Biomarkers Of Liver Fibrosis Research Articles

OS-085 - Use of antidiabetic and lipid-lowering medications associated with lower scores of liver fibrosis biomarkers in non-alcoholic steatohepatitis (NASH) patients

OS-085 - Use of antidiabetic and lipid-lowering medications associated with lower scores of liver fibrosis biomarkers in non-alcoholic steatohepatitis (NASH) patients

Clinical Significance of the Mac-2 Binding Protein Glycosylated Isomer as a Surrogate Marker of Graft Fibrosis After Pediatric Liver Transplantation

After pediatric liver transplantation, liver fibrosis may occur during long-term follow-up. Noninvasive markers for assessing this liver fibrosis are desired. Mac-2 binding protein glycosylated isomer (M2BPGi) has recently been reported as a useful biomarker for liver fibrosis. However, its usefulness in the pediatric population is yet to be established. This study investigated the clinical significance of M2BPGi levels as a surrogate marker of graft fibrosis after pediatric liver transplantation. We retrospectively identified 96 patients who underwent pediatric liver transplantation at our institution between 1991 and 2015. The association between M2BPGi levels and other fibrosis markers was analyzed in 60 patients in whom fibrosis markers were measured. The association between fibrosis marker levels and graft fibrosis was assessed in 42 patients who underwent biopsies between 2016 and 2022. The M2BPGi levels were statistically correlated with the hyaluronic acid and type-IV collagen levels. None of the fibrosis markers were significantly associated with liver graft fibrosis, although the levels of these markers were slightly higher in patients with severe liver fibrosis than in those with mild fibrosis. The M2BPGi levels had a limited ability to assess liver graft fibrosis after pediatric liver transplantation, similar to other fibrosis markers. Further studies with larger cohorts are required to validate these findings externally.

Analysis of Plasma Metabolomics of Liver Fibrosis Based on Bioinformatics

Objective: To explore the metabolites of liver fibrosis and their interactions based on bibliometrics, and to find biomarkers and therapeutic targets for liver fibrosis. Methods: Combined Chinese and English databases were used to collect plasma metabolomics studies of liver fibrosis. Recurring metabolites from the included studies were collected as liver fibrosis metabolite profiles, and metabolites were analyzed and processed on metabolism-related databases. Results: A total of 16 articles were included, and 24 recurring metabolites were selected as the metabolite spectrum of liver fibrosis, and they appeared in 24 metabolic pathways. Topological analysis of the pathways on the MetPA database revealed that aminyl tRNA synthesis, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, sphingolipid metabolism, phenylalanine metabolism, arginine and proline metabolism, bile acid biosynthesis, and glycolytic/glycoisogenic metabolic pathways were associated with liver fibrosis. Valine, arginine and leucine occur more than 5 times. Conclusion: The pathological mechanism of liver fibrosis involves the biological metabolism of amino acids, proteins, lipids, carbohydrates, and bile acids. Valine, arginine and leucine can be used as biomarkersof liver fibrosis.

Glaucocalyxin A attenuates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance.

Liver fibrosis refers to the pathophysiological process of dysplasia on the connective tissue of the liver, caused by a variety of pathogenic factors. Glaucocalyxin A (GLA) has anticoagulation, antibacterial, anti-inflammation, antioxidant and antitumour properties. However, whether GLA ameliorates liver fibrosis or not is still unclear. In this study, a liver fibrosis model was established using male C57BL/6 mice. The mice were treated with 5 and 10 mg/kg GLA via intraperitoneal injection, respectively. The ones that were treated with 5 mg/kg OCA were used as the positive control group. The levels of liver function, liver fibrosis biomarkers and liver pathological changes were then evaluated. We also explored the effects of GLA on inflammatory response and liver cell apoptosis. In addition, we investigated the gut microbiota mechanisms of GLA on liver fibrosis. The results from this study that GLA could significantly decrease the level of liver function (AST, ALT, TBA) and liver fibrosis (HA, LN, PC-III, IV-C). On the other hand, a significant decrease in inflammation levels (IL-1β, TNF-α) were also noted. GLA also improves CCl4-induced pathological liver injuries and collagen deposition, in addition to decreasing apoptosis levels. In addition, an increase in the ratio of Bacteroidetes and Firmicutes in liver disease was also observed. GLA also improves the gut microbiota. In conclusion, GLA attenuates CCl4-induced liver fibrosis and improves the associated gut microbiota imbalance.

Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications.

Liver fibrosis is a global health problem caused by chronic liver injury resulting from various factors. Hepatic stellate cells (HSCs) have been found to play a major role in liver fibrosis, and pathological stimuli lead to their transdifferentiation into myofibroblasts. Complex multidirectional interactions between HSCs, immune cells, and cytokines are also critical for the progression of liver fibrosis. Despite the advances in treatments for liver fibrosis, they do not meet the current medical needs. Exosomes are extracellular vesicles of 30-150 nm in diameter and are capable of intercellular transport of molecules such as lipids, proteins and nucleic acids. As an essential mediator of intercellular communication, exosomes are involved in the physiological and pathological processes of many diseases. In liver fibrosis, exosomes are involved in the pathogenesis mainly by regulating the activation of HSCs and the interaction between HSCs and immune cells. Serum-derived exosomes are promising biomarkers of liver fibrosis. Exosomes also have promising therapeutic potential in liver fibrosis. Exosomes derived from mesenchymal stem cells and other cells exhibit anti-liver fibrosis effects. Moreover, exosomes may serve as potential therapeutic targets for liver fibrosis and hold promise in becoming drug carriers for liver fibrosis treatment.

The Influence of Probiotic Supplementation on Depression, Anxiety, and Stress Level, as well as Inflammation, Anthropometric and Metabolic Parameters in Patients with Depressive Disorders - preliminary results of an RCT

IntroductionThere is a huge need to search for new treatment options for depression but as well as its comorbidities. Particularly, depression and metabolic abnormalities often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. Thus, the trials of microbiota interventions (e.g., probiotics) may establish a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacological treatment.ObjectivesThe paper presents preliminary results of an RCT on the effect of probiotic supplementation on depression, anxiety and stress level, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders.MethodsThe trial was a two-arm, parallel-group, prospective, randomized, double-blind, controlled design that included 43 participants and lasted 60 days. The probiotic preparation contained Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 in the amount of 3 × 109 colony forming units (CFU). We assessed depression level with Montgomery-Asberg Depression Rating Scale (MADRS), depressiveness, anxiety and stress level with 21-item version of Depression, Anxiety and Stress Scale (DASS-21), quality of life, blood pressure, body mass index and waist circumference, complete blood count, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, selected secondary markers of inflammation and metabolic risk, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4).ResultsThere were no differences in sociodemographic traits and psychometric questionnaires scores, as well as in anthropometric and basic laboratory findings between placebo and probiotic group at the start of the intervention period. Interestingly, there was a statistically significant improvement in MADRS score in both, placebo (p=0,010) and probiotic group (p=0,037) after intervention (see figure). The same finding was observed in total DASS-21 score as well as anxiety subscale of DASS-21. However, there were no differences in anthropometric, inflammation or metabolic laboratory parameters at the end of the study regardless of intervention.Image:ConclusionsWhilst probiotics may benefit some individuals who do not fully respond to antidepressant medications, our study did not show the superiority of probiotics over placebo in managing depressive and anxiety symptoms. However, the target clinical sample, as well as the intervention period and dosage of preparation for this intervention is not fully recognized. Moreover, larger clinical sample may be needed to detect differences between placebo and probiotics.Disclosure of InterestNone Declared

Performance of Non-invasive Biomarkers of Liver Fibrosis Amongst Hispanics and African Americans.

