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To determine hepatitis C virus (HCV) infection prevalence in each country of the Middle-East and the overall prevalence of the region.In this systematic review, we gathered all documents related to HCV infection prevalence among hemodialysis patients in 17 middle-east countries from April 2006 to March 2016. We selected only cross-sectional studies that had proper sampling and measurement methods as well as a valid statistical analysis.After screening of 7311 documents, 56 studies were selected reporting the prevalence of HCV infection among hemodialysis patients from 10 countries of the region. Seven countries including United Arab Emirates, Afghanistan, Qatar, Bahrain, Kuwait, Oman, Israel, and Cyprus did not have any relevant document; thus, their latest reports were just mentioned. We performed the meta-analysis and determined the prevalence rates for each country as well as the whole region. The overall HCV infection prevalence among hemodialysis patients in the region was reported to be 25.3%; Egypt and Syria had the highest reported rates while Iran and Lebanon had the lowest. Further investigations are still needed to provide more reliable databases, find main risk factors, and to improve diagnosis and treatment plans, particularly in higher prevalent countries.Controlling the prevalence and improving the management methods of HCV infection among hemodialysis patients are of a great concern in the Middle-East region.

To date, no studies have provided data on hepatitis B virus (HBV) prevalence among asymptomatic, healthy human T-lymphotropic virus (HTLV-I) positive carriers. This sero- and molecular epidemiology study was performed on patients in the Northeast of Iran, which is an endemic area for HTLV-I infection. A total of 109 sera were collected from HTLV-I positive healthy carriers who were admitted to Ghaem Hospital, Mashhad City. All were tested for HBV serology and subsequently, real time PCR was carried out on the samples, regardless of the results of the serology. Standard PCR and direct sequencing were applied on positive samples. All cases were negative for HBsAg, Anti-HBc, and anti-HBs were positive in 34 (31.1%), and 35 (32%) individuals, respectively. There were 19 (17.4%) cases that were positive only for anti-HBs, and they had already received HBV vaccine. 16 (15%) were positive for both anti-HBs and anti-HBc, indicating a past-resolved HBV infection. 18 (16.5%) were isolated as anti-HBc, and 56 (51.3%) were negative for all HBV serological markers. Only one subject (0.9%) had detectable HBV DNA (2153 copy/ml), and assigned as being an occult HBV infection. The low prevalence of HBsAg, despite the high percentage of anti-HBc positive cases, might be related to the suppression effect of HTLV-I on surface protein expression. The low prevalence of HBV infection among HTLV-I positive healthy carriers from an endemic region, indicates that the epidemiology of HTLV-I and HBV coinfection is related to the endemicity of HBV in that region, rather than HTLV-I endemicity. J. Med. Virol. 86:1861–1867, 2014. © 2014 Wiley Periodicals, Inc.

Objective There are several reports regarding the role of therapeutic diets for patients with non-alcoholic fatty liver disease (NAFLD). Therefore, the aim of this study was to determine the effects of a low-calorie, low-carbohydrate soy-containing diet on lipid profiles, liver enzymes, and coagulating factors in patients with NAFLD. Method This was a randomized parallel clinical trial involving 45 patients with NAFLD. The participants consumed three kinds of diets for 8 wk. Patients were randomly assigned to consume a low-calorie diet; a low-calorie, low-carbohydrate diet; or a low-calorie, low-carbohydrate soy-containing diet. Measurements were done according to the standard method. Results Changes in weight were not significantly different in the three groups. The low-calorie, low-carbohydrate soy-containing diet could reduce alanine aminotransferase (–15.2 ± 12.1 versus –6.8 ± 4.6 in the low-calorie, low-carbohydrate diet, and –6.4 ± 4.4 IU/L in the low-calorie diet; P = 0.02) and serum fibrinogen levels (–49.1 ± 60.1 versus –12.9 ± 8.1 and –17.4 ± 8.4 g/L, respectively; P = 0.01). Reductions in aspartate aminotransferase were significantly higher in the low-calorie, low-carbohydrate soy-containing group. Changes in lipid profiles did not differ significantly between the groups. The soy-containing diet did reduce malondialdehyde more than the other diets ( P = 0.01). Conclusion A low-calorie, low-carbohydrate soy-containing diet could have beneficial effects on liver enzymes, malondialdehyde, and serum fibrinogen levels in patients with NAFLD.

Interferons are able to exert an antiviral effect against hepatitis C virus (HCV) infection via induction of interferon-stimulated genes (ISGs). This study tested whether differential expression of an important ISG with antiviral properties, tripartite motif 22 (TRIM22), correlates with a response to Peg-IFNa-2a/RBV combination therapy in treatment-naive patients with chronic hepatitis C. A total of 32 patients with chronic hepatitis C were enrolled in this study and received standard Peg-IFNa-2a/RBV combination therapy. HCV viral load was measured during treatment, at the end of treatment, and 6 months later to determine the treatment outcome. Quantitative real-time PCR was used to assess the expression levels of TRIM22 in peripheral blood mononuclear cells (PBMCs) of the patients before antiviral therapy. Of the 32 patients, 26 (81.3%) were males. In this study, there were 16 (50%) individuals with a sustained virologic response (SVR), and a virologic relapse was observed in the remaining half of the subjects. Testing for the presence of genomic HCV RNA in blood during therapy revealed a rapid virologic response (RVR) in 10 (31.2%) and a partial and complete early virologic response (EVR) in 8 (25%) and 24 (75%) of the cases, respectively. TRIM22 mRNA levels were significantly higher in patients with a sustained virologic response than in relapsers (P ¼0.002) and in patients with a rapid virologic response than in the others (P ¼0.040). No statistically significant differ

Background: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS) seems to be associated with known host and viral factors which may influence the long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC), factors associated with HS in CHB are not clearly explored. Materials and Methods: 160 CHB patients were divided into two groups depending on the results of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group II comprised 89 patients without steatosis. The groups were compared in terms of basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP), serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral load, and histological findings. Results: In terms of host factors, male gender, older age, BMI, high serum FBS and lipid levels were associated with HS. On the other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis did not associate with HS. On multivariate analysis, parameters of sex, BMI, cholesterol and FBS levels were independently associated with HS. Regarding viral factors, HBeAg negativity was significantly associated with HS (81.7%, p value 0.006), but not HBV DNA level (p value 0.520). Conclusions: HS in CHB appears to be unrelated to the status of HBV replication. However, fibrosis progression in CHB is related to variable host factors. HS may be enhanced through these factors in HBV chronic patients.

Iran is a large country that covers the northern coast of the Persian Gulf. Iranian residents of this coastal region interact closely with people from neighboring countries because of historical and cultural relationships, as well as economic activities. In addition, the inhabitants of this border region have experienced several wars, which have affected public health infrastructures. This study characterized for the first time, the evolution of the full-length genome of HBV strains in asymptomatic carrier patients living in this particular region. In addition, this study was compared and complemented by a comprehensive evolutionary analysis of the worldwide geographical distribution of HBV subgenotype D1. Evolutionary analysis demonstrates that patients living in the northern coast of the Persian Gulf are mainly infected with HBV subgenotype D1, subtype ayw2. Specific mutations related to advanced liver disease were found more frequently in these strains compared to other strains isolated from asymptomatic carriers from other regions of Iran. This global comprehensive analysis showed that HBV subgenotype D1 strains have a worldwide distribution and that human mobility and immigration had a large impact on dispersal of HBV subgenotype D1, subtype ayw2 in Middle Eastern countries such as Iran, Syria, and Turkey. In addition to association of subtype ayw2 with subgenotype D1, it was demonstrated that other HBV subtypes like adw2, ayw1, and ayw3 are associated with HBV subgenotype D1 in different regions of the world. This study also revealed a remarkable distribution of subgenotype D1, subtype ayw4 although this particular subtype is associated with subgenotype D4 of HBV in European countries. J. Med. Virol. 86:745–757, 2014. © 2014 Wiley Periodicals, Inc.

