APRI Score Research Articles

Evaluation of FIB-4, NFS, APRI and Liver Function Tests as Predictors for SARS-CoV-2 Infection in the Elderly Population: A Matched Case-Control Analysis.

Several investigations have revealed that COVID-19 causes a significant death rate due to acute respiratory distress syndrome, alterations in the quantity of ACE2 receptor expression, or the intensity of cytokine storm. Similarly, patients with hepatic impairment that are co-infected with SARS-CoV-2 are more likely to display upregulations of ACE2 receptors and cytokine storm overload, which exacerbates hepatic impairment, potentially increasing the death rate. Moreover, it is expected that the aging population develops a higher degree of hepatic fibrosis in association with other comorbid conditions that are likely to influence the course of COVID-19. Therefore, this research was developed to describe the differences in liver test parameters in elderly individuals with COVID-19 in relation to other inflammatory markers and outcomes. This current observational single-center research followed a case-control design of elderly patients hospitalized for SARS-CoV-2 infection. The research was conducted at a tertiary emergency hospital in western Romania during a two-year period. There were 632 patients included in the analysis that were split into two equal groups matched 1:1 based on gender and body mass index. Three hundred sixteen patients made the group of cases with COVID-19 patients older than 65 years, while the other half were the 316 patient controls with COVID-19 that were younger than 65 years old. Disease outcomes showed a higher prevalence of ICU admissions (22.8% vs. 12.7%, p-value < 0.001) and in-hospital mortality (17.1% vs. 8.9%, p-value = 0.002) in the group of cases. Specific and non-specific liver biomarkers were identified as risk factors for mortality in the elderly, such as ALP (OR = 1.26), LDH (OR = 1.68), AST (OR = 1.98), and ALT (OR = 2.34). Similarly, patients with APRI and NFS scores higher than 1.5 were, respectively, 2.69 times and, 3.05 times more likely to die from COVID-19, and patients with FIB-4 scores higher than 3.25 were 3.13 times more likely to die during hospitalization for SARS-CoV-2 infection. Our research indicates that abnormally increased liver biomarkers and high liver fibrosis scores are related to a worse prognosis in SARS-CoV-2 infected individuals.

From the Editor’s Desk…

From the Editor’s Desk…

Relationship between non-invasively detected liver fibrosis and in-hospital outcomes in patients with acute coronary syndrome undergoing PCI

BackgroundPatients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) still experience a high rate of in-hospital complications. Liver fibrosis (LF) is a risk factor for mortality in the general population. We investigated whether the presence of LF detected by the validated fibrosis 4 (FIB-4) score may indicate ACS patients at higher risk of poor outcome.MethodsIn the prospective ongoing REAl-world observationaL rEgistry of Acute Coronary Syndrome (REALE-ACS), LF was defined by a FIB-4 score > 3.25. We repeated the analysis using an APRI score > 0.7. The primary endpoint was in-hospital adverse events (AEs) including a composite of in-hospital cardiogenic shock, PEA/asystole, acute pulmonary edema and death.ResultsA total of 469 consecutive ACS consecutive patients were enrolled. Overall, 21.1% of patients had a FIB-4 score > 3.25. Patients with LF were older, less frequently on P2Y12 inhibitors (p = 0.021) and admitted with higher serum levels of white blood cells (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001), C-reactive protein (p = 0.013), hs-TnT (p < 0.001), creatine-kinase MB (p < 0.001), D-Dimer levels (p < 0.001). STEMI presentation and higher Killip class/GRACE score were more common in the LF group (p < 0.001). 71 patients experienced 110 AEs. At the multivariate analysis including clinical and laboratory risk factors, FIB-4 > 3.25 (OR 3.1, 95%CI 1.4–6.9), admission left ventricular ejection fraction% below median (OR 9.2, 95%CI 3.9–21.7) and Killip class ≥ II (OR 6.3, 95%CI 2.2–18.4) were the strongest independent predictors of in-hospital AEs. Similar results were obtained using the APRI score.ConclusionLF detected by FIB-4 score > 3.25 was associated with more severe ACS presentation and worse in-hospital AEs irrespective of clinical and laboratory variables.Graphical abstract

Liver fibrosis progression in a cohort of young HIV and HIV/ HBV co-infected patients: A longitudinal study using non-invasive APRI and Fib-4 scores.

