Non-invasive Markers Of Liver Fibrosis Research Articles

Serum non-invasive liver fibrosis markers in patients with COVID-19

Serum non-invasive liver fibrosis markers in patients with COVID-19

No gender differences in the 24-month course of non-invasive liver fibrosis markers after DAA therapy in HCV-mono and HCV/HIV-coinfected patients

Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.

Skeletal muscle mass increases after viral eradication with direct-acting antivirals in patients with chronic hepatitis C: A longitudinal study.

Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.

Serum biomarkers associated with liver fibrosis in patients with type 2 diabetes

BACKGROUND: The diagnosis of liver fibrosis is an important task in the management of patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The currently used diagnostic methods have a number of disadvantages such as invasiveness and high cost, or insufficient sensitivity and specificity. Therefore, the search for new non-invasive markers of liver fibrosis remains an actual challenge.AIM: To assess a diagnostic value of serum growth differentiation factor-15 (GDF-15), microfibril-associated glycoprotein 4 (MFAP-4), collagen type IV alpha1 (COL4alpha1), Mac-2 binding protein (M2BPGI) and chitinase-3-like protein 1 (YKL-40) as markers of liver fibrosis in patients with type 2 diabetes and NAFLD.MATERIALS AND METHODS: A single center cross-sectional observational study was performed. The study included 74 patients, 23 men and 51 women, aged 18 to 74 years. Liver elastography was used as reference method for the fibrosis evaluation. APRI and fib-4, non-invasive fibrosis indices, were assessed. Serum concentrations of GDF-15, MFAP-4, COL4alpha1, M2BPGI, and YKL-40 were determined by ELISA. ROC analysis was used to evaluate the sensitivity and specificity of serum markers for the diagnosis of the liver fibrosis.RESULTS: Liver fibrosis stage 1 was verified in 16 subjects, stage 2 in 12, stage 3 in 7, and stage 4 in 19. Patients with advanced liver fibrosis (stages 3–4), compared with those without severe fibrosis (stages 0–2), had higher levels of GDF-15 (p=0.003), COL4alpha1 (p=0.007), and YKL-40 (p=0.04). Patients with stage 1-2 liver fibrosis had higher levels of COL4alpha compared to those without any signs of fibrosis (p=0.02). There were no significant differences in the level of MFAP-4 and M2BPGI between patients with different severity of fibrosis. According to the ROC analysis, GDF-15, COL4alpha1 and YKL-40 have diagnostic value in the detection of severe liver fibrosis comparable to that of the APRI and fib-4 indices.CONCLUSION: GDF-15, COL4alpha1 and YKL-40 could be considered as promising non-invasive markers of liver fibrosis in patients with type 2 diabetes and NAFLD.

Shear-wave elastography for monitoring Fontan-associated liver disease: A prospective cohort study.

The spectrum of Fontan-associated liver disease (FALD) varies from abnormal liver function tests to fibrosis and even cirrhosis. In this prospective study, we evaluated the role of shear-wave elastography (SWE) in predicting the presence of advanced FALD. Forty-eight patients (30 males, 13.9 [6-21] years) with a Fontan circulation were evaluated at 8.3 (2.1-18.7) years since the Fontan surgery. The median liver stiffness measurement (LSM) value was higher than values in normal children at 15.4 (9.5-38.7) kPa. The LSMs had a weak but significant correlation with age at the time of LSM (r = 0.25, p = 0.01) and duration post-Fontan surgery (r = 0.31, p = 0.02). It had a poor correlation with the concomitant aspartate transaminase-to-platelet ratio index (r = 0.1, p = 0.39). No difference in the elastography values between children with and without ultrasound evidence of advanced liver disease (17.7 [interquartile range, IQR: 4] vs. 16.1 [IQR: 6], p = 0.62] was observed. Further studies are required to determine the precise role of SWE as a noninvasive marker of liver fibrosis in FALD.

Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study

Background & AimsIn phase 2 studies, efruxifermin, an Fc–FGF21 analog, significantly reduced steatohepatitis and fibrosis in patients with non-alcoholic steatohepatitis (NASH), now called metabolic dysfunction-associated steatohepatitis (MASH), for which there is no approved treatment. Type 2 diabetes (T2D) and obesity are prevalent among patients with MASH and increasingly treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This study evaluated the safety and efficacy of efruxifermin in patients with MASH, fibrosis, and T2D taking a GLP-1RA. MethodsCohort D was a double-blind, placebo-controlled phase 2b study in adults with T2D and MASH with fibrosis (F1–F3) on stable GLP-1RA therapy randomized (2:1) to receive efruxifermin 50 mg or placebo, once weekly for 12 weeks. The primary endpoint was safety and tolerability of efruxifermin added to a stable dose of GLP-1RA. Secondary endpoints included changes in hepatic fat fraction (HFF), markers of liver injury and fibrosis, and metabolic parameters. ResultsAdults (N=31) with T2D and MASH fibrosis (F1–F3) on a stable GLP-1RA (semaglutide, 48.4%; dulaglutide, 45.2%; liraglutide, 6.5%) received efruxifermin 50 mg (N=21) or placebo (N=10) for 12 weeks. The addition of efruxifermin to a GLP-1RA appeared safe and well tolerated. The most frequent efruxifermin-related adverse events were mild–moderate gastrointestinal events. One patient receiving efruxifermin discontinued due to nausea, and another withdrew consent. There were no treatment-related serious adverse events. After 12 weeks, efruxifermin reduced HFF by 65% (P<.0001 vs placebo) compared to a 10% reduction for placebo (GLP-1RA alone). Efruxifermin also improved noninvasive markers of liver injury, fibrosis, glucose, and lipid metabolism while maintaining GLP-1RA–mediated weight loss. ConclusionsThe tolerability profile of efruxifermin added to GLP-1RA appeared comparable to that of either drug alone, while also significantly reducing HFF and noninvasive markers of fibrosis in patients with MASH and T2D. Liver health in patients already on a GLP-1RA may be further improved by addition of efruxifermin. Clinicaltrials.gov no. NCT05039450

Liver fibrosis index is associated with functional outcome among acute ischemic stroke patients

IntroductionThe fibrosis-4 (FIB-4) index and the fibrosis-5 (FIB-5) index are noninvasive markers of liver fibrosis in patients with nonalcoholic fatty liver disease. Although liver fibrosis a potential risk factor for stroke development, it is uncertain whether liver fibrosis influences stroke outcomes. We investigated the associations between these two indices and stroke patient outcomes and compared their predictive accuracy. MethodsWe conducted a double-center, hospital-based, retrospective study. Consecutive acute ischemic stroke patients (n=2399) were analyzed. We calculated the FIB-4 index and the FIB-5 index and evaluated their relationships with poor stroke outcome, which was defined as a modified Rankin Scale score of 3–6 at three months after stroke. We evaluated the ability of each index to predict stroke outcome according to cutoff values calculated from receiver operating characteristic (ROC) curves. ResultsOf 2399 recruited patients, 1549 patients (mean age, 73 years) were analyzed. The FIB-4 index and FIB-5 index had similar areas under their ROC curves for predicting stroke outcome (FIB-4 index, 0.675 and FIB-5 index, 0.683, P=0.334). The cutoff points of the FIB-4 index and FIB-5 index according to the ROC analysis were associated with poor stroke outcome in the multivariable analyses (odds ratio [OR] 2.23, 95 % confidence interval [CI] 1.72–2.89, OR 1.93, 95 % CI 1.47–2.54, respectively). ConclusionsLiver fibrosis scores may be useful for predicting outcomes in patients with acute stroke. The FIB-4 and FIB-5 indices should be considered comprehensive tools for assessing the outcome risk after ischemic stroke.

The Diagnostic Value of FibroTest and Hepascore as Non-Invasive Markers of Liver Fibrosis in Primary Sclerosing Cholangitis (PSC).