Liver biopsy is the gold standard for fibrosis staging. However, it is limited by significant complications. Non-invasive markers of fibrosis have been developed as an alternative to liver biopsy. The performance of these different markers varies with the etiology of liver fibrosis and possibly amongst different ethnicities. We aim to assess the performance of non-invasive markers of liver fibrosis amongst Hispanics and African Americans. This is a retrospective cohort analysis of patients who had liver biopsy as part of their evaluation of chronic liver disease. One hundred and twenty-six records were analyzed. Univariate and multivariate analyses were performed. Probit regression receiver operating characteristic curve analysis was used to assess the sensitivity of the different non-invasive biomarkers and underlying variables with respect to liver biopsy. The following non-invasive markers for fibrosis were used: Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), age-platelet, AST/alanine aminotransferase (AST/ALT) ratio, fibrosis cirrhosis index (FCI), and fibrosis index (FI). About two-thirds of the study population were African Americans with majority of the study population having chronic liver disease from viral infection. Minimal to no fibrosis by the METAVIR (an acronym for Meta-analysis of Histological Data in Viral Hepatitis) score was found in 58% of patients compared to 42% with moderate to severe fibrosis. Hispanics were more likely than Blacks to have hepatic steatosis. Age significantly increased the sensitivity and specificity of APRI and age-platelet scores. The AST/ALT score had a lower sensitivity for liver fibrosis in women compared to men in our study population. The sensitivity of FIB-4 and age-platelet was higher in Hispanics compared to African Americans while the opposite was the case for APRI, AST/ALT, FCI, and FI. Non-invasive biomarkers are useful in detecting liver fibrosis. FIB-4 and age-platelet have a high sensitivity in Hispanics while African Americans have a high sensitivity for APRI, AST/ALT, FCI, and FI. It is worth noting that these non-invasive biomarkers had variable performances when ethnicity, age, and sex were considered in our population.

Twin research shows glycan changes are more susceptible to environmental factors than their carrier glycoproteins.

Changes in protein glycosylation are clinically used as biomarkers. In the present study, we employed a twin cohort to investigate the contributions of genetic and environmental factors to glycan modifications of glycoproteins. Mac-2 binding protein (Mac-2bp), haptoglobin (Hp), and their glycosylated forms are liver fibrosis and cancer biomarkers. Sera from 107 twin pairs without clinical information were used as a training cohort for the Mac-2bp and Mac-2bp glycosylation isomer (M2BPGi) assay. As a validation cohort, 22 twin pairs were enrolled in the study. For each twin pair, one twin was diagnosed with liver or pancreatic disease. For the training cohort, the correlation ratios of serum Mac-2bp and M2BPGi levels in twin sera with random sequences were 0.30 and 0.018, respectively. The correlation ratios between twin pairs in the validation cohort for serum Mac-2bp and M2BPGi levels were 0.75 and 0.35, respectively. In contrast, correlation ratios of serum Hp and fucosylated haptoglobin (Fuc-Hp) levels between twin sera with liver and pancreatic disease were 0.49 and 0.16, respectively. Although serum protein levels of glycoproteins are susceptible to genetic factors, characteristic glycan changes of these glycoproteins are more susceptible to environmental factors, including liver and pancreatic disease.

Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis.

The cystic fibrosis (CF) transmembrane conductance regulator corrector/potentiator combinations lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor improve sweat chloride, pulmonary function, and nutrition. Yet it is unclear whether they may also impact the progression of liver fibrosis, which is a substantial source of morbidity and mortality for patients with CF. We conducted a retrospective, single-center analysis of children and adolescents with CF treated with lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor therapy, focusing on alterations in liver function tests and fibrosis indices using previously-established thresholds that corresponded with increased liver elastography. In pairwise comparisons of before and during treatment timepoints, we found that those with CF-associated liver involvement experienced significant decreases in gamma-glutamyl transferase, aspartate aminotransferase-to-platelet index, and gamma-glutamyl transferase-to-platelet ratio while on lumacaftor/ivacaftor. These differences were not observed in patients treated with elexacaftor/tezacaftor/ivacaftor, nor were they observed in patients without underlying CF-associated liver disease. These results provide the first evidence that lumacaftor/ivacaftor may improve liver fibrosis in children and adolescents with CF and suggest it may be beneficial in the treatment of CF-associated liver disease.

