FibroTest Research Articles

Increased serum fibroblast growth factor 23 predicts mortality in people with HIV/HCV coinfection.

People with HIV and hepatitis C virus (HCV) coinfection experience excess mortality due to multiple causes. Identification of biomarkers associated with mortality beyond that attributable to liver fibrosis may be relevant for prognostication. Fibroblast growth factor 23 (FGF23), a phosphotropic hormone, predicts adverse outcomes in several chronic conditions. We aimed to investigate whether elevated FGF23 predicts all-cause mortality in patients with HIV/HCV coinfection: Methods: We included patients with HIV/HCV coinfection from the Canadian Coinfection Cohort with available serum FGF23, fibrosis biomarker fibrosis-4 (FIB-4), and at least 1 year follow up. Elevated FGF23 and advanced liver fibrosis were defined as FGF23>241 reference unit/mL and FIB-4>3.25, respectively. All-cause mortality was analyzed using survival analysis. The effect of advanced liver fibrosis as a mediator on mortality was estimated by mediation analysis. 321 patients were included (24% with elevated FGF23, 19% with advanced liver fibrosis). During a mean follow-up period of 8.4 years, 34% of the cohort died. The incidence rate of all-cause mortality was higher in patients with elevated FGF23 (66.1 per 1000 person-years (PY), 95% CI 45.8-92.3) relative to patients without elevated FGF23 (37.5 per 1000 PY, 95% CI 29.6-46.9). After adjusting for potential confounders, elevated FGF23 was associated with significant direct and indirect effects (mediated through advanced liver fibrosis) on all-cause mortality, with 57% of deaths not mediated via advanced fibrosis. In patients with HIV/HCV coinfection, FGF23 may be used as prognostic biomarker for risk stratification accounting also for death causes other than those attributable to liver fibrosis.

Prevalence of Nonalcoholic Fatty Liver Disease at a Tertiary Care Center in Saudi Arabia.

To determine the prevalence of nonalcoholic fatty liver disease (NAFLD) in patients who received abdominal imaging and to assess the clinical and metabolic characteristics of NAFLD. This is a retrospective study of 500 family medicine patients (aged 18 years and older) who completed abdominal imaging at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, from January 2016 through June 2020. The patients enrolled had a mean age of 49.41 ± 14.80 years, with 300 females and 349 of Saudi nationality. The mean body mass index (BMI) was 29.43 ± 6.61 kg/m2, while 373 of the enrolled subjects were either overweight or obese. Half of our patients had some form of fatty liver in the imaging results. Regarding chronic medical conditions, 33.4%, 31.4%, and 29.4% had a history of hypertension, type 2 diabetes mellitus (DM2), and dyslipidemia, respectively. The mean Fibrosis-4 (FIB-4) index was 0.94 ± 0.72. Body mass index was higher among fatty liver patients (p = 0.001). Hypertension, coronary artery disease, dyslipidemia, and DM2 were more common in the fatty liver group. Our findings reiterate the significance of obesity and the coexistence of cardiovascular risk factors in NAFLD. Further studies are needed to corroborate and expand our findings, enabling more refined strategies for the prevention, risk prediction, early detection, and management of NAFLD.

Fibrosis-4 index is closely associated with clinical outcomes in acute cardioembolic stroke patients with nonvalvular atrial fibrillation.

