Severity Of Liver Fibrosis In Patients Research Articles

Interaction Between PNPLA3 and SIRT5 Genetic Variants in Association with Liver Fibrosis Severity in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

Interaction Between PNPLA3 and SIRT5 Genetic Variants in Association with Liver Fibrosis Severity in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

MR elastography vs a combination of common non-invasive tests for estimation of severe liver fibrosis in patients with hepatobiliary tumors.

To evaluate the accuracy of combined imaging and blood test indices related to liver fibrosis (LF) compared to magnetic resonance elastography (MRE) for estimating severe LF (F3-4) in preoperative patients. This retrospective study included patients who underwent MRE, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, and dynamic CT before liver resection. Liver stiffness measurement (LSM) using MRE, liver-to-spleen signal intensity ratio (LSR) using Gd-EOB-DTPA-enhanced MRI, and spleen volume normalized to body surface area (SV/BSA) using CT volumetry were measured. Laboratory parameters, including levels of type IV collagen 7S and hyaluronic acid, were also measured. Logistic regression and receiver operating characteristic analyses were performed to identify parameters that could estimate severe LF more accurately than LSM alone. A total of 81 patients (mean age, 67 years ± 9.9 [SD]; 58 men) were enrolled. Multivariable logistic regression analysis indicated that LSR (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.05-0.37, p < 0.001), SV/BSA (OR: 1.25, 95% CI: 1.02-1.52, p = 0.03) and type IV collagen 7S (OR: 1.84, 95% CI: 1.12-3.00, p = 0.02) were associated with severe LF. Receiver operating characteristic analysis showed that for estimating severe LF, the area under the curve was significantly larger for the combination of LSR, SV/BSA, and type IV collagen 7S than for LSM alone (0.95 vs 0.85, p = 0.04). The combined evaluation of LSR, SV/BSA, and type IV collagen 7S obtained by clinically common preoperative examinations was more accurate than MRE alone for estimating severe LF in preoperative patients. Question What indicators among the imaging and blood tests commonly performed preoperatively can provide a more accurate estimate of severe LF compared to MRE? Findings The combination of LSR, SV/BSA, and type IV collagen 7S was more accurate thanan LSM alone for estimating severe LF. Clinical relevance A combination of commonly performed non-invasive preoperative tests provides a more accurate estimation of severe LF than MR elastography, an examination with relatively limited.

Non-invasive assessment of severe liver fibrosis in patients with Fontan-associated liver disease: The VALDIG-EASL FONLIVER cohort

Background & AimsFontan-type surgery is used as a palliation for congenital heart disease with univentricular physiology but may, in the long term, lead to advanced chronic liver disease. This study assessed the accuracy of conventional non-invasive models in assessing liver fibrosis and introduces a new risk score employing non-invasive tools. MethodsA prospective, cross-sectional, observational study was conducted across five European centers and encompassing all consecutive adult patients with Fontan circulation, liver biopsy and non-invasive tests (elastography, APRI, FIB-4, Fibrosis score, Doha, GUCI, and AAR). The primary outcome was the identification of severe liver fibrosis on biopsy. Multivariable logistic regression identified non-invasive predictors of severe fibrosis, leading to the development and internal validation of a new scoring model named the FonLiver risk score. ResultsIn total, 217 patients (mean [standard deviation] age, 27.9 [8.9] years; 50.7% males) were included. Severe liver fibrosis was present in 47.9% (95% CI 41.2%–54.5%) and correlated with a lower functional class, protein-losing enteropathy, and compromised cardiopulmonary and systemic hemodynamics. The final FonLiver risk score incorporated liver stiffness measurement using transient elastography and platelet count and demonstrated strong discrimination and calibration (area under the receiver operating curve [AUROC] of 0.81). The FonLiver risk score outperformed conventional prediction models (APRI, FIB-4, Fibrosis score, Doha, GUCI, and AAR), which all exhibited worse performance in our cohort (AUROC < 0.70 for all). ConclusionSevere liver fibrosis is prevalent in adults following Fontan-type palliation and can be effectively estimated using with the novel FonLiver risk score. This scoring system can be easily incorporated into the routine assessment of patients with Fontan circulation.