The aim of this study was to evaluate the diagnostic usefulness of two non-invasive, validated, and patented markers of liver fibrosis, the Hepascore and FibroTest, in patients with primary sclerosing cholangitis (PSC). The study group consisted of 74 PSC patients and 38 healthy subjects. All patients had a liver biopsy. The Hepascore and FibroTest were calculated using specific algorithms. The ANOVA rank Kruskal-Wallis test revealed differences in the Hepascore and FibroTest between patients divided according to histological stage (p < 0.001 for both comparisons). The Hepascore and FibroTest had significantly higher results in patients with significant fibrosis (F ≥ 2) in comparison to those with no significant fibrosis (F1) (p < 0.001 for both tests) and higher values in patients with cirrhosis (F4) when compared to those without cirrhosis (F1-F3) (p < 0.001 for both comparisons). The Hepascore test showed a diagnostic sensitivity of 96.8%, a specificity of 100% for fibrosis (at cut-off 0.52) and a diagnostic sensitivity of 95.2%, and a specificity also of 100% for cirrhosis (at 0.80). The FibroTest in point 0.51 for the diagnosis of fibrosis obtained the following values: 58.6%, 90%, 89.5%, and 60%, respectively, and in point 0.73 for the diagnosis of cirrhosis: 42.9%, 100%, 100%, and 45.5, respectively. The Hepascore test reached an excellent diagnostic power in identifying both fibrosis and cirrhosis (AUC = 1.0). The FibroTest and Hepascore are highly valuable for the evaluation of the severity of liver fibrosis and cirrhosis in PSC patients and can be used as a primary screening method, allowing for a significant reduction in the need for liver biopsy. Both markers have the required sensitivity and specificity to detect liver fibrosis and cirrhosis and can be equally used in clinical practice, although the Hepascore seems to be a better test because it is more specific.

Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C

Background & aimsLife-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. Methods491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical–biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. ResultsDuring a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01–1.05), age (HR, 1.04; 95% CI, 1.01–1.08) and albumin levels (HR, 0.90; 95% CI, 0.84–0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08–1.37) and albumin (HR, 0.90; 95% CI, 0.84–0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. ConclusionSimple models based on non-invasive markers of liver fibrosis, LSM or FIB-4, together with age and albumin levels at SVR permit to identify subsets of patients with HCC risk clearly <1%/year, for whom HCC surveillance might not be cost-effective.

The Diagnostic Performance of Serum Hyaluronic Acid and Collagen III in Differentiating Liver Fibrosis in HCV-Induced Patients

Abstract Introduction/Objective Chronic liver diseases may lead to inflammation and progressive scarring, causing irreversible hepatic damage (cirrhosis). To avoid the complications of liver puncture biopsy, Collagen III and Hyaluronic acid are studied as non-invasive markers of liver fibrosis in chronic liver diseases. Aim of the work: Discovering the diagnostic role of serum Hyaluronic acid and Collagen III in liver fibrosis associated with chronic HCV patients. Methods/Case Report The study was performed on 118 patients with liver fibrosis associated with chronic HCV (60 males and 58 females) and 50 age-matched healthy subjects (27 males and 23 females). Liver function tests were measured, including ALT, AST, [AST/ ALT] ratio, albumin, total bilirubin, and platelets counts. APRI was also calculated as [AST/ (upper limits of normal)/ platelets count 109/L]×100. Serum levels of Collagen III (ng/ml) and hyaluronic acid (µg/L) were determined. Plotted receiver-operating characteristic (ROC) curves were used to assess and compare the diagnostic accuracy of biomarkers. Results (if a Case Study enter NA) The area under ROC curve of collagen III in discriminating liver fibrosis in patients associated with chronic HCV infection and healthy ones was 0.805; P&amp;lt; 0.0001. The Sensitivity and Specificity were 62% and 96%, respectively. While the area under ROC curve of hyaluronic acid in discriminating liver fibrosis patients associated with chronic HCV infection from healthy volunteers was 0.832; P &amp;lt; 0.0001. The Sensitivity and Specificity were 72% and 94%, respectively. Also, there was no significant correlation between levels of collagen III and hyaluronic acid; (r=0.01 &amp; P=0.714). Conclusion Collagen III and Hyaluronic acid can identify patients with liver fibrosis with a detection rate of 62% and 72%, respectively. So, both biomarkers are considered powerful non-invasive methods in discriminating and diagnosing liver fibrosis in chronic HCV patients.