Liver cirrhosis is a confirmed risk factor for poor prognosis of stroke; however, the contribution of clinically inapparent liver fibrosis to cardioembolic stroke (CES) and its outcomes are poorly understood. This study aimed to investigate the associations between liver fibrosis-measured by the Fibrosis-4 (FIB-4) score-and stroke severity and short-term clinical outcomes of patients with acute CES due to nonvalvular atrial fibrillation (NVAF). A total of 522 patients were followed for a median of 90days. We calculated the FIB-4 score and defined liver fibrosis as follows: likely advanced fibrosis (FIB-4 > 3.25), indeterminate advanced fibrosis (FIB-4, 1.45-3.25), and unlikely advanced fibrosis (FIB-4 < 1.45). Logistic regression analysis and Cox regression analysis were used to investigate the relations between the FIB-4 score and stroke severity, major disability at discharge, and all-cause mortality. Among these 522 acute CES patients with NVAF, the mean FIB-4 score (2.28) on admission reflected intermediate fibrosis, whereas liver enzymes were largely normal. In multivariate regression analysis, patients with advanced liver fibrosis were more likely to have a higher risk of severe stroke (OR = 2.21, 95% CI 1.04-3.54), major disability at discharge (OR = 4.59, 95% CI 1.88-11.18), and all-cause mortality (HR = 1.25, 95% CI 1.10-1.56) than their counterparts. Regarding sex, these associations were stronger in males but not significant in females. In patients with acute CES due to NVAF, advanced liver fibrosis is associated with severe stroke, major disability, and all-cause death. Our findings indicate that early screening and management of liver fibrosis may decrease stroke severity and risk of death in patients with NVAF, especially for male patients. Consequently, FIB-4 > 3.25 of male patients should receive ultrasound elastography to further determine the degree of liver fibrosis.

The effect of direct-acting antivirals (DAA) on confirmed noninvasive fibrous parameters in chronic hepatitis C patients

Aims: Chronic hepatitis C (CHC) is an important public health problem in terms of the number of people it affects worldwide and the diseases it causes. The high sustained virological response (SVR) rates achieved by the use of direct-acting antiviral (DAA) drugs in the recent period have shown that a new era has begun in this disease. It was aimed to evaluate the effect of DAAs on confirmed noninvasive fibrous parameters together with their effectiveness.&#x0D; Methods: 75 patients who were started on DAA treatment for CHC were included in the study. In addition, laboratory parameters values at the beginning of the treatment, 12 and 24 weeks after the end of the treatment, hepatitis C virus ribonucleic acid (HCV RNA) results and Aminotransferase-to-Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) scores were compared.&#x0D; Results: The most common comorbidity in patients is hypertension (HT), and the most common source of transmission is surgical operations. Genotype 1b was the dominant genotype. The SVR rates of all patients 12 and 24 weeks after the end of treatment were 100%. The APRI and FIB-4 scores of the patients decreased significantly at the 12th and 24th weeks at the end of the treatment compared to the beginning of the treatment.&#x0D; Conclusion: The confirmed noninvasive fibrous parameters used in the treatment of CHC are useful in evaluating the results of the treatments applied.

Elevated liver fibrosis-4 index predicts recurrence after catheter ablation for atrial fibrillation in patients with heart failure.

The fibrosis-4 (FIB-4) index is a noninvasive scoring system that is used to assess the progression of liver fibrosis. This study aimed to assess whether the FIB-4 index is associated with recurrent atrial fibrillation (AF) after catheter ablation in patients with and without heart failure (HF). We included 1,184 patients who underwent initial AF catheter ablation between 2016 and 2021. The patients were classified into low-risk (< 1.3), intermediate-risk (1.3-2.67), and high-risk (> 2.67) groups based on their FIB-4 indices at baseline. The patients were divided into HF (n = 552) and non-HF groups (n = 632); the HF group was further divided into paroxysmal AF (PAF) and non-PAF groups. AF recurrence after catheter ablation was then compared among the groups. In the non-HF group, no significant differences in recurrence after ablation were observed between the low-(n = 219), intermediate-(n = 364), and high-risk (n = 49) groups. In contrast, in the HF group, the intermediate-(n = 341) and high-risk (n = 112) groups had significantly higher recurrence rates than the low-risk group (n = 99) (log-rank test, p = 0.005). This association remained significant after multivariate analysis (hazard ratio [HR]:1.374; p = 0.027). The FIB-4 index increased incrementally as the brain natriuretic peptide levels and severity of tricuspid regurgitation increased. The FIB-4 index was an independent predictor of recurrence in the non-PAF HF group (HR:1.498; p = 0.007) but not in the PAF group. The FIB-4 index may be a useful predictor of AF recurrence after catheter ablation in patients with HF, particularly in those with non-PAF.

Combi-Elasto Evaluation of the Degree of Liver Fibrosis in Children with Cholestatic Liver Disease.

