Aspartate Aminotransferase-to-platelet Ratio Index Research Articles

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.

Fibrosis-4 index, a predictor for prognosis of hepatocellular carcinoma patients after curative hepatectomy even in hepatitis B virus dominant populations.

Liver fibrosis plays an important role in the development of hepatocellular carcinoma (HCC) and determining its prognosis. Although many staging systems and liver reserve models have been developed without the intention of predicting prognosis of HCC, some studies have investigated their prognostic values in HCC after curative liver resection (LR). The aim of this study is to evaluate prognostic value of non-invasive biomarkers after curative LR. Between 2006 and 2013, HCC patients underwent LR were included and total 962 patients were enrolled. All non-invasive biomarkers (fibrosis 4 index (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and albumin-bilirubin (ALBI) score) were measured at the time of HCC diagnosis. To binarize each biomarker, an optimal cut-off value for fibrosis stage was selected using the value of minimum distance from the left-upper corner of the receiver operating characteristic curve with a specificity >60%. We performed Cox regression analysis on 2-year recurrence-free survival (RFS) and overall survival (OS). The area under curve values for FIB-4 and APRI were the largest for fibrosis stage compared to other biomarkers, 0.669 (95% confidential interval (CI), 0.610-0.719) and 0.748 (95% CI, 0.692-0.800), respectively. Between those two indices, FIB-4 is considered a statistically significant prognostic factor of RFS in HCC patients after LR. The HR for 2-year RFS and OS were 1.81 (95% CI, 1.18-2.77; P = 0.007) and 2.36 (95% CI, 0.99-5.65; P = 0.054), respectively. FIB-4 is identified as a statistically significant predictor of HCC prognosis after curative LR even in HBV dominant populations.

A comparison of on-admission blood cell count-derived parameters on the development of contrast-induced nephropathy in acute coronary syndromes

Contrast-induced nephropathy (CIN) is a clinical entity closely associated with cardiac mortality and morbidity. We aimed to investigate the relationship between CIN after acute coronary syndrome and other bio-inflammatory parameters (Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio) as well as biomarkers such as AST/ALT, SIRI (Systemic Immnun Response Index), AISI (Aggregate Index of Systemic Inflammation), APRI (AST to platelet ratio index), SII (Systemic Immun Inflammation Index) NLR (Neutrophil to lymphocyte ratio), N/LPR (Neutrophil/ (lymphocyte x platelet), PLR (Platelet to lymphocyte ratio), MLR (Monocyte to lymphocyte ratio) and MPVLR (Mean platelet volume to lymphocyte ratio). In this retrospective cross-sectional study, we included 228 patients older than 18 years of age and underwent coronary angiography for acute coronary syndrome between January 2021 and May 2022. We applied the logistic regression analyzes to evaluate the relationship between patients' demographic, clinical characteristics, laboratory parameters, and contrast-induced nephropathy, and to evaluate the predictive power of the AST/ALT, AISI, SIRI, SII, NLR, PLR, MLR, N/LP ratio, MPVLR and other inflammatory based parameters on this primary endpoint. In the univariate analyses, prior history of coronary artery bypass, acute coronary syndrome type, prior ACEi/ARB usage, white blood cell count, hospitalization stay length, contrast amount, MLR, PLR, white blood cell to platelet ratio (WBCPR) were significantly associated with CIN. [p:0.039, p:0.017, p:0.025, p:0.044, p&lt;0.001, p:0.003, p: 0.045, p: 0.044, p:0.044, respectively]. However, multivariable logistic regression analysis showed that WBCPR [OR 0.00 (95% CI 0.00- 0.01) p:0.005] and MLR [OR 13.522 (95% CI 2.15-84.72) p:0.005] might be statistically a significant independent predictor of CIN beside contrast amount [OR 1.92 (95% CI 01.23-3.02) p:0.004]. The WBCPR can be a new valuable independent predictor of CIN. Also, MLR and contrast amount may be a good independent predictor of CIN in acute coronary syndrome.

Development and Validation of Nomograms to Predict the Prognosis of Patients With Unresectable Hepatocellular Carcinoma Receiving Transarterial Chemoembolization.

