Fibrosis Index Research Articles

Type 2 Diabetes and Hypertension as Risk Factors for Advanced Fibrosis in Biopsy Proven Metabolic Dysfunction-Associated Steatotic Liver Disease.

To identify the diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) related to liver fibrosis and to characterize patients with cryptogenic steatotic liver disease (SLD) (non-MASLD) among those previously diagnosed with nonalcoholic fatty liver disease (NAFLD). This multicenter retrospective study included 511 patients diagnosed with NAFLD via liver biopsy, and the prevalence of MASLD was assessed based on the diagnostic criteria. Patients were divided into those who met the MASLD criteria and those who did not, and the characteristics of advanced fibrosis and associated cardiometabolic factors were evaluated. Of the 475 patients with NAFLD, 458 (96.4%) met the criteria for MASLD, showing a high overlap between classical NAFLD and MASLD populations. Severe fibrosis was observed, regardless of the number of cardiometabolic factors. Hypertension and diabetes mellitus significantly contributed to advanced fibrosis (≥ F3), with odds ratio of 1.92 and 2.00 (95% confidence interval of 1.17-3.16 and 1.22-3.28, respectively; both p < 0.01) on multivariate analysis. The other seventeen (3.6%) patients did not meet the diagnostic criteria for MASLD. Among them, seven had significant fibrosis and a high fibrosis-4 index. Diabetes mellitus and hypertension are key metabolic factors associated with advanced fibrosis. Some cases, classified as cryptogenic SLD, also exhibit significant fibrosis. Consequently, identifying high-risk patients, including those undergoing noninvasive tests for fibrosis, is crucial.

Impact of Berberine Hydrochloride-assisted Metformin on the Metabolism of Glycolipids and Serum Levels of TIMP-1 and TGF-β1 in Individuals with Type 2 Diabetes

Background Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and impaired glucose metabolism, leading to hyperglycemia and increased risk of complications like renal fibrosis. Purpose This study’s purpose is to examine how berberine hydrochloride (BBR) and metformin (Met) work together to treat T2DM, as well as how these medications affect tissue type metalloproteinase-1 (TIMP-1), glucose, and lipid metabolism levels in the blood and transforming growth factor β1. Methods Using a random number table approach, overall, 100 individuals with T2DM between October 2020 and October 2022 were chosen and classified into two groups: An experimental group and an untreated group, each with 50 patients. The untreated group received Met therapy, whereas the experimental group received BBR based on the untreated group. The two groups were compared regarding efficacy, cholesterol and glucose metabolism, renal function and renal fibrosis indices, and the frequency of adverse responses. Results The experimental group’s effective rate was 96.00% higher than that of the untreated group (82.00%). Following treatment, the experimental group had lower levels of glycosylated hemoglobin (HbAlc), insulin resistance index (HOMA-IR), fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and cholesterol (TC) than the untreated group, while the untreated group had greater levels of high-density lipoprotein cholesterol (HDL-C). Following the course of therapy, the observation group’s levels of cystatin (Cys-C), urinary β2 microglobulin (β2-MG), urine albumin excretion rate (UAER), and urinary microalbumin (ALB) were all lesser compared to the untreated group. Following treatment, the experimental group’s transforming growth factor-β (TGF-β) levels, matrix metalloproteinase-9 (MMP-9), and TIMP-1 were lesser than those of the untreated group. Conclusion When Met and BBR are taken together, patients with type 2 diabetes can effectively control their glucose and lipid metabolism, as well as their levels of TGF-β1, MMP-9, and TIMP-1. They can also postpone renal interstitial fibrosis and eventually improve their kidney function, all with a high degree of safety and significant effects.

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

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.

Effect of elexacaftor-tezacaftor-ivacaftor on liver transient elastography, fibrosis indices and blood tests in children with cystic fibrosis.