Effect of fish oil supplementation on the concentration of miRNA-122, FGF-21 and liver fibrosis in patients with NAFLD: Study protocol for a randomized, double-blind and placebo-controlled clinical trial

To date, no specific drugs are available for non-alcoholic fatty liver disease (NAFLD), though the effect of fish oil supplementation on improving fibrosis in patients with NAFLD has been evaluated. N-3 polyunsaturated fatty acids (n-3 PUFA) may modulate the concentration of microRNAs (miRNAs) and fibroblast growth factor (FGF)-21, which have been identified as non-invasive markers of liver fibrosis. The present study aims to evaluate whether n-3 PUFA supplementation can modulate miRNA-122 and FGF-21 and improve liver fibrosis and steatosis, measured by transient hepatic elastography (THE), in individuals with NAFLD. A randomized, double-blind, placebo-controlled clinical trial will be conducted to evaluate the effect of 4g/day supplementation of fish oil (2100mg EPA and 924mg DHA) in patients with NAFLD over a 6-month period. Fifty-two patients aged >19 years will be randomly assigned to either a placebo (olive oil) or treatment (fish oil) group. Anthropometric data, food intake, physical activity, body composition, resting energy expenditure (evaluated using indirect calorimetry), liver enzymes, platelets, lipids and glucose profile, inflammatory markers (such as C-reactive protein, neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios), miRNA-122 and FGF-21 concentration, and incorporation of fatty acids into the erythrocyte membrane (analyzed using gas chromatography) as well as the degree of liver fibrosis and steatosis assessed using THE (Fibroscan® Touch 502, Paris, France) and liver biomarkers Steato-Brazilian Longitudinal Study of Adult Health, Fatty Liver Index, NAFLD Fibrosis Score, Fibrosis-4 score, and FibroScan-AST score will be evaluated at the beginning and end of the treatment. Continuous variables with normal distribution will be compared between placebo and intervention groups using Student's T test for independent samples; continuous non-parametric variables will be compared using Dunn or Mann-Whitney test. Associations between categorical variables will be analyzed using the chi-square test, and within-group differences will be evaluated using the Wilcoxon signed-ranks test. The criterion for determining significance will be set at 5%. The present study protocol will investigate the supplementation of EPA-rich fish oil as an alternative treatment for NAFLD and its feasibility in affecting the concentration of miRNA-122 and FGF-21 markers. Its findings will offer valuable contributions to the literature. ReBEC number RBR-8dp876.

P68 Liver fibrosis is independent of methotrexate use in patients with moderate-to-severe psoriasis

Abstract Methotrexate has been implicated for liver disease in patients with psoriasis for many years. Liver fibrosis (LF) has various established risk factors, but data on the impact of methotrexate on LF in patients with psoriasis are lacking. This cross-sectional cohort study aimed to determine the prevalence of LF using noninvasive LF markers in patients with psoriasis, and to evaluate the relationship between LF and the cumulative dose of methotrexate and other liver disease risk factors. Adults with moderate-to-severe chronic plaque psoriasis diagnosed by a dermatologist, who were selected for a LF assessment, were recruited from dermatology clinics in a tertiary centre between June 2020 and March 2021. Data were recorded as part of standard clinical care and at the time of recruitment. Patients underwent transient elastography to evaluate LF. Three values for liver stiffness measurement (LSM) were used, indicating ≥ mild LF (≥ 7 kPa), ≥ moderate LF (≥ 7.9 kPa) and ≥ advanced LF (≥ 9.5 kPa). Both continuous and categorical LSM values were used for evaluation. A total of 225 patients were included [median age 48, interquartile range (IQR) 37–57, 51% female]. Fifty-six per cent had a body mass index (BMI) ≥ 30 kg m−2, and the median alcohol use disorders identification test (AUDIT) score was 4 (IQR 1–7, 23% score ≥ 8). Ninety-one per cent had received methotrexate for a median duration of 36 months (IQR 14–78). Prevalence rates of LF were 31%, 21% and 13% using LSM ≥ 7 kPa, ≥ 7.9 kPa and ≥ 9.5 kPa, respectively. There was no association between methotrexate and continuous LSM values [unadjusted coefficient 0.16, 95% confidence interval (CI) 0.49–0.82; P = 0.63] or using the categorical LSM cutoff values: 7 kPa (unadjusted coefficient 1.06, 95% CI 0.98–1.15; P = 0.19), 7.9 kPa (unadjusted coefficient 1.03, 95% CI 0.94–1.12; P = 0.58) and 9.5 kPa (unadjusted coefficient 1.01, 95% CI 0.91–1.12; P = 0.84). Similarly, no significant relationship was found when adjusting for other risk factors for LF. The following risk factors were associated with higher LSM values: BMI (P &amp;lt; 0.001), waist circumference (P &amp;lt; 0.001), metabolic syndrome (P &amp;lt; 0.001), AUDIT score (P = 0.020) and Fib-4 score (P = 0.03). This study confirms a high prevalence of significant LF in patients with moderate-to-severe psoriasis. More importantly, it shows that cumulative methotrexate was not associated with LF, and other risk factors including BMI, waist circumference, metabolic syndrome, alcohol intake and Fib-4 score are important predictors for LF. The findings suggest that these risk factors should be assessed in this group of patients to identify patients requiring regular liver health monitoring. Further research is needed to determine whether methotrexate contributes to the progression of LF in the context of pre-existing LF.

