Non-invasive Fibrosis Markers Research Articles

Impact of Hepatitis C Treatment Uptake on Cirrhosis and Mortality in Persons Who Inject Drugs : A Longitudinal, Community-Based Cohort Study.

Hepatitis C virus (HCV) infection can be cured, and the United States has joined the World Health Organization in calling for HCV elimination by 2030. However, historically low uptake of HCV treatment among people who inject drugs (PWID) threatens HCV elimination and exacerbates social and racial health disparities. To assess whether all-oral HCV treatments were accessed by PWID and reduced liver disease burden and mortality. Community-based, longitudinal cohort study of persons with a history of injection drug use. Baltimore, Maryland. 1323 participants enrolled in the ALIVE (AIDS Linked to the IntraVenous Experience) study from 2006 to 2019 and chronically infected with HCV. Liver stiffness measures (LSMs) by transient elastography, HCV RNA, and mortality from the National Death Index. Among 1323 persons with evidence of chronic HCV infection at baseline, the median age was 49 years. Most were Black (82%), male (71%), and HIV-negative (66%). The proportion in whom HCV RNA was detected decreased from 100% (by definition) in 2006 to 48% in 2019. Across 10350 valid LSMs, cirrhosis was detected in 15% of participants in 2006, 19% in 2015, and 8% in 2019. Undetectable HCV RNA was significantly associated with reduced odds of cirrhosis (adjusted odds ratio, 0.28 [95% CI, 0.17 to 0.45]) and reduced all-cause mortality risk (adjusted hazard ratio, 0.54 [CI, 0.38 to 0.77]). Noninvasive markers of liver fibrosis have not been validated in persons with sustained virologic response. Many community-based PWID in Baltimore are receiving HCV treatment, which is associated with sharp decreases in liver disease and mortality. Additional efforts will be needed to reduce residual barriers to treatment and to eliminate HCV as a public health threat for PWID. National Institutes of Health.

Comparison of Mac‐2 binding protein glycosylation isomer (M2BPGi) with AST to platelet ratio index (APRI), fibrosis 4 Score (FIB‐4), and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for NAFLD patients

AbstractThe serum level of Mac‐2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis in biopsy‐proved nonalcoholic fatty liver disease (NAFLD). However, the comparison of M2BPGi with noninvasive fibrosis markers such as AST to platelet ratio index (APRI), Fibrosis 4 Score (FIB‐4), and NAFLD fibrosis score (NFS) in NAFLD patients remains unclear. The participants of Tzu Chi NAFLD cohort (TCNC) including health controls or NAFLD patients were enrolled in Taipei Tzu Chi Hospital. NAFLD was defined as fatty liver in imaging without hepatitis B virus (HBV), hepatitis C virus (HCV), drug, alcohol, or other known causes of chronic liver disease. A total of 777 subjects were included for final analysis. The serum levels of M2BPGi correlated with APRI, FIB‐4 score, and NFS, respectively (P < .001). Of them, 376 (48.4%) were NAFLD patients and 401 were healthy controls. In the group of health controls or NAFLD patients, the M2BPGi levels were significantly higher in female subjects than those of male subjects (P = .027 and 0.006, respectively). Categorized by age, the levels of M2BPGi were significantly higher in elder age groups either in healthy controls or NAFLD patients (P < .05). Compared with healthy controls, NAFLD patients had significantly higher levels of BMI, waist circumference, metabolic components, and liver fibrosis markers such as APRI, NFS, and M2BPGi (P < .05), but no difference in FIB‐4 score (P = .685). According to FIB‐4 score, “intermediate‐ or high‐risk group” had higher APRI, NFS, and M2BPGi than low‐risk group. The serum M2BPGi levels correlated with three noninvasive biomarkers of liver fibrosis including APRI, FIB‐4 score, and NFS. They were significantly higher in female or elder population. Furthermore, APRI, NFS, and M2BPGi were different between NAFLD patients and healthy controls, but no FIB‐4 score. According to FIB‐4 score to determine the risk of liver fibrosis, APRI, NFS, and M2BPGi were also different between low risk and “intermediate or high risk” of NAFLD patients, suggesting a surrogate marker for assessing liver fibrosis of NAFLD patients.

