FIB-4 Index Research Articles

Chronic liver disease questionnaire to manage patients with chronic liver diseases.

Although patients with chronic liver disease (CLD) usually show few symptoms, they exhibit decreased health-related QOL (HRQOL) with occurrence complications including hepatocellular carcinoma (HCC). Health-related QOL is an important indicator in the management of CLD. The Chronic Liver Disease Questionnaire (CLDQ) was established as a tool for assessment of HRQOL. In this study, we evaluate its usefulness for the management of daily clinical practice. Patients (N=190, median age 70years old) treated between 2016 and 2019 were registered and prospectively followed-up with annual CLDQ. Associations of liver function and development of factors for admission or death were evaluated. Of the 190 patients registered, median age 70years old, 140 were Child-A, 121 were Fib-4 index >2.67 and showed 80 HCC. All 6 domains including Systemic Symptoms (SS) were negatively correlated with Child-Pugh score more than with albumin-bilirubin score and Fib-4 index. A hundred four admission events and 49 deaths were found during observation period, and median event-free survival was 34.3months. Treatment for HCC was the most frequent cause of admission, and 37 liver-related deaths were found. Systemic Symptoms score 2years after registration was decreased in both HCC- and non-HCC cohort. Systemic Symptoms decreased and SS<4 might be predictive for event occurrence. CLDQ is useful to assess HRQOL in patients with CLD and is well correlated with liver function especially Child-Pugh. Chronic Liver Disease Questionnaire might be useful to predict the prognosis of CLD and can be a tool of management in clinical practice.

Distribution of FIB-4 index in the general population: analysis of 75,666 residents who underwent health checkups

BackgroundFatty liver is frequently found in a general population, and it is critical to detect advanced fibrosis. FIB-4 index is considered a useful marker for evaluating liver fibrosis but the distribution of FIB-4 index in the general population remains unknown.MethodsThis cross-sectional study included residents who underwent ultrasonography at health checkups in Hiroshima or Iwate prefectures. The distribution of FIB-4 index in the total study population (N = 75,666) as well as in non-alcoholic fatty liver disease (NAFLD) populations (N = 17,968) and non-drinkers without fatty liver populations (N = 47,222) was evaluated. The distribution of aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels was also evaluated.ResultsThe mean FIB-4 index in the total study population was 1.20 ± 0.63. FIB-4 index ≥ 2.67, which indicates a high risk of liver fibrosis, was found in 16.4% of those aged ≥ 70 years. In the NAFLD population, 58.1% of those in their 60 s and 88.1% of those ≥ 70 years met the criteria for referral to hepatologists by using the recommended FIB-4 index cutoff value (≥ 1.3). The mean FIB-4 index in the NAFLD population (1.12 ± 0.58) was significantly lower than in the non-drinkers without fatty liver (1.23 ± 0.63, p < 0.0001). The non-drinkers without fatty liver tended to have higher AST relative to ALT levels (60.0% with AST/ALT > 1.0), whereas the results in the NAFLD population were opposite (14.8% with AST/ALT > 1.0). AST > ALT resulted in a higher FIB-4 index in non-drinkers without fatty liver due to the nature of FIB-4 index formula.ConclusionsThe cutoff value of FIB-4 index (≥ 1.3) for triaging the elderly people with fatty liver for referral to hepatologists should be reconsidered to avoid over-referral. Due to the impact of age and characteristics of AST/ALT ratios, there is no prospect of using FIB-4 index for primary screening for liver fibrosis in a general population of unknown presence or absence of liver disease, even though it can be easily calculated using routine clinical indices. It is desired to develop a non-invasive method for picking up cases with advanced fibrosis latent in the general population.

