scholarly journals Plasma sgp130 is an independent predictor of non-alcoholic fatty liver disease severity

2022 ◽  
Author(s):  
Aysim Gunes ◽  
Laurent Bilodeau ◽  
Catherine Huet ◽  
Assia Belblidia ◽  
Cindy Baldwin ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Liver Disease ◽  
Disease Severity ◽  
Liver Stiffness ◽  
Morbidly Obese ◽  
Resonance Spectroscopy ◽  
Liver Pathology ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Nafld Fibrosis Score

Background: Nonalcoholic steatohepatitis (NASH) is a metabolic disease associated with liver failure and cancer. Accurate monitoring of advancing NASH is challenging. There are few reliable, non-invasive biomarkers of early NASH. Since liver inflammation is a main driver of fibrosis, we investigated relationships between circulating components of the interleukin-6 signaling pathway (IL-6, sIL-6R and sgp130) and liver pathology in subjects with NAFLD and NASH. Methods: Predictive performance of plasma IL-6, sIL-6R and sgp130 were investigated in two independent cohorts: 1) patients with biopsy-confirmed NASH (n=49), where magnetic resonance spectroscopy (MRS), imaging (MRI) and elastography (MRE) assessed liver fat, volume and stiffness; and 2) patients with morbid obesity (n=245) undergoing bariatric surgery where Bedossa algorithm and steatosis, activity, and fibrosis scores assessed NASH severity. Correlations were evaluated between circulating IL-6, sIL-6R and sgp130 and anthropomorphic characteristics, plasma markers of metabolic disease or liver pathology, adjusting for covariates of liver disease such as age, sex, BMI and diabetes. Results: In patients with NASH, plasma IL-6 and sgp130 strongly correlated with liver stiffness, which for sgp130, was independent of age, sex, BMI, and chronic disease (diabetes, hyperlipidemia, hypertension or history of HCC). Plasma sgp130 was the strongest predictor of liver stiffness compared to commonly used biomarkers and predictive algorithms. Plasma sIL-6R correlated with liver volume independent of age, sex, and BMI. In stepwise forward regression analysis, plasma sgp130 followed by NAFLD fibrosis score and plasma globulin, predicted up to 74% of liver stiffness with/without adjustment for sex. In morbidly obese subjects, circulating IL-6 correlated with hepatocellular ballooning and sgp130 correlated with advanced liver fibrosis. Conclusions: Circulating sgp130 could represent a robust biomarker of active NASH and may be used alone or in combination with other biomarkers as a non-invasive measure of liver disease severity.

scholarly journals Caspase-Cleaved Keratin 18 Measurements Identified Ongoing Liver Injury after Bariatric Surgery

2021 ◽  
Vol 10 (6) ◽  
pp. 1233
Author(s):  
Felix Hempel ◽  
Martin Roderfeld ◽  
Lucas John Müntnich ◽  
Jens Albrecht ◽  
Ziya Oruc ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Liver Disease ◽  
Liver Injury ◽  
Response To Treatment ◽  
Morbidly Obese ◽  
Alcoholic Fatty Liver ◽  
Laboratory Parameters ◽  
Nafld Fibrosis Score ◽  
Keratin 18 ◽  
One Year

Bariatric surgery has emerged as an effective treatment option in morbidly obese patients with non-alcoholic fatty liver disease (NAFLD). However, worsening or new onset of non-alcoholic steatohepatitis (NASH) and fibrosis have been observed. Caspase-cleaved keratin 18 (ccK18) has been established as a marker of hepatocyte apoptosis, a key event in NASH development. Thus, ccK18 measurements might be feasible to monitor bariatric surgery patients. Clinical data and laboratory parameters were collected from 39 patients undergoing laparoscopic Roux-en-Y gastric bypass at six timepoints, prior to surgery until one year after the procedure. ccK18 levels were measured and a high-throughput analysis of serum adipokines and cytokines was carried out. Half of the cohort’s patients (20/39) presented with ccK18 levels indicative of progressed liver disease. 21% had a NAFLD-fibrosis score greater than 0.676, suggesting significant fibrosis. One year after surgery, a mean weight loss of 36.87% was achieved. Six and twelve months after surgery, ccK18 fragments were significantly reduced compared to preoperative levels (p < 0.001). Yet nine patients did not show a decline in ccK18 levels ≥ 10% within one year postoperatively, which was considered a response to treatment. While no significant differences in laboratory parameters or ccK18 could be observed, they presented with a greater expression of leptin and fibrinogen before surgery. Consecutive ccK18 measurements monitored the resolution of NAFLD and identified non-responders to bariatric surgery with ongoing liver injury. Further studies are needed to elicit the pathological mechanisms in non-responders and study the potential of adipokines as prognostic markers.

scholarly journals Advances in non-invasive assessment of hepatic fibrosis

Gut ◽  
2020 ◽  
Vol 69 (7) ◽  
pp. 1343-1352 ◽  
Author(s):  
Rohit Loomba ◽  
Leon A Adams
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Stiffness ◽  
Chronic Liver ◽  
Response To Treatment ◽  
Fibrosis Score ◽  
Alcoholic Fatty Liver ◽  
Need For Treatment ◽  
Non Invasive ◽  
Confirmatory Tests

Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more ‘complex’ serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.