Utility of non-invasive liver fibrosis markers to predict the incidence of chronic kidney disease (CKD): A systematic review, meta-analysis, and meta-regression

Background and aimsChronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) share common risk factors and pathogenesis mechanisms. However, the association between the degree of liver fibrosis and the incidence of CKD remains unclear. This study aims to examine the utility of non-invasive fibrosis markers to predict the occurrence of CKD. MethodsCochrane Library, Scopus, and Medline were searched up to May 20th, 2023 using combined keywords. Literature that analyzes FIB-4, NFS, and APRI to predict CKD incidence was included in this review. We used random-effect models of odds ratio (OR) with 95% confidence intervals (CI) to express the outcomes in this review. ResultsTwenty-one studies were included. Our meta-analysis showed that high FIB-4 was associated with a higher incidence of CKD (OR 2.51; 95%CI: 1.87–3.37, p < 0.00001, I2 = 96%). Further regression analysis revealed that this association was significantly influenced by hypertension (p = 0.0241), NAFLD (p = 0.0029), and body mass index (BMI) (p = 0.0025). Our meta-analysis also showed that high NFS (OR 2.49; 95%CI: 1.89–3.30, p < 0.00001, I2 = 96%) and high APRI (OR 1.40; 95%CI: 1.14–1.72, p = 0.001, I2 = 26%) were associated with a higher incidence of CKD. ConclusionsThis study suggests that these non-invasive liver fibrosis markers can be routinely measured both in NAFLD patients and the general population to enable better risk stratification and early detection of CKD.

Fibrosis-4 Index as a Predictor for Disease Severity and Mortality in Patients with COVID-19

Objective: The Fibrosis-4 (FIB-4) index is a noninvasive marker of liver fibrosis in various patient populations. We examined whether there is a relationship between the severity and prognosis of COVID-19 disease and the FIB-4 index. Materials and Methods: This stuy is a cross-sectional and retrospective. The patients were divided into two groups as those hospitalized in the intensive care unit (ICU) and those hospitalized in the clinic (non- ICU). Results: Of the total 158 cases,86(54%) were male. Age, total bilirubin, AST levels and FIB-4 index were higher in ICU patients compared to non-ICUs (p&amp;lt;0.001,p=0.002, p=0.003, p&amp;lt;0.001 respectively). FIB-4 index non-survivors were also higher (p=0.002). When the effect of the FIB-4 index on the severity of COVID-19 disease and mortality was evaluated by ROC analysis, both ICU and non-survivors were found to be significant (respectively FIB-4 score;AUC=0.705,95%CI:0.624-785,p&amp;lt;0.001;AUC=0.654,95%CI:0.566-742,p=0.002). When the FIB-4 index cut-off value for disease severity was taken as 2.19, 70.0% sensitivity and 60% specificity were found in predicting disease severity. Moreover, when the FIB-4 index cut-off value for mortality was taken as 2.19, 71.2% sensitivity and 53% specificity were found in predicting mortality. Conclusion: The FIB-4 index is an independent predictor of severity and mortality in COVID-19 patients requiring ICU.