Metabolomics for biomarker discovery in schistosomiasis: A systematic scoping review

BackgroundMetabolomic based approaches are essential tools in the discovery of unique biomarkers for infectious diseases via high-throughput global assessment of metabolites and metabolite pathway dysregulation. This in-turn allows the development of diagnostic tools and provision of therapeutics. In this review, we aimed to give an overview of metabolite biomarkers and metabolic pathway alterations during Schistosoma haematobium and Schistosoma mansoni infections.MethodsWe conducted the review by systematically searching electronic databases and grey literature to identify relevant metabolomics studies on schistosomiasis. Arksey and O’Malley methodology for conducting systematic scoping reviews was applied. A narrative summary of results was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping review guidelines.ResultsTwelve articles included in the review identified 127 metabolites, whose concentrations were considerably altered during S. mansoni and S. haematobium infections. The metabolites were assigned to metabolic pathways involved in energy (34.6%), gut microbial (11.0%), amino acid (25.2%), nucleic acids (6.3%), immune proteins (8.7%) hormones (2.4%) and structural proteins/lipids (11.8%). Energy related metabolic pathways were the most affected during schistosome infections with metabolites such as succinate, citrate, aconitate and fumarate of the tricarbocylic acid cycle being significantly altered in organ, serum and plasma samples. Amino acid metabolism was also impacted during schistosome infections as phenylacetylglycine, alanine, taurine, 2-oxoisocaproate and 2-oxoisovalerate emerged as potent biomarkers. Elevated structural proteins such as actin, collagen and keratin concentrations were identified as biomarkers of liver fibrosis, a common pathological feature in chronic schistosomiasis infections. Hippurate was a major metabolite biomarker in the gut microbial related pathway.ConclusionsThe analysis of the literature revealed that energy related metabolic pathways are considerably altered during S. mansoni and S. haematobium infections. Therefore, their metabolites may provide biomarkers for diagnosis and prognosis in addition to providing therapeutics for parasitic infections. This scoping review has identified a need to replicate more schistosomiasis metabolomic studies in humans to complement animal-model based studies.

Evolution of liver fibrosis after interferon-based anti-hepatitis C virus therapy failure in 3,049 chronic hepatitis C patients without cirrhosis

Background and study aimsLiver fibrosis is the underlying causeof hepatitis C virus (HCV)-related disease progression to endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma. The aim of our study was to assess changes in hepatic fibrosis in patients with chronic HCV who had a fibrosis evaluation at two time points at least six months apart. Patients and MethodsThis was a retrospective cohort study that included patients who had failed interferon therapy and received HCV retreatment with direct-acting antivirals (DAAs) at least six months later. Patients were evaluated previously for fibrosis according to liver biopsy and fibrosis biomarkers were evaluated before pegylated interferon and ribavirin (PEG/RBV) therapy. Fibrosis was re-evaluated with fibrosis-4 (FIB-4) scores before starting DAAs. ResultsA total of 3,049 patients were included [age 43.47 ± 9.07 years, 55.20 % males] and baseline histopathology showed F1, F2, and F3 in 16.86 %, 46.21 %, and 36.93 %, respectively. The mean time interval between the last dose of previously failed IFN-therapy to the first dose of DAAs was 2.38 (±1.07) years. Overall, there was a significant increase in FIB-4 scores at retreatment times (from 11.71 ± 1.13 to 22.26 ± 1.68, p < 0.001). Patients with baseline FIB-4 < 1.45 (n = 1,569) and between 1.45 and 3.25 (n = 1,237) had significant increases in their FIB-4 at the retreatment time point [median difference; 0.41 (0.91) and 0.24 (1.5), p < 0.001, respectively], whereas patients with FIB-4 > 3.25 had significant reduction of their FIB-4 score at a retreatment timepoint [−0.98 (2.93), p ≤ 0.001]. ConclusionFibrosis progressed in most patients, even within six months for some patients, and this indicates retreatment of non-system vascular resistance patients even if they do not have significant fibrosis.