Establishing Reliability Criteria for Liver ElastPQ Shear Wave Elastography (ElastPQ-SWE): Comparison Between 10, 5 and 3 Measurements

2019 ◽  
Author(s):  
Davide Roccarina ◽  
Laura Iogna Prat ◽  
Elena Buzzetti ◽  
Marta Guerrero Misas ◽  
Francesco Marcello Aricó ◽  
...  
Keyword(s):  
Liver Disease ◽  
Diagnostic Performance ◽  
Liver Stiffness ◽  
Quality Criterion ◽  
Quality Criteria ◽  
Shear Wave Elastography ◽  
Primary Biliary Cholangitis ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
The Difference

Abstract Purpose ElastPQ is a new elastography technique for non-invasive liver fibrosis staging. However, it does not have validated reliability criteria. We tested the reliability of a different number of measurements in patients with chronic liver disease and explored whether the application of quality criteria improves the diagnostic performance. Materials and Methods All patients underwent liver stiffness assessment (LSM) with ElastPQ and Fibroscan (F-TE). The mean, median, standard deviation (SD) and interquartile range (IQR) of 10, 5 and 3 measurements were retrospectively collected for each patient and compared to each other. Liver histology was available in a subset of patients. Results Overall, 400 patients met the inclusion criteria. Non-alcoholic fatty liver disease (NAFLD) was the most represented etiology (75 %), followed by primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). The correlation of medians was significantly better between 10 and 5 measurements than between 10 and 3. The difference of medians was significant only in the comparison between 10 and 3 measurements. The correlation between ElastPQ and F-TE was equally good for 10 and 5 measurements and significantly improved after an IQR/median ≤ 30 % was applied. The diagnostic performance of ElastPQ was better with the median value of 10 and 5 measurements and improved if LSM values were obtained with IQR/M ≤ 30 %. Conclusion The median value of 5 valid LSMs suffices for the reliable estimation of liver stiffness using ElastPQ. The quality criterion of IQR/M ≤ 30 % should also be followed when using this technique.

scholarly journals Quantification of Liver Fibrosis, Steatosis, and Viscosity Using Multiparametric Ultrasound in Patients with Non-Alcoholic Liver Disease: A “Real-Life” Cohort Study

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 783
Author(s):  
Alexandru Popa ◽  
Felix Bende ◽  
Roxana Șirli ◽  
Alina Popescu ◽  
Victor Bâldea ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Plane Wave ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Real Life ◽  
Final Analysis ◽  
Multivariate Regression Analysis ◽  
Alcoholic Fatty Liver ◽  
Non Invasive

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. This study aimed to evaluate the performance of four ultrasound-based techniques for the non-invasive multiparametric (MPUS) assessment of liver fibrosis (LF), steatosis (HS), and inflammation in patients with NAFLD. We included 215 consecutive adult patients with NAFLD (mean age: 54.9 ± 11.7; 54.5% were male), in whom LF, HS, and viscosity were evaluated in the same session using four new ultrasound-based techniques embedded on the Aixplorer MACH 30 system: ShearWave Elastography (2D-SWE.PLUS), Sound Speed Plane-wave UltraSound (SSp.PLUS), Attenuation Plane-wave UltraSound (Att.PLUS), and Viscosity Plane-wave UltraSound (Vi.PLUS). Transient Elastography (TE) with Controlled Attenuation Parameter (CAP) (FibroScan) were considered as control. All elastographic measurements were performed according to guidelines. Valid liver stiffness measurements (LSM) were obtained in 98.6% of patients by TE, in 95.8% of patients by 2D-SWE.PLUS/Vi.PLUS, and in 98.1% of patients by Att.PLUS/SSp.PLUS, respectively. Therefore, 204 subjects were included in the final analysis. A strong correlation between LSMs by 2D-SWE.PLUS and TE (r = 0.89) was found. The best 2D-SWE.PLUS cut-off value for the presence of significant fibrosis (F ≥ 2) was 7 kPa. Regarding steatosis, SSp.PLUS correlated better than Att.PLUS with CAP values: (r = −0.74) vs. (r = 0.45). The best SSp.PLUS cut-off value for predicting the presence of significant steatosis was 1524 m/s. The multivariate regression analysis showed that Vi.PLUS values were associated with BMI and LSM by 2D-SWE.PLUS. In conclusion, MPUS was useful for assessing fibrosis, steatosis, and inflammation in a single examination in patients with NAFLD.

