Forns Index Research Articles

Forns index and fatty liver index, but not FIB-4, are associated with indices of glycaemia, pre-diabetes and type 2 diabetes: analysis of The Maastricht Study

ObjectiveGlucose metabolism status (GMS) is linked to non-alcoholic fatty liver disease (NAFLD). Higher levels of advanced glycation end products (AGEs) are observed in people with type 2 diabetes mellitus (T2DM)...

The clinical value of fibrosis indices for predicting the hemorrhagic transformation in patients with acute ischemic stroke after intravenous thrombolysis.

The incidence of stroke in China is approximately 343 per 100,000 people each year, the highest rate worldwide. Hemorrhagic transformation (HT), particularly symptomatic intracerebral hemorrhage (sICH) following acute ischemic stroke (AIS) with or without intravenous thrombolysis (IVT), can lead to rapid neurological deterioration, poor prognosis, and even death. Non-alcoholic fatty liver disease (NAFLD) has been identified as a risk factor for stroke occurrence and associated with poor long-term functional outcomes. Nonetheless, no studies have examined the association between liver fibrosis and HT in AIS patients who underwent IVT. A total of 826 patients with AIS who underwent IVT were included in this study. We calculated nine validated liver fibrosis indices to assess the extent of liver fibrosis. HT was detected by follow-up cranial CT/MRI within 24 h post-IVT and was classified as either hemorrhagic infarction (HI) or parenchymal hematoma (PH). Symptomatic intracranial hemorrhage was defined as a sudden symptomatic neurological deterioration, indicated by an increase in (National Institutes of Health Stroke Scale) NIHSS score of 4 points or more. The median values of fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aspartate aminotransferase (AST)-platelet ratio index (APRI), Forns index, alanine aminotransferase (ALT)/AST (ARR), AST/ALT ratio-platelet ratio index (AARPRI), fibrosis quotient (FibroQ), and Fibrosis Index were significantly higher, while the fibrosis-5 (FIB-5) was significantly lower in the HT and sICH groups (all P < 0.001). After adjusting for potential confounders, all nine liver fibrosis indices remained associated with HT and sICH. Receiver operating characteristic (ROC) curve analysis revealed that the FibroQ score had the best predictive ability for HT (AUC = 0.707, CI = 0.652-0.762, P < 0.001), while FIB-4 had the best predictive ability for sICH (AUC = 0.802, CI = 0.711-0.892, P < 0.001). Liver fibrosis, as validated by FIB-4, mFIB-4, FIB-5, APRI, Forns index, ARR, AARPRI, FibroQ, and Fibrosis Index, was associated with HT and sICH in AIS patients after IVT.

Establishment and Evaluation of a Noninvasive Metabolism-Related Fatty Liver Screening and Dynamic Monitoring Model: Cross-Sectional Study.

Metabolically associated fatty liver disease (MAFLD) insidiously affects people's health, and many models have been proposed for the evaluation of liver fibrosis. However, there is still a lack of noninvasive and sensitive models to screen MAFLD in high-risk populations. The purpose of this study was to explore a new method for early screening of the public and establish a home-based tool for regular self-assessment and monitoring of MAFLD. In this cross-sectional study, there were 1758 eligible participants in the training set and 200 eligible participants in the testing set. Routine blood, blood biochemistry, and FibroScan tests were performed, and body composition was analyzed using a body composition instrument. Additionally, we recorded multiple factors including disease-related risk factors, the Forns index score, the hepatic steatosis index (HSI), the triglyceride glucose index, total body water (TBW), body fat mass (BFM), visceral fat area, waist-height ratio (WHtR), and basal metabolic rate. Binary logistic regression analysis was performed to explore the potential anthropometric indicators that have a predictive ability to screen for MAFLD. A new model, named the MAFLD Screening Index (MFSI), was established using binary logistic regression analysis, and BFM, WHtR, and TBW were included. A simple rating table, named the MAFLD Rating Table (MRT), was also established using these indicators. The performance of the HSI (area under the curve [AUC]=0.873, specificity=76.8%, sensitivity=81.4%), WHtR (AUC=0.866, specificity=79.8%, sensitivity=80.8%), and BFM (AUC=0.842, specificity=76.9%, sensitivity=76.2%) in discriminating between the MAFLD group and non-fatty liver group was evaluated (P<.001). The AUC of the combined model including WHtR, HSI, and BFM values was 0.900 (specificity=81.8%, sensitivity=85.6%; P<.001). The MFSI was established based on better performance at screening MAFLD patients in the training set (AUC=0.896, specificity=83.8%, sensitivity=82.1%) and was confirmed in the testing set (AUC=0.917, specificity=89.8%, sensitivity=84.4%; P<.001). The novel MFSI model was built using WHtR, BFM, and TBW to screen for early MAFLD. These body parameters can be easily obtained using a body fat scale at home, and the mobile device software can record specific values and perform calculations. MFSI had better performance than other models for early MAFLD screening. The new model showed strong power and stability and shows promise in the area of MAFLD detection and self-assessment. The MRT was a practical tool to assess disease alterations in real time.

