Liver Fibrosis Biomarkers Accurately Exclude Advanced Fibrosis and Are Associated with Higher Cardiovascular Risk Scores in Patients with NAFLD or Viral Chronic Liver Disease

Liver fibrosis predicts liver-related and cardiovascular outcomes in chronic liver disease patients. We compared the diagnostic performance of various liver fibrosis biomarkers for identifying histological significant/advanced fibrosis. Additionally, the correlations of such liver fibrosis biomarkers with cardiovascular risk (CVR) scores were evaluated. 173 patients with viral hepatitis (157 HCV and 16 HBV) and 107 with a non-alcoholic fatty liver disease (NAFLD) were consecutively enrolled. Various liver fibrosis biomarkers: aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (ARR), AST to Platelet Ratio Index (APRI), Fibrosis-4 (FiB-4), Forns index, NAFLD fibrosis score (NFS), BARD (body mass index (BMI), AAR, Diabetes) score, and Hepamet fibrosis score (HFS), were used to identify significant/advanced fibrosis. CVR was assessed by using the SCORE, the Progetto CUORE, or the Framingham risk scoring systems. Liver fibrosis biomarkers performed better in predicting advanced rather than significant liver fibrosis in all patients, regardless of chronic liver disease aetiology. Forns index and HFS performed best in predicting advanced fibrosis in patients with viral chronic liver disease and NAFLD. Lower cut-offs of these liver fibrosis biomarkers had high negative predictive values for advanced fibrosis overall, as well as in patients with NAFLD or viral chronic liver disease. FIB-4, Forns index, NFS, and HFS were positively correlated with SCORE and Framingham risk scores. In conclusion, liver fibrosis biomarkers accurately exclude advanced fibrosis and positively correlate with CVR scores in patients with chronic liver disease.

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Advances in non-invasive assessment of hepatic fibrosis

Gut ◽

10.1136/gutjnl-2018-317593 ◽

2020 ◽

Vol 69 (7) ◽

pp. 1343-1352 ◽

Cited By ~ 9

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.

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The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease

Liver International ◽

10.1111/liv.12896 ◽

2015 ◽

Vol 36 (3) ◽

pp. 370-377 ◽

Cited By ~ 23

Author(s):

Katharine M. Irvine ◽

Leesa F. Wockner ◽

Mihir Shanker ◽

Kevin J. Fagan ◽

Leigh U. Horsfall ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Disease Progression ◽

Clinical Outcomes ◽

Chronic Liver ◽

Fibrosis Score

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A review of the clinical utility of the Enhanced Liver Fibrosis test in multiple aetiologies of chronic liver disease

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563219879962 ◽

2019 ◽

Vol 57 (1) ◽

pp. 36-43

Author(s):

Preya Janubhai Patel ◽

Declan Connoley ◽

Freya Rhodes ◽

Ankur Srivastava ◽

William Rosenberg

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Biopsy ◽

Chronic Liver Disease ◽

Clinical Utility ◽

Chronic Liver ◽

Biliary Cirrhosis ◽

Alcoholic Fatty Liver ◽

Functional Changes ◽

Non Invasive

The rising incidence of chronic liver disease continues to be an increasing health burden. The morbidity and mortality associated with chronic liver disease typically occur in patients with advanced fibrosis. Hence, early identification of those at-risk is of vital importance to ensure appropriate ongoing management. Currently, tools for appropriate risk stratification remain limited. Increasing awareness of the limitations of liver biopsy has driven research into alternative non-invasive methods of fibrosis assessment including serological markers assessing functional changes. One such biomarker, the Enhanced Liver Fibrosis test, was initially validated in a cohort of 1021 patients with mixed aetiology chronic liver disease and shown to perform well. Since this pathfinder study, it has been independently validated in cohorts of hepatitis C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. In addition to performing well as a diagnostic tool, the Enhanced Liver Fibrosis test has been shown to outperform liver biopsy in prognostic studies and is the only non-invasive marker to do so. However, questions remain regarding the use of this test, particularly regarding the possible effect age and alcohol may have on test scores. This review examines the current literature published in relation to the Enhanced Liver Fibrosis test and its clinical utility and highlights areas requiring further study.

