Liver Disease Patients Research Articles

Clinical and laboratory characteristics of Sjögren's syndrome-associated autoimmune liver disease: a real-world, 10-year retrospective study.

To investigate the clinical and laboratory features of Sjögren's syndrome-associated autoimmune liver disease (SS-ALD) patients and identify potential risk and prognostic factors. SS patients with or without ALD, who visited Tongji Hospital between the years 2011 and 2021 and met the 2012 American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome, were retrospectively enrolled. The clinical and laboratory data of the enrolled patients, including autoimmune antibodies, were collected and analyzed with principal component analysis, correlation analysis, LASSO regression, and Cox regression. A total of 117 SS-ALD patients were confirmed out of 568 SS patients. Compared to SS-non-ALD patients (n = 451), SS-ALD patients exhibited more severe involvement of the hepatic and hematologic systems, albeit with less pronounced typical SS symptoms. Disease activity was higher in SS-ALD patients, as indicated by elevated ESR, CRP, and IL-6 levels, particularly in the SS-overlap subgroup. Furthermore, SS-AIH patients without AIH-specific autoantibody testing or with negative testing results had higher AST and ALT levels than those who were autoantibody-positive. Our predictive model, incorporating IgG, IgM, AST, GGT, ALT, and C4, effectively identified ALD complications in SS patients, achieving an AUC of 0.924. Additionally, a grimmer prognosis was associated with higher baseline AST and ALT levels. SS-ALD patients often manifest with an insidious onset and atypical SS symptoms, yet frequently exhibit severe systemic involvement, intense inflammatory and immune responses, and a poor prognosis. To improve the clinical outcomes in SS-ALD patients, regular monitoring, early identification, and active treatment should be applied. Key Points • The study provided a detailed profile of clinical and laboratory features of SS-ALD and SS-non-ALD patients, contributing to a predictive model of ALD complications in SS patients • SS-ALD patients manifested with an insidious onset but exhibited severe systemic involvement, robust inflammatory and immune responses, and poor prognosis • SS-AIH patients without available testing for AIH-specific autoantibodies or with negative results demonstrated worse liver function, thus routine screening for autoimmune liver antibodies is recommended in SS patients • More severe baseline liver function status was associated with poorer therapeutic responses to routine medications, so early detection and timely intervention are essential for SS patients.

Safety and recommendation of voriconazole for invasive pulmonary aspergillosis in severe liver disease patients: a retrospective cohort study

BackgroundInvasive pulmonary aspergillosis (IPA) is a common opportunistic infection in patients with severe liver disease (SLD), which increases the mortality of patients. The aim of this study was to evaluate the efficacy and safety of voriconazole for IPA in patients with SLD and explore an optimal antifungal regimen.MethodsThis was a retrospective cohort study of SLD patients diagnosed with proven or probable IPA at Beijing Youan Hospital, Capital Medical University between January 1, 2012 to January 31, 2023. Univariate and multivariate logistic regression analysis were performed to identify the impact of voriconazole on outcomes of SLD patients with IPA.ResultsA total of 142 patients were enrolled and categorized into voriconazole group (n = 92), echinocandins group (n = 26) and a combination of voriconazole and echinocandins group (n = 24). The 28-day all-cause mortality was lower in voriconazole group compared to the other groups (p = 0.033). Voriconazole monotherapy was associated with lower short-term mortality (OR 0.223, 95%CI 0.070–0.650, p = 0.008) and did not seem to exacerbate hepatic function deterioration in SLD patients with IPA (OR 0.259, 95%CI 0.094–0.674, p = 0.007) when compared to echinocandins monotherapy. Among the three subgroups of voriconazole monotherapy, no-loading dose regime demonstrated a superior response to IPA therapy compared to the standard-dose regimen (OR 0.264, 95%CI 0.068–0.845, p = 0.035).ConclusionVoriconazole monotherapy demonstrated good tolerability with lower mortality in SLD patients with IPA. A no-loading dose voriconazole regimen is proposed for IPA treatment in SLD patients, yet pharmacokinetic studies combined with prospective studies are needed for further validation.