Diagnostic Role of Circulating miRNAs in the Grading of Chronic Hepatitis B-Related Liver Fibrosis: ASystematic Review and Meta-Analysis.

miRNAs are considered potential biomarkers that can be used for the grading of chronic hepatitis B (CHB)-related liver fibrosis. This meta-analysis aims to elucidate the diagnostic performance of miRNAs. Databases were used to search for meta-analyses. Abivariate model was used to calculate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). In addition, the area under the summary receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were calculated. A total of 9 studies with 1159 patients with CHB-related liver fibrosis were assessed. For diagnosis of significant liver fibrosis, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.73 (95% CI, 0.68-0.78), 0.78 (95% CI, 0.70-0.84), 3.32 (95% CI, 2.52-4.37), 0.34 (95% CI, 0.30-0.39), 9.70 (95% CI, 7.10-13.24), and 0.81 (95% CI, 0.77-0.84), respectively. miRNAs are potential biomarkers of CHB-related liver fibrosis.

Systematic review and individual-patient-data meta-analysis of non-invasive fibrosis markers for chronic hepatitis B in Africa

In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index and two other fibrosis biomarkers using a Bayesian bivariate model. Transient elastography was used as a reference test with liver stiffness measurement thresholds at 7.9 and 12.2kPa indicating significant fibrosis and cirrhosis, respectively. At the World Health Organization-recommended cirrhosis threshold (>2.0), aspartate aminotransferase-to-platelet ratio index had sensitivity (95% credible interval) of only 16.5% (12.5–20.5). We identified an optimised aspartate aminotransferase-to-platelet ratio index rule-in threshold (>0.65) for liver stiffness measurement >12.2kPa with sensitivity and specificity of 56.2% (50.5–62.2) and 90.0% (89.0–91.0), and an optimised rule-out threshold (<0.36) with sensitivity and specificity of 80.6% (76.1–85.1) and 64.3% (62.8–65.8). Here we show that the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index threshold is inappropriately high in sub-Saharan Africa; improved rule-in and rule-out thresholds can optimise treatment recommendations in this setting.

Association of iron status with non-alcoholic fatty liver disease and liver fibrosis in US adults: a cross-sectional study from NHANES 2017-2018.

Aims: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder resulting in a high risk of adverse prognosis, and its presence has been considered a cause or an outcome of metabolic syndrome. But the relative factors and mechanism of NAFLD are still unclear. The aim of this study is to explore the association between iron status indicators and NAFLD as well as liver fibrosis. Methods: This study evaluated whether serum iron status indicators are independently related to the risk of NAFLD. The independent variable was each one of the iron status indicators (iron intake, ferritin, iron, unsaturated iron binding force (UIBC), total iron binding capacity (TIBC), transferrin saturation, transferrin receptor, hemoglobin, and mean cell hemoglobin), and the dependent variables were NAFLD and advanced liver fibrosis. A multivariable logistic regression analysis and subgroup analysis were performed to evaluate the association between iron status indicators and NAFLD as well as liver fibrosis. Results: A total of 3727 patients were included. After adjusting for other covariates in multiple logistic regression models, the serum ferritin, UIBC, TIBC, and hemoglobin had a significant positive association with the NAFLD (odds ratio [OR] = 1.16, 95% confidence interval [CI]: 1.09, 1.23; 1.31, 95% CI: 1.06, 1.62; 1.82, 95% CI: 1.23, 2.67; 2.67, 95% CI: 1.48, 4.82, separately), and the risk of NAFLD diagnosed by VCTE or ALT/AST further increased in the fourth quartile group of serum ferritin (diagnosed by VCTE OR = 1.93, 95% CI: 1.49, 2.50; diagnosed by ALT/AST OR = 5.76, 95% CI: 3.96, 8.38). Moreover, the main positive correlation between serum ferritin and NAFLD was found in females, participants aged >41 years, with no diabetes. Conclusion: Our results indicated that iron status indicators were closely associated with the occurrence of advanced liver fibrosis, which may indicate that iron status indicators could be potential biomarkers of NAFLD and advanced liver fibrosis.

