there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD. To survey the effect of combining Dendrobium nobile Lindl. powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD. Eighty patients with mild to moderate NAFLD participated in this retrospective study, classified into two groups: The observation group (n = 40) and the control group (n = 40). In November 2020 and November 2022, the study was conducted at People's Hospital of Chongqing Liang Jiang New Area. The control group received standard treatment, while the observation group received Dendrobium nobile Lindl. powder based on the control group. The study compared differences in traditional Chinese medicine clinical syndrome scores, liver fibrosis treatment, liver function indicators, lipid levels, and serum inflammatory factor levels before and after treatment, and we calculated the incidence of adverse reactions for both groups. The total effective rate was 97.50% in the observation group and 72.5% in the control group. After 8 weeks of treatment, the main and secondary symptom scores remarkably decreased, especially in the observation group (P < 0.05), and there was a significant reduction in the serum levels of hyaluronic acid (HA), laminin (LN), human rocollagen III (PC III), and collagen type IV (CIV). The levels of HA, LN, PC III, and CIV were significantly lower in the observation group (P < 0.05). After 8 weeks, both groups indicated remarkable improvements in liver function and blood lipid levels, with the observation group having even lower levels (P < 0.05). Serum levels of interleukin-1β, tumor necrosis factor-α, and interleukin-8 also dropped significantly. The observation group had a lower rate of adverse reactions (5.00%) compared to the control group (22.50%). Adding Dendrobium nobile Lindl. powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease. It also enhances hepatic function and lipid profile, ameliorates liver fibrosis indices, and lowers the risk of side effects. Consequently, this therapeutic protocol shows promise for clinical implementation and dissemination.

35kDa SPECIFIC-SIZED HYALURONAN AMELIORATES HIGH-FAT DIET-INDUCED LIVER INJURY IN MURINE MODEL OF MODERATE OBESITY.

Obesity is a growing concern in the US and world-wide, associated with an increased risk for several cardiometabolic diseases, including metabolic associated steatotic liver disease (MASLD). Currently, therapeutic interventions to prevent and/or treat MASLD are limited, and research is needed to identify new therapeutic targets. The specific-sized 35kDa fragment of hyaluronan (HA35), has gut protective and anti-inflammatory properties and a previous pilot clinical study reported it is well tolerated in healthy individuals. Here we tested the hypothesis that HA35 treatment ameliorates high fat diet-induced liver injury. Five-week-old male C57BL/6J mice were allowed ad lib access to control chow or high fat fructose and cholesterol (FFC) diet over a period of 12 weeks. HA35 was administered at 15mg/kg via oral gavage on the last 6 days of the study as a therapeutic intervention. Mice on FFC diet-gained more body weight compared to those on chow diet, with final body weights ranging from 30.8-45.6 g. FFC diet caused hepatocyte injury, increased expression of inflammatory cytokine/chemokine mRNA, as well as indicators of liver fibrosis. When mice were stratified based on their final body weight, only mice <40g were protected by treatment with HA35. In this group, treatment with HA35 also restored tight junction integrity in the colon and increased expression of α -defensins in the small intestine. Taken together the data suggests that HA35 is an effective therapeutic in ameliorating high fat diet-induced liver inflammation and fibrosis in moderately obese, but not severe, conditions.

The clinical value of fibrosis indices for predicting the hemorrhagic transformation in patients with acute ischemic stroke after intravenous thrombolysis.

