Serum Markers Of Liver Fibrosis Research Articles

A machine learning-based model analysis for serum markers of liver fibrosis in chronic hepatitis B patients

Early assessment and accurate staging of liver fibrosis may be of great help for clinical diagnosis and treatment in patients with chronic hepatitis B (CHB). We aimed to identify serum markers and construct a machine learning (ML) model to reliably predict the stage of fibrosis in CHB patients. The clinical data of 618 CHB patients between February 2017 and September 2021 from Zhejiang Provincial People's Hospital were retrospectively analyzed, and these data as a training cohort to build the model. Six ML models were constructed based on logistic regression, support vector machine, Bayes, K-nearest neighbor, decision tree (DT) and random forest by using the maximum relevance minimum redundancy (mRMR) and gradient boosting decision tree (GBDT) dimensionality reduction selected features on the training cohort. Then, the resampling method was used to select the optimal ML model. In addition, a total of 571 patients from another hospital were used as an external validation cohort to verify the performance of the model. The DT model constructed based on five serological biomarkers included HBV-DNA, platelet, thrombin time, international normalized ratio and albumin, with the area under curve (AUC) values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the training cohort were 0.898, 0.891, 0.907 and 0.944, respectively. The AUC values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the external validation cohort were 0.906, 0.876, 0.931 and 0.933, respectively. The simulated risk classification based on the cutoff value showed that the classification performance of the DT model in distinguishing hepatic fibrosis stages can be accurately matched with pathological diagnosis results. ML model of five serum markers allows for accurate diagnosis of hepatic fibrosis stages, and beneficial for the clinical monitoring and treatment of CHB patients.

Liver fibrosis assessed via non-invasive tests is associated with incident heart failure in a general population cohort

To determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. Using UK Biobank data, we prospectively examined the relationship between non-invasive fibrosis markers [NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and AST to platelet ratio index (APRI)] and incident hospitalization/death from heart failure (n=413,860). Cox-regression estimated hazard ratios (HR) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype, and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high risk NFS score HR 1.59 [1.47-1.76], p<0.0001; FIB-4 HR 1.69 [1.55-1.84], p<0.0001; APRI HR 1.85 [1.56-2.19], p<0.0001; combined fibrosis scores HR 1.90 [1.44-2.49], p<0.0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD) and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3 a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score and heart failure. In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Serum β-klotho is a potential biomarker for the progression of hepatitis B virus-related liver diseases.

Hepatitis B virus (HBV) infection is a global epidemic that can lead to several liver diseases, seriously affecting people's health. This study aimed to investigate the clinical potential of serum β-klotho (KLB) as a promising biomarker in HBV-related liver diseases. This study enrolled 30 patients with chronic hepatitis B (CHB), 35 with HBV-related cirrhosis, 66 with HBV-related hepatocellular carcinoma (HCC), and 48 healthy individuals. ELISA measured the levels of serum KLB in the four groups. We then compared the differences in serum KLB levels among the groups and analyzed the relationship between serum KLB and routine clinical parameters. The concentrations of serum KLB levels were increased sequentially among the healthy subjects, the HBV-related CHB group, the HBV-related cirrhosis group, and the HBV-related HCC group (p < 0.05). Expression of KLB was positively correlated with alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, alkaline phosphatase, total bile acid, serum markers for liver fibrosis, ascites, cirrhosis, splenomegaly, and model for end-stage liver disease sodium, while negatively correlated with platelet count, albumin, and prothrombin activity (p < 0.05). In addition, serum KLB has better sensitivity in diagnosing HCC than AFP, and serum KLB combined with AFP has higher sensitivity and specificity than AFP alone in diagnosing HCC. Serum KLB level is associated with the severity of HBV-related liver diseases and has important diagnostic value for HCC. Therefore, it could be a predictive biomarker for monitoring disease progression.

Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer.

Pancreatic cancer (PC) is a challenging malignancy to treat. Mac-2-binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells invitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity invivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer-associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin-3, which binds to M2BPGi, did not affect the proliferation-promoting effect of M2BPGi in PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC-bearing xenograft mice. CAF-derived M2BPGi promotes the proliferation and invasion of PC cells. Targeting M2BPGi may represent a new therapeutic strategy to circumvent refractory PC.