Recent studies have shown that inflammatory indicators are closely related to the prognosis of patients with hepatocellular carcinoma, and they can serve as powerful indices for predicting recurrence and survival time after treatment. However, the predictive ability of inflammatory indicators has not been systematically studied in patients receiving transarterial chemoembolization (TACE). Therefore, the objective of this research was to determine the predictive value of preoperative inflammatory indicators for unresectable hepatocellular carcinoma treated with TACE. Our retrospective research involved 381 treatment-naïve patients in 3 institutions, including the First Affiliated Hospital of Soochow University, Nantong First People's Hospital, and Nantong Tumor Hospital, from January 2007 to December 2020 that received TACE as initial treatment. Relevant data of patients were collected from the electronic medical record database, and the recurrence and survival time of patients after treatment were followed up. Least absolute shrinkage and selection operator (LASSO) algorithm was used to compress and screen the variables. We utilized Cox regression to determine the independent factors associated with patient outcomes and constructed a nomogram based on multivariate results. Finally, the nomogram was verified from discriminability, calibration ability, and practical applicability. Multivariate analysis revealed that the levels of aspartate aminotransferase-to-platelet ratio index (APRI) and lymphocyte count were independent influential indicators for overall survival (OS), whereas the levels of platelet-to-lymphocyte ratio (PLR) was an independent influential index for progression. Nomograms exhibited an excellent concordance index (C-index), in the nomogram of OS, the C-index was 0.753 and 0.755 in training and validation cohort, respectively; and in the nomogram of progression, the C-index was 0.781 and 0.700, respectively. The time-dependent C-index, time-dependent receiver operating characteristic (ROC), and time-dependent area under the curve (AUC) of the nomogram all exhibited ideal discrimination ability. Calibration curves significantly coincided with the standard lines, which indicated that the nomogram had high stability and low degree of over-fitting. Decision curve analysis revealed a wider range of threshold probabilities and could augment net benefits. The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied significantly between risk categories (P < .0001). The developed prognostic nomograms based on preoperative inflammatory indicators revealed high predictive accuracy for survival and recurrence. It can be a valuable clinical instrument for guiding individualized treatment and predicting prognosis.

Pemafibrate improves liver dysfunction and non-invasive surrogates for liver fibrosis in patients with non-alcoholic fatty liver disease with hypertriglyceridemia: a multicenter study

BackgroundThis retrospective, multicenter study evaluated the effect of pemafibrate treatment on liver function and fibrosis by liver function tests (LFTs) and various fibrotic biomarkers including FibroScan in non-alcoholic fatty liver disease (NAFLD) with hypertriglyceridemia.MethodsA total of 138 NAFLD patients treated with pemafibrate at three hospitals between September 2018 and April 2021 were included. To evaluate the effect of pemafibrate treatment, FibroScan-aspartate aminotransferase (FAST) score, a novel index of steatohepatitis that can be calculated based on the aspartate aminotransferase (AST) value, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) was used.ResultsSerum TG levels were significantly decreased 4 weeks after pemafibrate treatment (p = 0.003). The levels of AST (p = 0.038), alanine aminotransferase (ALT) (p = 0.003), and gamma-glutamyl transferase (GGT) (p = 0.047) also significantly diminished 12 weeks after pemafibrate administration compared to before administration (p < 0.05). However, serum HDL-cholesterol (p = 0.193), LDL-cholesterol (p = 0.967), and eGFR (p = 0.909) levels were not significantly altered 12 weeks after pemafibrate administration. In addition, the fibrosis biomarkers’ Type IV collagen (p = 0.753) and FIB-4 index (p = 0.333) did not significantly differ, while Autotaxin (p = 0.006) and the AST-to-platelet ratio index (APRI) (p = 0.003) significantly decreased 48 weeks after pemafibrate administration. No significant reductions in LSM (p = 0.959) and CAP (p = 0.266) were detected using FibroScan 48 weeks after pemafibrate administration. FAST score was significantly improved (p = 0.0475).ConclusionPemafibrate improved LFTs, including fibrotic biomarkers and FAST score, due to the hepatic anti-inflammatory effect, suggesting that pemafibrate may prevent disease progression in NAFLD patients with hypertriglyceridemia.

Association of Alpha-1 Antitrypsin Pi*Z Allele Frequency and Progressive Liver Fibrosis in Two Chronic Hepatitis C Cohorts.