The role of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in the assessment of fibrosis in children with chronic hepatitis C

At present, noninvasive fibrosis markers are not available for the assessment of liver fibrosis in children with chronic hepatitis C. Sixty-three children with chronic hepatitis C were included. Changes in Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BPGi) levels were evaluated in l3 of 27 treatment-naive patients during the natural course of disease (median 4, range 3–6 years). Changes during treatment were evaluated in 27 of 36 patients for 4 (2–9) years of posttreatment follow-up. There were significant differences in the levels of M2BPGi between control group and HCV F0 group (P = 0.002) and between control group and HCV F1 group (P < 0.001). Receiver operating characteristic curve analysis showed that to discriminate stage F1 fibrosis from F0, the cut-off value was 0.95 for M2BPGi with a sensitivity of 52%, specificity of 90%, and area under the curve of 0.687. A substantial decrease in M2BPGi levels by treatment was shown from 0.98 ± 0.57 at pretreatment to 0.42 ± 0.15 at posttreatment (P < 0.001) in the 27 treated patients. Our study shows new findings that M2BPGi may be useful to predict the presence of a mild degree of fibrosis in children with chronic hepatitis C, and such mild fibrosis may be quickly resolved by treatment.

FRI060 - The MRI and AST (MAST) score is correlated with noninvasive and histologic markers of fibrosis in patients with advanced fibrosis due to NASH

FRI060 - The MRI and AST (MAST) score is correlated with noninvasive and histologic markers of fibrosis in patients with advanced fibrosis due to NASH

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

BackgroundNonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH.MethodsThis is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers.ResultsOf 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75–1); CAP, 0.94 (0.88–1); FLI, 0.81 (0.58–1); HSI, 0.74 (0.62–0.87); and TyG, 0.75 (0.49–1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82–1), 0.96 (0.90–1), 0.97 (0.93–1), and 0.85 (0.68–1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97–1, P < .001) and 0.92 (0.77–1, P < .001).ConclusionsUltrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

ВЗАИМОСВЯЗЬ РЕТИНОЛА И РЕТИНОЛ-СВЯЗЫВАЮЩЕГО БЕЛКА С НЕИНВАЗИВНЫМИ МАРКЕРАМИ ФИБРОЗА (PDGF-BB,TGF-β1) ПРИ ХРОНИЧЕСКИХ ПОРАЖЕНИЯХ ПЕЧЕНИ

Background. Perisinusoidal lipocytes (HSC) and retinol (R) metabolism play an important role in liver fibrosis. Objective. To estimate R and retinol-binding protein type 4 (RBP4) correlation with non-invasive fibrosis markers in patients with chronic liver diseases. Material and methods. The subjects of the study were 129 adult patients with chronic diffuse liver diseases, who were divided into 2 groups: those with chronic hepatitis - 104 patients, and those with liver cirrhosis - 25 patients. In addition, 48 patients were further subdivided according to liver fibrosis stages. Blood levels of R, RBP4, platelet growth factor BB, and transforming growth factor β1 (TGF-β1) were determined in the patients. Results. Differences in R and RBP4 content were established in the patients with different stages of liver fibrosis, the most informative values and coefficients for liver fibrosis staging were found. High blood levels of retinol and TGF-β1 are indicative of transformation of HSC into myofibroblasts, increased synthesis of profibrogenic factors, including TGF-β1, and the progression of liver fibrosis. Conclusions. Laboratory monitoring of R, RBP4 and TGF-β1 levels as well as of RBP4/R and PDGF-BB/R coefficients is an additional test for the diagnosis of liver fibrosis in chronic liver diseases.

Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index for Detecting Liver Fibrosis in Patients With Autoimmune Hepatitis: A Meta-Analysis

BackgroundAspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are the two most widely studied noninvasive markers of liver fibrosis. We aimed to assess the diagnostic accuracy of APRI and FIB-4 for liver fibrosis in patients with autoimmune hepatitis (AIH) using liver biopsy as the reference standard.MethodsPubMed, EMBASE, Cochrane Library and Web of Science databases were searched for studies (published as of May 1st, 2021) that assessed the diagnostic performance of APRI and FIB-4 for liver fibrosis in AIH. The summary area under receiver operating characteristics curve (AUROC), sensitivity, specificity, diagnostic odds ratios were used to assess the diagnostic accuracy of APRI and FIB-4 for detecting liver fibrosis.ResultsFourteen studies (including 1015 patients) were selected with 13 studies each evaluating the use of APRI and FIB-4 for detecting different stages of fibrosis in AIH. For prediction of significant fibrosis, advanced fibrosis, and cirrhosis, the summary AUROC value was 0.66 [95% confidence interval (CI): 0.61–0.70], 0.71 (95% CI: 0.67–0.75), and 0.75 (95% CI: 0.71–0.79) for APRI, and the summary AUROC value was 0.75 (95% CI: 0.71–0.79), 0.73 (95% CI: 0.69–0.77) and 0.79 (95% CI: 0.75–0.82) for FIB-4, respectively. The summary sensitivity and specificity for diagnosis of significant fibrosis, advanced fibrosis, and cirrhosis were 90% and 36%, 78% and 55%, and 77% and 61% for APRI, and 70% and 70%, 65% and 70%, and 78% and 65% for FIB-4, respectively.ConclusionsAPRI and FIB-4 showed suboptimal diagnostic performance for identifying liver fibrosis in AIH with mediocre sensitivity and specificity.

Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated with Severity of Fibrosis in Patients with Primary Sclerosing Cholangitis.

The soluble urokinase-type plasminogen activator receptor (suPAR) has evolved as a useful biomarker for different entities of chronic liver disease. However, its role in patients with primary sclerosing cholangitis (PSC) is obscure. We analyzed plasma levels of suPAR in 84 patients with PSC and compared them to 68 patients with inflammatory bowel disease (IBD) without PSC and to 40 healthy controls. Results are correlated with clinical records. suPAR concentrations were elevated in patients with PSC compared to patients with IBD only and to healthy controls (p < 0.001). Elevated suPAR levels were associated with the presence of liver cirrhosis (p < 0.001) and signs of portal hypertension (p < 0.001). suPAR revealed a high accuracy for the discrimination of the presence of liver cirrhosis comparable to previously validated noninvasive fibrosis markers (area under the curve (AUC) 0.802 (95%CI: 0.702–0.902)). Further, we demonstrated that suPAR levels may indicate the presence of acute cholangitis episodes (p < 0.001). Finally, despite the high proportion of PSC patients with IBD, presence of IBD and its disease activity did not influence circulating suPAR levels. suPAR represents a previously unrecognized biomarker for diagnosis and liver cirrhosis detection in patients with PSC. However, it does not appear to be confounded by intestinal inflammation in the context of IBD.

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.

Impact of sustained virologic response in regression of portal hypertension in Egyptian patients with hepatitis C virus-associated cirrhosis and portal hypertension