Liver fibrosis stage based on the four factors (FIB-4) score or Forns index in adults with chronic hepatitis C.

Liver fibrosis stage based on the four factors (FIB-4) score or Forns index in adults with chronic hepatitis C.

Noninvasive liver fibrosis markers are independently associated with carotid atherosclerosis risk in patients with nonalcoholic fatty liver disease

Objective Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for cardiovascular disease (CVD). The overall morbidity and mortality of CVD increase with higher fibrosis stage in NAFLD. Carotid atherosclerosis (CAS) is an important predictor of cardiovascular events. However, the relationship between liver fibrosis degree and the risk of CAS in NAFLD patients remains uncertain. We aimed to investigate the relationship between noninvasive liver fibrosis markers and CAS risk in patients with NAFLD. Materials and Methods This study included 3,302 participants with NAFLD. Participants were divided into a CAS group and a non-CAS group based on carotid artery ultrasound results. They were then stratified into quartiles using various noninvasive liver fibrosis markers (fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aminotransferase to platelet ratio index (APRI), aminotransferase to alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and Forns index) to assess the associations between these markers and the risk of CAS. Results In the NAFLD population, individuals with CAS exhibited elevated levels of blood pressure, glucose, lipids, and noninvasive liver fibrosis markers (p < 0.001). The higher quartiles of noninvasive liver fibrosis markers, including FIB-4, mFIB-4, AAR, AARPRI, and Forns index, were significantly associated with increased risks of CAS, even after adjusting for multiple CVD risk factors. Conclusions In individuals with NAFLD, increased noninvasive liver fibrosis markers were independently associated with elevated CAS risk, which may be beneficial in assessing the risk of CVD in individuals with NAFLD.

Aspartate Aminotransferase to Platelet Ratio Index (APRI) as a Predictor of Metabolic Syndrome (MetS) Development in Individuals With Type 2 Diabetes Mellitus.

Despite ongoing findings on the relationship between liver fibrosis in nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), this association in diabetic patients remains unclear. Early diagnosis of liver fibrosis is important due to the easily available diagnostic tools, such as noninvasive indices that combine clinical and laboratory variables, and the possibility of preventing its complications in type 2 diabetes mellitus (T2DM) patients with MetS. This study examines the potential predictive values of non-invasive liver fibrosis indices for MetS in T2DM patients. Over the course of a two-year prospective, observational, clinical study, 80 individuals with T2DMrandomly selected from the Diabetes Counseling Centers of the Public Institution Health Center of Sarajevo Canton were divided into two groups: T2DM-MetS and T2DM-non-MetS, based on the development of MetS. The studyincludedindividuals with T2DM aged30 to 60who were clinically diagnosed without MetS, voluntarily agreed to participate, and provided complete data in the collection forms. Serum samples from the patients were assessed for levels of liver enzymes, platelet counts, total cholesterol, high-density lipoprotein cholesterol, fasting glucose, and triglycerides. Various equations were utilized to calculate liver fibrosis indices, including the Aspartate Aminotransferase to Platelet Ratio Index (APRI), Aspartate Aminotransferase to Gamma-Glutamyl Transferase to Platelet Ratio (AGPR), Aspartate Aminotransferase to Alanine Aminotransferase Ratio to Platelet Ratio Index (AARPRI), Fibrosis-4 (FIB-4) Index, Forns Index, and Gamma-Glutamyl Transpeptidase to Platelet Ratio (GPR). Receiver operating characteristic (ROC) analysis was utilized to determine the usefulness of noninvasive liver fibrosis indices for diagnosing MetS in individuals with T2DM. Logistic regression analysis was used to predict the onset of MetS in T2DM patients. Significant differences in the values of APRI (p<0.001), AGPR (p<0.05), AARPRI (p<0.001), and the FIB-4 index (p=0.001) were observed in T2DM-MetS individuals compared to T2DM-non-MetS. According to ROC analysis, the area under the curve (AUC) was found to be highest for APRI (0.84), followed by FIB-4 (0.783) and AARPRI (0.747). Logistic regression analysis identified APRI as an independent positive predictor of MetS (OR 18.179, 95% CI 6.035-24.58, p=0.015). This research highlights the effectiveness of the APRI index as a reliable predictor of MetS development in individuals with T2DM.