Performance of Non-invasive Biomarkers of Liver Fibrosis Amongst Hispanics and African Americans.

Liver biopsy is the gold standard for fibrosis staging. However, it is limited by significant complications. Non-invasive markers of fibrosis have been developed as an alternative to liver biopsy. The performance of these different markers varies with the etiology of liver fibrosis and possibly amongst different ethnicities. We aim to assess the performance of non-invasive markers of liver fibrosis amongst Hispanics and African Americans. This is a retrospective cohort analysis of patients who had liver biopsy as part of their evaluation of chronic liver disease. One hundred and twenty-six records were analyzed. Univariate and multivariate analyses were performed. Probit regression receiver operating characteristic curve analysis was used to assess the sensitivity of the different non-invasive biomarkers and underlying variables with respect to liver biopsy. The following non-invasive markers for fibrosis were used: Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), age-platelet, AST/alanine aminotransferase (AST/ALT) ratio, fibrosis cirrhosis index (FCI), and fibrosis index (FI). About two-thirds of the study population were African Americans with majority of the study population having chronic liver disease from viral infection. Minimal to no fibrosis by the METAVIR (an acronym for Meta-analysis of Histological Data in Viral Hepatitis) score was found in 58% of patients compared to 42% with moderate to severe fibrosis. Hispanics were more likely than Blacks to have hepatic steatosis. Age significantly increased the sensitivity and specificity of APRI and age-platelet scores. The AST/ALT score had a lower sensitivity for liver fibrosis in women compared to men in our study population. The sensitivity of FIB-4 and age-platelet was higher in Hispanics compared to African Americans while the opposite was the case for APRI, AST/ALT, FCI, and FI. Non-invasive biomarkers are useful in detecting liver fibrosis. FIB-4 and age-platelet have a high sensitivity in Hispanics while African Americans have a high sensitivity for APRI, AST/ALT, FCI, and FI. It is worth noting that these non-invasive biomarkers had variable performances when ethnicity, age, and sex were considered in our population.

Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C

Background & aimsLife-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. Methods491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical–biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. ResultsDuring a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01–1.05), age (HR, 1.04; 95% CI, 1.01–1.08) and albumin levels (HR, 0.90; 95% CI, 0.84–0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08–1.37) and albumin (HR, 0.90; 95% CI, 0.84–0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. ConclusionSimple models based on non-invasive markers of liver fibrosis, LSM or FIB-4, together with age and albumin levels at SVR permit to identify subsets of patients with HCC risk clearly <1%/year, for whom HCC surveillance might not be cost-effective.

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated

The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers. Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements. A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9kPa (adjusted odds ratio= 3.19; 95% CI 1.95-5.20; p <0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio= 1.76; 95% CI 1.20-2.56; p= 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis. The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX. Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients' metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate.

Dynamic changes in the liver fibrosis marker FIB-4 as a predictor of adverse cardiovascular events in patients with high and very high cardiovascular risk

The aim of the study was to assess the prognostic significance of dynamic changes in the surrogate noninvasive liver fibrosis marker FIB-4 in relation to the development of adverse cardiovascular events in patients with high and very high cardiovascular risk (CVR). Materials and Methods. Men and women aged 40-67 years with high and very high CVR were included in the study. Fibrosis-4 index (FIB-4) was used as a noninvasive marker of liver fibrosis. The combined end point was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization. Results. 105 patients with high and very high CVR were included in the study. The duration of the follow-up period was 34.6 (15.0; 52.3) months. Events constituting the combined end point occurred in 26 (24.7%) patients. During the follow-up period, FIB-4 index values of <1.45 (0.90 (0.68; 1.23) at study inclusion changed to ≥1.45 (1.66 (1.61; 1.90) in 13 (12.4%) patients. Over the follow-up period, the median FIB-4 change was -23.0% (-1.81; 11.5) and by the end of the follow-up period, the median FIB-4 values were 1.17 (0.97; 1.47). According to Kaplan-Meier analysis, the cumulative risk of events constituting the combined end point was found to be significantly higher in patients with an increase in FIB-4. By Cox single-factor regression analysis, an increase in FIB-4 (from values <1.45 to ≥1.45) was associated with a 4.42-fold increase in the relative risk (RR) of events constituting the combined end point (95% CI 1.33-14.7; p=0.015). Conclusion. In patients with high and very high CVR over 40 years of age, an increase in FIB-4 liver fibrosis index from values <1.45 to ≥1.45 during 2.8 years of follow-up was associated with a 4.42-fold increase in the RR of adverse cardiovascular events (95% CI 1.33-14.7; p=0.015).

