FibroTest Research Articles

Screening for Metabolic Dysfunction-Associated Steatotic Liver Disease-Related Advanced Fibrosis in Diabetology: A Prospective Multicenter Study.

Screening for advanced fibrosis (AF) resulting from metabolic dysfunction-associated steatotic liver disease (MASLD) is recommended in diabetology. This study aimed to compare the performance of noninvasive tests (NITs) with that of two-step algorithms for detecting patients at high risk of AF requiring referral to hepatologists. We conducted a planned interim analysis of a prospective multicenter study including participants with type 2 diabetes and/or obesity and MASLD with comprehensive liver assessment comprising blood-based NITs, vibration-controlled transient elastography (VCTE), and two-dimensional shear-wave elastography (2D-SWE). AF risk stratification was determined by a composite criterion of liver biopsy, magnetic resonance elastography, or VCTE ≥12 kPa depending on availability. Of 654 patients (87% with type 2 diabetes, 56% male, 74% with obesity), 17.6% had an intermediate/high risk of AF, and 9.3% had a high risk of AF. The area under the empirical receiver operating characteristic curves of NITs for detection of high risk of AF were as follows: Fibrosis-4 (FIB-4) score, 0.78 (95% CI 0.72-0.84); FibroMeter, 0.74 (0.66-0.83); Fibrotest, 0.78 (0.72-0.85); Enhanced Liver Fibrosis (ELF) test, 0.82 (0.76-0.87); and SWE, 0.84 (0.78-0.89). Algorithms with FIB-4 score/VCTE showed good diagnostic performance for referral of patients at intermediate/high risk of AF to specialized care in hepatology. An alternative FIB-4 score/ELF test strategy showed a high negative predictive value (NPV; 88-89%) and a lower positive predictive value (PPV; 39-46%) at a threshold of 9.8. The FIB-4 score/2D-SWE strategy had an NPV of 91% and a PPV of 58-62%. The age-adapted FIB-4 score threshold resulted in lower NPVs and PPVs in all algorithms. The FIB-4 score/VCTE algorithm showed excellent diagnostic performance, demonstrating its applicability for routine screening in diabetology. The ELF test using an adapted low threshold at 9.8 may be used as an alternative to VCTE.

Screening high-risk Veterans for cirrhosis: taking a stepwise population health approach

BackgroundBecause cirrhosis is often unrecognized, we aimed to develop a stepwise screening algorithm for cirrhosis in the Veterans Health Administration (VHA) and assess this approach’s feasibility and acceptability.MethodsVHA hepatology clinicians (“champions”) were invited to participate in a pilot program from June 2020 to October 2022. The VHA Corporate Data Warehouse was queried to identify Veterans with possible undiagnosed cirrhosis using Fibrosis-4 (FIB-4) ≥ 3.25 and at least one risk factor for liver disease (e.g., obesity), and generate an age-stratified sample. Champions at four sites reviewed charts to confirm eligibility and contacted Veterans to offer further evaluation with elastography. Feasibility was defined as protocol implementation with completion of at least one elastography test and acceptability was defined based on Veteran- and clinician-reported surveys. Participation in the program, patient outcomes, adaptations to the protocol, and implementation barriers were also assessed.ResultsFour sites were able to implement the screening protocol. Adaptations included type of outreach (primary care vs. hepatology, phone vs. mail) and type of elastography used. One site chose to refer patients with clear evidence of cirrhosis directly to hepatology (n = 12) rather than to elastography. Key implementation barriers included staffing, primary care provider (PCP) comfort with interpreting and communicating results, and appointment availability during the COVID-19 pandemic. Of 488 patients whose charts were reviewed, 230 were excluded from outreach based on predefined criteria (e.g., advanced cancer, prior or current referral to hepatology). Champions and PCPs attempted to contact 165 of 246 Veterans who were deemed eligible for evaluation with elastography. Among 53 Veterans who completed elastography, 22 (42%) had findings consistent with significant fibrosis and were referred to hepatology. Clinicians and Veterans reported high acceptability of the program on surveys (80% of Veterans who completed survey).ConclusionsThis pilot demonstrated the feasibility, acceptability, and challenges of a multisite approach to cirrhosis screening.

