The Effects of Human Reoviruses on Cancer Cells Derived from Hepatocellular Carcinoma Biopsies.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer around the world. Since this cancer is highly resistant to the existing treatments, we used a novel method, which selectively targets HCC cancer cells to improve the treatment process. As normal cells are resistant to reovirus replication, we used oncolytic reoviruses, which can infect, replicate in, and destroy cancer cells. In this study, the effects of oncolytic human reoviruses on cancer cells, derived from HCC biopsies, were investigated. METHODS: First, reoviruses were purified. Then a plaque assay was performed to estimate the number of viruses and determine the multiplicity of infection (MOI). To evaluate the effects of reoviruses on cancer cells derived from HCC biopsies, replication of reovirus RNA, viral protein production, cytopathic effects (CPE), and cancer cell viability were assessed at different intervals post-infection. RESULTS: Replication of reovirus RNA and viral protein production were detected in cancer cells. Also, different levels of viral protein production, CPE, cytotoxicity, and cancer cell viability were observed at different intervals post-infection with human reoviruses. In contrast, normal human fibroblasts, which were used as negative control, remained unchanged. CONCLUSIONS: For the first time, the effects of human reoviruses on HCC biopsies were investigated. The results showed that human reoviruses could replicate in and destroy cancer cells derived from HCC biopsies. Overall, human reoviruses can be potentially used for the treatment of HCC.

A Systematic Review and Meta-analysis on the Prevalence of HBsAg in Health Care Workers from Eastern Mediterranean and Middle Eastern Countries.

BACKGROUND: The present study aimed to determine the prevalence of HBsAg in Health Care Workers (HCWs) in Eastern Mediterranean Region Office (EMRO) and Middle Eastern countries from 2000 to 2016. METHODS: In a meta-analysis study, the databases of PubMed, ISI, Ovid, Scopus, Google Scholar, and Persian databases were searched for relevant articles on the prevalence of HBsAg in HCWs in EMRO and Middle Eastern countries. Homogeneity was assessed based on Cochran's Q-test results. RESULTS: A total of 43 articles (110,179 people) were included. The pooled prevalence of HBsAg in HCWs of EMRO and Middle East countries was found 2.77% (95%CI: 2.64-2.83). The specific prevalence of HBsAg was 2.84% (95% CI: 2.6-3.11) in EMRO and 2.22% (95%CI: 2.13-2.31) in Middle Eastern countries. The highest and lowest prevalence rates of HBsAg among HCWs for countries with more than one study were 6.85% (95% CI: 5.74%-8.16%) in Sudan and 1.00% (95% CI: 0.94%-1.07%) in Turkey, respectively. The trends of HBsAg prevalence among HCWs decreased from 2000 to 2016. CONCLUSIONS: Based on the World Health Organization classification of HBV prevalence, intermediate HBsAg prevalence rates were detected in HCWs of EMRO and Middle East countries during 2000-2016.

Gender bias in Iranian living kidney transplantation program: a national report.

INTRODUCTION: Strong challenges exist about living kidney transplantation practices worldwide. One of these concerns is based on the observation that in many places women constitute the majority of living kidney donors but the minority of recipients. We studied this issue in Iran by using national data for kidney transplantation. METHODS: Data of the Iranian national registry for kidney transplantation which comprises data of all renal transplantations performed in the country during a 22 yr period were included in the study. Data of 16,672 living donors (living related [LR]=16%, living unrelated [LUR]=86%) were analyzed. RESULTS: Males received 62.2% of all kidney transplants. From 16,672 living donors, 20% and 80% were women and men, respectively. Recipients were more likely to receive kidney allograft from their own gender groups (p<0.05). In living related donations, mothers, brothers and sons were significantly more often donors than their counterparts of opposite gender. CONCLUSION: In contrast with previous reports from other countries, this study of Iranian national data revealed that in Iran, most related and unrelated living kidney donors are male and the percentage of recipients who are female exceeds the percentage of donors who are female. Considering previous reports from other countries, our findings suggest that Iran is the only country in which females are more likely to be recipients of a kidney allograft than donors. The reason for the predominance of male kidney donors in Iran is probably multifactorial and associated with economical, social and cultural issues. The financial incentives paid to living unrelated donors may be an attraction for males to donate a kidney although, even in living related donations, males constitute the majority of donors.

Occult hepatitis B infection and its possible impact on chronic hepatitis C virus infection.

As a well-recognized clinical phenomenon, persistent detectable viral genome in liver or sera in the absence of other serological markers for active hepatitis B virus (HBV) replication is called occult HBV infection. The main mechanism through which occult infection occurs is not completely understood and several possible explanations, such as integration into human genome and maintenance in peripheral mononuclear cells, exist. Occult HBV infection has been reported in different populations, especially among patients with Hepatitis C (HCV) related liver disease. The probable impact of occult HBV in patients with chronic HCV infection has been previously investigated and the evidence suggests a possible correlation with lower response to anti-viral treatment, higher grades of liver histological changes, and also developing hepatocellular carcinoma. However, in the absence of conclusive results, further studies should be conducted to absolutely assess the impact of occult HBV contamination on the HCV related liver disease.

Effect of levamisole supplementation on hepatitis B virus vaccination response in hemodialysis patients.

