FIB-4 Index Research Articles

Examining the prevalence of hepatic steatosis and advanced fibrosis using non-invasive measures across Canada: A national estimate using the Canadian Health Measures Survey (CHMS) from 2009-2019

Prevalence estimates are crucial for enhancing preparedness to prevent and manage chronic diseases. This is the first study to estimate the prevalence of hepatic steatosis and advanced fibrosis in Canada, leveraging a nationally representative survey and multiple validated non-invasive tests (NITs). The Canadian Health Measures Survey (CHMS) is Canada's largest direct health measures survey, which collects data on sociodemographic, clinical factors, and blood chemistry. We determined steatosis using two NITs: the Hepatic Steatosis Index (HSI) and the NAFLD Ridge Score (NRS). The FIB-4 Index and NAFLD fibrosis score (NFS) were used to assess the risk of advanced fibrosis among adults with steatosis. Survey weights were incorporated to account for oversampling, survey nonresponse, and post-stratification. Between 2009 and 2019, 1365 children (55% males, median age 13 (IQR: 10-15) and 4664 adults (51% males, median age 45 (IQR: 34-62), 57% reporting weekly alcohol consumption) were included in our study. The weighted steatosis prevalence ranged from 9-11% among children to 38-48% among adults based on the NRS and HSI, respectively. Between 86-87% of adults with type 2 diabetes and 65-72% with hypertension had evidence of steatosis. Overall, 1.2-2.4% of adults with steatosis were at risk of advanced liver fibrosis. We estimate between 1 in 3 and 1 in 2 adults have hepatic steatosis, and 195,000-406,200 are at high risk of advanced liver fibrosis in Canada. No routine screening guidelines for liver fibrosis exist in Canada, and most patients are unaware of their condition. Prevalence studies are essential for raising awareness and advocating for the inclusion of steatotic liver disease on national public health agendas.

Aspartate aminotransferase-to-platelet ratio index outperforms Fibrosis-4 in 2843 Korean patients with metabolic dysfunction-associated steatotic liver disease.

The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD. This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed. Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis≥F3, and 0.890, 0.884, and 0.889 for fibrosis≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis≥F2, 0.788, 0.814, and 0.79 for fibrosis≥F3, and 0.846, 0.859, and 0.856 for fibrosis≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64years for fibrosis≥F4. The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis.

Histological Improvement of Hepatic Fibrosis of Decompensated Liver Cirrhosis after Prednisolone and Azathioprine Treatment in a Patient with Autoimmune Hepatitis.

The treatment of the underlying cause of liver disease may potentially reverse hepatic fibrosis. However, it remains uncertain whether improvement in fibrosis can be observed in decompensated liver cirrhosis (LC). Here, we present a case of autoimmune hepatitis (AIH)-related LC in which histological improvement of fibrosis was achieved despite the presence of decompensated LC. A Japanese female in her 20s was initially identified as having liver function impairments during her employment medical checkup. Following a laparoscopic liver biopsy, she was diagnosed with AIH-related decompensated LC (F4 and A3) with a Child-Pugh score of 10. The patient initially received treatment with prednisolone at a daily dose of 40 mg, followed by 20 mg/day of prednisolone plus 25 mg/day of azathioprine (subsequent increase of azathioprine to 100 mg/day). With this treatment, the abnormal serum marker levels returned to normal, thereby enabling the patient to avoid liver transplantation eight months after the initiation of treatment. Moreover, marked improvement was observed in non-invasive tests for hepatic fibrosis, including the FIB-4 index and FibroIndex, as well as liver stiffness evaluated by FibroScan®. Eleven months after diagnosis, the patient developed a cholestatic liver injury and was diagnosed with drug-induced cholestatic liver disease (azathioprine overcapacity as the causative agent). By percutaneous liver biopsy at this point, hepatic fibrosis (F2-3) was markedly improved compared with that at the diagnosis. Along with the improvement of hepatic fibrosis, notable improvements were also observed in patient-reported outcomes such as the SF-36® score and chronic liver disease questionnaire. In this report, we first described a case of AIH that showed a histological improvement of hepatic fibrosis even in decompensated LC by treatment with prednisolone and azathioprine.