FibroScan-aspartate transaminase: A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) with hepatic histological NAFLD activity score ≥ 4 and fibrosis stage F ≥ 2 is regarded as "at risk" non-alcoholic steatohepatitis (NASH). Based on an international consensus, NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), respectively; hence, we introduced the term "high-risk MASH". Diagnostic values of seven non-invasive models, including FibroScan-aspartate transaminase (FAST), fibrosis-4 (FIB-4), aspartate transaminase to platelet ratio index (APRI), etc. for high-risk MASH have rarely been studied and compared in MASLD. To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH. A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital, between January 2012 and December 2020. After screening for MASLD and the exclusion criteria, 279 patients were included and categorized into high-risk and non-high-risk MASH groups. Utilizing threshold values of each model, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), were calculated. Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve (AUROC). MASLD diagnostic criteria were met by 99.4% patients with NAFLD. The MASLD population was analyzed in two cohorts: Overall population (279 patients) and the subgroup (117 patients) who underwent liver transient elastography (FibroScan). In the overall population, FIB-4 showed better diagnostic efficacy and higher PPV, with sensitivity, specificity, PPV, NPV, and AUROC of 26.9%, 95.2%, 73.5%, 72.2%, and 0.75. APRI, Forns index, and aspartate transaminase to alanine transaminase ratio (ARR) showed moderate diagnostic efficacy, whereas S index and gamma-glutamyl transpeptidase to platelet ratio (GPR) were relatively weaker. In the subgroup, FAST had the highest diagnostic efficacy, its sensitivity, specificity, PPV, NPV, and AUROC were 44.2%, 92.3%, 82.1%, 67.4%, and 0.82. The FIB-4 AUROC was 0.76. S index and GPR exhibited almost no diagnostic value for high-risk MASH. FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI, Forns index, ARR, S index, and GPR; FAST is superior to FIB-4.

Non-invasive Assessment of Liver Damage Degree in Patients with Viral Hepatitis: Is It Feasible and Acceptable?

Background: Hepatitis C and B virus infections significantly contribute to global chronic liver disease mortality. Objectives: This study explores the role of serum markers (AST/ALT ratio, APRI Score, FIB-4 Score, and Forns index) in non-invasively assessing liver damage in patients with chronic hepatitis C and B. Methods: In this single-center, retrospective, observational study, we analyzed data from 327 patients to establish correlations between serological markers and fibrosis grade using Spearman's correlation. Receiver operator characteristic (ROC) analysis evaluated the ability of these markers to predict advanced fibrosis. Results: In hepatitis B and C cohorts, all markers show significant positive correlations with liver fibrosis (P &lt; 0.001). FIB-4 and the Forns index exhibit moderate correlation (Spearman’s rho 0.48), while AST/ALT and APRI score show mild correlation (Spearman’s rho 0.21 and 0.31). In hepatitis C, the Forns index (0.814) and FIB-4 (0.80) outperform other markers. In hepatitis B, Forns (AUC = 0.73), APRI (AUC = 0.68), and FIB-4 (AUC = 0.68) demonstrate significant predictive ability. Conclusions: FIB-4 and the Forns index hold clinical significance as fibrosis biomarkers in the management of chronic viral hepatitis. FIB-4 is a universal marker, while the interpretation of the Forns index requires consideration of the etiology of chronic viral hepatitis.