The incidence of stroke in China is approximately 343 per 100,000 people each year, the highest rate worldwide. Hemorrhagic transformation (HT), particularly symptomatic intracerebral hemorrhage (sICH) following acute ischemic stroke (AIS) with or without intravenous thrombolysis (IVT), can lead to rapid neurological deterioration, poor prognosis, and even death. Non-alcoholic fatty liver disease (NAFLD) has been identified as a risk factor for stroke occurrence and associated with poor long-term functional outcomes. Nonetheless, no studies have examined the association between liver fibrosis and HT in AIS patients who underwent IVT. A total of 826 patients with AIS who underwent IVT were included in this study. We calculated nine validated liver fibrosis indices to assess the extent of liver fibrosis. HT was detected by follow-up cranial CT/MRI within 24 h post-IVT and was classified as either hemorrhagic infarction (HI) or parenchymal hematoma (PH). Symptomatic intracranial hemorrhage was defined as a sudden symptomatic neurological deterioration, indicated by an increase in (National Institutes of Health Stroke Scale) NIHSS score of 4 points or more. The median values of fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aspartate aminotransferase (AST)-platelet ratio index (APRI), Forns index, alanine aminotransferase (ALT)/AST (ARR), AST/ALT ratio-platelet ratio index (AARPRI), fibrosis quotient (FibroQ), and Fibrosis Index were significantly higher, while the fibrosis-5 (FIB-5) was significantly lower in the HT and sICH groups (all P < 0.001). After adjusting for potential confounders, all nine liver fibrosis indices remained associated with HT and sICH. Receiver operating characteristic (ROC) curve analysis revealed that the FibroQ score had the best predictive ability for HT (AUC = 0.707, CI = 0.652-0.762, P < 0.001), while FIB-4 had the best predictive ability for sICH (AUC = 0.802, CI = 0.711-0.892, P < 0.001). Liver fibrosis, as validated by FIB-4, mFIB-4, FIB-5, APRI, Forns index, ARR, AARPRI, FibroQ, and Fibrosis Index, was associated with HT and sICH in AIS patients after IVT.

The Interplay Between Depression, Probiotics, Diet, Immunometabolic Health, the Gut, and the Liver-A Secondary Analysis of the Pro-Demet Randomized Clinical Trial.

(1) Background: Depression, metabolic alternations, and liver diseases are highly comorbid. Studies have shown that probiotics might be helpful in the treatment of the above-mentioned states. The aim of this secondary analysis was to search for possible predictors of probiotics' efficacy on liver-related outcome measures. (2) Methods: Data from 92 subjects from a randomized clinical trial on the effect of probiotics on depression were analyzed. The shift in liver steatosis and fibrosis indices was assessed in the context of baseline immunometabolic, psychometric, dietary, and intestinal permeability factors. Correlation analysis and linear regression models were used. (3) Results: A total of 30% of the variance of the improvement in the score of the aspartate transferase to platelet ratio index was explained by probiotic use, higher pre-intervention triglycerides, cholesterol, C-reactive protein levels, increased cereal intake, and a lower consumption of sweets. Then, the model of the change in alanine transferase indicated that probiotics were efficient when used by subjects with higher basal levels of intestinal permeability markers. (4) Conclusions: Probiotics being used along with a healthy diet may provide additional benefits, such as decreased cardiovascular risk, for patients with measures consistent with the immunometabolic form of depression. Probiotic augmentation may be useful for liver protection among subjects with a suspected "leaky gut" syndrome. ClinicalTrials.gov: NCT04756544.

The structure elucidation and alleviating effect on liver fibrosis in vivo of a pectin-like polysaccharide isolated from Buddleja officinalis

Buddleja officinalis has been used as a traditional Chinese medicine for years. Although evidence has demonstrated it can enhance liver function, the active material basis remains unknown. We hypothesize polysaccharides from Buddleja officinalis may be the active material against liver disease. Herein, we elucidated the structure of a novel pectin-like polysaccharide designed BOM0.05S2 with a molecular weight of 13.6 kDa. Combined with endo-1, 4-β-Mannanase degradation, we found its backbone consists of alternate 1, 2, 4-linked α-Rhap and 1, 4-linked α-GalpA (RG-I type pectin) and mannoglucan, with branches of 1, 4-, 1, 6- and 1, 3, 6-linked β-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf, T-linked β-Manp and T-linked α-Glcp substituted at C-4 of 1, 2, 4-linked α-Rhap and C-6 of 1, 4, 6-linked α-Glcp. As speculated, BOM0.05S2 showed a significant improvement on carbon tetrachloride (CCl4)-induced liver damage in mice. Bioactivity test showed that BOM0.05S2 reduced AST, ALT and four indexes of liver fibrosis including LN, HA, IV-C, PC-III. Further, we demonstrated that BOM0.05S2 attenuated the collagenous fiber and α-SMA in liver. These findings highlight the potential of BOM0.05S2 as a lead compound for the treatment of liver fibrosis.