A Clinical Algorithm for Screening Compensated Advanced Chronic Liver Disease Utilizing Ultrasonography, Platelet Count, and Albumin Levels, With Transient Elastography as Reference.

Background and aims Compensated advanced chronic liver disease (cACLD) refers to asymptomatic patients with advanced fibrosis who do not yet exhibit clinical or radiological signs of portal hypertension. Early detection of cACLD is essential for effective risk stratification and timely management, potentially preventing progression to more severe and irreversible stages of liver disease. Transient elastography (TE) is the primary diagnostic method for cACLD, with several diagnostic thresholds commonly used. Ultrasonography (USG) is widely used as an initial diagnostic tool for liver disease, but its effectiveness in diagnosing cACLD is not well established. To the best of our knowledge, this study is the first to systematically evaluate the diagnostic accuracy of USG in detecting cACLD, using TE as a reference standard based on validated diagnostic thresholds. We also examined whether combining USG findings with platelet count and serum albumin could enhance diagnostic utility. Additionally, we discuss the strengths and limitations of established non-invasive scoring systems, including the Enhanced Liver Fibrosis (ELF) test, Fibrosis-4 (Fib-4) index, and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS), to determine if our approach offers a more accessible and practical solution in clinical settings Methods This retrospective cross-sectional study was conducted at the Royal Wolverhampton NHS Trust,Wolverhampton, England, including patients with suspected liver disease who underwent USG, TE, and blood tests. Valid TE readings followed manufacturer guidelines, and patients with USG-detected portal hypertension or confounding conditions (e.g., acute hepatitis, heart failure) were excluded. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of USG against TE, with TE values >15 kPa confirming and <10 kPa excluding cACLD. Results Among 1,528 patients (mean age 51 years, range 16-89), 982 were male (64.3%) and 546 were female (35.7%). The cohort predominantly comprised Caucasian (n=1,087, 71.1%) and South-East Asian (n=256, 16.8%) patients. USG showed a sensitivity of 64.6% (95%CI: 58.3-70.6%) and specificity of 78.2% (95%CI: 75.6-80.6%) for cACLD, with a PPV of 40.2% (95%CI: 36.7-43.7%) and an NPV of 90.7% (95%CI: 89.2-92.1%). High NPV was consistent across all etiologies. In patients with a normal liver on USG, NPV improved to 92.7% (95%CI: 90.9-94.6%) when serum albumin >35 g/L and platelet count >150 x 109/L were present. In patients with sonographic signs of liver disease, PPV increased to 84.1% (95%CI: 73.3-94.9%) when platelet count and albumin were low but dropped to 20.8% (95%CI: 15.4-26.3%) when both were normal. Conclusions USG alone has limited reliability in diagnosing cACLD but is valuable for ruling out advanced fibrosis in asymptomatic patients due to its high NPV. Adding platelet and albumin levels improves diagnostic accuracy, though TE remains essential for definitive diagnosis. This approach may streamline screening and optimize resource use, particularly in settings with limited TE access. USG combined with platelet count and serum albuminoffers a cost-effective, accessible, and practical solution for the initial assessment of cACLD. Further studies are needed to validate these findings in broader populations.

ASO Author Reflections: Synergistic Role of FIB-4 Index and Tumor Burden Score in Predicting Recurrence After Hepatectomy for Intrahepatic Cholangiocarcinoma.

ASO Author Reflections: Synergistic Role of FIB-4 Index and Tumor Burden Score in Predicting Recurrence After Hepatectomy for Intrahepatic Cholangiocarcinoma.