Elexacaftor-tezacaftor-ivacaftor (ETI) has significantly improved the clinical course of people with cystic fibrosis (pwCF) and eligible CFTR variants. In this study, we prospectively evaluated liver elastography, liver fibrosis indices and liver tests in children with CF aged 6-12 years started on ETI therapy. Body mass index, sweat test, percent predicted forced expiratory volume in one second, serum markers of liver injury or portal hypertension, liver fibrosis indices, controlled attenuation parameter and liver stiffness were assessed before starting ETI and three and twelve months post-ETI, according to new international guidelines. 27 children with CF were enrolled, 14 with liver involvement and 13 without liver involvement at baseline. A significant improvement in sweat chloride after ETI was observed in all subjects. In those with liver involvement, liver stiffness significantly decreased at 12 months of ETI, with all individuals achieving normalization or near-normalization of liver stiffness. The majority of individuals with abnormal AST, ALT, GGT, or liver fibrosis indices at baseline experienced normalization by 12 months of ETI (AST: 67%, ALT: 100%, GGT: 50%, APRI: 100%, GPR: 100%). In the no liver involvement group, the only significant change in liver health metrics at 12 months was a significant reduction in platelets (P<0.05) that remained within the normal range. ETI is associated with improvement in liver stiffness, liver function tests and fibrosis indices in pwCF and liver involvement. ETI may reduce the development of advanced CF liver disease, but longer observations with larger cohorts are needed.

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.

A randomized clinical study to evaluate the possible antifibrotic effect of zinc sulfate in chronic HCV patient receiving direct-acting anti-viral therapy

ObjectiveThis study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy.MethodsThis randomized controlled study included 50 chronic HCV-infected patients with fibrosis stage (F1 & F2). Participants were randomly assigned to two groups: Group 1 (Control group, n = 25) received standard direct-acting antiviral therapy for 3 months, while Group 2 (Zinc group, n = 25) received 50 mg/day of zinc sulfate in addition to the standard direct-acting antiviral therapy for the same duration. Baseline and 3-month post-intervention assessments included evaluating serum levels of hyaluronic acid, transforming growth factor beta-1, and fibronectin. Furthermore, indices of liver fibrosis, such as the Fibrosis Index based on the 4 factors (FIB-4) and the Aspartate Transaminase-to-Platelet-Ratio Index (APRI), were calculated during these assessments.ResultsAt baseline, the two studied groups had no statistical difference in demographic and laboratory data. After treatment, serum zinc levels significantly increased in the zinc-treated group compared to the control group. Additionally, serum fibronectin and hyaluronic acid levels were significantly reduced in group 2 (zinc group) compared to group 1 (control group). Moreover, zinc group showed lower APRI scores than the control group after a 3-month follow-up period, but there was non-significant difference in FIB-4 scores between the two groups after treatment. Furthermore, total bilirubin levels were reduced after zinc therapy for 3 months.ConclusionsAdministering zinc sulfate could potentially serve as a safe and efficient therapeutic strategy for the management of hepatic fibrosis in individuals with chronic hepatitis C virus.Trial RegistrationClinicalTrials.gov identifier: NCT05465434, On 19/7/2022.

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.

Quantification of Vascular Remodeling and Sinusoidal Capillarization to Assess Liver Fibrosis with Photoacoustic Imaging.

