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Background: The impact of liver fibrosis on the clinical outcomes of patients with sepsis-induced coagulopathy (SIC) is not well understood. This study aimed to evaluate the association between liver fibrosis scores and in-hospital mortality in SIC patients. Methods: In this retrospective observational cohort study, data were collected from patients diagnosed with sepsis and admitted to the ICU at the First Affiliated Hospital of Wenzhou Medical University between January 2017 and December 2023. Liver fibrosis was evaluated using three scores: Fibrosis-4 (Fib-4), Aspartate Aminotransferase–to–Platelet Ratio Index (APRI), and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Patients were divided into tertiles according to their liver fibrosis scores, and the primary outcome was in-hospital mortality. Multivariable logistic regression and restricted cubic spline regression analyses were used to assess associations, complemented by sensitivity analyses through subgroup evaluations. Results: The cohort included 948 patients diagnosed with SIC with an in-hospital mortality of 26.16%. Multivariate logistic regression analysis revealed a significant association between higher liver fibrosis scores and increased in-hospital mortality. Specifically, patients in the highest tertile of Fib-4, APRI, and NFS scores had significantly higher odds of mortality (FIB-4: OR 3.62, 95% CI 1.03–12.69; APRI: OR 2.16, 95% CI 0.88–5.30; NFS: OR 6.80, 95% CI 2.11–21.93) compared to those in the lowest tertile. The restricted cubic spline regression model showed a linear increase in the risk of in-hospital mortality with increasing liver fibrosis score. Sensitivity analysis confirmed the consistency and stability of the results across the different subgroups. Conclusion: Our study suggests that elevated liver fibrosis scores, particularly Fib-4 and NFS, are associated with higher in-hospital mortality in SIC patients. Further research, especially larger prospective studies, are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Aims: To estimate the incidence of major adverse cardiovascular events (MACE), expanded MACE, and MACE or Death across Fibrosis- 4 score (FIB-4) categories in people with type 2 diabetes and to determine whether efpeglenatide's effect varies with increasing FIB-4 severity. Materials and methods: AMPLITUDE-O trial data were used to estimate the relationship of FIB-4 score categories to the hazard of MACE, expanded MACE, and MACE or death. Interactions on these outcomes between baseline FIB-4 score, and between FIB-4 score and efpeglenatide were also assessed. Results: Baseline FIB-4 score was available for 4059 participants (99.6%) allowing subdivision of the population in tertiles. During a median follow-up of 1.8 years, numerical increases in the incidence of all 3 outcomes did not change significantly across tertiles of FIB-4 score (P for trend ≥ 0.25) with negligible relationship of the score to incident outcomes (MACE HR, per 1 SD higher score, 95% CI: 1.00, 0.89–1.13). Efpeglenatide's effect on all MACE outcomes did not vary across FIB-4 tertiles (all interaction p values ≥ 0.64). Conclusions: In high-risk people with type 2 diabetes, the degree of liver fibrosis, as estimated by FIB-4 score, was not related to incident cardiovascular outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of FIB-4 category. [ABSTRACT FROM AUTHOR]

Abstract Background The impact of liver fibrosis on the clinical outcomes of patients with sepsis-induced coagulopathy (SIC) is not well understood. This study aimed to evaluate the association between liver fibrosis scores and in-hospital mortality in SIC patients. Methods In this retrospective observational cohort study, data were collected from patients diagnosed with sepsis and admitted to the ICU at the First Affiliated Hospital of Wenzhou Medical University between January 2017 and December 2023. Liver fibrosis was evaluated using three scores: Fibrosis-4 (Fib-4), Aspartate Aminotransferase–to–Platelet Ratio Index (APRI), and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Patients were divided into tertiles according to their liver fibrosis scores, and the primary outcome was in-hospital mortality. Multivariable logistic regression and restricted cubic spline regression analyses were used to assess associations, complemented by sensitivity analyses through subgroup evaluations. Results The cohort included 948 patients diagnosed with SIC with an in-hospital mortality of 26.16%. Multivariate logistic regression analysis revealed a significant association between higher liver fibrosis scores and increased in-hospital mortality. Specifically, patients in the highest tertile of Fib-4, APRI, and NFS scores had significantly higher odds of mortality (FIB-4: OR 3.62, 95% CI 1.03–12.69; APRI: OR 2.16, 95% CI 0.88–5.30; NFS: OR 6.80, 95% CI 2.11–21.93) compared to those in the lowest tertile. The restricted cubic spline regression model showed a linear increase in the risk of in-hospital mortality with increasing liver fibrosis score. Sensitivity analysis confirmed the consistency and stability of the results across the different subgroups. Conclusion Our study suggests that elevated liver fibrosis scores, particularly Fib-4 and NFS, are associated with higher in-hospital mortality in SIC patients. Further research, especially larger prospective studies, are needed to validate these findings.

Abstract Aims To estimate the incidence of major adverse cardiovascular events (MACE), expanded MACE, and MACE or Death across Fibrosis- 4 score (FIB-4) categories in people with type 2 diabetes and to determine whether efpeglenatide’s effect varies with increasing FIB-4 severity. Materials and methods AMPLITUDE-O trial data were used to estimate the relationship of FIB-4 score categories to the hazard of MACE, expanded MACE, and MACE or death. Interactions on these outcomes between baseline FIB-4 score, and between FIB-4 score and efpeglenatide were also assessed. Results Baseline FIB-4 score was available for 4059 participants (99.6%) allowing subdivision of the population in tertiles. During a median follow-up of 1.8 years, numerical increases in the incidence of all 3 outcomes did not change significantly across tertiles of FIB-4 score (P for trend ≥ 0.25) with negligible relationship of the score to incident outcomes (MACE HR, per 1 SD higher score, 95% CI: 1.00, 0.89–1.13). Efpeglenatide’s effect on all MACE outcomes did not vary across FIB-4 tertiles (all interaction p values ≥ 0.64). Conclusions In high-risk people with type 2 diabetes, the degree of liver fibrosis, as estimated by FIB-4 score, was not related to incident cardiovascular outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of FIB-4 category.

Evaluation of inflammation and liver fibrosis by using well established indices of serum biomarkers in hepatitis caused by viral agents has been reported in recent studies. But the diagnostic performance and prediction of liver damage in S. capitata infections has not yet been reported. The aim of the current study was to investigate the levels of systemic inflammatory indices based on liver enzymes and platelets, their effectiveness in detecting S. capitata infection and its degree of damage to the liver.