Background: Occult hepatitis B infection (OBI) is determined by finding hepatitis B virus (HBV) DNA in the liver cells of the patients with negative tests for HBV surface antigen. It is more common in patients with hepatitis C virus (HCV) infection which can be transmitted by blood transfusion and is frequently seen in hemophilia and thalassemia patients. Objectives: The aim of this study was to assess the prevalence of OBI among Iranian patients with hematological disorders (thalassemia, hemophilia and other coagulation factor deficiencies) infected with chronic hepatitis C (CHC). Methods: In this descriptive cross-sectional study, all patients with hematological disorders (thalassemia, hemophilia or other coagulation factor deficiencies) who had simultaneous CHC infection and were referred to the Tehran hepatitis center between 2009 and 2010 were enrolled. Occult hepatitis B infection identification was based on serum HBV-DNA tests. Data analysis was performed with SPSS software. Results: All patients were HBsAg-negative and HCV RNA-positive. Only 145 patients were evaluated for HBV DNA (126 male and 19 female patients). The mean age (SD) was 28.12 (8.6) years. Thirty-five patients had thalassemia, 95 patients had hemophilia, and 15 patients had coagulation factor deficiencies. Serum HBV-DNA was negative for all cases. Conclusions: Based on our results, it seems that there were no cases of OBI among chronic HCV-infected patients with thalassemia and bleeding disorders, particularly hemophilia. However, to improve decisions concerning OBI screening, especially in transfusion centers, and concerning the use of comprehensive screening methods, more original studies with more precise laboratory techniques and larger sample sizes are needed.

Background: Transient elastography (TE) is a new modality for the diagnosis of liver fibrosis caused by various etiologies. This study was conducted to determine the accuracy of TE in detecting the different stages of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) patients. Methods: MEDLINE/PubMed, Embase, Ovid, Cochrane Library, American College of Physicians (ACP) Journal Club, Google Scholar, Database of Abstracts of Reviews of Effects, and Web of Science that evaluated the liver stiffness by means of TE and liver biopsy were enrolled in this systematic review and meta-analysis. Published articles were extracted from 2002 to March 2015. Results: A total of 7 articles from 114 papers were included which consisted of 698 patients. The results indicated that when F ≥3, the outcomes were 93.7% (95% confidence interval (CI): 92-95.5), 91.1% (95% CI: 89-93.2), 82.4% (95% CI: 79.9-84.9), and 95.9% (95% CI: 94.4-97.4) for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), respectively. With fibrosis stage ≥4, it has reached the sensitivity of 96.2 % (95% CI: 94.5-97.8), a specificity of 92.2% (95% CI: 89.9-94.6), a PPV of 5.5% (95% CI: 51.2-59.8) and NPV of 98.5% (95% CI: 97.4-99.5). Conclusion: We concluded that as the pathological fibrosis increases, the sensitivity, specificity and NPV of TE in the diagnosis of fibrosis improves in NAFLD patients. TE can be considered as a unique alternative instead of liver biopsy in NAFLD patients and it has an important role in the exclusion of liver cirrhosis. More studies are required to confirm the results.

Background: The hepatitis C virus (HCV) infection is one of the major causes of progressive liver diseases worldwide. Despite the new treatments for HCV infection, antiviral therapy with a combination of pegylated interferon-α 2a plus ribavirin (Peg-IFNα-2a/RBV) is still used in developing countries. Objectives: The aim of the current study was to determine the relationship between rs12979860 polymorphism in the interleukin 28B gene (IL28B) and response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients with chronic HCV infection. Methods: A total of 72 Azerbaijani patients with established chronic HCV-1b took part in this cross-sectional study between January 2010 and September 2015. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) of the patients and the rs12979860 single nucleotide polymorphism was diagnosed by polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Results: The mean age of the patients was 36.9 ± 12.4 (range of 27 - 57 years) and 42 (58.3%) out of 72 were male. Concerning the IL28B polymorphism in rs12979860, the results indicated the presence of CC, CT, and TT genotypes in 24 (33.3%), 42 (58.3%), and 6 (8.3%) patients, respectively. There was a significant association between IL28B genotypes and response to HCV combination therapy with peg-IFNα-2a/RBV (P = 0.001). Conclusions: The results of this study indicate that the rs12979860 CC genotype of IL28B was associated with a response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients with HCV-1b infection. Therefore, host genetics may be useful in predicting the response to hepatitis C treatment.

Background: The combination of sofosbuvir and daclatasvir can be used to treat all genotypes of hepatitis C. Current guidelines for treating hepatitis C cirrhosis do not clarify weather 12 weeks or 24 weeks of treatment is appropriate. Objectives: In the present study, we aimed at evaluating the efficacy of sofosbuvir, daclatasvir, and ribavirin given for 12 weeks in treating cirrhotic patients with hepatitis C genotypes 1 and 3 infections. Methods: One hundred patients with hepatitis C and cirrhosis infected with Genotypes 1 and 3 were included in the present study. They were treated with 1 tablet of a combination pill of 400 mg sofosbuvir and 60 mg daclatasvir daily and weight-based ribavirin for 12 weeks. Response to treatment was assessed 12 weeks after the end of the treatment with a sensitive assay (SVR12). This study was registered with ClinicalTrials.gov, ID: NCT02596880. Results: One patient developed increased creatinine level following severe diarrhea and gastroenteritis and was excluded, 1 patient died due to unrelated reasons and 4 others were lost to follow-up. Among the 94 patients who finished the study, 92 achieved SVR12 (98%, per-protocol, 92% intention-to-treat). None of the patients reported any side effects. Of the 100 original patients, 56 were Genotype 1 and 44 were Genotype 3. One of the two patients not achieving SVR12 was Genotype 1, and the other two were Genotype 3. Conclusions: The fixed-dose combination drug of sofosbuvir and daclatasvir given together with weight-base ribavirin for 12 weeks is extremely effective and safe in treating HCV patients with Genotypes 1 and 3 and cirrhosis.