Background Photoacoustic microscopy (PAM) can be used to detect strong absorption from endogenous and exogenous contrast material, making it promising for detailed structural and functional imaging of hepatic sinusoids, including dynamic visualization of permeability. Purpose To evaluate whether PAM-based quantitative parameters of liver function and integrity (lacunarity, blood oxygen saturation [Sao2], and Evans blue [EB] permeability) are associated with histopathologic indexes of fibrosis in a mouse model. Materials and Methods Between October 2022 and July 2023, a total of 35 male C57BL/6 mice were included in this study and received intraperitoneal injection of carbon tetrachloride to establish mouse models of progressive liver fibrosis, with seven mice in each group. PAM was performed to visualize vascular structure, Sao2 distribution, and EB penetration within the hepatic lobule. Histologic findings were used as the reference standard. Associations between the PAM parameters and the pathologic results were evaluated with Spearman rank correlation. Results Mean lacunarity, a PAM parameter, gradually increased with liver fibrosis stage (control: 0.018 arbitrary units [au] ± 0.004 [SD]; fibrosis: 1 week, 0.024 au ± 0.002; 2 weeks, 0.028 au ± 0.003; 4 weeks, 0.034 au ± 0.002; 10 weeks, 0.040 au ± 0.005; P < .001) and was positively correlated with collagen-positive area (Spearman r = 0.88-0.90; P < .001). PAM revealed that Sao2 decreased with disease progression (control, 0.921 au ± 0.017; 1 week, 0.875 au ± 0.019; 2 weeks, 0.846 au ± 0.020; 4 weeks, 0.802 au ± 0.025; 10 weeks, 0.732 au ± 0.036; P < .001) and was inversely related to hypoxia-inducible factor 1α expression (Spearman r = -0.83; P < .001). EB permeability, indicative of hepatic sinusoid capillarization, was reduced at advanced stages of fibrosis (control: 11.6% [IQR, 11.2%-11.8%]; fibrosis: 1 week, 24.8% [IQR, 23.3%-25.8%]; 2 weeks, 18.4% [IQR, 18.4%-20.0%]; 4 weeks, 5.1% [IQR, 4.9%-6.2%]; 10 weeks, 3.7% [IQR, 3.4%-4.5%]; P < .001). Conclusion PAM-based structural and functional parameters were associated with liver fibrosis severity, and PAM imaging of EB dynamics helped detect sinusoidal capillarization. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Li and Yao in this issue.

Development, validation, and prognostic evaluation of LiverPRO for the prediction of significant liver fibrosis in primary care: a prospective cohort study.

Clinically significant liver fibrosis is associated with future adverse events in patients with steatotic liver disease. We designed a software tool for detection of clinically significant liver fibrosis in primary care. In this prospective cohort study, we developed and validated LiverPRO using six independent cohorts from Denmark, Germany, and England that included patients from primary and secondary care with steatotic liver disease related to alcohol or metabolic dysfunction. We used clinically significant fibrosis (histology stage ≥F2) and advanced fibrosis (≥F3) as outcomes for variable selection in the development cohort and built the model with fractional polynomial regression. In all cohorts, we independently validated the tool for prediction of elevated liver stiffness by transient elastography (≥8 kPa and ≥12 kPa) and for the 2-year and 5-year risk of liver-related events. Diagnostic performance was assessed using the area under the receiver operating curve (AUC), with clinical performance evaluated through sensitivity, specificity, and Harrell's C-statistic for prognostic purposes. In the development cohort (n=462), we derived 466 multivariable models consisting of age in combination with three to nine variables from a list of nine blood tests (aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, international normalised ratio, albumin, sodium, bilirubin, platelet count, and cholesterol). In the development cohort, LiverPRO diagnosed clinically significant fibrosis with good accuracy (transient elastography ≥8 kPa area under the receiver operating characteristic curve [AUC] 0·86 [95% CI 0·83-0·90]). In the DECIDE validation cohort (n=6468), LiverPRO detected participants with a transient elastography of 8 kPa or higher with good accuracy (AUC 0·80 [95% CI 0·78-0·82]), comparable to enhanced liver fibrosis testing (0·78 [0·75-0·80]) and the LiverRisk score (0·81 [0·79-0·84]), but superior to the Fibrosis-4 index (0·69 [0·66-0·72]) and NAFLD Fibrosis Score (0·74 [0·72-0·77]). Findings were consistent in three other validation cohorts (n=2554), albeit accuracy was slightly lower. Using a rule-out cutoff of less than 25% (indicating no further examinations required), LiverPRO had a rule-out sensitivity of 80·6% (95% CI 76·4-84·3) and a rule-out negative predictive value of 98·0% (95% CI 97·5-98·4) in the DECIDE cohort. Similarly, with a rule-out cutoff of less than 1·3, FIB-4 had a rule-out sensitivity of 53·8% (48·5-58·9) and a rule-out negative predictive value of 95·8% (95·1-96·4). For rule-in thresholds, using a cutoff of more than 65% (indicating referral to a hepatologist required) LiverPRO had a rule-in specificity of 95·5% (95% CI 94·9-96·0) and a rule-in positive predictive value of 33·0% (95% CI 28·5-37·8) in the DECIDE cohort whereas FIB-4, with a rule-in threshold of 2·67, had a rule-in specificity of 98·7% (94·9-96·0) and a rule-in positive predictive value 35·6% (27·0-44·9). Using UK Biobank data, LiverPRO predicted liver-related events with a C-statistic of 0·80 (0·77-0·84) at 2 years. LiverPRO reliably identifies clinically significant liver fibrosis and elevated liver stiffness, predicts the risk of liver-related events in primary care, and is adaptable to the availability of different liver blood test analytes. On the basis of these results LiverPRO was certified according to IVDR class b, obtaining European CE approval in 2024. EU Horizon 2020 research and innovation programme and Novo Nordisk Foundation.