Diagnostic and prognostic value of plasma lipocalin-2 levels in patients with metabolic dysfunction–associated steatotic liver disease

Abstract Background Non-Alcoholic Fatty Liver Disease, recently better recognised as Metabolic Dysfunction–Associated Steatotic Liver Disease, is the most prevalent form of chronic liver disease at present time. It is estimated to impact 32% of the world's population, hence representing a significant health burden. Aim of the work To assess the significance of plasma Lipocalin-2 (LCN2) levels in the diagnosis and prognosis of NAFLD patients. Patients and methods In this retrospective case–control study we recruited 102 subjects aged between 18 and 70 years. The included participants were split into two study groups. Group I: 51 NAFLD patients (61% men, 39% females) and Group II: 51 healthy controls (51% men and 49% females), for whom plasma LCN2 levels were assessed and correlated with NAFLD fibrosis score, FIB4 and fatty liver index. Results In this study, LCN2 levels in NAFLD patients were significantly greater compared to individuals in the control group (p &lt; 0.001), with a mean of 1893.214 ± 1002.852 ng/dL in the cases and a mean of 466.020 ± 397.699 ng/dL in the controls. This suggests the use of LCN2 as a possible diagnostic marker of NAFLD. The mean LCN2 levels in this study also significantly increased as the grade of fatty liver increased from I to III (p &lt; 0.001). This in turn proposes the use of LCN2 as a prognostic marker for NAFLD progression. LCN2 also significantly correlated with the fatty liver index and NAFLD Fibrosis scoring systems, but not with Fib-4. With an area under the ROC of 0.906, it demonstrated excellent diagnostic performance with 84% sensitivity, 90% specificity, 89.6% PPV and 85.2% NPV for the prediction of NAFLD patients. Conclusion Lipocalin-2 performs as a diagnostic and a possible prognostic marker for metabolic dysfunction-associated steatotic liver disease.

Addition of neutrophil-to-lymphocyte ratio to Pre-DAA FIB-4 does not increase prediction value for de novo liver complications in hepatitis C

Background and aimsDirect-acting antiviral agents (DAAs) achieve high sustained virologic response (SVR) in chronic hepatitis C patients; yet a proportion of patients still experience de novo liver complications after SVR. Identification of risk factors is clinically important. FIB-4 index is a useful noninvasive tool to assess fibrosis, while neutrophil-to-lymphocyte ratio (NLR) is a biomarker for systemic inflammation. Our study aimed to investigate whether the addition of NLR can increase the prediction power of pre-DAA FIB-4 for de novo liver complications after SVR. MethodsWe recruited patients via The Taiwan HCV Registry (TACR) and National Health Insurance Registry Database. The inclusion criteria were patients who achieved SVR12 after DAA and were followed for at least 24 months after SVR12. Liver complications included ascites, hepatic encephalopathy, variceal bleeding, and HCC. ResultsTotally 7657 patients were recruited from 2013 to 2018. Among them, 3674 patients (48.0%) had a FIB-4 value > 3.25 and 491 patients (6.4%) had a NLR >4 before DAA. After two-year of follow-up after SVR 12, 214 patients (2.8%) developed de novo liver complications. Factors associated with liver complications included male gender, diabetes mellitus, hyperlipidemia, chronic kidney disease, and pre-DAA FIB-4 >3.25 in multivariate analyses. Addition of NLR slightly did not increase the power of predicting liver complications. ConclusionsThe overall incidence of de novo liver complications after SVR is low during short-term follow-up. Elevated pre-DAA FIB-4 is associated with de novo liver complications after SVR, whereas the addition of pre-DAA NLR does not increase the prediction power.

