Evaluation of hepatic fibrosis in patients with chronic hepatitis B virus by non-invasive methods: Aspartate-to-platelet ratio index, Fibrosis-4, fibrotest and fibroscan

Background: The process of hepatic fibrosis is common to the various etiologies of chronic liver disease such as viral hepatitis B. Objective: To evaluate hepatic fibrosis by non-invasive markers such as Aspartate-to-Platelet Ratio Index (APRI), fibrosis-4 (FIB-4), fibrotest and fibroscan. Patients and Method: This was a descriptive study during a period of 32 months. Included in our study were the records of outpatients, chronic carriers of hepatitis B virus without viral co-infection C, D or HIV, followed in the Gastroenterology unit of the Campus Teaching Hospital of Lome-Togo. Results: We retained 222 patients. Among the patients, 148 patients (66.67%) were classified in Phase 3 (inactive carrying). Only 10 patients (4.50%) had a APRI score indicating a fibrosis stage ≥ F4 (presence of cirrhosis). A FIB-4 score indicating the presence of cirrhosis was found in 12 patients (5.40%). The most represented stage at fibrotest was the F0 stage (45.45%). Cirrhosis was noted in 6.06% of cases at fibroscan. Patients with APRI score ≤ 2 (96.23%) had a FIB-4 score ≤ 3.25, (p = 0.0088). Conclusion: The evaluation of hepatic fibrosis during chronic hepatopathies is essential for patients care because it influences therapeutic decisions.

231 In-hospital outcomes following an acute coronary syndrome in patients with liver fibrosis: results from the real-world observational registry of acute coronary syndromes (REALE-ACS)

Aims The prognostic role of liver fibrosis (LF) in acute coronary syndrome (ACS) patients is unclear. Biochemical markers and scoring systems, such as the APRI score and the FIB-4 score, have recently been shown to be reliable in predicting LF. We aimed to investigate the relationship between LF and in-hospital outcomes in consecutive ACS patients. Methods and results The REALE-ACS is a real-world monocentric observational study to investigate characteristics, management and outcomes of patients admitted for ACS from January 2016 to January 2020. LF was defined by an APRI score >0.70 and FIB-4 score >3.25. We investigated the association of APRI and FIB-4 with in-hospital adverse events (AEs) defined as cardiogenic shock and death. 469 consecutive ACS patients were included. Mean age was 65.7 ± 13.0 years and 108 (23%) were women. Overall, 7.9% of patients had LF. STEMI was more common in LF patients (86.5% vs. 40.8%, P < 0.001). Patients with LF had lower hypertension (64.9% vs. 81.7%, P = 0.015), and higher GRACE score upon admission (155.3 ± 48.4 vs. 131.6 ± 38.9, P = 0.001). Higher serum levels of aspartate aminotransferase [242 (184.5–363) vs. 22 (17–34), P < 0.001], alanine aminotransferase [67 (51.5–115) vs. 20 (15–29), P < 0.001], white blood cells [12 000 (10 145–14 350) vs. 8935 (7262.5–11 267), P < 0.001], percentage of neutrophils (97.3 ± 104.5 vs. 68.5 ± 13.7, P < 0.001), D-dimer [1039 (435.5–2100) vs. 436 (275–894), P < 0.001], and lower percentage of lymphocytes (12.3 ± 6.0 vs. 21.7 ± 11.21, P < 0.001) were reported in LF patients. Globally, 49 AEs were recorded. At stepwise multivariable logistic regression analysis including clinical and biochemical factors, COPD [odds ratio (OR): 2.47, 95% confidence interval (CI): 1.15–5.29, P = 0.020], HS-troponin levels (OR: 2.05, 95% CI: 1.02–4.10, P = 0.043), and APRI > 0.70 (OR: 2.58, 95% CI: 1.07–6.22, P = 0.035) were associated with AEs. Conclusions ACS patients with LF have a high STEMI rate and are at higher risk of worse in-hospital AEs. Our findings suggest that LF may contribute to the identify ACS patients at high-risk for adverse events and mortality.