Evaluation of soluble suppression of tumorigenicity 2 (sST2) as serum marker for liver fibrosis

Background & aimsWith the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C.Methods424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman’s correlation and AUROC analyses.ResultsData of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman’s rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65–0.83), and 0.67(95%CI 0.56–0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests.ConclusionssST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4.

Serum liver fibrosis markers predict hepatic decompensation in compensated cirrhosis

Background and aimThe literature is sparse on the association between serum liver fibrosis markers and the development of hepatic decompensation in patients with compensated cirrhosis. We aimed to assessed whether the serum liver fibrosis markers are predictive of the occurrence of hepatic decompensation.MethodsWe ascertained 688 cirrhotic patients with varying etiologies, between December 2015 to December 2019. Serum hyaluronic acid (HA), laminin (LN), collagen IV (CIV), and N-terminal propeptide of type III collagen (PIIINP) levels were measured at enrollment. All subjects were followed for at least 6 months for occurrence of hepatic decompensation. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of hepatic decompensation during follow-up.ResultsDuring a median follow-up of 22.0 (13.0–32.0) months, decompensation occurred in 69 (10.0%) patients. Multivariate analysis indicated that higher LN (HR: 1.008, 95% confidence interval [CI]: 1.002–1.014, P = 0.011) and CIV (HR: 1.004, 95% CI: 1.001–1.007, P = 0.003) levels were independently associated with hepatic decompensation. Furthermore, patients in the tertile 2 and tertile 3 groups for CIV levels had HRs of 4.787 (1.419, 16.152) (P = 0.012) and 5.153 (1.508, 17.604) (P = 0.009), respectively, for occurrence of decompensation event compared with those in the tertile 1 group.ConclusionSerum liver fibrosis markers, particularly in CIV, appeared to be reliable biomarkers of disease progression and liver decompensation in patients with compensated cirrhosis with varying etiologies.

Utility of the Enhanced Liver Fibrosis score as a blood biomarker of pulmonary fibrosis secondary to SARS-CoV-2 pneumonia

IntroductionSARS-CoV-2 pneumonia can lead to several sequelae, among them, pulmonary fibrosis. The Enhanced Liver Fibrosis (ELF) score is a panel of serum markers of liver fibrosis. We aimed to describe the utility of the ELF score as a biomarker of pulmonary fibrosis secondary to COVID-19 pneumonia. MethodsChest computed tomography (CT) scan, lung function tests (LFT) and blood analysis were obtained at three months after discharge. Data were analysed according to ELF scores and posteriorly divided into ELF tertiles. ResultsOne hundred twenty-nine patients were recruited; of these, 85.7% presented bilateral pneumonia at diagnosis of SARS-CoV2 infection. At 3 months after discharge, CT scan was available in 123 patients, 73 (59.3%) of whom presented parenchymal lung abnormalities (PLA) and LFT showed impairment in 28 (22.7%) patients. Globally, the most frequent PLA was ground glass opacities (50%), followed by bronchial thickening (26.8%), reticular pattern (19.5%), consolidation (10.5%) and air bronchogram sign (7.3%). Radiological findings were only significant in the higher tertile of ELF, with a reticular pattern as the predominant PLA (p = 0.002). Moreover, patients with both PLA and LFT impairment, presented a trend towards higher levels of ELF compared with patients with only PLA or LFT impairment, or no impairment (9.9 (0.7) vs 9.6 (0.8), 9.1 (1.1) and 9.3 (0.7); p = 0.054). ConclusionPatients with both PLA and LFT alteration at 3 months after SARS-CoV-2 pneumonia had higher ELF scores. The ELF score may be useful to identify patients with risk of fibrotic changes after SARS-CoV-2 pneumonia.