Background: In the 21st century, nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder. The prevalence of NAFLD within the general population in India ranges from 9 to 53%. The gold standard for assessing the severity of liver fibrosis is liver biopsy. However, due to various difficulties involved with liver biopsy, it is imperative to identify different non-invasive tools that can replace liver biopsy. Methodology: A prospective observational study of 130 patients meeting the inclusion criteria for NAFLD was done for a period of 18 months. We aimed to compare the performance characteristics of different noninvasive scores [fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI)] in predicting advanced fibrosis as assessed by FibroScan. Results: In the study, 76.9% of patients were male. Advanced fibrosis was seen in 12.3% of the patients. Majority of the patients with advanced fibrosis had metabolic syndrome. Based on the area under the receiver operating characteristic curve (AUROC), the new cut-off for ruling out advanced fibrosis for FIB-4, NFS, and APRI were 1.18, -0.9, and 0.65, respectively, and APRI had the best AUROC (0.768). Conclusion: Abnormal glycemic status and metabolic syndrome were risk factors for advanced fibrosis. The newly derived cut-offs for the FIB-4 score, NFS score, and APRI score had a better Negative predictive value compared to the original cut-offs. [ABSTRACT FROM AUTHOR]

Purpose of Review: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease affecting 30% of the global population. In this article, we summarize current expert guidelines, review clinical practice implications, and provide insight into the utility of non-invasive tests (NITs). Recent Findings: The burden of MASLD is growing with the obesity epidemic, yet disease awareness and diagnosis is low. Patients can progress to metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), which can advance to liver fibrosis, cirrhosis, hepatic decompensation, and liver cancer. NITs help identify high-risk patients who may benefit from specialty referral and MASH-directed therapy. Summary: Global societies offer various recommendations for the screening and diagnosis of MASLD utilizing evidence-based, widely accessible methods such as serum indices, NITs, and liver biopsy. Several targeted steatotic liver disease (SLD) screening tools and novel therapies are under development. [ABSTRACT FROM AUTHOR]

Background High-dose methotrexate (HDMTX) is a mainstay of primary central nervous system lymphoma (PCNSL) treatment. Transient hepatotoxicity from HDMTX has been characterized in pediatric patients but not in adults. We sought to characterize hepatotoxicity in adult PCNSL patients undergoing HDMTX treatment. Methods Retrospective study of 65 PCNSL patients treated at the University of Virginia from 02/01/2002 to 04/01/2020 was performed. Hepatotoxicity was defined using National Cancer Institute Common Toxicity Criteria (CTC) for adverse events, fifth version. High-grade hepatotoxicity was defined as a bilirubin or aminotransferase CTC grade of 3 or 4. Relationships between clinical factors and hepatotoxicity were assessed with logistic regression. Results Most patients (90.8%) had a rise of at least one aminotransferase CTC grade during HDMTX treatment. 46.2% had high-grade hepatotoxicity based on aminotransferase CTC grade. No patients developed high-grade bilirubin CTC grades during chemotherapy. Liver enzyme test values decreased to low CTC grade or normal in 93.8% of patients after the conclusion of HDMTX treatment without treatment regimen changes. Prior ALT elevation (P =.0120) was a statistically significant predictor of high-grade hepatotoxicity during treatment. Prior history of hypertension was associated with increased risk of toxic serum methotrexate levels during any cycle (P =.0036). Conclusions Hepatotoxicity develops in the majority of HDMTX-treated PCNSL patients. Transaminase values decreased to low or normal CTC grades in almost all patients after treatment, without modification of MTX dosage. Prior ALT elevation may predict patients' increased hepatotoxicity risk, and hypertension history may be a risk factor for delayed MTX excretion. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. Methods The study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student’s t test were used as appropriate. P values were adjusted for multiple comparisons. Results HCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females. Conclusions The decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV.

Background/purpose: A nomenclature of "metabolic associated fatty liver disease" (MAFLD) with a new definition was proposed in 2020 instead of the previous "non-alcoholic fatty liver disease" (NAFLD). Whether it better coheres with the clinical demand remains controversial. Methods: The participants with fatty liver on ultrasonography in Taiwan bio-bank cohorts were included. MAFLD is defined as the presence of fatty liver, plus any of the following three conditions: overweight/obesity, type 2 diabetes mellitus (DM), or metabolic dysfunction. The severity of liver fibrosis was determined using fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS). The risk of atherosclerotic cardiovascular disease was assessed using intima–media thickness (IMT) or plaques of carotid duplex ultrasound. Results: A total of 9,719 subjects (ages 55.9 ± 10.8; males 42.6%) were distributed among 4 groups: "overlapping group", "MAFLD only", "NAFLD only", and "neither fatty liver disease (FLD)" with the percentages of 79.7, 12, 7.1, and 1.2%, respectively. Compared with NAFLD patients, MAFLD patients had a greater percentage of males, higher levels of BMI, waist circumference, HbA1c, and triglyceride. In addition, they had higher levels of serum ALT, AST, GGT, fatty liver index (FLI), NFS, and IMT, but no difference in FIB-4 index and the percentage of carotid plaques. To note, "MAFLD only group" had greater levels of AST, ALT, GGT, FLI, FIB-4, NFS, IMT and a higher percentage of carotid plaques than the "NAFLD only group". Conclusion: The grand, population-based study showed MAFLD with new diagnostic criteria to aid in identifying a greater number of high-risk patients of metabolic, liver, and cardiovascular complications, suggesting MAFLD may be a better nomenclature than NAFLD in clinical practice. [ABSTRACT FROM AUTHOR]