Gadoxetic acid-enhanced magnetic resonance imaging predicts hyperbilirubinemia induced by glecaprevir during hepatitis C virus treatment

Glecaprevir is a substrate for organic anion-transporting polypeptide (OATP) 1B1/1B3, which transports bilirubin. Hyperbilirubinemia is an adverse event during anti-hepatitis C virus treatment with glecaprevir and pibrentasvir. Gadoxetic acid is also transported by OATP1B1/1B3, and we aimed to evaluate whether gadoxetic acid-enhanced magnetic resonance (MR) imaging was associated with glecaprevir trough concentrations (Ctrough). We further determined whether this was predictive of hyperbilirubinemia development in a cohort of 33 patients. The contrast enhancement index (CEI), a measure of hepatic enhancement effect on the hepatobiliary image, was assessed. Glecaprevir Ctrough was determined 7 days after administration. Five of the 33 patients (15%) developed Common Terminology Criteria for Adverse Events grade ≥ 2 hyperbilirubinemia. We found a negative relationship between CEI and Ctrough (r = − 0.726, p < 0.001). The partial correlation coefficient between CEI and Ctrough was − 0.654 (p < 0.001), while excluding the effects of albumin, FIB-4 index, and indirect bilirubin at baseline. The Ctrough was significantly higher in patients with hyperbilirubinemia than in those without (p = 0.008). In multivariate analysis, CEI ≤ 1.71 was an independent factor influencing the development of hyperbilirubinemia (p = 0.046). Our findings indicate that gadoxetic acid MR imaging can help predict glecaprevir concentration and development of hyperbilirubinemia.

Prognostic Values of Inflammation-Based Scores and Fibrosis Markers in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

Background: Inflammation is a key feature shaping the microenvironment of hepatocellular carcinoma (HCC), and liver fibrosis is associated with the prognosis of patients with HCC. In this study, we investigated whether baseline inflammation-based scores and serum fibrosis markers can help in predicting the prognosis of HCC patients treated with transarterial chemoembolization (TACE). Methods: A total of 605 consecutive patients with HCC treated by TACE were included. The systemic immune-inflammation index (SII), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), FIB-4 index, and aspartate aminotransferase-to-platelet ratio index (APRI) were analyzed regarding their associations with disease progression and survival. Results: All tested inflammation-based scores and fibrosis markers were significantly associated with tumor progression and overall survival in the univariate analyses. In the multivariate analysis, NLR (hazard ratio [HR], 1.06; p = 0.007) and FIB-4 (HR = 1.02, p = 0.008) were independent risk factors for disease progression, along with α-fetoprotein (AFP) levels, maximum tumor size and number, and presence of vascular invasion. Furthermore, NLR (HR, 1.09; p < 0.001) and FIB-4 (HR, 1.02; p = 0.02) were independent prognostic factors for survival. Conclusions: High baseline NLR and FIB-4 levels might help the prediction of disease progression and death in patients with HCC after TACE.

Prevalence and clinical-epidemiologic characteristics of a Mexican population with metabolic (dysfunction) associated fatty liver disease: An open population study

Introduction and aimsThe risk factors for fatty liver disease are frequent in the Mexican population and the available studies appear to underestimate its prevalence. Our aims were to know the prevalence of metabolic (dysfunction) associated fatty liver disease (MAFLD) in an open population and determine the clinical and sociodemographic characteristics, nutritional status, physical activity level, and prevalence of metabolic syndrome, in the affected population. Materials and methodsVolunteers from the general public were invited to take part in the study. Three separate questionnaires were applied to 1) determine the sociodemographic characteristics and health status of the participants, 2) evaluate the quality of their diet, and 3) to evaluate their level of physical activity. The participants underwent somatometry, laboratory tests, liver ultrasound, and FIB-4 index determination, and transition elastography (FibroScan®) was carried out on all subjects with signs suggestive of liver fibrosis that agreed to undergo the procedure. The statistical analysis was carried out using SPSS for Windows, version 22, software. ResultsA total of 585 volunteers were studied, resulting in a prevalence of MAFLD of 41.3%, a predominance of men above 50 years of age, poor dietary habits, and sedentary lifestyle. Male sex, obesity, metabolic syndrome, and elevated ALT were risk factors for the disease and 40% of those affected had advanced fibrosis. ConclusionsThe prevalence of MAFLD in our population is one of the highest in the world. The conditioning factors of the disease can be modified. Therefore, public policies that redirect the current trend are required.