Noninvasive Assessment of the Severity of Liver Fibrosis in MASLD Patients with Long-Standing Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), which have a reciprocal relationship compounded by obesity, are highly prevalent in the Middle East affecting morbidity, mortality, and healthcare costs. This study aimed to assess the severity of MASLD and liver fibrosis among adult Emirati patients with long-standing T2DM. This cross-sectional study used noninvasive methods to assess the severity of MASLD and fibrosis progression in an adult cohort of Emirati patients (N = 546) with a mean T2DM duration of 16years. Fatty liver infiltration was assessed by hepatic steatosis index (HSI), while fibrosis was assessed by the fibrosis-4 (FIB-4) index and aspartate aminotransferase/platelet ratio index (APRI). Of those, 108 patients were randomly subjected to ultrasound-based FibroScan® to assess controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). All patients had fatty liver with ~ 83% being categorized as having severe steatosis. Serum-based fibrosis biomarker panels detected significant liver fibrosis in ~ 2.5% of these patients. The APRI appeared to be more restrictive in detecting moderate fibrosis (1.5%) than the FIB-4 index (25.5%). CAP significantly correlated with the LSM, indicating that the two methods contributed to the same underlying pathophysiology. Liver steatosis was more severe in female patients, who were older and had a higher body mass index (BMI) than those with moderate or no significant fibrosis. They also had higher serum liver enzymes and were more likely to have age-related changes in kidney function. Interestingly, severity of both steatosis and fibrosis remained unaffected by age and duration of T2D except for fibrosis severity detected by FibroScan®. This study highlights the critical need for routine screening of MASLD among Emirati patients with long-standing T2DM, given the high point prevalence of severe steatosis (~ 83%), predominantly among women in this population.

The associations between diet-induced inflammation and the improvement or worsening of hepatic steatosis and fibrosis: a longitudinal analysis of RaNCD cohort study

BackgroundPersistent inflammation plays a crucial role in the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD). We aimed to scrutinize the associations of diet-induced inflammation with the improvement or worsening of hepatic steatosis and fibrosis in MASLD.MethodsThis longitudinal study involved 2,537 participants from the Ravanser Non-Communicable Disease (RaNCD) cohort (2015–2023). Dietary intake was assessed using the 118-item food frequency questionnaire (FFQ), and diet-induced inflammation was determined using the dietary inflammatory index (DII). The AST to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were used as confirmed predictive indicators for hepatic fibrosis and the hepatic steatosis index (HSI) was used for hepatic steatosis.ResultsAdherence to an inflammatory diet independently increases the risk of worsening hepatic steatosis (RR:1.39; 95%CI: 1.02–1.93; P-value: 0.04) and reduces the risk of improving hepatic steatosis (RR: 66; 95% CI: 0.48–0.98; P-value: 0.01) compared to an anti-inflammatory diet. The DII scores did not show any connection to hepatic fibrosis, as determined by FIB-4 (β: − 1.08; 95%CI: − 2.43 to 0.27; P-value: 0.12) and APRI (β: 0.22; 95%CI: − 1.51 to 1.95; P-value: 0.80).ConclusionsThese results underscore the importance of dietary composition in managing hepatic steatosis and highlight the need for further research to explore the mechanisms underlying these associations.

The Effects of Oral Semaglutide on Hepatic Fibrosis in Subjects with Type 2 Diabetes in Real-World Clinical Practice: A Post Hoc Analysis of the Sapporo-Oral SEMA Study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important common comorbidity in subjects with type 2 diabetes, and liver fibrosis is a factor directly related to its prognosis. Glucagon-like peptide-1 receptor agonists are useful treatment options for MASLD; however, the efficacy of oral semaglutide in treating liver steatosis/fibrosis has not been fully elucidated. A secondary analysis of a multicenter, retrospective, observational study investigating the efficacy and safety of oral semaglutide in Japanese subjects with type 2 diabetes in a real-world clinical setting (the Sapporo-Oral SEMA study) was conducted. Subjects in the original cohort were divided into groups as follows: subjects with suspected MASLD (alanine aminotransferase > 30 U/L) were placed in an overall group; a subpopulation from an overall group at high risk for hepatic fibrosis (fibrosis-4 (FIB-4) index ≥ 1.3 or platelet count < 200,000/µL) was placed in a high-risk group; and the remaining subjects were placed in a low-risk group. Changes in the hepatic steatosis index and FIB-4 index after oral semaglutide induction were explored using a paired t-test or the Wilcoxon signed-rank test. Overall, 169 subjects (including 131 that switched from other medications) were analyzed, and 67 and 102 subjects were selected for the high-risk and low-risk groups, respectively. Oral semaglutide significantly improved the hepatic steatosis index (from 46.1 to 44.6, p < 0.001) and FIB-4 index (from 1.04 to 0.96, p < 0.001) as well as several metabolic parameters in all cohorts. The efficacy of semaglutide in treating liver fibrosis was confirmed by the addition of, and switching from, existing agent groups. Furthermore, improvement in the FIB-4 index was significantly negatively correlated with the baseline FIB-4 index. The induction of oral semaglutide might be a useful treatment option for subjects with type 2 diabetes at high risk for liver fibrosis, even when switching from conventional medications for diabetes.

