Aspartate Aminotransferase-to-platelet Ratio Index Index Research Articles

Aspartate Aminotransferase to Platelet Ratio Index (APRI) as a Predictor of Metabolic Syndrome (MetS) Development in Individuals With Type 2 Diabetes Mellitus.

Despite ongoing findings on the relationship between liver fibrosis in nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), this association in diabetic patients remains unclear. Early diagnosis of liver fibrosis is important due to the easily available diagnostic tools, such as noninvasive indices that combine clinical and laboratory variables, and the possibility of preventing its complications in type 2 diabetes mellitus (T2DM) patients with MetS. This study examines the potential predictive values of non-invasive liver fibrosis indices for MetS in T2DM patients. Over the course of a two-year prospective, observational, clinical study, 80 individuals with T2DMrandomly selected from the Diabetes Counseling Centers of the Public Institution Health Center of Sarajevo Canton were divided into two groups: T2DM-MetS and T2DM-non-MetS, based on the development of MetS. The studyincludedindividuals with T2DM aged30 to 60who were clinically diagnosed without MetS, voluntarily agreed to participate, and provided complete data in the collection forms. Serum samples from the patients were assessed for levels of liver enzymes, platelet counts, total cholesterol, high-density lipoprotein cholesterol, fasting glucose, and triglycerides. Various equations were utilized to calculate liver fibrosis indices, including the Aspartate Aminotransferase to Platelet Ratio Index (APRI), Aspartate Aminotransferase to Gamma-Glutamyl Transferase to Platelet Ratio (AGPR), Aspartate Aminotransferase to Alanine Aminotransferase Ratio to Platelet Ratio Index (AARPRI), Fibrosis-4 (FIB-4) Index, Forns Index, and Gamma-Glutamyl Transpeptidase to Platelet Ratio (GPR). Receiver operating characteristic (ROC) analysis was utilized to determine the usefulness of noninvasive liver fibrosis indices for diagnosing MetS in individuals with T2DM. Logistic regression analysis was used to predict the onset of MetS in T2DM patients. Significant differences in the values of APRI (p<0.001), AGPR (p<0.05), AARPRI (p<0.001), and the FIB-4 index (p=0.001) were observed in T2DM-MetS individuals compared to T2DM-non-MetS. According to ROC analysis, the area under the curve (AUC) was found to be highest for APRI (0.84), followed by FIB-4 (0.783) and AARPRI (0.747). Logistic regression analysis identified APRI as an independent positive predictor of MetS (OR 18.179, 95% CI 6.035-24.58, p=0.015). This research highlights the effectiveness of the APRI index as a reliable predictor of MetS development in individuals with T2DM.

Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment.

To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.

A Significant Effect of Pemafibrate on Hepatic Steatosis and Fibrosis Indexes in Patients With Hypertriglyceridemia.

We previously reported that the selective peroxisome proliferator-activated receptor alpha modulator, pemafibrate, significantly reduced serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) and significantly increased serum albumin levels at 3, 6 and 12 months after the start of pemafibrate, with an improvement of atherogenic dyslipidemia, in patients with hypertriglyceridemia. We performed a post hoc analysis of our previous data obtained from patients with hypertriglyceridemia who had been prescribed pemafibrate continuously for 1 year or longer. We compared the indexes for hepatic steatosis (hepatic steatosis index (HSI)) and fibrosis (nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), AST to platelet ratio index (APRI) and FIB-4 index) at baseline with the data at 1 year after the start of pemafibrate. Pemafibrate significantly reduced HSI at 1 year after the start of pemafibrate. NFS did not show a significant change after 1 year. However, APRI was significantly reduced by pemafibrate after 1 year. FIB-4 index significantly decreased in patients with baseline FIB-4 index ≥ 1.45 at 1 year after the start of pemafibrate. HSI at baseline tended to be negatively correlated with change in HSI after 1 year. There was no significant correlation between NFS at baseline and change in this score after 1 year. APRI and FIB-4 index at baseline were significantly and negatively correlated with changes in APRI and FIB-4 index at 1 year after the start of pemafibrate. The 1-year pemafibrate treatment improved hepatic steatosis and fibrosis indexes in patients with hypertriglyceridemia.