Background Prisoners are at high risk of blood borne and sexually transmitted infections due to their high involvement in risky behaviors. In this descriptive/cross-sectional study, the prevalence, sero-prevalence, and risk factors for bloodborne tumor viruses including HTLV-I, HBV, HCV, and KSHV were evaluated among inmates of two central prisons in the northeast of Iran. Methods Blood samples of 1114 inmates were analyzed for the presence of anti HTLV-I, KSHV, and HCV antibodies and HBsAg by ELISA. PCR tests were performed to confirm the presence of these viruses in plasma and identify the current infections. Results The sero-prevalence of HCV, HBV, HTLV-I, and KSHV was 24.5%, 4.2%, 3.4%, and 3.2% and the prevalence of HCV, HBV, HTLV-I, and KSHV was 19.1%, 2.1%, 2%, and 3%, respectively. HCV infection was significantly associated with history of imprisonment, tobacco consumption, alcohol consumption, intravenous drug use, length of imprisonment, and type of crime committed. Thirty one (2.8%) prisoners had HCV-KSHV co-infection, 16 (1.5%) had HCV-HTLV-I co-infection, and 14 (1.3%) had HBV-HCV co-infection. Triple co-infection was observed in seven cases and one case had four infections concomitantly. Conclusions This epidemiological study indicated different rates and transmission risks for these viruses. HCV was the most contagious viral infection and HTLV-I was the weakest in the prisoners. Apart from KSHV infection which its prevalence was as twice as in the general population, the prevalence of HBV and HTLV-I in prisoners was nearly in ranges of the general population.

Introduction: Hepatitis B virus (HBV) infection is a global public health problem. Serum HBV DNA measurement is a non-invasive test that predicts the liver disease progression. The aim of this study was to determine the HBV DNA level and look for a relation between the HBV DNA level and liver histology. Methods: This was a cross sectional study on chronic hepatitis B infected patients in Tehran Hepatitis Center from 2006 to 2010. Percutaneus liver biopsy was performed in all patients. Patients with a history of any treatment and co-infection of HCV, HDV and HIV were excluded. Results: 301 patients were included in this study. The mean age was 34.63±13.25 years. Mean serum HBV DNA level was 1.35* 108 ± 10.5*109 copies/ml. Mean inflammatory score (grade) was 5.54±3.26 and fibrosis (stage) was 1.93±1.56. There wasn’t any significant relation between age and sex with liver histology. No significant relation was seen between liver histology and the HBV DNA level. HBe Ag positive patients had a higher serum HBV DNA level. Conclusion: There wasn’t any significant relation between liver histology and the HBV DNA level. We suggest using liver biopsy as a golden standard. In addition we need more studies in this field.

The genetic diversity of the HBV S gene has a significant impact on the prophylaxis and treatment of hepatitis B infection. The effect of selective pressure on this genetic alteration has not yet been studied in Iranian blood donors. To explore HBV evolution and to analyze the effects and patterns of hepatitis B surface antigen (HBsAg) mutations on blood screening assays, 358 Iranian blood donors diagnosed as asymptomatic HBV carriers were enrolled in this nationwide study. Large S and partial S genes were amplified and sequenced. HBV (sub) genotypes and synonymous and nonsynonymous mutations were investigated. The impact of naturally occurring mutations on HBsAg ELISA results was explored. Phylogenetic analyses revealed that isolated strains were of genotype D. The dominant subgenotype/subtype was D1/ayw2. Deletions and naturally occurring stop codons in the pre-S1 and major hydrophilic region (MHR) were identified. In total, 32.8% of the studied strains harbored 195 single or multiple mutations in the MHR, the majority of which were located at the first loop of the “a determinant” domain. The ayw2 subtype showed a significant effect on the ELISA signal/cut-off value and carried fewer mutations in the MHR. Nonsynonymous/synonymous substitution value indicated that negative selection was the dominant evolutionary force in the HBV S gene. This nationwide study revealed that mutation frequency of HBsAg among Iranian blood donors was much higher than previous reports from the different local regions. These findings regarding the significant differences in reactivity of ELISA among different subtypes of HBV and its correlation with the number of mutations at the MHR will be valuable to public health authorities. J. Med. Virol. 86:144–155, 2014. © 2013 Wiley Periodicals, Inc.

Hepatitis D is returning to western Europe through immigration. The clinical presentation recapitulates the typical features of a florid hepatitis D. Hepatitis D is also being rediscovered in the developing world and in the United States. Hepatitis D virus (HDV) remains endemic in many countries and efforts are underway to map the infection at local levels and improve the medical alert to hepatitis D. In the United States it is generally thought that HDV has gone and hepatitis D is no longer a problem. Awareness of hepatitis D in the country has recently been revived.

Mutations within the coding region of hepatitis B surface antigen (HBsAg) have been found naturally in chronic carriers. To characterize the mutations of HBsAg from Iranian chronic carriers who were vaccine and/or medication naive. The surface genes from 360 patients were amplified and directly sequenced. The distribution of amino acid substitutions was classified according to different immune epitopes of the surface protein. All isolates belonged to genotype D. 222 (61.6%) of 360 patients contained at least one amino acid substitution. 404 (74.5%) of 542 amino acid changes occurred in different immune epitopes of HBsAg, of which 112 (27.7%) in 32 residues of B-cell epitopes (62 in the 'a' determinant); 111 (27.4%) in 32 residues of T helper; and 197 (48.7%) in 32 residues inside cytotoxic T lymphocyte (CTL) epitopes. One Th (186-197) and two CTL (28-51 and 206-215) epitopes were found to be hotspot motifs for the occurrence of 213 (52.7%) substitutions. 20 stop codons were identified in different epitopes. There was a significant association between amino acid substitutions and anti-HBe seropositivity; however, the correlation between such changes with viral load and ALT levels was not significant. In chronic hepatitis B virus(HBV) carriers, positive selection in particular outside the 'a' determinant appeared to exert influence on the surface proteins. These changes could be immune escape mutations naturally occurring due to the host immune surveillance especially at the T-cell level.

Background. Recent studies have demonstrated that prevention of hepatitis B virus (HBV) transmission remains a challenge in hemodialysis (HD) patients. The aim of this study is to explore factors which increase the possibility of occult HBV (OHB) infection in patients under HD in Iran. Material and methods. Among 2188 cases who spent an average of 60.2 ± 61.1 months under HD, we selected 103 cases with isolated antihepatitis B virus core antibody (anti-HBc) and 231 controls without any HBV, hepatitis D virus (HDV) and hepatitis C virus (HCV) serologic markers. Socio-demographic data, past medical history, and clinical signs and symptoms were assessed. Results. The frequency of checking hepatitis B serologic markers was 15.3%. The rate of OHB infection in HD patients who were monitored for their HBV markers was 4.9%. Cases with isolated anti-HBc had significantly higher percentage of positive HBV DNA [odds ratio: OR (95% confidence interval: 95% CI) = 12.1 (1.4-105)], visual disturbances [OR (95% CI) = 1.8 (1.1-3.03)], history of diabetes mellitus [OR (95% CI) = 2.1 (1.3-3.5)], higher age, higher age when dialysis started and were mostly married, illiterate, disabled and retired. Diabetes mellitus was the only independent predictor of HBV DNA status in cases with isolated anti-HBc. Conclusion. In our region, OHB infection is prevalent among hemodialysis patients and displays a direct correlation with factors which are age related except diabetes mellitus. Thus, the presence of isolated anti-HBc should prompt the clinician to evaluate a possible OHB infection especially when it is detected in conjunction with a history of diabetes mellitus.

Student Research Committee (SRC) has been developed a subset of each university's Vice chancellor for research in purpose of research training for motivated students and conducting their research interests. In this paper, we evaluated effect of SRCs on Iran's research through Scopus database and showed that SRCs has a remarkable impact on Iran's publication performance.