Correlation between serum liver fibrosis markers and early gastroesophageal varices among patients with compensated liver cirrhosis: a cross-sectional analysis

Background and aimPortal hypertension is a common complication of chronic liver diseases responsible for most liver cirrhosis consequences. In patients with portal hypertension, oesophagogastric variceal bleeding is a leading cause of death. Most research has focused on high-risk gastroesophageal varices and bleeding, with only a few studies on early varices. However, early intervention of gastroesophageal varices was found to better improve the prognosis and reduce mortality, but there is still no relevant research. Ultrasonic endoscopy is a combination of endoscopy and ultrasonic imaging. It can gastroscopically detect varices around the oesophagus and stomach and detect oesophageal collateral veins and perforating veins earlier, which is helpful for the early diagnosis of varices. Therefore, this study aimed to explore the correlation between serum fibrosis markers and early gastroesophageal varices in compensated cirrhosis patients.MethodsThis study included 791 patients with compensated cirrhosis. The selected patients were categorized into three groups. The early gastroesophageal varices group included patients with gastroesophageal varices found by endoscopic ultrasonography but not by gastroscopy. The no gastroesophageal varices group underwent endoscopic ultrasonography and gastroscopy without varices. In addition, gastroesophageal varices can be detected with both techniques. Multiple logistic regression analysis explored the association of serum fibrosis markers with early gastroesophageal varices.ResultsAmong the 791 compensated liver cirrhosis patients, 198 patients were without gastroesophageal varices, 279 patients had early gastroesophageal varices, 314 patients had gastroesophageal varices, and both techniques could detect varices. There was a positive correlation between serum fibrosis markers and early gastroesophageal varices. In univariate logistic regression analysis, the patients with early gastroesophageal varices had lower platelet counts (P = 0.034) and higher aspartate aminotransferase (P = 0.046), total bilirubin (P = 0.041), hyaluronic acid (P < 0.001), laminin (P < 0.001), type III procollagen (P = 0.005), type IV collagen (P = 0.002), liver stiffness measurement (P = 0.001), APRI (P = 0.019) and FIB-4 (P = 0.002). Multivariate analysis showed that laminin (OR 1.011; 95% CI 1.004-1.017, P = 0.001) was an independent risk factor for predicting early gastroesophageal varices in compensated cirrhosis patients.ConclusionHigher laminin was independently associated with early gastroesophageal varices in compensated cirrhosis patients.

Diagnostic significance of serum type IV collagen (IVC) combined with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio in liver fibrosis.

Liver fibrosis is a necessary stage for various chronic liver diseases to develop into cirrhosis. The detection of serum markers of liver fibrosis is a commonly used method for early screening of liver fibrosis, mainly including type IV collagen (IVC), hyaluronic acid (HA), laminin (LN), and type III procollagen (PCIII). However, the high cost of the instrument and the slow detection speed are not conducive to mass screening and detection of the population. In this study, the widely used biochemical platform was used to jointly detect the liver fibrosis marker IVC and aspartate aminotransferase (AST) and alanine aminotransferase (ALT), We investigated the feasibility of serum IVC combined with the AST and ALT ratio (AST/ALT ratio) as a marker for liver fibrosis. A total of 81 patients with liver disease by clinical liver biopsy comprised the study group, and 50 healthy people who underwent physical examination in the study period were selected as the control group. Serum IVC, AST and ALT levels were detected by biochemical testing, AST/ALT ratio was calculated, and four serum markers of liver fibrosis (IVC, HA, LN, and PCIII) were measured by chemiluminescence. Moreover, imaging by color Doppler ultrasound (B-ultrasound) was performed for statistical analysis. (I) Serum IVC and the AST/ALT ratio were significantly higher in the study group than in the control group (P<0.05). (II) The sensitivity of serum IVC combined with AST/ALT ratio detected biochemically and the four markers of liver fibrosis detected by chemiluminescence in the diagnosis of liver cirrhosis was 95.83%, 97.92%, without significant difference, but the specificity and accuracy of IVC + AST/ALT ratio in the diagnosis of liver cirrhosis were significantly higher (94.00%, 94.90%). (III) The detection rate of serum IVC + AST/ALT ratio for the diagnosis of early liver fibrosis was significantly higher than with imaging examination (45.45% vs. 21.21%). Serum IVC + AST/ALT ratio determined by biochemical analysis has high diagnostic accuracy in the diagnosis of liver fibrosis and liver cirrhosis, and is worthy of clinical application and promotion.