scholarly journals Disease Severity in Non-alcoholic Fatty Liver Disease (NAFLD) Patients with No Prior Diagnosis of Cirrhosis – A Unique Insight Using Vibration-Controlled Transient Elastography (VCTE)

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
David Muschi ◽  
Dr. Raj Vuppalanchi
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Disease Severity ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Small Sample ◽  
Study Cohort ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background and Hypothesis:  The severity of fibrosis is a strong prognostic indicator in patients with non-alcoholic fatty liver disease (NAFLD). However, routine evaluation with a liver biopsy in patients with NAFLD is not feasible and as such, the assessment of disease severity is often limited in small sample sizes. Vibration-controlled transient elastography (VCTE) is a non-invasive tool that can simultaneously assess for both liver fibrosis and steatosis by estimating liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) respectively.  The aim of the current study is to estimate the prevalence of (1) abnormal LSM indicative of any fibrosis based on LSM ≥ 6.5 kPa, (2) compensated Advanced Chronic Liver Disease (cACLD) – suggestive(10-15kPa) and highly suggestive (>15 kPa), and (3) severe steatosis   Experimental Design or Project Methods:  Patients seen at digestive and liver disorders clinic at Indiana University Hospital that underwent VCTE between 8/2013-4/2018 were identified from the Fibrocan502 Touch data table. The ICD10 codes used as the indication for performing the VCTE were extracted and confirmed with the review of electronic health records.   Results:  1240 patients met the criteria.  The prevalence of abnormal LSM in the study cohort was 66% with 38.5 % having LSM suggestive of cACLD and 22% having LSM highly suggestive of cACLD. The prevalence of severe steatosis was 77%. The proportion of NAFLD patients with cACLD (suggestive and highly suggestive) during the study period was not significantly different (Figure1).    Conclusion and Potential Impact:   There are many NAFLD patients with liver stiffness indicative of abnormal LSM and 22% have LSM that is highly suggestive of cACLD. The proportion of patients with cACLD is steady over the study duration. 

Evaluation of MicroRNA-122 as A Non-invasive Diagnostic Biomarker For Non-Alcoholic Fatty Liver Disease and NASH related Cirrhosis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nevine Ibrahim Musa ◽  
Sara Hassan Agwa ◽  
Heba Ahmed Faheem ◽  
Ahmed Mohamed Gharib Alam El-din
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Invasive Technique ◽  
University Hospitals ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Nafld Fibrosis Score ◽  
Normal Controls

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. NAFLD is considered to represent the hepatic manifestation of metabolic syndrome. NAFLD was traditionally considered as a relatively benign liver disease. However, some patients with NAFLD progress to liver fibrosis, cirrhosis and hepatocellular carcinoma 8-13. Therefore, the precise diagnosis and staging of NAFLD patients is clinically important. Liver biopsy is the gold standard for the evaluation of NAFLD patients in terms of staging. However, liver biopsy is an invasive technique, and the identification of noninvasive biomarkers is required. Objective To assess the value of MicroRNA-122 as a non-invasive biomarker for diagnosis of NAFLD and NASH related Cirrhosis. Patients and Methods In the present study, we assess the value of MicroRNA-122 as a noninvasive biomarker for diagnosis of NAFLD and NASH related Cirrhosis. Gastroenterology and Hepatology outpatient clinic at: Ain Shams University Hospitals, Shebin El-Kom Teaching Hospital, Kafr Elsheikh University Hospitals. Clinical Pathology department at Faculty of Medicine, Ain Shams University. Results Patients with NASH had higher NAFLD score than patients with NAFLD than normal control. Patients with NASH had significantly higher frequency of upregulated miRNA-22. Patients with NASH had higher miRNA 122 expression than normal controls and patients with NAFLD. Likewise, patients with NAFLD had higher miRNA 122 expression than normal controls. The miRNA 122 was a significant discriminator of NAFLD and NASH with a sensitivity of 75% and specificity of 82% for NAFLD and a sensitivity of 91% and specificity of 86% for the NASH. Conclusion miRNA-122 is a sensitive and specific biomarker in the early detection of NAFLD and NASH as they are linked to the lipid metabolism reducing the need for liver biopsy. NAFLD fibrosis score had high sensitivity in differentiating the NAFLD groups from the control group and in differentiating the steatosis group from the NASH group. Serum levels of miRNA-122 were positively correlated with BMI, ALT and AST.