BackgroundPortal hypertension (PH) is a common consequence in hepatitis C virus cirrhotic patients. With interferon alpha-based therapy, SVR was linked to improved PH and fibrosis regression. SVR to oral antiviral regimens is linked to reduced portal pressure in patients with clinically significant portal hypertension (CSPH) at baseline. However, CSPH continues in most of the patients. This study aims to assess the reversibility and/or improvement of PH in Egyptian patients with HCV-related cirrhosis and CSPH after achieving SVR with DAAs. The second aim is to evaluate performance of the noninvasive markers of fibrosis in prediction of the presence and/or reversibility of the CSPH in correlation to radiological and endoscopic parameters.Subjects and methodsWe evaluated noninvasive parameters, radiological and endoscopic signs of PH at baseline, and/or SVR 24 and SVR 48 post-DAA therapy in 40 patients with cirrhosis and CSPH (group A) and another 40 patients with cirrhosis only (group B).ResultsIn group A, the spleen diameter decreased from baseline (15.74 ± 1.53 cm), and SVR 24 (15.48 ± 1.51), to SVR 48 (15.35 ± 1.49 cm). No ascites detected at SVR 48 in 62.5%. Portal vein diameter and portal vein blood velocity reduced to 13.53 ± 1.07 mm and 14.14 ± 2.2 cm/s at SVR 48, with reversibility of hepatic vein waveform towards the triphasic pattern. Medium to large esophageal varices regressed from 52.5% to 2.5%, and up to 70% of patients showed no EVs at SVR 48. In group A, 24 patients showed complete reversibility of CSPH, and 16 patients showed improvement of CSPH. Child-Pugh score, FIB-4 index, King’s score, and Lok index revealed higher significance for detection of the presence of PH. Child-Pugh score, PC/SD ratio, and Lok index revealed higher significance for detection of reversibility of PH.ConclusionWe concluded that CSPH improved after SVR with DAAs and completely regressed in some patients. Upon predicting the presence of PH, Child-Pugh score, FIB-4 index, King’s score, and Lok index were the most significant noninvasive scores. While for predicting the reversibility of PH, Child-Pugh score, PC/SD ratio, and Lok index were the most significant scores.

Trends in indirect liver function marker testing in Wales from 2000 to 2017 and their association with age and sex: an observational study

ObjectiveIf non-invasive markers of liver fibrosis were recorded frequently enough in clinical practice, it might be feasible to use them for opportunistic community screening for liver disease. We aimed to...

Staging Fibrosis in Chronic Viral Hepatitis.

Staging fibrosis accurately has always been a challenge in viral hepatitis and other liver diseases. Liver biopsy is an imperfect gold standard due to its intra and interobserver agreement limitations and additional characteristics such as its safety and cost. Hence, non-invasive tests have been developed to stage liver fibrosis. In addition to serological biomarkers, physical tests with reasonable accuracy are available and adopted in the daily clinic regarding viral hepatitis fibrosis staging. In this review, we discuss the published data regarding the staging of liver fibrosis in chronic hepatitis B and C, emphasizing non-invasive markers of fibrosis, both serological and physical. Moreover, we also discuss a persistent central gap, the evaluation of liver fibrosis after HCV cure.

Fontan-associated liver disease.

Fontan-associated liver disease.

24-month decline of non-invasive liver fibrosis markers in HCV-mono and HCV/HIV coinfection after direct-acting antiviral therapy

Long term liver fibrosis (LF) changes and their best -monitoring non-invasive markers (NILFM) after effective anti-HCV DAA therapy are little- known. Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs) are pivotal in liver inflammation repair. Their plasma levels might assess long-term LF changes after therapy. Overall 374 HCV-infected adult patients, 214 HCV-HIV coinfected, were followed-up for 24 months after starting DAA. LF was assessed by transient elastometry (TE), biochemical indexes (APRI, Forns, FIB-4) and, in 61 individuals, by MMPs and TIMP-1 plasma levels. Several MMPs and TIMP-1 SNPs were genotyped in 319 patients. TE was better than biochemical indexes for early and long-term LF monitoring. MMPs-2,-8,-9 and-TIMP-1 levels and TE displayed parallel declining curves although only TIMP-1 correlated with TE (P = 0.006) and biochemical indexes (P < 0.02). HCV monoinfected had significantly higher baseline NILFM and TIMP-1 plasma values, but lower MMPs levels than coinfected patients. No differences in NILFM course were observed between mono-and coinfected or between different DAA regimens. Only the MMP-2 (-1306 C/T) variant TT genotype associated with higher values of NILFM NILFM decline extends 24 months after therapy. TE and TIMP1 are reliable LF-monitoring tools. NILFM courses were similar in mono-and coinfected patients, DAA regimens type did not influence NILFM course.

GPR, King's Score and S-Index are superior to other non-invasive fibrosis markers in predicting the liver fibrosis in chronic Hepatitis B patients.