Cholestatic liver disease is a common liver disease in infants and young children. Liver fibrosis is a key factor affecting the prognosis, and liver transplantation is the only treatment option for liver cirrhosis. This study aimed to explore the efficacy of Combi-elasto for diagnosing liver fibrosis in children affected by cholestatic liver disease. A total of 64 children with S1-S4-grade liver fibrosis were enrolled. The general data, routine ultrasound, Combi-elasto, aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score were compared among children with different grades of liver fibrosis, and the efficacy of the above indexes for evaluating the degree of liver fibrosis was reported. There were remarkable differences in liver size, liver echogenicity, Young's modulus (E), fibrosis index (FI), activity index (AI) and FIB-4 score among the groups (all p < 0.05). E and liver echogenicity were the independent impact factors of liver fibrosis. The areas under the curve of E, APRI, FIB-4 score and the combined model (E+ liver echogenicity) in the evaluation of liver fibrosis were 0.84, 0.61, 0.66 and 0.90, respectively. Ultimately, we concluded that CE is an effective method to evaluate liver fibrosis in children with cholestatic liver disease.

Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis.

Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis. Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index >36); elevated transaminases [alanine transaminase (ALT) >33 (males) and >25 IU/L (females)]; and fibrosis-4 (FIB-4) index scores >3.25, >2.67 and >1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma-glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure. ALT, aspartate aminotransferase and gamma-glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB-4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB-4 subgroups by 52% (>3.25), 39% (>2.67) and 24% (>1.30) (p values for interaction = .01, .13 and .03, respectively). Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB-4 scores who were at high risk of developing cardiovascular complications.

PNPLA3 rs738409 Genetic Variant Inversely Correlates with Platelet Count, Thereby Affecting the Performance of Noninvasive Scores of Hepatic Fibrosis.

Noninvasive tests (NITs) including platelets (PLTs) have been proposed to replace hepatic biopsy for the diagnosis of nonalcoholic fatty liver disease (NAFLD), or as more recently redefined, metabolic dysfunction-associated steatotic liver disease (MASLD). There has been reported an inverse correlation between PLTs and progressive MASLD, which is also affected by the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C>G mutation. However, the correlation between low PLTs and PNPLA3 genotype has been poorly investigated. We stratified 1155 biopsy-proven MASLD patients according to PNPLA3 genotype. The hepatic expression of genes involved in megakaryopoiesis was investigated in n = 167 bariatric patients by RNAseq. PLT count progressively decreased according to the number of PNPLA3 at-risk alleles, irrespective of the presence of advanced fibrosis. The hepatic expression of genes involved in PLT biogenesis was associated with the PNPLA3 GG genotype. Finally, the presence of the PNPLA3 homozygosity flattened the accuracy of fibrosis-4 (FIB-4) in discriminating histological fibrosis stages. The PNPLA3 GG genotype may underpower the accuracy of NITs which include PLT count in identifying those patients with potentially reversible stages of fibrosis.

Interactions between Metabolic Syndrome, MASLD, and Arterial Stiffening: A Single-Center Cross-Sectional Study.

Metabolic-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), has emerged as a prominent global cause of chronic liver disease and is increasingly recognized as associated with atherosclerotic vascular illness, consolidating its position along traditional cardiovascular risk factors. Individuals with MASLD exhibit a combination of metabolic syndrome risk factors, carotid atherosclerosis, and increased arterial stiffness, hinting at shared pathogenesis. In this study, we aim to explore liver involvement and arterial stiffness within metabolic syndrome. We enrolled 75 patients (30 male and 45 female) with either liver steatosis on conventional ultrasound, altered liver function tests, or the presence of cardiometabolic risk factors after excluding liver pathology other than MASLD. Clinical evaluation, laboratory measurements, abdominal and carotid ultrasounds, vibration-controlled transient elastography (VCTE, Fibroscan), and assessment with the Arteriograph (Tensiomed) were performed. The 26 patients diagnosed with MetS had significantly higher liver involvement as quantified via the hepatic steatosis index (HSI), Fibrosis-4 (FIB4), aspartate aminotransferase to platelet ratio index (APRI) category, and VCTE measurements, as well as Agile 3+ and Agile 4 scores which use a combination of clinical and laboratory parameters together with results obtained from VCTE to reflect the probability of advanced liver fibrosis or cirrhosis. Patients with MetS also exhibited more pronounced vascular involvement as quantified via arterial stiffness measurements and CIMT (carotid intima-media thickness). We applied a two-step clustering algorithm to enhance our analysis, which gave us pertinent insight into the interplay between metabolic syndrome elements and typologies of hepatic steatosis and arterial stiffness degrees. Notably, of the three obtained clusters, the cluster showing increased levels of hepatic steatosis and arterial stiffness also exhibited the highest prevalence of metabolic syndrome and its constituting components. The results have significant clinical implications, advocating for a comprehensive diagnostic approach when MetS or MASLD is suspected.