BackgroundThe risk of liver fibrosis increases over time in HIV and HIV-HBV individuals even under antiretroviral treatment (ART), warranting a rigorous and periodic monitorization. Given the lower availability of transient elastography, we aimed to assess the longitudinal variation of two non-invasive liver fibrosis scores, APRI and Fib-4, in cases with HIV monoinfection, HIV-HBV co-infection and individuals with HBsAg-seroclearance.MethodsWe performed an observational retrospective study between 2013 and 2019 on 212 HIV patients including 111 individuals with HIV mono-infection, 62 individuals with HIV-HBV co-infection and positive HBsAg and 39 cases with HIV-HBV infection and HBsAg-loss. The groups were followed at 36, 48, and 60 months. Liver fibrosis was indicated by an APRI >0.5 or Fib-4≥1.45 score and advanced fibrosis by an APRI score >1.5 or Fib-4 >3.25. Logistic regression with generalized estimating equations (GEE) was used to assess the predictors for the presence of liver fibrosis over time.ResultsDuring a median follow-up of 58.5 months the prevalence of liver fibrosis in all patients increased with 0.5% reaching 11.3% using an APRI score and with 0.9% reaching 10.8% using the Fib-4 score. At the visit corresponding to 60 months the prevalence of liver fibrosis was higher in all HIV-HBV patients compared with individuals with HIV mono-infection, namely: 16.1% on APRI and 12.9% on the Fib-4 score in HIV-HBV/HBsAg-positive individuals, 12.8% on both APRI and Fib-4 scores in HIV-HBV/HBsAg-negative individuals vs. 8.1 and 9%, respectively in HIV mono-infection. The presence of liver fibrosis over the study period was independently associated with plasma HIV RNA, CD4+T cell counts, HIV-HBV co-infection (for APRI >0.5) and ART non-adherence (for Fib-4 >1.45). At the final visit, non-adherence to ART and CD4+T cell counts remained associated with liver fibrosis.ConclusionsThe study found a slow progression of APRI and Fib-4 scores over time in young PLWH with extensive ART. Liver fibrosis scores continued to increase in patients with HIV mono-infection yet remained lower than in HIV-HBV patients irrespective on the presence of HBsAg. The periodic follow-up using non-invasive scores on the long-term could help improve the surveillance in low-income settings and high scores should be followed by additional diagnostic methods.

Impact of HIV-1 Infection on the Natural Progress of an Anti-HCV Positive Population in an Impoverished Village in China from 2009 to 2017.

Our study aimed to determine the impact of HIV coinfection on the natural progression of liver disease in treatment-naive HCV-infected patients. From 2009 to 2017, we tracked non-invasive markers of liver fibrosis and end-stage liver disease (ESLD)-associated mortality among HCV mono-infected and HIV/HCV coinfected patients in an impoverished village in China. The study cohort consisted of 355 HBsAg-negative and anti-HCV (+) or anti-HIV (+) patients recruited in July 2009, 164 of whom were diagnosed with HIV-1 infection. The surviving patients were re-evaluated in August 2017. During the follow-up, the disease status, liver biochemical, and non-invasive indicators of liver fibrosis (APRI and FIB-4) were measured. The transaminases ALT and AST were significantly higher in HIV-positive HCV resolvers (HIV+ HCVr) than in HIV-negative HCV resolvers (HCVr) (p = 0.019 and p < 0.0001, respectively). APRI and FIB-4 scores of HIV-positive chronic HCV carriers (HIV+ HCVc) were significantly higher than in HIV-negative chronic HCV carriers (HCVc) (p < 0.001). Similarly, APRI and FIB-4 scores were higher in the HIV+ HCVr group than in the HCVr group (ps < 0.001). From 2009 to 2017, the levels of ALT (p = 0.006), AST (p = 0.003), APRI (p = 0.015), and FIB-4 (p = 0.025) were significantly elevated in the HIV/HCV coinfected patients with CD4+ T counts below 500 cells/l. ESLD-related mortality was significantly greater in HIV/HCV-infected cases than in HCV mono-infected patients (73.3% vs. 31.3%, p = 0.009) among patients (n = 45) who died between 2009 and 2017 during follow-up. These findings suggest a higher risk of ESLD-related death and rapid progression of liver fibrosis in HIV/HCV coinfected individuals compared with HCV mono-infected patients. During HIV/HCV coinfection, HIV infection may aggravate HCV-associated liver injury.