Aim: To conduct a post hoc analysis to explore indices of hepatic steatosis/fibrosis and cardiorenal outcomes in the VERTIS CV study. Materials and Methods: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. Liver steatosis and fibrosis were assessed post hoc using the hepatic steatosis index (HSI) and fibrosis‐4 (FIB‐4) index to explore associations with cardiorenal outcomes (ertugliflozin and placebo data pooled, intention‐to‐treat analysis set). Cardiorenal outcomes (major adverse CV events [MACE]; hospitalization for heart failure [HHF]/CV death; CV death; HHF; and a composite kidney outcome) were stratified by baseline HSI and FIB‐4 quartiles (Q1‐Q4). Change in liver indices and enzymes over time were assessed (for ertugliflozin vs. placebo). Results: Amongst 8246 participants, the mean age was 64.4 years, body mass index 32.0 kg/m2, HSI 44.0 and FIB‐4 score 1.34. The hazard ratios (HRs) for MACE, HHF/CV death, CV death, and HHF by FIB‐4 score quartile (Q4 vs. Q1) were 1.48 (95% confidence interval [CI] 1.25, 1.76), 2.0 (95% CI 1.63, 2.51), 1.85 (95% CI 1.45, 2.36), and 2.94 (95% CI 1.98, 4.37), respectively (P < 0.0001 for all). With HSI, the incidence of HHF was higher in Q4 versus Q1 (HR 1.52 [95% CI 1.07, 2.17]; P < 0.05). The kidney composite outcome did not differ across FIB‐4 or HSI quartiles. Liver enzymes and HSI decreased over time with ertugliflozin. Conclusion: In VERTIS CV, higher FIB‐4 score was associated with CV events. HSI correlated with HHF. Neither measure was associated with the composite kidney outcome. Ertugliflozin was associated with a reduction in liver enzymes and HSI. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic liver diseases of all etiologies exist along a spectrum with varying degrees of hepatic fibrosis. Despite accumulating evidence implying associations between liver fibrosis and cognitive functioning, there is limited research exploring the underlying neurobiological factors and the possible mediating role of inflammation on the liver-brain axis. Methods: Using data from the UK Biobank, we examined the cross-sectional association of liver fibrosis (as measured by Fibrosis-4 score) with cognitive functioning and regional grey matter volumes (GMVs) while adjusting for numerous covariates and multiple comparisons. We further performed post-hoc preliminary analysis to investigate the mediating effect of C-reactive protein (CRP) on the association between liver fibrosis and both cognitive functioning and GMVs. Findings: We analysed behaviour from up to 447,626 participants (N ranged from 45,055 to 447,533 per specific cognitive metric) 37 years and older. 38,244 participants (age range 44–82 years) had GMV data collected at a median 9-year follow-up. Liver fibrosis showed significant associations with cognitive performance in reasoning, working memory, visual memory, prospective memory, executive function, and processing speed. Subgroup analysis indicated larger effects sizes for symbol digital substitution but smaller effect sizes for trail making in middle-aged people than their old counterparts. Neuroimaging analyses revealed significant associations between liver fibrosis and reduced regional GMVs, primarily in the hippocampus, thalamus, ventral striatum, parahippocampal gyrus, brain stem, and cerebellum. CRP levels were significantly higher in adults with advanced liver fibrosis than those without, indicating an elevated systemic inflammation. Moreover, the serum CRP significantly mediated the effect of liver fibrosis on most cognitive measures and regional GMVs in the hippocampus and brain stem. Interpretation: This study provides a well-powered characterization of associations between liver fibrosis, cognitive impairment, and grey matter atrophy. It also highlights the possibly mediating role of systemic inflammation on the liver-brain axis. Early surveillance and prevention of liver diseases may reduce cognitive decline and brain GMV loss. Funding: National Science Foundation, and National Institutes of Health.

Introduction and Objectives: Liver fibrosis is an important prognosis marker in non-alcoholic fatty liver disease (NAFLD). Biopsy has been considered the gold-standard method for measuring liver fibrosis; however, it is an invasive procedure. Non-invasive diagnostic tools have been developed, such as clinical scores and magnetic resonance elastography (MRE), which is the most accurate non-invasive method to determine liver fibrosis. Thus, the aim was to determine the NAFLD Fibrosis Score (NFS) and the Fibrosis-4 Score (FIB-4) cut-off points that best identify NAFLD patients at risk for developing liver fibrosis. Patients and Methods: Single-center cross-sectional study with prospective recruitment of NAFLD (trainingcohort) and MAFLD (validation-cohort) patients undergoing MRE. The NFS and the FIB-4 cut-off points that best-differentiated patients with fibrosis, using the MRE as the standard method, were determined. Results: Two cohorts were analyzed, a training cohort that included the initial 183 patients with NAFLD and a validation cohort that included 289 patients. In the training cohort, 60.1% hadmild steatosis and 11.5% had liver fibrosis ≥ F1 by MRE. ROC curves were developed for FIB-4 and NFS, and the cut-off points chosen were 1.505 (sensitivity=85% and specificity=86%) for FIB-4 and -0.835 (sensitivity=100% and specificity=70%) for NFS, showing greater specificity than the cut-off points currently used (51% and 76%, respectively). The two cohorts exhibited similar characteristics and similar sensitivity and specificity results for the chosen cut-off points. Conclusions: This study has shown cut-off points with greater specificity and excellent sensitivity to guide the indication for further liver evaluation by MRE in NAFLD patients. [ABSTRACT FROM AUTHOR]

Background: Fibrosis‐4 score (FIB4) was a non‐invasive surrogate to estimate the amount of liver scarring in chronic hepatitis. Considering the presence of increased central venous pressure and congestive hepatopathy in patients with decompensated heart failure, we therefore investigated the prognostic values of FIB4 in acute heart failure (AHF) patients. Method: Patients hospitalised primarily for HF were drawn from an intramural registry. FIB4 was calculated according to age, aspartate aminotransferase, alanine aminotransferase and platelet count. All‐cause mortality up to 5 years after discharge was obtained by linking to the national death registry. Results: Among a total of 1854 participants, 940 patients died during a mean follow‐up of 28.3 ± 21.8 months. FIB4 score was related to mortality and the composite of cardiovascular death or HF rehospitalisation, independent of age, sex, left ventricular ejection fraction, left atrial dimension, sodium and haemoglobin levels, estimated glomerular filtration rate, comorbidities, and medications [hazard ratio and 95% confidence interval of mortality: 1.009 (1.002–1.015), and the composite of cardiovascular death or HF hospitalisation: 1.020 (1.010–1.031)]. The prognostic value of FIB4 was predominantly in the subjects with heart failure and preserved or mildly reduced ejection fraction (HFpEF and HFmrEF), or coronary artery disease (CAD) than the counterparts [interaction p‐value <0.001, and 0.004, respectively]. Conclusions: FIB4 was an independent predictor of survival in AHF patients, irrespective of the phenotypes of HF. The higher predictive value of mortality of FIB4 was observed in the subjects with HFpEF, HFmrEF or CAD. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. Methods: The study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student’s t test were used as appropriate. P values were adjusted for multiple comparisons. Results: HCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females. Conclusions: The decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV. [ABSTRACT FROM AUTHOR]

Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays providing total cholesterol levels. Hence, these studies do not account for the individual cholesteryl ester (CE) species, which have different properties according to acyl chain length and desaturation. Methods: Free cholesterol (FC) and 15 CE species were quantified by flow injection analysis high-resolution Fourier Transform mass spectrometry (FIA-FTMS) in the serum of 178 patients with chronic HCV before therapy and during treatment with DAAs. Results: Serum CEs were low in HCV patients with liver cirrhosis and, compared to patients without cirrhosis, proportions of CE 16:0 and 16:1 were higher whereas % CE 20:4 and 20:5 were reduced. FC levels were unchanged, and the CE/FC ratio was consequently low in cirrhosis. FC and CEs did not correlate with viral load. Four CE species were reduced in genotype 3 compared to genotype 1-infected patients. During DAA therapy, 9 of the 15 measured CE species, and the CE/FC ratio, increased. Relative to total CE levels, % CE 16:0 declined and % CE 18:3 was higher at therapy end. At this time, % CE 14:0, 16:0 and 16:1 were higher and % CE 20:4 and 22:6 were lower in the cirrhosis than the non-cirrhosis patients. Viral genotype associated changes of CEs disappeared at therapy end. Conclusions: The serum CE composition differs between patients with and without liver cirrhosis, and changes through the efficient elimination of HCV. Overall, HCV infection and cirrhosis are associated with a higher proportion of CE species with a lower number of carbon atoms and double bonds, reflecting a less-favorable CE profile. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Liver fibrosis is an important prognosis marker in non-alcoholic fatty liver disease (NAFLD). Biopsy has been considered the gold-standard method for measuring liver fibrosis; however, it is an invasive procedure. Non-invasive diagnostic tools have been developed, such as clinical scores and magnetic resonance elastography (MRE), which is the most accurate non-invasive method to determine liver fibrosis. Thus, the aim was to determine the NAFLD Fibrosis Score (NFS) and the Fibrosis-4 Score (FIB-4) cut-off points that best identify NAFLD patients at risk for developing liver fibrosis. Patients and Methods: Single-center cross-sectional study with prospective recruitment of NAFLD (training-cohort) and MAFLD (validation-cohort) patients undergoing MRE. The NFS and the FIB-4 cut-off points that best-differentiated patients with fibrosis, using the MRE as the standard method, were determined. Results: Two cohorts were analyzed, a training cohort that included the initial 183 patients with NAFLD and a validation cohort that included 289 patients. In the training cohort, 60.1% had mild steatosis and 11.5% had liver fibrosis ≥ F1 by MRE. ROC curves were developed for FIB-4 and NFS, and the cut-off points chosen were 1.505 (sensitivity=85% and specificity=86%) for FIB-4 and -0.835 (sensitivity=100% and specificity=70%) for NFS, showing greater specificity than the cut-off points currently used (51% and 76%, respectively). The two cohorts exhibited similar characteristics and similar sensitivity and specificity results for the chosen cut-off points. Conclusions: This study has shown cut-off points with greater specificity and excellent sensitivity to guide the indication for further liver evaluation by MRE in NAFLD patients.

Background: In patients with nonalcoholic fatty liver disease, liver fibrosis was associated with a higher risk of cardiovascular events. However, the relationship between liver fibrosis scores and clinical outcomes in patients with cardiovascular disease remains unclear. Methods: Searching from PubMed, EMBASE and Cochrane Library databases yielded cohort studies that reported adjusted effect size between liver fibrosis scores (Fibrosis‐4 score [FIB‐4] or NAFLD fibrosis score [NFS]) and prognosis in patients with cardiovascular disease. The effect size was computed using a random‐effects model. Results: This meta‐analysis included twelve cohort studies involving 25,252 patients with cardiovascular disease. Participants with the highest baseline level of FIB‐4 or NFS had a significantly increased risk of cardiovascular events (FIB‐4, HR: 1.75, 95% CI: 1.53–2.00, I2 = 0%; NFS, HR: 1.92, 95% CI: 1.50–2.47, I2 = 47%). This finding was consistent with the analysis of FIB‐4 or NFS as a continuous variable (per 1‐unit increment FIB‐4, HR: 1.15, 95% CI: 1.06–1.24, I2 = 72%; NFS, HR: 1.15, 95% CI: 1.07–1.24, I2 = 71%). Furthermore, participants with the highest levels of FIB‐4 or NFS had a greater risk of cardiovascular mortality (FIB‐4, HR: 2.07, 95% CI: 1.19–3.61, I2 = 89%; NFS, HR: 3.72, 95% CI: 2.62–5.29, I2 = 60%) and all‐cause mortality (FIB‐4, HR: 1.81, 95% CI: 1.24–2.66, I2 = 90%; NFS, HR: 3.49, 95% CI: 2.82–4.31, I2 = 25%). This result was also consistent as a continuous variable. Conclusion: Higher levels of FIB‐4 and NFS are related to an increased risk of cardiovascular events, cardiovascular mortality and all‐cause mortality in patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]

Long-term exposure to air pollutants and residential greenness related to advanced fibrosis have been sparsely studied in low- and middle-income countries. A total of 29883 participants were selected from a cross-sectional survey of the Henan Rural Cohort. Concentrations of air pollutants (particulate matter with an aerodynamic diameter ≤ 1.0 μm (PM1), ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10) and nitrogen dioxide (NO2)) for participants were predicted by using a spatiotemporal model. Residential greenness of each participant was indicated by Enhanced Vegetation Index (EVI) and Normalized Difference Vegetation Index (NDVI). Independent and joint associations of air pollutants and residential greenness indices with prevalent advanced fibrosis reflected by fibrosis-4 score (FIB4), aspartate-to-platelet-ratio index (APRI) and ALT/AST ratio were analyzed by generalized linear mixed models and their interactive effect on prevalent advanced fibrosis were visualized by using the interplot method. Long-term exposure to PM1, PM2.5, PM10 and NO2 were positively related to FIB4 or APRI as well as prevalent intermediate-high advanced fibrosis; EVI was negatively related to FIB4 or APRI as well as prevalent intermediate-high advanced fibrosis. Negative associations of residential greenness indices (EVI or NDVI) with prevalent advanced fibrosis were decreased as increased air pollutants (PM1, PM2.5, PM10 or NO2) (P < 0.05 for all). This study indicated that residential greenness may partially attenuate negative effect of long-term exposure to air pollutants related to increased prevalent intermediate-high advanced fibrosis, implying that residential greenness may be an effective strategy to reduce the burden of prevalent hepatic fibrosis and its related disease in association with exposure high levels of air pollutants. The Henan Rural Cohort study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699, http://www.chictr.org.cn/showproj.aspx?proj=11375) [ABSTRACT FROM AUTHOR]

Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays providing total cholesterol levels. Hence, these studies do not account for the individual cholesteryl ester (CE) species, which have different properties according to acyl chain length and desaturation. Methods: Free cholesterol (FC) and 15 CE species were quantified by flow injection analysis high-resolution Fourier Transform mass spectrometry (FIA-FTMS) in the serum of 178 patients with chronic HCV before therapy and during treatment with DAAs. Results: Serum CEs were low in HCV patients with liver cirrhosis and, compared to patients without cirrhosis, proportions of CE 16:0 and 16:1 were higher whereas % CE 20:4 and 20:5 were reduced. FC levels were unchanged, and the CE/FC ratio was consequently low in cirrhosis. FC and CEs did not correlate with viral load. Four CE species were reduced in genotype 3 compared to genotype 1-infected patients. During DAA therapy, 9 of the 15 measured CE species, and the CE/FC ratio, increased. Relative to total CE levels, % CE 16:0 declined and % CE 18:3 was higher at therapy end. At this time, % CE 14:0, 16:0 and 16:1 were higher and % CE 20:4 and 22:6 were lower in the cirrhosis than the non-cirrhosis patients. Viral genotype associated changes of CEs disappeared at therapy end. Conclusions: The serum CE composition differs between patients with and without liver cirrhosis, and changes through the efficient elimination of HCV. Overall, HCV infection and cirrhosis are associated with a higher proportion of CE species with a lower number of carbon atoms and double bonds, reflecting a less-favorable CE profile.

Introduction and aim. In chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy, therapeutic decision currently depends on histopathology of the liver. We aimed to evaluate if acoustic radiation force impulse (ARFI) in conjunction with aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) score could replace liver biopsy to indicate treatment for CHB.Material and methods. We prospectively enrolled 101 clinically non-cirrhotic patients whose serum alanine aminotransferase was mildly elevated (1-2 folds above the upper normal limit) despite a high viral load (HBV DNA > 2,000 IU/mL). All participants underwent liver biopsy, and measurement of ARFI, APRI and FIB-4. The ability of the markers to distinguish fibrosis ≥ METAVIR F2 was evaluated.Results. According to histopathology, liver fibrosis was METAVIR F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients, and was correlated with ARFI (p = 0.0001), APRI (p = 0.012), and FIB-4 (p = 0.004). The six patients with cirrhosis were included for analysis, and received antiviral therapy. The C statistics of ARFI, APRI, and FIB-4 for fibrosis ≥ F2 were 0.70 (95% confidence interval [CI], 0.59-0.80), 0.62 (95% CI, 0.51-0.73), and 0.64 (0.53-0.75), respectively. The cut-off values for 95% sensitivity and 95% specificity to identify significant fibrosis were 0.97 m/sec and 1.36 m/sec for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. Using a combination of these 3 indices, 44 patients (43.6%) could be spared a liver biopsy procedure.Conclusions. A combination of ARFI, APRI, and FIB-4 may spare some CHB patients with equivocal indication for antiviral treatment a liver biopsy.

Liver fibrosis is the common consequence of chronic liver diseases (CLD). Recently liver stiffness measurements (LSM) = 9.1 kPa, as determined by transient elastography (TE), were demonstrated to predict significant fibrosis (stages = F2) in a population-based setting. The PNPLA3 (adiponutrin) p.I148M polymorphism enhances the risk of liver injury. The aim of our study was to investigate the association between the procholestatic ABCB4 polymorphism c.711A>T and LSM = 9.1 kPa in humans as well as the interaction between ABCB4 and PNPLA3 in a mouse model of chronic cholestasis. Prospectively, we recruited 712 patients with CLD (278 women, age 50 ± 13 years) with available TE results; liver biopsy results were available in 165 individuals. The ABCB4 c.711 genotype was determined by PCR-based assays. Pnpla3 expression and liver injury were studied in Abcb4-/- mice and wild-type controls. Overall, median LSM in our cohort was 6.7 kPa, and 226 individuals had LSM = 9.1 kPa. Carriers of the ABCB4 variant c.711A presented more frequently with LSM = 9.1 kPa (OR = 1.33, P = 0.020) and FIB-4 score = 2.67 (OR = 1.38, P = 0.040). The presence of the risk allele was associated (P = 0.002) with FIB-4. In a multivariate model, the ABCB4 variant (OR = 1.43, P = 0.047) as well as BMI (P = 0.043, OR = 1.04) and age (OR = 1.02, P < 0.010) were independent risk factors for fibrosis stage = F2. Abcb4 deficiency in mice led to enhanced liver injury, coupled with a decrease (P = 0.020) of hepatic Pnpla3 expression. To conclude, the procholestatic variant ABCB4 c.711A>T might represent a new genetic risk factor for clinically significant liver fibrosis. Lower expression of Pnpla3 in fibrotic Abcb4-/- livers points to the interaction between phospholipid metabolism and PNPLA3 in progressive liver injury. [ABSTRACT FROM AUTHOR]

Previous studies using microRNA (miRNA or miR) microarrays have demonstrated that miR-1273g-3p is upregulated in patients with hepatitis C virus (HCV)-associated fibrosis. As miRNAs have been suggested to be promising non-invasive biomarkers, the aim of the present study was to assess whether miR-1273g-3p may be useful as a potential indicator of fibrosis progression in patients with HCV. Liver biopsies were performed on 112 patients with chronic hepatitis C (CHC) and liver stiffness measurements (LSM) were performed using FibroTouch. Liver fibrosis was determined based on Meta-analysis of Histological Data in Viral Hepatitis classification, and the aspartate aminotransferase (AST)-to-platelet count (PLT) ratio index (APRI) and Fibrosis-4 score (FIB-4) were calculated. The diagnostic performance of miR-1273g-3p, LSM, APRI and FIB-4 in predicting fibrosis stage were evaluated and compared by receiver operating characteristic (ROC) analysis. It was demonstrated that miR-1273g-3p levels were significantly positively correlated with the liver fibrosis stage (r=0.657, P<0.001). The results of LSM, APRI and FIB-4, the three non-invasive diagnostic methods, had good consistency with liver biopsy results, and their correlation coefficients with fibrosis staging were 0.815, 0.417 and 0.522, respectively. The areas under the ROC curves of miR-1273g-3p for F≥2 and F=4 stage samples were 0.841 and 0.933, respectively, which were lower than LSM (0.890 and 0.937), and higher than FIB-4 (0.791 and 0.766) and APRI (0.719 and 0.760). Spearman analysis demonstrated that serum miR-1273g-3p levels were significantly positively correlated with age, body mass index, alanine aminotransferase, AST and total bilirubin (all P<0.05), and negatively correlated with PLT (P<0.05). However, no significant correlation was observed between miR-1273g-3p levels, baseline HCV RNA loads and genotype. Therefore, the results demonstrated that miR-1273g-3p levels, as a novel non-invasive test, may be a useful and easy method for predicting the stage of liver fibrosis in patients with CHC, and has a better diagnostic performance than FIB-4 and APRI. Further prospective studies are required to validate the efficacy of miR-1273g-3p as a predictor of liver fibrosis. [ABSTRACT FROM AUTHOR]