Shorter pruritus period and milder disease stage are associated with response to nalfurafine hydrochloride in patients with chronic liver disease

Nalfurafine hydrochloride, a selective κ-opioid receptor agonist has been approved for pruritus in patients with chronic liver disease. However, not all patients respond to nalfurafine hydrochloride. The aim of this study was to clarify the efficacy of nalfurafine hydrochloride. The subjects were patients with chronic liver disease complicated by pruritus who were treated with nalfurafine hydrochloride between May, 2015, and May, 2021. The degree of pruritus was evaluated based on the Visual Analog Scale (VAS) score and the Kawashima’s pruritus score. Nalfurafine hydrochloride 2.5 μg was orally administered once a day for 12 weeks. A decrease in the VAS score of ≥ 25 mm or the Kawashima’s pruritus score of ≥ 1 scores was designated as relevant response. The former of ≥ 50 mm or the latter of ≥ 2 scores as remarkable response. The 326 patients who were evaluated the efficacy at 12 weeks. The median time suffering from pruritus to administration of nalfurafine hydrochloride was 4 months. The median VAS score improved from 70.0 mm before administration to 40.0 and 30.0 mm at 4 and 12 weeks of treatment, respectively. On multivariate analysis, shorter itching period and lower FIB-4 index value were extracted as the independent factors related to remarkable responder. On multivariate analysis, shorter itching period was extracted as the only independent factor related to relevant responder. In conclusion, this study suggested nalfurafine hydrochloride treatment markedly improves pruritus in patients with chronic liver disease. A short pruritus period and less-advanced fibrosis were associated with response to nalfurafine hydrochloride.

Non-invasive biomarkers, FIB-4 and APRI index, as predictors for prognosis of hepatocellular carcinoma patients after curative hepatectomy

Non-invasive biomarkers, FIB-4 and APRI index, as predictors for prognosis of hepatocellular carcinoma patients after curative hepatectomy

Clinical Differences and Non-Alcoholic Fatty Liver Disease-Related Factors of Lean and Non-Lean Patients with Metabolic Syndrome.

This study investigated differences in the clinical data and prevalence of lean and non-lean patients with non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). Data on patients with MetS who had results of ultrasonography or transient elastography were collected from a Thai university hospital database. Patients with exclusion criteria for NAFLD diagnosis were excluded. Patients’ clinical characteristic and the performances of three non-invasive scoring systems (fatty liver index [FLI], fibrosis-4 [FIB-4] index, and NAFLD fibrosis score [NFS]) were evaluated. The 743 subjects were classified into two groups: lean MetS (131 patients) and non-lean MetS (612 patients). The NAFLD prevalence in the non-lean group (62.6%) was higher than that in the lean group (31.3%). The age-adjusted odds ratio was 3.43. Advanced fibrosis was detected in 7.6% of lean patients and 10.8% of non-lean patients. FLI was not sensitive enough to detect NAFLD in the lean group at a high cutoff, but it performed acceptably at a low cutoff. FIB-4 performed better than NFS in determining advanced fibrosis. NAFLD was more common in non-lean than lean patients. Lean patients with MetS had a relatively higher risk of NAFLD than the general population. FLI and FIB-4 index performed acceptably in both groups.

An elevated FIB-4 score is associated with an increased incidence of liver cancer: A longitudinal analysis among 248,224 outpatients in Germany