AST TO PLATELET RATIO INDEX (APRI) AND DEGREE OF SEVERITY BASED ON CHILD-PUGH CLASSIFICATION AMONG CIRRHOSIS PATIENTS AT INTERNAL MEDICINE WARD IN A TERTIARY HOSPITAL

Highlights: 1. The Child-Pugh score is an instrument to assess the degree of severity and prognosis of chronic liver disease. 2. the rise in APRI score may predict the advance of cirrhosis stages. Abstract: Background: Simple diagnostic and screening methods are needed to assist with liver biopsy, which is not always available in local health facilities. Objective: To assess the AST-to-Platelet Count Index (APRI) as a means to predict the advance of cirrhosis stages as indicated in Child-Pugh classification. Material and Method: This research employed an observational descriptive study design to examine laboratory values such as serum AST and platelet count, which were then compared to Child-Pugh profiles among cirrhosis patients at an inpatient facility in a tertiary hospital of Dr Soetomo General Academic Hospital, Surabaya, Indonesia on 1 January – 31 December 2015. The sampling method for this research was total sampling from medical histories. Result: Data obtained were then analyzed and tabulated using the descriptive technique. As many as 191 samples were obtained, consisting of male (N=129, 67.54%) and female patients (N=62, 32.46%) with a ratio of 2.08:1. APRI score showed an increase in age, with a peak frequency of 68 patients (35.6%) in the range 50-59 years old. Male patients had a higher average APRI score (2.11) than their female counterparts (1.93). Patients from Child C were the majority in this research, consisting of 105 patients (54.9%), followed by Child B (N=65, 34.03%) and A (N=21, 10.9%). Conclusion: The proportion of patients with APRI score &gt; 1.5 is increasing along with the degree of severity according to the Child-Pugh classification. This indicates that the rise in APRI score may predict the advance of cirrhosis stages.

Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation.

Liver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating PPi homeostasis. To that aim, we compared [PPi]pl before liver transplantation (LT) and 3 months after LT. We also assessed the expression of four key regulators of PPi in liver tissues and established correlations between AC, and scores of liver fibrosis and liver failure in these patients. LT candidates with various liver diseases were included. AC scores were assessed in coronary arteries, abdominal aorta, and aortic valves. Liver fibrosis was evaluated on liver biopsies and from non-invasive tests (FIB-4 and APRI scores). Liver functions were assessed by measuring serum albumin, ALBI, MELD, and Pugh–Child scores. An enzymatic assay was used to dose [PPi]pl. A group of patients without liver alterations from a previous cohort provided a control group. Gene expression assays were performed with mRNA extracted from liver biopsies and compared between LT recipients and the control individuals. [PPi]pl negatively correlated with APRI (r = −0.57, p = 0.001, n = 29) and FIB-4 (r = −0.47, p = 0.006, n = 29) but not with interstitial fibrosis index from liver biopsies (r = 0.07, p = 0.40, n = 16). Serum albumin positively correlated with [PPi]pl (r = 0.71; p < 0.0001, n = 20). ALBI, MELD, and Pugh–Child scores correlated negatively with [PPi]pl (r = −0.60, p = 0.0005; r = −0.56, p = 0.002; r = −0.41, p = 0.02, respectively, with n = 20). Liver fibrosis assessed on liver biopsies by FIB-4 and by APRI positively correlated with coronary AC (r = 0.51, p = 0.02, n = 16; r = 0.58, p = 0.009, n = 20; r = 0.41, p = 0.04, n = 20, respectively) and with abdominal aorta AC (r = 0.50, p = 0.02, n = 16; r = 0.67, p = 0.002, n = 20; r = 0.61, p = 0.04, n = 20, respectively). FIB-4 also positively correlated with aortic valve calcification (r = 0.40, p = 0.046, n = 20). The key regulator genes of PPi production in liver were lower in patients undergoing liver transplantation as compared to controls. Three months after surgery, serum albumin levels were restored to physiological levels (40 [37–44] vs. 35 [30–40], p = 0.009) and [PPi]pl was normalized (1.40 [1.07–1.86] vs. 0.68 [0.53–0.80] µmol/L, p = 0.0005, n = 12). Liver failure and/or fibrosis correlated with AC in several arterial beds and were associated with low plasma PPi and dysregulation of key proteins involved in PPi homeostasis. Liver transplantation normalized these parameters.

Unconjugated hyperbilirubinemia may exacerbate certain underlying chronic liver diseases.