Comparison of patients using lamivudine, entecavir, and tenofovir according to liver fibrosis markers fibrosis-4 and aspartate aminotransferase-to-platelet ratio index scores.

It was intended to assess the efficacy of lamivudine, entecavir, and tenofovir regimens in the management of chronic hepatitis B (CHB) guided by Fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) scores. Our study was conducted on patients who applied to the hepatitis outpatient clinic between 2008 and 2015 retrospectively. Lamivudine, entecavir, and tenofovir regimens used in the practice of CHB cases were compared by measuring noninvasive FIB tests. Entirely 199 patients involved in the research were evaluated in three treatment arms; 48 used lamivudine, 46 used entecavir, and 105 used tenofovir. Similar statistical characteristics were observed between research arms regarding age, gender, and alanine aminotransferase normalization by years (P > 0.05). Totally 5 (13.5%) of patients developed Hepatitis B e antigen (HBeAg) seroconversion among 36 HBeAg positivity, and similar statistical features were seen by comparing the groups (P > 0.05). In the entecavir and tenofovir arms, a significant decrease was seen in FIB-4, and APRI index values in the 1st year of treatment (P < 0.001). At the graph curve, a plateau was observed in the APRI test after the 1st year, and a plateau was observed in the FIB-4 test after the 2nd year. Consistent with the study outcome, when we consider FIB regression, tenofovir and entecavir regimens were found more effective than lamivudine. In addition, entecavir was more effective than the other two drugs after the 1st year.

Fc receptor-like 5 gene polymorphisms and mRNA expression are associated with liver fibrosis in chronic hepatitis B.

Objective: To investigate the associations of Fc receptor-like 5 (FCRL5) gene polymorphisms and mRNA expression with liver fibrosis in chronic hepatitis B (CHB).Methods: A total of 114 CHB patients with liver fibrosis and 120 CHB patients without liver fibrosis were selected for this study. The gender, age, body mass index (BMI), alanine transaminase (ALT) value, aspartate aminotransferase (AST) value, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) were recorded. Two polymorphisms of the FCRL5 gene (rs6427384 and rs6692977) were genotyped. The mRNA expression level of FCRL5 in peripheral blood monocytes was determined.Results: ALT, AST, APRI, and FIB-4 in patients with fibrosis were significantly higher than those in non-fibrosis patients. There was statistically significant difference between fibrosis and non-fibrosis groups in the genotype distribution (χ2 = 7.805, p = 0.020) and allele frequencies (χ2 = 13.252, p < 0.001) at FCRL5 rs6692977. When compared with CC genotype, the genotype CT or TT at rs6692977 was significantly associated with a increased risk of liver fibrosis in CHB patients (CT vs. CC: OR = 1.921, 95% CI = 1.093–3.375, p = 0.023; TT vs. CC: OR = 2.598, 95% CI = 1.067–6.324, p = 0.031). The mRNA relative expression levels of FCRL5 in patients with liver fibrosis were significantly higher than those in the non-fibrosis group (t = 13.456, p < 0.001). The fibrosis patients carried TT or CT genotype of rs6692977 had significantly higher FCRL5 mRNA expression levels than those carried CC genotype (t = 2.859, p = 0.005). The mRNA expression levels of FCRL5, APRI, and FIB-4 index showed predictive efficacy in liver fibrosis with cut-off values of 0.75 (AUC = 0.896, 95% CI = 0.856–0.935), 0.45 (AUC = 0.852, 95% CI = 0.802–0.902) and 1.84 (AUC = 0.765, 95% CI = 0.703–0.826), respectively.Conclusion: FCRL5 gene rs6692977 polymorphisms and mRNA expression levels are associated with liver fibrosis in CHB patients.