Liver Fibrosis Assessment in a Cohort of Greek HIV Mono-Infected Patients by Non-Invasive Biomarkers

2019 ◽  
Vol 17 (3) ◽  
pp. 173-182
Author(s):  
Theodoros Androutsakos ◽  
Maria Schina ◽  
Abraham Pouliakis ◽  
Athanasios Kontos ◽  
Nikolaos Sipsas ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Sensitivity And Specificity ◽  
Transient Elastography ◽  
Standard Procedure ◽  
Liver Stiffness ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Metavir Score ◽  
Significant Liver Fibrosis

Background: Non-alcoholic Fatty Liver Disease (NAFLD) is common in HIV-infected individuals. Liver biopsy remains the gold-standard procedure for the diagnosis of liver fibrosis, but both Transient Elastography (TE) and Non-invasive Biomarkers (NIBMs) have emerged as alternatives. Objectives: Our study’s aim was to validate commonly used NIBMs for the assessment of liver fibrosis in a cohort of Greek HIV-mono-infected patients. Methods: Inclusion criteria were confirmed HIV-infection and age>18 years and exclusion criteria HBV or HCV seropositivity, liver disease other than NAFLD, alcohol abuse, ascites, transaminases levels>4xULN(upper limit of normal) and Body-Mass index(BMI)>40. Liver stiffness (LS) measurement with TE and thorough laboratory work up and medical history were acquired at study entry. FIB-4, APRI, NFS, BARD, Forns and Lok scores were calculated for each patient. Results: A total of 157 patients were eligible for this study. Significant liver fibrosis, compatible with Metavir score of F3-F4, was found in only 11(7%) patients. These findings were in accordance with those of the NIBMs; the BARD score constituting the only exception, allocating 102(65%) patients as having significant liver fibrosis. In order to obtain a balance between sensitivity and specificity new cut-offs for each NIBM were calculated; FIB-4 score yielded the best results, since by changing the cut-off to 1.49 a sensitivity and specificity balanced for both close to 85% was achieved. Conclusions: Our findings suggest that NIBMs can be used for the evaluation of liver fibrosis in HIV mono-infected patients. New cut-offs for NIBMs should probably be calculated, to help distinguishing patients with significant from those with mild/no fibrosis.

scholarly journals Elastography—A Bona Fide Non-Invasive Method for Assessing Non-Alcoholic Fatty Liver Disease in Children

2021 ◽  
Vol 11 (7) ◽  
pp. 3240
Author(s):  
Cristina Oana Mărginean ◽  
Lorena Elena Meliț ◽  
Maria Oana Săsăran
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Stiffness ◽  
Major Public Health Problem ◽  
Systemic Complications ◽  
Alcoholic Fatty Liver ◽  
Non Invasive

Pediatric obesity has become a major public health problem worldwide, resulting in a wide spectrum of systemic complications. Liver disease associated with obesity, also known as nonalcoholic fatty liver disease (NAFLD), is currently the most common chronic liver condition in children. Therefore, its timely and proper diagnosis is essential for preventing further development of cirrhosis. Multiple studies focused on identifying the most accurate non-invasive diagnostic method for liver fibrosis or cirrhosis. Although liver biopsy remains the gold-standard in terms of this hepatopathy, elastography methods emerged as a relatively reliable alternative to liver biopsy. Thus, recent studies revealed the great importance of these non-invasive methods not only in diagnosing pediatric NAFLD, but also in its staging. MRE is commonly considered to have a greater accuracy than ultrasound-based elastography methods, but with lower availability and higher costs. Ultrasound-based elastography methods (transient elastography (TE), p-SWE, and 2-dimensional shear wave elastography (2D-SWE)) were proved to have similar accuracy in NAFLD staging. Nevertheless, multiple confounding factors account for potential challenges when using elastography for liver stiffness measurement, such as age, obesity itself (i.e., BMI), transaminase levels, or portal flow. A potential solution for facing these challenges might be represented by a complex approach based on the combination between elastography, clinical and laboratory findings. Although the studies that assessed the role of elastography in pediatric NAFLD staging are scarce, the current knowledge underlines a crucial role of these techniques taking into account their ability to distinguish between fibrosis degrees, their non-invasive patterns, lower costs and side effects when compared to liver biopsy. Therefore, elastography might become a cornerstone in staging pediatric NAFLD.

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