Significance of Fib4 index as an indicator of alcoholic hepatotoxicity in health examinations among Japanese male workers: a cross-sectional and retrospectively longitudinal study

BackgroundFib4 index (Fib4) is clinically used as a noninvasive marker of liver fibrosis. In this study, we aimed to preliminarily investigate whether Fib4 can be used to detect individuals who need assessment for alcoholic liver disease (ALD) in the general population by clarifying the detailed association of Fib4 with alcohol consumption and gamma-glutamyl transferase (GGT) among male workers.MethodsWe analyzed data sets on the comprehensive medical examinations of male workers as cross-sectional and retrospectively longitudinal studies. We enrolled 10 782 males (mean age: 52.2 ± 10.2 years) in FY2019 and 7845 males (mean follow-up: 12.6 ± 6.7 years) who could be consecutively followed up for 20 years from FY2000 to FY2019. Data were evaluated using logistic regression and COX proportional analysis.ResultsIn the cross-sectional setting, the rate of Fib4 ≥ 2.67 in heavy drinkers (≥ 40 g of ethanol/day) was increased dose dependently in those over 65 years old, and that of body mass index ≥ 30 kg/m2 was increased in those over 60 years old, but not in those with fatty liver. The odds ratio (OR) (95% confidence interval [CI]) for heavy drinking was 4.30 (95% CI = 1.90–9.72), and GGT ≥ 200 IU/L was considerably high (OR = 29.05 [95% CI = 17.03–49.56]). In the longitudinal setting, heavy drinkers and those with GGT ≥ 200 IU/L at 10 years after the baseline showed an increased risk for Fib4 ≥ 2.67 (hazard ratio = 2.17 [95% CI = 1.58–2.98] and 7.65 [95% CI 5.26–11.12], respectively).ConclusionsThe development of Fib4 ≥ 2.67 after 10 years was associated with heavy alcohol drinking and GGT level ≥ 200 IU/L. Therefore, Fib4 combined with GGT could indicate high risk of ALD. However, clinical examinations and course observations are essentially needed.

Prospects for the use of drugs from the group of agonists of glucagon-like peptide-1 receptors in the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. To a large extent, the development of this disease is associated with metabolic syndrome. There is a pathogenetic association of NAFLD with obesity, type 2 diabetes mellitus (DM2), cardiovascular diseases and chronic kidney disease. Numerous studies demonstrate that an increase in the incidence of NAFLD occurs in parallel with an increase in the prevalence of obesity and DM 2. A number of scientific studies in the field of medicine have made it possible to identify the main pathogenetic mechanisms of the development of the disease, as well as the possibility of using various pharmacological drugs to correct these conditions. Currently, the possibility of using in the future a group of drugs that have a single mechanism for controlling the development of hepatic steatosis, and further progression with the formation of inflammation, cirrhosis and, in some cases, hepatocellular carcinoma, is being considered. Of particular interest is a class of drugs intended for the treatment of type 2 diabetes and obesity – glucagon-like peptide-1 receptor agonists (arGLP-1). A search was made of clinical studies, meta-analyses, literature reviews in databases and registries of medical publications over a period of 10 years. Changes in anthropometric indications, changes in non-invasive markers of liver steatosis, inflammation and fibrosis, as well as histological data on the background of the use of drugs of the arGLP-1 class were studied. It has been demonstrated that the study drug class may have a significant potential for impact on NAFLD. However, further studies with sufficient duration and histological evaluation are needed to fully evaluate the effectiveness of arGLP-1 in the treatment of NAFLD.