(1) Background: The inherited alpha-1 antitrypsin (A1AT) deficiency variant 'Pi*Z' emerged as a genetic modifier of chronic liver disease. Controversial data exist on the relevance of heterozygous Pi*Z carriage ('Pi*MZ' genotype) as an additional risk factor in patients with chronic viral hepatitis C to develop progressive liver fibrosis. (2) Methods: Two prospectively recruited cohorts totaling 572 patients with therapy-naïve chronic viral hepatitis C (HCV) were analyzed. The Frankfurt cohort included 337 patients and a second cohort from Leipzig included 235 patients. The stage of liver fibrosis was assessed by liver biopsy, AST-to-platelet ratio index (APRI) score and Fibrosis-4 (FIB-4) score (Frankfurt) as well as liver stiffness measurement (LSM) via transient elastography (Leipzig). All patients were genotyped for the Pi*Z variant (rs28929474) of the SERPINA1 gene. (3) Results: In the Frankfurt cohort, 16/337 (4.7%) patients carried the heterozygous Pi*Z allele while 10/235 (4.3%) in the Leipzig cohort were Pi*Z carriers. In both cohorts, there was no higher proportion of Pi*Z heterozygosity in patients with cirrhosis compared to patients without cirrhosis or patients with cirrhosis vs. no liver fibrosis. Accordingly, Pi*Z frequency was not different in histological or serological stages of liver fibrosis (F0-F4) and showed no clear association with LSM. (4) Conclusions: Evaluation in two representative HCV cohorts does not indicate Pi*Z heterozygosity as a clinically relevant disease modifier in chronic HCV infection. However, validation in even larger cohorts with longitudinal follow-up is warranted.

Association between liver fibrosis and thrombotic or bleeding events in acute coronary syndrome patients

BackgroundThe prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome.MethodsWe included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS).ResultsDuring the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups.ConclusionsIn ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.

Blood pressure stratification for predicting liver fibrosis risk in metabolic dysfunction associated fatty liver disease

Introduction and ObjectivesThe optimal blood pressure (BP) range for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is currently unknown. This study aimed to explore the relationship between stratified BP levels and MAFLD progression. Patients and MethodsThe data of adults who underwent yearly health check-ups were screened to establish both a cross-sectional and a 6-year longitudinal cohort of individuals with MAFLD. BP was classified into the following categories optimal, normal, high-normal, and hypertension. Liver fibrosis was diagnosed with fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). ResultsA total of 10,232 individuals were included in the cross-sectional cohort. In the MAFLD population, individuals with liver fibrosis had significantly higher BP levels and hypertension prevalence (P < 0.001) than those without. Furthermore, liver fibrosis score was significantly associated with BP levels (P < 0.001). In the 6-year longitudinal cohort of 3661 individuals with MAFLD without liver fibrosis, the incidence rates of liver fibrosis increased with increasing BP levels as follows optimal=11.20%, normal=13.90%, high-normal=19.50%, hypertension=26.20% (log-rank 22.205; P < 0.001). Cox regression analysis showed that both baseline high-normal BP (hazard ratio [HR], 1.820; P=0.019) and hypertension (HR, 2.656; P < 0.001) were predictive of liver fibrosis. ConclusionsBP stratification may be useful in predicting the progression of MAFLD. Individuals having MAFLD with concurrent hypertension or high-normal BP are at a higher risk of liver fibrosis. These findings may provide a criteria for early intervention of MAFLD to prevent liver fibrosis.

1276. Noninvasive Assessment of Change in Hepatic Fibrosis Following Initiation of Integrase Inhibitors in Women Living with HIV