Advancing Chronic Liver Disease Diagnoses: Targeted Proteomics for the Non-Invasive Detection of Fibrosis

Chronic liver disease poses significant challenges to healthcare systems, which frequently struggle to meet the needs of end-stage liver disease patients. Early detection and management are essential because liver damage and fibrosis are potentially reversible. However, the implementation of population-wide screenings is hindered by the asymptomatic nature of early chronic liver disease, along with the risks and costs associated with traditional diagnostics, such as liver biopsies. This study pioneers the development of innovative, minimally invasive methods capable of improving the outcomes of liver disease patients by identifying liver disease biomarkers using quantification methods with translational potential. A targeted mass spectrometry assay based on stable isotope standard protein epitope signature tags (SIS-PrESTs) was employed for the absolute quantification of 108 proteins in just two microliters of plasma. The plasma profiles were derived from patients of various liver disease stages and etiologies, including healthy controls. A set of potential biomarkers for stratifying liver fibrosis was identified through differential expression analysis and supervised machine learning. These findings offer promising alternatives for improved diagnostics and personalized treatment strategies in liver disease management. Moreover, our approach is fully compatible with existing technologies that facilitate the robust quantification of clinically relevant protein targets via minimally disruptive sampling methods.

Hemoglobin glycation index and mortality risk in metabolic dysfunction-associated steatotic liver disease patients: a novel U-shaped association

Identifying dependable prognostic indicators is essential for the efficient management of metabolic dysfunction-associated steatotic liver disease (MASLD). The index of hemoglobin glycation (HGI) has been demonstrated to be closely linked to the onset and advancement of MASLD. Currently, no studies have investigated the relationship between HGI and mortality rates among MASLD patients. This study analyzed data from the National Health and Nutrition Examination Surveys (NHANES) covering 1999 to 2018, involving 8,257 adult patients diagnosed with MASLD. The HGI was determined using a linear regression model that correlated hemoglobin A1c (HbA1c) with fasting plasma glucose (FPG). The study employed Kaplan-Meier survival curves and weighted Cox proportional hazards models to evaluate the independent association between HGI and mortality risk. The study utilized restricted cubic splines (RCS) to visually depict the relationship between HGI and mortality risk. Over a median follow-up duration of 97.0 months, there were 1,352 recorded deaths, among which 386 were attributed to cardiovascular disease (CVD). Participants were classified into two groups based on their HGI values: the high HGI group (≥ 0.4605) and the low HGI group (< 0.4605). The results from the weighted Cox proportional hazards model indicated that individuals in the high HGI group faced a significantly higher risk of all-cause mortality (HR 1.47, 95% CI 1.19–1.82, P < 0.001). However, no significant increase in CVD mortality risk was observed (HR 1.38, 95% CI 0.95–1.99, P = 0.090). The RCS analysis identified a U-shaped association between HGI and both all-cause mortality and CVD mortality, with critical points at -0.0564 and − 0.0573, respectively. Below the critical points, HGI was negatively correlated with all-cause mortality (HR 0.82, 95% CI: 0.72–0.92, P < 0.001) and not significantly associated with CVD mortality (HR 0.78, 95% CI: 0.57–1.07, P = 0.126). Above the critical points, HGI was significantly positively correlated with both all-cause mortality (HR 1.36, 95% CI: 1.20–1.53, P < 0.001) and CVD mortality (HR 1.44, 95% CI: 1.11–1.88, P = 0.007). Further subgroup and interaction analyses corroborated the reliability of these findings. HGI could potentially function as a useful and dependable marker for evaluating all-cause mortality and cardiovascular mortality in MASLD patients.

Sarcopenia in MASLD-Eat to Beat Steatosis, Move to Prove Strength.