Comparison of invasive and non-invasive methods for assessment of liver fibrosis in patients with chronic hepatitis B and hepatitis C virus infections

Introduction: Different methods are employed to determine the severity of chronic viral hepatitis and liver fibrosis Objectives: This study was conducted to compare invasive and non-invasive tests for assessment of liver fibrosis in the patients with chronic hepatitis B and C. Patients and Methods: In this study, the results of liver biopsy based on the METAVIR scoring system were compared with biomarkers, including fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) for identifying liver fibrosis. Results: Out of 194 patients, 63 and 131 patients had hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, respectively. There was a significant difference between patients with METAVIR stages 0-1 and patients with METAVIR stages 2-3, based on the FIB-4, aspartate aminotransferase (AST) to platelet ratio index (APRI) and the mean prothrombin time (PT), international normalized ratio (INR), platelet (PLT), alanine transaminase (ALT) and AST. A correlation was found between the FIB-4 and APRI indices and the METAVIR score of patients with hepatitis. The FIB-4 index, with a cut-off value &lt;1.1 for detecting liver fibrosis in patients with HBV infection, showed sensitivity of 83.3%, specificity of 64.7%. Further, a positive predictive value (PPV) of 35.7%, and a negative predictive value (NPV) of 94.3% was detected. On the other hand, the APRI index, with a cut-off value &lt;0.73, showed 59% sensitivity, 76.5% specificity, PPV of 33.3% and NPV of 86.7%. The FIB-4 index, with a cut-off value &lt;1.47 for detecting liver fibrosis in patients with HCV infection, showed 73.7% sensitivity, 73.2% specificity, PPV of 31.8%, and NPV of 94.3%. Additionally, the APRI index, with a cut-off value &lt;1.7, showed 42.1% sensitivity, 97.3% specificity, PPV of 72.7% and NPV of 90.8%. Conclusion: According to the results, in patients with chronic hepatitis, the severity of liver fibrosis increased with an increase in the APRI and FIB-4 indices. Therefore, these two indices can replace biopsy under certain circumstances.

Fibro-indices versus liver stiffness for prediction of significant fibrosis in hepatitis B virus-infected Egyptian patients; a single-center experience

ABSTRACTBackground: Liver fibrosis assessment is a key factor for disease management in hepatitis B virus (HBV). Several serum biomarkers have been introduced for noninvasive fibrosis assessment. This study aims to evaluate the validity of simple noninvasive indices, namely Fibrosis-4 score (FIB4), aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), Goteborg University Cirrhosis Index (GUCI), and fibrosis index in evaluation of liver fibrosis in chronic HBV.Methods: 226 patients with chronic HBV genotype D were included. FIB4, APRI, GUCI, and fibrosis index were performed. Receiver operating characteristic (ROC) curves were used to predict ≥F2 fibrosis.Results: The mean age of patients was 39.00 years and 72.27% of patients were treatment naïve. Patients with ≥F2 hepatic fibrosis had significantly higher FIB-4 (1.58 ± 1.46 vs. 1.15 ± 1.09), APRI (0.68 ± 0.71 vs. 0.43 ± 0.37), GUCI score (0.75 ± 0.94 vs. 0.42 ± 0.29) and Fibrosis index (2.18 ± 0.84 vs. 1.84 ± 0.69). All studied indices were able to diagnose ≥F2 fibrosis. APRI had the highest area under the ROC (AUROC) of 0.67. Predictivity of all indices was higher in on-treatment vs naive patients.Conclusion: FIB4, APRI, and GUCI scores are acceptable, noninvasive, and cheap simple indices that can be helpful on treatment follow-up of fibrosis regression in the setting of low socioeconomic conditions compared to the relatively expensive fibroscan modality.