Serum Fibroblast Growth Factor 19 as a Biomarker in Hepatitis B Virus-Related Liver Disease

Background: Past research has found that fibroblast growth factor 19 (FGF19) is associated with several hepatic disorders, such as alcoholic liver disease and primary biliary cirrhosis. However, there is currently a lack of relevant studies on the relationship between FGF19 and hepatitis B virus (HBV)-related liver disease. Objectives: This study aimed to assess the role of serum FGF19 as a new biomarker for HBV-related liver disease and provide scientific data to show the clinical value of this biomarker. Methods: A retrospective study included 37 patients with chronic hepatitis B (CHB), 33 patients with HBV-related cirrhosis (HBV-cirrhosis), and 32 patients with HBV-related hepatocellular carcinoma (HBV-HCC). Furthermore, 33 normal people were randomly selected as healthy controls. The serum levels of FGF19 were measured by ELISA. Results: Serum FGF19 levels were increased sequentially in the CHB group, HBV-cirrhosis group, and HBV-HCC group. Furthermore, serum FGF19 levels positively correlated with alpha-fetoprotein, prothrombin time, international normalized ratio, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, alkaline phosphatase, total bile acid, serum markers for liver fibrosis, ascites, cirrhosis, Child-Pugh classification and model for end-stage liver disease sodium (MELD-Na) score, while negatively correlated with platelet count, prothrombin activity, and albumin. The diagnostic threshold of serum FGF19 for HBV-related HCC was 165.32 pg/mL, with a sensitivity of 81.25% and specificity of 58.57%. Conclusions: Serum FGF19 levels are positively associated with cholestasis, hepatocyte damage, and liver fibrosis but negatively correlated with liver synthetic function and liver functional reserve in HBV-related liver disease. Diverse changes in serum FGF19 may be used as a predictive marker for the progression of HBV-related liver disease. In addition, serum FGF19 has a potential role in monitoring carcinogenesis in patients with HBV-related liver disease.

Transient elastography and serum markers of liver fibrosis associate with epicardial adipose tissue and coronary artery calcium in NAFLD

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease morbimortality. However, it is not clear if NAFLD staging may help identify early or subclinical markers of cardiovascular disease. We aimed to evaluate the association of liver stiffness and serum markers of liver fibrosis with epicardial adipose tissue (EAT) and coronary artery calcium (CAC) in an observational cross-sectional study of 49 NAFLD patients that were seen at Clínica Universidad de Navarra (Spain) between 2009 and 2019. Liver elastography and non-invasive fibrosis markers were used to non-invasively measure fibrosis. EAT and CAC, measured through visual assessment, were determined by computed tomography. Liver stiffness showed a direct association with EAT (r = 0.283, p-value = 0.049) and CAC (r = 0.337, p-value = 0.018). NAFLD fibrosis score was associated with EAT (r = 0.329, p-value = 0.021) and CAC (r = 0.387, p-value = 0.006). The association of liver stiffness with CAC remained significant after adjusting for metabolic syndrome features (including carbohydrate intolerance/diabetes, hypertension, dyslipidaemia, visceral adipose tissue, and obesity). The evaluation of NAFLD severity through liver elastography or non-invasive liver fibrosis biomarkers may contribute to guide risk factor modification to reduce cardiovascular risk in asymptomatic patients. Inversely, subclinical cardiovascular disease assessment, through Visual Scale for CAC scoring, may be a simple and effective measure for patients with potential liver fibrosis, independently of the existence of other cardiovascular risk factors.

The Role and Significance of Non-invasive Methods, with a Particular Focus on Shear Wave Elastography in Hepatic Fibrosis Staging

Shear Wave Elastography (SWE) represents a new, non-invasive method, used in the diagnosis of diffuse liver diseases. The method has been widely used instead of liver biopsy - an invasive procedure with potential major risk complications. Compared to liver biopsy, SWE provides an examination of larger areas of the liver, thus providing better staging of hepatic fibrosis. &#x0D; 30 patients were included in the study on basis of previous clinical, biochemical, and ultrasound findings indicating a presence of a chronic liver lesion. Patients were divided into three groups: 6 patients with steatosis, 13 patients with viral hepatitis, and 11 patients with liver cirrhosis. Liver damage biochemical markers, serum markers of liver fibrosis, and SWE were determined in all patients. Statistical analysis revealed a positive correlation between SWE results, and the values of biochemical markers of the hepatic lesion, as well as serum markers of liver fibrosis.