The connections between sarcopenia and various chronic conditions, including type 2 diabetes (T2DM), metabolic syndrome (MetS), and liver disease have been highlighted recently. There is also a high occurrence of sarcopenia in metabolic dysfunction-associated steatotic liver disease (MASLD) patients, who are often disregarded. Both experimental and clinical findings suggest a complex, bidirectional relationship between MASLD and sarcopenia. While vitamin D, testosterone, and specific drug therapies show promise in mitigating sarcopenia, consensus on effective treatments is lacking. Recent focus on lifestyle interventions emphasizes dietary therapy and exercise for sarcopenic obesity in MASLD. Challenges arise as weight loss, a primary MASLD treatment, may lead to muscle mass reduction. The therapeutic approach to sarcopenia in morbidly obese MASLD patients also includes bariatric surgery (BS). BS induces weight loss and stabilizes metabolic imbalances, but its impact on sarcopenia is nuanced, underscoring the need for further research. Our aim is to provide a comprehensive review of the interplay between sarcopenia and MASLD and offer insight into the most recent therapeutic challenges and discoveries, as sarcopenia is often overlooked or unrecognized and poses significant challenges for managing these patients.

Pain in chronic liver disease compared to other chronic conditions: Results from a contemporary nationally representative cohort study.

Pain is common in patients with chronic liver disease. Our limited understanding of patterns and severity of pain in this population hinders the development of effective cirrhosis-specific pain management strategies. Using cross-sectional data from the 2016-2021 National Health Interview Survey, we examined rates, severity, and functional limitations due to pain in respondents with liver disease (viral hepatitis, cirrhosis, and liver cancer), compared to the general population and those with other chronic conditions associated with pain (ie, arthritis, diabetes, and chronic kidney disease). Categorical and continuous variables were compared using χ2 and t test. Multivariable logistic regression was used to determine the predictors associated with pain and opioid use. Our liver disease cohort comprised 5267 participants (63% viral hepatitis, 49% cirrhosis, and 2% liver cancer). Participants with liver disease were more likely to report pain than those without liver disease (42% vs. 22%); they were also more likely to report severe pain (42% vs. 30%) and functional limitations by pain (28% vs. 13%) (p < 0.001 for all). On multivariable logistic regression, liver disease is an independent predictor of pain (OR: 2.31, 95% CI: 2.05-2.59, p < 0.001), even after adjustment for demographic factors. Liver disease respondents had similar rates of pain as those with diabetes (p = 0.8) and were more functionally limited by pain than those with arthritis (p < 0.001). Adjusted for demographic and pain-related factors, liver disease was also an independent predictor of chronic opioid use (OR: 1.47, 95% CI: 1.12-1.92, p = 0.0054). Liver disease independently increases the likelihood of experiencing widespread and debilitating pain. Clinicians should consider liver disease a painful condition, ensuring that they are frequently assessing and appropriately treating pain in all liver disease patients.

Comparison of deep learning schemes in grading non-alcoholic fatty liver disease using B-mode ultrasound hepatorenal window images with liver biopsy as the gold standard