An Elevated FIB-4 Score is associated with the severity of heart failure

Abstract Background Liver disease and heart failure (HF) 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 liver fibrosis and to stratify the risk of liver-related outcomes in patients with chronic liver diseases. Purpose Thus, our goal was to evaluate the connection between the FIB-4 index, heart failure, associated comorbidities, and cardiological biomarkers that predict the risk of liver fibrosis in patients with heart failure. Methods HF patients hospitalized in the cardiology department were divided into a group with an FIB-4 index &amp;lt;1.3 (indicating a low risk of liver fibrosis) (n=53) and a group with an FIB-4 index ≥1.3 (indicating intermediate and high risk of fibrosis) (n=59). Clinical examinations, laboratory results, echocardiography with Vivid E95-GE Healthcare, non-invasive body mass analysis with Body Composition Analyzer (Tanita Pro), and measurements of NT-proBNP, growth differentiation factor 15 (GDF-15), galectin-3, fatty acid-binding protein (FABP), copeptin, and vascular endothelial growth factor (VEGF) concentrations were performed. Results The patients with an FIB-4 index ≥1.3 had significantly higher: left ventricular volume index (LAVI) (p=0.004), E/E’ ratio (p=0.004) and lower left ventricular ejection fraction (p=0.003) compared to group with low risk of liver fibrosis. There were no differences in body mass compartments between groups except for ECW/TBW (%) - an index of body water distribution, which was lower in low-risk liver fibrosis group (p=0.0002). Patients with an FIB-4 index ≥1.3 had also lower: GFR MDRD (median 59.95 vs 85.1 mL/min/1.73 m²; p&amp;lt;0.001), total cholesterol (116.5 vs 15 mg/dL; p=0.002), LDL cholesterol (median 56 vs 93 mg/dL; p&amp;lt;0.0001) and HDL cholesterol (median 39 vs 47 mg/dL; p=0.03). Regarding heart failure biochemical biomarkers, patients with low risk of liver fibrosis had significantly lower level of NT-proBNP (median 37 vs 161 pg/ml; p&amp;lt;0.0001), GDF-15 (median 399.6 vs 898.9 pg/ml; p&amp;lt;0.0001) and FABP (median 101 vs 264,7 pg/ml; p=0.04). In a multiple logistic regression model the factors that were independently associated with the risk of liver fibrosis in HF patients based on an FIB-4 index were GDF-15 &amp;gt;724 pg/ml (OR 33.7, 95%CI: 6.5-174.2; p=0.0001), and NT-proBNP &amp;gt;129 pg/ml (OR 19.9, 95% CI: 3.8-103; p=0.0001) (Figure 1) Conclusion Our study suggests association between an elevated FIB-4 score and heart functions, and kidney impairment with fluid overload but not with higher total and low density cholesterols fractions or percentage of fat. Higher GDF-15 and NT-proBNP levels are independently associated with the risk of liver fibrosis based on an FIB-4 index. FIB-4 index in HF patients is an easy method to monitor the risk of liver fibrosis and might help to predict the HF progression and CVD complications.

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and MACE in patients with established CVD. The clinical value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the clinical value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease (heart failure, coronary artery disease, MASLD, chronic kidney disease). The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels (OR: 1.004, 95% CI:1.000-1.009, P=0.049) and increased triglyceride levels (OR: 1.007, 95%CI: 1.001-1.012, P=0.033) after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score&amp;lt;2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

Changes in interoception before and after treatment in patients with alcohol use disorder.

To investigate the factors associated with interoception in patients with alcohol use disorder and determine whether treatment causes changes in their interoception. The Body Perception Questionnaire-Body Awareness ultra-short version Japanese version (BPQ-BAVSF-J) was used to measure interoception in 50 alcohol-dependent participants (27 in the inpatient group and 23 in the outpatient group). The BPQ-BAVSF-J was administered and data on aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), mean corpuscular volume, platelet count, and Fib-4 index were extracted at admission and immediately before discharge for the inpatient group and at the first outpatient visit and approximately 3 months after the visit for the outpatient group. The mean age of the 50 participants was 51.0 ± 12.3 years. Significant associations were found between the BPQ-BAVSF-J and Fib-4 index and AST. The BPQ-BAVSF-J score significantly decreased at discharge in the inpatient group. AST, ALT, γ-GTP, and Fib-4 index of liver function were also significantly lower at discharge. In contrast, in the outpatient group, there were no significant changes in the BPQ-BAVSF-J score, AST level, ALT level, γ-GTP level, and Fib-4 index between at the first outpatient visit and approximately 3 months after the visit. Interoception in patients with alcohol use disorder increased with worsening liver function and decreased with improvement in liver function owing to treatment. This suggests that the BPQ-BAVSF-J score, an easily accessible scale, may be used to detect early deterioration of liver function through regular administration.