The relationship between the use of nucleos(t)ide analogs and metabolic parameters in patients with chronic hepatitis B.

In the treatment of chronic hepatitis-B (CHB), although viral replication load is reduced with the use of nucleos(t)ide analogs, the risk of cirrhosis and hepatocellular carcinoma (HCC) remains. We aimed to investigate the relationship between metabolic syndrome (MetS) and CHB of nucleos(t)ide analogs, which are effective in mortality-morbidity. In patients who applied to the gastroenterology outpatient clinic between 2021 and 2022, we compared inactive HBsAg-positive patients who did not receive treatment with nucleos(t)ide analogs [entecavir (ETV), lamivudine (LAM), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF)] and medical treatment. Demographic characteristics of the patients were recorded. Lipid profile, Hemoglobin A1c (HbA1c), and HOMA-IR were recorded. The presence of hepatosteatosis was graded ultrasonographically. APRI, Forns Index, and FIB-4 score, which are indicators of non-invasive liver fibrosis, were evaluated. Of the 265 patients, 55.5% (n=147) were males and 44.5% (n=118) were females. The ages of the participants ranged from 18 to 80, with a mean age of 46.54±14.03. It was observed that 62.3% (n=165) of the cases received medical treatment. When the drugs used by those receiving medical treatment were examined, 70.3% (n=116) TDF, 6.1% (n=10) TAF, 3% (n=5) LAM, and 20.6% (n=34) ETV, LDL, HDL, and total cholesterol measurement values of those who received medical treatment were lower, while HOMA-IR values were higher compared to those who did not receive the medical treatment. While the HbA1c value of the patients using ETV was found to be high, the liver stiffness indicator scores of those using TDF were found to be significantly higher. In this study, in patients with CHB, it has been shown that medical treatment also affects MetS parameters.

The NAFLD burden on mortality and morbidities in general population: A community-based longitudinal study (NASH-CO study).

The impact of non-alcoholic fatty liver disease (NAFLD) on morbidity and mortality has yet to be documented at the general population level. This study aimed to assess whether NAFLD was associated with morbidities and mortality and to estimate its impact on health status and mortality. The study population consisted of 137 206 participants from Constances cohort. Non-invasive diagnosis of NAFLD and advanced fibrosis was performed using the fatty liver index and Forns index, respectively. Constances data were linked to health care and hospitalization data to identify liver-related events, cardiovascular diseases (CVD), extrahepatic cancers (EHC), chronic kidney disease (CKD) and all-cause mortality. The prevalence of NAFLD was 18.3% in subjects without other chronic liver diseases, among whom 2.7% had fibrosis. NAFLD after IPTW-weighted remained associated with an increased risk of death (HR 1.26, 95% CI 1.01-1.57), hepatic-related complications (HR 2.48, 95% CI 1.99-3.29), CVD (HR 1.42, 95% CI 1.30-1.55), EHC (HR 1.11, 95% CI 1.01-1.28) and CKD (HR 1.81, 95% CI 1.53-2.07) compared to those without chronic liver diseases risk factors (Non-NAFLD). In the trend analysis over the study period of inclusion and compared to Non-NAFLD, NAFLD has shown a fastest growing cause of hepatic events (HR 1.38, 95% CI 1.07-1.76 per year), CVD (HR 1.08, 95% CI 1.03-1.12), CKD (HR 1.16, 95% CI 1.07-1.25), and death (HR 1.39, 95% CI 1.39-1.50). This large community-based cohort showed that NAFLD was associated with excess morbidity and mortality and demonstrated a fastest-growing trend.

Efficacy of Serum Ferritin-Zinc Ratio for Predicting Advanced Liver Fibrosis in Patients with Autoimmune Hepatitis.