Background/IntroductionTo evaluate the performance of pre-trained deep learning schemes (DLS) in hepatic steatosis (HS) grading of Non-Alcoholic Fatty Liver Disease (NAFLD) patients, using as input B-mode US images containing right kidney (RK) cortex and liver parenchyma (LP) areas indicated by an expert radiologist. MethodsA total of 112 consecutively enrolled, biopsy-validated NAFLD patients underwent a regular abdominal B-mode US examination. For each patient, a radiologist obtained a B-mode US image containing RK cortex and LP and marked a point between the RK and LP, around which a window was automatically cropped. The cropped image dataset was augmented using up-sampling, and the augmented and non-augmented datasets were sorted by HS grade. Each dataset was split into training (70%) and testing (30 %), and fed separately as input to InceptionV3, MobileNetV2, ResNet50, DenseNet201, and NASNetMobile pre-trained DLS. A receiver operating characteristic (ROC) analysis of hepatorenal index (HRI) measurements by the radiologist from the same cropped images was used for comparison with the performance of the DLS. ResultsWith the test data, the DLS reached 89.15 %–93.75 % accuracy when comparing HS grades S0-S1vs.S2-S3 and 79.69 %–91.21 % accuracy for S0vs.S1vs.S2vs.S3 with augmentation, and 80.45–82.73 % accuracy when comparing S0-S1vs.S2-S3 and 59.54 %–63.64 % accuracy for S0vs.S1vs.S2vs.S3 without augmentation. The performance of radiologists’ HRI measurement after ROC analysis was 82 %, 91.56 %, and 96.19 % for thresholds of S ≥ S1, S ≥ S2, and S = S3, respectively. ConclusionAll networks achieved high performance in HS assessment. DenseNet201 with the use of augmented data seems to be the most efficient supplementary tool for NAFLD diagnosis and grading.

Early Integration of Palliative Care in Non-Oncological Patients: A Systematic Review.

Palliative care (PALC) is traditionally linked to end-of-life cancer care but also benefits advanced non-oncological diseases. This systematic review evaluated the impact of early PALC on quality of life (QOL), symptom management, advance care planning (ACP), and healthcare resource utilization (HRU) among non-oncological patients. PubMed, Web of Science, and Scopus databases were searched for randomized controlled trials and clinical studies published between January 2018 and April 2023. Participants were adult patients with non-oncological diseases exposed to PALC interventions compared to usual care. Outcomes included QOL, symptom management, ACP, and HRU. The risk of bias was assessed using Cochrane tools. Seven studies were included involving 1118 patients. Early PALC positively affects pain interference and fatigue in heart failure (HF) patients and time until first readmission and days alive outside the hospital in end-stage liver disease (ESLD) patients. Benefits were noted in symptom burden for patients with Human Immunodeficiency Virus (HIV), anxiety and depression in stroke patients, and ACP in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) patients. However, results for anxiety and depression in HF patients are inconsistent, and no significant differences in QOL were observed in HF, ESLD, IPF, and COPD. The intervention did not improve overall QOL in HIV. The impact of early PALC on health outcomes in non-oncological diseases is inconsistent. Addressing barriers to early PALC integration and conducting further high-quality research are essential for optimizing care pathways and enhancing patient outcomes.

Higher Incidence of Diabetes in Asymptomatic Healthy Fatty Liver Patients of Bangladesh: Prompt Intervention can Avert Complications.

The strong association between type 2 diabetes mellitus (T2DM) and fatty liver is well known, and its nomenclature has even recently changed to metabolic dysfunction-associated steatotic liver disease (MASLD). Healthy MASLD patients are frequently overlooked and maltreated, especially in Bangladesh. In this present study, we tried to correlate T2DM burden in apparently healthy, incidentally diagnosed fatty liver patients on ultrasound. This cross-sectional study was done in Sheikh Hasina Medical College Hospital, Tangail, Bangladesh, from August 2022 to February 2023. A total of 92 patients with ultrasonological evidence of grade II fatty change in the liver were included and evaluated. Known T2DM, hypothyroidism, consumption of alcohol, HBV or HCV infection, Wilson's disease, autoimmune liver disease, hemochromatosis, and any other chronic liver or kidney disease patients were excluded. The patients were then assessed for the presence and absence of T2DM using OGTT (2 hours 75 gm glucose ≥ 11.1 mmol/L) and/or HbA1c (≥6.5%) as diagnostic criteria. Data was analyzed by SPSS, version 23. Out of 92 patients, 48 were male and 44 were female. A total of 50 patients (54.3%) were newly diagnosed with T2DM. Statistically significant differences were seen in the T2DM group and non-DM group for AST (50.33 IU vs 36.53 IU) and TG (270 mg/dL vs 189 mg/dL). Although no noteworthy differences were evident in mean age (41 years vs 38 years), ALT (58.9 IU vs 60.23 IU), and BMI (28.85 vs 29.29). In the present study, more than 54% of patients with grade II fatty liver were newly diagnosed with T2DM. They would later present with more advanced T2DM and related complications. Although a larger study is needed, physicians and healthcare workers in Bangladesh should be more concerned about treating MASLD patients with early diagnosis of T2DM, recommending prompt lifestyle interventions, and prescribing drugs if necessary. Gani ABMS, Mahmood AA, Alam AFMS, et al. Higher Incidence of Diabetes in Asymptomatic Healthy Fatty Liver Patients of Bangladesh: Prompt Intervention can Avert Complications. Euroasian J Hepato-Gastroenterol 2024;14(2):172-175.

