Clinical Significance of Annexin A4 as a Biomarker in the Early Diagnosis of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent cancer worldwide. Early detection of HCC is crucial to improve prognosis and survival. Nearly 30 % of HCC patients present with normal serum alpha fetoprotein (AFP), which highlights the need for new biomarkers for HCC. Annexin A4 (ANXA4) is one of the annexin family with high expressions found in gastric, liver, lung, colorectal and ovarian cancers. AIM: to evaluate the clinical significance of ANXA4 in the early diagnosis of HCC. METHODS: Thirty patients with hepatitis C virus (HCV) related HCC were enrolled in this study. They were stage A according to Barcelona Clinic Liver Cancer (BCLC) staging and they were grade A or B according to Child Pugh Classification. Twenty patients with HCV-related liver cirrhosis and 20 healthy persons seronegative for both HCV and HBV served as control group. ANXA4 and AFP were measured in serum of all cases. RESULTS: Serum ANXA4 level was significantly higher in HCC patients compared to patients with liver cirrhosis and healthy controls (188, IQR 42-428 and 23, IQR 24-33 and and 21, IQR 22-24 ng Ì· ml, respectively). By using the ROC curve, the area under the curve of ANXA4 was 0.972 and the best cut-off value was115 ng/ml, with sensitivity 95% and specificity 80%. CONCLUSION: The serum level of ANXA4 might be a good biomarker for the early detection of HCC.
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Clinical significances and diagnostic utilities of both miR-215 and squamous cell carcinoma antigen-IgM versus alpha-fetoprotein in Egyptian patients with hepatitis C virus-induced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It has been widely established that the early detection of HCC enables more treatment options with improvements in prognosis and survival. OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of both circulating miR-215 and squamous cell carcinoma antigen-IgM (SCCA-IgM) as serum biomarkers for HCC by examining their diagnostic sensitivity, specificity, accuracy, and predictive values in hepatitis C virus (HCV)-induced HCC patients. SUBJECTS AND METHODS: This study included 60 patients with HCV-related HCC. In addition, 60 patients with HCV-related liver cirrhosis (LC) and 60 apparently healthy subjects were involved, and served as diseased and healthy control groups, respectively. The relative expression levels of miR-215 were detected using quantitative real-time PCR. SCCA-IgM levels in serum were measured by enzyme immunoassay. We used receiver operating characteristic (ROC) curve to calculate the diagnostic accuracy against alpha-fetoprotein (AFP). RESULTS: Relative miR-215 expression levels increased the most in HCC patients compared to that in healthy or diseased controls (P<0.001). Serum concentration of SCCA-IgM was significantly higher in HCC group than that in the two control groups. We performed multivariate analysis using AFP level, focal lesion size, and portal vein thrombosis as independent variables. ROC curves showed that the optimum diagnostic miR-215 cutoff value for identifying HCC patients from cirrhotic ones was 417 (sensitivity, 97%; specificity, 91%) and for SCCA-IgM was 95 AU/mL (sensitivity, 92%; specificity, 98%). Moreover, the superiority of both miR-215 and SCCA-IgM to AFP is obvious in our study and this superiority is more evident in distinguishing HCC with AFP levels <200 ng/mL and HCC patients with small-sized focal lesions from cirrhotic patients. CONCLUSION: Cell-free miR-215 and serum SCCA-IgM could be used for early diagnosis of HCC either each one as a single marker or with AFP complement measurement.

A study of the circulating fibroblast growth factor 21 as a novel noninvasive biomarker of hepatic injury in genotype-4 chronic hepatitis C: Egyptian patients and their response to direct-acting antiviral agents.