BackgroundNon-invasive tests such as the FIB-4 index (calculated on the basis of patients’ age, AST/ALT levels and platelet count) have been recommended by different guidelines to rule out advanced fibrosis and stratify the risk of liver-related outcomes in patients with chronic liver diseases. An elevated FIB-4 index ≥1.3 is an independent predictor for liver cancer development among patients with NAFLD. However, the predictive value of an elevated FIB-4 index regarding (liver) cancer development among the general population is unknown. MethodsUsing the Disease Analyzer database (IQVIA) which compiles diagnoses, laboratory values, and basic medical and demographic data for over 7.5 million patients followed in general practices in Germany, we identified 248,224 patients with available lab values for FIB-4 index calculation between 2005 and 2019. Patients with an average FIB-4 index of <1.3 were matched 1:1 to patients with a FIB-4 index of ≥1.3 by age and sex. ResultsWithin 10 years of the index date, the cumulative incidence of liver cancer was significantly higher in patients with a FIB-4 index ≥1.3 (0.25% versus 0.04%, p < 0.001). In a multivariate Cox-regression analysis, this association was found to be higher in patients with pre-existing liver disease (hazard ratio, HR: 10.54 versus 3.79). The risk of liver cancer development was most pronounced among men (HR: 9.40, p < 0.001) and patients ≤50 years of age (HR: 16.36, p < 0.001). A persistently high or increasing FIB-4 index over time was a strong predictor for liver cancer. Notably, the cumulative incidence of cancer in general was comparable among patients with a low/high FIB-4 index (15.7% versus 16.6%; p = 0.060). ConclusionOur data support the use of the FIB-4 index to estimate the risk of liver cancer development even in unselected patients without pre-existing liver disease. By contrast, the index does not appear to have any predictive value for other tumour sites.

An Elevated FIB-4 Score Is Associated with an Increased Incidence of Depression among Outpatients in Germany.

Background: Liver disease and depression are known to be closely associated. Non-invasive tests (NIT), such as the FIB-4 score, have been recommended by different guidelines to rule out advanced fibrosis and to stratify the risk of liver-related outcomes in patients with chronic liver diseases. However, the predictive value of an elevated FIB-4 score regarding the development of depression and/or anxiety disorders among the general population is unknown. Methods: By using the Disease Analyzer database (IQVIA), which compiles diagnoses and laboratory values as well as basic medical and demographic data of patients followed in general practices in Germany, we identified 370,756 patients with available lab values for FIB-4 score calculation between 2005 and 2019. Patients with an FIB-4 score < 2 were matched 1:1 to patients with an FIB-4 index ≥ 2 by age, sex and yearly consultation frequency. Results: In regression analysis, the incidence rate ratio (IRR) of depression was significantly higher among patients with an FIB-4 score ≥ 2.0 compared to patients with a lower FIB-4 score <2.0 (IRR: 1.12, p < 0.001). This association was significant for both female (IRR: 1.10, p = 0.004) and male (IRR: 1.15, p < 0.001) patients and strongest in the age groups ≤50 years (IRR: 1.42, p < 0.001) and 51-60 years (IRR: 1.34, p < 0.001). There was no significant association between an elevated FIB-4 score ≥ 2.0 and the incidence of depression among patients aged 60 years and older. There was no significant increase in the IRR of anxiety disorders for patients with high or low FIB-4 scores. Conclusion: Our study suggests a previously unknown association between an elevated FIB-4 score and an increased incidence of depression. This finding suggests that the FIB-4 score is not only a valuable tool for the prediction of liver-specific endpoints but also may be of relevance for the prediction of extrahepatic comorbidities, which in turn may argue for clinical screening programs in patients with an elevated FIB-4.

Prediction of hepatocellular carcinoma in Hepatitis C patients with advanced fibrosis after sustained virologic response

Background & AimsPrediction of hepatocellular carcinoma (HCC) occurrence in patients with chronic hepatitis C (HCV) who achieved a sustained virological response (SVR) after direct acting antivirals (DAAs) remains challenging. MethodsAmong HCC-free HCV patients with advanced fibrosis enrolled in the ANRS CO22 HEPATHER cohort who achieved SVR 12 weeks after treatment with DAAs, HCC predictive models were developed using Cox multivariable regression. The derived score was externally validated in a large Egyptian cohort. Our main outcome was the HCC-free survival. ResultsDuring follow-up (median 3.05 years), 153 out of 3531 patients developed a HCC. Main variables associated with HCC occurrence were: male gender, HCV genotype 3, esophageal varices, albumin < 40 g/L, total bilirubin >11 µmol/L and hypercholesterolemia before DAA initiation, together with age > 58 years, FIB-4 index ≥3.25 evaluated at SVR. A score was established allowing the stratification of patients by high (score ≥ 12/22), intermediate (7 ≤ score <12) and low risk of HCC (score < 7/22) with 3-yrs HCC incidence of 18.96%, 5.50% and 1.65%, respectively. The integrated time‐dependent area under the ROC curve (i-AUC) was 0.76 in our patients and 0.61 in the validation cohort. ConclusionThe externally validated HEPATHER HCC score has good short-term predictive performance in HCV- patients who achieved SVR12 after DAAs allowing to identify high-risk patients in whom HCC screening may be cost-effective and low-risk patients in whom HCC screening may be superfluous in the first 3 years after SVR.

