CD24 Gene Expression as a Risk Factor for Non-Alcoholic Fatty Liver Disease.

In light of increasing NAFLD prevalence, early detection and diagnosis are needed for decision-making in clinical practice and could be helpful in the management of patients with NAFLD. The goal of this study was to evaluate the diagnostic accuracy of CD24 gene expression as a non-invasive tool to detect hepatic steatosis for diagnosis of NAFLD at early stage. These findings will aid in the creation of a viable diagnostic approach. METHODS: This study enrolled eighty individuals divided into two groups; a study group included forty cases with bright liver and a group of healthy subjects with normal liver. Steatosis was quantified by CAP. Fibrosis assessment was performed by FIB-4, NFS, Fast-score, and Fibroscan. Liver enzymes, lipid profile, and CBC were evaluated. Utilizing RNA extracted from whole blood, the CD24 gene expression was detected using real-time PCR technique. RESULTS: It was detected that expression of CD24 was significantly higher in patients with NAFLD than healthy controls. The median fold change was 6.56 higher in NAFLD cases compared to control subjects. Additionally, CD24 expression was higher in cases with fibrosis stage F1 compared to those with fibrosis stage F0, as the mean expression level of CD24 was 7.19 in F0 cases as compared to 8.65 in F1 patients but without significant difference (p = 0.588). ROC curve analysis showed that CD24 ∆CT had significant diagnostic accuracy in the diagnosis of NAFLD (p = 0.034). The optimum cutoff for CD24 was 1.83 for distinguishing patients with NAFLD from healthy control with sensitivity 55% and specificity 74.4%; and an area under the ROC curve (AUROC) of 0.638 (95% CI: 0.514-0.763) was determined. CONCLUSION: In the present study, CD24 gene expression was up-regulated in fatty liver. Further studies are required to confer its diagnostic and prognostic value in the detection of NAFLD, clarify its role in the progression of hepatocyte steatosis, and to elucidate the mechanism of this biomarker in the progression of disease.

Performance of serum CD163 as a marker of fibrosis in patients with NAFLD.

BACKGROUND AND AIMS: CD163, a surface hemoglobin-haptoglobin scavenger receptor, is expressed on macrophages and monocytes and up-regulated during macrophage activation. This study aimed to evaluate CD163 in nonalcoholic steatohepatitis patients as a diagnostic and prognostic marker in such patients. METHODS: Serum samples were collected from 41 NAFLD patients and 14 healthy controls. All cases were subjected to clinical assessment, abdominal ultrasound examination, laboratory assessment including liver function and enzymes, kidney function, and lipid profile. Fib-4 and NAFLD fibrosis score were calculated for all patients. Also, serum levels of CD163 were detected by ELISA technique. RESULTS: The present study showed that BMI, NAFLD fibrosis score (NFS), uric acid, cholesterol, and triglyceride levels were significantly elevated in the NAFLD cases compared with healthy controls (P < 0.05). The serum level of sCD163 was considerably higher in NAFLD cases (9.97 ± 9.97 ng/ml) vs. healthy controls (1.87 ± 0.83 ng/ml) (p < 0.001). Circulating level of sCD163 was significantly higher in the obese-diabetic subjects and diabetic non-obese patients as compared with the lean healthy subjects (11.15 ± 7.69 ng/ml) and 11.46 ± 13.83 ng/ml vs. 1.87 ± 0.83 ng/ml, P < 0.05; respectively. The sensitivity and specificity of this marker was 85.4%, and 92.9 for distinguishing patients with NAFLD in obese and/or diabetic subjects from healthy controls. CONCLUSION: serum level of CD163 can be used as a diagnostic marker for individuals with NAFLD. However, it didn't correlate with NAFLD fibrosis score of those patients and thus couldn't predict the severity of disease.

IL-21 as a Predictor of Sustained Virologic Response in Patients with Chronic Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection is a significant public health problem. The crucial role of interleukin (IL)-21 in HCV has been established. Thus, we aimed to investigate the association of serum IL-21 levels with the virological response to interferon (IFN)-based therapy in a group of Egyptian patients with chronic hepatitis C (CHC). Clinical data were collected from 58 HCV-positive Egyptian patients treated with IFN/ribavirin therapy and 10 non-HCV-infected healthy subjects. Liver and renal function tests, complete blood count, viral markers, and pretreatment IL-21 levels were determined in all patients and healthy controls. Patients who achieved sustained virologic response (SVR) had higher pretreatment median serum IL-21 levels than those who did not. Thus, this study concluded that higher pretreatment serum IL-21 may be useful in predicting SVR in CHC patients.

Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study.

BACKGROUND: Stem cell-based therapy has received attention as a possible alternative to organ transplantation. The aim of this study was to assess the safety and efficacy of autologous transplantation of bone marrow (BM)-derived stromal cells in post-HCV liver cirrhosis patients. METHODOLOGY: 10 × 10(6) of isolated human bone marrow (HBM)-stromal cells in 10 mL normal saline were injected in the spleen of 20 patients with end-stage liver cirrhosis guided by the ultrasonography, and then patients were followed up on monthly basis for six months. RESULTS: A statistically significant decrease was detected in the total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) (p-value<0.01), prothrombin time (PT), and international normalized ratio (INR) levels (p-value<0.05), while a statistically significant increase in the albumin and PC (p-value<0.05) after follow-up. CONCLUSION: This study suggested the safety, feasibility, and efficacy of the intrasplenic injection of autologous BM stromal cells in improving liver function in Egyptian patients with cirrhosis.