Distinct Gut Microbial Signature and Host Genetic Variants in Association with Liver Fibrosis Severity in Patients with MASLD.

Gut microbiota might affect the severity and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to characterize gut dysbiosis and clinical parameters regarding fibrosis stages assessed by magnetic resonance elastography. This study included 156 patients with MASLD, stratified into no/mild fibrosis (F0-F1) and moderate/severe fibrosis (F2-F4). Fecal specimens were sequenced targeting the V4 region of the 16S rRNA gene and analyzed using bioinformatics. The genotyping of PNPLA3, TM6SF2, and HSD17B13 was assessed by allelic discrimination assays. Our data showed that gut microbial profiles between groups significantly differed in beta-diversity but not in alpha-diversity indices. Enriched Fusobacterium and Escherichia_Shigella, and depleted Lachnospira were found in the F2-F4 group versus the F0-F1 group. Compared to F0-F1, the F2-F4 group had elevated plasma surrogate markers of gut epithelial permeability and bacterial translocation. The bacterial genera, PNPLA3 polymorphisms, old age, and diabetes were independently associated with advanced fibrosis in multivariable analyses. Using the Random Forest classifier, the gut microbial signature of three genera could differentiate the groups with high diagnostic accuracy (AUC of 0.93). These results indicated that the imbalance of enriched pathogenic genera and decreased beneficial bacteria, in association with several clinical and genetic factors, were potential contributors to the pathogenesis and progression of MASLD.

Serum autotaxin is a prognostic indicator of liver-related events in patients with non-alcoholic fatty liver disease.

Circulating autotaxin (ATX) levels have been reported to correlate with liver inflammation activity and liver fibrosis severity in patients with non-alcoholic fatty liver disease (NAFLD). The objective of this study is to investigate whether serum ATX could predict liver-related events (LRE) in NAFLD patients. This retrospective investigation includes 309 biopsy-proven NAFLD patients registered at Shinshu University Hospital. All patients are followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, hepatic encephalopathy, ascites, and esophagogastric varices, is investigated in relation to ATX levels at the time of liver biopsy. During the median follow-up period of 7.0 years, LRE are observed in 20 patients (6.5%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE are 0.81 and 1.227 mg/l, respectively. Multivariate Cox proportional hazards models for LRE determine ATX and advanced fibrosis as independently associated factors. Furthermore, in a competing risk analysis that considered non-liver-related death as a competing event, ATX (HR 2.29, 95% CI 1.22-4.30, p = 0.010) is identified as an independent factor associated with LRE, along with advanced fibrosis (HR 8.01, 95% CI 2.10-30.60, p = 0.002). The predictive utility of ATX for LRE is validated in an independent cohort. Serum ATX may serve as a predictive marker for LRE in patients with NAFLD.

Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease

ObjectiveHyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of...

Analytical performance of the Enhanced Liver Fibrosis (ELF) Test on the Atellica IM Analyzer