In this study, we investigated the efficacy of nine non-invasive fibrosis markers in the assessment of the degree of fibrosis in patients with chronic Hepatitis B (CHB) in comparison with liver biopsy. A total of 1454 untreated CHB patients from two different centers who underwent liver biopsy were included in the study. Laboratory results of patients were reviewed retrospectively and the pathology slides were re-evaluated in accordance with the Ishak score. Degree of fibrosis ≥ 3 was accepted as "significant fibrosis", ≥ 4 as "advanced fibrosis", and ≥ 5 as cirrhosis. The diagnostic performance of the markers Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis-4 score (FIB-4), Aspartate aminotransferase to Alanine aminotransferase Ratio (AAR), AAR to Platelet Ratio Index (AAPRI), Gamma-glutamyl transpeptidase to Platelet Ratio (GPR), King's Score, Fibro quotient (Fibro-Q), S Index and Platelet to Lymphocyte Ratio (PLR) were evaluated with ROC analysis. In detecting significant fibrosis, APRI, GPR, King's Score and S Index had AUROC values over 0.70. For advanced fibrosis, all of the models except AAPRI; and for cirrhosis, all of the models had AUROC values over 0.70. In accordance with the chosen staging system, GPR, King's Score and S Index had high diagnostic efficacy whereas APRI, FIB-4, FibroQ and PLR had moderate diagnostic efficacy, AAR and AAPRI had low diagnostic efficacy. GPR, King's Score and S Index had moderate diagnostic performance in detecting significant fibrosis and advanced fibrosis, and high diagnostic performance in detecting cirrhosis.

Hepatic fibrosis changes in patients with chronic hepatitis C infection who respond to direct-acting antivirals.

BACKGROUND: Clearance of hepatitis C virus (HCV) can potentially slow or reverse liver fibrosis and cirrhosis. Studies of fibrosis changes after treatment with direct-acting antivirals (DAAs) are limited.OBJECTIVES: We aimed to assess the impact of DAAs on fibrosis in HCV treatment responders.DESIGN: Retrospective cohort study.SETTING: Tertiary care centers.PATIENTS AND METHODS: This study included adult patients who received DAA treatment for HCV (naïve and experienced) from June 2015 to January 2019 who were treatment responders. Biochemical and hematological data and noninvasive fibrosis markers were recorded at baseline and follow-up.MAIN OUTCOME MEASURES: Aspartate aminotransferase/platelet ratio index (APRI), fibrosis-4 score (FIB-4) and liver stiffness measurements (LSM) at baseline and follow-up.SAMPLE SIZE AND CHARACTERISTICS: 172 HCV treatment responders, mean (SD) age 54.1 (14.1) and body mass index 28.8 (6.5) kg/m2 at baseline; 96 (55.8%) were females.RESULTS: Fifty-eight (33.7%) patients were HCV treatment-experienced. Most patients were genotype 4 (n=125, 73%) and the mean follow-up was 141 (57.9) weeks. Compared with baseline, changes in alanine aminotransferase (P<.001), aspartate aminotransferase (P<.001), and albumin (P=.01) were statistically significant. Changes in LSM (15.09 kPa [11.4] vs. 10.19 kPa [7.4], P<.001), APRI (0.81 [0.7] vs. 0.34 [0.2], P<.001), and FIB-4 (1.99 [1.4) vs.1.35 [0.9], P<.001), and AST/ALT ratio (0.86 [0.32] vs. 0.95 [0.41], P=.015) were statistically significant. Differences in many of the same parameters were statistically significant between patients with low fibrosis (F0-F1) (n=59, 34.3%) and significant fibrosis (≥F2) (n=113, 65.7%).CONCLUSIONS: Our findings confirm that clearance of HCV with DAAs is associated with significant improvement in fibrosis as assessed by noninvasive liver fibrosis measures, which supports the concept of post-treatment fibrosis regression. Long follow-up studies are needed to assess the impact on morbidity and mortality.LIMITATIONS: Absence of histological correlation with these noninvasive scores. No assessment of fibrosis changes based on HCV geno-type or treatment regimen.CONFLICT OF INTEREST: None.