Background & Aims: We tested whether non-invasive tests for liver disease severity can stratify hepatocellular carcinoma (HCC) risk in chronic hepatitis B virus (HBV)-infected patients showing low-level viremia (LLV, HBV DNA <2000 IU/mL). Methods: A retrospective cohort of 1006 chronic hepatitis B patients showing persistently LLV, defined by at least two consecutive assessments in the year before enrolment, was assessed for HCC development. Two non-invasive serum biomarkers, the aspartate aminotransferase to platelet ratio index (APRI) and the Fibrosis-4 (FIB-4), were tested. Cirrhosis was defined with ultrasonography. Results: During a median 5.1 years of follow-up, HCC developed in 36 patients. HCC incidence rate at 5 years was significantly higher for cirrhotic patients (19/139, 13.7%), but was not null for non-cirrhotic patients (17/867, 2.0%, P<.001). APRI at a cut-off of 0.5 was more specific but less sensitive for HCC development, and FIB-4 at a cut-off of 1.45 was more sensitive but less specific. When both APRI and FIB-4 were used to group patients, the 5-year cumulative HCC incidence rate was 13.9%, 1.4% and 1.2% for both high, any high, and both low APRI and FIB-4 score among all patients (n=1006, P<.001), respectively, and was 11.4%, 1.5% and 0.4% in the same respective order among non-cirrhotic patients (n=867, P<.001). Conclusions: The combined use of two non-invasive serum biomarkers (APRI and FIB-4) could stratify HCC risk for chronic HBV-infected patients with LLV. [ABSTRACT FROM AUTHOR]

Background: Chronic liver diseases of all etiologies exist along a spectrum with varying degrees of hepatic fibrosis. Despite accumulating evidence implying associations between liver fibrosis and cognitive functioning, there is limited research exploring the underlying neurobiological factors and the possible mediating role of inflammation on the liver-brain axis., Methods: Using data from the UK Biobank, we examined the cross-sectional association of liver fibrosis (as measured by Fibrosis-4 score) with cognitive functioning and regional grey matter volumes (GMVs) while adjusting for numerous covariates and multiple comparisons. We further performed post-hoc preliminary analysis to investigate the mediating effect of C-reactive protein (CRP) on the association between liver fibrosis and both cognitive functioning and GMVs., Findings: We analysed behaviour from up to 447,626 participants (N ranged from 45,055 to 447,533 per specific cognitive metric) 37 years and older. 38,244 participants (age range 44-82 years) had GMV data collected at a median 9-year follow-up. Liver fibrosis showed significant associations with cognitive performance in reasoning, working memory, visual memory, prospective memory, executive function, and processing speed. Subgroup analysis indicated larger effects sizes for symbol digital substitution but smaller effect sizes for trail making in middle-aged people than their old counterparts. Neuroimaging analyses revealed significant associations between liver fibrosis and reduced regional GMVs, primarily in the hippocampus, thalamus, ventral striatum, parahippocampal gyrus, brain stem, and cerebellum. CRP levels were significantly higher in adults with advanced liver fibrosis than those without, indicating an elevated systemic inflammation. Moreover, the serum CRP significantly mediated the effect of liver fibrosis on most cognitive measures and regional GMVs in the hippocampus and brain stem., Interpretation: This study provides a well-powered characterization of associations between liver fibrosis, cognitive impairment, and grey matter atrophy. It also highlights the possibly mediating role of systemic inflammation on the liver-brain axis. Early surveillance and prevention of liver diseases may reduce cognitive decline and brain GMV loss., Funding: National Science Foundation, and National Institutes of Health., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: The new name and diagnostic criteria of metabolic-associated fatty liver disease (MAFLD) was proposed in 2020. Although chronic HBV infection has protective effects on lipid profiles and hepatic steatosis, the impact of chronic HBV infection on clinical outcomes of MAFLD requires further investigation., Methods: The participants from a Taiwan bio-bank cohort were included. MAFLD is defined as the presence of hepatic steatosis plus any of the following three conditions: overweight/obesity, type 2 diabetes mellitus, and metabolic dysfunction. The patients with positive glycated haemoglobin were considered as having chronic HBV infection. Atherosclerosis was determined as having carotid plaques on duplex ultrasound. Advanced liver fibrosis was defined as Fibrosis-4 >2.67. Based on the status of MAFLD and HBV infection, the participants were distributed into four groups: 'dual aetiology', 'MAFLD alone', 'HBV alone', and 'healthy controls'., Results: A total of 20,460 participants (age 55.51 ± 10.37; males 32.67%) were included for final analysis. The prevalence of MAFLD and chronic HBV infections were 38.8% and 10.3%, respectively. According to univariate analysis, 'HBV alone' group had lower levels of glycated haemoglobin, lipid profiles, and intima media thickness than healthy controls. The 'dual aetiology' group had lower levels of triglycerides, cholesterol, γ-glutamyl transferase, intima media thickness, and percentage of carotid plaques than 'MAFLD alone' group. Using binary logistic regression, chronic HBV infection increased the overall risk of advanced liver fibrosis; and had a lower probability of carotid plaques in MAFLD patients, but not in those without MAFLD., Conclusions: The large population-based study revealed chronic HBV infection increases the overall risk of liver fibrosis, but protects from atherosclerosis in patients with MAFLD., Impact and Implications: Patients with metabolic-associated fatty liver disease can also be coinfected with chronic HBV. Concomitant HBV infection increases the overall risk of liver fibrosis, but protects from atherosclerosis in patients with MAFLD., Competing Interests: All authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of advanced liver disease in the USA. Liver biopsy, the gold standard diagnostic test for evaluating liver fibrosis, is associated with significant risk and expense. The accuracy of ultrasound elastography and Fibrosis-4 index (FIB-4) in the obese NAFLD population is unknown. We aimed to compare the accuracy of ultrasound elastography and FIB-4 to liver biopsy in ruling out cirrhosis in NAFLD patients at a tertiary, transplant referral center in the US., Methods: We retrospectively evaluated 93 patients with a mean age of 53 years (SD: 13 years) who underwent liver ultrasound elastography and liver biopsy, and additionally calculated their FIB-4 at the time of biopsy. We compared the liver stiffness measurement (LSM) obtained from ultrasound elastography and FIB-4 with the pathology results for ruling out cirrhosis., Results: 85% of the patients were white, 53% were female, average BMI was 34.7 (SD: 6.7), 52% had diabetes, and 53% had hypertension. For biopsy-proven cirrhosis (prevalence 15%), a cut-off value of 12.5 kilopascals (kPa) for F4 had a sensitivity of 92% and a specificity of 54%. Values below this threshold excluded cirrhosis with 98% certainty. Compared to FIB-4, ultrasound elastography showed higher accuracy in ruling out cirrhosis (92% vs. 80% sensitivity, 98% vs. 95% negative predictive value (NPV), respectively)., Conclusion: To our knowledge, this is the first study in a tertiary transplant referral center in the USA to show that ultrasound elastography was superior to FIB-4 and can be used as a reliable screening test to rule out cirrhosis in obese NAFLD patients at a 12.5 kPa cut-off. Therefore, helping to avoid the risk and expense associated with liver biopsy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Damjanovska et al.)