BACKGROUND: Negative correlations have been described between elevated serum unconjugated bilirubin levels and the prevalence/severity of various chronic inflammatory conditions. Whether a similar association exists for patients with unconjugated hyperbilirubinemia (UCB) and underlying chronic liver diseases (CLD) has yet to be reported. The aim of this study was to document hepatic necro-inflammatory disease activity and fibrosis in CLD patients with and without UCB and otherwise normal liver function tests (albumin and INR). METHODS: Necro-inflammatory disease activity was assessed by serum aminotransferase levels and fibrosis by APRI and FIB-4 calculations. UCB patients were matched 1:2 by age, gender, and underlying CLD to patients with normal bilirubin levels. RESULTS: From a database of 9,745 CLD patients, 208 (2.1%) had UCB and 399 served as matched controls. Overall, UCB patients had significantly higher serum aminotransferase levels, APRI, and FIB-4 scores. The differences were driven by patients with underlying chronic viral or immune mediated liver disorders rather than non-alcoholic fatty liver disease, alcohol-related liver disease, or 'other' CLDs. CONCLUSIONS: These results suggest UCB is associated with increased rather than decreased hepatic necro-inflammatory disease activity and fibrosis in patients with certain CLDs.

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

BackgroundNonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH.MethodsThis is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers.ResultsOf 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75–1); CAP, 0.94 (0.88–1); FLI, 0.81 (0.58–1); HSI, 0.74 (0.62–0.87); and TyG, 0.75 (0.49–1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82–1), 0.96 (0.90–1), 0.97 (0.93–1), and 0.85 (0.68–1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97–1, P < .001) and 0.92 (0.77–1, P < .001).ConclusionsUltrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

Diagnostic Performance of NLR, Type IV Collagen and Fibrosis Score in Chronic Hepatitis B

Hepatitis B Virus (HBV) infection cause damage to the liver parenchym and continuous injury resulting in liver fibrosis. The neutrophil-lymphocyte ratio is a non-invasive marker of inflammation. Type IV collagen is a direct marker of hepatic fibrosis indicating transformation of the extracellular matrix of the liver, and its concentration is proportional to the degree of damaged liver cells and impaired liver function. APRI score and FIB-4 index are non-invasive methods for determining the degree of liver fibrosis. This study aimed to determine the performance of the neutrophil lymphocyte ratio, type IV collagen and fibrosis score on liver fibrosis in chronic hepatitis B. The study design was analytical observational with cross-sectional approach. The subjects included 42 chronic hepatitis B patients who admitted to Internal Medicine Department of Dr. Moewardi Hospital Surakarta from September to November 2020. The subject were grouped into fibrosis 21(50%) and non fibrosis groups 21(50%) based on transient elastography. Neutrophil lymphocyte ratio, type IV collagen and fibrosis score cut off point was determined with receiver operating curve (ROC) and diagnostic test was performed with 2x2 table. The cut-off point of 1.89 from the neutrophil lymphocyte ratio obtained sensitivity 61.9% and specificity of 38.1% with an AUC value of 0.524, while type IV collagen with a cut off point of 18.32 ng/mL obtained sensitivity 80.9% and specificity of 42.6% with an AUC of 0.642, a cut off 0.25 from the APRI score obtained a sensitivity of 81% and specificity of 61.9% with an AUC of 0.857, and cut-off FIB-4 of 0.68 obtained a sensitivity of 85.7% and specificity of 71.4 with AUC of 0.827. Neutrophil lymphocyte ratio with cutoff point of 1.89 has a weak diagnostic value on liver fibrosis in chronic hepatitis B. Further study by comparing or combining with other markers are needed. Type IV collagen with a cut off of 18.32 ng/mL, APRI score with a cut off of 0.25 and a FIB-4 index with a cut off of 0.68 can be used for screening liver fibrosis in chronic hepatitis B patients

C-reactive protein to lymphocyte count ratio is a promising novel marker in hepatitis C infection: the clear hep-c study.