Background/Aims: The search for noninvasive biomarkers that can efficiently estimate the extent of liver fibrosis progression is ongoing. Although Fibrosis-4 (FIB-4), the aspartate transaminase-to-platelet ratio index (APRI), and the Forns index have been reported as useful biomarkers, their investigation in autoimmune hepatitis (AIH) is limited. This study aimed to examine the usefulness of these serological indices and a newly developed index in predicting liver fibrosis progression in AIH. Methods: The study analyzed data from 190 patients diagnosed with AIH at our institution between 1990 and 2015. Their histological liver fibrosis progression and clinical long-term prognosis were evaluated retrospectively (cohort 1). In 90 patients, receiver operating characteristic (ROC) curves were compared to choose severe fibrosis cases with respect to existing indices (FIB-4, APRI, and Forns index) and the ferritin-zinc ratio (cohort 2). Results: In cohort 1, liver-related death and hepatocellular carcinoma rates were significantly higher in the severe (n = 27) than in the mild (n = 63) fibrosis group (p = 0.0001 and 0.0191, respectively). In cohort 2, liver-related death in the severe fibrosis group was significantly frequent (p = 0.0071), and their ferritin-zinc ratio was higher (median 2.41 vs. 0.62, p = 0.0011). ROC analyses were performed to compare the ability of the ferritin-zinc ratio, FIB-4, APRI, and the Forns index to predict severe and mild fibrosis. Accordingly, areas under the ROC were 0.732, 0.740, 0.721, and 0.729, respectively. Conclusions: The serum ferritin-zinc ratio can noninvasively predict liver fibrosis progression in AIH and be applied to predict long-term prognosis.

Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO Study).

The severity of liver injury and clinical outcomes in lean individuals with NAFLD is a subject of debate and very few studies have been performed in the general population. The aim of this study was to compare subject characteristics and mortality between lean and nonlean NAFLD in a community setting. The study population included 169,303 participants from the nationwide Constances cohort. Subjects with excessive alcohol consumption, viral hepatitis, or other liver diseases were excluded and 137,206 subjects were analyzed. The diagnosis of NAFLD and fibrosis was performed using the Fatty Liver Index and the Forns Index. The median follow-up was 3.58 years. The prevalence of NAFLD was 5.3% (95% CI: 5.2-5.4) in lean subjects, while 16.3% (95% CI: 15.7-16.8) of NAFLD subjects were lean. Despite their better metabolic profile, the prevalence of advanced fibrosis was significantly higher in lean than in nonlean NAFLD (3.7% vs. 1.7%, respectively, p < 0.01). Among NAFLD subjects and after adjustment for demographics, metabolic risk factors and lifestyle, lean status was associated with advanced fibrosis (OR=1.26, 95% CI: 1.20-1.65, p = 0.005), an increased risk of liver-related events (adjusted HR=5.84, 95% CI: 4.03-8.46), chronic kidney disease (adjusted HR=2.49, 95% CI: 1.49-4.16), and overall mortality (adjusted HR=3.01, 95% CI: 2.21-4.11). Liver-related events and overall mortality were related to the severity of fibrosis, both in lean and nonlean NAFLD subjects, whatever the usual risk factors. This study in a large community-based cohort confirms that NAFLD in lean subjects is more severe for fibrosis, the progression of liver disease, chronic kidney disease, and overall mortality.

Environmental exposures are important risk factors for advanced liver fibrosis in African American adults