The impact of changes in sleep duration and sleep quality over time on the risk of non-alcoholic fatty liver disease (NAFLD) is not known. We investigated whether changes in sleep duration and in sleep quality between baseline and follow-up are associated with the risk of developing incident NAFLD. The cohort study included 86,530 Korean adults without NAFLD and with a low fibrosis score at baseline. The median follow-up was 3.6 years. Sleep duration and quality were assessed using the Pittsburgh Sleep Quality Index. Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (Cis). A total of 12,127 subjects with incident HS and 559 with incident HS plus intermediate/high FIB-4 was identified. Comparing the decrease in sleep duration of >1 h, with stable sleep duration, the multivariate-adjusted HR (95% CIs) for incident HS was 1.24 (1.15–1.35). The corresponding HRs for incident HS plus intermediate/high FIB-4 was 1.58 (1.10–2.29). Comparing persistently poor sleep quality with persistently good sleep quality, the multivariate-adjusted HR for incident HS was 1.13 (95% CI, 1.05–1.20). A decrease in sleep duration or poor sleep quality over time was associated with an increased risk of incident NAFLD, underscoring an important potential role for good sleep in preventing NAFLD risk. [ABSTRACT FROM AUTHOR]

Background: Identifying hepatic fibrosis is crucial for nonalcoholic fatty liver disease (NAFLD) management. The fibrosis-8 (FIB-8) score, recently developed by incorporating four additional variables into the fibrosis-4 (FIB-4) score, showed better performance in predicting significant fibrosis in NAFLD., Aim: To validate the FIB-8 score in a biopsy-proven NAFLD cohort and compare the diagnostic performance of the FIB-8 and FIB-4 scores and NAFLD fibrosis score (NFS) for predicting significant fibrosis., Methods: We collected the data of biopsy-proven NAFLD patients from three Asian centers in three countries. All the patients with available variables for the FIB-4 score (age, platelet count, and aspartate and alanine aminotransferase levels) and FIB-8 score (the FIB-4 variables plus 4 additional parameters: The body mass index (BMI), albumin to globulin ratio, gamma-glutamyl transferase level, and presence of diabetes mellitus) were included. The fibrosis stage was scored using nonalcoholic steatohepatitis CRN criteria, and significant fibrosis was defined as at least fibrosis stage 2., Results: A total of 511 patients with biopsy-proven NAFLD and complete data were included for validation. Of these 511 patients, 271 (53.0%) were female, with a median age of 51 (interquartile range: 41, 58) years. The median BMI was 29 (26.3, 32.6) kg/m 2 , and 268 (52.4%) had diabetes. Among the 511 NAFLD patients, 157 (30.7%) had significant fibrosis (≥ F2). The areas under the receiver operating characteristic curves of the FIB-8 and FIB-4 scores and NFS for predicting significant fibrosis were 0.774, 0.743, and 0.680, respectively. The FIB-8 score demonstrated significantly better performance for predicting significant fibrosis than the NFS ( P = 0.001) and was also clinically superior to FIB-4, although statistical significance was not reached ( P = 0.073). The low cutoff point of the FIB-8 score for predicting significant fibrosis of 0.88 showed 92.36% sensitivity, and the high cutoff point of the FIB-8 score for predicting significant fibrosis of 1.77 showed 67.51% specificity., Conclusion: We demonstrated that the FIB-8 score had significantly better performance for predicting significant fibrosis in NAFLD patients than the NFS, as well as clinically superior performance vs the FIB-4 score in an Asian population. A novel simple fibrosis score comprising commonly accessible basic laboratories may be beneficial to use for an initial assessment in primary care units, excluding patients with significant liver fibrosis and aiding in patient selection for further hepatologist referral., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Simple Summary: Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancy and represents the fourth leading cause of cancer-related deaths. However, most HCC cases are insidious in the early stages leading to a delay in diagnosis with limited treatment options. In patients with chronic liver diseases, advanced liver fibrosis and cirrhosis are the leading risk factors for the development of HCC. Cartilage oligomeric matrix protein (COMP) and Golgi protein-73 (GP73) are two biomarkers that have been associated with the progression of chronic liver disease, including inflammation, fibrosis, and HCC. The aim of our study was to assess the performance of the combination of these biomarkers. We confirmed, in a large cohort of 288 patients with chronic liver diseases, that the combination of GP73 and COMP had a high discriminative ability to detect severe fibrosis/cirrhosis and is efficient in predicting the development of HCC. The cartilage oligomeric matrix protein (COMP) and Golgi-protein-73 (GP73) have been proposed as markers of liver fibrosis and hepatocellular carcinoma (HCC). Our aim was to assess the performance of the combination of these markers in diagnosing cirrhosis and predicting HCC development. Sera from 288 consecutive patients with chronic liver diseases were investigated by using COMP and GP73-ELISAs. Dual positivity for COMP (>15 U/L) and GP73 (>20 units) was observed in 24 (8.3%) patients, while 30 (10.4%) were GP73(+)/COMP(−), 37/288 (12.8%) GP73(−)/COMP(+), and 197 (68.5%) GP73(−)/COMP(−). Positivity for both markers was associated with cirrhosis [23/24 (95.8%) for GP73(+)/COMP(+) vs. 22/30 (73.3%) for GP73(+)/COMP(−) vs. 25/37 (67.6%) for GP73(−)/COMP(+) vs. 46/197 (23.4%) for GP73(−)/COMP(−); P < 0.001]. The combination of GP73, COMP, the aspartate aminotransferase/platelets ratio index, and the Fibrosis-4 score had even higher diagnostic accuracy to detect the presence of cirrhosis [AUC (95% CI): 0.916 (0.878–0.946)] or significant liver fibrosis (METAVIR ≥ F2) [AUC (95% CI): 0.832 (0.768–0.883)] than each marker alone. Kaplan-Meier analysis showed that positivity for both GP73 and COMP was associated with higher rates of HCC development (P < 0.001) and liver-related deaths (P < 0.001) during follow-up. In conclusion, the combination of GP73 and COMP seems efficient to detect cirrhosis and predict worse outcomes and the development of HCC in patients with chronic liver diseases. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) has an increased prevalence in end-stage renal disease (ESRD) due to similar risk factors. The aim of this study was to assess non-invasive testing including transient elastography (TE) for liver stiffness (LS), controlled attenuated parameter (CAP) for steatosis, Fibrosis-4 (FIB-4) score, aspartate aminotransferase (AST) to platelet ratio index (APRI) and NAFLD fibrosis score (NFS), for evaluation of NAFLD along with advanced fibrosis (AF) in patients with ESRD undergoing renal transplant evaluation., Methods: Data were retrospectively collected within 12 weeks of TE. Primary outcomes were AF, defined by LS ≥ 9 kPa compared to APRI > 1.5, FIB-4 > 2.67, and NFS of 0.675, and ≥ 5% steatosis by CAP ≥ 263 dB/m compared to liver histology when available., Results: A total of 171 patients were evaluated: mean age 56, 65% male, 36% obese, 47% had diabetes, 96% hypertension, and 56% dyslipidemia. Mean LS was 6.5 kPa with 21% having AF. Mean CAP was 232 dB/m, with 25% having steatosis. Those with AF were older with higher NFS. Those with steatosis were obese and had diabetes without higher LS or fibrosis scores. Only NFS was associated with LS ≥ 9 kPa. In those with liver histology, AF was associated with LS ≥ 9 kPa but not with APRI, FIB-4, or NFS., Conclusions: Despite normal liver enzymes, non-invasive assessment via TE in ESRD patients exhibited high prevalence of AF and steatosis not detected by APRI or FIB-4 scores. This high prevalence was secondary to the common risk factors such as obesity and diabetes, among patients with NAFLD and ESRD., Competing Interests: None to declare., (Copyright 2021, Syed et al.)