BackgroundThe Enhanced Liver Fibrosis (ELFTM) Test comprises 3 direct serum markers of fibrosis—hyaluronic acid (HA), amino-terminal pro-peptide of type III procollagen (PIIINP), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)—whose results are combined in an algorithm to generate the ELF score. Outside the U.S., the ELF Test and score are CE marked for assessment of liver fibrosis severity in patients with signs, symptoms, or risk factors of chronic liver disease to support diagnosis of fibrosis staging or prognosis for likelihood of progression to cirrhosis and liver-related clinical events. In the U.S., the FDA granted de novo marketing authorization to aid prognostic evaluation of disease progression (to cirrhosis and liver-related clinical events) in nonalcoholic steatohepatitis patients with advanced liver fibrosis. We describe the analytical performance of the ELF analytes and score on the Atellica® IM Analyzer. MethodsClinical and Laboratory Standards Institute protocols were followed for detection capability (limits of blank [LoB], detection [LoD], and quantitation [LoQ]), precision, interference, linearity, hook effect, and ELF reference interval. ResultsAll parameters met predetermined requirements: HA (LoB 1.00 ng/mL, LoD 2.00 ng/mL, LoQ 3.00 ng/mL); PIIINP (LoB 0.50 ng/mL, LoD 0.75 ng/mL, LoQ 1.00 ng/mL); TIMP-1 (LoB 3.0 ng/mL, LoD 4.0 ng/mL, LoQ 5.0 ng/mL). Across the 3 assays, repeatability was ≤5.4% CV; within-lab precision was ≤8.5% CV. ELF score repeatability was ≤0.6% CV, within-lab precision ≤1.3% CV, and reproducibility ≤1.1% CV. Good correlation was obtained between the Atellica IM ELF and ADVIA Centaur ELF Tests (y = 1.01x − 0.22, r = 0.997). Assays were linear across analytical measuring ranges. ConclusionsAnalytical performance validation results for the ELF Test and ELF score were excellent making the test acceptable for routine clinical use.

Клинические проявления у пациентов с генотипами 1 и 3 вируса гепатита С в зависимости от выраженности фиброза печени

Aim: to compare the clinical manifestations in patients with genotypes 1 and 3 of viral hepatitis C (HCV) depending on the severity of liver fibrosis (LF). Study Design: a comparative study of randomized groups of patients treated in an inpatient or outpatient setting. Materials and methods. A total of 297 patients with HCV genotype 1 and 231 patients with HCV genotype 3 were examined. The diagnosis of chronic viral hepatitis C was established according to the recommendations of the European Association for the Study of the Liver. All patients underwent clinical and biochemical blood tests, ultrasound examination of the liver and pancreas. LF was studied by shear wave transient elastometry with METAVIR score. Results. Severe LF was associated in both groups of patients with an increase in the frequency of liver complaints, hepatomegaly and splenomegaly, an increase in the content of bilirubin and alanine aminotransferase in the blood, a decrease in the number of platelets and the concentration of albumin in the blood. Only in patients with HCV genotype 3 was an increase in viral load and a trend towards a decrease in the proportion of neutrophils in the blood in patients with stages 3–4 LF compared with 0–2 stages of LF according to METAVIR. Conclusion. We think that the explanation for the higher incidence of severe LF in patients with HCV genotype 3 is probably a more significant deformation of the immune response, leading to an increase in viral load and an aggressive course of pathology. Keywords: viral hepatitis C, virus genotype, liver fibrosis, clinical manifestations.

Principles of diagnosis and treatment of alcohol-induced liver fibrosis

Alcohol-related liver diseases are one of the leading causes of death worldwide, primarily due to complications of liver cirrhosis (LC). Early detection of alcohol-induced liver fibrosis (LF) is a difficult task, since often alcoholic liver disease (ALD) is clinically manifested only at late stages. Given that not all alcoholic suffer from ALD, the widespread use of liver biopsy to verify the diagnosis is not advisable. Despite the variety of proposed non-invasive methods for assessing the severity of LF in patients with ALD, none of them has sufficient validation and therefore cannot be recommended for widespread use in clinical practice. The most well-studied transient elastography, due to its suboptimal specificity, can be effectively used only to exclude clinically significant LF or LC. The only proven approach to treat ALD is persistent and total alcohol abstinence. While the therapeutic options for patients with severe forms of acute hepatitis remain unchanged since the 70s of the last century and are based mainly on the use of corticosteroids, currently, there are no approaches to antifibrotic therapy of ALD approved by the guidelines. At the same time, modern achievements in understanding the pathophysiological mechanisms of this disease have served as an impetus for the development of ways to solve the problem. In particular, providing intestinal eubiosis may be an important goal for the prevention and treatment of alcohol-induced LF. Randomized controlled multicenter trials involving a large number of patients are needed to confirm this and other hypotheses related to antifibrotic therapy of ALD and to accept them as a standard of medical care.

Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis

Background. In recent years, as a result of the growing expansion of the pharmaceutical market, there has been a clear trend towards an increase in the incidence of chronic toxic drug-induced hepatitis of drug genesis (TDIH). The appearance of fibrosis is considered the most important histological change that determines the further course of the disease. Therefore, the search for non-invasive or minimally invasive markers for assessing fibrotic changes in the liver remains an urgent issue in clinical practice. The purpose was to determine the diagnostic value of immunological parameters for stratification of the severity of liver fibrosis in patients with TDIH. Materials and methods. The study included 41 patients with TDIH, who were divided into three groups: group I consisted of 12 people without liver fibrosis (F0), group II— 22 patients with moderate fibrosis (F1-F2), group III— 7 individuals with severe liver fibrosis (F3-F4). Shear wave elastography was performed using a Soneus P7 system (Ukraine-Switzerland). All patients underwent a biochemical blood test with the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST). The subpopulation composition of lymphocytes, circulating immune complexes (CIC), the level of interleukins (IL-6, IL-10) and tumor necrosis factor α were assessed. Results.The progression of liver fibrosis is accompanied by an increase in cytolytic syndrome: patients with severe fibrosis have a 3.3-fold increase in the ALT (p&lt;0.05) compared to the controls and a 2.1-fold (p&lt;0.05) compared to that in patients with moderate fibrosis. The AST level is significantly higher— by 4.6 times (p=0.023) in patients with severe fibrosis than in those with moderate fibrosis. With the progression of liver fibrosis, there is a significant decrease in cellular immunity, an increase in the level of CIC and pro-inflammatory cytokines with a simultaneous decrease in the content of anti-inflammatory cytokines, which is confirmed by correlations between the liver stiffness index according to shear wave elastography data and the level of T-helpers (r=–0.466; p=0.03), IL-6 (r=0.364; p=0.01), IL-10 (r=–0.331; p=0.039) and CIC (r=0.381; p=0.017). Conclusions. Markers of the diagnosis of severe liver fibrosis in patients with TDIH are indicators such as the ratio of IL-6/IL-10 higher than 0.83 (sensitivity 81.8%, specificity 78.9%), CIC level more than 4.3 optical density units (sensitivity 77.3%, specificity 72.2%), the ratio of T-helpers/T-suppressors is less than or equal to 1.6 (sensitivity 72.7%, specificity 57.9%).

The Difference of Hypoxic Inducible Factor-1α, Vascular Endothelial Growth Factor, and Transforming Growth Factor-β1 Based on Liver Fibrosis Severity in Patients with Chronic Hepatitis B

BACKGROUND: Hepatitis B is a global health problem. The disease damages hepatocytes and creates tissue hypoxic condition. Hypoxia triggers production of several mediators such as hypoxic inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1. The mediators act in liver fibrosis and cirrhosis, and hepatocellular carcinoma.&#x0D; AIM: The objective of the study was to determine the difference in serum HIF-1α, VEGF, and TGF-β1 levels based on liver fibrosis severity in patients with chronic hepatitis B.&#x0D; MATERIALS AND METHODS: This cross-sectional study was performed in Haji Adam Malik Hospital Medan, Indonesia, from January to July 2020. Subjects were chronic hepatitis B patients aged 18 years or older. Exclusion criteria were other chronic diseases, malignancies, or pregnancy. Liver fibrosis was determined using shear wave elastography and categorized as follow: F1, F2, F3, and F4. Serum HIF-1α, VEGF, and TGF-β1 levels were measured using enzyme-linked immunosorbent assay. Specimens were obtained from venous blood.&#x0D; RESULTS: A total of 63 patients were enrolled in this study with mean age of 40.3 (SD 11.69) years. Subjects were dominated by males (58.7%). There were no differences in serum HIF-1α, VEGF, and TGF-β1 levels based on liver fibrosis grading and also based on hepatitis B envelope antigen (HBeAg) status and gender. Associations between liver fibrosis grading, HBeAg, and gender were absent. There was a positive correlation between liver fibrosis severity and age (r = 0.311, p = 0.013).&#x0D; CONCLUSION: Serum HIF-1α, VEGF, and TGF-β1 levels were not different among chronic hepatitis B patients based on liver fibrosis severity.

Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (NAFLD)

BackgroundDysfunctional metabolism lies at the centre of the pathogenesis for Non-Alcoholic Fatty Liver Disease (NAFLD) and involves mitochondrial dysfunction, lipid dysmetabolism and oxidative stress. This study, for the first time, explores real-time energy changes in peripheral blood and corresponding metabolite changes, to investigate whether mitochondria-related immunometabolic biomarkers can predict progression in NAFLD. MethodsThirty subjects divided into 3 groups were assessed: NAFLD with biopsy-proven mild fibrosis (n = 10), severe fibrosis (n = 10) and healthy controls (HC, n = 10). Mitochondrial functional analysis was performed in a Seahorse XFp analyzer in live peripheral blood mononuclear cells (PBMCs). Global metabolomics quantified a broad range of human plasma metabolites. Mitochondrial carbamoyl phosphate synthase 1(CPS-1), Ornithine transcarbamoylase (OTC), Fibroblast growth factor-21 (FGF-21) and a range of cytokines in plasma were measured by ELISA. ResultsNAFLD patients with severe fibrosis demonstrated reduced maximal respiration (106 ± 25 versus 242 ± 62, p < 0.05) and reserve capacity (56 ± 16 versus 184 ± 42, p = 0.006) compared to mild/moderate fibrosis. Comparing mild/moderate vs severe liver fibrosis in patients with NAFLD, 14 out of 493 quantified metabolites were significantly changed (p < 0.05). Most of the amino acids modulated were the urea cycle (UC) components which included citrulline/ornithine ratio, arginine and glutamate. Plasma levels of CPS-1 and FGF-21 were significantly higher mild versus severe fibrosis in NAFLD patients. This novel panel generated an area under the ROC of 0.95, sensitivity of 100% and specificity 80% and p = 0.0007 (F1-F2 versus F3-F4). ConclusionProgression in NAFLD is associated with mitochondrial dysfunction and changes in metabolites associated with the urea cycle. We demonstrate a unique panel of mitochondrial-based, signatures which differentiate between stages of NAFLD. Lay summaryMitochondrial dysfunction in peripheral cells along with alterations in metabolites of urea cycle act as a sensor of hepatocyte mitochondrial damage. These changes can be measured in blood and together represent a unique panel of biomarkers for progression of fibrosis in NAFLD.

Clinical Utility of Quantitative Hbsag in Chronic Hepatitis B Infection

The prevalence of hepatitis B infection in Indonesia is still alarming, while its therapies cannot eradicate the virus and only aim for long term viral suppression. HBsAg quantification has become an emphasis on researches, regarding its capacity to identify the natural history of hepatitis B virus infection and predict the outcome of therapies. This review aims to determine the clinical role of HBsAg in chronic hepatitis B infection by reviewing textbooks, journal articles, and review articles without language restriction. This review finds that HBsAg is capable of predicting degrees of liver fibrosis severity in patients with chronic hepatitis B infection. Furthermore, HBsAg quantification can be used to distinguish inactive carriers from patients with HBeAg-negative chronic hepatitis B. The decrease of HBsAg is a good predictor of HBsAg loss, and it denotes discontinuation of nucleoside/nucleotide analog therapy. HBsAg quantification is also used in combined PEG-IFN and nucleoside/nucleotide analog therapy. Nevertheless, this role is still controversial. Additionally, HBsAg cannot replace the major roles of HBV DNA measurement in therapy management. Using either HBsAg or HBV DNA in therapy algorithm decreases its predictive value, hence recommendation to use both. In identifying patients with occult hepatitis B infection (OBI), HBV DNA still cannot be replaced by HBsAg quantification. Furthermore, HBsAg quantification may not be a good predictor of hepatocellular carcinoma in patients with OBI. Future studies are expected to demonstrate the role of HBsAg in current hepatitis B therapy and also future therapies.

Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis

The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to estimate the accuracy of this test against biopsy. In this systematic review, we searched MEDLINE, Embase, Web of Science and the Cochrane Library for studies that included patients with NAFLD and that used both liver biopsy (as the reference standard) and the ELF test. Two authors independently screened the references, extracted the data and assessed the quality of included studies. Due to the variation in reported thresholds, we used a multiple thresholds random effects model for meta-analysis (diagmeta R-package). The meta-analysis of 11 studies reporting advanced fibrosis and 5 studies reporting significant fibrosis showed that the ELF test had a sensitivity of >0.90 for excluding fibrosis at a threshold of 7.7. However, as a diagnostic test at high thresholds, the test only achieved specificity and positive predictive value >0.80 in very high prevalence settings (>50%). To achieve a specificity of 0.90 for advanced and significant fibrosis, thresholds of 10.18 (sensitivity: 0.57) and 9.86 (sensitivity: 0.55) were required, respectively. The ELF test showed high sensitivity but limited specificity to exclude advanced and significant fibrosis at low cut-offs. The diagnostic performance of the test at higher thresholds was found to be more limited in low-prevalence settings. We conclude that clinicians should carefully consider the likely disease prevalence in their practice setting and adopt suitable test thresholds to achieve the desired performance. The enhanced liver fibrosis test has been suggested as a non-invasive blood test to aid the diagnosis of severe liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Our study results showed that the test has a high negative predictive value, especially in populations with low disease prevalence (likely encountered in primary care); so, it can exclude advanced fibrosis in patients with NAFLD. However, when prevalence is low, the positive predictive value of the enhanced liver fibrosis test is low, suggesting that additional strategies may be needed to make a positive diagnosis in such settings.

Altered Metabolic Profile and Adipocyte Insulin Resistance Mark Severe Liver Fibrosis in Patients with Chronic Liver Disease

Metabolomics/lipidomics are important tools to identify novel biomarkers associated with liver damage. Patients with chronic liver disease (CLD) and hepatitis C virus (HCV) infection often have alterations in glucose, lipid and protein metabolism. The aim of this study was to evaluate if dysfunctional lipid and amino acid metabolism was associated with fibrosis severity and insulin resistance in CLD/HCV patients. We analyzed the baseline sera of 75 subjects with CLD/HCV infection HCV genotype-1, with proven liver biopsy prior to antiviral treatment. We measured amino acid (AA) and lipid concentration by gas and liquid chromatography-mass spectrometry respectively. Alterations in peripheral glucose metabolism due to insulin resistance (IR) were assesed by HOMA-IR (Glucose x Insulin/22.5), while adipose tissue IR was estimated as (Adipo-IR = Free Fatty Acids x Insulin). Baseline HOMA-IR and Adipo-IR were related to the degree of liver fibrosis. Reduction in ceramides 18:1/22:0, 18:1/24:0, diacylglycerol 42:6 and increased phosphocholine 40:6 were associated with higher fibrosis. Adipo-IR was related to lower levels of lysophosphatidylcholine 14:0 and 18:2 and with higher levels of sphingomyelin 18:2/24:0 and 18:2/24:1. Almost all AA were positively associated with Adipo-IR but not with HOMA-IR. We further confirmed the potential use of metabolomics and lipidomics in CLD/HCV subjects finding novel biomarkers of hepatic fibrosis and show that the adipose tissue IR is associated with more severe liver disease and is an important marker not only of altered lipid but also AA metabolism.