Predictive value of the aspartate aminotransferase to platelet ratio index and aspartate aminotransferase to alanine aminotransferase ratio in early diagnosis of intrahepatic cholestasis in pregnancy

Objective: We aimed to investigate the predictive value of the first-trimester aspartate aminotransferase/platelet count ratio index (APRI) and aspartate aminotransferase/alanine aminotransferase ratio for intrahepatic cholestasis in pregnancy (ICP). Material and Methods: The clinical data of patients who admitted to the Obstetrics Department of Umraniye Training and Research Hospital, between 2015-2020 were analyzed retrospectively. The study group consisted of 44 patients with ICP and the control group consisted of randomly selected 92 healthy pregnant women. Results: The two groups were similar in terms of age, BMI, first and third-trimester platelet count and third-trimester hemoglobin level. Patients with ICP had a significantly higher first-trimester APRI and a lower first trimester AST/ALT ratio than the healthy controls (p <0.001, p = 0.001, respectively). According to the ROC analysis, the optimal cut-off value of the APRI to predict ICP was 0.191, with the sensitivity of 0.66 and specificity of 0.66 (AUC: 0,727), and the optimal cut-off value for AST/ALT ratio was 1.07, with the sensitivity of 0.64, and specificity of 0.62 (AUC: 0,681). Conclusion: The first-trimester APRI score and AST/ALT ratio is an easy, inexpensive, and non-invasive tool that may be useful in predicting ICP early.

Liver Fibrosis and 8-Year All-Cause Mortality Trajectories in the Aging Cohort of the Salus in Apulia Study

Age is a major contributor to the liver fibrosis rate and its adverse health-related outcomes, including mortality, but older populations are still under-explored. We investigated multimorbidity and inflammatory biomarkers in relation to the increasing liver fibrosis risk to delineate 8-year all-cause mortality trajectories in 1929 older adults from the population-based Salus in Apulia Study. Liver fibrosis risk was assumed using the fibrosis-4 (FIB-4) score, assigned to three liver fibrosis risk groups (low, intermediate, high). In the secondary analyses, the APRI score was also calculated to allow for comparisons. Male subjects (prevalence difference: −13.49, 95% confidence interval (CI): −18.96 to −8.03), a higher multimorbidity burden (effect size, ES: −0.14, 95% CI: −0.26 to −0.02), a higher prevalence of physical frailty (ES: 6.77, 95% CI: 0.07 to 13.47), and a more pronounced inflammatory pattern as indicated by tumor growth factor-α circulating levels (ES: −0.12, 95% CI: −0.23 to −0.01) were significantly more common in the highest-risk FIB-4 score group. Liver function characterized by lipid profile and platelet levels worsened with increasing FIB-4 risk score. The 8-year risk of death was nearly double in subjects in the highest-risk FIB-4 score group, even after controlling for possible confounders. Furthermore, a steeper mortality curve was clearly observed for FIB-4 scores as compared with the APRI scoring system with respect to liver fibrosis risk. In conclusion, using a scoring tool based on simple routine biomarkers to detect liver fibrosis risk may enhance biological knowledge of age-related outcomes of chronic liver disease and be helpful in the clinical setting to identify subjects at risk for adverse health-related outcomes, including mortality.

Assessment of liver fibrosis in children with chronic HBV infection by non!invasive methods