Effects of SGLT2i and Pioglitazone on FIB-4 Index in Patients with Metabolic Dysfunction Associated Steatotic Liver Disease—A Real World Retrospective Study from India

Aims: Several studies support type 2 diabetes mellitus (T2DM) as one of the risk factors of metabolic dysfunction associated steatotic liver disease (MASLD). Recently, the use of pioglitazone and sodium-glucose co-transporter 2 inhibitors (SGLT2i) has been on the rise considering its beneficial effects in reducing liver dysfunction. We aim to determine the clinical effectiveness of these drugs in improving MASLD and T2DM. Materials and methods: We conducted a retrospective study of 279 T2DM patients with MASLD who were prescribed pioglitazone and/or SGLT2i from two clinics in India. The primary endpoint was change in fibrosis (FIB-4) index and the aspartate aminotransferase to platelet ratio index (APRI) score at one year follow-up. Appropriate statistical tests were applied to assess the significance of the outcomes. Results: Of the total (276) patients, 46% of patients were at low risk of advanced fibrosis, 11% were at high risk for advanced fibrosis, and the majority (50%) were on SGLT2i treatment. At follow-up, there is a statistically significant reduction in the mean (SD) FIB-4 index (1.92 [1.22] vs. 1.68 [0.99]) and APRI score (0.42 [0.34] vs. 0.33 [0.21]); p &lt; .001. Among treatment groups, there is a significant difference in the mean FIB-4 index both at baseline (F: 4.23; p &lt; .05) and follow-up (F: 3.45; p &lt; .05). These scores were highly significant in the combination treatment with SGLT2i and pioglitazone ( p &lt; .05). Conclusions: Our results indicate a combination therapy with SGLT2i and pioglitazone might be beneficial in managing MASLD, especially in reducing the FIB-4 index and APRI score in Indian T2DM patients with MASLD.

Characteristics of diabetes mellitus patients with nonviral chronic liver disease who developed hepatocellular carcinoma.

Type 2 diabetes mellitus (T2DM) is a well-known risk factor for hepatocellular carcinoma (HCC). However, HCC is often diagnosed at an advanced stage in patients with diabetes because of the lack of the best criteria for surveillance candidates. The aim of this study was to identify risk factors for HCC development in patients with diabetes with nonviral chronic liver disease. Three hundred thirty T2DM patients with nonviral chronic liver disease who underwent surveillance for HCC by imaging techniques between 2009 and 2020 were enrolled in this multicenter cross-sectional retrospective study. Theclinical and laboratory parameters of patients with and without HCC were compared. Age ≥65years, alcohol intake, lack of hepatic steatosis, triglyceride level <111mg/dL, Mac2 binding protein glycosylation isomer (M2BPGi) ≥0.9 cut-off index (COI), α-fetoprotein concentration ≥5ng/mL, and des-γ-carboxy prothrombin concentration ≥26mAU/mL were independently associated with HCC development. When stratified by age, only alcohol intake (odds ratio [OR] 114.19, p<0.001) was associated with HCC development in patients aged <65years, and medication for diabetes mellitus (OR 5.72, p=0.001), lack of hepatic steatosis (OR 4.47, p=0.002), lactate dehydrogenase ≥198IU/L (OR 2.751, p=0.031), M2BPGi ≥1.18 COI (OR 9.05, p<0.001), and FIB-4 index ≥2.59 (OR 3.22, p=0.017) were associated with HCC development in patients aged ≥65years. In addition to age and advanced liver fibrosis, alcohol intake in younger T2DM patients and medication for DM and lack of hepatic steatosis in older T2DM patients should be considered for HCC surveillance by imaging.