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.

Hepatitis B core-related antigen serum levels are associated with significant liver fibrosis in treatment-naive chronic HBV infection patients.

Several hepatitis B virus (HBV) serum markers have been identified as risk factors for liver fibrosis in patients with chronic HBV infection, and several noninvasive fibrosis tests based on serum indexes are now used to identify the severity of liver fibrosis. We aimed to identify the relationship between hepatitis B core-related antigen (HBcrAg) serum levels and liver fibrosis in treatment-naive chronic HBV infection patients. A total of 246 treatment-naive chronic HBV infection patients were enrolled in this study. All of the patients underwent liver biopsies at baseline. Using the METAVIR fibrosis stages, there were 15, 140, 50, 26 and 15 patients in the F0, F1, F2, F3 and F4stages (METAVIR scoring system), respectively. The biochemical, serological and virological parameters were measured using standard laboratory procedures. The HBcrAg serum levels of the patients were examined via ELISA. HBcrAg serum levels of F2, F3 and F4stage patients were significantly higher than those of nonsignificant liver fibrosis patients (METAVIR F0-F1), but there were no significant differences among F2, F3 and F4stage patients. Serum HBcrAg (OR, 2.18; 95% confidence interval [CI], 1.51-3.16), albumin (ALB) (OR, 0.60; 95% CI, 0.41-0.87), prothrombin activity (PTA) (OR, 0.58; 95% CI, 0.40-0.83) and platelet (PLT) counts (OR, 0.38; 95% CI, 0.25-0.57) were associated with significant liver fibrosis (METAVIR F2-F4). The serum HBcrAg value enabled the correct identification of patients with significant fibrosis, with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.75-0.88). The APRI, FIB-4 index and ALBI score can identify significant liver fibrosis with an area under the ROC curve of 0.74 (95% CI, 0.66-0.81), 0.73 (95% CI, 0.65-0.80) and 0.63 (95% CI, 0.55-0.72), respectively. Compared with these three indexes, the accuracy rate of diagnosis of significant fibrosis based on HBcrAg was higher than that of the FIB-4 index (p=0.0479) and ALBI score (p=0.0030). HBcrAg, ALB, PTA serum levels and PLT counts were associated with significant liver fibrosis in treatment-naive chronic HBV infection patients. HBcrAg serum levels enabled the correct identification of patients with significant fibrosis (METAVIR F2-F4), and HBcrAg was moreeffective than the FIB-4 index and ALBI score.

Accuracy of noninvasive fibrosis scores in predicting advanced fibrosis in pediatric patients after liver transplantation