OR24-05 High Waist Circumference Is Strongly Predictive Of Hepatic Steatosis And Significant Fibrosis

Abstract Disclosure: N. Janakiram: None. S. Puri: None. A. Thirumalai: None. Vibration-controlled transient elastography (TE) can measure controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) in non-alcoholic fatty liver disease (NAFLD) patients. A high skin-to-capsule distance can challenge the accuracy of this imaging technique. Therefore, high waist circumference (WC), a known risk factor for NAFLD, can hamper assessment in high-risk patients. Studies investigating the relationship between WC and TE measurements have yielded conflicting results. We used the 2017-2018 National Health and Nutrition Examination Survey (NHANES) data to explore this relationship in a large cohort of the general population. We hypothesized that high WC would be associated with (1) higher failure rate for completion of TE, (2) worse CAP and LSM measurements and (3) be predictive of presence of steatosis and significant fibrosis. We summarized the primary reason for incomplete TE in normal and high WC participants of male (M; WC ≥ 102 cm = high) and female (F; WC ≥ 88 cm = high) gender. We compared mean CAP and LSM between normal and high WC participants using unpaired t-tests. We calculated area under receiver operator curve (AUROC) for WC predicting presence of steatosis (CAP ≥248 dB/m) and significant fibrosis (LSM ≥8 kPa) and compared this with fibrosis-4 (FIB-4) and NAFLD fibrosis scores (NFS). We analyzed the 5757 patients (2880 F, 2877 M) with complete or partial TE status, based on WC. Proportion of patients with partial TE status was higher in those with high WC (8.9% F, 9% M) than normal WC patients (6.5% F, 6.4% M). We analyzed the 446 patients with partial TE status (231 F, 215 M) by cause. The proportion of patients who were unable to complete TE, either due to an IQR/medium &amp;gt; 30% or not having 10 valid measurements among the high WC population (66%) was significantly higher than those with normal WC (23%), in both women (X2 (1, n=231) = 29.63; p&amp;lt;.001) and men (X2 (1, n=215) = 49.43; p&amp;lt;.001).Among those with complete TE (n=2313; 1090 M, 1223 F), mean CAP was significantly higher (p&amp;lt;0.001) in high WC patients (308 dB/m M, 278 dB/m F) compared to normal WC patients (250 dB/m M, 225 dB/m F). Mean LSM was significantly higher (p&amp;lt;0.001) in high WC patients (6.8 kPa M, 5.7 kPa F) compared to normal WC patients (5.7 kPa M, 4.5 kPa F). The AUROC for WC predicting presence of steatosis was 0.77 in F and 0.80 in M (p&amp;lt;0.001 for both). The AUROC for WC predicting the presence of significant fibrosis (≥8 kPa) was 0.73 in F and 0.71 in M (p&amp;lt;0.001 for both). In AUROC analyses, WC performed better than FIB-4 and NFS in predicting presence of significant fibrosis and steatosis. Therefore, we conclude that high WC is more likely to result in an incomplete TE, but among those with a valid exam, it is highly predictive of presence of steatosis and significant fibrosis. Presentation: Saturday, June 17, 2023

Identifying High-Risk Patients With Nonalcoholic Fatty Liver Disease: An Opportunity for Intervention Within the Primary Care Setting.