Comparative Analysis of the Discriminatory Performance of Different Well-Known Risk Assessment Scores for Extended Hepatectomy

The aim of this study was to assess and compare the discriminatory performance of well-known risk assessment scores in predicting mortality risk after extended hepatectomy (EH). A series of 250 patients who underwent EH (≥5 segments resection) were evaluated. Aspartate aminotransferase-to-platelet ratio index (APRI), albumin to bilirubin (ALBI) grade, predictive score developed by Breitenstein et al., liver fibrosis (FIB-4) index, and Heidelberg reference lines charting were used to compute cut-off values, and the sensitivity and specificity of each risk assessment score for predicting mortality were also calculated. Major morbidity and 90-day mortality after EH increased with increasing risk scores. APRI (86%), ALBI (86%), Heidelberg score (81%), and FIB-4 index (79%) had the highest sensitivity for 90-day mortality. However, only the FIB-4 index and Heidelberg score had an acceptable specificity (70% and 65%, respectively). A two-stage risk assessment strategy (Heidelberg–FIB-4 model) with a sensitivity of 70% and a specificity 86% for 90-day mortality was proposed. There is no single specific risk assessment score for patients who undergo EH. A two-stage screening strategy using Heidelberg score and FIB-4 index was proposed to predict mortality after major liver resection.

Application of acoustic radiation force impulse elastography combined with serum markers in Child-Pugh grading

OBJECTIVES:Acoustic radiation force impulse (ARFI) elastography, the aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), and the fibrosis-4 (FIB-4) index are widely used to assess liver fibrosis. However, efficacies of these methods in the evaluation of hepatic functional reserve remain unclear. In this study, we investigated the relationship between ARFI elastography combined with either AAR, APRI, or FIB-4 index and Child-Pugh (CP) class for the evaluation of hepatic functional reserve in patients with chronic hepatitis B (CHB)-related cirrhosis.METHODS:The shear wave velocities of 104 patients with clinically confirmed CHB-related cirrhosis were determined using the ARFI; and clinical serum markers (e.g. ALT, AST, PLT) were used to calculate the AAR, APRI, and FIB-4 index. Cirrhosis patients were scored according to their CP class. The ARFI, AAR, APRI, and FIB-4 index were compared with the CP class. The efficacy of each indicator in diagnosis was analyzed using the receiver operating characteristic (ROC) curve and the ARFI combined with either the AAR, APRI, or FIB-4 index, which is used to predict decompensated cirrhosis.RESULTS:No significant differences were observed in gender and age among CP classes A, B, and C patients (p>0.05). The ARFI values and the AAR, APRI, and FIB-4 index of patients with CP classes A, B, and C were significantly different (p<0.05). With an increasing CP class, the ARFI, AAR, APRI, and FIB-4 values increased. The correlation between the ARFI and the CP class was stronger than that between the AAR, APRI, and FIB-4 index and the CP class. The area under the ROC curve for the diagnosis of decompensated cirrhosis using the ARFI was 0.841, which was higher than that for the AAR, APRI, and FIB-4 index. According to the area under the curve results, no significant differences were found when the ARFI was combined with either the AAR, APRI, or FIB-4 index and when the ARFI alone was used.CONCLUSIONS:The ARFI value has a strong correlation with the CP class. Therefore, ARFI elastography complements CP class in the assessment of the hepatic functional reserve in patients with CHB-related cirrhosis.

Subgroup analysis of the predictive ability of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) for assessing hepatic fibrosis among patients with chronic hepatitis C.

There are many laboratory indices to assess liver fibrosis. Aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index have been used as well-known serum markers of liver fibrosis. With the increasing use of non-invasive fibrosis assessment, it is important to recognize the limitations of these tests. The factors influencing the diagnostic accuracy to evaluate liver fibrosis are not well-established. This study aimed to perform a subgroup analysis of the predictive ability of laboratory indices. Overall, 113 patients with chronic hepatitis C infection who underwent liver biopsy were retrospectively examined. The histological assessment of liver fibrosis was performed using the METAVIR scoring system, and the values of several laboratory tests were also evaluated on the same day. We categorized our study population by treatment status, body mass index (BMI), and age. The two laboratory indices APRI and FIB-4 index could predict advanced (F3-4) liver fibrosis and cirrhosis (F4), with the area under the receiver operating characteristic curve (AUROC)>0.8 and accuracy >70%. The AUROCs and accuracies were higher among patients with sustained virological response (SVR) than among those without SVR. A higher predictive ability was also observed among patients with BMI <25kg/m2. Age did not appear to affect liver fibrosis predictability. The laboratory indices APRI and FIB-4 index exhibit good diagnostic performance for determining advanced fibrosis and cirrhosis among patients with hepatitis C infection. The diagnostic accuracy appears better among patients with SVR and those with BMI <25kg/m2.