Clinical Relevancies of Sarcopenic Obesity in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD).

Sarcopenic obesity (SO) is associated with adverse outcomes in diseased patients. This study aimed to examine the prevalence and risks associated with SO, with a focus on the impact of SO on cardiovascular risk in patients with MASLD. In this cross-sectional study, patients with MASLD were prospectively enrolled. Through dual-energy X-ray absorptiometry (DXA) scans, their body compositions were analyzed to identify who had SO and osteopenia/osteoporosis. The primary aim is to investigate risks associated with SO, followed by analyzing the association between SO and cardiovascular disease (CVD). Two hundred and twenty-three patients with MASLD were enrolled. The prevalence of SO was 47.1%, respectively. Patients coexisted with MASLD and SO had increased visceral adipose tissue (VAT), higher fatty liver index (FLI) and fibrosis 4 (FIB-4) score. Regression analysis revealed higher FLI and FIB-4 score, as well as history of hypertension, were risks associated with SO. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was higher in patients coexisted with MASLD and SO compared to those without (10.1% vs. 7.3%, p = 0.006). Regression analysis showed that increased VAT and FIB-4 score were associated with raised risk of ASCVD. Prevalence of SO in MASLD patients is considerable. The presence of SO also linked to higher risk of ASCVD. Therefore, the recognition of SO in patients with MASLD is important in clinical care.

FLAME: Training and Validating a Newly Conceived Model Incorporating Alpha-Glutathione-S-Transferase Serum Levels for Predicting Advanced Hepatic Fibrosis and Acute Cardiovascular Events in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Alpha-Glutathione-S-transferase (alphaGST) is a liver enzyme whose serum levels increase with the worsening of fibrosis in alcoholic and viral chronic hepatitis. Its usefulness in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remains unexplored. From January 2016 to December 2017, 200 patients with MASLD and 30 controls were enrolled. AlphaGST serum levels were measured. Variables related to advanced fibrosis (AF) were selected via Principal Component Analysis (PCA), and the best cut-off (BCO) was estimated using ROC analysis. Liver stiffness measurement (LSM), NAFLD fibrosis (NFS), Fibrosis-4 (FIB-4), and BMI-AST/ALT Ratio-Diabetes (BARD) scores were determined. The first acute cardiovascular events (ACE) in ACE-naïve subjects were recorded over five years. A validation cohort of 60 MASLD patients was enrolled from January 2018 to May 2019 and followed for five years. AlphaGST levels increased with fibrosis stage (p < 0.0001) in both cohorts, showing high accuracy in predicting AF (TrC: AUC 0.89, VlC: AUC 0.89). PCA-selected variables were HbA1c, HDL, and alphaGST, forming the "FLAME" model. FLAME showed superior predictive performance for AF and ACEs compared to other models and scores. FLAME represents a novel tool that accurately predicts AF and ACEs in MASLD.

Association of steatotic liver disease with all-cause and cardiovascular mortality among prehypertensive or hypertensive patients.

Prehypertension and hypertension often coexist with non-alcoholic fatty liver disease (NAFLD) during the progression of cardiovascular disease (CVD). International academic liver societies have recently reached a consensus to replace NAFLD with the new term 'steatotic liver disease' (SLD). In this study, we aimed to evaluate the impact of different SLD subtypes on all-cause and CVD mortality in individuals with prehypertension or hypertension. We included 6074 adults from the National Health and Nutrition Examination Survey (2003-18). The US fatty liver index was used as the diagnostic criterion for SLD, and participants were classified into no SLD, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD). For cases of MASLD, MetALD, and ALD, we further assessed advanced fibrosis using the fibrosis-4 (FIB-4) index. Additionally, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models to assess the associations of SLD subtypes and advanced fibrosis with all-cause and CVD mortality. There were 3505 (57.7%) participants with no SLD, 1284 (21.1%) with MASLD, 777 (12.8%) with MetALD, and 508 (8.4%) with ALD. During a median follow-up period of 8.2 years, the risk of all-cause and CVD mortality progressively increased in participants with MASLD (HR = 1.28; 95% CI = 1.01-1.63 and HR = 1.55; 95% CI = 1.04-2.33, respectively), MetALD (HR = 1.41; 95% CI = 1.05-1.88 and HR = 1.78; 95% CI = 1.10-2.87, respectively), and ALD (HR = 1.83; 95% CI = 1.32-2.53 and HR = 1.80; 95% CI = 1.01-3.19, respectively). Among the individuals with MASLD, MetALD, and ALD, advanced fibrosis was also associated with an increased risk of all-cause and CVD mortality. Individuals with MASLD, MetALD, and ALD had a higher risk of all-cause and CVD mortality than those without SLD. Therefore, early intervention strategies targeting SLD prevention and management may help individuals with prehypertension and hypertension to improve their long-term health.