Effects of SGLT2 inhibitors on the onset of esophageal varices and extrahepatic cancer in type 2 diabetic patients with suspected MASLD: a nationwide database study in Japan

Background & aimSGLT2 inhibitors (SGLT2i) improve hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) and MASLD. We aimed to investigate the impact of SGLT2i on the incidence of liver-related events and extrahepatic cancer compared to DPP4 inhibitors (DPP4i) in patients with T2DM and suspected MASLD using a medical claims database in Japan.MethodsWe conducted a retrospective study using a Japanese medical claims database. Among patients with T2DM who were prescribed SGLT2i or DPP4i (n = 1,628,656), patients with suspected MASLD were classified into SGLT2i (n = 4204) and DPP4i (n = 4204) groups. Effects of SGLT2i on the following outcomes were compared to DPP4i: (1) changes in HbA1c and ALT levels after 6 months, (2) changes in hepatic fibrosis index, and (3) the incidence of liver-related events/extrahepatic cancer over 12 months.ResultsAfter 6 months, DPP4i significantly decreased HbA1c levels compared to SGLT2i. In contrast, SGLT2i significantly decreased ALT levels compared to DPP4i. SGLT2i significantly decreased FIB-4 index compared to DPP4i over 12 months. Although no significant difference was observed in the incidence of overall liver-related events between the two groups, SGLT2i significantly reduced the incidence of esophageal varices (HR 0.12, 95%CI 0.01–0.95, P = 0.044). Moreover, SGLT2i significantly suppressed the incidence of extrahepatic cancer (HR 0.50, 95%CI 0.30–0.84, P = 0.009) compared to DPP4i.ConclusionSGLT2i was more beneficial than DPP4i in improving the hepatic inflammation and fibrosis indices. Moreover, SGLT2i suppressed the incidence of esophageal varices and extrahepatic cancer compared to DPP4i. SGLT2i may suppress life-threatening events in patients with T2DM and suspected MASLD.

Fatty Liver Disease and its Impaction on Insulin Resistance

Abstract Background Non-alcoholic fatty liver disease (NAFLD) involves excess liver fat accumulation without specific causes like alcohol or viral infections, categorized into simple steatosis and nonalcoholic steatohepatitis (NASH). While simple steatosis is generally stable, NASH is linked to progressive liver disease. Diagnosis excludes secondary causes, and NAFLD, marked by hepatocyte changes, inflammation, and fibrosis, may lead to severe complications. Strongly associated with insulin resistance in liver and adipose tissues, NAFLD disrupts glucose-insulin interplay, compromising insulin's regulatory functions and contributing to metabolic disorders and disease progression. Aim of the Work The aim of the study is to investigate fatty liver disease and evaluate its impact of on insulin resistance. Patients and Methods This cross-sectional study, conducted at Ain Shams University, focuses on adults with NAFLD to assess insulin resistance. Inclusion criteria involve fatty liver disease, impaired glucose tolerance, and informed consent, while exclusions include alcohol intake and hepatitis. Data collection comprises demographics, anthropometrics, metabolic syndrome assessment, ultrasound grading of steatosis, and laboratory tests for liver function, FIB-4 index, and insulin resistance using HOMA-IR. The study aims to understand the relationship between NAFLD and insulin resistance in a clinical setting. Results In this study of 98 patients with Non-alcoholic Fatty Liver Disease (NAFLD), characterized by liver fat accumulation, insulin resistance (IR) was prevalent in 63.3%. The cases, predominantly females (52%), had mean age of 43 years, 50% were hypertensive, and 48% were diabetic. IR was directly related to age, and its prevalence was significantly higher in patients with diabetes and hypertension. IR correlated positively with body weight, BMI, ALT, AST, FIB-4, TG, and cholesterol. Fatty liver grading showed a significant association with IR, particularly in grade 2 cases. The optimal HOMA-IR cutoff for distinguishing between grade I and II fatty liver was &amp;gt;2.56, with high sensitivity (100%) and specificity (88.73%). These findings emphasize the intricate relationship between NAFLD, IR, and associated metabolic factors. Conclusion The study established a robust link between insulin resistance (IR) and Non- alcoholic Fatty Liver Disease (NAFLD), noting a 63.3% prevalence of IR in the subjects. Employing HOMA-IR, a cutoff point &amp;gt;2.56 effectively differentiated between NAFLD grades I and II, demonstrating 100% sensitivity, 88.73% specificity, and a remarkable AUC of 98. This underscores HOMA-IR's valuable role in identifying and stratifying NAFLD, especially in individuals with diabetes.