Liver biopsy is the gold standard to stage fibrosis in liver disease. Several scoring systems have been studied to predict advanced fibrosis in liver disease. Those scores have not been validated in pediatric liver transplant patients. Evaluate the performance of three fibrosis scores (FSc) in assessing the presence of advanced fibrosis (AF) in children after orthotopic liver transplantation (OLT). Patients < 20 years of age who underwent liver biopsy post-OLT with laboratory values within 1month of the biopsy were included. Fibrosis was determined by an experienced pathologist (F0-4). We defined AF as F3-4. The following FSc were calculated: AST/ALT ratio, APRI, and FIB-4 index. Receiver operating characteristic curve analysis was done to assess the FSc performance in predicting AF. A total of 232 biopsies were analyzed, of those 42 (18.1%) showed AF (F3-4). FIB-4 was significantly higher in patients with AF compared to those without AF [median value of 1.1 [0.7, 3.0] and 0.6 [0.2, 1.4], respectively (p=.02)]; however, FIB-4 had satisfactory accuracy to diagnose AF with significant overlap and AUC of 0.68 (CI 0.56-0.81). Cutoff points of 0.2 and 3.03 were used to rule in and rule out AF, respectively. AST/ALT and APRI were not significantly different between patients with and without AF. Even though FIB-4 had satisfactory accuracy in detecting AF in pediatric transplant patients, noninvasive hepatic FSc developed in adults still performed poorly. Our results highlight the need to develop a reliable pediatric FSc.

Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, and Regional Amyloid-β and Tau Pathology in Middle-Aged Adults: The Framingham Study.

Liver steatosis and fibrosis are emerging as risk factors for multiple extrahepatic health conditions; however, their relationship with Alzheimer's disease pathology is unclear. To examine whether non-alcoholic fatty liver disease (NAFLD) and FIB-4, a non-invasive index of advanced fibrosis, are associated with brain amyloid-β (Aβ) and tau pathology. The study sample included Framingham Study participants from the Offspring and Third generation cohorts who attended exams 9 (2011-2014) and 2 (2008-2011), respectively. Participants underwent 11C-Pittsburgh Compound-B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging and abdomen computed tomography, or had information on all components of the FIB-4 index. Linear regression models were used to assess the relationship of NAFLD and FIB-4 with regional tau and Aβ, adjusting for potential confounders and multiple comparisons. Of the subsample with NAFLD information (N = 169; mean age 52±9 y; 57% males), 57 (34%) had NAFLD. Of the subsample with information on liver fibrosis (N = 177; mean age 50±10 y; 51% males), 34 (19%) had advanced fibrosis (FIB-4 > 1.3). Prevalent NAFLD was not associated with Aβ or tau PET. However, FIB-4 index was significantly associated with increased rhinal tau (β= 1.03±0.33, p = 0.002). Among individuals with prevalent NAFLD, FIB-4 was related to inferior temporal, parahippocampal gyrus, entorhinal and rhinal tau (β= 2.01±0.47, p < 0.001; β= 1.60±0.53, p = 0.007, and β= 1.59±0.47, p = 0.003 and β= 1.60±0.42, p = 0.001, respectively) and to Aβ deposition overall and in the inferior temporal and parahippocampal regions (β= 1.93±0.47, p < 0.001; β= 1.59±0.38, p < 0.001, and β= 1.52±0.54, p = 0.008, respectively). This study suggests a possible association between liver fibrosis and early Alzheimer's disease pathology, independently of cardio-metabolic risk factors.

Noninvasive fibrosis tools in NAFLD: validation of APRI, BARD, FIB-4, NAFLD fibrosis score, and Hepamet fibrosis score in a Portuguese population