SUMMARYOBJECTIVE:Chronic hepatitis C (CHC) is one of the most important health problems affecting the significant rate of world population and it may lead to cirrhosis and hepatocellular carcinoma. C-reactive protein to lymphocyte count ratio (CLR) is used in estimating inflammatory burden. Therefore, this study aimed to compare CLR values between CHC patients and healthy controls and between CHC patients with and without fibrosis.METHODS:Patients with CHC infection who visited outpatient and inpatient internal medicine clinics of our institution between January 2021 and December 2021 were enrolled to this retrospective study. CLR of the patients with CHC and healthy controls were compared. We further compared CLR of CHC patients with and without fibrosis.RESULTS:Median CLR of CHC and control subjects was 2.61 (5.13%) and 0.31 (0.37%), respectively. CLR of the CHC group was significantly increased compared to the CLR of the controls (p<0.001). There was a significant positive correlation between CLR and APRI score (r=0.15, p=0.04). The sensitivity and specificity of CLR in determining CHC above 0.58% level were 84% and 82%, respectively (AUC: 0.884, p<0.001, 95%CI 0.84–0.93). In subgroup analysis, CLR was 3.97 (6.6%) for CHC patients with fibrosis and 1.7 (4.4%) for CHC subjects without fibrosis (p=0.001). CONCLUSION:Increased CLR in patients with CHC may be an alarming finding of liver fibrosis, as CLR is associated with both CHC and hepatic fibrosis.

NON-INVASIVE BIOCHEMICAL SCORES OF NAFLD AND CAROTID MORPHOFUNCTIONAL ALTERATIONS IN NEVER TREATED ESSENTIAL HYPERTENSIVE PATIENTS

Objective: The non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular events. At the same time a subclinical carotid change is associated with mortality and morbidity in hypertension. However it's unclear if there is a relationship between NAFLD and subclinical carotid damage in essential hypertension (EH). We searched for relationships between biochemical non-invasive NAFLD scores and subclinical carotid damage in a group of naïve EH patients. Design and method: In 299 naïve EH subjects (age 50 ± 13 years, 132 males) we evaluated clinical characteristics, biochemical scores of liver steatosis, as liver Fat Score (LFS), and fibrosis, as NAFLD Fibrosis Score (NFS), APRI, Fibrometer, and FIB-4, presence of echographic steatosis, metabolic syndrome, diabetes, levels of glucose, insulin, HOMA, lipids, glomerular filtration rate (GFR), reactive C protein (RCP), liver tests, platelet count, smoking habit and physical activity. By ultrasound carotid examination we measured the intima-media thickness (IMT), presence of carotid plaques, and in 115 subjects we calculated the carotid stiffness indexes, as the distension coefficient, the beta-stiffness, and the Young elastic module. Results: The IMT significantly increased across quartiles of LFS (P = 0.036), NFS (P = 0.001) and FIB-4 (P = 0.003). IMT was independently associated with FIB-4 (B = 0.380, P = 0.003) and NFS (B = 0.221, P = 0.013) scores. A IMT &gt; 0.9 mm was independently associated with FIB-4 (P = 0.042). Patients with plaques had higher APRI (P = 0.005), Fibrometer (0.023), NFS (P &lt; 0.001) and FIB-4 (P = 0.005) scores, and prevalence of plaques increased progressively across quartiles of LFS (P = 0.046), NFS (P &lt; 0.001) and FIB-4 (P = 0.005). There was an independent association between carotid distension coefficient and Fibrometer (B = -0.360, P = 0.029), and between beta-stiffness and Fibrometer (B = 0.340, P = 0.036). Conclusions: In naïve EH patients the carotid IMT and carotid stiffness are independently associated with non-invasive NAFLD indexes. This association could induce to a more careful evaluation of a non-alcoholic liver damage in EH patients with subclinical carotid alterations. Moreover, studies are needed to clarify if profibrotic mechanisms are the base of both damages.

Non-Invasive Diagnostic Test for Advanced Fibrosis in Adolescents With Non-Alcoholic Fatty Liver Disease.

IntroductionNon-alcoholic fatty liver disease (NAFLD) is a multifaceted disease that includes a wide spectrum of liver damage. The presence and the degree of fibrosis are considered important factors for the prognosis of NAFLD and in predicting the risk of developing cirrhosis. Our aim was to evaluate the usefulness of four fibrosis scores (aspartate aminotransferase/Platelet Index [APRI], FIB-4, NAFLD Fibrosis Score [NFS], and Hepamet) in predicting different degrees of fibrosis among children with biopsy-proven NAFLD.MethodsAbout 286 adolescents [mean age 14.3 years ± 2.5; 154 (53.6%) males], referred between January 2014 and December 2019, with biopsy-proven NAFLD were enrolled.ResultsAbout 173 (60.4%) patients presented fibrosis at histological analysis. In particular: 140 (49.3%) patients had F = 1, 31 (10.8%), had F = 2 and 2 (0.66%) had F = 3. APRI (AUROC 0.619, 95% CI 0.556–0.679) and Hepamet (AUROC 0.778, 95% CI 0.722–0.828) scores had significant (p < 0.001) accuracy to distinguish subjects with fibrosis; while NFS and FIB-4 had not. APRI had a positive predictive value (PPV) of 62.77% (95% CI 57.96–67.35) and an negative predictive value (NPV) of 52.01% (95% CI 46.54–57.43); Hepamet a PPV of 63.24% (95% CI 59.95–66.41) and an NPV of 61.29% (52.9–69.01).ConclusionsOur study showed that Hepamet and APRI perform better than NFS and FIB-4 for identifying fibrosis in patients with NAFLD, but do not have PPVs so high to be considered diagnostic. Therefore, they cannot be employed, in children, for a certain diagnosis of fibrosis or its progression and cannot replace liver biopsy as the gold diagnostic standard. It is, therefore, necessary to continue to research and develop new markers of exclusive fibrosis.

