Simultaneous Hepatitis C Virus Genotyping and Variant Detection in Patients with Thalassemia: A Single-Center Phylogenetic Study.

BACKGROUND: Hepatitis C virus (HCV) genotype distribution is different in various regions. A variety of strategies could be used to detect HCV genotypes and subtypes. The aim of the present study was to introduce a genotyping method by an in-house protocol that could be used to determine HCV drug-resistant variants and phylogeny studies. METHODS: Samples from 91 patients with thalassemia were used for HCV genotyping by Cobas 4800 platform, and 50 cases of 1a, 1b, and 3a genotypes underwent amplification and sequencing of NS5A and NS5B by using consensus primers via conventional reverse transcription-polymerase chain reaction (RT-PCR) method. An ABI 3730xl system used for direct sequencing. Raw sequences were analyzed by popular bioinformatics software MEGA6 and CLC workbench 5. Phylogenetic construction was drawn using 1000 replicates bootstrap by the neighbor-joining method. Multiple sequence alignment (MSA) was performed for mutation detection. RESULTS: Sequencing results of 50 HCV isolates subtypes 1a (31/45), 3a (15/22) and 1b (4/8) NS5A and NS5B genes showed there were 72 NS5A and 105 NS5B mutations. Moreover, 8 resistant associated substitutions (RASs) were identified in nine thalassemia cases by multiple sequence alignment (MSA) protein analysis. The phylogenetic tree construct drew confirmed by the Cobas HCV genotyping results. CONCLUSION: The phylogenetic analysis could be a useful tool for HCV genotyping in case of determining the drug-resistant substitutions; however, it is time-consuming and needs expert analysis and interpretation. This preliminary study in Iranian patients with thalassemia introduces specific conventional RT-PCR to find RASs to direct acting antivirals (DAAs) and subtype determination at the same time.

The Ability of the Framingham Steatosis Index (FSI) to Predict Non-alcoholic Fatty Liver Disease (NAFLD): A Cohort Study.

BACKGROUND: The utilization of indexes for the diagnosis of non-alcoholic fatty liver disease (NAFLD) can be valuable. This study was conducted to determine the ability of the Framingham steatosis index (FSI) to distinguish between people with NAFLD and those without and to predict people at risk of NAFLD to establish the need for lifestyle modifications in such individuals. METHODS: Our study was conducted in two phases from 2009-2010 (phase I) to 2016-2017 (phase II). A total of 4670 people in northern Iran were included. NAFLD was diagnosed by ultrasound. The FSI was calculated based on age, sex, hypertension, diabetes mellitus status, liver enzyme levels and triglyceride levels. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory and predictive abilities of the FSI. To remove the confounding effects of potential mediators, logistic regression was performed in which NAFLD was considered the outcome and the FSI as the predictor. RESULTS: The odds ratios of the FSI when the outcome was the prevalence of NAFLD in phase I and when the outcome was new cases of NAFLD from 2009-2010 to 2016-2017 were 4.909 (4.243-5.681) and 2.453 (2.024-2.972), respectively (P<0.001). The areas under the curve (AUCs) for the discriminatory and predictive abilities of the FSI were 0.8421 (95% CI: 0.8314-0.8527) and 0.7093 (95% CI: 0.6863-0.7322), respectively. CONCLUSION: The FSI has a strong ability to diagnose NAFLD while it has an acceptable ability to predict the occurrence of new cases of NAFLD.

Occult HCV Infection: The Current State of Knowledge.

CONTEXT: Occult HCV infection (OCI) is defined as the presence of HCV-RNA in hepatocytes and the absence of HCV in the serum according to usual tests. We aimed to define OCI and provide information about the currently available diagnostic methods. Then we focus on specific groups that are at high risk of OCI and finally investigate immune responses to OCI and the available treatment approaches. EVIDENCE ACQUISITION: PubMed, Scopus and Google Scholar were comprehensively searched with combination of following keywords: "occult", "hepatitis C virus" and "occult HCV infection". The definition of OCI, diagnostic methods, specific groups that are at high risk and available treatment approaches were extract from literature. An analysis of available articles on OCI also was done based on Scopus search results. RESULTS: OCI has been reported in several high-risk groups, especially in hemodialysis patients and subjects with cryptogenic liver disease. Furthermore, some studies have proposed a specific immune response for OCI in comparison with chronic hepatitis C (CHC). CONCLUSIONS: With a clinical history of approximately 11 years, occult HCV infection can be considered an occult type of CHC. Evidences suggest that considering OCI in these high-risk groups seems to be necessary. We suggest that alternative diagnostic tests should be applied and that there is a need for the participation of all countries to determine the epidemiology of this type of HCV infection. Additionally, evaluating OCI in blood transfusion centers and in patients who receive large amounts of blood and clotting factors, such as patients with hemophilia, should be performed in future projects.