Patients with metabolic syndrome (MetS) are likely to have nonalcoholic fatty liver disease (NAFLD), which can progress to advanced fibrosis. Early recognition of those at highest risk may ameliorate outcomes. Noninvasive liver fibrosis assessment through validated scoring systems such as the fibrosis-4 (FIB-4) index is helpful to identify these high-risk patients, with the process ideally beginning in the primary care setting. The primary objective of this study was to determine rates of disease recognition and initial management of patients with NAFLD and advanced fibrosis in a diverse primary care setting. The secondary objective was to define demographic and clinical predictors of NAFLD identification and management in this population. Medical charts from patients seen at three university-based primary care practices in New York City from January 2016 to December 2019 were reviewed. Inclusion criteria consisted of: age 18 years and above, persistent alanine transaminase (ALT) elevation (2 values ≥40IU/mL ≥6mo apart), and body mass index ≥30kg/m 2 . Patients with viral hepatitis or alcohol misuse were excluded. Patients were defined as likely having NAFLD if they met 2 of the following criteria indicating MetS: systolic blood pressure >135mmHg or diastolic blood pressure >85mmHg or active treatment for hypertension; high-density lipoprotein <40g/dL; triglycerides >150mg/dL or active treatment for hyperlipidemia; or hemoglobin A1c ≥5.7% or active treatment for insulin resistance. The primary study endpoints were the frequency of providers' recognition of NAFLD and referral to specialist and/or for imaging based on visit diagnosis codes or chart documentation. The secondary endpoints were frequency of detecting those with NAFLD and advanced fibrosis utilizing previously defined FIB-4 index cutoffs as well as predictors of disease recognition and management. Analysis was completed using descriptive statistics and logistical regression modeling. A total of 295 patients were identified as having persistently elevated ALT, a body mass index ≥30kg/m 2 , and MetS consistent with likely NAFLD diagnosis. In patients meeting these criteria, ALT elevation was documented by primary care providers in 129 patients (43.7%), NAFLD was noted in chart documentation in 76 patients (25.8%), and a NAFLD ICD-10 diagnosis was assigned to 7 patients (2.4%). 50 patients (16.9%) were referred for ultrasound. Among 51 patients (17.2%) at high risk for advanced fibrosis based on FIB-4 >3.25, 23 patients (45.1%) had NAFLD recognized by their provider and 3 (5.9%) were referred to a specialist. On logistic regression, female gender, dyslipidemia, and private insurance were predictors of disease identification by the primary care physician. ALT elevation and NAFLD are under recognized among patients with MetS in the primary care setting. Importantly, while 17.2% of patients with likely NAFLD in our cohort were high risk for advanced fibrosis, less than half of this group had a NAFLD diagnosis recognized by their primary care provider and only three were referred to a liver specialist. Further investigation of disease recognition and management algorithms in the primary care setting are necessary to enhance NAFLD detection, implement clinical care pathways, and reduce disease progression and complications.

PREVALENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AMONG CORONARY ARTERY DISEASE PATIENTS AND ITS ASSOCIATION WITH CAD SEVERITY

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing concern due to its potential to lead to liver transplants and its association with cardiovascular disease (CVD). However, the relationship between NAFLD and CVD remains debated, and non-invasive diagnostic methods for NAFLD are recommended. This study aimed to estimate the prevalence of NAFLD among patients with CAD and explore the association between CAD severity and the probability of developing NAFLD.&#x0D; Methodology: A cross-sectional study was conducted among CAD patients. Patients with a history of infectious liver disease, pregnant or lactating individuals, and those with excessive alcohol consumption were excluded. Coronary angiography was performed to assess CAD severity using the Gensini score. Ultrasonography and non-invasive assessments, such as the Fibrosis-4 (FIB-4) index, were used to diagnose and stage NAFLD.&#x0D; Result: The study included 156 CAD patients, with 79 (50.6%) being male. Out of total, 31 (19.8%) had severe, 79(50.6%) had moderate, and 46 (29.48%) had mild NAFLD. Male patients showed a significantly higher prevalence of severe NAFLD compared to females. There was no significant difference in the mean age of CAD patients across NAFLD severities. Severe NAFLD was associated with higher mean Gensini scores and FIB-4 values compared to mild to moderate NAFLD patients. A positive correlation was found between Gensini score and FIB4, suggesting that Gensini score could be an alternative to FIB4 in diagnosing NAFLD severity among CAD patients.&#x0D; Conclusion: The study revealed a high prevalence of NAFLD among CAD patients, with severe NAFLD being associated with higher CAD severity.

Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease Is Independently Associated With Reduced Renal Function

The large global population of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been shown to have an association with chronic kidney disease (CKD) due to a host of proposed mechanisms, one of which being lipoprotein dysmetabolism. Furthermore, metabolic comorbidities have been concurrently prevalent in MASLD and CKD independently. This study aimed at analyzing risk and predictive traits among an obese population for both MASLD and CKD. A retrospective chart review of 546 obese patients with a diagnosis of either MASLD or metabolic dysfunction-associated steatohepatitis between January 2020 and June 2021 was performed. Markers of liver and kidney function in addition to demographic data and renoprotective medications were recorded. Both univariable and multivariable linear regression analyses were performed to understand possible associations between MASLD markers, renal function, and markers of metabolic derangements. Univariate analysis revealed that increased age (P < .001), elevated alanine aminotransferase (defined as alanine aminotransferase ≥ 30 IU/L, P= .01), low albumin (P= .011), and increasing fibrosis-4 (FIB-4) (P= .005) were statistically associated with a reduced renal function. A reduction in glomerular filtration was associated with an increase in FIB-4 (effect size [beta] of a one-unit increase in glomerular filtration on FIB-4=-0.013, P < .001) in univariate linear regression. In multivariate linear regression, type 2 diabetes (T2D) was independently associated with increased liver fibrosis (effect size of T2D on FIB-4= 0.387925, P < .02). Our study shows that in a patient population with obesity and a diagnosis of MASLD, advanced fibrosis is independently associated with reduced renal function.

A Comparison of the Prognostic Value of Liver Fibrosis Scores in Acute Myocardial Infarction Patients With and Without Type 2 Diabetes.

Liver fibrosis scores have been demonstrated to be associated with poor prognosis after percutaneous coronary intervention (PCI). However, no studies have compared the prognostic value of these scores in acute myocardial infarction (AMI) patients with and without diabetes. We retrospectively enrolled 1576 AMI patients who underwent PCI. There were 177 all-cause deaths and 111 cardiac deaths during follow-up (median 3.8years). The non-alcoholic fatty liver disease fibrosis score (NFS) showed a better prognostic value than the fibrosis-8 (FIB-8) score (Harrell's C-index: 0.703 vs 0.671, P = .014) and the fibrosis-4 (FIB-4) score (Harrell's C-index: 0.703 vs 0.648, P < .001) in the overall population. In the time-dependent receiver operating characteristic analysis, the NFS also had the highest area under the curve across all time points. Consistent results were observed in diabetic and non-diabetic populations. Adding the NFS to traditional cardiovascular risk factors significantly improved the prediction both for all-cause mortality (Harrell's C-index: 0.806 vs 0.771, P < .001) and cardiac death (Harrell's C-index: 0.800 vs 0.771, P = .014). The NFS showed a better prognostic value than the FIB-8 score and the FIB-4 score in patients with AMI undergoing PCI, which might be preferable for estimating the risk of mortality regardless of the presence or absence of diabetes.

The relationship of circulating MOTS-c level with liver fibrosis and metabolic components in patients with metabolic dysfunction-associated fatty liver disease.