Increased Levels of CHI3L1 and HA Are Associated With Higher Occurrence of Liver Damage in Patients With Obstructive Sleep Apnea.

BackgroundObstructive sleep apnea-hypopnea syndrome (OSA) may cause liver fibrosis, and liver fibrosis serum biomarkers plays an important role on the diagnosis of liver fibrosis. In addition, this study aimed to observe the changes of 4 serum markers and Chitinase 3-like protein 1 (CHII3L1) levels in OSA patients with different disease severity and explore their interactions. And then, we examined whether intermittent hypoxia (IH) exposure can activate hepatic stellate cell.Methods74 OSA patients in Second Xiangya hospital from January 2021 to October 2021 was selected and categorized into mild, moderate, and severe groups according to AHI. In addition, 20 subjects were selected as the control group. Serum levels of liver fibrosis markers were determined by electrochemiluminescence immunoassay. Hepatic stellate cells were exposed to intermittent IH or normoxia (RA). Results were analyzed using the SPSS software.ResultsThere was a significant increase in serum hyaluronic acid (HA), collagen type IV (CIV) and CHI3L1 levels in OSA patients compared with control group. Specifically, serum liver fibrosis markers HA, CIV and CHI3L1 levels were positively correlated with apnea-hypopnea index (AHI), but negatively correlated with the lowest saturation oxygen (LSaO2) respectively. The LX-2 cells (human hepatic stellate cell line) exposed to IH showed significant increases in fibrotic protein expression.ConclusionOSA might either directly or indirectly trigger or exacerbate liver fibrosis, possibly via IH-related pathways.

The Results of Serum Markers of Liver Fibrosis in Patients with Posthepatic Fibrosis and in Patients with Non-alcoholic Fatty Liver Disease Depending on Body Weight

The Results of Serum Markers of Liver Fibrosis in Patients with Posthepatic Fibrosis and in Patients with Non-alcoholic Fatty Liver Disease Depending on Body Weight

Non-alcoholic fatty liver disease - a look at diagnostic prospects

This article observes the main trends in the diagnosis of non-alcoholic hepatic steatosis, which have been observed in world practice recently. From a practical point of view, one of the most significant events was the introduction of a new term “metabolically associated fatty liver disease” (MAFLD), which partly replaced the previously used term “primary non-alcoholic fatty liver disease”. The new nomenclature induces clear diagnostic criteria for MAFLD, and this disease has ceased to be a diagnosis of exclusion, as a result. In the near future, the practical aspects of the application of this nomenclature and new diagnostic criteria are to be evaluated. The second important trend is the increasing role of direct serum markers of liver fibrosis in the diagnosis and prognosis of MAFLD. Thus, collagen type 3 propeptide (PRO-C3), as well as M2BPGi (Mac2 Binding Proteine Glycosylation isomer), look very promising, since research data have demonstrated a higher diagnostic value of these markers in comparison with indirect fibrosis indices, which are most often used in clinical practice. In addition, the search continues for new direct serum markers of fibrosis, which would be more sensitive for detecting liver fibrosis of stages 1-2. In general, one should expect a gradual replacement by serological markers of fibrosis of technically more complex and expensive diagnostic methods, such as magnetic resonance elastography and fibroelastometry.

Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator‐activated receptor α modulator (SPPARMα), versus placebo in patients with non‐alcoholic fatty liver disease

SummaryBackgroundPemafibrate is a novel, selective peroxisome proliferator‐activated receptor α modulator (SPPARMα). In mice, Pemafibrate improved the histological features of non‐alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT).AimsTo evaluate the efficacy and safety of Pemafibrate in patients with high‐risk, non‐alcoholic fatty liver disease (NAFLD).MethodsThis double‐blind, placebo‐controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2 mg Pemafibrate or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included liver fat content of ≥10% by magnetic resonance imaging‐estimated proton density fat fraction (MRI‐PDFF); liver stiffness of ≥2.5 kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI‐PDFF from baseline to week 24. The secondary endpoints included MRE‐based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters.ResultsThere was no significant difference between the groups in the primary endpoint (−5.3% vs −4.2%; treatment difference −1.0%, P = 0.85). However, MRE‐based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference −5.7%, P = 0.036), and was maintained at week 72 (treatment difference −6.2%, P = 0.024), with significant reduction in ALT and LDL‐C. Adverse events were comparable between the treatment groups and therapy was well tolerated.ConclusionsPemafibrate did not decrease liver fat content but had significant reduction in MRE‐based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.

P-32 EVALUATION OF HEPATIC FIBROSIS THROUGH NON-INVASIVE METHODS IN PATIENTS WITH CHRONIC VIRAL HEPATITIS B AND C

Biopsy has been considered the method of choice for staging fibrosis in liver disease. However, as it is an invasive method subject to sampling errors and morbidity, new non-invasive methods have been proposed for the assessment of liver fibrosis. To evaluate and compare serum fibrosis biomarkers (APRI and FIB4) with transient liver elastography (THE), gold standard in this study in patients with chronic viral hepatitis B and C. Cross-sectional study of patients with chronic hepatitis B or C virus undergoing THE. The patients were evaluated using serum liver fibrosis markers APRI and FIB4. The degree of fibrosis ≥ 2 of the Metavir classification was defined as significant fibrosis. The diagnostic performance of both methods was calculated and compared using the ROC curve (AUROC). The study included 73 patients, 50 with HBV and 23 with HCV; 50.7% were female, mean age 48.6 ± 13.3 years. Significant fibrosis was observed in 31 patients. The accuracy of serum markers in the diagnosis of liver fibrosis was determined by AUROC, APRI 0.79 and FIB4 0.76 (P = .0.42); PPV and NPV APRI 91.7% and 76.9% respectively; FIB4, PPV = 87.5% and NPV = 77.8%. The study demonstrated that there was no difference in diagnostic performance between the APRI and FIB4 methods, which were considered tests with good accuracy in the diagnosis of significant fibrosis in patients with chronic viral hepatitis.

Value of liver/spleen stiffness combined with serum adenosine deaminase in predicting severe esophageal varices in patients with hepatitis B cirrhosis

Objective To investigate the value of liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) based on FibroTouch (FT) transient elastography combined with serum adenosine deaminase (ADA) in predicting severe esophageal varices (EV) in patients with hepatitis B cirrhosis. Methods Related clinical data were collected from 120 patients with hepatitis B cirrhosis who attended Department of Infectious Diseases, Changsha First Hospital, from December 2017 to June 2020. FT was used to measure LSM and SSM, and related examinations were performed, including electronic gastroscopy and serum levels of ADA, hemoglobin, albumin, alanine aminotransferase, and aspartate aminotransferase and platelet count. The serum liver fibrosis markers aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase/alanine aminotransferase ratio (AAR), and fibrosis-4 (FIB-4) were calculated. According to the severity of EV under gastroscopy, the subjects were divided into severe EV group with 58 patients and non-severe EV (without EV or with mild-to-moderate EV) group with 62 patients. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Spearman rank correlation test was used to investigate the correlation of LSM, SSM, and ADA with severe EV. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of LSM, SSM, and ADA in the diagnosis of severe EV, and sensitivity and specificity were calculated. A multivariate binary logistic regression analysis was performed to calculate the area under the ROC curve (AUC) of the combined indicators, and the Z test was used for comparison of AUC. Results There were significant differences in LSM, SSM, and ADA between the two groups (all P Conclusion Liver/spleen stiffness combined with serum ADA has a good value in predicting severe EV, which can provide a preliminary diagnostic basis for severe EV in patients who refuse to undergo gastroscopy.

Hepatic stellate cell as a Mac-2-binding protein-producing cell in patients with liver fibrosis.