Cost-effectiveness analysis of adding low dose ribavirin to peginterferon alfa-2a for treatment of chronic hepatitis C infected thalassemia major patients in iran.

BACKGROUND: The prevalence of hepatitis C in Iran is 1% and 18% in general population and thalassemia patients respectively. The cost effectiveness analysis of adding Ribavirin to Peginterferon alfa-2a (PEG IFN alfa-2a) as a combination treatment strategy of chronic hepatitis C in thalassemia patients in comparison with monotherapy could help clinicians and policy makers to provide the best treatment for the patients. OBJECTIVES: In this study we aimed to assess whether adding Ribavirin to PEG IFN alfa-2a is a cost effective strategy in different genotypes and different subgroups of 280 patients with chronic hepatitis C infection from the perspective of society in Iranian setting. PATIENTS AND METHODS: A cost effectiveness analysis including all costs and outcomes of treatments for chronic hepatitis C infected thalassemia major patients was conducted. We constructed a decision tree of treatment course in which a hypothetical cohort of 100 patients received "PEG IFN alfa-2a" or "Peg IFN alfa-2a plus Ribavirin." The cost analysis was based on cost data for 2008 and we used 9300 Iranian Rials (IR Rial) as exchange rate declared by the Iranian Central Bank on that time to calculating costs by US Dollar (USD). To evaluate whether a strategy is cost effective, one time and three times of GDP per capita were used as threshold based on recommendation of the World Health Organization. RESULTS: The Incremental Cost Effectiveness Ratio (ICER) for combination therapy in genotype-1 and genotypes non-1 subgroups was 2,673 and 19,211 US dollars (USD) per one Sustain Virological Response (SVR), respectively. In low viral load and high viral load subgroups, the ICER was 5,233 and 14,976 USD per SVR, respectively. The calculated ICER for combination therapy in subgroup of patients with previously resistant to monotherapy was 13,006 USD per SVR. Combination therapy in previously resistant patients to combination therapy was a dominant strategy. CONCLUSIONS: Adding low dose of Ribavirin to PEG IFN alfa-2a for treatment of chronic hepatitis C patients with genotype-1 was "highly cost effective" and in patients with low viral load and in previous monotherapy resistant patients was "cost effective."

Citation Analysis of Hepatitis Monthly by Journal Citation Report (ISI), Google Scholar, and Scopus.

BACKGROUND: Citation analysis as one of the most widely used methods of bibliometrics can be used for computing the various impact measures for scholars based on data from citation databases. Journal Citation Reports (JCR) from Thomson Reuters provides annual report in the form of impact factor (IF) for each journal. OBJECTIVES: We aimed to evaluate the citation parameters of Hepatitis Monthly by JCR in 2010 and compare them with GS and Sc. MATERIALS AND METHODS: All articles of Hepat Mon published in 2009 and 2008 which had been cited in 2010 in three databases including WoS, Sc and GS gathered in a spreadsheet. The IFs were manually calculated. RESULTS: Among the 104 total published articles the accuracy rates of GS and Sc in recording the total number of articles was 96% and 87.5%. There was a difference between IFs among the three databases (0.793 in ISI [Institute for Scientific Information], 0.945 in Sc and 0.85 GS). The missing rate of citations in ISI was 4% totally. Original articles were the main cited types, whereas, guidelines and clinical challenges were the least ones. CONCLUSIONS: None of the three databases succeed to record all articles published in the journal. Despite high sensitivity of GS comparing to Sc, it cannot be a reliable source for indexing since GS has lack of screening in the data collection and low specificity. Using an average of three IFs is suggested to find the correct IF. Editors should be more aware on the role of original articles in increasing IF and the potential efficacy of review articles in long term impact factor.