Comparison of Referral Rates and Costs Using Fibrosis-4 and Enhanced Liver Fibrosis (ELF) Testing Strategies for Initial Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Veteran Population.

Global metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is estimated at 30% and projected to reach 55.7% by 2040. In the Veterans Affairs (VA) healthcare system, an estimated 1.8 million veterans have metabolic dysfunction-associated steatohepatitis (MASH). Adult patients at risk for MASLD in a VA healthcare system underwent Fibrosis-4 (FIB-4) and Enhanced Liver Fibrosis (ELF®) testing. Referral rates and cost savings were compared among 6 noninvasive testing (NIT) strategies using these 2 tests independently or sequentially at various cutoffs. Enrolled patients (N = 254) had a mean age of 65.3 ± 9.3 years and mean body mass index (BMI) of 31.7 ± 6, 87.4% male: 78.3% were non-Hispanic/Latino, and 96.5% had type 2 diabetes mellitus (T2DM). Among the 6 evaluated strategies, using FIB-4 followed by ELF at a 9.8 cutoff yielded the highest proportion of patients retained in primary care without need of referral to hepatology clinic (165/227; 72.7%), and was associated with the lowest costs ($407.62). Compared to the FIB-4 only strategy, FIB-4/ELF with a 9.8 cutoff strategy resulted in 26% fewer referrals and 8.47% lower costs. In the subgroup of patients with BMI >32, there were 25.17% fewer referrals and costs were 8.31% lower. Our study suggests that sequential use of ELF with a 9.8 cutoff following indeterminate FIB-4 tests results in lower referral rates and lower care costs in a veteran population at risk of MASLD. Adding ELF as a sequential test after indeterminate FIB-4 might help reduce the number of referrals and overall cost of care.

Effects of the SGLT2 inhibitor ipragliflozin and metformin on hepatic steatosis and liver fibrosis: Sub-analysis of a randomized controlled study.

To compare the effects of ipragliflozin, a sodium-dependent glucose transporter-2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi-centre, open-label, blinded-endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis. In total, 103 Japanese patients with type-2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m2 and glycated haemoglobin level of 7%-10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. Various parameters, including hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS), liver fibrosis indices, AST to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index, were compared in the sub-analyses. The correlations between changes in each index and VFA were evaluated. At baseline, patients demonstrated moderate hepatic steatosis, with FLI scores of 52.9 ± 26.6 and 57.8 ± 29.0 in the ipragliflozin and metformin groups, respectively. At 24 weeks, compared with metformin, ipragliflozin showed improvements in hepatic steatosis indices: FLI (-9.24 ± 10.7 vs. -3.45 ± 11.8, p = 0.013), HSI (-1.45 ± 2.32 vs. -0.45 ± 1.87, p = 0.021), NAFLD-LFS (-0.70 ± 1.46 vs. -0.04 ± 0.98, p = 0.011) and liver fibrosis index: APRI (-0.110 ± 0.323 vs. 0.033 ± 0.181, p = 0.010). In the ipragliflozin group, changes in FLI and HSI were correlated with VFA reduction (r = 0.340, p = 0.024; r = 0.367, p = 0.011, respectively). Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early-stage liver disease associated with T2D.

Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C.

Direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV). This study investigated whether metabolic dysfunction influences the likelihood of fibrosis regression after DAA treatment in patients with chronic hepatitis C (CHC). This multicenter, retrospective study included 8,819 patients diagnosed with CHC who were treated with DAAs and achieved a sustained virological response (SVR) between January 2014 and December 2022. Fibrosis regression was defined as a 20% reduction in noninvasive surrogates for liver fibrosis, such as liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) and the fibrosis-4 (FIB-4) score. Hypercholesterolemia (h-TC) were defined as >200 mg/dL. The median age of the study population was 59.6 years, with a predominance of male patients (n = 4,713, 57.3%). Genotypes 1, 2, and others were confirmed in 3,872 (46.2%), 3,487 (41.6%), and 1,024 (12.2%) patients, respectively. Diabetes mellitus (DM) was present in 1,442 (17.2%) patients and the median LS was 7.50 kPa (interquartile range, 5.30-12.50). Multivariate analysis revealed that the presence of DM and pre-DAA h-TC were independently associated with a decreased probability of fibrosis regression by VCTE Additionally, pre-DAA h-TC was independently associated with a decreased probability of fibrosis regression by the FIB-4. Metabolic dysfunction has an unfavorable influence on fibrosis regression in patients with CHC who achieve SVR after DAA treatment.

Association between non-invasive liver biomarkers and graft outcomes in kidney transplantation recipients.

Although studies have suggested that metabolic risk profiles are prognostic factors in kidney transplantation recipients (KTRs), the prognostic value of fatty liver, a known surrogate of metabolic risk, in KTRs remain to be elucidated. The objective of this study was to investigate the association between non-invasive liver biomarkers used to assess hepatic steatotic and fibrotic burdens and graft outcomes in KTRs. A total of 3,092 patients who underwent deceased or living donor kidney transplantation (KT) between January 2000 and December 2022 were enrolled. Postoperative hepatic fibrotic burdens of KTRs were assessed using the Fibrosis-4 (FIB-4) score and the non-alcoholic fatty liver disease fibrosis score (NFS). The primary outcome was a composite of 50% estimated glomerular filtration rate (eGFR) decline and graft failure. Secondary outcomes included individual outcomes of 50% eGFR decline, graft failure, and acute rejection. For the primary outcome, during a mean follow-up of 6.0 years, the composite outcome occurred in 519 (16.8%) participants. When stratified into three groups according to FIB-4 score categories, the highest score group (FIB-4≥2.67) had a 2.05-fold (95% confidence interval [CI], 1.44-2.91; P<0.001) higher risk of the composite outcome compared to the lowest score group (FIB-4<1.30). Furthermore, the highest score group showed higher risk of the secondary outcomes, with hazard ratios (95% CI) of 1.75 (1.16-2.66), 1.62 (1.06-2.46), and 2.23 (1.43-3.46) for 50% eGFR decline, acute rejection and graft failure, respectively. Similar findings were observed for NFS. Higher hepatic fibrotic burdens were associated with unfavorable graft outcomes in KTRs.

Age-dependent differences in FIB-4 predictions of fibrosis in patients with MASLD referred from primary care.

Fibrosis 4 (FIB-4) is widely used to triage patients with metabolic dysfunction-associated steatotic liver disease. Given that age is part of FIB-4, higher scores may be expected in the elderly population. This led to the proposal of using a higher threshold of FIB-4 to triage patients aged ≥65. Our main objective is to evaluate how age modifies the association between the FIB-4 index and disease severity based on the vibration-controlled transient elastography (VCTE) "rule of 5s." In this cross-sectional study, we prospectively analyzed data from a primary care referral pathway. We used liver stiffness measurement by VCTE as a reference standard for liver risk. We modeled with ordinal regression the exceedance probabilities of finding different liver stiffness measurement thresholds according to FIB-4, and how age modifies FIB-4 predictions. Nine hundred eighty-five participants with complete data were used for modeling. Participants aged ≥65 had a higher prevalence of advanced liver disease estimated by VCTE and higher FIB-4 values than those <65 (85.9% vs. 20.2% for FIB-4 ≥1.3, and 46.5% vs. 6.5% for FIB-4 ≥2.0). In participants age ≥65, the negative predictive value for VCTE ≥10kPa of FIB-4 <1.3 was 100% versus FIB-4 <2.0 was 83%. Age significantly modified FIB-4-based prediction of fibrosis, but predictions at a threshold of 1.3 or 2 were only minimally altered. For higher FIB-4 threshold (ie, 2.7), age strongly modified FIB-4 predictions of liver stiffness measurement. Age does not relevantly modify FIB-4 predictions when using the common threshold of 1.3. Our data suggest no rationale for increasing the FIB-4 threshold to 2 for undergoing further testing in patients aged ≥65. However, the meaning of a FIB-4 of 2.7 strongly changes with age. This cutoff for ages over 65 is not enough to define high-risk and would not warrant direct referral.