Context Hepatitis C virus (HCV) is characterized by a high degree of genetic heterogeneity and classified into 7 genotypes and different subtypes. It heterogeneously distributed through various risk groups and geographical regions. A well-established phylogenetic relationship can simplify the tracing of HCV hierarchical strata into geographical regions. The current study aimed to find genetic phylogeny of subtypes 1a and 1b of HCV isolates based on NS5B nucleotide sequences in Iran and other members of Eastern Mediterranean regional office of world health organization, as well as other Middle Eastern countries, with a systematic review of available published and unpublished studies. Evidence acquisition The phylogenetic analyses were performed based on the nucleotide sequences of NS5B gene of HCV genotype 1 (HCV-1), which were registered in the GenBank database. The literature review was performed in two steps: 1) searching studies evaluating the NS5B sequences of HCV-1, on PubMed, Scopus, and Web of Science, and 2) Searching sequences of unpublished studies registered in the GenBank database. Results In this study, 442 sequences from HCV-1a and 232 from HCV-1b underwent phylogenetic analysis. Phylogenetic analysis of all sequences revealed different clusters in the phylogenetic trees. The results showed that the proportion of HCV-1a and -1b isolates from Iranian patients probably originated from domestic sources. Moreover, the HCV-1b isolates from Iranian patients may have similarities with the European ones. Conclusions In this study, phylogenetic reconstruction of HCV-1 sequences clearly indicated for molecular tracing and ancestral relationships of the HCV genotypes in Iran, and showed the likelihood of domestic origin for HCV-1a and various origin for HCV-1b.

Background The past two decades have seen a large increase in investment in global public health research. There is a need for increased coordination and accountability, particularly in understanding where funding is being allocated and who has capacity to perform research. In this paper, we aim to assess global, regional, national and sub–national capacity for public health research and how it is changing over time in different parts of the world. Methods To allow comparisons of regions, countries and universities/research institutes over time, we relied on Web of ScienceTM database and used Hirsch (h) index based on 5–year–periods (h5). We defined articles relevant to public health research with 98% specificity using the combination of search terms relevant to public health, epidemiology or meta–analysis. Based on those selected papers, we computed h5 for each country of the world and their main universities/research institutes for these 5–year time periods: 1996–2000, 2001–2005 and 2006–2010. We computed h5 with a 3–year–window after each time period, to allow citations from more recent years to accumulate. Among the papers contributing to h5–core, we explored a topic/disease under investigation, “instrument” of health research used (eg, descriptive, discovery, development or delivery research); and universities/research institutes contributing to h5–core. Results Globally, the majority of public health research has been conducted in North America and Europe, but other regions (particularly Eastern Mediterranean and South–East Asia) are showing greater improvement rate and are rapidly gaining capacity. Moreover, several African nations performed particularly well when their research output is adjusted by their gross domestic product (GDP). In the regions gaining capacity, universities are contributing more substantially to the h–core publications than other research institutions. In all regions of the world, the topics of articles in h–core are shifting from communicable to non–communicable diseases (NCDs). There is also a trend of reduction in “discovery” research and increase in “delivery” research. Conclusion Funding agencies and research policy makers should recognise nations where public health research capacity is increasing. These countries are worthy of increased investment in order to further increase the production of high quality local research and continue to develop their research capacity. Similarly, universities that contribute substantially to national research capacity should be recognised and supported. Biomedical journals should also take notice to ensure equity in peer–review process and provide researchers from all countries an equal opportunity to publish high–quality research and reduce financial barriers to accessing these journals.

Background: Despite the introduction of new drug regimens with high effectiveness for the hepatitis C virus (HCV) patients, especially in HCV genotype 1, no cost-effectiveness study on the selection of the superior drug strategy in Iran has been conducted yet.\ud \ud Objectives: This study is aimed to assess the cost-effectiveness of the three drug regimens of pegylated interferon and ribavirin (PR), sofosbuvir (SOF) + PR and ledipasvir and sofosbuvir (LDV/SOF) in patients with HCV genotype 1 in Iran in the year 2014.\ud \ud Methods: A Markov micro-simulation model was used to evaluate the cost-effectiveness of the three drug strategies for a cohort of 10000 patients. Quality-adjusted life-years (QALYs) were extracted from published studies. Cost data was estimated through the review of medical records and obtaining experts opinion.\ud \ud Results: The results showed that the SOF + PR drug compared with PR had a lower cost and was more effective, but compared with the LDV/SOF, in spite of its lower cost, it was less efficient. The QALY values obtained for PR, SOF + PR and LDV/SOF, respectively, were 10.98, 12.08 and 12.28 and their costs were $ 41,741, $ 7,676 and $ 46,993. Moreover, the results obtained from acceptability curves showed that SOF + PR were the most cost-effective treatment for thresholds below $ 45,270 PPP.\ud \ud Conclusions: The use of SOF + PR regimen or LDV/SOF can significantly reduce the incidence of complications associated with the disease. For example, short and long-term outcomes are better than the current drug regimens for HCV genotype 1 patients in all stages of the disease.

Background Hepatitis B virus (HBV) as an infectious disease that has nine genotypes (A - I) and a 'putative' genotype J. Objectives The aim of this study was to identify the rare codon clusters (RCC) in the HBV genome and to evaluate these RCCs in the HBV proteins structure. Methods For detection of protein family accession numbers (Pfam) in HBV proteins, the UniProt database and Pfam search tool were used. Protein family accession numbers is a comprehensive and accurate collection of protein domains and families. It contains annotation of each family in the form of textual descriptions, links to other resources and literature references. Genome projects have used Pfam extensively for large-scale functional annotation of genomic data; Pfam database is a large collection of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). The Pfam search tools are databases that identify Pfam of proteins. These Pfam IDs were analyzed in Sherlocc program and the location of RCCs in HBV genome and proteins were detected and reported as translated EMBL nucleotide sequence data library (TrEMBL) entries. The TrEMBL is a computer-annotated supplement of SWISS-PROT that contains all the translations of European molecular biology laboratory (EMBL) nucleotide sequence entries not yet integrated in SWISS-PROT. Furthermore, the structures of TrEMBL entries proteins were studied in the PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software®. Results The Pfam search tool found nine protein families in three frames. Results of Pfams studies in the Sherlocc program showed that this program has not identified RCCs in the external core antigen (PF08290) and truncated HBeAg gene (PF08290) of HBV. By contrast, the RCCs were identified in gene of hepatitis core antigen (PF00906 and the residues 224 - 234 and 251 - 255), large envelope protein S (PF00695 and the residues 53-56 and 70 - 84), X protein (PF00739 and the residues 10 - 24, 29 - 83, 95 - 99. 122 - 129, 139 - 143), DNA polymerase (viral) N-terminal domain (PF00242 and the residues 59 - 62, 214 - 217, 407 - 413) and protein P (Pf00336 and the residues 225 - 228). In HBV genome, seven RCCs were identified in the gene area of hepatitis core antigen, large envelope protein S and DNA polymerase, while protein structures of TrEMBL entries sequences found in Sherlocc program outputs were not complete. Conclusions Based on the location of detected RCCs in the structure of HBV proteins, it was found that these RCCs may have a critical role in correct folding of HBV proteins and can be considered as drug targets. The results of this study provide new and deep perspectives about structure of HBV proteins for further researches and designing new drugs for treatment of HBV.