Hepatitis B core-related antigen serum levels are associated with significant liver fibrosis in treatment-naive chronic HBV infection patients.

Several hepatitis B virus (HBV) serum markers have been identified as risk factors for liver fibrosis in patients with chronic HBV infection, and several noninvasive fibrosis tests based on serum indexes are now used to identify the severity of liver fibrosis. We aimed to identify the relationship between hepatitis B core-related antigen (HBcrAg) serum levels and liver fibrosis in treatment-naive chronic HBV infection patients. A total of 246 treatment-naive chronic HBV infection patients were enrolled in this study. All of the patients underwent liver biopsies at baseline. Using the METAVIR fibrosis stages, there were 15, 140, 50, 26 and 15 patients in the F0, F1, F2, F3 and F4stages (METAVIR scoring system), respectively. The biochemical, serological and virological parameters were measured using standard laboratory procedures. The HBcrAg serum levels of the patients were examined via ELISA. HBcrAg serum levels of F2, F3 and F4stage patients were significantly higher than those of nonsignificant liver fibrosis patients (METAVIR F0-F1), but there were no significant differences among F2, F3 and F4stage patients. Serum HBcrAg (OR, 2.18; 95% confidence interval [CI], 1.51-3.16), albumin (ALB) (OR, 0.60; 95% CI, 0.41-0.87), prothrombin activity (PTA) (OR, 0.58; 95% CI, 0.40-0.83) and platelet (PLT) counts (OR, 0.38; 95% CI, 0.25-0.57) were associated with significant liver fibrosis (METAVIR F2-F4). The serum HBcrAg value enabled the correct identification of patients with significant fibrosis, with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.75-0.88). The APRI, FIB-4 index and ALBI score can identify significant liver fibrosis with an area under the ROC curve of 0.74 (95% CI, 0.66-0.81), 0.73 (95% CI, 0.65-0.80) and 0.63 (95% CI, 0.55-0.72), respectively. Compared with these three indexes, the accuracy rate of diagnosis of significant fibrosis based on HBcrAg was higher than that of the FIB-4 index (p=0.0479) and ALBI score (p=0.0030). HBcrAg, ALB, PTA serum levels and PLT counts were associated with significant liver fibrosis in treatment-naive chronic HBV infection patients. HBcrAg serum levels enabled the correct identification of patients with significant fibrosis (METAVIR F2-F4), and HBcrAg was moreeffective than the FIB-4 index and ALBI score.

The Impact of Direct-Acting Antiviral Agents on Cytomegalovirus Reactivation in Chronic Hepatitis C Infection.

Objective:The co-infection of HCV/CMV may accelerate the progression of liver diseases and worsen responsiveness to IFN treatment. The Direct-acting antiviral agents (DAAs), currently approved therapy for HCV, may cause a transient change in immune status, favoring the reactivation of other viruses. The current study aims to evaluate the impact of DAAs treatment on the reactivation of latent CMV in HCV patients. Methods:The serological IgG, IgM Abs against CMV were detected by ELISA on192 HCV patients. The seronegative CMV IgM patients received (sofosbuvir/daclatasvir) regimen, then the CMV reactivation was examined by measuring the CMV IgM by ELISA and CMV DNA by real-time PCR. Results:The serological data revealed that all patients were positive for CMV IgG (100%) while (64%) patients were positive for CMV IgM. The seronegative CMV IgM (36%) received the DAAs protocol. The sustained virological response was monitored by measuring the HCV RNA viremia in the patient sera. The serological data revealed that 28.6% of patients had a reactivation of CMV, while 18.5% of patients had detectable CMV DNA viremia. Moreover, there was a significant improvement in liver function as well as a decrease in FIB-4 and APRI scores at EOT. SVR was reached 97.4% among the total studied patients (N= 192). Conclusion:CMV co-infection has no impact on the response rate to DAAs. However, the CMV reactivation might have occurred after the complete eradication of HCV by DAAs.