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in persons with HIV and can lead to hepatic fibrosis. Integrase strand-transfer inhibitors (INSTIs), first-line agents in antiretroviral therapy (ART), are associated with increased body mass index (BMI), particularly in women living with HIV (WLWH). We evaluated change in hepatic fibrosis risk following INSTI initiation in WLWH. Table 1.Change over time in hepatic fibrosis scores among group switching to INSTI-regimens versus group staying on non-INSTI regimens INSTI=integrase strand-transfer inhibitor; SD=standard deviation; FIB-4=Fibrosis-4 Score (calculated by Age*AST/[platelet count*ALT1/2]; APRI=AST to Platelet Ratio Index (calculated by [AST/AST upper limit of normal]/platelet count); NFS = Non Alcoholic Fatty Liver Disease Fibrosis Score (calculated by -1.675+(0.037*age) + (0.094*body mass index)+(1.13*hyperglycemia or diabetes [yes=1, no=0])+ (0.99*AST/ALT)-(0.013*platelet count)-(0.66*albumin)); CI=Confidence Interval. Linear regression model with unstructured covariance matrix for repeated observations with a person. Adjusted models for all outcomes included the following covariates: age, race/ethnicity, education, baseline CD4 lymphocyte count, baseline antiretroviral anchor drug, and abacavir, tenofovir disoproxil fumarate, and tenofovir alafenamide use. Body mass index was included in models for FIB-4 and APRI only. Age was included for APRI only. Methods Data from 2007-2020 were analyzed from virologically-suppressed WLWH enrolled in the Women’s Interagency HIV Study (WIHS). We excluded WLWH with untreated viral hepatitis, heavy alcohol use and autoimmune or metabolic chronic liver disease. WLWH who switched to or added an INSTI to ART were compared to women who remained on non-INSTI ART. Outcomes included change in noninvasive markers of hepatic fibrosis: Fibrosis-4 (FIB4), AST to Platelet Ratio Index (APRI), and NAFLD fibrosis score (NFS), measured 4-12 months before and 4-19 months post INSTI switch/add. Longitudinal linear regression models compared change over time in each outcome by group, adjusted for covariates. Results 872 WIHS participants (323 INSTI, 549 non-INSTI) were followed for a median 3.0 years (Q1 2.0, Q3 4.5). Mean age was 47.2 years (SD 9.0), 61% were Non-Hispanic Black, and mean BMI was 31.4 (8.8) kg/m2. Absolute mean changes in FIB4, APRI, and NFS scores were +0.021, -0.005, +0.194, respectively, in the INSTI group compared to +0.003, -0.011, +0.016, respectively, in the non-INSTI group (Table 1). No significant differences in mean AST and ALT change between the INSTI and non-INSTI groups were noted. There was a significant increase in NFS score in the INSTI group (p&amp;lt; 0.0001) and this difference remained in adjusted models (p=0.0135). Compared to the non-INSTI group, a larger proportion of participants in the INSTI group changed to a higher NFS risk category: 15.7% vs 9.0%, p=0.014. Conclusion Starting INSTIs was associated with minimal change in FIB4 and APRI scores but increased NFS score in WLWH. The increase in NFS score likely reflects BMI gain with INSTI use, as BMI is not factored into FIB4 or APRI calculators and AST and ALT did not change significantly. Nonetheless, patients starting INSTIs need close monitoring of metabolic changes and low thresholds for additional noninvasive liver fibrosis testing. Disclosures Michael A. Yu, MD, Ligera: Advisor/Consultant Maria L L. Alcaide, MD, Gilead: Advisor/Consultant Adaora A. Adimora, MD, MPH, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support Jennifer C. Price, MD, PhD, Abbvie: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support Phyllis C. Tien, MD, MSc, Gilead: Grant/Research Support|Merck: Grant/Research Support Cecile D. Lahiri, MD, MS, Theratechnologies: Advisor/Consultant.

Non-invasive Assessment of Liver Fibrosis Regression in Patients with Chronic HepatitisB: A Retrospective Cohort Study.

Non-invasive tests (NITs) have been alternative methods of liver biopsy for the cross-sectional assessment of liver fibrosis in patients with chronic hepatitisB (CHB). However, there are limited data on the longitudinal association between NITs and histological changes of liver fibrosis. This study aimed to evaluate whether NITs can be used to assess liver fibrosis regression (LFR) during anti-HBV treatment. This retrospective study included 337 patients with CHB who underwent contemporaneous NITs, such as liver stiffness measurement (LSM), the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), and the γ-glutamyl transpeptidase to platelet ratio (GPR), and liver biopsy at baseline and followed by a repeated liver biopsy and NITs assessment. The LFR was defined as fibrosis regression by at least one stage assessed by METAVIR scoring system. The median interval between the two paired liver biopsy assessment was 31months (IQR 24-45). At the first liver biopsy, the fibrosis stage was F2 in 159 (47.2%), F3 in 68 (20.2%), and F4 in 110 (32.6%) patients. At the second liver biopsy, the number of patients with fibrosis stages F0-1, F2, F3, and F4 was 102 (30.3%), 106 (31.5%), 63 (18.7%), and 66 (19.6%), respectively. At follow-up liver biopsy, 169 patients (50.1%) had LFR, 128 patients (38.0%) had no change in fibrosis stage, and 40 patients (11.9%) had liver fibrosis progression on histology. A decrease in liver stiffness measurement (LSM) by 25% is the optimal cutoff for predicting LFR. Patients with a 25% or larger decrease in LSM value had more LFR than those with a less than 25% decrease in LSM value (78.1% vs 22.9%, p < 0.001). LSM might be used to monitor regression of liver fibrosis during antiviral treatment using nucleos(t)ide analogues (NUCs) in patients with CHB.