Effects of Bifidobacterium and rosuvastatin on metabolic-associated fatty liver disease via the gut–liver axis

Background/aimsResearch has indicated that treatment with rosuvastatin can improve liver pathology in metabolic-associated fatty liver disease (MAFLD) patients and that treatment with Bifidobacterium can improve MAFLD. Therefore, the effects of Bifidobacterium, rosuvastatin, and their combination on related indices in a rat model of diet-induced MAFLD need to be investigated.MethodsForty rats were divided into five groups: the normal diet group (N), high-fat diet (HFD) model group (M), HFD + probiotic group (P), HFD + statin group (S), and HFD + probiotic + statin group (P-S). To establish the MAFLD model, the rats in Groups M, P, S, and P-S were fed a HFD for 8 weeks. The treatments included saline in Group N and either Bifidobacterium, rosuvastatin, or their combination in Groups P, S, and P-S by intragastrical gavage. After 4 weeks of intervention, the rats were euthanized, and samples were harvested to analyze gastrointestinal motility and liver function, pathological changes, inflammatory cytokine production, and the expression of proteins in key signaling pathways.ResultsHFD feeding significantly increased the body weight, liver index, and insulin resistance (IR) index of the rats, indicating that the MAFLD model was successfully induced. Bifidobacterium reduced the liver of MAFLD rats, while Bifidobacterium with Rosuvastatin decreased the liver index, IR index, and levels of aspartate aminotransferase and alanine aminotransferase in MAFLD rats. The MAFLD model showed altered expression of proteins in signaling pathways that regulate inflammation, increased production of inflammatory cytokines, an elevated MAFLD activity score (MAS), and pathological changes in the liver. The MAFLD model also showed reduced relative counts of intestinal neurons and enteric glial cells (EGCs), altered secretion of gastrointestinal hormones, and slowed gastrointestinal emptying. Bifidobacterium, rosuvastatin, or their combination inhibited these various changes. HFD feeding changed the rats’ gut microbiota, and the tested treatments inhibited these changes. These results suggest that the gastrointestinal motility disorder and abnormal liver function in MAFLD rats may be related to a reduction in Escherichia-Shigella bacteria and an increase in Asticcacaulis bacteria in the gut microbiota and that the improvement in liver function induced by Bifidobacterium plus rosuvastatin may be related to increases in Sphingomonas and Odoribacter bacteria and a decrease in Turicibacter bacteria in the gut microbiota.ConclusionsThe combined use of Bifidobacterium and rosuvastatin could better regulate the gut microbiota of MAFLD model rats, promote gastrointestinal emptying, and improve liver pathology and function than single treatment with Bifidobacterium or rosuvastatin. This provides a better strategy for the treatment of MAFLD.

Non-obese non-alcoholic fatty liver disease and the risk of chronic kidney disease: a systematic review and meta-analysis.