ABSTRACT Objectives The burden of nonalcoholic fatty liver disease (NAFLD) is increasing, with an estimated prevalence in Europe of 20–30%. Although most patients present with simple steatosis, some progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Definite diagnosis and staging require liver biopsy, which is not feasible given the high prevalence of NAFLD. As such, several noninvasive tools have been formulated. However, to date, none have been validated in the Portuguese population. The aim of this study was to determine the diagnostic accuracy of the aspartate aminotransferase to platelet ratio (APRI), the BMI, AST/ALT ratio and Diabetes (BARD), the FIB-4 Index (FIB-4), the Hepamet fibrosis score (HFS), and the NAFLD fibrosis score (NFS) in a Portuguese population. Methods A retrospective review of liver biopsies from two hospital centers was performed. Patients with NAFLD and no decompensated cirrhosis, liver cancer, or terminal illness were included. APRI, BARD, FIB-4, HFS, and NFS were calculated for each patient. Results A total of 121 individuals were included, of which 21.5% had advanced fibrosis (F ≥ 3). There was a moderate or high correlation between most tools. The negative predictive factor (NPV) and area under receiver operating curve (AUROC) were 89.9% and 0.80 for APRI, 91.8% and 0.84 for BARD, 95.7% and 0.88 for FIB-4, 96.4% and 0.88 for HFS, and 93.0% and 0.86 for NFS, respectively. Conclusion The tools analyzed had excellent performance (AUROC ≥ 0.80) and were adequate for ruling out advanced fibrosis (NPV ≥ 89.9%) in a Portuguese population. As such, they are adequate for use in clinical practice or as a part of referral and follow-up programs wherever this population is treated. Abbreviations APRI – aspartate aminotransferase to platelet ratio, ALT – alanine aminotransferase, AST – aspartate aminotransferase, BARD – BMI, AST/ALT ratio and Diabetes, BMI – body mass index, FIB-4 – FIB-4 index, HCC – hepatocellular carcinoma, HFS – Hepamet fibrosis score, HOMA-IR – homeostatic model assessment for insulin resistance, IQR – interquartile range, MAFLD – metabolic associated fatty liver disease, NAFLD – nonalcoholic fatty liver disease, NASH – nonalcoholic steatohepatitis, NFS – NAFLD fibrosis score, OMIC – genomics, transcriptomics, proteomics, and metabolomics, T2DM – type 2 diabetes mellitus

Noninvasive, Blood-Based Biomarkers as Screening Tools for Hepatic Fibrosis in People With Type 2 Diabetes.

Nonalcoholic fatty liver disease (NAFLD) is dramatically increasing in parallel with the pandemic of type 2 diabetes. Here, the authors aimed to assess the performance of the most commonly used noninvasive, blood-based biomarkers for liver fibrosis (FibroTest, NAFLD fibrosis score, BARD score, and FIB-4 Index) in subjects with type 2 diabetes. Liver stiffness measurement was estimated by two-dimensional shear wave elastography. Finally, the authors assessed the diagnostic role of ActiTest and NashTest 2 in liver fibrosis in the examined population.

JCL Roundtable. Obesity, Diabetes, and Liver Disease in Relation to Cardiovascular Risk

Metabolic risk for cardiovascular and other systems includes much more than just LDL cholesterol. This JCL Roundtable brings together 3 experts to address new opportunities to reduce the risks posed by obesity, diabetes, and fatty liver disease. Successful nutritional approaches to weight loss are diverse and need to be matched with individual preferences. Topiramate plus extended-release phentermine has been shown to promote meaningful weight loss in randomized trials, but the patented drug combination is expensive. Clinical experience suggests that generic topiramate and phentermine may also be effective. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown favorable tolerability and efficacy for cardiovascular disease in randomized trials, an achievement without precedent among earlier diabetes medications. These 2 drug classes differ in their effects. GLP-1 RAs decrease atherosclerotic cardiovascular events and also decrease hemoglobin A1c, body weight, blood pressure, and possibly diabetic renal disease. SGLT2 inhibitors are effective in reducing heart failure events even among nondiabetic patients. They also decrease progression of diabetic renal disease. The presence of nonalcoholic fatty liver disease signifies risk for atherosclerotic cardiovascular disease as well as cirrhosis and serious hepatic decompensation, including hepatocellular carcinoma. The key to identifying cirrhosis risk is to assess pre-emptively liver fibrosis, which can be predicted initially with blood test risk scores (e.g., FIB-4 index) and more definitively by transient elastography and other imaging techniques and/or liver biopsy. Some medications approved for the treatment of type 2 diabetes may reduce liver fat (SGLT2 inhibitors, insulin) or even reverse steatohepatitis in paired liver biopsy studies (GLP-1 RAs or pioglitazone) Overall the field of preventive metabolic medicine is expanding. Clinical lipidologists should become familiar with recent advances.

Assessment of Liver Fibrosis Using Non-invasive Screening Tools in Individuals With Diabetes Mellitus and Metabolic Syndrome.