Molecular evaluation of apoptotic versus antiapoptotic angiogenic markers in hepatocellular carcinoma.

OBJECTIVE: To assess the role of HO-1 in HCC progression and to study the expression of apoptotic factors represented by TNF-alpha, and Fas-L versus antiapoptotic and angiogenic factors represented by HO-1, TGF-beta, HGF, and VEGF in HCC compared to non cancerous cirrhotic liver. DESIGN AND METHODS: Liver biopsies were taken from twelve patients with grade II HCC confined to the liver and twelve patients with non cancerous liver cirrhosis (served as control). RT-PCR of previous genes was evaluated. RESULTS: HO-1, VEGF, HGF, and TNF-alpha genes were significantly increased (P<0.05) in HCC compared to control. Fas-L showed a significant decrease (P<0.05) in HCC compared to control. TGF-beta was higher in HCC than control but the difference was not statistically significant (P>0.05). HGF showed significant positive correlation with HO-1 (r=0.8217, P=0.001). CONCLUSION: HCC is associated with increased expression of VEGF, HGF, and TGF-beta, and with suppression of Fas-L. In addition, HO-1 is highly significantly expressed in HCC. The significant positive correlation between HO-1 and HGF was first reported in Egyptian human liver biopsies, and this suggests that it may play a role in the progression of hepatocellular carcinoma.

Evaluation of the inhibitory effect of antisense oligodeoxynucleotides on the growth of hepatitis C-associated hepatocellular carcinoma cells in vitro.

OBJECTIVE: Hepatitis C virus (HCV) RNA is invariably detected in the serum and tumor tissue of anti-HCV-positive patients with hepatocellular carcinoma (HCC). The inflammation and cirrhosis caused by HCV could be the promoter for development of HCC or HCC could be the consequence of HCV infection independent of the effect of cirrhosis. The ability of the core protein of HCV to modulate gene transcription, cell proliferation and cell death by interacting with cellular genes that regulate cell growth and differentiation is involved in the pathogenesis of HCC. HCV NS3 protease is an attractive target for antiviral agent development because it is required for viral replication. Recent studies that constructed an in vitro model of HCC demonstrated that antisense oligodeoxynucleotides (AS-ODN) interfered with NS3 translation in a dose-dependent fashion and significantly inhibited protease activity. We studied the in vitro effect of AS-ODN on the rate of growth of the HCC cells grown in culture associated with HCV. METHODS: Core biopsy was taken from 20 patients with HCC associated with HCV and each one was divided into two parts: group I to which antisense was added and group II which served as a control group. Comparison of cell viability between tubes with and without AS-ODN was done using MTT assay, LDH assay, cell cycle analysis, trypan blue exclusion test and colony formation in soft agar. RESULTS: Colony formation in soft agar was inhibited in group I compared with the control group and the inhibition was highly significant (P < 0.01). The LDH concentration in culture supernatant and the trypan blue exclusion test, both reflecting cellular death, was higher in group I than group II and the difference was highly significant (P < 0.01). MTT assay showed a highly significant decrease in cell activation in group I than in group II (P < 0.01). The percentage of cells in the G(0)/G(1) phase was higher in group I than in group II and the difference was significant (P = 0.04). There was an insignificant difference between both groups in the percentage of cells in S phase (P = 0.378). The inhibitory effect of AS-ODNs on tumor cells in G(2)/M phase was highly significant compared with the control group (P < 0.01). CONCLUSIONS: AS-ODN has a significant inhibitory effect on the growth of HCV-associated HCC cells grown in fluid culture, and there is potential for the use of AS-ODN as oncotherapy.

Cardiac involvement in patients with systemic lupus erythematosus and correlation of valvular lesions with anti-Ro/SS-A and anti-La/SS-B antibody levels.

The aim of this study was to evaluate the incidence of morphologic and functional cardiac abnormalities in patients with systemic lupus erythematosus (SLE) and to correlate the findings with levels of anti-Ro/SS-A, anti-La/SS-B, and anti-cardiolipin antibody (aCL). Sixty-two patients with SLE were enrolled in this study. All patients underwent complete history taking, clinical assessment, and standard two-dimensional and Doppler echocardiography. Anti-Ro/SS-A, anti-La/SS-B, and aCL levels were measured using a standardized ELISA test. The patients were subdivided into two subgroups based on the presence or absence of valvular involvement. The two subgroups were then compared. Valvular involvement was present in 19 patients (30.6%), pericardial effusion in 12 patients (19.4%), impaired left ventricular relaxation abnormalities in 2 patients (3.2%), and pulmonary hypertension in 3 patients (4.8%). More patients in the valvular involvement group had positive anti-Ro/SS-A antibodies than in the valvular noninvolvement group (7/19 vs. 4/43). The difference was significant, with P < 0.01. Serum levels of anti-Ro/SS-A levels were significantly higher in the valvular involvement group (33.7 +/- 36.0 vs. 13.7 +/- 25.1; P < 0.01), as were the serum anti-La/SS-B levels (21.9 +/- 23.5 vs. 10.7 +/- 17.8; P < 0.05). The results suggest a causative correlation between anti-Ro/SS-A and anti-La/SS-B antibodies and the pathogenesis of the valvular lesions in SLE patients.