Association Between Non-invasive Diagnostic Methods of Liver Fibrosis and Type 2 Diabetes in Pediatric Patients With Non-alcoholic Fatty Liver Disease.

Background and PurposeThe prevalence of non-alcoholic fatty liver disease (NAFLD) in children has been increasing associated with insulin resistance. However, there is a scarcity of related studies in children with NAFLD with type 2 diabetes mellitus (T2DM) compared to adults. We conducted this study to investigate the association between non-invasive diagnostic methods of liver fibrosis and T2DM in pediatric patients with NAFLD.MethodsWe enrolled a total of 152 patients aged <18 years with NAFLD, and compared their data according to the presence of T2DM. We evaluated fibrosis by transient elastography (TE, FibroScan®), and calculated the following fibrosis scores for each patient: NAFLD fibrosis score (NFS), AST: platelet ratio index (APRI), Fibrosis-4 (FIB-4) index, and pediatric NAFLD fibrosis index (PNFI).ResultsIn the NAFLD–T2DM group, the NFS and mean controlled attenuation parameter in FibroScan were significantly higher than those in the nondiabetic group. The receiver operating characteristic (ROC) curve values for predicting the presence of T2DM were 0.78 for NFS, 0.64 for FIB-4, 0.62 for PNFI, and 0.61 for APRI. The cutoff HbA1c levels for predicting fibrosis progression in APRI, NFS, and PNFI were 5.7% [area under the curve (AUC) 0.74], 6.4% (AUC 0.71), and 6.4% (AUC 0.55), respectively. In the multivariate analysis, hepatosteatosis on abdomen sonography, NFS, FibroScan F, and APRI were independently associated with T2DM risk.ConclusionsWe significantly characterized non-invasive fibrosis markers and elastography in pediatric NAFLD with T2DM compared with the nondiabetic group. We suggest evaluating the progression of fibrosis in the prediabetic stage in children using a combination of these non-invasive methods.

Characteristics of immune checkpoint regulators and potential role of soluble TIM-3 and LAG-3 in male patients with alcohol-associated liver disease.

The involvement of immune checkpoint regulators (ICs) in alcohol-associated liver diseases (ALDs) is still largely unknown. Here, we analyzed the levels of 16 soluble ICs (sICs) in male patients with ALD to determine their clinical significance. The 16 sICs were measured using a luminex-based multiplex assay in 115 patients with ALD and 47 healthy controls (HCs). The expressions of membrane-type (m) PD-1 and mCTLA-4 on CD4+ and CD8+ T lymphocytes and NK cells of 28 patients with ALD and 8HCs were also measured. Correlation test and risk assessment were also conducted to evaluate biomarkers of ALD in clinical practice. Our results show that four sICs were upregulated (sCTLA-4, sTIM-3, sCD27, and sGITR) and two sICs were downregulated (sLAG-3 and sHVEM) in ALD. mPD-1 expression was significantly more greatly increased on CD4+T lymphocytes in the ALD group than in the HC group (p=0.009). sTIM-3 was positively correlated, while sLAG-3 was negatively correlated with non-invasive liver fibrosis markers (AST/ALT, APRI, GPR, and FIB-4) and Maddrey discriminant function score. Risk factor analysis showed that sTIM-3 was consistently associated with ALD severity in both MDF and FIB-4 scores, and sLAG-3 was associated with FIB-4 scores. This study revealed the involvement of sCTLA-4, sTIM-3, sCD27, sGITRL, sLAG-3, and sHVEM in discriminating male patients with ALD. Expressions of sTIM-3 and sLAG-3 were correlated with liver fibrosis markers and significantly associated with ALD severity, which can be further studied as diagnostic markers and therapeutic targets in ALD.