Accuracy of noninvasive methods for the diagnosis of liver fibrosis in children with chronic viral hepatitis.

Liver biopsy is the reference standard for assessing liver fibrosis. Moreover, it is an invasive procedure. Transient elastography (TE) is an accurate, noninvasive method for evaluating liver stiffness as a surrogate of liver fibrosis. The aspartate aminotransferase to platelet ratio index (APRI) and Hyaluronic acid (HA) are noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. This study aimed to identify the accuracy of APRI, HA, and TE concerning liver biopsy in children with chronic viral hepatitis. This cross-sectional study included 50 children, 5-18years with chronic viral hepatitis B (HBV) or hepatitis C (HCV) who underwent liver biopsy within nine months of laboratory tests, determining APRI & performing TE. Twenty healthy children of age and sex-matching patients were included as a control group for the serum HA levels. The histopathological findings of the studied cases showed seven cases with (F0) fibrosis, 36 cases with mild (F1,2), two children with moderate (F3,4), and five children with severe (F5,6). The median (IQR) of steatosis was 4 (three had HCV). When correlating TE, APRI, and HA values in all cases with their laboratory data, there was a positive correlation between ALT and APRI values (P-value = 0.000), a positive correlation between AST and HA values (P-value = 0.02), and a negative correlation between stiffness and APRI. The sensitivity of HA, APRI, and TE compared to fibrosis detected by histopathology was 60.5, 65.1, and 60.5%, and their specificity was 71.4, 57.1, and 85.7%, respectively. TE was significantly higher in a group with (moderate to severe) fibrosis. APRI, HA, and TE are good indicators of the presence of fibrosis almost with the same accuracy. TE is the only method to differentiate mild cases from those with significant fibrosis.

Reliability of Non-invasive Liver Fibrosis Assessment Tools Versus Biopsy in Pre- and Post-bariatric Surgery Patients with Non-alcoholic Fatty Liver Disease.

Liver biopsy (LBx) remains the gold standard to assess fibrosis in non-alcoholic fatty liver disease (NAFLD). Biochemical markers are also useful, but their reliability is not clear in patients with morbid obesity. We assessed the performance of six non-invasive fibrosis assessment tools before and after bariatric surgery (BSx) using LBx. This is a cross-sectional and prospective cohort study. LBx was performed at the time of BSx and 12-month post-operatively and assessed using the Brunt system. Clinical and biochemical measurements were collected at the same time points and six non-invasive fibrosis assessment tools were calculated. One hundred seventy patients had BSx; 79.4% female; age was 46.6 ± 9.8years, and BMI was 48.6 ± 7.5kg/m2. From liver histology, 88% had F0-F2 and 11.2% F3-F4. At BSx, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 had better accuracy (0.86 and 0.88) with specificity of 96.6% and 94.0% and negative predictive values (NPV) of 88.9% and 93.7%. However, sensitivity (6.7% and 40.0%) and positive predictive values (PPV) (20.0% and 46.2%) were low. Twelve months post-surgery (n = 54), 88.9% of patients had F0-F2 and 11.1% had F3-F4. Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) had the best accuracy (0.79 and 0.77) with specificity of 83.7% and 86.9% and NPV of 92.3% and 86.9%. However, sensitivity (25% and 0%) and PPV (12.5% and 0%) were low. Overall, FIB-4, APRI, and NFS showed similar performances with higher accuracy, specificity, and NPV. Sensitivity and PPV were low. These tests are more useful at excluding advanced fibrosis.

Diagnostic performance of two non-invasive biomarkers used individually and in sequential combination for cirrhosis associated with hepatitis C virus infection