The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States. Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999-2018). Advanced liver fibrosis was defined as Fibrosis-4 ≥2.67 and/or Forns index ≥6.9 and elevated alanine aminotransferase. The estimated number of people with advanced liver fibrosis increased from 1.3 million (95% CI 0.8-1.9) to 3.5 million (95% CI 2.8-4.2), a nearly threefold increase. Prevalence was higher in non-Hispanic Black and Mexican American persons than in non-Hispanic White persons. In multivariable logistic regression analysis, cadmium was an independent risk factor in all racial/ethnic groups. Smoking and current excessive alcohol use were risk factors in most. Importantly, compared with non-Hispanic White persons, non-Hispanic Black persons had a distinctive set of risk factors that included poverty (odds ratio [OR] 2.09; 95% CI 1.44-3.03) and susceptibility to lead exposure (OR 3.25; 95% CI 1.95-5.43) but did not include diabetes (OR 0.88; 95% CI 0.61-1.27; p=0.52). Non-Hispanic Black persons were more likely to have high exposure to lead, cadmium, polychlorinated biphenyls, and poverty than non-Hispanic White persons. The number of people with advanced liver fibrosis has increased, creating a need to expand the liver care workforce. The risk factors for advanced fibrosis vary by race/ethnicity. These differences provide useful information for designing screening programmes. Poverty and toxic exposures were associated with the high prevalence of advanced liver fibrosis in non-Hispanic Black persons and need to be addressed. Because liver disease often produces few warning signs, simple and inexpensive screening tests that can be performed by non-specialists are needed to allow timely diagnosis and linkage to care. This study shows that non-Hispanic Black persons have a distinctive set of risk factors that need to be taken into account when designing liver disease screening programs. Exposure to exogenous toxins may be especially important risk factors for advanced liver fibrosis in non-Hispanic Black persons.

Letter to the editor: Association between birth weight, preterm birth, and nonalcoholic fatty liver disease in a community-based cohort.

To the editor, While we commend Amadou et al.1 for their fine study reporting a U-shaped association between birth weight and risk of NAFLD, we have some concerns. NAFLD was defined using the fatty liver index. This index was, however, developed as a risk stratification tool (not as a diagnostic instrument) and has a rather low positive predictive value for the diagnosis of NAFLD (67%).2 Furthermore, the fatty liver index may perform poorly in young individuals with normal body mass index,3 as in the current French study population (mean age 38 y, normal body mass index).1 Given that the fatty liver index formula is largely driven by body mass index and waist circumference, the question arises whether the found associations rather explain a higher risk of obesity and would especially miss individuals with lean NAFLD. While in women, there was a positive association between high birth weight and risk of NAFLD, the mediation analysis revealed that in men high birth weight did neither have a direct nor a total effect on the later risk of NAFLD—in contrast the indirect effect seemed even protective. Against this background, how do the authors explain the contradictive results on high birth weight and NAFLD risk in men andwomen? The authors found a slight negative association between birth weight and the Forns index, which was used as proxy for liver fibrosis. Here, we see two limitations that make the interpretation of these results challenging: first, the Forns index was originally developed to noninvasively rule-out significant fibrosis and has not been validated to be used as a continuous variable. Second, it was derived in high-risk cohorts of patients with chronic hepatitis C infection,4 while the current study applied it in a general population setting. Hence, we are eager to know if the authors could confirm these results using FIB-4 instead, which is recommended by international guidelines.5

Systematic screening for advanced liver fibrosis in patients with coronary artery disease: The CORONASH study

Coronary artery disease (CAD) and advanced liver fibrosis (AdLF) are commonly associated in patients with non-alcoholic fatty liver disease (NAFLD). However, the prevalence of AdLF and the diagnostic performance of non-invasive fibrosis tests (NITs) in CAD patients remains unknown. We aimed to prospectively screen for AdLF in patients with documented CAD using NITs and Fibroscan. High and intermediate zones of NITs were combined to define AdLF. AdLF was suspected whenever APRI ≥ 0.5, Forns index ≥ 4.2, NAFLD fibrosis score (NFS) (≥ −1.455/0.12 for age </≥ 65 yrs), Fib4 (≥ 1.30/2.0 for age </≥ 65 yrs) and eLIFT ≥ 8. A presumed AdLF assessed by Fibroscan ≥ 8 kPa was the primary outcome measure. Results were given on the basis of intent-to-diagnose liver stiffness ≥ 8 kPa. Among 189 patients (age 60 ± 7 years), 10 (5.3%) had a Fibroscan ≥ 8 kPa, of whom 5 underwent liver biopsy (F3/F4: n = 3; no fibrosis: n = 2). AdLF was suspected in 31% of cases using eLIFT (specificity, Sp 70%), 85% with Forns (Sp 16%), 38% with NFS (Sp 63%), 25% with Fib4 (Sp 74%), and 10% with APRI (Sp 91%). In 149 patients “at-risk” of NAFLD (i.e., elevated ALT or diabetes or hypertriglyceridemia or BMI ≥ 25 kg/m2), AdLF ranged between 10% (APRI) to 84% (Forns). In this subgroup, the most efficient NITs to predict Fibroscan ≥ 8 kPa were eLIFT (Se 60%, Sp 70%) and NFS (Se 70%, Sp 60%). In CAD patients with risk factors for NAFLD, NFS or the more user-friendly eLIFT are the most attractive first-line biochemical NITs to discriminate good candidates for Fibroscan.

Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality

Liver fibrosis is critical for liver-related outcomes and mortality in chronic liver disease, irrespective of etiology, including nonalcoholic fatty liver disease (NAFLD). NAFLD has been viewed as an independent correlate of cardiovascular risk. This review article briefly describes the cellular and molecular pathomechanisms underlying hepatic fibrosis. We then address noninvasive assessment of liver fibrosis. Finally, we discuss published evidence supporting fibrosis biomarkers’ role in assessing cardiovascular risk among patients with NAFLD. While histological assessment is the diagnostic standard of hepatic fibrosis, we specifically address noninvasive techniques, including equations based on anthropometric parameters, laboratory indices, and elastometry obtained with imaging techniques. The former group includes AST: ALT ratio, the Forns Index, the AST-to-platelet ratio index score, BARD (BMI, AAR, Diabetes) score, the fibrosis-4 index (FIB-4), the NAFLD fibrosis score, the gamma-glutamyl transferase-to-platelet ratio, and the Hepamet fibrosis score. The latter comprises elastographic techniques associated with ultrasonography or magnetic resonance. Our literature review identified numerous studies demonstrating that biomarkers of fibrosis (the most common being FIB-4) and elastographic techniques predict overall mortality and major cardiovascular events among NAFLD patients. The mechanisms accounting for this association are briefly reviewed. In addition to assessing hepatic fibrosis at baseline, during follow-up, and after therapeutic interventions in NAFLD patients, noninvasive assessment of hepatic fibrosis may predict cardiovascular events and overall mortality in these patients.

Improvement of liver fibrosis verification using new minimally invasive markers in patients with chronic diffuse liver diseases

The aim of our research was to obtain new minimally invasive serum markers of fibrotic changes of liver in patients with chronic diffuse liver diseases of different etiology and compare them with traditional markers. 364 patients aged 30 to 66 years were examined: 221 women (60.7%) and 143 men (39.3%). Depending on the etiological factors, all patients were divided into 4 groups: group I consisted of 108 patients with non-alcoholic fatty liver disease (NAFLD), group II – 143 patients with chronic hepatitis associated with virus C (CHC), group III – 56 patients with alcoholic liver disease (ALD), group IV – 57 patients with toxic drug-induced hepatitis (TH). The control group consisted of 30 practically healthy people. Using correlation and ROC-analyzes, we obtained minimally invasive diagnostics markers that show the risk of developing liver fibrosis. For patients with NAFLD these were the levels of HOMA-IR, TNFα/IL-10 and α1-acid glycopeptide content, which are better in quality of the diagnostic model than the traditional Forns index, APRI, FIB-4, AAR. For patients with CHC, these were the protein-bound hydroxyproline (HPp/b) /HPf ratio, phospholipids content, and IL-6, CD4+ levels, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. The following markers were obtained for patients with ALD – TNFα levels, HPp/b and glycosaminoglycans content, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. For patients with TH, these were medium molecular weight peptides content, IL-6/IL-10 ratio and CD4+/CD8+, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. Thus, new minimally invasive markers of fibrosis in patients with chronic diffuse liver diseases have been obtained.