BACKGROUND: Fibroblast growth factor (FGF) 21 was reported to be induced by different injurious agents, including chronic hepatitis C (CHC) virus, affecting the liver. The aims of this study were to evaluate the FGF21 levels in CHC patients before and after the treatment with direct-acting antiviral agents (DAAs) in comparison to that in control subjects and to correlate these levels with insulin resistance (IR), lipid profile, and fibrosis stages. PATIENTS AND METHODS: We studied 75 naive CHC patients and 40 age- and gender-matched healthy control subjects. Patients were divided into five groups based on the severity of fibrosis as detected by Fibroscan as follows: F0, n=2; F1, n=13; F2, n=23; F3, n=16; F4, n=21. We estimated the FGF21 levels at the start of the study for all the participants and for the patients only at the end of treatment with simisipivir (SIM) and sofosbuvir (SOF). These levels were compared between the patients and the control subjects and also for the patients before and after the treatment with DAAs. The FGF21 levels were correlated to IR, lipid profile, and stages of liver fibrosis. RESULTS: The FGF21, fasting blood sugar (FBS), fasting insulin, and homeostasis model of IR (HOMA-IR) were significantly higher in CHC patients compared to control (5.04±0.75 vs 4.7±0.52, 20.15±5.13 vs 13.15±4.2, 4.49±1.28 vs 2.72±0.87, and 123.7±52.6 vs 21.8±8.8; P≤0.01, P≤0.001, P≤0.001, and P≤0.001, respectively). The posttreatment FGF21 levels were significantly reduced when compared to the pretreatment levels (123.7±52.5 vs 60.5±32.7, P≤0.001). FGF21 levels showed significant negative correlation with FBS and positive correlation with serum albumin (P≤0.05 and P≤0.003, respectively). The multiple linear regression analysis revealed that serum albumin, high-density lipoprotein cholesterol (HDL-c), and the stage of liver fibrosis were independent risk factors for FGF21. CONCLUSION: Besides its metabolic modulator role, FGF21 strongly introduced itself as a novel biomarker of hepatic injury in Egyptian, genotype-4, CHC patients.

The prevalence of functional dyspepsia using Rome III questionnaire among chronic hepatitis C patients.

BACKGROUND: Hepatitis C virus (HCV) is a common chronic infection that is widely associated with symptoms of fatigue and abdominal pain. The aim of the present study was to determine the prevalence of functional dyspepsia (FD) among patients with hepatitis C. METHODS: This study included 252 patients with chronic hepatitis C and 150 healthy volunteers. Clinical and laboratory data were recorded for every patient. All patients and controls were administered a questionnaire of FD according to Rome III criteria. RESULTS: The percentage of patients with FD was significantly higher in patients with chronic HCV than normal controls (65.9 % vs 28.7 %, respectively). In chronic HCV patients, post prandial distention syndrome (PDS) subtype was the predominant type (86.1 %). The percentage of patients with a high fibrosis score (F2-3) and raised ALT were significantly higher in patients with FD than in patients without FD (P < 0.001; P < 0.04; respectively). A multivariate regression analysis revealed a significant association between fibrosis score, BMI and FD CONCLUSION: FD is more prevalent in patients with chronic hepatitis C. Obese chronic HCV and those with higher fibrosis scores are more likely to have FD.

Hepatitis C, hepatitis B and HIV infection among Egyptian prisoners: seroprevalence, risk factors and related chronic liver diseases.

BACKGROUND AND AIM: Prisons in Egypt do not currently screen for blood-borne viruses, and there are no statistics concerning the prevalence of hepatitis C virus, hepatitis B virus or human immunodeficiency virus among prisoners. This study was performed to detect the prevalence of antibodies against hepatitis C, hepatitis B core and human immunodeficiency virus among Egyptian prisoners. METHODS: The study was conducted in an Egyptian prison. The prisoners voluntarily completed a risk factor questionnaire and provided blood specimens for testing for antibodies against hepatitis C virus, hepatitis B virus core antigen and human immunodeficiency virus. Positive results were confirmed by the detecting HCV RNA via polymerase chain reaction. Multivariate regression analysis was performed to determine the factors that were independently associated with positive HCV serology. RESULTS: Five hundred resident prisoners were screened. The prevalence of hepatitis C virus antibodies was 15.8% (79/500), and viremia was confirmed by PCR in 77.2% (61/79) of the antibody-positive prisoners. The prevalence of antibodies to hepatitis B core antigen was 9.8% (49/500), and 1.2% (6/500) of prisoners were dually infected with HBV and HCV. Antibodies to human immunodeficiency virus were not detected in any of the prisoners. The best predictor for hepatitis C and hepatitis B infection was a history of intravenous drug use (P<0.011 for HBV and P<0.001 for HCV), a period of >10 years spent in prison (P<0.052 for HBV and P<0.021 for HCV) and shared toiletries (P<0.059 for HBV and P<0.002 for HCV). CONCLUSION: Hepatitis C and hepatitis B virus infections constitute an important public health problem in prisons. Public health strategies to prevent morbidity and mortality from these infections should include hepatitis B vaccination, HCV testing, counseling and medical management of infected prisoners.