Data on risk of developing chronic kidney disease (CKD) between non-obese and obese non-alcoholic fatty liver disease (NAFLD) patients are limited. We aimed to reveal the risk difference of incident CKD between non-obese and obese NAFLD patients. We searched PubMed, Embase, and Web of Science databases for studies which reported the incidence of CKD in non-obese and obese NAFLD from inception to 10 March 2024. The primary and secondary outcomes were pooled. Subgroup analysis was used to examine the heterogeneity. A total of 15 studies were incorporated. The incidence of CKD in non-obese and obese NAFLD were 1,450/38,720 (3.74%) and 3,067/84,154 (3.64%), respectively. Non-obese NAFLD patients had a comparable risk of CKD as obese NAFLD (odds ratio [OR] 0.92, 95% confidence interval [95% CI] [0.72-1.19], I2 = 88%). No differences in estimated glomerular filtration rate and serum creatinine between non-obese and obese NAFLD were found. The mean differences (MD) and 95% CI were 0.01 [-0.02 to 0.04] and 0.50 [-0.90 to 1.90], respectively. In subgroup analyses, non-obese NAFLD had higher eGFR when diagnosed with ultrasound (MD 1.45, 95% CI [0.11-2.79], I2 = 21%). Non-obese NAFLD had higher creatinine in non-Asian (MD 0.06, 95% CI [0.01-0.11], I2 = 55%) and when taking BMI > 30 as the criterion for obesity (MD 0.06, 95% CI [0.00-0.12], I2 = 76%). The occurrence of CKD did not differ when non-obese NAFLD were categorized into overweight and normal-weight types. Non-obese NAFLD patients experienced the same risk of CKD compared to obese NAFLD.

Comparative analysis of ferritin levels and liver enzyme activity in liver disease patients within Benin City

Comparative analysis of ferritin levels and liver enzyme activity in liver disease patients within Benin City

The salivary microbiome and oral health status in HBeAg-negative chronic hepatitis B

Background/purposeDysbiosis of oral microbiota has been reported in late stage of chronic hepatitis B (CHB) infection with cirrhosis. CHB is characterized by the constant virus-induced liver injury which may lead to liver cirrhosis and hepatocellular carcinoma (HCC). However, some patients show normal liver function without antiviral treatment, associating with favourable prognosis. The oral microbiota composition and oral health status in these patients is unidentified. Materials and methodsThe study focuses on the composition of oral microbiota and oral health status in individuals with CHB and HBV vaccinees as controls. The CHB patients were hepatitis B 'e' antigen (HBeAg)-negative, with or without elevated liver enzyme increase at time of sampling, The 16S rRNA high-throughput sequencing and bioinformatic analysis were applied to investigate oral bacterial diversity, and oral examination including decay-missing-filled teeth (DMFT) index, probing depth (PD) and mucosal status was performed, along with oral health questionnaire, to assess the oral health status in CHB patients and healthy controls. ResultsOur results indicate that their oral microbiome compositions are not significantly different though some have increased ALT/AST liver enzyme levels at the time of sampling, compared to the healthy control participants who are vaccinated e.g. protected from this viral disease. CHB patients here bore a good oral health status and life-style habits as comparing to healthy controls. ConclusionThese findings suggest that a health-associated salivary microflora is present in CHB without severe liver injury. Continued regular dental health and lifestyle support in liver disease patients is therefore justified.

Cross-sectional and Mendelian randomization study of fibroblast growth factor 19 reveals causal associations with metabolic diseases.