Evaluation of elastography combined with serological indexes for hepatic fibrosis in patients with chronic hepatitis B.

AIMTo investigate the value of ultrasound elastography combined with serological indexes in diagnosing liver fibrosis and assessing its severity.METHODSA total of 338 chronic hepatitis B (CHB) patients were divided into a disease group (patients with hepatic fibrosis) and control group (subjects without hepatic fibrosis). The disease group was further divided into S1-S4 according to the degree of fibrosis. Independent risk factors for hepatic fibrosis were analyzed using multivariate logistic regression. The diagnostic values of hepatic fibrosis from different indicators were compared using receiver operating characteristic (ROC) curves. The combination of elastography and serological indexes was explored to assess the severity of hepatic fibrosis.RESULTSThe multivariate logistic regression analysis results revealed that shear wave velocity (SWV), hyaluronic acid (HA), type IV collagen (CIV) and aspartate aminotransferase-to-platelet ratio index (APRI) significantly affected the occurrence of hepatic fibrosis. The ROC curve revealed that the accuracy of the diagnosis of hepatic fibrosis for SWV and HA were 87.3% and 84.8%, respectively. The accuracy of SWV combined with HA was 88.9%. The multiple linear regression analysis revealed that SWV, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), HA, CIV, APRI and fibrosis index based on the 4 factor (FIB-4) were screened as statistically significant independent factors. The established regression equation was: Fibrosis level = -4.046 + 1.024 × SWV + 1.170 × AST/ALT + 0.011 × HA + 0.020 × CIV + 0.719 × APRI + 0.379 × FIB-4.CONCLUSIONSWV combined with serological indexes can improve the accuracy of diagnosis for CHB hepatic fibrosis. Serum indexes can help diagnose the degree of hepatic fibrosis.

Performance of simple noninvasive scoring systems for the prediction of advanced fibrosis in patients with chronic hepatitis B.

The aim of the study was to analyze the diagnostic performance and clinical utility of simple noninvasive tests for the detection of advanced fibrosis in patients with chronic hepatitis B (CHB) infection seen at a tertiary referral center in Germany. We retrospectively analyzed 239 adult CHB patients with available liver biopsies. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging, and histology were recorded. The sensitivity, specificity, and positive and negative predictive values were determined along with the area under receiver operating characteristic curves (AUROC) using published formulas and cut-off values for fibrosis index based on the four factors, aspartate aminotransferase-alanine aminotransferase ratio index (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), and age-platelet index. The median documented duration of CHB infection was 31 months (range: 6-340 months); 86% of the patients were Caucasian and 71% were men. The AUROCs for the detection of advanced fibrosis were 0.75 [95% confidence interval (CI): 0.67-0.82], 0.72 (95% CI: 0.64-0.80), 0.48 (95% CI: 0.39-0.56), and 0.73 (95% CI: 0.66-0.81) for fibrosis index the four factors, APRI, AAR, and age-platelet index, respectively. Patients with advanced fibrosis on biopsy were misclassified as having mild fibrosis in 35% (APRI) to 82% (AAR) of cases. Because of their moderate test performance (AUROCs: 0.48-0.75) and their high misclassification rate, we could not confirm a reliable clinical utility for the analyzed noninvasive fibrosis scoring systems for the prediction of advanced fibrosis in mostly Caucasian CHB patients.

Serum Fibrosis Marker Panels FIB-4 Index and Aspartate Aminotransferase (AST)-to-Platelet Ratio Index (APRI) Are Equivalent to AST Alone at Predicting Liver Fibrosis in a Cohort of 1731 Patients Infected with Hepatitis C Virus.