Mitochondrial open reading frame of the 12s ribosomal RNA type-c (MOTS-c) is a novel identified mitochondrial signal transmission peptide that plays an important role in glucose, amino acid and lipid metabolism. In this study, we aimed to investigate the relationship of circulating MOTS-c level with noninvasive scores of fibrosis and the components of metabolic syndrome (MetS) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). This was a single-center cross-sectional study, and the participants were divided into two groups based on their liver ultrasound results: the fatty liver group and the healthy control group. The MOTS-c level was measured by the ELISA method. Non-alcoholic fatty liver disease fibrosis score (NFS) and fibrosis 4 (FIB-4) were used to determine the level of liver fibrosis. Statistical analyses were performed using Statistical Package for Social Science 15.0 package program. One hundred fifty patients (male, n=57) with MAFLD [median age 41.0 (14) years] and 84 healthy controls (male, n=34) [median age 36.0 (22) years] were included in this study. Patients with MAFLD had significantly lower MOTS-c levels than the healthy controls (p=0.009). The MOTS-c level was significantly lower in subjects with MetS (n=48) compared to those without MetS (n=186) (p=0.01). In the total population (n=234), MOTS-c levels negatively correlated with the presence of MAFLD, NFS, FIB-4, and components of MetS. Individuals diagnosed with MetS and MAFLD tend to have lower levels of MOTS-c. Additionally, these lower levels are inversely correlated with both the components of MetS and noninvasive fibrosis scores. MAFLD negatively correlated to the MetS components and noninvasive scores of fibrosis.

Cirrhosis and the surgical patient

Cirrhosis can be challenging to recognize and manage in the perioperative setting. The Fibrosis 4 (FIB-4) score is a screening test that can help determine the likelihood of underlying advanced fibrosis or cirrhosis in patients with chronic liver disease. Liver stiffness correlates with severity of fibrosis and cirrhosis and can be measured noninvasively with transient elastography or MR elastography; a normal liver stiffness effectively rules out cirrhosis. Perioperative risk calculators include the Child-Turcotte-Pugh Score, the Mayo Risk Score, the Veterans Outcomes and Costs Associated with Liver Disease-Penn (VOCAL-Penn) score; each has its limitations. In addition to reviewing the above tools, we will briefly discuss common perioperative dilemmas in patients with cirrhosis, including selection of patients for umbilical hernia repair or bariatric surgery, and will highlight methods to optimize patients with cirrhosis prior to surgical interventions.

Correlation of Transient Elastography with Liver Iron Concentration and Serum Ferritin Levels in Patients with Transfusion-Dependent Thalassemia Major from Oman.

In a longitudinal study, we aimed to assess the correlation between ultrasound transient elastography (TE), serum ferritin (SF), liver iron content (LIC) by magnetic resonance imaging (MRI) T2* along with the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis among chronically transfusion-dependent beta-thalassemia (TDT) patients. The study was conducted at a tertiary health center treating TDT patients. Transient elastography was performed within 3 months of Liver MRI T2* examinations at the radiology department over a median of one-year duration. T-test for independent data or Mann-Whitney U test was used to analyze group differences. Spearman correlation with linear regression analysis was used to evaluate the correlation between TE liver stiffness measurements, Liver MRI T2* values, and SF levels. In this study on 91 patients, the median age (IQR) of the subjects was 33 (9) years, and the median (IQR) body mass index was 23.8 (6.1) kg/m2. Median (IQR) TE by fibroscan, MRI T2*(3T), Liver iron concentration (LIC) by MRI Liver T2*, and SF levels were 6.38 (2.6) kPa, 32.4 (18) milliseconds, 7(9) g/dry wt., and 1881 (2969) ng/mL, respectively. TE measurements correlated with LIC g/dry wt. (rS =0.39, p=0.0001) and with SF level (rS =0.43, P=0.001) but not with MRI T2* values (rS =-0.24; P=0.98). In TDT patients, liver stiffness measured as TE decreased significantly with improved iron overload measured as LIC by MRI and SF levels. However, there was no correlation of TE with the fibrosis-4 (FIB-4) score.

Association between liver fibrosis and stroke recurrence in young patients with ischemic stroke