431 Galectin-3 as a Biomarker and Potential Therapeutic Target in Biliary Atresia

OBJECTIVES/GOALS: Biliary atresia (BA) is a progressive congenital disease that is characterized by periductular inflammation and fibrosis that leads to bile duct destruction and cholestasis in neonates. Galectin-3 (Gal3) plays a key role in inflammation and fibrosis. The aim of this study was to evaluate plasma Gal3 levels in early and late BA. METHODS/STUDY POPULATION: Samples from our institutional Pediatric Liver Biobank were used for this study. Patients were categorized as early BA (at diagnosis), late BA (at liver transplant), early other cholestatic liver disease (CLD), late other CLD, or controls without cholestasis or structural liver disease. Plasma Gal3 levels were measured by standard ELISA. Inflammatory cytokines were measured in a subset of samples using MSD Proinflammatory Panel 1 multiplex ELISA. Liver fibrosis was categorized as none (Ishak or METAVIR 0), mild (Ishak 1-2 or METAVIR 1), moderate (Ishak 3-4 or METAVIR 2-3), and severe (Ishak 5-6 or METAVIR 4) based on histology. Data are presented as median (IQR) and compared using Kruskal-Wallis test. Spearmans correlation was used to assess the relationship between Gal3 and clinical and inflammatory markers. RESULTS/ANTICIPATED RESULTS: Samples from 10 controls, 26 early BA, 24 late BA, 13 early other CLD, and 8 late other CLD patients were used for this study. Gal3 levels in late BA (20.8 [12.4-30.5] ng/mL) and late other CLD (21.8 [16.9 – 27.2] ng/mL) were significantly higher than in controls (10.2 [7.6 – 14.5] ng/mL, p &lt; 0.02) and early BA (11.3 [8.7 – 16.8] ng/mL, p &lt; 0.01), but not significantly different from early other CLD (15.7 [11.9 – 21.4] ng/mL, p &gt; 0.05). Gal3 positively correlated with fibrosis score (rho 0.3, p = 0.01), total bilirubin (rho 0.3, p = 0.002), ALT (rho 0.3, p = 0.01), AST (rho 0.3, p = 0.005), and APRI score (rho 0.3, p = 0.009), and negatively correlated with albumin (rho -0.3, p = 0.01). Out of the 10 cytokine proinflammatory panel, Gal3 was significantly correlated with IL-6 (rho 0.3, p = 0.006). DISCUSSION/SIGNIFICANCE: Gal3 is elevated in late BA and other CLD at time of transplant and correlated with degree of fibrosis, suggesting it may play a role in disease progression to cirrhosis. If targeted in the early disease stage, blocking Gal3 in pediatric cholestatic liver diseases may help delay the progression to cirrhosis and need for transplant.

Non-invasive tests for liver fibrosis assessment in patients with chronic liver diseases: a prospective study

There is an urgent need of non-invasive tests (NITs) for monitoring treatment response and disease progression in chronic liver disease. Liver stiffness (LS) evaluated by transient elastography (TE), shear wave elastography (SWE), and magnetic resonance elastography (MRE) and serum markers e.g. APRI and FIB-4 scores were assessed at baseline and the 1-year follow-up. In all, 89 chronic hepatitis C virus (HCV) patients with sustained virological response and 93 non-alcoholic fatty liver disease (NAFLD) patients were included. There was a significantly strong correlation among imaging techniques. Using MRE as the reference standard, the area under the receiver operating characteristics curves for TE, SWE, APRI, and FIB-4 in detecting stage1–4 fibrosis were 0.88–0.95, 0.87–0.96, 0.83–0.89, and 0.79–0.92, respectively. In chronic HCV patients, the values of TE, SWE, MRE, APRI and FIB-4 significantly decreased from baseline to the 1-year follow-up. Liver steatosis did not significantly change over time. In NAFLD, compared to obese patients, non-obese patients had less LS and steatosis at baseline, and these values did not show significant changes at the 1-year follow-up. Our study suggests that the current NITs have a good correlation and accuracy in monitoring the treatment outcomes in patients with chronic liver diseases.

Endoscopic Ultrasound-Guided Porto-systemic Pressure Gradient Measurement Correlates with Histological Hepatic Fibrosis.