This cross-sectional study evaluated the performance of the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) and the Fibrosis-4 (FIB-4) Index when they were used individually and in sequential combination to diagnose cirrhosis associated with hepatitis C virus infection. The final evaluation involved 906 people living with hepatitis C. The diagnostic performance of individual biomarkers at cut-off scores of 1.5 and 2.0 for the APRI and at 3.25 for the FIB-4 index was assessed. For the sequential combination method, the cirrhosis status of individuals with an APRI score between 1.0 and 1.5 were reassessed using the FIB-4. Transient elastography (TE) was used as the reference standard for diagnosing cirrhosis. The APRI, at a cut-off score of 1.5, showed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 44.9%, 97.6%, 91.1% and 76.3%, respectively. Increasing the cut-off score to 2.0 produced a much lower sensitivity (29.6%) and NPV (71.9%). The FIB-4, at a cut-off score of 3.25, yielded a sensitivity, specificity, PPV and NPV of 40.8%, 97.3%, 89.1% and 75.0%, respectively. The sequential combination method demonstrated a much more optimal diagnostic performance (50.2% sensitivity, 96.6% specificity, 89.0% PPV and 77.9% NPV). Overall, the APRI and FIB-4 Index performed better in diagnosing cirrhosis associated with hepatitis C when they were used in sequential combination.

Clinical features of chronic hepatitis B patients with lean nonalcoholic fatty liver disease.

The clinical features have been well described in obese chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). However, little is known about the clinical features of lean CHB-NAFLD patients. The study retrospectively included treatment-naïve CHB patients who underwent ultrasound between 2015 and 2021. Liver fibrosis was assessed by aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis-4 score (FIB-4), NAFLD fibrosis score (NFS), and transient elastography. Among 1226 CHB-NAFLD patients, 25.0% patients were lean. The age, gender, and platelet, alanine aminotransferase, AST, and albumin levels were comparable between lean CHB-NAFLD and nonlean patients. The levels of plasma glucose, triglycerides, total cholesterol, and uric acid, as well as proportions of concurrent hypertension and diabetes, were lower in lean patients. Lean patients presented higher hepatitis B surface antigen (HBsAg) levels (3.4 log10 IU/ml vs. 3.2 log10 IU/ml, p=0.006), hepatitis B virus (HBV) DNA levels (4.1 log10 IU/ml vs. 3.2 log10 IU/ml, p<0.001), and hepatitis B e antigen (HBeAg) positive proportions (40.4% vs. 30.2%, p=0.002) than nonlean patients. The values of APRI, FIB-4, and liver stiffness were comparable between two groups. However, lean patients had lower NFS values (-3.0 vs. -2.6, p<0.001) and lower proportions (12.6% vs. 21.1%, p=0.003) of advanced fibrosis (NFS≥-1.5) than nonlean patients. Similar results were observed in HBeAg-positive and HBeAg-negative subgroups. Nearly a quarter of CHB-NAFLD patients were lean. Lean patients had lower proportions of metabolic abnormalities and advanced liver fibrosis than nonlean patients. However, lean CHB-NAFLD patients had higher HBsAg levels, HBV DNA levels, and HBeAg-positive proportions. Registry and registration no. of the study/trial: Clinicaltrials.gov, Identifier: NCT03097952.

The NAFLD Decompensation Risk Score: External Validation and Comparison to Existing Models to Predict Hepatic Events in a Retrospective Cohort Study

The NAFLD decompensation risk score (the Iowa Model) was recently developed to identify patients with nonalcoholic fatty liver disease (NAFLD) at highest risk of developing hepatic events using three variables-age, platelet count, and diabetes. We performed an external validation of the Iowa Model and compared it to existing non-invasive models. We included 249 patients with NAFLD at Boston Medical Center, Boston, Massachusetts, in the external validation cohort and 949 patients in the combined internal/external validation cohort. The primary outcome was the development of hepatic events (ascites, hepatic encephalopathy, esophageal or gastric varices, or hepatocellular carcinoma). We used Cox proportional hazards to analyze the ability of the Iowa Model to predict hepatic events in the external validation (https://uihc.org/non-alcoholic-fatty-liver-disease-decompensation-risk-score-calculator). We compared the performance of the Iowa Model to the AST-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), and the FIB-4 index in the combined cohort. The Iowa Model significantly predicted the development of hepatic events with hazard ratio of 2.5 [95% confidence interval (CI) 1.7-3.9, P < 0.001] and area under the receiver operating characteristic curve (AUROC) of 0.87 (CI 0.83-0.91). The AUROC of the Iowa Model (0.88, CI: 0.85-0.92) was comparable to the FIB-4 index (0.87, CI: 0.83-0.91) and higher than NFS (0.66, CI: 0.63-0.69) and APRI (0.76, CI: 0.73-0.79). In an urban, racially and ethnically diverse population, the Iowa Model performed well to identify NAFLD patients at higher risk for liver-related complications. The model provides the individual probability of developing hepatic events and identifies patients in need of early intervention.