Mac-2 binding protein (M2BP) glycosylated isomer (M2BPGi) is a serum marker of liver fibrosis; M2BPGi is a glycosylated form of M2BP. Hepatocytes and hepatic stellate cells (HSCs) have been studied to determine the source of M2BP. This study proposes to identify the origin of M2BP in fibrotic liver. Using liver fibrosis tissue specimens from 15 patients with liver cancer, M2BP mRNA and M2BP were detected by in situ hybridization and immunohistochemistry, respectively. The expression levels of M2BP mRNA were evaluated with scores of 3, 2, and 1. Fluorescent in situ hybridization was carried out to evaluate the distribution of M2BP mRNA and the activated-HSC marker αSMA mRNA; multicolor fluorescent immunohistochemistry was used for protein localization of M2BP, αSMA, and CD68. The Kruskal-Wallis test analyzed the relationship between M2BP mRNA expression and existing serum fibrosis markers. M2BP mRNA was expressed in spindle-shaped cells along the fibrous septa and in the perisinusoidal area of the fibrotic liver. The HSC markers αSMA mRNA and M2BP mRNA were colocalized in the spindle-shaped cells; on the protein level, M2BP was expressed in Kupffer cells. M2BP mRNA expression was positively correlated with serum M2BPGi levels. Aspartate transaminase-to-platelet ratio index, Fibrosis-4, hyaluronic acid, and the 15-minute indocyanine green retention rate were significantly correlated with M2BP mRNA expression. M2BP mRNA transcription in fibrotic liver was primarily observed in HSCs but not at the M2BP level, which suggests that HSCs might produce and introduce M2BP to Kupffer cells and serum.

Handgrip Strength and Vitamin D as Predictors of Liver Fibrosis and Malnutrition in Chronic Hepatitis C Patients.

Background In patients with chronic hepatitis C (CHC), a negative impact of associated malnutrition on both morbidity and mortality was reported. We aimed to elucidate the efficacy of serum liver fibrosis markers (fibronectin (FN), hydroxyproline (Hyp), and hyaluronic acid (HA)) and their respective indices (HA index, Hyp index, and FN index) and vitamin D status in predicting malnutrition associated with liver fibrosis in CHC patients and to investigate their association with the value of current clinical malnutrition assessment tools subjective global assessment (SGA), handgrip strength (HGS), and muscle mass scores (SGA, BMI, MAMC, and HGS). Materials and Methods A cross-sectional study was conducted on 80 patients aged 40-60 years with proven viremia, HCV antibodies, HCV-RNA positivity, genotype determinations, and established chronic hepatitis C virus for more than 6 years and 80 control subjects. SGA, HGS, and muscle mass score (MAMC) were estimated in both patients and control subjects. Based on SGA scores, CHC patients were classified into three groups: well nourished (n = 12; SGA-A); mild or moderately malnourished (n = 25; SGA-B); and severely malnourished (n = 43; SGA-C). Liver fibrosis markers, inflammatory indicator α-Fetoprotein (AFP), tumor necrosis factor-alpha (TNF-α), 25-hydroxyvitamin D, and PTH were estimated using immunoassay techniques. Results CHC patients with moderate and severe malnutrition SGA scores showed a significant decline in the levels of vitamin D, increased PTH, and lower values of HGS and muscle mass indices compared to well-nourished patients and control subjects. In addition, malnutrition, vitamin D deficiency, and lower values of HGS, MAC, TSF, and MAMC showed significant correlation with liver severity among CHC patients. Liver fibrosis markers Hyp, HA, FN, APRI, HypI, HAI, and FNI as noninvasive biomarkers showed significant correlation with both severity of liver diseases and associated malnutrition, especially in cirrhotic HCV patients (F4) compared to those with significant fibrosis (F2–F3). Conclusion The results showed that deficiency in vitamin D levels, HGS, SGA, and muscle mass scores (MAC, MAMC, or TSF) could be used as markers of liver pathogenicity in patients with CHC. In addition, the study concluded that noninvasive biomarkers Hyp, HA, FN, APRI, HypI, HAI, and FNI separately or in association with vitamin D status, HGS, SGA, and muscle mass scores (MAC, MAMC, or TSF) were significantly associated with an incidence of malnutrition between ~70.5% and 89.6% of CHC patients with significant fibrosis and cirrhosis.