Assessing the Impact of Pioglitazone on Fibrosis Progression amongst People with Type 2 Diabetes Mellitus (T2D): A Retrospective, Multi-centric Real-World Study in Indian Population

Background: NAFLD (Non-Alcoholic Fatty Liver Disease) or metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver disorders and is the primary cause of chronic liver disease worldwide. The present study seeks to evaluate the effect of Pioglitazone on fibrosis progression, assessed by Fibrosis 4 (FIB-4) in individuals with type 2 diabetes mellitus (T2D). Materials and Methods: In the present two-center retrospective study, adults with T2D who had at least 2 visits and 2 FIB4 values measured at least 90 days apart (from April 2021 to May 2024) were enrolled. Data was analyzed for descriptive statistics and compared for significance between groups. Statistical differences between the groups were determined by applying the Wilcoxon Signed-Rank Test and paired t-test. Results: 54 individuals with a mean age of 57.5 years (±12.7) were included for analysis. HbA1c [from 8.93% to 7.58% (p&lt;0.01)] significantly improved while the BMI remained unchanged. Mean FIB-4 scores also significantly dropped from 1.99 at baseline to 1.54 at follow-up (p&lt;0.01). FIB-4 scores declined from baseline in both the indeterminate and high-risk groups. Conclusion: HbA1c and FIB-4 scores were reduced with pioglitazone. It has a protective role against fibrosis progression in people with T2D.

Liver Fibrosis and Cardiovascular Events.

Liver fibrosis represents a common sequela of nonalcoholic fatty liver disease (NAFLD) and other chronic liver diseases. Noninvasive liver fibrosis scores (LFSs) aim to evaluate the severity of liver fibrosis. Whether LFSs can predict the risk of future cardiovascular events (CVEs) remains unclear. This systematic review aimed to clarify the association between liver fibrosis and CVEs by studying the value of LFSs, namely the Fibrosis-4 (FIB-4) Index for Liver Fibrosis score and the NAFLD Fibrosis Score (NFS), for predicting CVEs. PubMed, Scopus, Web of Science, and Cochrane Library were searched for relevant prospective studies. Retrieved articles were screened to confirm their eligibility for the systematic review. We evaluated the quality of the included studies using the National Institutes of Health tool. Twelve studies of high to fair quality were included in this systematic review. Of note, 10/12 studies reported an independent association between high LFSs and the risk of CVEs, cardiovascular mortality, and all-cause mortality (all P < 0.05). In addition, an advanced histological grade of liver fibrosis (grade 3 or 4) was suggestive of CVE occurrence. NAFLD also appeared to be associated with a higher risk of CVEs at any severity of fibrosis (all P < 0.05). The findings of this review suggest that liver fibrosis in patients with NAFLD is an independent predictor of future adverse CVEs, cardiovascular mortality, and all-cause mortality. Noninvasive and easy-to-perform LFSs, including FIB-4 score and the NFS, appear useful in predicting such events in patients with a spectrum of cardiovascular diseases and the general population without known cardiovascular disease.

Five-Year Prospective Follow-Up of Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antiviral Agents.

The research intended to present prospective data on the long-term prognosis of individuals with hepatitis C virus (HCV) infection who received direct-acting antiviral agent (DAA) treatment. Patients who received DAA treatment at Tianjin Third Central Hospital and Tianjin Second People's Hospital were prospectively enrolled and subsequently underwent a longitudinal follow-up. This research monitored occurrences of virological relapse, hepatocellular carcinoma (HCC), mortality, and liver disease progression. The annualized incidence rates (AIRs), cumulative incidence rates of adverse events and risk factors were investigated. Changes in liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI) score, fibrosis-4 (FIB-4) index, as well as the albumin-bilirubin (ALBI) scores were also documented. A total of 862 individuals were followed up for 4.86 (P25, P75; 4.48, 5.48) years. The proportion of all participants with undetectable HCV-RNA exceeded 98% at all follow-up time points. Patients experienced virological relapse, HCC, death and disease progression with a cumulative AIRs of 1.03% (95% confidence interval [CI] 0.6-1.5), 1.76% (95% CI 1.2-2.3), 1.51% (95% CI 1.0-2.0), and 5.81% (95% CI 4.8-6.8), respectively. Cirrhotic patients were at a heightened risk of virological relapse (adjusted hazard ratio [aHR] 3.20, 95% CI 1.59-9.75; p = 0.016), HCC (aHR 6.57, 95% CI 2.66-16.28; p < 0.0001), and unfavorable prognosis (aHR 6.93, 95% CI 2.56-18.74; p < 0.0001). Additionally, patients with diabetes faced an elevated risk of HCC (aHR 2.33, 95% CI 1.05-5.15; p = 0.038) and poor prognosis (aHR 2.72, 95% CI 1.13-6.55; p = 0.026). Furthermore, liver stiffness measurement (LSM) exhibited a significant decrease compared to baseline. Additionally, patients in the cirrhosis group showed reductions in APRI score, FIB-4 index and ALBI score to different degrees. Cirrhotic patients exhibited increased susceptibility to virological relapse, HCC, unfavorable prognosis, and liver disease progression following DAA treatment. Consequently, it is imperative to implement a rigorous monitoring protocol for all cirrhotic patients after DAA treatment.