Low dose ribavirin for treatment of hepatitis C virus infected thalassemia major patients; new indications for combination therapy.

BACKGROUND: Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients. OBJECTIVES: Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far. PATIENTS AND METHODS: Two hundred eighty thalassemia patients with detectable HCV-RNA PCR (≥ 50 IU/mL) and liver histology consistent with chronic HCV infection were self-assigned to receive peginterferon alfa-2a (n = 81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n = 199). Treatment experienced patients were eligible for this study. RESULTS: Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51 % vs. 38 % P = 0.02). In multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95 % CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin < 2006 ng/mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load < 600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8 %). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin. CONCLUSIONS: According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.

The more publication, the higher impact factor: citation analysis of top nine gastroenterology and hepatology journals.

BACKGROUND: The impact factor (IF), as the most important criterion for journal's quality measurement, is affected by the self-citation and number of publications in each journal. OBJECTIVES: To find out the relationship between the number of publications and self-citations in a journal, and their correlations with IF. MATERIALS AND METHODS: Self-citations and impact factors of nine top gastroenterology and hepatology journals were assessed during the seven recent years (2005-2011) through Journal Citation Reports (JCR, ISI Thomson Reuters). RESULTS: Although impact factors of all journals increased during the study, five out of nine journals increased the number of publications from 2005 to 2011. There was an increase in self-citation only in the journal of HEPATOLOGY (499 in 2005 vs. 707 in 2011). Impact factors of journals (6.5 ± 3.5) were positively correlated with total number of publications (248.6 ± 91.7) (R: 0.688, P < 0.001). Besides, the self-citation rate (238.73 ± 195.317) was highly correlated with total number of publications in each journal (248.6 ± 91.7) (R: 0.861, P < 0.001). On the other hand, impact factor without self-citation (6.08 ± 3.3) had a correlation (R: 0.672, P < 0.001) with the number of published items (248.6 ± 91.7). CONCLUSIONS: The number of articles and self-citation have definite effects on IF of a journal and because IF is the most prominent criterion for journal's quality measurement, it would be a good idea to consider factors affecting on IF such as self-citation.

Lipid Profiles and Hepatitis C Viral Markers in HCV-Infected Thalassemic Patients.

BACKGROUND/AIMS: The distribution of blood lipids, glucose and their determinants in thalassemic patients with chronic hepatitis C virus (HCV) infection has rarely been investigated. Thus, we aimed to investigate the relationship between both liver histologic findings and viral markers and serum lipids in thalassemic patients chronically infected with HCV. METHODS: We enrolled 280 polytransfused thalassemic patients with chronic hepatitis C. HCV viral load was determined using the Amplicor test. Genotyping was performed using genotype specific primers. Fasting serum lipid, glucose, ferritin and liver function enzyme concentrations were measured. A modified Knodell scoring system was used to stage liver fibrosis and to grade necroinflammatory activity. Perls' staining was used to assess hepatic siderosis. RESULTS: Just one subject had total cholesterol >200 mg/dL, and 7% had triglycerides >150 mg/dL. The mean high-density lipoprotein cholesterol (HDL-C) and glucose levels were 37 and 104 (97-111) mg/dL, respectively. Viral markers, liver histological findings and aminotransferase activity were not associated with serum lipid levels. Serum triglycerides, total cholesterol and ferritin were independent risk factors for impaired glucose tolerance or diabetes in these patients. CONCLUSIONS: The majority of the patients had blood lipid levels (with the exception of HDL) within the defined normal range; viral and liver histological factors do not appear to play a significant role in changing the levels of serum lipids or glucose in these patients.

WITHDRAWN: Low dose ribavirin for treatment of HCV infected thalassemia major patients: New indications for combination therapy.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Peginterferon alpha-2a and ribavirin treatment of patients with haemophilia and hepatitis C virus infection: a single-centre study of 367 cases.