Response to Comments on “Fibrosis-4 index stratifies risks of hepatocellular carcinoma in patients with chronic hepatitis C″

Response to Comments on “Fibrosis-4 index stratifies risks of hepatocellular carcinoma in patients with chronic hepatitis C″

Targeted Plasma Bile Acid Metabolomic Analysis in Metabolic Dysfunction-Associated Steatohepatitis and Alcoholic Hepatitis.

Background: Even though many metabolic liver diseases can now be diagnosed using blood tests and diagnostic imaging, early diagnosis remains difficult. Understanding mechanisms contributing to the progression from Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Alcoholic Hepatitis (AH) to cirrhosis is critical to reduce the burden of end-stage liver disease. Monitoring individual bile acids has been proposed as a way to distinguish various liver disorders. Methods: This study explored bile acid profiles in patients with MASH and AH. Plasma samples from patients with MASH, AH, and a control group were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify bile acid concentrations. Targeted metabolomic analysis was performed to compare bile acid levels between the hepatitis and control groups. Results: Concentrations of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) were significantly elevated in the hepatitis group. Correlation analysis revealed strong positive relationships between the total and direct bilirubin levels and TUDCA and GCDCA. Aspartate aminotransferase (AST) showed strong positive correlations with TCDCA and GCDCA. Child-Pugh score, Fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score were positively correlated with GCA, whereas the aspartate aminotransferase-to-platelet ratio correlated with TCA, TCDCA, and GCA. The model for end-stage liver disease (MELD) score showed a strong positive correlation with GCDCA. Implications: GCDCA may serve as a predictive biomarker for liver damage, potentially enabling early diagnosis and targeted intervention in patients with MASH and AH.

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.

Hepatic Encephalopathy Scoring Model in Hepatic Cirrhosis Based on Clinical and Laboratory Parameter

Background: Hepatic Encephalopathy (HE) is a serious complication with a wide spectrum of clinical symptoms, from minimal changes to profound coma. HE is hard to diagnose without advanced laboratory parameters such as ammoni. This study aims to develop a scoring model to diagnose HE using clinical and laboratory parameters. Methods: An analytical cross-sectional study collected data from 96 hospitalized patients with liver cirrhosis from November 2021 to January 2022. Employing multivariate logistic regression analysis, the study aimed to identify autonomous factors associated with HE. Each significant variable was used to calculate patient probabilities. The score for each variable was computed utilizing the (B/SE)/lowest(B/SE) formula, demonstrating robust discriminatory capability. The scoring model was formulated and evaluated based on its sensitivity and specificity.Results: Nineteen point eight percent, equivalent to ninenteen patients, were admitted with HE. The scoring model was crafted based on nineteen variables. There were four significant variables in this model: Aspartate Aminotransferase (AST) (p=0.01), Total Bilirubin (p=0.007), Fibrosis-4-Index (FIB-4) (p=0.014), and Ascites (p=0.016). Each variable was scored as 1 for AST, -1 for total bilirubin, 1 for FIB-4-index, and 1 for Ascites. The probability was 2%, 14.2%, 57%, 91.4%, and 50%, following the total score of -1, 0, 1, 2, and 3, respectively. The sensitivity and specificity of the scoring model were 68.4% and 85.3%, respectively (AUC=84.7%).Conclusion: Daily laboratory and clinical manifestations related to hepatic cirrhosis could give a clue to diagnosing hepatic encephalopathy.Keywords: Clinical parameters, hepatic encephalopathy, laboratory parameters, scoring, scoring model