Endoscopic ultrasound is a novel diagnostic approach to chronic liver diseases (CLDs), and EUS-guided porto-systemic pressure gradient measurement (EUS-PPG) is an important expansion with a well-developed technique. However, the clinical value and applicability of EUS-PPG measurement in predicting histologically advanced hepatic fibrosis remain unknown. This was a single-center retrospective study on patients with various CLDs undergoing EUS-PPG and EUS-guided liver biopsy (EUS-bx) to assess if EUS-PPG measurements correlate with histological fibrosis stage and various surrogate markers for severity of CLDs and its safety. Cases with EUS-PPG were identified at the University of California Irvine, a tertiary endoscopy center, between January 2014 and March 2020. In 64 patients, the mean age was 57.5; 40 (62.5%), males; mean Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores, 5.9 and 10.4, respectively. The procedure success rate was 100%. Twenty-nine (45.3%) had EUS-PPG ≥ 5mmHg that was associated with clinical cirrhosis (p < 0.0001), clinical portal hypertension (p = 0.002), hepatic decompensation (p = 0.013), MELD-Na > 10 (p = 0.036), PLTs ≤ 120 × 109/L (p = 0.001), INR ≥ 1.05 (p = 0.007), presence of EV, GV, or PHG (p < 0.0001), biopsy-proven fibrosis stage ≥ 3 (p = 0.002), APRI > 2 (p = 0.001), and FIB-4 > 3.25 (p = 0.001). Multivariable analysis confirmed that EUS-PPG ≥ 5mmHg was significantly associated with liver biopsy-proven fibrosis stage ≥ 3 (LR 27.0, 95% CI = 1.653-360.597, p = 0.004), independent of C-cirrhosis, C-PHTN, thrombocytopenia, splenomegaly, and APRI score > 2, and FIB-4 score > 3.25. There were no serious complications related to EUS-PPG procedures. EUS-PPG measurements provide excellent correlation with histological hepatic fibrosis stage and various clinical, laboratory, endoscopic and imaging variables indicative of advanced liver disease without serious adverse events.

Performance of routine risk scores for predicting cirrhosis-related morbidity in the community

Models predicting an individual's 10-year risk of cirrhosis complications have not been developed for a community setting. Our objectives were to assess the performance of existing risk scores - both with and without genetic data - for predicting cirrhosis complications in the community. We used a 2-stage study design. In stage 1, a systematic review was conducted to identify risk scores derived from routine liver blood tests that have demonstrated prior ability to predict cirrhosis-related complication events. Risk scores identified from stage 1 were tested in a UK Biobank subgroup, comprising participants with a risk factor for chronic liver disease (stage 2). Cirrhosis complications were defined as hospitalisation for liver cirrhosis or presentation with hepatocellular carcinoma. Discrimination of risk scores with and without genetic data was assessed using the Wolbers C-index, Harrell's adequacy index, and cumulative incidence curves. Twenty risk scores were identified from the stage-1 systematic review. For stage-2, 197,509 UK biobank participants were selected. The cumulative incidence of cirrhosis complications at 10 years was 0.58%; 95% CI 0.54-0.61 (1,110 events). The top performing risk scores were aspartate aminotransferase-to-platelet ratio index (APRI: C-index 0.804; 95% CI 0.788-0.820) and fibrosis-4 index (FIB-4: C-index 0.780; 95% CI 0.764-0.795). The 10-year cumulative incidences of cirrhosis complications for participants with an APRI score exceeding the 90th, 95th and 99th percentile were 3.30%, 5.42% and 14.83%, respectively. Inclusion of established genetic risk loci associated with cirrhosis added <5% of new prognostic information to the APRI score and improved the C-index only minimally (i.e. from 0.804 to 0.809). Accessible risk scores derived from routine blood tests (particularly APRI and FIB-4) can be repurposed to estimate 10-year risk of cirrhosis morbidity in the community. Genetic data improves performance only minimally. New approaches are needed in community settings to reduce the late diagnosis of chronic liver disease. Thus, in a community cohort, we assessed the ability of 20 routine risk scores to predict 10-year risk of cirrhosis-related complications. We show that 2 routine risk scores in particular - "APRI" and "FIB-4" - could be repurposed to estimate an individual's 10-year risk of cirrhosis-related morbidity. Adding genetic risk factor information to these scores only modestly improved performance.

Ficolin-2 Plasma Level Assesses Liver Fibrosis in Non-Alcoholic Fatty Liver Disease.

Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2–F3–F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.