Dear editor, We read with much interest the recently published article by Foroughi et al 1 in your journal. They have demonstrated that the prevalence of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among street and labour children is 4.5%, 1.7% and 2.6% in Iran, respectively, and well discussed about HIV infection in this population. However, we would like to highlight some points about HBV …

BACKGROUND The hepatitis C virus (HCV) has six major genotypes. The purpose of this study was to phylogenetically investigate the differences between the genotypes of HCV, and to determine the types of amino acid codon usage in the structure of the virus in order to discover new methods for treatment regimes. METHODS The codon usage of the six genotypes of the HCV nucleotide sequence was investigated through the online application available on the website Gene Infinity. Also, phylogenetic analysis and the evolutionary relationship of HCV genotypes were analyzed with MEGA 7 software. RESULTS The six genotypes of HCV were divided into two groups based on their codon usage properties. In the first group, genotypes 1 and 5 (74.02%), and in the second group, genotypes 2 and 6 (72.43%) were shown to have the most similarity in terms of codon usage. Unlike the results with respect to determining the similarity of codon usage, the phylogenetic analysis showed the closest resemblance and correlation between genotypes 1 and 4. The results also showed that HCV has a GC (guanine-cytosine) abundant genome structure and prefers codons with GC for translation. CONCLUSIONS Genotypes 1 and 4 demonstrated remarkable similarity in terms of genome sequences and proteins, but surprisingly, in terms of the preferred codons for gene expression, they showed the greatest difference. More studies are therefore needed to confirm the results and select the best approach for treatment of these genotypes based on their codon usage properties.

The high rate of hepatitis C virus (HCV) infection among transfusion related risk groups such as patients with inherited bleeding disorders highlighting the investigation on prevalent subtypes and their epidemic history among this group. In this study, 166 new HCV NS5B sequences isolated from patients with inherited bleeding disorders together with 29 sequences related to hemophiliacs obtained from a previous study on diversity of HCV in Iran were analyzed. The most prevalent subtype was 1a (65%), followed by 3a (18.7%),1b (14.5%),4(1.2%) and 2k (0.6%). Subtypes 1a and 3a showed exponential expansion during the 20th century. Whereas expansion of 3a started around 20 years earlier than 1a among the study patients, the epidemic growth of 1a revealed a delay of about 10 years compared with that found for this subtype in developed countries. Our results supported the view that the spread of 3a reached the plateau 10 years prior to the screening of blood donors for HCV. Rather, 1a reached the plateau when screening program was implemented. The differences observed in the epidemic behavior of HCV-1a and 3a may be associated with different transmission routes of two subtypes. Indeed, expansion of 1a was more commonly linked to blood transfusion, while 3a was more strongly associated to drug use and specially IDU after 1960. Our findings also showed HCV transmission through blood products has effectively been controlled from late 1990s. In conclusion, the implementation of strategies such as standard surveillance programs and subsiding antiviral treatments seems to be essential to both prevent new HCV infections and to decline the current and future HCV disease among Iranian patients with inherited bleeding disorders.

Iran has progressed significantly in control and treatment of patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections during recent 25 years. The view of the issue in the region mandate us to work more for medical tourism. I will present the data about our opportunity to have more people from our neighbors such as Iraq and Kuwait for medical purposes in field of hepatology here.

Context Direct acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus (HCV) infection, which is a major public health problem. Among the known DAAs, daclatasvir (DCV), an inhibitor of the non-structural 5A protein, has been used in combination with several drugs for treatment of infection with HCV of different genotypes under different conditions. We conducted a systematic review and meta-analysis of combination therapy with DCV. Evidence Acquisition We performed a systematic search in PubMed, Scopus, Science Direct and Web of Science with appropriate keywords for DCV. Studies that evaluated any regimen containing DCV and reported the sustained virological response (SVR) 12 weeks after therapy based on the HCV genotype, treatment duration and use of ribavirin (RBV) were included. The selected studies were considered for meta-analysis using STATA 11.0. Results We found six different regimens containing DCV: DCV/asunaprevir (ASV), DCV/ASV/beclubavir, DCV/pegylated interferon lambda or alpha/RBV with or without ASV, DCV/simeprevir, DCV/VX-135 and DCV/sofosbuvir (SOF). Most of these regimens were used for the treatment of HCV genotype 1 infections, and in most cases, treatment failure was noted in subtype 1a infections. Among all these regimens, DCV/SOF with or without RBV for 12 or 24 weeks was found to be an efficacious approach for treatment of different types of patients with infections with different HCV genotypes. Conclusions Among the treatment regimens containing DCV, DCV/SOF has the highest SVR rate for the treatment of infection with different HCV genotypes in different patient contexts; thus, this regimen shows promise for the treatment of HCV infections.

Context Patients with hepatic dysfunction suffer from many problems and associated complications in organs other than the liver. Therefore, it is very important to investigate the effects of different drugs in the treatment of these patients. Due to the high consumption of non-steroidal anti-inflammatory drugs (NSAIDs), studying the effects of these drugs in patients with hepatic dysfunction is particularly important. Evidence acquisition Research studies published from 1958 to 2014 were investigated in the present study. The literature search was conducted based on the following keywords: non-steroidal anti-inflammatory drugs (NSAIDs), liver dysfunction, cirrhosis, pharmaceutical complications, drug-induced liver injury (DILI), and similar words from reliable resources. In total, 63 articles and two books (out of 179 initially identified resources) were included in the study. Results In addition to significant hemostatic disorders and cardiovascular disorders, disorders of the renal, respiratory, and gastrointestinal systems, as well as disorders of the central nervous system, occur in patients with hepatic dysfunction. The various NSAIDs have different effects on different bodily systems. Therefore, the appropriate drug should be chosen based on both the condition of the disease and the severity of the dysfunction. Conclusions Due to the potential adverse effects of NSAIDs in patients with hepatic disease, their impact on all bodily systems should be emphasized when determining whether their use is necessary. Further, the appropriate medication should be selected after a careful assessment of the severity of the disease and any associated complications. It is logical that medicines should only be prescribed by a qualified physician.

Context: Hepatitis C virus (HCV) infection is a major public health issue worldwide, including Iran. The new direct-acting antiviral agents (DAAs) with high efficacy have changed the landscape of HCV treatment. This guideline provides updated recommendations for clinical management of HCV infection in Iran. Evidence Acquisition: The recommendations of this guideline are based on international and national scientific evidences and consensus-based expert opinion. Scientific evidences were collected through a systematic review of studies that evaluated efficacy and safety of DAA regimens, using PubMed, Scopus and Web of Science. Expert opinion was based on the consensus of Iran Hepatitis Scientific Board (IHSB) in the 3rd national consensus on management of Hepatitis C in Iran, held on 22nd of July 2016. Results: Pegylated Interferon alpha (PegIFN), Ribavirin (RBV), Sofosbuvir (SOF), Ledipasvir (LDV) and Daclatasvir (DCV) are currently available in Iran. Pre-treatment assessments include HCV RNA level, HCV genotype and resistance testing, assessment of liver fibrosis, and underlying diseases. In HCV genotype 1 and 4, DCV/SOF and LDV/SOF are recommended. In HCV genotype 2, SOF plus RBV and in HCV genotype 3, DCV/SOF is recommended. Additional care for underlying diseases should be considered. Conclusions: Affordable new HCV treatment regimens are available in Iran, providing an opportunity for HCV elimination. Recommendations provided in this current national guideline can facilitate evidence-based management of HCV infection.