Effective Screening of Advanced Fibrosis in Patients with MASLD using the FIB-4 Index Combined with Metabolic Syndrome-Related Factors

Effective Screening of Advanced Fibrosis in Patients with MASLD using the FIB-4 Index Combined with Metabolic Syndrome-Related Factors

A metabolome-derived score predicts metabolic dysfunction-associated steatohepatitis and mortality from liver disease

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related mortality. However, biomarkers predicting both MASH and mortality are missing. We developed a metabolome-derived prediction score for MASH and examined whether it predicts mortality in Chinese and European cohorts. MethodsThe MASH prediction score was developed using a multi-step machine learning strategy, based on 44 clinical parameters and 250 plasma metabolites measured by proton nuclear magnetic resonance (1H-NMR) in 311 Chinese adults undergoing a liver biopsy. External validation was conducted in a Finnish liver biopsy cohort (n=305). We investigated association of the score with all-cause and cause-specific mortality in the population-based Shanghai Changfeng Study (n=5,893) and the UK Biobank (n=111,673). ResultsA total of 24 clinical parameters and 194 1H-NMR metabolites were significantly associated with MASH in the Chinese liver biopsy cohort. The final MASH score included body mass index, aspartate transaminase, tyrosine, and the phospholipids-to-total lipids ratio in very-low density lipoprotein. The score identified patients with MASH with AUROCs of 0.87 (95% CI, 0.83-0.91) and 0.81 (95% CI, 0.75-0.87) in the Chinese and Finnish cohorts, with high negative predictive values. Participants with a high or intermediate risk of MASH based on the score had a markedly higher risk of MASLD-related mortality than those with a low risk in Chinese (HR, 23.19; 95%CI, 4.80-111.97) and European individuals (HR, 27.80; 95%CI, 15.08-51.26) after 7.4 and 12.6 years of follow-up. The MASH prediction score was superior to the FIB-4 index and the NAFLD Fibrosis Score in predicting MASLD-related mortality. ConclusionThe metabolome-derived MASH prediction score accurately predicts risk of MASH and MASLD-related mortality in both Chinese and European individuals. Impact and implicationsMetabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related death. However, biomarkers predicting not only MASH, but also death due to liver disease, are missing. We established a MASH prediction score based on 44 clinical parameters and 250 plasma metabolites using a machine learning strategy. This metabolome-derived MASH prediction score could accurately identify patients with MASH among both Chinese and Finnish individuals, and it was superior to the FIB-4 index and the NAFLD Fibrosis Score in predicting MASLD-related death in the general population. Thus, the new MASH prediction score is a useful tool for identifying individuals with a markedly increased risk of serious liver-related outcomes among at-risk and general populations.

Residual metabolic burden in young psoriasis patients successfully treated with biologics

Metabolic disorders are common in patients with psoriasis and contribute significantly to an increased cardiovascular risk. While biologic therapy is very successful in clearing skin lesions, its impact on metabolic parameters is uncertain. Our aim was to investigate the residual metabolic burden in psoriasis patients successfully treated with biologic therapy. We conducted a cross-sectional study of 80 young patients (54 men, 26 women, aged 30–45 years) successfully treated with either adalimumab, secukinumab or guselkumab and topical therapy or methotrexate, and 20 healthy controls. Anthropometric parameters, lipid levels and metabolic indices (HOMA-IR, TyG index and FIB-4 index) were measured. Patients did not receive any other treatments to exclude confounding effects. After analysis, we found that patients treated with three different biologics had similar metabolic status, only the FIB-4 index was higher in the adalimumab group than in the secukinumab and guselkumab treatment groups. There were no significant differences between the patients treated with biologics and the control group. The comparison with patients treated topically or with methotrexate showed that only triglyceride levels, HOMA-IR, TyG index, and FIB-4 index were elevated in patients treated with adalimumab compared to patients treated with topical therapy. Finally, metabolic status was also similar in patients treated with methotrexate or topical therapy. In conclusion, this study suggests that psoriasis patients successfully treated with biologics have similar metabolic parameters to the control group and patients treated with topical therapy or methotrexate. This indicates that there is no significant residual metabolic burden in young patients successfully treated with biologics. These results are clinically relevant and should be considered in the treatment of psoriasis patients.The study is registered at http://clinicaltrials.gov (identifier: NCT05957120). Date of registration: 24th of July 2023.