AIM: As an immune-modulating agent, levamisole has been reported to stimulate depressed T-cell activity, enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. There are a number of recent studies claiming that levamisole can improve response rate to hepatitis B virus (HBV) vaccination in haemodialysis patients. The present study has examined this hypothesis amongst some Iranian patients, using double-blind randomized clinical trial. METHODS: During a 12 month period, 70 patients on maintenance haemodialysis with negative anti-hepatitis B surface antibody (HBsAb) and HBV core antibody (HBcAb), from four different dialysis centres were enrolled into the study. The patients were randomized to two groups. The first group (levamisole group) received 40 microg doses of recombinant HBV vaccine i.m. at 0, 1 and 6 months, plus 100 mg levamisole p.o., after each haemodialysis session. The second group (placebo group) received the same vaccination protocol, except for the placebo instead of levamisole. The patients were followed on serum HBsAb level. Those with an HBsAb level of above 10 mIU/mL, 1 month after the third dose of vaccination, were considered as responders. RESULTS: The levamisole group was comprised of 38 patients and the placebo group of 32 patients. Thirty-one patients (81.6%) of levamisole group and 26 patients (81.3%) of placebo group responded to vaccination. The difference between two groups was not significant. CONCLUSION: This study indicated that in a haemodialysis population with high response to HBV vaccination, levamisole might have no significant effect in enhancing the response. Further studies with higher power can give more accurate results.

Distribution frequency of hepatitis C virus genotypes in 2231 patients in Iran.

AIM: Given the importance of frequency distribution of HCV genotypes, we studied genotypic distribution of HCV in Iran. In this cross-sectional study, 2231 patients with hepatitis C who presented in hepatitis clinics in Tehran were investigated for HCV genotypes. METHODS: Genotyping was performed by genotype specific primers. RESULTS: The highest frequency was for genotype 1a, with 886 (39.7%) of subjects. Genotype 3a and 1b were the other frequent genotypes, with 613 (27.5%) and 271 (12.1%) subjects, respectively. Of the samples, 401 (18%) had an undetermined genotype. Mixed genotypes were also found in 33 samples (1.6%). Genotype 1b frequency in patients under 20 years old was 10.2%, while its frequency in patients over 60 years old was 18.5%. Genotype 1b frequency significantly increased by age (P = 0.02). CONCLUSION: This study indicates that the dominant HCV genotype among patients living in Tehran was 1a.

Occult hepatitis B among chronic liver disease patients.

OBJECTIVE: Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Diagnosis of occult HBV infection requires sensitive HBV-DNA polymerase chain reaction (PCR) assay. Occult hepatitis B is a new entity and the prevalence of it and its clinical importance has not been investigated yet in Iran. The aim of this study is to investigate the prevalence and clinical importance of occult hepatitis B among chronic liver disease patients in Iran. METHODS: We studied 35 consecutive paraffin-embedded liver tissues cases referred to Research Center for Gastroenterology and Liver Diseases, Tehran, Iran during the year 2001 to 2002 for liver biopsy due to its elevation of alanine aminotransferase (ALT) levels for more than 6 months. Liver biopsies were reviewed and HBV-DNA and HBsAg and Hepatitis B core antigen were assayed in liver tissue by PCR and immunohistochemistry (IHC). RESULTS: Our patients with chronic liver disease (CLD) included hepatitis C (77.1%), cryptogenic liver disease (20%), and autoimmune hepatitis (2.9%). Histologically, chronic hepatitis, cirrhosis and non-specific changes were reported. Hepatitis B virus-DNA was detectable in 8 (22%) patients; however, IHC was negative in all. CONCLUSION: Occult hepatitis B is relatively frequent among patients with CLD in Iran. It maybe associated with more advanced liver pathology (cirrhosis) and more aggressive clinical course (decompensated cirrhosis). Occult HBV infection causes strong suppression of viral gene expression.

Prevalence and determinants of diabetes mellitus among Iranian patients with chronic liver disease.

BACKGROUND: Alterations in carbohydrate metabolism are frequently observed in cirrhosis. We conducted this study to define the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in Iranian patients with chronic liver disease (CLD), and explore the factors associated with DM in these patients. METHODS: One hundred and eighty-five patients with CLD were enrolled into the study. Fasting plasma glucose and two-hour plasma glucose were measured in patients' sera. DM and IGT were diagnosed according to the latest American Diabetes Association criteria. RESULTS: The subjects included 42 inactive HBV carriers with a mean age of 42.2 +/- 12.0 years, 102 patients with HBV or HCV chronic hepatitis with a mean age of 41.2 +/- 10.9 years, and 41 cirrhotic patients with a mean age of 52.1 +/- 11.4 years. DM and IGT were diagnosed in 40 (21.6%) and 21 (11.4%) patients, respectively. Univariate analysis showed that age (P = 0.000), CLD status (P = 0.000), history of hypertension (P = 0.007), family history of DM (P = 0.000), and body mass index (BMI) (P = 0.009) were associated with DM. Using Multivariate analysis, age (OR = 4.7, 95%CI: 1.8-12.2), family history of DM (OR = 6.6, 95%CI: 2.6-17.6), chronic hepatitis (OR = 11.6, 95%CI: 2.9-45.4), and cirrhosis (OR = 6.5, 95%CI: 2.4-17.4) remained as the factors independently associated with DM. When patients with cirrhosis and chronic hepatitis were analyzed separately, higher Child-Pugh's score in cirrhotic patients (OR = 9.6, 95%CI: 1.0-88.4) and older age (OR = 7.2, 95%CI: 1.0-49.1), higher fibrosis score (OR = 59.5, 95%CI: 2.9-1211.3/ OR = 11.9, 95%CI: 1.0-132.2), and higher BMI (OR = 30.3, 95%CI: 3.0-306.7) in patients with chronic hepatitis were found to be associated with higher prevalence of DM. CONCLUSIONS: Our findings indicate that patients with cirrhosis and chronic hepatitis are at the increased risk of DM occurrence. Older age, severe liver disease, and obesity were associated with DM in these patients.