Glucometabolic Efficacy of the Empagliflozin/Metformin Combination in People with Type 1 Diabetes and Increased Cardiovascular Risk: A Sub-Analysis of a Pilot Randomized Controlled Trial.

Background/Objectives: People with type 1 diabetes have an unmet need for cardiovascular protection due to the lack of new recommended antidiabetic therapies with cardiovascular benefits. We examined whether the addition of an empagliflozin/metformin combination, and each drug alone, can complement insulin to improve glucometabolic parameters in overweight people with type 1 diabetes at high cardiovascular risk. Methods: This pilot, single-center double-blind randomized controlled trial included 40 people with type 1 diabetes. In addition to insulin, they received empagliflozin (25 mg daily), metformin (2000 mg daily), an empagliflozin/metformin combination, or a placebo. The intervention period was 12 weeks. Glycemic parameters, insulin requirements, and blood and urine samples were analyzed. Indices for liver fibrosis were calculated. Due to potential safety concerns, participants regularly measured blood ketone values. Results: The empagliflozin/metformin combination decreased HbA1c (-0.6%, p < 0.05) and weight (-6.1 kg, p < 0.05). Empagliflozin decreased the urinary albumin-to-creatinine ratio (-31.4 ± 4.9%, p = 0.002). The empagliflozin/metformin combination and empagliflozin decreased the estimated daily proteinuria (-34.6 ± 5.0%, p = 0.006 and -35.9 ± 6.2%, p = 0.03, respectively), the calculated FIB-4 (up to -17.8 ± 5.2%, p = 0.04 and -10.7 ± 3.7%, p = 0.02, respectively), and other liver fibrosis indices and uric acid values. No significant side effects occurred during the study. Conclusions: The empagliflozin/metformin combination improved glycemic control, reduced weight and insulin requirements, and produced several additional beneficial metabolic effects in overweight people with type 1 diabetes with increased cardiovascular risk.

Diagnostic accuracy of FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis in patients with chronic hepatitis B with metabolic dysfunction-associated fatty liver disease

Objective To evaluate the diagnostic value of the FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis (NASH) in patients with chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods All patients with CHB and MAFLD who underwent liver biopsy at the Zhenjiang Third Hospital affiliated with Jiangsu University between August 2010 and December 2022 were included in the analysis. The diagnostic accuracy of FAST, NFS, FibroScan, and FIB-4 for diagnosing NASH and liver fibrosis were evaluated based on the area under the receiver-operating characteristic curve (AUC). Results A total of 156 patients with CHB combined with MAFLD were included, including 69 with NASH and fibrosis stage 2 or higher (NASH+F ≥ 2), and 16 with NASH and cirrhosis (NASH+F4). The AUC of FAST, NFS, liver stiffness measurement (LSM), and FIB-4 for diagnosing NASH+F ≥ 2 was 0.739 (p < 0.001), 0.643 (p = 0.006), 0.754 (p < 0.001), and 0.665 (p = 0.003), respectively. The specificity of FAST, NFS, LSM, and FIB-4 was 67%, 51.8%, 78.6% and 76.8%, respectively, and the sensitivity was 75%, 78.6%, 67.9%, and 53.6%, respectively. No significant differences were found between groups. The AUC of FAST, NFS, LSM, and FIB-4 for diagnosing NASH+F4 was 0.650 (p = 0.038), 0.725 (p = 0.001), 0.851 (p < 0.001), and 0.560 (p = 0.533), respectively. The specificity of the FAST, NFS, LSM, and FIB-4 was 55.9%, 50.0%, 71.6%, and 75.5%, respectively and the sensitivity was 80.0%, 100%, 100%, and 50.0%, respectively. The differences between AUCs of FIB-4 and FAST compared with LSM were 0.291 and 0.201, respectively (p < 0.05). Conclusion In patients with CHB combined with MAFLD, FAST did not have better accuracy than NFS and FIB-4 for predicting fibrotic NASH, whereas LSM had better accuracy than FAST and FIB-4.