Fibroblast growth factor 19 (FGF19) is an intestinal-derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR). Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021. Dividing the subjects into different subgroups to compare FGF19 levels. We conducted a two-sample MR analysis of genetically predicted circulating FGF19 in relation to alcohol, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available genome-wide association study summary statistics data. The circulating FGF19 levels in nonalcoholic fatty liver disease (NAFLD) patients were lower than those without NAFLD (P<0.001). The FGF19 levels in participants with obese were lower than those without obese (P<0.001). In two-sample MR analyses, genetically predicted higher circulating FGF19 levels was significantly associated with lower aspartate aminotransferase, γ-glutamyltransferase, triglycerides, total cholesterol, low-density lipoprotein, and C-reactive protein concentrations (P<0.05) and a negative correlation with cardiovascular disease and cirrhosis whereas a positive association with type 2 diabetes mellitus (P<0.05). Our study found that circulating FGF19 levels were lower in NAFLD and obese populations. Additionally, our MR research results support the causal effects of FGF19 on improved liver function, lipids, and reduced the occurrence of inflammation, cardiovascular disease, and cirrhosis. We found a positive correlation with diabetes, which may indicate a compensatory increase in regulating above FGF19 resistance states in humans.

EPH82 Characterising Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis Patients in Secondary Care in England

EPH82 Characterising Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis Patients in Secondary Care in England

NLRP3 activation maintains intestinal epithelial barrier and reduces liver injury in alcoholic liver disease mice.

Alcoholic liver disease (ALD) patients with bacterial infections usually exhibit high mortality rates. Infections frequently involve bacteria such as Vibrio vulnificus and Enterococcus faecalis. Nevertheless, the mechanisms predisposing ALD patients to bacterial infections and the role of the NLRP3 inflammasome in the intestinal epithelial barrier in ALD remain unclear. We established ALD mice models of WT, Nlrp3-/- and Gsdmd-/- through chronic alcohol consumption feeding and acute alcohol induction. We compared alterations in gut microbiota, ileitis, and adhesion protein expression, to analyze the role and potential mechanism of NLRP3 in the early onset of ALD. Concurrently, we examined the changes in inflammation and liver damage in the ileum of ALD and healthy mice following foodborne infection with V. vulnificus. Compared with the control group, the expression levels of ZO-1, Claudin-1 and E-cadherin were reduced in the ileum of ALD mice, while those of NLRP3, caspase-1(p20), GSDMD-N and IL-1β were elevated. Nlrp3-/- and Gsdmd-/- ALD mice showed an increased gut bacterial load, decreased ileal expression of E-cadherin, more severe ileitis, pronounced liver damage, steatosis and higher plasma levels of FITC-dextran, D-LA and ZO-1 compared with WT mice. Notably, Nlrp3-/- ALD mice exhibited a higher presence of Deferribacterota and Enterobacteriaceae. Furthermore, ALD mice infected with V. vulnificus infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections. This study indicated that NLRP3 activation in the ileum of ALD mice stabilizes the inflammation-related gut microbiota, preserves the intestinal epithelial barrier, and diminishes inflammation and liver injury. Furthermore, the compromised immune defence in ALD mice may contribute to their heightened susceptibility to bacterial pathogens. Activation of the NLRP3-GSDMD pathway in the ileum of Alcoholic liver disease (ALD) mice. NLRP3 activation maintains homeostasis of gut microbiota and intestinal epithelial barrier in ALD mice. ALD mice infected with V. vulnificus infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections.

Diagnostic performance of FibroTouch® in assessing hepatic steatosis and fibrosis in patients with metabolic dysfunction-associated steatotic liver disease: An Asian experience.