Purpose — to assess liver fibrosis in children with chronic HBV infection with nonEinvasive methods: instrumental (shear wave elastography) and serological (APRI score). Materials and methods. 70 children with HCV aged 2–17 years were examined. The stage of liver fibrosis was determined by the APRI index and the method of shear wave elastography. Results. The majority (82.8%; n=58) of children were diagnosed with HBeAgEpositive HBV infection: HBeAg-positive chronic hepatitis occurred in 54.3% (n=38) of children, HBeAg-positive chronic infection in 28.6% (n=20). 15.7% (n=11) of children had HBeAg-negative chronic infection, and only one (1.4%) patient had HBeAg-negative chronic hepatitis. According to the results of shear wave elastography, in 64.3% (n=45) the stage of liver fibrosis F0-1 was diagnosed; in 35.7% (n=25) — stage of fibrosis >F2. According to APRI score, 63.0% (n=44) had liver fibrosis F0-1, and liver fibrosis stage >F2 was diagnosed in 37.2% (n=26). According to liver elastography, 42.0% of patients with HBeAg-positive chronic hepatitis were diagnosed with liver fibrosis stage >F2. According to APRI score, almost 66% (n=46) of children with HBeAg-positive chronic hepatitis had progressive liver fibrosis >F2. According to the correlation analysis results, a direct correlation was found between liver enzymes levels and APRI score — ALT (τ=0.67; p<0.05), AST (τ=0.72; p<0.05) and GGT (τ=0.26; p<0.05). Conclusions. Most children with chronic HBV infection had stage F0-1 liver fibrosis according to both elastography and APRI score (64% and 63%, respectively). Elastography fibrosis stage >F2 was diagnosed in 42% of HBeAg-positive chronic hepatitis, while APRI index fibrosis stage >F2 was diagnosed in 66% of patients with HBeAg-positive chronic hepatitis. Thus, the results of the liver fibrosis evaluation according to the liver elastography and APRI score in children with chronic HBV infection are similar and can be used in clinical practice to select patients who require antiviral therapy. The APRI score depends on the activity of hepatitis and its use in children with HBeAg-positive chronic hepatitis has certain limitations. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, chronic HBV infection, fibrosis, shear wave elastography, APRI.

RELATIONSHIP OF SERUM ADIPONECTIN AND RESISTIN LEVELS WITH THE SEVERITY OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B

Background: Recent research has closely linked adipocytokines to progression of liver inflammation and fibrosis in patients with non-alcoholic liver disease. The aim of this study was to determine the relationship ofserum adiponectin and resistin levels with the severity of liver fibrosis in patients with chronic hepatitis B (CHB), depending on the duration of antiviral therapy. Methods: The cross-sectional studyincluded75 patients with CHB divided into two groups: T1 group(on antiviral therapy for up to 2 years) and T2 group (on antiviral therapy over 2 years). Control group consisted of 40 healthy persons. Serum concentrations of adiponectin and resistin were estimated with ELISA method, while degree of liver fibrosis was determined using FIB-4and APRIscore. Results:The higher values of serum resistin concentration were verified in patients with CHBcompared to healthy controls. The mean level of serum resistin concentration was significantly higher in group of patients with higher FIB-4 score (9.12±3.39 vs. 5.58±3.36 ng/mL, p = 0.001), as well as APRI score (17.45 ± 3.96ng/mL vs.4.82 ± 1.11 ng/mL, p = 0.001). Positive correlation was found between serum resistin levels and degree of liver fibrosis (p < 0.001). There was no significant difference between mean serum adiponectin levels according to the values of FIB-4 and APRI scores. Conclusions:Serum resistin concentration could be a potential noninvasive biomarker of the severity of liver fibrosis in patients with chronic hepatitis B on antiviral therapy.

Assessment of Hepatic Steatosis Before and After Treatment In Egyptian HCV Patients Treated With DAAs Using Non Invasive Parameters

Background Hepatitis C virus (HCV) is a major health problem worldwide. More than one million people die each year from hepatitis C virus (HCV) related diseases. Aim of the Work to evaluate the effect of direct acting antiviral drugs on hepatic steatosis in naïve HCV chronically infected Egyptian patients after reaching SVR12. Patients and Methods study was carried out on 100 treatment naive patients with chronic infection of HCV attending the out-patient clinic. The patients were diagnosed having HCV by detecting HCV antibodies by ELISA & PCR for HCV RNA at The Gastro-enterolgy and Hepatology Department, Ain Shams University and Kobry El Koba Military Hospital between August 2017 till February 2019. Results The mean TG, mean s. cholesterol and APRI Score decreased significantly showing a high statistical significant difference between baseline and SVR12. The mean HDL and LDL significantly increased showing a high statistical significant difference between baseline and SVR12. NAFLD Score increased from baseline to SVR12 showing a statistical significant difference in NAFLD Score between baseline and SVR12. Fibroscan median mean decreased showing a highly statistical difference in Fibroscan Median between baseline and SVR12. Out of 100 patients, cirrhosis regressed to F3 in 33 patients, F2 in 3 patients and didn’t regress to F1 in any patient, while the majority (43 patients) remained as F4 at SVR12. Conclusion APRI Score mean and Fibroscan median mean were significantly decreased, while NAFLD Score was increased among the studied groups from baseline and SVR12.