Clinical utility of the Fibrosis-4 index for predicting mortality in patients with heart failure with or without metabolic dysfunction-associated steatotic liver disease: a prospective cohort study

BackgroundThe liver-heart axis potentially influences the risk of mortality in patients with heart failure. We aimed to identify the clinical utility of the fibrosis-4 (FIB-4) index in patients with heart failure in the context of metabolic dysfunction-associated steatotic liver disease (MASLD). MethodsPatients with heart failure and a subsample of healthy participants were enrolled in the MyoVasc study (NCT04064450) and followed for nine years. Participants with excessive alcohol consumption were excluded. The Fatty Liver Index (FLI) and FIB-4 index were used to classify MASLD and hepatic fibrosis, respectively. Data were adjusted for potential confounders. The primary endpoint was all-cause mortality. Findings2726 participants, including 172 healthy individuals, were included in the study. The participants had a mean age of 64·4 ± 11·2 years and a median FIB-4 index of 1·59 (interquartile range [1·17; 2·17]). There were 532 deaths. The FIB-4 index was predictive for all-cause mortality (hazard ratio (HR) 1·341, 95% confidence interval (CI) [1·273; 1·412], p<0·0001). The HRs and 95% CIs for the FIB-4 index in FLI categories were 1·597 [1·256; 2·031] (p=0·00013, FLI<30), 1·802 [1·519; 2·138] (p<0·0001, FLI 30 to 60), and 1·292 [1·215; 1·374] (p<0·0001, FLI≥60). The interaction term for the FIB-4 index with FLI≥60 (reference FLI<30) was HR 0·774 [0·617; 0·972] (p=0·027), indicating a smaller impact of the FIB-4 index in FLI≥60 than in FLI<30 (HR 1·664 [1·333; 2·077], p<0·0001). Multivariable linear regressions revealed relevant independent relationships between the FIB-4 index and N-terminal pro-B-type natriuretic peptide, systolic dysfunction, diastolic dysfunction and left ventricular hypertrophy in participants with a FLI below 60. InterpretationIn patients with heart failure, the FIB-4 index predicts all-cause mortality and relates to cardiac functional and structural changes, especially in those without MASLD. FundingJohannes Gutenberg-University Mainz

Fibrosis-4 and Ultrasonography Assessment of Metabolic Dysfunction-associated Steatotic Liver Disease: A Cross-sectional, Observational Study

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease, has now emerged as endemic. Fibrosis-4 (FIB-4) can grade the risk of evolving liver fibrosis utilizing inexpensive easily available parameters, and ultrasonography (USG) is the attainable initial imaging modality to detect the presence of MASLD. This study aimed to determine the prevalence and grades of MASLD along with fibrosis risk stratifications according to the FIB-4 index among the urban diabetic population of Bangladesh. Methods: This cross-sectional observational study was performed at National Healthcare Network Uttara, Dhaka, Bangladesh, from November 2022 to October 2023 with ethical clearance among nonpregnant adults having type 2 diabetes mellitus, aged 18 years to ≤74 years. The presence of MASLD with grading was ascertained by USG of the hepatobiliary system, and the fibrosis risk score was calculated according to the FIB-4 index. Results: Overall, 167 subjects were studied (male-to-female ratio of 1:1.7). USG revealed that 94.6% had fatty changes in the liver, among them 37.7% had Grade 1, 48.5% had Grade 2, and 8.4% had Grade 3 fatty changes. Risk stratification by the FIB-4 index revealed that 65.3% had low risk, 31.7% indeterminate risk, and 3.0% high risk for hepatic fibrosis. Most subjects in the indeterminate and high-risk group had HbA1c% ≥7 than the low-risk group for fibrosis. The study found that 41.9% of patients were overweight, 47.3% were obese, and central abdominal obesity was seen in 85.6% of patients. Conclusion: This study revealed a considerable prevalence of MASLD, with varying degrees of liver fibrosis among the diabetic population. Case-finding strategies using USG and noninvasive tests (such as FIB-4) should be applied to rule out or in advanced fibrosis.