External Validation of the FSAC Model Using On-Therapy Changes in Noninvasive Fibrosis Markers in Patients with Chronic Hepatitis B: A Multicenter Study

Simple SummaryWe externally validated the recently suggested FSAC prediction model for hepatocellular carcinoma (HCC) in treatment-naïve Asian chronic hepatitis B patients starting potent antiviral therapy (AVT). The model reflects age, sex, presence of cirrhosis, and on-therapy changes in non-invasive fibrosis markers (NFMs) after 12 months of antiviral therapy, such as APRI and FIB-4. Our results highlighted better predictive performance for the FSAC model for HCC (Harrell’s c-index: 0.770) than the PAGE-B, modified PAGE-B, modified REACH-B, LSM-HCC, and CAMD models, which only use baseline parameters. A simplified version of FSAC score (i.e., FSAC (2)), including only NFMs at 12 months, also showed a high c-index value (0.763). Our retrospective study suggests that the accurate measurement of intra-hepatic fibrotic burden during adequate AVT is necessary for predicting HCC development.Antiviral therapy (AVT) induces the regression of non-invasive fibrosis markers (NFMs) and reduces hepatocellular carcinoma (HCC) risk among chronic hepatitis B (CHB) patients. We externally validated the predictive performance of the FSAC prediction model for HCC using on-therapy NFM responses. Our multicenter study consecutively recruited treatment-naïve CHB patients (n = 3026; median age, 50.0 years; male predominant (61.3%); cirrhosis in 1391 (46.0%) patients) receiving potent AVTs for >18 months between 2007 and 2018. During follow-up (median 64.0 months), HCC developed in 303 (10.0%) patients. Patients with low FIB-4 or APRI levels at 12 months showed significantly lower HCC risk than those with high NFM levels at 12 months (all p < 0.05). Cumulative 3-, 5-, and 8-year HCC probabilities were 0.0%, 0.3% and 1.2% in the low-risk group (FSAC ≤ 2); 2.1%, 5.2%, and 11.1% in the intermediate-risk group (FSAC 3−8); and 5.2%, 15.5%, and 29.8% in the high-risk group (FSAC ≥ 9) (both p < 0.001 between each adjacent pair). Harrell’s c-index value for FSAC score (0.770) was higher than those for PAGE-B (0.725), modified PAGE-B (0.738), modified REACH-B (0.737), LSM-HCC (0.734), and CAMD (0.742). Our study showed that the FSAC model, which incorporates on-therapy changes in NFMs, had better predictive performance than other models using only baseline parameters.

Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Liver Failure After Resection of Colorectal Liver Metastases.

Chemotherapy agents for metastatic colorectal cancer can cause liver injury, increasing the risk of post-hepatectomy liver failure after hepatectomy for metastases. The role of noninvasive fibrosis markers in this setting is not well established. To evaluate the aspartate aminotransferase-to-platelet ratio index (APRI) as a predictor of postoperative liver failure. The National Surgical Quality Improvement Program database was utilized to identify patients who received preoperative chemotherapy and underwent hepatectomy for colorectal metastases between 2015 and 2017. Concordance index analysis was conducted to determine APRI's contribution to the prediction of liver failure. The optimal cutoff value was defined and its ability to predict post-hepatectomy liver failure and perioperative bleeding were examined. A total of 2374 patients were identified and included in the analysis. APRI demonstrated to be a better predictor of postoperative liver failure than MELD score, with a statistically significant larger area under the curve. The optimal APRI cutoff value to predict liver failure was 0.365. The multivariable logistic regression showed that APRI ≥ 0.365 was independently associated with PHLF, odds ratio (OR) 2.51, 95% confidence interval (CI) 1.67-3.77, P < .0001. Likewise, APRI ≥ 0.365 was independently associated with perioperative bleeding complications requiring transfusions, OR 1.41, 95% CI 1.13-1.77, P = 0.002. MELD score was not statistically associated with PHLF or bleeding complications. APRI was independently associated with post-hepatectomy liver failure and perioperative bleeding requiring transfusions after resection of colorectal metastases in patients who received preoperative chemotherapy. Concordance index showed APRI to add significant contribution as a predictor of postoperative liver failure.