The hepatitis B virus (HBV), a type of hepatitis viruses, can lead to morbidity and mortality in the world (1). Despite the progress occurred in antiretroviral therapy, the number of people who die due to chronic HBV infection or the number of cancer cases associated with hepatitis B are increasing (1). It is estimated that about 2 billion people worldwide have serologic evidence of hepatitis B, of which 240 million are chronic carriers and one of them die due to cirrhosis or hepatocellular carcinoma every year (2).

Background: There is growing evidence that deficiencies observed in the mitochondrial DNA (mtDNA) functions could play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We hypothesized that genetic variations in mtDNA could affect the mitochondrial function and contribute to the NAFLD susceptibility. Objectives: In this study, the possible association of the mtDNA copy number and 4,977-bp deletion levels with NAFLD susceptibility in a sample of Iranian population was evaluated. Methods: This case-control study included 43 NAFLD patients and 20 control subjects. Genomic DNA was extracted from fresh liver tissue samples by using a DNA isolation kit. The mtDNA copy number and mtDNA deletion levels were measured by quantitative real-time PCR and multiplex PCR. Results: The relative expression of mtDNA copy number was 3.7 fold higher in NAFLD patients than healthy controls (P < 0.0001). The results remained significant after adjustment for age, BMI, and gender (P = 0.02). In addition, the mtDNA copy number was 4.3 (P < 0.0001) and 3.2-fold (P < 0.0001) higher in nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) patients than healthy controls, respectively. Finally, the results showed that the 4,977-bp deletion is not detected in any of liver tissue samples obtained from the 20 control subjects whereas 8 out of 43 NAFLD patients (18.6%) showed the 4,977 -bp deletion in their liver tissues (P = 0.039). Conclusions: This study indicated an association between mtDNA content in the liver tissue and NAFLD susceptibility that may be a consequence of compensatory response to the cumulative exposures to oxidative damage.

Context Despite the great breakthroughs we have witnessed in the last 50 years in the prevention, diagnosis, and treatment of hepatitis B, we are still far from eradicating or even curing the disease. Achieving further progress in controlling this disease will not be possible without discovering the exact pathogenesis behind it. One prime suspect in the pathogenesis of various diseases is oxidative stress. This review will exclusively explore hepatitis B in the context of oxidative stress to obtain a more comprehensive clinical perspective on its pathogenesis and eventual medical therapy. Evidence acquisition We systematically searched PubMed, Google Scholar, Web of Science, EMBASE, and Scopus using an extensive list of keywords in the following three categories: 1) Hepatitis B and oxidation 2) Hepatitis B and antioxidant system 3) Effects of approved anti-hepatitis B drugs on redox status. All relevant articles were obtained and reviewed carefully after the exclusion criteria were deployed. Results There is great evidence indicating extensive oxidative stress occurs in hepatitis B. This oxidative stress takes place on multiple levels, including lipid peroxidation, DNA oxidation, protein oxidation, and reactive oxygen and nitrogen species production. However, there are also conflicting results with regard to antioxidant therapy and antioxidant status in hepatitis B, some of which may be explained by the concept of "compensatory gaps." Nevertheless, further studies are indicated to reach a more thorough judgment. Conclusions Despite the presence of vast oxidative stress in hepatitis B, antioxidant therapy is not always effective as a treatment strategy, especially considering that antioxidants can act as "double-edged swords" or antioxidants; if not used at the right time or place or in the right combination, these substances can easily become pro-oxidants. Therefore, several studies will be needed to determine suitable antioxidant therapies. We propose the "2-step Combined Antioxidant Adjuvant Therapy for hepatitis B (2CAAT Hep B)" as a new strategy for antioxidant adjuvant therapy. We also suggest developing an international platform and database for antioxidant adjuvant therapy in hepatitis B (IPAATH and IDAATH) to canalize this field of research in a standardized direction, especially when complexity is a problem.

Context The hepatitis C virus (HCV) is classified into seven genotypes and more than 100 subtypes. The treatment regimen, duration and efficacy of HCV therapy may vary according to the HCV genotype. Therefore, the HCV genotype should be determined prior to antiviral therapy. The objective of the current study was to review systematically all studies reporting the distribution of HCV genotypes in the countries that make up the Middle East. Evidence acquisition Articles were identified by searching electronic databases, including Scopus, PubMed and Google scholar, with timeline limits (articles published between 1995 and 2016). We carried out a systematic search regarding the distribution of HCV genotypes in Middle Eastern countries. Results A total of 579 studies were identified by the electronic search. Of these, a total of 187 were identified as eligible papers including 60,319 patients who were meta-analyzed for pooled distribution of HCV genotypes. In Turkey, Israel, Cyprus, and Iran, genotype 1 was the most prevalent HCV genotype with rates of 82% (95% CI, 82%-83%), 68% (95% CI, 67%-69%), 68% (95% CI, 59%-77%), and 55% (95% CI, 54%-55%), respectively. In Egypt, Iraq, Saudi Arabia, and Syria, HCV genotype 4 was the most common genotype with rates of 86% (95% CI, 85%-88%), 60% (95% CI, 56%-64%), 56% (95% CI, 54%-55%), and 57% (95% CI, 54%-61%), respectively. On the basis of adjusted data, HCV genotype 4 was the most prevalent genotype in the Middle East region, with a rate of 74.7% (95% CI, 73.4%-76%), followed by genotype 1 at 15.1% (95% CI, 14.1%-16%). Conclusions Our results showed that HCV genotype 4 is the most prevalent genotype in the Middle East region. However, HCV genotype 1 is the most prevalent among non-Arab countries in the region including Turkey, Iran, Cyprus, and Israel.

Background Chronic hepatitis C virus (HCV) infection is emerging as the leading cause of viral hepatitis-related liver disease in Iran. Objectives This study estimated the current and future disease burden of HCV infection in Iran and assessed the impact of various strategies in access to HCV treatment on reducing the disease burden. Materials and methods A modelling approach was used to estimate the size of HCV infected population, and disease progression from 2014 to 2030. Literature review and expert consensus informed the model parameters. Base case scenario assumed the currently utilized Interferon (IFN)-based treatment. Five other scenarios assumed utilizing IFN-free direct acting anti-viral regimens with 1, the base case diagnosis and treatment uptake; 2, restricting treatment to severe liver fibrosis; 3, treatment uptake being doubled; 4, stepwise increase in treatment uptake (doubled by 2017, quadrupled thereafter); 5, targeting at least 90% reduction in HCV infections by 2030. Results In 2014, an estimated 186,500 individuals are living with HCV infection in Iran (median age: 30 years). By 2030, this number will increase to 213,700, while three to four fold increase is expected in the case numbers of decompensated cirrhosis (DC, n = 620), hepatocellular carcinoma (HCC, n = 510), and liver disease death (n = 400), assuming the current diagnosis/treatment settings. As compared with the base case scenario, scenarios 1 and 2 will have a limited impact on HCV disease burden, while scenarios 3 and 4 will result in 45% - 49% decrease in the number of individuals living with HCV infection and 60% - 69% decrease in DC, HCC and liver disease deaths by 2030. For at least 90% reduction in HCV infections by 2030 (scenario 5), diagnosis and treatment rates should be increased to 12,000 and 9,000 individuals per year in 2016, respectively and to 24,000 and 18,000 individuals per year, respectively in 2018 onward. Conclusions An increasing burden of HCV-related liver disease is expected in Iran under the current diagnosis and treatment levels. Increased diagnosis and treatment uptake is required in combination with enhanced treatment efficacy to reduce the HCV burden. The relatively young age of the HCV infected population, provides an opportunity for timely interventions to avert the projected rising HCV disease burden in Iran.