Evaluation of prognostic efficacy of liver immune status index in predicting postoperative outcomes in hepatocellular carcinoma patients: A multi-institutional retrospective study.

Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths globally. Despite treatment advances, high post-hepatectomy recurrence rates (RR), especially with liver fibrosis and hepatitis C virus infection, remain challenging. Key prognostic factors include vascular invasion and perioperative blood loss, impacting extrahepatic recurrence. Natural killer (NK) cells are crucial in countering circulating tumor cells through TRAIL-mediated pathways. The aim of this study was to validate the liver immune status index (LISI) as a predictive tool for liver NK cell antitumor efficiency, particularly in HCC patients with vascular invasion. A retrospective analysis of 1337 primary HCC hepatectomies was conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Clinicodemographic data were extracted from electronic medical records. Prognostic indices (FIB-4, ALBI, ALICE, GNRI, APRI, and LISI) were evaluated using area under the receiver operating characteristic curve values. Survival analyses employed Kaplan-Meier estimations and log-rank tests. LISI significantly correlated with other prognostic markers and stratified patients into risk groups with distinct overall survival (OS) and RR. It showed superior predictive performance for 2-year OS and RR, especially in patients with vascular invasion. Over longer periods, APRI and FIB-4 index reliabilities improved. The HISCO-HCC score, combining LISI, tumor burden score, and alpha-fetoprotein levels, enhanced prognostic accuracy. LISI outperformed existing models, particularly in HCC with vascular invasion. The HISCO-HCC score offers improved prognostic precision, guiding immunotherapeutic strategies and individualized patient care in HCC.

High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitisB patients treated with nucleos(t)ide analogs.

Patients with chronic hepatitisB (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitisB virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitisC. We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15. Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB-4 index, alpha-fetoprotein and gamma-glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0ng/mL, gamma-glutamyl transpeptidase ≥22U/L, FIB-4 index≥1.93, and GDF-15≥1.17ng/mL groups. In patients with no or more than three of these five risk factors, the 10-year HCC cumulative incidence rates were 0% and 41.0%, respectively. High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs.

Association between fibrosis-4 index and cognitive impairment in elderly patients with hypertension: A cross-sectional study.

The fibrosis-4 index (FIB-4) is a noninvasive fibrosis test that is recommended for patients who are at risk of developing hepatic fibrosis. The aim of the study was to explore the correlation between FIB-4 index and the decline of cognitive function among older patients with hypertension. The study used a cross-sectional design to analyze data obtained from the NHANES 2011-2014. The significance of the FIB-4 index correlation with cognitive function in individuals over the age of 60 was evaluated via multivariate regression models. The nonlinear link was described and fitted smoothed curves. There were a total of 2039 participants in the study, and those with a higher FIB-4 index were more susceptible to developing cognitive decline. In the completely adjusted model, the association remained statistically significant between the FIB-4 index and poor cognitive function as measured by CERAD: Total Score (OR=0.72, 0.57-0.91), Animal Fluency Score (OR=0.66, 0.48-0.91), and Digit Symbol Score (OR=0.36, 0.17-0.77). A nonlinear association was found between the FIB-4 and poor cognitive ability: Total Score, CERAD: Score Delayed Recall, Digit Symbol Score, and Animal Fluency Score. In elderly patients with hypertension, a high FIB-4 index is correlated with an increased prevalence of cognitive decline. Hence, the FIB-4 index could potentially serve as a valuable tool for determining individuals with hypertension who are susceptible to both liver-related complications and cognitive impairment.