Background: Chronic hepatitis C infection is common among people with history of substance use. Liver fibrosis assessment is a barrier to linkage to care, particularly among those with history of substance users. The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination, especially in countries where transient elastography (TE) is not available. We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population., Methods: HCV patients with history of substance use between 2011 and 2016 were analyzed. All patients had TE for liver fibrosis assessment. Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared. Youden's index was used to determine optimal cut-off of the novel score., Results: A total of 579 patients were included. In multivariate logistic regression, cirrhosis on TE was associated with age (P = 0.002), aspartate aminotransferase (AST) (P = 0.004), and platelet count (P < 0.001), but not alanine aminotransferase (ALT) (P = 0.896). These form the components of modified AST-to-platelet ratio index (APRI) score. Modified APRI was superior to APRI in predicting cirrhosis (AUROC, 0.796 vs. 0.770, P = 0.007), but not fibrosis-4 score (FIB-4) (P = 1.00). Modified APRI at cut-off of 4 has sensitivity, specificity and negative predictive value (NPV) of 94.4%, 26.9% and 92.6%, respectively, and at 19, has sensitivity, specificity and positive predictive value (PPV) of 33.3%, 96.2% and 77.1%, respectively. FIB-4 has a NPV and PPV of 88.6%, 41.8% and 78.5%, 77.6%, at cut-off of 1.45 and 3.25, respectively. Using the cut-off of 4 and 14 for modified APRI, 32.5% of patients can be correctly classified and misses out only 5.6% of cirrhosis patients., Conclusions: Modified APRI score is superior in predicting cirrhosis in HCV population, with 32.5% of the population being correctly classified using cut-off of 4 and 14. Further studies are required to validate the findings., (Copyright © 2018. Published by Elsevier B.V.)

Introduction and Aim: In chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy, therapeutic decision currently depends on histopathology of the liver. We aimed to evaluate if acoustic radiation force impulse (ARFI) in conjunction with aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) score could replace liver biopsy to indicate treatment for CHB., Material and Methods: We prospectively enrolled 101 clinically non-cirrhotic patients whose serum alanine aminotransferase was mildly elevated (1-2 folds above the upper normal limit) despite a high viral load (HBV DNA &gt; 2,000 IU/mL). All participants underwent liver biopsy, and measurement of ARFI, APRI and FIB-4. The ability of the markers to distinguish fibrosis ≥ METAVIR F2 was evaluated., Results: According to histopathology, liver fibrosis was METAVIR F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients, and was correlated with ARFI (p = 0.0001), APRI (p = 0.012), and FIB-4 (p = 0.004). The six patients with cirrhosis were included for analysis, and received antiviral therapy. The C statistics of ARFI, APRI, and FIB-4 for fibrosis ≥ F2 were 0.70 (95% confidence interval [CI], 0.59-0.80), 0.62 (95% CI, 0.51-0.73), and 0.64 (0.53- 0.75), respectively. The cut-off values for 95% sensitivity and 95% specificity to identify significant fibrosis were 0.97 m/sec and 1.36 m/sec for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. Using a combination of these 3 indices, 44 patients (43.6%) could be spared a liver biopsy procedure., Conclusions: A combination of ARFI, APRI, and FIB-4 may spare some CHB patients with equivocal indication for antiviral treatment a liver biopsy.

Objective To evaluate whether gamma-glutamyl transpeptidase to platelet ratio index (GPRI) can diagnose the extent of liver fibrosis in Chinese patients with chronic hepatitis B (CHB) infection. Methods This prospective observational study used liver biopsy results as the gold standard to evaluate the ability of GPRI to predict hepatic fibrosis compared with two other markers, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The clinical and demographic factors that affected GPRI, independent of liver fibrosis, were assessed using multivariate linear regression analyses. Results This study enrolled 312 patients with CHB. GPRI had a significantly positive correlation with liver fibrosis stage and the correlation coefficient was higher than that for APRI and FIB-4. The areas under the receiver operating curves for GPRI for significant fibrosis, bridging fibrosis, and cirrhosis were 0.728, 0.836, and 0.842, respectively. Of the three indices, GPRI had the highest diagnostic accuracy for bridging fibrosis and cirrhosis. Age, elevated AST and elevated total bilirubin levels were independent determinants of increased GPRI. Conclusion GPRI was a more reliable laboratory marker than APRI and FIB-4 for predicting the stage of liver fibrosis in Chinese patients with CHB.