Prognostic study of acute-on-chronic liver failure patients: Usefulness of the fibrosis-4 index.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of liver function in cirrhotic patients. Since treatment of this condition is difficult, its prevention is of paramount importance. The predictors of ACLF are yet to be identified. To determine the prognosis of cirrhotic and ACLF patients, we conducted a retrospective study to analyze each parameter in ACLF patients. Cirrhotic patients with serum total-bilirubin level ≥5.0 mg/dL and prothrombin time (PT) value ≤40% after acute insults were diagnosed with ACLF, whereas patients who met one of the above criteria were diagnosed with extended type of ACLF (EX-ACLF). Overall, in this study, 18 ACLF and 16 EX-ACLF patients retrospectively investigated between 2008 and 2020, and each data was analyzed during and before acute insults. In the analysis during acute insults, renal and coagulation functions showed significant differences between the ACLF and EX-ACLF groups. Furthermore, the mortality rate in the ACLF group was higher than that in the EX-ACLF group. In the analysis before acute insults, aspartate aminotransferase (AST), Fibrosis-4 (FIB-4) index score, and AST to platelet ratio index (APRI) showed significant differences between the two groups. Among these, the FIB-4 index score correlated best with ACLF severity for identifying cirrhotic patients with poor prognosis. The FIB-4 index is the most useful predictor of ACLF severity. Careful management of cirrhotic patients with a high FIB-4 index score is considered beneficial to prevent ACLF occurrence.

Indirect serum biomarkers perform sub optimally in screening for significant liver fibrosis among HIV-infected and uninfected adults in Uganda.

Indirect serum bio-markers present an acceptable noninvasive and cheap alternative for screening of significant liver fibrosis (SLF). Evaluation of their use in resource limited settings is important to determine their utility. We conducted a cross sectional study among 520 HIV infected and HIV uninfected adults attending care clinics in Kampala Uganda. Presence of SLF was determined using Fibroscan® liver stiffness measurement of ≥7.2KPa. The diagostic value of indirect serum bio-markers for diagnosis of SLF was evaluated using the area under the receiver operating characteristics curve (AUROC) using Fibroscan® as gold standard. Overall AUROC values for Age Platelet Index (API), Aspartate to Alanine Ratio (AAR), AST-to-Platelet Ratio Index (APRI), Fibrosis Index based on 4 Factors (FIB-4) and Gamma glutamyl transferase to Platelet Ratio Index (GPR) were 0.52, 0.49, 0.55, 0.55 and 0.54 respectively. Among HIV-infected participants AUROC values were slightly improved at predicting presence of SLF but still under 70%. Despite APRI and FIB-4 being more likely to identify participants with SLF, the overall diagnostic value of all serum bio-markers was poor with and without stratification by HIV status. We recommend the use of Fibroscan® technology as more accurate non-invasive diagnostic method for screening of SLF.

Clinical characteristics and construction of a predictive model for patients with sepsis related liver injury

BackgroundSepsis-related liver injury (SRLI) is a common condition in critically ill patients, and it is associated with poor outcomes. Early identification of liver injury in sepsis can provide clinicians withthe abundance of information for optimizing treatment strategies and improve quality of life. Therefore, the purpose of this study was to establish a predictive model to assess the early predictive value of liver injury in sepsis. MethodIn this retrospective study, a total of 1116 patients with sepsis enrolled from the Biobank of First Affiliated Hospital of Xi’an Jiaotong University were included. According to the diagnosis of SRLI, all patients were divided into SRLI group and sepsis group. Multivariable analysis was performed using stepwise logistic regression to identify the independent risk factors of SRLI. Based on the results of multivariate regression analysis, we constructed a prediction model. The receiver operating characteristic curve (ROC) was used to determine the predictive value of the model on SRLI. ResultsFrom December 2015 to December 2021,1116 cases met the inclusion criteria and were included in this study. The median age was 58 years, of which 458 (41.04 %) were female. We discoveredthat procalcitonin (PCT), AST-to-platelet ratio index (APRI), alanine aminotransferase (ALT), lactate (Lac), blood urea nitrogen (BUN), Neutrophil and Cardiovascular disease were independent predictors for SRLI. We used to enter methods for constructing the predictive model and finally found that the indicators of model 2 (AUC = 0.832) were readily available and had good predictive value for SRLI. Furthermore, we also found that model 2 (AUC = 0.763), with a sensitivity of 81.4 %, demonstrated excellent predictive value for predicting 28-day mortality in patients with septic liver injury. ConclusionsThis study explored the risk factors of SRLI, and established a prediction model that can accurately and effectively predict the occurrence of SRLI. Furthermore, model 2 is easy to obtain and has the highest sensitivity, which can contribute to early warning and appropriate clinical decision-making.