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Non‐invasive detection of portal hypertension by enhanced liver fibrosis score in patients with different aetiologies of advanced chronic liver disease

Liver International ◽

10.1111/liv.14498 ◽

2020 ◽

Vol 40 (7) ◽

pp. 1713-1724 ◽

Cited By ~ 1

Author(s):

Benedikt Simbrunner ◽

Rodrig Marculescu ◽

Bernhard Scheiner ◽

Philipp Schwabl ◽

Theresa Bucsics ◽

...

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Chronic Liver ◽

Fibrosis Score ◽

Non Invasive

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Abstract P671: Association Between Liver Fibrosis and Postoperative Stroke

Stroke ◽

10.1161/str.52.suppl_1.p671 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Marialaura Simonetto ◽

Cenai Zhang ◽

Santosh Murthy ◽

Babak B Navi ◽

Hooman Kamel ◽

...

Keyword(s):

Platelet Count ◽

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Aspartate Aminotransferase ◽

Chronic Liver ◽

Sensitivity Analyses ◽

Fibrosis Score ◽

Improvement Program ◽

Increased Risk

Introduction: Chronic liver disease is associated with aberrant hemostasis, resulting in an increased risk of clotting and bleeding. We hypothesized that liver fibrosis, a manifestation of progressive chronic liver disease, is associated with stroke among people who have been subjected to the hemostatic stress of surgery. Methods: We conducted a retrospective, multicenter cohort study using data from 680 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), a prospective registry of 30-day outcomes. Quality measures, such as stroke, have been validated and have 95% inter-observer agreement. We included adults who underwent major surgery, except neurosurgery, from 2005-2016. The exposure was the Aspartate aminotransferase to Platelet Ratio Index (APRI) liver fibrosis score, calculated from preoperative aspartate aminotransferase and platelet count. The primary outcome was incident stroke, reported by NSQIP as a composite of ischemic and hemorrhagic stroke. We used multivariable Cox proportional hazards models to assess the relationship between APRI and incident stroke, adjusting for demographics, comorbidities, and surgical characteristics (surgical type and American Society of Anesthesiologists preoperative fitness classification). In a sensitivity analysis, we also adjusted for preoperative platelet count and coagulation indices. Results: Among 2,729,995 patients, the mean age was 57 (SD, 17) years and 58% were women. A total of 6,886 patients had stroke within 30 days (0.25%). In unadjusted analyses, a 1-point increase in APRI was associated with a 3% increased risk of stroke (HR, 1.03; 95% CI, 1.02-1.03). The association remained significant in models adjusted for comorbidities and surgical characteristics (HR, 1.02; 95% CI, 1.01-1.03). Sensitivity analyses also adjusted for platelet count and coagulation indices were consistent (HR, 1.03; 95% CI, 1.01-1.04). Conclusions: A liver fibrosis score calculated from routine preoperative laboratory data was independently, albeit modestly, associated with an increased risk of stroke within 30 days after surgery. Whether preoperative assessment of liver disease markers has clinical utility requires investigation.

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Growth differentiation factor (GDF) -15– a novel biomarker to assess the extent of liver fibrosis in patients with chronic liver disease?

Zeitschrift für Gastroenterologie ◽

10.1055/s-0029-1191796 ◽

2009 ◽

Vol 47 (01) ◽

Cited By ~ 1

Author(s):

T Rädle-Hurst ◽

E Herrmann ◽

G Hess ◽

S Zeuzem ◽

F Lammert ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Chronic Liver ◽

Differentiation Factor

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Mac‐2 Binding Protein Glycan Isomer as non‐invasive tool to assess liver fibrosis in children with chronic liver disease

Hepatology Research ◽

10.1111/hepr.13608 ◽

2021 ◽

Author(s):

Ola G Behairy ◽

Soha A El‐Gendy ◽

Dalia Y Ibrahim ◽

Amira I Mansour ◽

Ola S El‐Shimi

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Binding Protein ◽

Chronic Liver ◽

Non Invasive

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Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211023410 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110234

Author(s):

Mario Romero-Cristóbal ◽

Ana Clemente-Sánchez ◽

Patricia Piñeiro ◽

Jamil Cedeño ◽

Laura Rayón ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Injury ◽

Chronic Liver Disease ◽

Critically Ill ◽

Cox Regression ◽

Chronic Liver ◽

Cox Regression Analysis ◽

Risk Of Death ◽

The Impact

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan–Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis ( p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11–1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99–1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

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