Effects of Nigella sativa on outcome of hepatitis C in Egypt

AIM: To evaluate the safety, efficacy and tolerability of Nigella sativa (N. sativa ) in patients with hepatitis C not eligible for interferon (IFN)-α. METHODS: Thirty patients with hepatitis C virus (HCV) infection, who were not eligible for IFN/ribavirin therapy, were included in the present study. Inclusion criteria included: patients with HCV with or without cirrhosis, who had a contraindication to IFN-α therapy, or had refused or had a financial constraint to IFN-α therapy. Exclusion criteria included: patients on IFN-α therapy, infection with hepatitis B or hepatitis Ⅰ virus, hepatocellular carcinoma, other malignancies, major severe illness, or treatment non-compliance. Various parameters, including clinical parameters, complete blood count, liver function, renal function, plasma glucose, total antioxidant capacity (TAC), and polymerase chain reaction, were all assessed at baseline and at the end of the study. Clinical assessment included: hepato and/ or splenomegaly, jaundice, palmar erythema, flapping tremors, spider naevi, lower-limb edema, and ascites. N. sativa was administered for three successive months at a dose of (450 mg three times daily). Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. RESULTS: N. sativa administration significantly improved HCV viral load (380808.7 ± 610937 vs 147028.2 ± 475225.6, P = 0.001) and TAC (1.35 ± 0.5 vs 1.612 ± 0.56, P = 0.001). After N. sativa administration, the following laboratory parameters improved: total protein (7.1 ± 0.7 vs 7.5 ± 0.8, P = 0.001), albumin (3.5 ± 0.87 vs 3.69 ± 0.91, P = 0.008), red blood cell count (4.13 ± 0.9 vs 4.3 ± 0.9, P = 0.001), and platelet count (167.7 ± 91.2 vs 198.5 ± 103, P = 0.004). Fasting blood glucose (104.03 ± 43.42 vs 92.1 ± 31.34, P = 0.001) and postprandial blood glucose (143.67 ± 72.56 vs 112.1 ± 42.9, P = 0.001) were significantly decreased in both diabetic and non-diabetic HCV patients. Patients with lower-limb edema de     

Liver diseases in pregnancy: Diseases not unique to pregnancy

Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver.Liver disease can cause significant morbidity and mortality in both pregnant women and their infants.Few challenges arise in reaching an accurate diagnosis in light of such physiological changes.Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment.Other challenges entail the methods of treatment and their safety for both the mother and the baby.This review summarizes liver diseases that are not unique to pregnancy.We focus on viral hepatitis and its mode of transmission,diagnosis,effect on the pregnancy,the mother,the infant,treatment,and breast-feeding.Autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,Wilson’s disease,Budd Chiari and portal vein thrombosis in pregnancy are also discussed.Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis.Variceal bleeding can happen in up to 38%of cirrhotic pregnant women.Management of portal hypertension during pregnancy is discussed.Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones.We discuss some of the interventions for gallstones in pregnancy if symptoms arise.Finally,we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy.     

Hepatitis C virus-related mixed cryoglobulinemia: Is genetics to blame?

Mixed cryoglobulinemia(MC)is the extrahepatic manifestation most strictly correlated with hepatitis C virus(HCV)infection;it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in5%-10%of cases.MC is reputed to be a multistep and multifactorial process whose pathogenicity is still poorly understood.It is still unknown why only some chronically infected HCV patients develop MC and only some of these exhibit systemic symptoms(MC syndrome).Several studies have investigated the pathogenetic basis of MC and the most recent ones suggest that the virus is able to trigger such a disorder only in the presence of genetic factors that are still unknown.Here,we try to clarify the complex relationship between HCVrelated MC and the host’s genetic background.The data that we report are heterogeneous and sometimes even conflicting.Therefore,large,multicenter studies are clearly needed.The identification of a characteristic genetic signature of cryoglobulinemic patients would be an important step toward a personalized approach in their clinical care.The new wide-ranging genomics technologies will hopefully help to resolve these complex issues.     