Impact of CFTR modulatory therapies on liver function and fibrosis indices in cystic fibrosis patients: a retrospective analysis from two Romanian medical centers

Background. Patients with cystic fibrosis (CF) frequently require modulatory therapies such as Lumacaftor/Ivacaftor (LI) and Elexacaftor/Tezacaftor/Ivacaftor (ETI) to manage their condition. Given the potential hepatic complications associated with CF, it is critical to understand the impact of these therapies on liver function and fibrosis indices. This study aimed to evaluate the changes in liver function markers and fibrosis indices in CF patients undergoing LI and ETI therapies, with a specific focus on the influence of underlying hepatic disease. Methods. In this retrospective analysis, liver function markers and fibrosis indices were assessed in CF patients receiving ETI (n=24), LI (n=4), or a combination of both (LI/ETI, n=8). Key liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, platelet count, and fibrosis indices (APRI and FIB-4), were measured at baseline and at various time points up to 12 months. Results. In patients receiving LI therapy, ALT and AST levels demonstrated a slight but non-significant decrease over six months, accompanied by significant fluctuations in total bilirubin levels. Among those receiving ETI therapy, ALT and AST levels initially increased but stabilized over time, while total bilirubin levels significantly increased from baseline to 12 months. No significant differences were observed in liver function markers between patients with and without hepatic disease under ETI therapy. Trends in fibrosis indices (APRI and FIB-4) were modest and largely non-significant across both therapies. Conclusions. ETI therapy appears to be safe for CF patients, including those with pre-existing hepatic disease, with no significant deterioration in liver function over a 12-month period. However, the observed fluctuations in bilirubin levels underscore the necessity for ongoing monitoring. Further research is warranted to investigate the long-term hepatic effects of LI and ETI therapies.

An investigation of the association between atrial fibrillation and the liver fibrosis-4 index in patients who underwent coronary computed tomography angiography.

Liver fibrosis scores, such as the fibrosis-4 index (FIB-4I), a representative index of liver fibrosis, have recently been linked to heart failure, coronary artery disease (CAD), and atrial fibrillation (AF). We investigated the association between FIB-4I and AF in patients who underwent coronary computed tomography angiography (CCTA). This study included 1525 patients clinically suspected of having CAD or about to undergo treatment for AF, such as catheter ablation. FIB-4I and the presence or absence of AF were the primary endpoints. FIB-4I was higher in the AF group than in the sinus rhythm group (1.93 ± 0.94 versus [vs.] 1.75 ± 1.03, p = 0.001). No significant difference was observed in the FIB-4I between the paroxysmal AF and persistent AF groups (1.93 ± 0.99 vs. 1.94 ± 0.78, p = 0.922). Furthermore, FIB-4I was higher in the hypertension (HTN) group than in the non-HTN group (1.84 ± 1.04 vs. 1.62 ± 0.91, p < 0.001). Low FIB-4I (≤1.29) was proven to be a contributing factor for the absence of AF in all patients (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.39-0.78, p < 0.001) as well as the HTN and non-HTN (OR: 0.53, 95% CI: 0.37-0.78, p < 0.001 and OR: 0.39, 95% CI: 0.23-0.68, p < 0.001, respectively) groups. Thus, FIB-4I may serve as a diagnostic indicator of the absence of AF in patients undergoing CCTA. The liver fibrosis-4 index as a diagnostic indicator of the absence of atrial fibrillation in patients undergoing coronary computed tomography angiography.