Mona A. Amin

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

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.

Serum Levels of Tissue Inhibitors of Metalloproteinase 2 in Patients With Systemic Sclerosis With Duration More Than 2 Years: Correlation With Cardiac and Pulmonary Abnormalities

In this study, we measured the serum concentration of TIMP-2 in patients with systemic sclerosis (SSc) and explored its possible correlation with cardiac and pulmonary lesions. We studied 42 patients with SSc, with duration equal to or more than 2 years. CT chest, ECG, echocardiography, and serum TIMP-2 concentration measurement using ELISA technique were performed in all patients and in 25 normal controls. The mean serum levels of TIMP-2 in patients was higher than in controls (P = .005). The mean CT score of dSSc patients with elevated TIMP-2 levels was significantly higher than dSSc patients with normal levels (P = .013). Four patients out of five with elevated TIMP-2 levels showed diastolic dysfunction (80%), compared to 2 out of 15 lSSc patients with normal levels (13.3%), with P = .014. Our research, though involving a small group of patients, points to the probable role of TIMP-2 in the development of pulmonary lesions in dSSc patients and cardiac lesions in lSSc patients with duration equal to or more than 2 years.

Comparative diagnostic study of biomarkers using FibroMax™ and pathology for prediction of liver steatosis in patients with chronic hepatitis C virus infection: an Egyptian study

Background: Steatosis is common in patients with hepatitis C virus (HCV) infection and may be a major determinant of progression of liver injury. This study evaluated FibroMax™ for noninvasive diagnosis of steatosis in patients with chronic HCV. Methods: This cross-sectional study included 44 patients naïve to treatment who were referred to our hepatology clinic for assessment of fitness for antiviral therapy. Chronic HCV infection was diagnosed by viral markers. Investigations included assessment of abdominal ultrasonography, liver biopsy, calculation of body mass index, and biomarker parameters in serum using FibroMax. Results: Histopathology of liver biopsies showed steatosis in 30 of 44 (68%) patients. FibroMax results were positively correlated with viral load by quantitative polymerase chain reaction and histopathological findings. Body mass index was significantly higher in steatotic patients (P = 0.003) and was significantly associated with the results on FibroMax (P = 0.005). Conclusion: FibroMax was correlated with histopathology and body mass index in patients with HCV. Abdominal ultrasonography could not be used as a single tool to diagnose steatosis with HCV. Steatosis is correlated with viral load, which suggests a direct viral effect. We recommend FibroMax assessment in a larger number of patients to assess its applicability in patients with HCV and steatosis.

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.

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.

Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response

AIM To correlate a genetic polymorphism of the low-density lipoprotein (LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus (HCV) patients. METHODS Our study included 657 HCV-infected patients with genotype 4 who received interferon-based combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index (BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction (PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor (LDLR) genotype study of LDLR exon8c.1171G>A and exon10c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases. RESULTS There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8c.1171G>A genotype between cases (AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls (AA: 3.8%, GA: 53.1% and GG: 43.1%) (P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders (AA: 3.6%, GA: 15.2%, GG: 81.2%) and non-responders (AA: 52.2%, GA: 30.6%, GG: 17.2%) (P < 0.001). The G allele of LDL receptor exon8c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders (P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for non-response. There was a significant association between LDL receptors exon8 c.1171G>A and HAI (P < 0.011). There was a significant association between LDL receptors exon8c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype (28.7 ± 4.7 kg/m(2)) followed by the GA genotype (28.1 ± 4.8 kg/m(2)). The lowest BMI was the GG genotype (26.6 ± 4.3 kg/m(2)) (P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis (P < 0.001). CONCLUSION LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptians infected with chronic HCV.