Plasma levels of sPD-1 and PD-1 genetic variants are associated with hepatitis B infection and related liver disease progression

Background Programmed cell death-1 (PD-1) variants and circulating levels of soluble PD-1 are associated with susceptibility to malignant and infectious disease. This study aimed to examine the association of PD-1.5 and PD-1.9 variants, and plasma sPD-1 levels with HBV infection and disease progression. Methods The study cohort consists of HBV-infected adults (n = 513) stratified by clinical course, including chronic hepatitis B (CHB, n = 173), liver cirrhosis (LC, n = 134), hepatocellular carcinoma (HCC, n = 206), and matched healthy controls (HC, n = 196). The PD-1.5 (rs2227981 C/T) and PD-1.9 (rs2227982 C/T) genetic variants were genotyped by Sanger sequencing, and then sPD-1 levels were quantified by enzyme immunoassay. Results The plasma sPD-1 levels were significantly high among HBV patients. The highest plasma sPD-1 levels were observed in CHB patients, followed by the LC and HCC groups. In addition, the plasma sPD-1 levels correlated positively with liver inflammation (aspartate transaminase, AST: rho = 0.57, P < 0.0001 and alanine aminotransferase, ALT: rho = 0.57, P < 0.0001) and were positively correlated with liver fibrosis (AST to Platelet Ratio Index, APRI score: rho = 0.53, P < 0.0001). The PD-1.9 TT genotype was less frequent in CHB patients compared to LC, HCC and HCC + LC patients in both codominant and recessive models (P < 0.01) and was found to be a risk factor for HCC predisposition [HCC vs. non-HCC: OR = 2.0 (95% CI: 1.13–3.7), Padj=0.017]. The PD-1.5 CT genotype was associated with a reduced risk of acquiring HCC [OR = 0.6 (95%CI: 0.4–0.9), Padj=0.031]. Conclusion Our study concludes that sPD-1 levels are associated with liver inflammation and progression of liver fibrosis and the PD-1.5 and PD-1.9 variants are associated with HBV infection and progression of liver disease.

Role of serum Nogo-B as a biomarker for diagnosis of chronic liver diseases and its severity

Background Nogo-B is one of the members of the reticulon family. Nogo-B influences the proliferation of the hepatic stellate cells inducing liver fibrotic changes. We aimed at measuring the serum levels of Nogo-B in patients with chronic liver disease (CLD) with different etiologies. Ninety subjects were included, 18 of them were normal healthy individuals and 72 had liver disease (fibrosis/cirrhosis) with different etiologies: post-hepatitis C infection, post-hepatitis B infection, NASH, and autoimmune hepatitis. Serum Nogo-B was assessed using ELISA. Patients were subdivided according to the Child-Pugh score into 3 groups: group 1—Child A (24 patients); group 2—Child B (24 patients); and group 3—Child C (24 patients). Results Serum Nogo-B levels were found to be significantly higher in patients (1477.92 ± 1113.50) when compared with healthy control (301.28 ± 180.87) (p < 0.001). There was a statistically significant difference in serum Nogo-B level between the three sub-groups of patients (p < 0.001). A positive correlation was found between serum Nogo-B and MELD score (r = 0.46, p-value < 0.001). However, there was no correlation found between Nogo-B and FIB-4 index or APRI score. There was a significant positive correlation between serum Nogo-B level and coagulation profile and serum bilirubin. An inverse correlation was found between serum Nogo-B with serum albumin. A ROC curve was done to examine the validity of Nogo-B in the diagnosis of liver cirrhosis, and the area under the curve was found to be 0.979, a cutoff value of 600 with a sensitivity of 97.2% and a specificity of 94.4% (p-value < 0.001). Conclusion Nogo-B had a high value in the identification of patients with any severity of CLD. There is a highly significant correlation between Nogo-B and the synthetic function of the liver; it could be used as a measure of hepatic functional reserve.