Prognostic Value of Serum Retinoic Acid Receptor Responder Protein 2 (RARRES2) on Chronic Hepatitis C Patients

INTRODUCTION

A major worldwide health issue impacting 1% of the global population is infection with chronic hepatitis C virus (HCV).²

Egypt has the greatest prevalence of HCV worldwide, representing 14.7% of the population, yet deaths from hepatocellular carcinoma (HCC) and cirrhosis remain a major problem in Egypt. HCV infection causes chronic hepatitis in around 60–80% of cases, and cirrhosis develops in 10–20% of those cases in 20–30 years. Patients with cirrhotic livers can develop HCC in 1% to 5% of cases.⁴ HCV infection increases pro-inflammatory cytokine secretion, oxidative stress and tissue damage, all of which lead to progressive fibrosis, cirrhosis, liver failure and cancer.⁹ CHC includes a variety of characteristics that distinguish it not just as a viral illness but also as a metabolic liver illness that includes liver steatosis, insulin resistance (IR), lipid metabolism disturbances, and T2DM or glucose intolerance.⁶Further research revealed chemerin to be a retinoid-responsive gene, leading to its designation as RARRES2. Chemerin's retinoic acid responsiveness has been subsequently validated in many cells and tissues.⁵

Inflammatory chemokine chemerin has initially been identified as a new retinoic acid-responsive gene in psoriasis cutaneous lesions, suggesting a role of immunomodulation.¹¹

It was discovered that it was expressed in a range of tissues, including the pancreas, liver, and lungs, and also in adipose tissue. One of the primary organs that secretes chemerin is the liver.⁷

It was demonstrated to be connected to insulin resistance, blood pressure, plasma triglycerides (TG), and body mass index (BMI).

It is a chemoattractant protein that is involved in glucose homeostasis, adipogenesis, and angiogenesis. Chemerin could be involved in liver physiology and pathology because of the expression of its receptors in the liver.¹

Because it is both pro-and anti-inflammatory, it has a chimeric nature.The activation and recruitment of macrophages and natural killer (NK) cells into the inflamed tissue produces the pro-inflammatory effect.¹⁰Nevertheless, the anti-inflammatory activity happens via inhibition of pro-inflammatory mediators' production and promoting the expression of adiponectin.¹³

Chemerin expression has been verified in the livers of CHC patients

PATIENTS AND METHODS

Type of study: A case control study.

Patients: This study was carried out on conducted on (40) subjects. The included subjects will be classified into 2 groups Group I: included (25) subjects with normal- weight chronic hepatitis C virus disease Group II: included (15) healthy normal weight subjects as a control group.

The selection of participants in this research has been based on the following: Inclusion criteria: Female aged middle age 25 -45 years old, Positive anti-HCV antibody test and HCV RNA, Normal body weigh 18.5-24.9. Patients with the following criteria were excluded from the study: Obesity, Diabetes mellitus, Coinfection with HBV, HIV, Hepatocellular carcinoma, Heart or renal failure, Pregnancy or lactation.

Methods: All enrolled people will be exposed to the following: Full medical history, paying particular attention to the duration of hepatitis C infection, manifestation of liver cell failure (jaundice, ascites, hematemesis melena, hepatic comma), Clinical examination for each studied patients including measurement of body mass index and general and abdominal examination, Laboratory investigations will include the following:-  Complete blood picture to assess: ● RBCs, HB%, platelets counts ● Differential of WBCS (neutrophil, lymphocyte) ● Neutrophil to lymphocyte ratio (NLR) b) Kidney function tests (serum creatinine and blood urea, eGFR), Liver function tests (serum albumin, total &direct bilirubin, SGOT, SGPT), Coagulation profiles (PT, PC, INR), lipid profiles, which include cholesterol and triglyceride, LDL, HDL, and hepatitis markers, are used to rule out co-infection with other viruses in the patients' group and to confirm that the controls are HBV and HCV seronegative. The diagnosis of CHC has been validated by using RT-PCR to detect serum HCV-RNA, serum alpha-fetoprotein to rule out hepatocellular carcinoma, fasting insulin and ELISA (enzyme-linked immunosorbent assay) kits to measure RARRES2, and abdominal ultrasonography to document the presence of cirrhosis and rule out co-existing hepatic focal lesion.

Samples collection & Preparation: The first sample, 8 ml of peripheral venous blood, was collected under complete aseptic conditions using a plastic disposable syringe from all subjects after fasting for 9 hours.

Statistical analysis: Microsoft Excel 2016 and the SPSS software (Statistical Package for Social Sciences) version 26.0 will be used to tabulate and statistically analyze the obtained data. Descriptive statistics have been computed for numerical parametric data using the mean±SD (standard deviation), minimum, and maximum of the range; for numerical non-parametric data using the median and first and third interquartile ranges; and for categorical data using percentage and number. When two independent patients had parametric data, independent t-tests were used for inferential analyses; when two independent patients had non-parametric data, Mann-Whitney U tests have been used. Inferential analysis of qualitative data has been conducted utilizing the Chi-square test for independent patients. The linear correlation coefficient [r] was used to detect any connection between two quantitative variables in a single group. The ROC curve is a valuable tool for assessing the specificity and sensitivity of quantitative diagnostic tests that classify patients into one of two groups. The significance level has been set at a P value of less than 0.05, which indicates that the data is significant; otherwise, it is not.  

RESULTS

Table 1:Comparison between the study groups as per AFP.

Table 2: Comparison between the study groups as per glucose and fasting insulin.

Table 3: US findings among the studied groups.

Table 4: Comparison between the study groups regarding RARRES2.

Table 5: Correlation between RARRES2 and other parameters among the study groups.

Table 6: Validity of RARRES2 in prediction of HCV patients