Native liver T1 mapping on magnetic resonance imaging for an evaluation of congestive liver injury in children with congenital heart disease.

Fontan-associated liver disease (FALD) may be caused by chronic liver congestion due to high central venous pressure (CVP). Recently, the usefulness of liver native T1 mapping in magnetic resonance imaging (MRI) in adulthood has been reported. To evaluate the usefulness of native liver T1 mapping in children with congenital heart disease (CHD), we investigated the utility of native liver T1 relaxation time (LT1) in pediatric Fontan patients in comparison to other CHDs. Correlations between LT1 and laboratory biomarkers or hemodynamic data were also assessed. A total of 155 patients with CHD (biventricular repair, n = 42; bidirectional Glenn circulation, n = 38; and Fontan circulation, n = 75) underwent blood tests, cardiac catheterization, and cardiac MRI within 48h. Both CVP and LT1 levels were higher in Fontan patients than in bidirectional Glenn and biventricular patients. There were significant correlation in the overall population and weak correlation in Fontan patients between CVP and LT1(correlation coefficient 0.644 [0.541-0.728] and 0.244 [0.0179-0.446], P < 0.001 and 0.035, respectively). Among the laboratory data, the multiple linear regression analysis revealed that the fibrosis-4 index and alanine aminotransferase were significantly correlated with LT1 in the overall population (P = 0.008,0.012), and the fibrosis-4 index was correlated with LT1 in Fontan patients (P = 0.019). LT1 might have some role to predict elevated CVP and liver injury in children with CHD.

Real-World Screening Data for Liver Fibrosis in Psoriasis Patients Treated with Biologics

Metabolic dysfunction-associated steatotic liver disease (MASLD) is positively associated with the prevalence and severity of psoriasis. The fibrosis-4 (FIB-4) index was developed to predict significant liver fibrosis. Using the FIB-4 index, the present study evaluated screening data for liver fibrosis, including MASLD, in patients with refractory psoriasis treated with biologics. All adult patients with psoriasis who were prescribed biologics at Nippon Medical School from August 2023 to May 2024 were included in this study. The FIB-4 index was classified as high (≥2.67), intermediate (1.30-2.66), and low (<1.30). Patients younger than 65 years were referred to a hepatologist if the FIB-4 index was high. If the score was intermediate, type IV collagen 7S (4COL7S) was checked, and they were referred to a hepatologist if it was ≥4.8 ng/mL. Patients aged ≥65 years were referred to a hepatologist if the FIB-4 index was high. If it was 2.00-2.66, they were referred to a hepatologist if the 4COL7S level was ≥4.8 ng/mL. Data from 96 patients were analyzed. The FIB-4 index was high in 10 patients, intermediate in 35 patients, and low in 51 patients. Eleven of 96 registered patients were newly referred to a hepatologist. Of these 11 patients, 5 received lifestyle guidance. For patients with refractory psoriasis, close cooperation between dermatologists and hepatologists is essential to prevent progression of liver fibrosis.