Baseline Interleukin-6 as a Preoperative Biomarker for Liver Fibrosis

Introduction: Liver (hepatic) fibrosis (LF) is characterized by impaired function and regenerative capacity of the liver and can lead to significantly increased morbidity and mortality in the context of surgical liver resection (LR). For this reason, it is crucial to identify the extent of LF preoperatively. Interleukin-6 (IL-6) is known to play a key role in the pathogenesis of LF, but its exact value as a preoperative marker is unknown. This study aimed to investigate the correlation between preoperatively determined IL-6 and the presence of LF. Methods: In this prospective study, IL-6 was determined in 134 consecutive patients undergoing LR. Patients with liver cirrhosis (LC) and patients with clinical or laboratory signs of inflammation were excluded. LF was graded by a blinded pathologist with regard to the degree of LF according to the Desmet classification (0–4). Baseline IL-6 and degree of LF were correlated. Results: A total of 134 patients were prospectively included prior to LR. For 104 patients, LF was graded and inflammatory parameters were available. Thirty-five of these patients showed LC (Desmet 4), and another 33 patients showed preoperatively elevated inflammatory markers. Two of the remaining patients were liver transplant patients. These patients were excluded from the final analysis. According to Desmet, the remaining 34 patients had LF grade 0 or 1 (none or minimal LF) in 26 cases and LF grade 2 or 3 (moderate-to-severe LF) in 8 cases. Correlation of LF with preoperatively determined IL-6 yielded significantly higher IL-6 levels in the group of patients with moderate-to-severe LF (Desmet 2 or 3) compared to the group with none or minimal LF (Desmet 0 or 1; p = 0.0495). Conclusion: In the context of LR, our results showed a correlation of preoperatively determined IL-6 with the extent of LF present. Higher serum baseline IL-6 concentrations were associated with a higher degree of LF, whereas no other blood parameter or score was that predictive for LF. Our results suggest that baseline IL-6 might serve as a valuable parameter to assess LF prior to LR. More patients need to be analyzed to further evaluate and confirm the predictive accuracy of IL-6 for LF.

Biomarkers reflecting pericellular fibrosis improve together with liver histology after bariatric surgery in early non-alcoholic fatty liver disease

AimNon-invasive tests for non-alcoholic fatty liver disease (NAFLD) are needed for assessing disease stage, prognosis and treatment efficacy. Extracellular matrix biomarkers, such as PRO-C3, are useful as biomarkers of advanced liver fibrosis. However, non-invasive biomarkers of early-stage NAFLD, characterized by pericellular fibrosis, are lacking. Here, we measured serological biomarkers of type IV and VIII collagens reflecting the remodeling of the pericellular basement membrane to explore the effect of bariatric surgery on pericellular fibrosis in patients with early NAFLD. MethodsSeventy patients with severe obesity underwent bariatric surgery. The cohort consisted of 61 % females who had a mean age of 44. Patients had a median NAFLD activity score of 3 and mild-to-moderate fibrosis F0 (3 %), F1 (86 %), and F2 (11 %). Blood samples were taken at baseline, three, six and 12 months after surgery. At 12 months, 40 patients had a follow-up liver biopsy. The biomarkers PRO-C3, PRO-C4, C4M, and PRO-C8 were measured using indirect competitive ELISAs. ResultsTwelve months after surgery patients had significantly lower levels of ALT, GGT, HbA1c, fasting glucose, and CRP. The pericellular fibrosis biomarkers, C4M, PRO-C4, and PRO-C8 decreased by 24 %, 18 % and 44 %, respectively (p < 0.0001), while the interstitial matrix fibrosis marker PRO-C3 remained unchanged. Furthermore, baseline C4M was associated with histologically assessed hepatocyte ballooning and lobular inflammation in patients with (p = 0.032) and without (p = 0.032) steatosis, respectively. ConclusionBiomarkers of pericellular fibrosis decrease in early-stage NAFLD after patients undergo bariatric surgery and potentially reflect an improvement in liver histology.

Demonstrating HOCl as a potential biomarker for liver fibrosis using a highly sensitive fluorescent probe

The spatiotemporal inspection of ROS behavior during liver fibrosis (LF) progression can facilitate its diagnosis and anti-oxidant therapy. However, none of fluorescent probes for ROS has been devoted to this issue. In this study, we proposed a HOCl-specific fluorescent probe to monitor LF process for the first time. The probe was featured with easy preparation, high selectivity, superb sensitivity (0.97 nM), rapid response (within seconds), and good membrane permeability. It can monitor delicate cellular HOCl changes from various endo-sources, and discriminate different cell types (normal or cancer) according to their inherent HOCl levels. Especially, we constructed two LF rat models by either chemical treatment (CCl4 injection) or surgical operation (bile duct ligation), and for the first time observed that HOCl level in LF tissues increased along with its stage of development while that during acute liver injury or liver cirrhosis was unchanged or reduced. The results strongly evident the potential of HOCl as a unique biomarker for LF detection and even clinical diagnosis.