Efficient tools are needed to stage liver disease before treatment of patients infected with hepatitis C virus (HCV). Compared to biopsy, several studies demonstrated favorable performance of noninvasive multianalyte serum fibrosis marker panels [fibrosis-4 (FIB-4) index] and aspartate aminotransferase (AST)-to-platelet ratio index (APRI), but suggested cutoffs vary widely. Our objective was to evaluate FIB-4 index and APRI and their component tests for staging fibrosis in our HCV-infected population and to determine practical cutoffs to help triage an influx of patients requiring treatment. Transient elastography (TE) results from 1731 HCV-infected patients were mapped to an F0-F4 equivalent scale. Each patient's APRI and FIB-4 index were calculated. Areas under the receiver operator curve (AUROCs) and false-positive and false-negative rates were calculated to retrospectively compare the performance of the indices and their component tests. The highest AUROCs for distinguishing severe (F3-F4) from mild-to-moderate (F0-F2) fibrosis had overlapping 95% CIs: APRI (0.77; 0.74-0.79), FIB-4 index (0.76; 0.73-0.78), and AST (0.74; 0.72-0.77). Cutoffs had false-negative rates of 2.7%-2.8% and false-positive rates of 6.4%-7.4% for all 3 markers. AST was as effective as FIB-4 index and APRI at predicting fibrosis. Published cutoffs for APRI and FIB-4 index would have been inappropriate in our population, with false-negative rates as high as 11%. For our purposes, no serum fibrosis marker was sufficiently sensitive to rule-out significant fibrosis, but cutoffs developed for AST, FIB-4 index, and APRI all had specificities of 79.2%-80.3% for ruling-in severe fibrosis and could be used to triage 1/3 of our population for treatment without waiting for TE or liver biopsy.

Comparison of serological assessments in the diagnosis of liver fibrosis in bile duct ligation mice.

Liver fibrosis assessment is essential to make a prognosis and to determine the appropriate anti-fibrosis treatment. Non-invasive serum markers are widely studied in patients to assess liver fibrosis due to the limitations of liver biopsy. When using animal models to study the mechanism and intervention of hepatic fibrosis, serum markers might be useful for the continuous assessment of liver fibrosis in individual animals, which could avoid the influence of biological differences between individuals. However, it is unclear whether serum markers can assess hepatic fibrosis in the animal model. In the present study, we evaluated and compared the ability of four serum markers to assess liver fibrosis in bile duct ligation mice. According to the stages of liver fibrosis assessed by pathological changes, mice in this study were divided into five groups (F0, F1, F2, F3, and F4). Subsequently, four serum markers, aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4), and Forns Index, were calculated for each group. Furthermore, the correlations between serum markers and pathological stages and the ability of serological markers to evaluate liver fibrosis were analyzed. AAR, APRI, FIB-4, and Forns Index could significantly distinguish F0-2 from F3-4 mice. APRI, FIB-4, and Forns Index could detect F0-3 from F4 mice. Among these four markers, FIB-4 was the best able to distinguish ≥F2 and ≥F3, with area under the curve values of 0.882 and 0.92, respectively. Forns Index was best for diagnosing F4 with area under the curve value of 0.879. These results demonstrated that serum markers could be used for assessing liver fibrosis in bile duct ligation mice, and therefore, these markers might lead to more accurate diagnostic and therapeutic studies through continuous monitoring in individual animals. Impact statement The assessment of liver fibrosis is essential for making a prognosis and determining the appropriate anti-fibrosis treatment. In studies focusing on the mechanism and treatment of liver fibrosis using animal models, it would be more accurate to continuously evaluate liver fibrosis in a single animal to avoid individual biological differences. Unfortunately, it is difficult to perform continuous assessment through liver biopsy in the most commonly used rodent models. It is unclear whether serum markers, which have been used in hepatic fibrosis patients, could be used in animal models. Our results demonstrate that serum markers could be used for assessing liver fibrosis in bile duct ligation mice. This study might contribute to more accurate diagnostic and therapeutic studies through continuous monitoring in individual animals.