Hepatitis C and pregnancy

Acute hepatitis C is a rare event in pregnancy. The most common scenario is chronic hepatitis C virus(HCV) infection in pregnancy. During pregnancy in women with chronic HCV infection a significant reduction in mean alanine aminotransferase levels has been reported,with a rebound during the postpartum period. In few cases exacerbation of chronic hepatitis C has been reported in pregnancy. A cofactor that might play a role in the reduction of liver damage is the release of endogenous interferon from the placenta. Observations regarding serum HCV-RNA concentration have been variable.In some women HCV-RNA levels rise toward the end of pregnancy. In general,pregnancy does not have a negative effect on HCV infection. Conversely,chronic hepatitis does not appear to have an adverse effect on the course of pregnancy,or the birth weight of the newborn infant. The role of spontaneous abortion is approximately the same as in the general population. The overall rate of mother-to-child transmission for HCV is3%-5% if the mother is known to be anti-HCV positive.Co-infection with human immunodeficiency virus(HIV)increases the rate of mother-to-child transmission up to19.4%. Numerous risk factors for vertical transmission have been studied. In general,high viral load defined as at least 2.5 × 106viral RNA copies/mL,HIV co-infection,and invasive procedures are the most important factors. Both interferon and ribavirin are contraindicated during pregnancy. Viral clearance prior to pregnancy increases the likelihood that a woman remains nonviremic in pregnancy with a consequent reduced risk of vertical transmission.     

Dipeptidyl peptidase-4: A key player in chronic liver disease

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.     

Genetic Factors,Viral Infection,Other Factors and Liver Cancer: An Update on Current Progress

Primary liver cancer is one of the most common cancers at the global level, accounting for half of all cancersin some undeveloped countries. This disease tends to occur in livers damaged through alcohol abuse, or chronicinfection with hepatitis B and C, on a background of cirrhosis. Various cancer-causing substances are associatedwith primary liver cancer, including certain pesticides and such chemicals as vinyl chloride and arsenic. Thestrong association between HBV infection and liver cancer is well documented in epidemiological studies. It isgenerally acknowledged that the virus is involved through long term chronic infection, frequently associatedwith cirrhosis, suggesting a nonspecific mechanism triggered by the immune response. Chronic inflammation ofliver, continuous cell death, abnormal cell growth, would increase the occurrence rate of genetic alterations andrisk of disease. However, the statistics indicated that only about one fifth of HBV carries would develop HCCin lifetime, suggesting that individual variation in genome would also influence the susceptibility of HCC. Thegoal of this review is to highlight present level of knowledge on the role of viral infection and genetic variationin the development of liver cancer.     

High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay

Viruses are extremely heterogeneous entities; the size and the nature of their genetic information, as well as the strategies employed to amplify and propagate their genomes, are highly variable. However, as obligatory intracellular parasites, replication of all viruses relies on the host cell. Having co-evolved with their host for several million years, viruses have developed very sophisticated strategies to hijack cellular factors that promote virus uptake, replication, and spread. Identification of host cell factors (HCFs) required for these processes is a major challenge for researchers, but it enables the identification of new, highly selective targets for anti viral therapeutics. To this end, the establishment of platforms enabling genome-wide high-throughput RNA interference (HT-RNAi) screens has led to the identification of several key factors involved in the viral life cycle. A number of genome-wide HT-RNAi screens have been performed for major human pathogens. These studies enable first inter-viral comparisons related to HCF requirements. Although several cellular functions appear to be uniformly required for the life cycle of most viruses tested (such as the proteasome and the Golgi-mediated secretory pathways), some factors, like the lipid kinase Phosphatidylinositol 4-kinase IIIα in the case of hepatitis C virus, are selectively required for individual viruses. However, despite the amount of data available, we are still far away from a comprehensive understanding of the interplay between viruses and host factors. Major limitations towards this goal are the low sensitivity and specificity of such screens, resulting in limited overlap between different screens performed with the same virus. This review focuses on how statistical and bioinformatic analysis methods applied to HT-RNAi screens can help overcoming these issues thus increasing the reliability and impact of such studies.     