FibroTouch® has shown efficacy in staging hepatic fibrosis in patients with chronic viral hepatitis B, but its performance in assessing liver steatosis and fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients remains understudied. We aimed to evaluate the diagnostic performance of FibroTouch® in assessing steatosis and fibrosis in the MASLD population. Liver stiffness measurements and steatosis were assessed using FibroTouch® and FibroScan®, with FibroScan® as the reference standard. Pearson's correlation test evaluated correlations, and kappa statistics determined agreement between the two methods. Optimal cut-off values of FibroTouch® for predicting hepatic steatosis and fibrosis stages were determined through ROC curve analysis with the Youden index method. Strong correlations were observed between FibroTouch® UAP and FibroScan® CAP (rho=0.74) and LSM values (rho=0.87) (p < 0.001 for both) in a total of 380 patients. The mean CAP value for the entire cohort was 285 ± 51 dB/m, and the median LSM for the cohort was 5 .3kPa. The optimal FibroTouch® UAP cutoffs were 229 dB/m for S0 vs. S1, 267 dB/m for S1 vs. S2, and 294 dB/m for S2 vs. S3. For FibroTouch® LSM, the optimal cutoffs were 6.0 kPa for F0-F1 vs. F2, 7.9 kPa for F2 vs. F3, and 10.6 kPa for F3 vs. F4. Moreover, FibroTouch® effectively assessed hepatic steatosis and fibrosis in patients with different BMIs. FibroTouch® proved valuable in assessing hepatic steatosis and liver fibrosis staging in MASLD patients, enhancing its applicability in various clinical settings as a suitable and convenient option for MASLD patients.

Therapeutic effects of curcumin supplementation on liver enzymes of nonalcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized clinical trials.

Curcumin, as an antioxidant agent, has been proposed as a potential treatment for nonalcoholic fatty liver disease (NAFLD). The aim of the current systematic review and meta-analysis was to summarize earlier findings regarding the effect of curcumin supplementation on liver enzymes and ALP in NAFLD patients. All studies published up to November 18, 2022, were searched through the PubMed, SCOPUS, and Web of Science databases to collect all randomized clinical trials (RCTs) on NAFLD patients in which curcumin was used as a treatment. A random-effects model was used to measure pooled effect sizes. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to report pooled effect sizes. Subgroup analysis was utilized to investigate heterogeneity. A total of 14 studies were included in this systematic review and meta-analysis. Our pooled meta-analysis indicated a significant decrease in alanine aminotransferase (ALT) following curcumin therapy by pooling 12 effect sizes (WMD: -8.72; 95% CI: -15.16, -2.27, I 2 = 94.1%) and in aspartate aminotransferase (AST) based on 13 effect sizes (WMD: -6.35; 95% CI: -9.81, -2.88, I 2 = 94.4%). However, the pooled analysis of five trials indicated that there was no significant association between curcumin therapy and alkaline phosphatase (ALP) in NAFLD patients (WMD: -4.71; 95% CI: -13.01, 3.58, I 2 = 64.2%). Nevertheless, subgroup analyses showed significant effects of curcumin on ALP with a longer duration of supplementation. The findings of this systematic review and meta-analysis support the potential effect of curcumin on the management of NAFLD. Further randomized controlled trials should be conducted in light of our findings.

Analysis of Predictive Value of Non Invasive Scoring System Fibrosis-4 for the Extent of Coronary Calcification in Non Alcoholic Fatty Liver Disease Patients.

Analysis of Predictive Value of Non Invasive Scoring System Fibrosis-4 for the Extent of Coronary Calcification in Non Alcoholic Fatty Liver Disease Patients.

A brain-to-liver signal mediates the inhibition of liver regeneration under chronic stress in mice

As the ability of liver regeneration is pivotal for liver disease patients, it will be of high significance and importance to identify the missing piece of the jigsaw influencing the liver regeneration. Here, we report that chronic stress impairs the liver regeneration capacity after partial hepatectomy with increased mortality in male mice. Anatomical tracing and functional mapping identified a neural circuit from noradrenergic neurons in the locus coeruleus (LC) to serotonergic neurons in the rostral medullary raphe region (rMR), which critically contributes to the inhibition of liver regeneration under chronic stress. In addition, hepatic sympathetic nerves were shown to be critical for the inhibitory effects on liver regeneration by releasing norepinephrine (NE), which acts on adrenergic receptor β2 (ADRB2) to block the proinflammatory macrophage activation. Collectively, we reveal a “brain-to-liver” neural connection that mediates chronic stress-evoked deficits in liver regeneration, thus shedding important insights into hepatic disease therapy.