Association of Serum Lipids with Hepatic Steatosis, Stage of Liver Fibrosis and Viral Load in Chronic Hepatitis C.

Hepatitis C Virus (HCV) relies on host lipids for its life cycle contributing to lipid abnormalities and hepatic steatosis. Disease progression is influenced by viral factors interacting with host immune and metabolic pathways. The significance of serum lipids for Chronic Hepatitis C (CHC) assessment is not clearly established yet. Our aim was to investigate serum lipids' association with stage of liver fibrosis, steatosis and genotypes in patients with CHC. A total of 112 CHC patients (54 male, 58 female, aged 48.6±13.7 years) were studied - 98 genotype 1 (G1) and 14 genotype 3 (G3). Liver cirrhosis (F4) was diagnosed in 31 cases. Steatosis was present in 75 of all patients on ultrasound. Liver biopsy was done in 65 patients and histology showed steatosis in 28, stages of fibrosis (F1-F3) in 56 and F4 in 9 patients (METAVIR). Laboratory panel included complete blood count, liver tests and serum lipid levels (mmol/l) with Friedewald equation estimations. Indirect noninvasive fibrosis scores FIB-4, Aspartate aminotransferase to Platelet Ratio Index (APRI) and Forns index were calculated. HCV RNA was quantified by RT-PCR. Statistical analysis included Spearman's rho, Mann-Whitney U test, Receiver Operating Characteristic (ROC) curve. Total Cholesterol (TCh) (p=0.002) and Low-Density Lipoprotein (LDL) (p=0.003) in G1 patients were higher when steatosis was present. TCh (p<0.001), High-Density Lipoprotein (HDL) (p=0.018) and LDL (p=0.003) were lower in G1 F4 compared with F1-F3 patients. Triglyceride (TG) levels correlated with FIB-4 (r=0.364, p=0.029), APRI (r=0.333, p=0.047) and Forns index (r=0.423, p=0.010) in G1 patients without steatosis. TG to LDL ratio (TG/LDL) (p=0.001) was higher in F4 than in F1-F3 patients. TG/LDL ratio predicted the presence of F4 in G1 patients without steatosis by an area under the ROC curve 0.900 (p<0.001). TG/LDL ratio > 0.52 was highly specific for F4 without steatosis. Specificity dropped to 76% when steatosis was present. TG/LDL < 0.32 negatively predicted liver cirrhosis. HCV RNA correlated with TG levels (r=0.330, p=0.009) in G1 patients with steatosis and with histological percent of fatty hepatocytes (r=0.585, p=0.028) in G3 patients. Lipid levels in CHC G1 patients depend on the presence of steatosis and cirrhosis. HCV RNA is associated with TG levels in G1 patients with steatosis, but not in G3 patients. In cirrhotic CHC G1 patients cholesterol is low with relatively increased TG. TG/LDL ratio is a potential marker of liver cirrhosis in CHC G1 patients.

Study of miR-29a-5p Expression in HIV Positive and HIV/HCV Co-Infected Patients in Sanandaj-Iran

Background: Co-infection of human immunodeficiency virus (HIV) with hepatitis virus accelerates liver injury. Recently, there has been paid more attention to micro RNAs (miRs) as new tools for determination of liver injury. Previous studies revealed that miR-29 inhibits HIV replication. It has been also shown that miR-29 decreases in hepatocytes of hepatitis C virus (HCV) infected patients. The present study aimed to determine the miR-29a-5p expression as a possible diagnostic marker in HIV- and HIV-HCV co-infected patients. Methods: In this cross-sectional study, blood samples were collected from 40 healthy, 44 HIV-positive, and 121 HIV/HCV co-infected subjects. Blood CD4+ (cluster of differentiation 4) cell counts were recorded and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities, miR-29a-5p expression, fibrosis-4 (FIB-4), and AST to platelet ratio index (APRI) index were determined. Data were analyzed by SPSS version 16 and p value less than 0.05 was considered statistically significant. Results: Serum ALT and AST activities and FIB-4 and APRI were significantly higher in HIV-HCV-co-infection group than the control group (P< 0.05); however, miR-29a-5p was down-regulated in patients compared to controls. CD4+ cell counts markedly decreased in all patients and showed a significant direct correlation with miR-29a-5p (rs = 0.225, P < 0.045). The inverse significant correlation of FIB4 and APRI with miR-29a-5p expression was also seen (rs = -0.691, P = 0.005 and rs = -0.712, p<0.001, respectively). Conclusions: miR-29a-5p was significantly down-regulated in HIV- and HIV/HCV-co-infected patients and showed a correlation with liver injury. Down-regulation of miR-29a-5p was directly associated with CD4+ cell counts and reversely correlated with FIB-4 and APRI index. Therefore, the determination of miR-29a-5p may be useful, among other markers, for diagnosis of these diseases.

Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C.

Fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac-2 bp) are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively. The serum levels of both Fuc-Hpt and Mac-2 bp increased with the progression of liver fibrosis. The multivariate analysis revealed that Mac-2 bp was an independent factor associated with moderate liver fibrosis (F ≥ 2). In contrast, Fuc-Hpt was an independent factor associated with advanced liver fibrosis (F ≥ 3). In terms of evaluating liver fibrosis, the serum levels of these glycomarkers were correlated with well-known liver fibrosis indexes, such as the aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB4) index. An assay that combined the APRI or FIB4 index and the Fuc-Hpt or Mac-2 bp levels increased the AUC value for diagnosing hepatic fibrosis. Interestingly, the cumulative incidence of hepatocellular carcinoma (HCC) was significantly higher in the patients with elevated serum levels of Fuc-Hpt and Mac-2 bp. In conclusion, both Fuc-Hpt and Mac-2 bp could be useful glyco-biomarkers of liver fibrosis and predictors of HCC in patients with chronic hepatitis C.

Prediction of esophageal varices and variceal hemorrhage in patients with acute upper gastrointestinal bleeding

In patients with upper gastrointestinal bleeding (UGIB), identifying those with esophageal variceal hemorrhage prior to endoscopy would be clinically useful. This retrospective study of a large cohort of patients with...

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

To investigate the combined diagnostic accuracy of acoustic radiation force impulse (ARFI), aspartate aminotransferase to platelet ratio index (APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage (all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI (P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage (Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI (Z = 0.958, P = 0.338). ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

Value of Egy‐Score in diagnosis of significant, advanced hepatic fibrosis and cirrhosis compared to aspartate aminotransferase‐to‐platelet ratio index, FIB‐4 and Forns' index in chronic hepatitis C virus

Serum markers and developed scores are of rising importance in non-invasive diagnosis of hepatic fibrosis. Aspartate aminotransferase-to-platelet ratio index (APRI), FIB-4 and Forns' index are validated scores used for diagnosis of liver fibrosis. The Egy-Score is a newly developed score for detection of hepatic fibrosis with promising results. We aimed to assess the accuracy of the Egy-Score in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis compared to APRI, FIB-4 and Forns' in chronic hepatitis C virus (HCV) patients. A retrospective study including 100 chronic hepatitis C naïve Egyptian patients was performed. Patients were classified according to stages of fibrosis into three groups: significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4). Egy-Score, APRI, FIB-4 and Forns' index were calculated. Regression analysis and receiver-operator curves were plotted to assess the sensitivity, specificity and predictive values for the significant scores with the best cut-off for diagnosis. An Egy-Score of 3.28 or more was superior to APRI, FIB-4 and Forns' index for detecting advanced fibrosis with a sensitivity of 91% and specificity of 78%. An Egy-Score of 3.67 or more was superior to APRI, FIB-4 and Forns' index for detecting cirrhosis with a sensitivity of 82% and specificity of 87%. Forns' index was superior to Egy-Score, FIB-4 and APRI for detecting significant fibrosis. The Egy-Score is a promising, accurate, easily calculated, cost-effective score in the prediction of hepatic fibrosis in chronic HCV patients with superiority over APRI, FIB-4 and Forns' index in advanced hepatic fibrosis and cirrhosis.