HPV病毒负荷量与TSLC-1在宫颈鳞癌及癌前病变中的相关性研究

目的：探讨肺癌肿瘤抑制因子1（TSLC-1）与人乳头瘤病毒（HPV）病毒负荷量在癌及癌前病变中的相关性。方法：收集2008—2010年就诊于兰州大学第一医院100例慢性宫颈炎、宫颈上皮内瘤变及宫颈鳞状上皮癌患者的宫颈脱落上皮细胞,采用杂交捕获法（HC-Ⅱ）检测HPV病毒负荷量,免疫组化（SP）法检测相应组织TSLC-1蛋白表达,分析两者在宫颈病变进展中的关系。结果：100例标本HPV阳性54例,1≤病毒负荷量（RLU/CO）≤100共27例,100～1 000共23例,≥1 000为4例。TSLC-1蛋白阴性为42例,阳性58例,按不同表达强度分别为“+”23例,“++”20例,“+++”15例。Spearman秩相关分析显示,HPV病毒负荷量与TSLC-1表达有相关性（rs=0.586,P=0.000）。结论：随宫颈癌前病变进展至宫颈鳞癌,HPV病毒负荷量与TSLC-1表达减低有相关性,可将两者联合检测应用于临床,预测宫颈癌前病变的进展。     

Human papillomavirus screening in north Indian women

Objectives: Human papillomavirus (HPV) is the major etiological agent of cervical cancer, a leading cause ofmorbidity and mortality in women worldwide. Screening strategies for reducing the burden of HPV-mediatedcarcinogenesis are emerging as an effective means for cervical cancer control and prevention in developingcountries. Our study, therefore, aimed to identify HPV infection status in North Indian women during randompopulation screening. Methodology: Cervical/vaginal exfoliated cells and/or Pap smear specimens were collectedfrom 890 women of North Indian ethnicity residing in Lucknow and adjoining areas, during random populationscreening from June 2009-March 2012. HPV viral loads in clinical specimens were determined by the HybridCapture (hc)-2 HPV DNA assay, and subsequently, positive/negative/borderline HPV status was calculated.Results: The HPV incidence in the present study was 11.7%. 751 out of a total of 890 women (84.4%) participatingin our HPV screening program were HPV negative (HPV -), 104 (11.7%) tested positive (HPV +) while 35 (3.9%)showed borderline (HPV *) infection status. Furthermore, in the HPV + subjects (N=104), 18 (17.3%) showedstrong positivity. We observed that HPV positivity tends to increase with age in North Indian women; the higherthe viral load with increasing age, higher is the susceptibility to HPV-mediated cervical cancer. Conclusions:HPV viral load/genotyping may help in identifying women at risk of developing cervical cancer. However, costeffectiveHPV screening protocols with a wider population coverage are warranted so as to reduce the burdenof cervical cancer in women worldwide in the vaccine-era.     

Face up to challenge of virology world

Welcome to the World Journal of Virology (WJV), a new member of the World Journal Series. The World Journal Series was first launched as a peer-reviewed scientific journal covering aspects of research, diagnostics and clinical practice in biomedicine in 1995. WJV is an online and open-access peer-reviewed periodical focusing on virology. WJV covers a variety of topics in different areas of virology, including advances in basic research, updates in nomenclature, the development of novel diagnostic assays, the epidemiology of viral disorders and, new developments in the clinical management of viral diseases, including new vaccines and antiviral therapeutics. The purpose in launching the WJV is to promote knowledge exchange related to the classic human viruses as well as newly emerging viruses and their associated clinical disorders. Continually updating knowledge in a timely manner in this field where information related to the unceasing evolution of viruses is becoming available at a rapid pace is challenging. Thanks to the World-Wide-Web we are able to provide a podium for all authors and readers of WJV to address this challenge. I would like to acknowledge the Baishideng publisher, the members of the editorial board, and all contributing authors involved in this inaugural issue of the WJV. I sincerely hope all readers, i.e. future contributing authors, will like WJV and we look forward to your input in assisting WJV to grow and mature.