Association of liver fibrosis biomarkers with overall and CVD mortality in the Korean population: The Dong-gu study.

This study evaluated the associations of liver fibrosis biomarkers [non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4), aspartate aminotransferase/platelet ratio index (APRI), and BARD score] with mortality in Korean adults aged ≥50 years. We analyzed 7,702 subjects who participated in Dong-gu Study. The associations of liber fibrosis biomarkers with mortality were investigated using Cox proportional hazards models. Overall mortality increased with increasing NFS level [adjusted hazard ratio (aHR) 4.3, 95% confidence interval (CI) 3.3-5.5 for high risk vs. low risk], increasing FIB-4 level (aHR 3.5, 95% CI 2.9-4.4 for high risk vs. low risk), and increasing APRI level (aHR 3.5, 95% CI 2.1-5.8 for high risk vs. low risk) but not with BARD score. The Harrell's concordance index for overall mortality for the NFS and FIB-4 was greater than that for the APRI and BARD score. In conclusion, NFS, FIB-4, and APRI showed a significant relationship with the overall mortality, and NFS and FIB-4 showed a significant relationship with the CVD mortality after adjustment for covariates. In addition, the NFS and FIB-4 were more predictive of overall mortality than the APRI and BARD score in Korean adults aged ≥50 years.

Noninvasive imaging biomarkers for liver fibrosis in nonalcoholic fatty liver disease: current and future.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide and becoming a major cause of liver disease-related morbidity and mortality. The presence of liver fibrosis in patients with NAFLD is closely related to prognosis, including the development of hepatocellular carcinoma and other complications of cirrhosis. Therefore, assessment of the presence of significant or advanced liver fibrosis is crucial. Although liver biopsy has been considered the "gold standard" method for evaluating the degree of liver fibrosis, it is not suitable for extensive use in all patients with NAFLD owing to its invasiveness and high cost. Therefore, noninvasive biochemical and imaging biomarkers have been developed to overcome the limitations of liver biopsy. Imaging biomarkers for the stratification of liver fibrosis have been evaluated in patients with NAFLD using different imaging techniques, such as transient elastography, shear wave elastography, and magnetic resonance elastography. Furthermore, artificial intelligence and deep learning methods are increasingly being applied to improve the diagnostic accuracy of imaging techniques and overcome the pitfalls of existing imaging biomarkers. In this review, we describe the usefulness and future prospects of noninvasive imaging biomarkers that have been studied and used to evaluate the degree of liver fibrosis in patients with NAFLD.

Noninvasive serum biomarkers for liver fibrosis in NAFLD: current and future.

In the last 20 years, noninvasive serum biomarkers to identify liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) have been developed, validated against liver biopsy (the gold standard for determining the presence of liver fibrosis) and made available for clinicians to use to identify ≥F3 liver fibrosis. The aim of this review is firstly to focus on the current use of widely available biomarkers and their performance for identifying ≥F3. Secondly, we discuss whether noninvasive biomarkers have a role in identifying F2, a stage of fibrosis that is now known to be a risk factor for cirrhosis and overall mortality. We also consider whether machine learning algorithms offer a better alternative for identifying individuals with ≥F2 fibrosis. Thirdly, we summarise the utility of noninvasive serum biomarkers for predicting liver related outcomes (e.g., ascites and hepatocellular carcinoma) and non-liver related outcomes (e.g., cardiovascular-related mortality and extra hepatic cancers). Finally, we examine whether serial measurement of biomarkers can be used to monitor liver disease, and whether the use of noninvasive biomarkers in drug trials for non-alcoholic steatohepatitis can accurately, compared to liver histology, monitor liver fibrosis progression/regression. We conclude by offering our perspective on the future of serum biomarkers for the detection and monitoring of liver fibrosis in NAFLD.