Mohamed I. Radwan

Cytokines genes polymorphisms in chronic hepatitis C: impact on susceptibility to infection and response to therapy.

BACKGROUND Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection, the production of abnormal cytokine levels appears to contribute in the progression of the disease, viral persistence, and affects response to therapy. Cytokine genes polymorphisms located within the coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of the study was to evaluate the association of of IL28B rs12979860, TGF-β1-509, TNF-α 308, and IL-10-1082 polymorphisms with the susceptibility to hepatitis C virus genotype 4 infection and response to pegylated interferon-α and ribavirin therapy. METHODS IL28B, TGF-β1 and TNF-α genes polymorphisms were genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay while IL-10 gene polymorphism was detected by sequence specific primer-PCR in 220 healthy individuals and 440 hepatitis C infected patients (220 sustained virological response and 220 non-responder to combination therapy). RESULTS IL28 B CT and TT, TGF-β1 CT and TT and TNF-α AG and AA genotypes were significantly associated with susceptibility to hepatitis C infection and response to therapy. While no association was found between IL-10 gene polymorphism and susceptibility to HCV infection and response to treatment. CONCLUSIONS These results suggested that inheritance of IL28B CT and TT, TGF-β1 CT and TT and TNF-α AG and AA genotypes which appear to affect the cytokine production may be associated with susceptibility to HCV infection and resistance to combined antiviral therapy.

Influence of transforming growth factor-β1 and tumor necrosis factor-α genes polymorphisms on the development of cirrhosis and hepatocellular carcinoma in chronic hepatitis C patients

BACKGROUND Host genetic factors may affect clinical outcomes of hepatitis C virus (HCV) infection; however, the possible mechanisms remain largely unknown. This study aimed to evaluate transforming growth factor-β1 (TGF-β1)-509 and tumor necrosis factor-α (TNF-α)-308 genes polymorphisms as a risk factors for cirrhosis and hepatocellular carcinoma (HCC) in chronic hepatitis C patients. MATERIALS AND METHODS Two hundred and eighty HCV patients (152 patients with cirrhosis, 128 patients with HCC) and 160 controls were enrolled in the study. Polymorphisms of TGF-β1-509 and TNF-α-308 gene were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum TGF-β1 and TNF-α were determined using ELISA. RESULTS TGF-β1-509 TT, TNF-α-308 AA and GA genotypes frequencies were significantly increased in cirrhotic and HCC groups. Serum TGF-β1 and TNF-α level were significantly increased in TGF-β1-509 TT and TNF-α-308 AA genotypes respectively. CONCLUSION TGF-β1-509 and TNF-α-308 genes polymorphisms are associated with risk of liver cirrhosis and HCC in patients with chronic HCV infection.

Emerging Role of Probiotics in the Management of Helicobacter Pylori Infection: Histopathologic Perspectives

There is growing evidence from preclinical and clinical studies that emphasizes the efficacy of probiotics in the management of Helicobacter (H) pylori infection; it increased the eradication rate, improved patient clinical manifestations and lowered treatment associated side effects.

Polymorphisms of hemochromatosis, and alpha-1 antitrypsin genes in Egyptian HCV patients with and without hepatocellular carcinoma

Hereditary hemochromatosis and alpha-1antitrypsin deficiency are genetic diseases characterized by endoplasmic reticulum (ER) stress with subsequent development of liver disease. Our aim was to estimate the frequency of hemochromatosis gene (HFE) mutant alleles (C282Y and H63D) and alpha-1 antitrypsin S/Z variants among Egyptian HCV cirrhotic patients and in hepatocellular carcinoma patients and to evaluate their effects on disease progression. HFE and alpha-1 antitrypsin polymorphisms were characterized in 200 Egyptian patients with HCV infection (100 patients complicated with cirrhosis, 100 patients with HCC) and 100 healthy subjects who had no history of any malignancy. The frequencies of HD genotype of H63D mutation were significantly increased in HCC patients compared to control group and to cirrhosis group. Also, the frequencies of DD genotype were significantly increased In HCC group compared to control group and to cirrhosis group. Our results suggested that Carriers of the D allele of H63D mutation were significantly more likely to develop HCC.

MAGE-3 and MAGE-4 genes as possible markers for early detection of metastases in hepatitis C virus Egyptian patients complicated by hepatocellular carcinoma

The dissemination of hepatocellular carcinoma (HCC) cells into the circulation plays a critical role in post-operative recurrence and metastasis. Early detection of metastatic tumor cells is critical to identify HCC patients at high risk of relapse. MAGE-3 and -4 genes were evaluated by reverse transcription polymerase chain reaction for the possibility of using them as new markers for early detection of metastases in 160 chronic HCV Egyptian patients, 115 of them were complicated with HCC. The expressions of MAGE-3 and MAGE-4 mRNA in peripheral blood of patients with metastatic HCC were 36 and 52%, respectively. While the expressions of MAGE-3 and MAGE-4 mRNA in peripheral blood of patients with localized HCC were 12.5 and 15%, respectively. Moreover, at least one type of mRNA was found in the peripheral blood of 68% of the metastatic HCC patients and in 20% of the localized HCC patients. While neither the controls nor the cirrhotic patients show expression of MAGE-4 mRNA in their peripheral blood. MAGE-3 and MAGE-4 may be a promising diagnostic tool for monitoring the prognosis of HCC patients and early detection of occult hematogenous metastasis of HCC.

Interleukin-4 polymorphisms and response to combination therapy in Egyptian chronic hepatitis C patients

In hepatitis C infection, the production of inappropriate cytokines levels may contribute to viral persistence and may affect the response to antiviral therapy. We investigate the effect of IL4 C-590T and C-33T polymorphisms on the response to combination therapy with interferon and ribavirin in chronic HCV patients. These single nucleotide polymorphisms were determined by PCR-RFLP in 235 responder and 210 non-responder to combination therapy. The IL4-590 T/T and -33 T/T genotypes were associated with resistance to the therapy (p<0.001, p=0.001 respectively). Haplotypes T(-590) T(-33) and T(-590) C(-33) were associated with a higher risk in non-responder patients than the responders (p<0.001 for each) while frequency of haplotype C(-590) C(-33) (with all wild alleles) was significantly higher in responders as compared to non-responders (p<0.001). These results suggest that inheritance of the IL4 polymorphisms may be associated with resistance to combined antiviral therapy in Egyptian HCV patients.

Successful treatment of activated occult hepatitis B in a non-responder chronic hepatitis C patient

We reported a 23 years old male with chronic hepatitis C virus infection, discontinued from pegylated interferon/ribavirin combination therapy due to a lack of early virological response. He has developed activation of occult hepatitis B virus that was successfully treated by a one year of lamivudine therapy.

Hemobilia and Melena After Liver Biopsy: A Case Report and Review of Literature

Liver biopsy is the gold standard for assessment of hepatic fibrosis although it is associated with many complications. We reported a 28-year-old chronic HCV patient who developed gall bladder hematoma with hemobilia and melena after liver biopsy. The hematoma resolved with conservative management.

Image Case:Extraction of an Impacted Coin in Upper Esophagus in 3 Years Old Female

mobile:002010688872 85 Received :11 / 6 /2012 Accepted after revision: 30 /6 /2012 A 3-year-old female swallowed a large metallic coin (one Egyptian pound; the largest coin in Egypt). Laryngeal examination failed to demonstrate the coin and serial X ray films showed the coin impacted in the upper esophagus. Extraction under general anesthesia was done 5 days after swallowing. Areas of pressure necrosis at the site of impaction, as well as changes in the coin were noticed.