The possibilities of transabdominal sonographic diagnosis of liver and intestinal lesions in comorbid gastroesophageal reflux disease

Introduction. The spread of gastroesophageal reflux disease (GERD), comorbid with non-alcoholic fatty liver disease, requires modification of methods for non-invasive diagnosis of liver steatosis and fibrosis and concomitant gastrointestinal syndromes. Aim. Substantiation of a modified complex outpatient transabdominal sonographic diagnosis of combined lesions of the liver and intestines in comorbid GERD. Materials and methods. 165 outpatients with GERD (mean age 40.4 ± 2.9 years) underwent clinical and laboratory examinations, ultrasound examination (UE) of the gastrointestinal tract (GIT), liver shear wave elastometry (SWE), esophagogastroduodenoscopy, colonoscopy (CS). Results and discussion. In patients with GERD, a pronounced transsyndromic comorbidity was observed. The degrees of steatosis and fibrosis of the liver according to SWE positively correlated with the biochemical indices APRI and FORNS. ST-index of liver steatosis was statistically significantly associated with the presence of esophagitis, bile sludge, gallbladder polyps and thickening of the colon wall according to ultrasound criteria, sigmoiditis according to CS. Steatosis on ultrasound was associated with male sex, increased waist circumference, lactase deficiency and deficiency of cholecalciferol in the blood, the presence of yeast-like fungi in feces. Liver fibrosis according to the FORNS index directly correlated with the volume of HE-reflux, duodenitis and intestinal damage according to the results of ultrasound, and according to the APRI index, it inversely correlated with the concentration of vitamin D3 in the blood. Fibrosis according to the ESP criteria directly correlated with the presence of hiatal hernia, bile sludge, and the volume of HE-refluxate according to ultrasound criteria; with lactase deficiency, as well as esophagitis and colitis on endoscopic signs. Conclusions. To identify steatosis and liver fibrosis, the SWE methodology can be considered priority, and serum panels of biomarkers – alternative. Ultrasound of the gastrointestinal tract and SWE allow you to identify the degree of steatosis and fibrosis of the liver, the pathology of the esophagus, colon and the biliary system.

Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B.

Objectives We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients. Methods A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis. Results We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80–0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79–0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10–17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3. Conclusion Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.

Non-invasive Liver Fibrosis Scores Are Associated With Recurrence of Postoperative Chronic Subdural Hematoma.

ObjectiveAlthough liver diseases have already been identified as a risk factor for increased recurrence and mortality in patients with chronic subdural hematoma (CSDH), the association between subclinical liver disease, specifically liver fibrosis (LF), and CSDH remains unknown. In the present study, we aimed to investigate the association between the LF scores and CSDH recurrence.MethodsWe retrospectively analyzed consecutive patients with CSDH who underwent burr-hole irrigation in the First Affiliated Hospital of Wenzhou Medical University between January 2015 and December 2018. The clinical data were collected, and the LF scores were calculated including aspartate aminotransferase–platelet ratio index (APRI), fibrosis-4 (FIB-4), and Forns index. Multivariable logistic regression analysis was applied to identify the association between the LF scores and CSDH recurrence, and Cox regression model and Fine–Gray competing risks model were performed to calculate hazard ratios (HRs) for CSDH recurrence based on time-to-event outcomes. The C-statistic, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI) evaluated the additive value of the LF scores to predict the recurrence of CSDH.ResultsA total of 419 patients with CSDH were included, hematoma recurrence was observed in 62 patients (14.80%) within 1 year after surgery. The LF scores were significantly higher in those who recurred, whereas the standard hepatic assays were mostly normal. The patients were assigned to groups of high and low LF scores based on the validated cut-offs; compared with the subjects with low scores, those with high score levels had significantly higher recurrence rates. After adjusting for potential confounders, the LF scores were independently associated with CSDH recurrence, multivariable-adjusted HRs (95% CI) for those with higher levels of APRI, FIB-4, and Forns score were 4.32 (1.37–13.60), 2.56 (1.20–5.43), and 2.02 (1.07–3.79) for the recurrence of CSDH, respectively. Moreover, adding the APRI to the conventional model improved the C-statistic from 0.731 to 0.763, with an NRI and IDI of 7.50 and 1.35%, respectively. Two further commonly-used LF score indices (FIB-4 score and Forns index) yielded comparable results.ConclusionsThe data from this study first indicated that the high LF scores were significantly associated with the recurrence of CSDH and that careful follow-up in these patients may be needed.