Introduction: Despite the rising prevalence of liver fibrosis and its potentially life-threatening complications, there are currently no recommendations or guidelines to screen individuals with diabetes mellitus (DM) or high body mass index (BMI) for non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). This is mainly due to the uncertain performance and feasibility of presently available screening tools. This research was carried out to assess the diagnostic accuracy of non-invasive screening tools in predicting liver fibrosis in individuals with DM and metabolic syndrome.Methods: For this study, 140 patients with DM and metabolic syndrome were identified between March 2020 and October 2021. Liver stiffness measurement by point shear wave elastography was considered the gold standard in our study. Five non-invasive scores such as aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, aspartate aminotransferase to platelet ratio index (APRI) score, fibrosis-4 (FIB-4) index, BARD score, and NAFLD fibrosis score were determined in all of the participants. Using receiver operator characteristic (ROC) curve analysis, sensitivity, specificity, both negative predictive value (NPV) and positive predictive value (PPV) were calculated for each of these scores. The area under the ROC curve (AUROC) was used to calculate the diagnostic accuracy of these scores.Results: Of the 507 individuals screened, 140 were enrolled for the study. Among the 140 participants, 83 were male (59.29%), 30 (21.43%) had liver fibrosis as per liver stiffness measurement by point shear wave elastography, and 110 (78.57%) did not have fibrosis. The mean age and mean BMI were 54.53±12.42 and 27.37±2.73 respectively in the ‘Fibrosis’ group and 56.20 ±11.76 and 27.10±4.22 in the ‘No fibrosis’ group. The major finding of our study was that all these scores had relatively high NPV (>85 %) for predicting liver fibrosis in our cohort. The AST/ALT ratio had the highest NPV (90.28%) followed by APRI Score (88.94%). The AUROC for FIB-4 Score, NAFLD-fibrosis score, APRI score, AST/ALT ratio, and BARDd score were 0.6669, 0.657, 0.655, 0.637 and 0.599, respectively. The FIB-4 index (p=0.005) had the highest AUROC, followed by the NAFLD-fibrosis score (p =0.009). But all the scores had relatively low specificity (<60 %), PPV (<35 %), and accuracy (<63 %).Conclusion: The FIB-4 index and NAFLD-fibrosis score can be used reliably to exclude liver fibrosis in individuals with DM and metabolic syndrome in the Indian population, but may not be useful in accurately diagnosing liver fibrosis. Utilization of these non-invasive and cost-effective screening tools in routine practice may have promising results in predicting liver fibrosis in ‘at risk’ populations.

Prevalencia y características clínico-epidemiológicas de una población mexicana con enfermedad del hígado graso asociada a disfunción metabólica: un estudio en población abierta

Introduction and aimsThe risk factors for fatty liver disease are frequent in the Mexican population and the available studies appear to underestimate its prevalence. Our aims were to know the prevalence of metabolic (dysfunction) associated fatty liver disease (MAFLD) in an open population and determine the clinical and sociodemographic characteristics, nutritional status, physical activity level, and prevalence of metabolic syndrome, in the affected population. Material and methodsVolunteers from the general public were invited to take part in the study. Three separate questionnaires were applied to determine the sociodemographic characteristics and health status of the participants, evaluate the quality of their diet, and to evaluate their level of physical activity. The participants underwent somatometry, laboratory tests, liver ultrasound, and FIB-4 index determination, and transition elastography (Fibroscan®) was carried out on all subjects with signs suggestive of liver fibrosis that agreed to undergo the procedure. The statistical analysis was carried out using SPSS® for Windows®, version 22, software. ResultsA total of 585 volunteers were studied, resulting in a prevalence of MAFLD of 41.3%, a predominance of men above 50 years of age, poor dietary habits, and sedentary lifestyle. Male sex, obesity, metabolic syndrome, and elevated ALT were risk factors for the disease and 40% of those affected had advanced fibrosis. ConclusionsThe prevalence of MAFLD in our population is one of the highest in the world. The conditioning factors of the disease can be modified. Therefore, public policies that redirect the current trend are required.