Context: Hepatitis is a term used to describe any type of hepatitis inflammation. Screening for the virus antigen during pregnancy is mandatory in some parts of the world and is recommended in others. so that, most women are aware of and understand the disease if they have it when they are pregnant. Thus, the major concerns of these women are both the virus transmission to the fetus and the effects of hepatitis B on pregnancy outcome. Evidence Acquisition: According to a specific protocol, we searched in the Pub med, Scopus, ISI web of science from 1990 to February 2015 to find the original articles, which investigated the hepatitis B effects in pregnant women with normal singleton pregnancy who were previously diagnosed with inactive CHB or were incidentally found to be HBsAg positive in routine antenatal blood test. We included any cohort, case control and cross sectional studies if they had a healthy control group and reported one or more considered maternal or prinatal outcomes in pregnant women. Meta-analysis was performed with Review manager 5.4 and Stata 11 software. We assessed the effect size that was pooled odds ratio (OR) and 95% confidence intervals (CIs) using the random effects model. We explored statistical heterogeneity using the chi-squared (Chi2), I2 and tau-squared (Tau2) statistical tests. Results: From a total of 156 identified studies, 56 studies were chosen for a detailed review, and 18 studies which met the inclusion and exclusion criteria were included in the meta analysis. Among the included studies, the outcomes were small for gestational age (SGA) large for gestational age (LGA), intra uterine growth restriction (IUGR), fetal distress, fifth minutes apgar score, first minute Apgar score, low birth weight (LBW) and Fetal Macrosomia. Conclusions: In this study, hepatitis B had a cause effect on LGA and fetal Macrosomia. Among the other considered adverse pregnancy outcomes; it didn’t have any significant effect.

Background: Cancerous cells proliferate as fast as possible without a proper surveillance system. This rapid cell division leads to enormous mutation rates, which help a tumor establish. Objectives: This study evaluated the potential of inducing apoptosis using Noxa and Puma in a hepatocarcinoma cell line. Methods: The current study generated two recombinant lentiviruses, pLEX-GCN and pLEX-GCP, bearing Noxa and Puma, respec- tively. Transduction of both genes to hepatocarcinoma (HepG2) was verified using fluorescent microscopic analysis, western blot- ting, and quantitative real-time polymerase chain reaction (PCR). To evaluate the potential of Noxa and Puma to initiate apoptosis, a caspase-9 real-time, MTT assay, and a 4', 6-diamidino-2-phenylindole (DAPI) reagent were performed to stain apoptotic cells. Results: The data verified successful transduction to HepG2 and HEK293T. Higher relative expression of Noxa and Puma rather than the untransduced cell line showed these genes are expressed more in HepG2 in comparison to HEK293T. The results of the real-time PCR, MTT assay, and DAPI reagent illustrated that higher cells initiated apoptosis following Puma transduction rather than Noxa. Conclusions: In this approach, the suicide gene was transferred to transformed cells and ignited apoptosis to exterminate them. Puma is a more potent killer gene and has higher capabilities to start intrinsic apoptosis pathway.

Liver diseases caused by viral hepatitis infections have a negative impact on global health. Approximately 30 million people in the USA and 29 million people in the European Union suffer from chronic liver disease. There are many kinds of diseases of the liver, caused by viruses, such as hepatitis A, hepatitis B and hepatitis C, or by certain drugs and poisons including excessive alcohol consumption. Many herbal medicines are used in traditional medicine for their protective and therapeutic properties against liver diseases. Among their bioactive components, flavonoids have been found to be active against liver dysfunction and damage caused by liver diseases. Extensive evidences report that quercetin (QE), a major flavonol commonly found in apple, berries, onion, citrus fruits, cruciferous vegetables, tea, pepper, tomato, whole gain, cocoa and red wine, displays a wide range of healthy properties, including anti-oxidative, anti-inflammatory, anti-apoptotic and hepatoprotective activities against various hepatic ailments. This review aims to critically analyze the available literature regarding the hepatoprotective effects of QE with special emphasis on its mechanisms of actions. To provide a complete picture of QE, its distribution, chemistry, biosynthesis and bioavailability are reported. Overall, data in literature shows that QE appears to be a promising hepatoprotective compound.

Department of Obstetrics and Gynecology, Tehran University of Medical Sciences, Tehran, IR Iran Department of Anesthesiology and Critical Care, Iran University of Medical Sciences, Tehran, IR Iran Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran Tehran Hepatitis Center, Tehran, IR Iran Corresponding author: Seyed Moayed Alavian, Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran. Tel: +98-2188945186, Fax: +98-2188945188, E-mail: alavian@thc.ir

Dear Editor, Migraine, defined as a recurrent unilateral pulsatile headache, which is usually accompanied by nausea, vomiting, phonophobia, and photophobia, is a major cause of chronic headaches. It has been ranked the eight most disabling disorder, and its prevalence is higher in females (17% vs. 6%) (1). Hepatitis C virus (HCV) infection infects more than 170-million individuals worldwide and is as an important healthcare problem. According to published studies, the prevalence of HCV is less than 1% in the general population. A combination of ribavirin, an antiviral nucleoside analogue, and interferon is the most common treatment for chronic hepatitis C (2-5). This method of treatment is also used in occult hepatitis C infections, which is a chronic form (6). HCV treatment was reported to be associated with severe migraine attacks, with the source of the attacks attributed to ribavirin-related hemolytic anemia. Hemolytic anemia is a common and reversible side effect of ribavirin therapy, caused by the hemoglobin (Hb) level decreasing by at least 30 g/L in more than 50% of patients treated with this drug. About 7–10% of ribavirin-treated patients develop severe anemia, with a Hb level of 2 mg/dL or more in the Hb level 2 weeks after the start of treatment require special care (8). The ribavirin dose has to be reduced significantly more often in females than in males. Normally, females have lower baseline Hb levels. This may explain why females have a higher risk of hemolytic anemia then males. Older patients (≥ 55 years) are much more likely than younger patients (≤ 55 years) to require a dose reduction of ribavirin. The underlying reason for the increased prevalence of dose reductions among elderly people is unknown, but it may be associated with the presence of erythrocyte membrane anomalies and renal dysfunction among the elderly. A low baseline platelet count was reported to be another risk factor for the development of more severe ribavirin-induced anemia (2). A significant relationship was reported between the ribavirin dose per kilogram and the incidence of anemia. Anemia was observed to be more common in patients receiving > 12 mg/kg than in those receiving 2 g/dL within 2 weeks after starting the treatment, female sex, older age (≥ 55 years), receiving ribavirin of > 12 mg/kg, and a low baseline platelet count. Patients with these risk factors must receive more care for better management and prevention of developing migraine attacks during the treatment.