Non-Invasive Tests of Non-Alcoholic Fatty Liver Disease: Perspective Review

Cirrhosis and hepatocellular carcinoma often develop from Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive condition characterized by hepatic steatosis, inflammation and varying degrees of fibrosis. The increasing incidence of non-alcoholic steatohepatitis (NASH) highlights the need for effective diagnostic and treatment methods. Non-invasive tests (NITs) have emerged as promising tools for evaluating and monitoring NAFLD, offering safer and more cost-effective alternatives to invasive liver biopsies. This review focuses on the current state of NITs in NAFLD management, emphasizing their diagnostic accuracy, prognostic significance, and role in guiding treatment. NITs discussed include transient elastography, magnetic resonance imaging (MRI), magnetic resonance elastography (MRE) and serum biomarker panels such as the NAFLD fibrosis score, Fibro Test, and Enhanced Liver Fibrosis (ELF) test. Recent advancements in MRI and MRE have greatly improved the non-invasive assessment of liver fibrosis and steatosis, enhancing sensitivity and specificity for early detection and risk stratification. Additionally, combined serum biomarker panels have shown promise in predicting disease severity and progression, aiding in the identification of high-risk patients who could benefit from early intervention. By enabling prompt diagnosis, comprehensive risk assessment and monitoring of disease progression, the integration of NITs into standard clinical practice offers significant potential for improving NAFLD management. Ongoing research efforts are focused on developing new NITs and optimizing existing methods to enhance diagnostic precision and prognostic evaluation in NAFLD patients. This evolving landscape of non-invasive assessment tools could revolutionize the approach to managing this increasingly prevalent liver disease. Keywords: Fatty liver, Liver biopsy, Transient Elastography, Serum biomarkers, Hepatic Cell Carcinoma.

Assessment of Non-alcoholic Fatty Liver Disease and Level of Risk of Fibrosis in Diabetic and Non-diabetic Individuals.

Background and aim Non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD), is more common in people with type-2 diabetes mellitus (T2DM) than in people without diabetes mellitus (non-DM). This disease can lead to cirrhosis or hepatic cancer. There is limited data on NAFLD prevalence and thelevel of risk of fibrosis in Bangladeshi individuals. This study aimed to assess NAFLD prevalence and compare the proportion of NAFLD and thelevel of risk of fibrosis between T2DM and non-DM Bangladeshi individuals. Methods A cross-sectional analytical study was conducted for six months in 2024 in the outpatient section of the Department of Medicine at Holy Family Red Crescent Medical College, Dhaka, Bangladesh. Among the patients seeking outpatient care, a total of 179 male and non-pregnant female participants aged 18 years and older were selected using a purposive sampling technique. Individuals with a history of alcohol use, diagnosed cases of chronic liver diseases, prior use of hepatotoxic drugs, and primary biliary cholangitis were excluded from the study. Detailed demographic characteristics, comorbidities, family history of diabetes and liver disease, physical measurements, and biochemical tests were done. Ultrasonography (USG) of the hepatobiliary system was employed to ascertain the existence of NAFLD. The presence or absence of T2DM was evaluated through prior medical documents, corroborated by laboratory analyses of random blood glucose (RBS) and glycosylated hemoglobin (HbA1c) levels. The Fibrosis-4 (FIB-4) index score was utilized to evaluate the risk of liver fibrosis. Results Themean age of the participants was 49.11±12.25 years and 107 (59.8%) of participants were female. Almost two-thirds of the participants were suffering from T2DM. About 17 (9.5%) of the study participants were suffering from NAFLD, which was much higher among T2DM (15 (12.5%)) than non-DM individuals (two (3.3%)). T2DM and family history of liver disease were found to significantly increase the risk of suffering from NAFLD by 5.247 times (95% CI: 1.081-25.468) and 4.202 times (95% CI: 1.249-14.135), respectively. About one (6.7%) of T2DM individuals with NAFLD were at high risk for fibrosis. Conclusion Almost one in 10 people had NAFLD, and it was way more common among those with T2DM, who also exhibit a higher risk of hepatic fibrosis. Moreover, T2DM and a family history of liver disease can independently increase therisk of NAFLD.