A randomized, open-label and prospective study to compare the efficacy and safety of synbiotics and rosuvastatin along with concomitant ursodeoxycholic acid in non-alcoholic fatty liver disease in North India

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder without significant alcohol consumption with a global prevalence of 32%. It is strongly associated with dyslipidemia, obesity, insulin resistance and gut dysbiosis with no current USFDA approved pharmacotherapy. Thus, this study aims to compare the efficacy and safety of Synbiotics and Rosuvastatin along with concomitant Ursodeoxycholic Acid (UDCA), in treatment of NAFLD. Methods: An interventional, randomized, open-label, prospective and parallel study of 12 weeks with patients randomly divided into two groups- A and B of thirty each. Group A was prescribed Synbiotics (Velgut) 5 billion CFUs BD and Group B was prescribed Rosuvastatin 20 mg OD along with UDCA 300mg BD in both the groups. Patients were followed up every 15 days and mainly assessed on hepatic profile, ultrasound grading, FibroScan, fibrosis indices and lipid profile along with safety profile and compliance. Results: On comparison, Group A showed significant improvement in hepatic parameters (p&lt;0.001) whereas Group B showed better improvement in lipid profile (p&lt;0.001). In case of ultrasonography for hepatic steatosis and assessment of liver stiffness by FibroScan, both Group A and B showed comparable improvement over 90 days (p=0.143 and p=0.722, respectively) with no worsening of any grades. Both groups performed similarly in terms of safety (p&gt;0.05) and patients showed good compliance (p&gt;0.05). Conclusion: Combination of Synbiotics and UDCA (Group A) seems to be more efficacious than Rosuvastatin and UDCA (Group B) in North-Indian NAFLD patients over a period of 3 months. Further extensive research with more sample size and studies with longer duration are needed to validate the role of these combination therapies in NAFLD.

Triglycerides to apolipoprotein A1 ratio: an effective insulin resistance-associated index in identifying metabolic dysfunction-associated fatty liver disease in type 2 diabetes mellitus

BackgroundThe triglycerides to Apolipoprotein A1 ratio (TG/APOA1) holds promise to be a more valuable index of insulin resistance for the diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus (T2DM). This study aims to evaluate the correlation between TG/APOA1 and MAFLD, as well as compare the efficacy of TG/APOA1 with triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-c) and triglyceride-glucose (TyG) index in identifying MAFLD among individuals with T2DM.MethodThis study consecutively recruited 779 individuals with T2DM for the investigation. The unenhanced abdominal CT scans were conducted to measure CT liver-spleen attenuation measurement (CTL-S). The CTL-S less than 1.0 and without other liver comorbidities were considered to be MAFLD. The binomial logistic regression analysis and restricted cubic spines (RCS) were employed to evaluate the association between TG/APOA1 and MAFLD. The receiver operating characteristic (ROC) curve analysis was performed to compare the efficacy of TG/APOA1 with TG/HDL-c and TyG index identifying MAFLD.ResultsThe TG/APOA1 exhibited a substantial increase in the MAFLD group (P&amp;lt;0.05). Even after adjustments for potential confounding factors, TG/APOA1 exhibited significant associations with nonalcoholic fatty liver disease fibrosis score (β=0.266, P&amp;lt;0.001), fibrosis-4 index (β=0.123, P=0.029), aspartate aminotransferase-to-platelet ratio index (β=0.113, P=0.037), and CTL-S (β=-0.225, P&amp;lt;0.001). Meanwhile, TG/APOA1 contributed to an independent variable for MAFLD, the odds ratio with a 95% CI was 2.092 (1.840-2.380) in the total population, 2.123 (1.810-2.511) in men, and 2.162 (1.824-2.587) in women. Additionally, the results also revealed a nonlinear association between elevated TG/APOA1 and higher MAFLD risk according to the RCS analysis whether in the total population, men, or women (P for nonlinearity and overall &amp;lt;0.001). Furthermore, TG/APOA1 had higher AUC level compared to TG/HDL-c and TyG index in the total population (0.769 vs 0.742, P=0.025; 0.769 vs 0.694, P &amp;lt; 0.001), men (0.776 vs 0.744, P=0.044; 0.776 vs 0.709, P &amp;lt; 0.001), and women (0.762 vs 0.728, P=0.041; 0.762 vs 0.674, P &amp;lt; 0.001).ConclusionTG/APOA1 serves as an effective index of insulin resistance in identifying MAFLD, offering advantages in the screening of MAFLD in T2DM.