Background Vaccine-escaped hepatitis B virus (HBV) mutations occur within the "a" determinant area, which is located in the major hydrophilic region (MHR) of the hepatitis B surface antigen (HBsAg) protein. It is now well established that the common G145R mutation is highly capable of escaping from HBsAg immune recognition. However, the impacts of this mutation on the structure and immunogenic activity of HBsAg have been poorly investigated. Objectives The present study analyzed the effects of the G145R mutation on the structure and immunogenic activity of the HBsAg. Materials and methods Three-dimensional (3D) structure of HBsAg for both the wild-type and G145R mutant were predicted and refined using several web tools. After quantitative evaluations, the effects of the G145R mutation on the secondary and 3D structures of the HBsAg were investigated. In parallel, the immunogenic activity of the wild-type and mutant HBsAg was also analyzed using a ClusPro docking server as well as the IEDB web tool. Further analyses were performed via molecular dynamics (MD) simulations using the GROMACS v5.0.2 simulation package. Results The G145R mutation causes a considerable reduction in the immunogenic activity of the HBsAg through a conformational change in the HBsAg antigenic loops. This mutation inserts a new β-strand in the "a" determinant region of the HBsAg, leading to a reduced binding affinity to its monoclonal antibody, MAb12. The G145R mutation also increased the compactness and stability of the HBsAg by enhancing the rigidity of the "a" determinant. Conclusions These data will be beneficial for designing more advanced antibodies for the recognition of the HBsAg in diagnostics. In addition, the results of this study may assist in the design or development of more effective hepatitis B vaccines.

Background: Molecular studies have demonstrated that the hepatitis C virus (HCV) genotype and host genetics play predictive roles in the management of patients infected with HCV. Objectives: This study aimed to investigate the HCV genotype, core amino acid (aa) 70 substitution, and polymorphisms near the IFNL3 gene (including rs12979860 and rs8099917) among Iranian patients with chronic hepatitis C (CHC). Patients and Methods: In this cross-sectional study, the molecular profiles of the HCV genotype, core aa 70 substitution, and rs12979860 and rs8099917 polymorphisms and plasma HCV RNA levels were determined in 429 CHC patients including 141 hemophilic, 84 thalassemic, and 204 non-hemophilic, non-thalassemic patients. Results: The hepatitis C virus subtype 1a was the most common subtype in the study population. Core aa substitution Arg70Gln was strongly associated with cirrhosis (OR = 2.49; 95% CI = 1.13 - 5.50; P = 0.020). Core aa 70 substitutions were more frequently observed in patients with the HCV subtype 1b than in patients with any other HCV subtypes (P < 0.001). Core aa 70 substitutions were also more common in patients with the rs12979860 TT genotype than in patients with non-TT genotypes (17.3% vs. 8.5%, P = 0.022) and also in rs8099917 non-TT genotypes than in the TT genotype (14.0% vs. 7.0%, P = 0.026). The HCV genotypes and rs8099917 polymorphisms were correlated in which HCV subtype 1b was in favor of rs8099917 GG and HCV subtype 3a favored rs8099917 TT (P = 0.021). Furthermore, the rs12979860 TT and rs8099917 GG genotypes showed significantly lower HCV RNA levels than the other genotypes (P < 0.001). Conclusions: There is an as yet unexplained association between HCV and host parameters with unknown mechanisms in patients with chronic HCV infection. The assessments of core aa 70 substitution and polymorphisms near theIFNL3 gene could oer promis- ing steps to improve the management of patients with HCV.

Context Hepatitis C virus (HCV) infection is a major global public health issue. The Eastern Mediterranean regional office (EMRO) of the world health organization (WHO) seems to have one of the highest prevalence rates worldwide, with at least 21.3 million HCV-infected patients. Objectives The aim of the present study was to review systematically all epidemiological data related to the prevalence of HCV genotypes in infected patients in EMRO countries. Data sources A systematic search was conducted of peer-reviewed journals indexed in electronic databases (PubMed, Scopus, ISI, PakMediNet, and IMEMR, and Persian-specific databases including SID, Iran Medex, and MagIran). Study selection A systematic search was performed with temporal limits (papers published between January 2000 up to June 2015), regarding the prevalence and distribution of HCV genotypes in EMRO countries. Data extraction The prevalence rates of HCV genotypes were pooled by metan command in Stata 14. Statistical heterogeneity was explored using the I-square at the 5% significance level. Publication bias was assessed, graphically and statistically, by funnel plot and Begg and Egger tests. Results A total of 563 records were identified through the electronic search. Of these records, 134 studies comprising 67681 HCV-infected individuals were included in the meta-analysis. In Iran, subtype 1a was the predominant subtype with a rate of 42% (95% CI, 39 - 46), followed by subtype 3a, 35% (95% CI, 31 - 38). In Pakistan, Subtype 3a was the most common subtype with a rate of 56% (95% CI, 49 - 62), followed by subtype 3b, 10% (95% CI, 7 - 12). In Saudi Arabia and Egypt, genotype 4 was the most prevalent genotype with a rate of 65% (95% CI, 59 - 72) and 69% (95% CI, 36 - 100) respectively. In Tunisia and Morocco, subtype 1b was the most common subtype with a rate of 69% (95% CI, 50 - 88) and 32% (95% CI, 7 - 56) respectively. Conclusions The genotype distribution of HCV takes diverse patterns in EMRO countries. Genotypes 1 and 3 were predominant in Iran and Pakistan, while genotype 4 and 1 were the most common genotypes in the Middle East Arab countries and North African Arab countries. Understanding the genotypes of HCV can help policy makers in designing good strategies for treatment.

Context After the introduction of safe and highly effective hepatitis C virus (HCV) treatments, eradication of HCV in the next 20 years is the ultimate goal. Since 2011, the advent of first generation direct acting antivirals (DAAs) were started and followed by the introduction of a new wave of DAAs in 2013 which exhibit outstanding efficacy. It is obvious that the eradication of hepatitis C is not restricted to development of DAAs. Evidence Acquisition An electronic search of available literature published was conducted in all peer-reviewed journal indexed in PubMed, Scopus and Google scholar. The literature search was done among articles related treatment of hepatitis C with DAAs in different patient groups with mass screening of the patients and cost benefit of new treatments as main key words. Results There are major steps that should be taken to eradicate HCV, including (1) the development of screening strategies, particularly for groups such as intravenous drug users and recipients of blood or blood products before the introduction of HCV screening in donors; (2) the development of strategies to overcome issues with the high cost of recently introduced treatments; (3) special attention to special patient groups, such as HIV/HCV co-infection, hemophilia, thalassemia, hemodialysis, and liver-transplant patients; and (4) development of preventive strategies, such as the development of an efficient HCV vaccine, special attention to harm reduction in high-risk groups, and promotion of mass awareness of HCV. Conclusions The eradication of HCV will require significant governmental financial investment for screening, prevention, and treatment of infected patients. Although, we have a long way to eradication of HCV, the next steps could be including proper planning to patient finding, availability of new treatments to all patients and development of HCV prevention strategies such as vaccines.

Inducing interference patterns of shear wave is one of the proposed methods for reducing the frame rate in measuring wave speed during tissue elastography. Previously, the Nyquist rate must be met in order to provide an appropriate image for extracting the patterns with a reasonable accuracy. In this article we propose a technique based on image registration, and apply it to ultrasound images acquired before and after inducing the shear waves to estimate the amplitude of displacement. The displacement of the tissue is then used to form the interference pattern of shear waves. The method does not induce any restrictions on the time interval between images, so the tissue elasticity can be calculated independent of the imaging rate. The average error in measuring the elasticity of the simulated phantom is 13.7%.