Sarcopenic obesity in fatty liver

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steato hepatitis have an increasing prevalence among liver diseases. Overweight and obesity are frequently associated conditions in patients with fatty liver. Skeletal muscle mass depletion may also coexist with chronic liver disease even in obese patients. This review will focus on the relationship between sarcopenic obesity and fatty liver. Obesity and sarcopenia are frequently encountered in patients with NAFLD. Adipose tissue is able to release molecules (adipokines) that regulate lipid metabolism, interact with insulin sensitivity and may contribute to induce fibrogenesis in the liver. Skeletal muscle tissue is able to secrete myokines regulating muscle metabolism and insulin sensitivity. Myokines perturbation has been reported to influence adipose tissue mass and fat deposition in the liver. Sarcopenia has been reported as independent risk factor for the development of NAFLD, and for a more severe liver fibrosis in patients with NAFLD. The interaction between skeletal muscle, adipose tissue and the liver may play a role in the development of NAFLD. Sarcopenia and sarcopenic obesity are risk factors for the development of fatty liver and associated with more severe liver fibrosis. Management is not standardized, but dietary counseling and physical training have been proposed as promising strategies. Bariatric surgery may be considered in patients with severe 'resistant' obesity.

Correlation Between miR-125b Expression and Liver Fibrosis in Patients with Chronic Hepatitis C

Objectives: The study aimed to investigate the role of miR-125b as a non-invasive biomarker in chronic hepatitis C. Methods: An observational study was conducted on 94 treatment-naive HCV-infected patients (mean age 49.8 ± 11.5 years, 59.6% females). Liver fibrosis was assessed by transient elastography (TE) and the expression of miR-125b in plasma was quantified by real-time PCR. Results: All patients were infected with HCV genotype 1b and had active viral replication, 42.6% had significant cytolysis, and 73.4% had increased serum gamma-glutamyl transferase (GGT) values. Significant fibrosis (liver stiffness measured by TE of > 7.1 kPa) was present in 61.7% of the patients. No significant associations were found between miR-125b expression and baseline HCV viral load (P = 0.56), IL28B polymorphisms (P = 0.5), alpha-fetoprotein levels (P = 0.27), and patients’ gender (P = 0.13) or age (P = 0.5). In a univariate analysis, the miR-125b expression level was significantly correlated with ALT (P = 0.001) and GGT levels (P < 0.0001). An up-regulated expression of miR-125b was found in plasma samples from patients with advanced liver fibrosis as compared to those with mild/moderate fibrosis [mean miR-125b value = 0.002 versus 0.001 (P = 0.02)]. In a multiple regression analysis, an upregulated miR-125b expression level remained independently in association only with significant fibrosis and increased GGT level (P = 0.026; R2 = 0.242). Conclusions: An up-regulated miR-125b expression might be an indicator of severe liver fibrosis in patients with chronic hepatitis C, independent of the viral replication level.

P475 High prevalence of severe liver fibrosis in patients with longstanding IBD

P475 High prevalence of severe liver fibrosis in patients with longstanding IBD

Serial combination of non-invasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with NAFLD.

The accuracy of available non-invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited. To assess the diagnostic performance of paired or serial combination of non-invasive tools in NAFLD patients. We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan. LSM, NFS and FIB-4 were the best non-invasive tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB-4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB-4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB-4 values (<-1.455 and <1.30, respectively) overall increased the diagnostic performance generating an accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to 20.4% and a rate of wrong classification ranging from 9.2% to 11.3%. The serial combination of LSM with FIB-4/NFS has a good diagnostic accuracy for the non-invasive diagnosis of severe fibrosis in NAFLD.

Serial combination of noninvasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with nonalcoholic fatty liver disease

Serial combination of noninvasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with nonalcoholic fatty liver disease