Red blood cell distribution width derivatives in alcohol-related liver cirrhosis and metabolic-associated fatty liver disease

BACKGROUNDLooking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring. There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIMTo study red blood cell distribution width (RDW), RDW-to-platelet ratio (RPR) and RDW-to-lymphocyte ratio (RLR) in alcohol-related liver cirrhosis (ALC) and metabolic-associated fatty liver disease (MAFLD).METHODSThe study group was composed of 302 people: 142 patients with ALC and 92 with MAFLD; 68 persons were included as controls. RDW, RPR and RLR were measured in each person. Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index (APRI), fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio (GPR), procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin]. MELD score in ALC patients and non-alcoholic fatty liver disease (NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group. The achieved results were compared to controls. Then a correlation between assessed markers was done. Diagnostic value of each investigated parameter and its suggested cut-off in the research group were evaluated with area under the curve (AUC).RESULTSRDW, RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls (ALC: P < 0.0001; NAFLD: P < 0.05, P < 0.0001 and P < 0.0001, respectively). RPR correlated positively with MELD score (P < 0.01) and indirect indices of liver fibrosis (FIB-4 and GPR; P < 0.0001) in ALC patients; negative correlations were found between PDGF-AB and both: RDW and RPR (P < 0.01 and P < 0.0001, respectively). RPR correlated positively with NAFLD fibrosis score and APRI (P < 0.0001) in the MAFLD group; a positive relationship was observed between RDW and FIB-4, too (P < 0.05). AUC values and suggested cut-offs for RDW, RPR and RLR in ALC patients were: 0.912 (> 14.2%), 0.965 (> 0.075) and 0.914 (> 8.684), respectively. AUC values and suggested cut-offs for RDW, RPR and RLR in MAFLD patients were: 0.606 (> 12.8%), 0.724 (> 0.047) and 0.691 (> 6.25), respectively.CONCLUSIONRDW with its derivatives appear to be valuable diagnostic markers in patients with ALC. They can also be associated with a deterioration of liver function in this group.

Diagnostic Accuracy of Red Cell Distribution Width to Platelet Ratio for Detection of Liver Fibrosis Compared with Fibroscan in Chronic Hepatitis B Egyptian patients

Background and Aims: The decision to treat chronic hepatitis B Virus infection (CHB) may necessitate an assessment of the degree of liver fibrosis. Guidelines recommend Fibroscan examination in such cases. However, it is costly and not widely available. Red cell distribution width (RDW) and platelet count are simple parameters obtained from the blood pictures; and their ratio RDW to platelet ratio (RPR) was claimed to correlate with liver fibrosis. We aimed to assess the ability of RPR to replace the costly fibroscan in the detection of significant fibrosis in chronic hepatitis B patients. Patients and Methods: This cross-sectional study was conducted in the Tropical medicine department, Tanta University, Egypt, between December 2018 and September 2019. One hundred and twenty-five patients with CHB were included and divided according to the fibroscan examination into: Group I: patients with no significant fibrosis (n=66), Group II: patients with significant (≥ F2) fibrosis (n=59). RPR was calculated for all patients and tested against Fibroscan results. Results: Both groups were matched in regards to age, sex, viral load, and steatosis. There was a significant positive correlation between the degree of stiffness measured by FibroScan in patients with a significant degree of fibrosis and serum bilirubin, a quantitative polymerase chain reaction of hepatitis B virus DNA (HBV DNA PCR), and fibrosis-4 score (FIB-4 score) (P value= 0.020, 0.049, and 0.0402, respectively). However, RPR was not correlated to the degree of fibrosis in fibroscan examination. Conclusions: The accuracy of RDW to platelet ratio (RPR) for the detection of fibrosis in CHB patients is questionable. FIB-4 is correlated with liver stiffness measurement (LSM) in patients with significant fibrosis (F2 or more). Neither RPR, AST to Platelet Ratio Index (APRI) or FIB4 can replace fibroscan for grading of fibrosis in CHB patients for evaluation to start therapy.