Background and aimStroke incidence rates are rising among young adults. Liver fibrosis has recently been recognized as a risk factor for cardiovascular events and stroke in the general population. It remains unclear whether liver fibrosis influences the prognosis of stroke. We aimed to evaluate the association between liver fibrosis and stroke recurrence in young stroke patients. Methods and resultsYoung adults with first-ever ischemic stroke were enrolled from a prospective stroke registry and were followed up for stroke recurrence. Liver fibrosis was evaluated by Fibrosis-4 (FIB-4) score and was stratified into three categories. Cox regression analysis was performed to assess the relationship between liver fibrosis and stroke recurrence. Over a median follow-up of 3.1 (1.7–4.6) years, 72 (11.6%) recurrent strokes occurred among 621 patients. According to the FIB-4 score, 73 (11.7%) patients had indeterminate fibrosis, while 11 (1.8%) had advanced fibrosis. Univariate Cox analysis revealed that patients with a high FIB-4 score were more likely to experience stroke recurrence than those with a low FIB-4 score (hazard ratio 3.748, 95% confidence interval 1.359–10.332, P = 0.011). After adjusting for potential confounders in the multivariate analysis, FIB-4 score remained an independent risk factor. ConclusionsYoung stroke patients with advanced liver fibrosis were at a greater risk of stroke recurrence. Evaluating liver fibrosis may provide valuable information for stroke risk stratification, and the FIB-4 score could serve as a useful tool.

A decision tree model to predict liver cirrhosis in hepatocellular carcinoma patients: a retrospective study.

The severity of liver cirrhosis in hepatocellular carcinoma (HCC) patients is essential for determining the scope of surgical resection. It also affects the long-term efficacy of systemic anti-tumor therapy and transcatheter arterial chemoembolization (TACE). Non-invasive tools, including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), and γ-glutamyl transferase to platelet ratio (GPR), are less accurate in predicting cirrhosis in HCC patients. We aimed to build a novel decision tree model to improve diagnostic accuracy of liver cirrhosis. The Mann-Whitney U test, χ2 test, and multivariate logistic regression analysis were used to identify independent cirrhosis predictors. A decision tree model was developed using machine learning algorithms in a training cohort of 141 HCC patients. Internal validation was conducted in 99 HCC patients. The diagnostic accuracy and calibration of the established model were evaluated using receiver operating characteristic (ROC) and calibration curves, respectively. Sex and platelet count were identified as independent cirrhosis predictors. A decision tree model integrating imaging-reported cirrhosis, APRI, FIB-4, and GPR was established. The novel model had an excellent diagnostic performance in the training and validation cohorts, with area under the curve (AUC) values of 0.853 and 0.817, respectively. Calibration curves and the Hosmer-Lemeshow test showed good calibration of the novel model. The decision curve analysis (DCA) indicated that the decision tree model could provide a larger net benefit to predict liver cirrhosis. Our developed decision tree model could successfully predict liver cirrhosis in HCC patients, which may be helpful in clinical decision-making.

Fibrosis-4 index is associated with the risk of hepatocellular carcinoma in patients with cirrhosis and nonalcoholic steatohepatitis.

Identification of high-risk patients for hepatocellular carcinoma (HCC) is essential for long term monitoring of nonalcoholic steatohepatitis (NASH) cirrhosis progression. We sought to evaluate the association between Fibrosis-4 (FIB-4) index and incidence of HCC risk among patients with NASH cirrhosis. We conducted a retrospective cohort study of adult patients with NASH cirrhosis (n= 1,338) who were evaluated in a single medical center between 2005 and 2015. Those who developed HCC were identified through electronic medical records using International Classification of Diseases (ICD) 9 and 10 codes until the end of September 2021. During a median follow-up time of 3.7 years, 157 (11.7%) patients with NASH cirrhosis developed HCC. At index visit, the study population had a median age 57 years, 43% males, 78.8% White, and mean FIB-4 index 4.2. The final multivariable Cox regression model revealed that male sex, BMI 25-29.9 kg/m2, and hypertension were independent factors associated with development of HCC in patients with NASH cirrhosis. Compared to patients with FIB-4 ¾ 1.45, patients with FIB-4 between 1.45-3.25 had a similar hazard of HCC (Hazard Ratio [HR] 1.12, 95% CI: 0.67-1.86, p=0.670), whereas patients with FIB-4 >3.25 had a 1.93 (95% CI: 1.22-3.05, p=0.005) increased hazard of HCC. FIB-4 > 3.25 was an independent factor associated with increased HCC risk among NASH cirrhosis patients. FIB-4 index is a promising tool for determining high-risk patients and may be used in routine clinical practice to monitor risk of HCC in patients with NASH cirrhosis.