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.

Meta-analysis of the efficacy of the Fuzheng Huayu formula in the treatment of hepatitis B-associated liver fibrosis or cirrhosis

Objective: To systematically evaluate the efficacy of Fuzheng Huayu (FZHY) tablets/capsules on hepatitis B-associated liver fibrosis or cirrhosis based on randomized controlled trials (RCTs) in order to provide more accurate evidence-based medicine for clinical rational drug use. Methods: Randomized controlled clinical trial research reports related to the treatment of hepatitis B-associated liver fibrosis or cirrhosis with FZHY published in SCI and statistical source core journals were retrieved from databases such as PubMed, Cochrane Library, and China National Knowledge Infrastructure (CNKI). RevMan 5.3 and Stata18.0 software were used to conduct a meta-analysis of the improvement rate of liver tissue inflammatory activity (HAI) and Ishak stage of liver fibrosis, the decrease value of liver stiffness measurement (LSM), hyaluronic acid (HA), laminin (LN), type Ⅲ procollagen (PC-Ⅲ), type Ⅳ collagen (IV-C), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (Alb). The Q test was used for the heterogeneity test, with a random-effect model selected for large heterogeneity and a fixed-effect model for less heterogeneity. Results: A total of 852 articles were retrieved. Duplicate articles, non-RCT articles, non-SCI/statistical source/core journal articles, and other articles that did not meet the inclusion criteria were sequentially excluded. Finally, a total of 2 746 cases (1 382 cases in the FZHY group and 1 364 cases in the control group) were included from 25 studies. The results of statistical analysis showed that the improvement rates of HAI grade of liver inflammation were 75.56% (68/90) and 42.22% (38/90, P<0.001) in the FZHY group and the control group at 24-48 weeks of treatment, while the improvement rates of Ishak stage of liver fibrosis were 67.90% (110/162) and 40.91% (63/154, P=0.005), respectively. Compared with the control group (95%CI -5.10-1.77, P<0.001) the mean △LSM of the FZHY group decreased by 3.43 kPa (P<0.001)and 0.30 kPa (P=0.93) at 48 and 72 weeks of treatment. The standardized mean differences (SMDs) of △HA, △LN, △PC-Ⅲ and △Ⅳ-C were -1.12, -1.00, -0.89 and -1.10 (P<0.001) after 24 weeks of treatment between the FZHY group and the control group. The SMDs of △HA, △IV-C, △LN and △PC-Ⅲ were -1.13 (P=0.01), -1.51 (P<0.001), -0.53 (P=0.14) and -0.42 (P=0.19) after 48 weeks of treatment between the two groups. The △TBil, △ALT, △AST, and △ALB was -12.99 μmol/L (P=0.007), -36.91 U/L (P<0.001), -22.05 U/L (P=0.12), and 6.09 g/L (P=0.05) after 24 weeks of treatment between the two groups. The observation on indicators such as aspartate aminotransferase and platelet ratio index, fibrosis-4 index, and hepatocellular carcinoma incidence in current RCT studies remained deficient. Conclusion: FZHY can significantly improve the degree of histologic liver inflammation and fibrosis, LSM values, reduce serum liver fibrosis indexes, and serum bilirubin and transaminase levels in patients with hepatitis B-associated liver fibrosis or cirrhosis. Therefore, it is necessary to further explore the optimal course of FZHY and its long-term effects on the risk of complications of cirrhosis such as hepatocellular carcinoma, ascites, and esophageal varicose bleeding, through prospective large-sample multicenter real-world cohort studies.