BACKGROUND/AIMS: Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti-HCV therapy but there is little information about safety and efficacy of peginterferon alpha-2a and ribavirin combination therapy in these patients. MATERIAL AND METHODS: In an open-label single-treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 microg of Pegasys and 800-1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR). RESULTS: Two hundred and twenty-five subjects [61%, 95% confidence interval (CI) 56-66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1-3.1), genotype non-1 OR=1.8 (95% CI 1.1-3.2), BMI<25 OR=2.1 (95% CI 1.3-3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1-3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow-up after treatment cessation. CONCLUSIONS: Peginterferon alpha-2a in combination with weight-based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non-1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non-1 are the major determinants of SVR achievement in these patients.

The frequency of hepatitis D virus in patients with hepatitis B in Iran: an increasing rate?

This study sought to determine the seroprevalence of the hepatitis D virus (HDV), the risk factors and its association with the severity of liver disease. Continuous patients at Tabriz and Tehran Hepatitis Clinics were enrolled during 2007-2008 in a cross-sectional study. Demographic data and possible risk factors for infection were recorded for all hepatitis B surface antigen positive patients. The blood samples of 847 patients infected with the hepatitis B virus were evaluated. The seroprevalence of HDV was 9.3%. This rate was significantly higher after reaching 40 years of age. The rate was 12.7% in patients with chronic hepatitis B and 4.7% in patients with in-active hepatitis B; the difference was statistically significant. A history of dental interventions and several trips abroad were good predictors of HDV infection in logistic regression. No significant difference in liver function tests was found. The seroprevalence of HDV was higher than in some other studies from Iran but a decrease was noted in younger age.

Distribution of hepatitis C virus genotype in Iranian multiply transfused patients with thalassemia.

BACKGROUND: Hepatitis C virus (HCV) infection is the most common transfusion-transmitted disease in multiply transfused patients worldwide. In this study, the aim was to investigate distribution of HCV genotypes in Iranian patients with thalassemia. STUDY DESIGN AND METHODS: Blood samples were received from 280 multiply transfused patients with thalassemia with chronic hepatitis C who were referred to us to start pegylated interferon-alpha plus ribavirin for duration of 48 weeks. HCV RNA viral load was detected using Amplicor test (Version 2, Roche Molecular Systems). Genotyping was performed by genotype-specific primers. RESULTS: HCV genotype distribution was 1 in 57%, 3 in 35%, 2 in 1%, and mixed in 4% (1 + 3 in 2.8%, 3 + 4 in 0.4%, mixed subtypes in 0.8%) cases. A total of 2.5% of isolates were nontypable. Genotype 1 was associated with higher rate of splenectomy and greater serum ferritin. CONCLUSION: Genotype 1 is the most frequently detected HCV genotype in Iranian patients with thalassemia and might cause more need for splenectomy and more severe iron overloading. Higher HCV viral load could be regarded as another risk factor for greater iron overloading.

Seroepidemiologic study of hepatitis B virus, hepatitis C virus, human immunodeficiency virus and syphilis infections in Iranian blood donors.

To determine the frequency of hepatitis B, hepatitis C, Human Immunodeficiency Virus (HIV) and syphilis infections in Iranian blood donors. The prevalence of serological markers of hepatitis B, hepatitis C, HIV and syphilis infections were evaluated in 318029 consecutive volunteer blood donors attending to Tehran blood transfusion service from March 2005 to March 2006. Those positive for hepatitis B surface antigen, anti-HCV, anti-HIV1/2 and VDRL (venereal disease research laboratory) reactivity were analyzed with a second independent HBsAg enzyme immunoassay (EIA) and neutralization assay; an additional independent anti-HCV EIA and HCV-RIBA assay; second independent anti-HIV1/2 test, HIV western blot and fluorescent Treponemal Antibody Absorbed (FTA-ABS), respectively. In 318029 participants, prevalence of positive HBsAg, HCV RNA, HIV western blot and FTA-ABS was 1684 (0.487%), 323 (0.093%), 11 (0.003%) and 19 (0.005%), respectively. In 1014 subjects randomly selected from these 318029 participants, besides standard interview, physical exam and routine serologic tests; anthropometric and biochemical were studies. In this selected group frequency of HBsAg was 3 (0.29, 95% CI: 0-0.64%); frequency of anti-HCV was 21 (2.07%), but it was (0.09%, 95% CI: 0-0.30%) by confirmatory HCV RNA test; frequency of HIV-Abl, 2 was 8 (0.78%), but it was 2 (0.19%, 95% CI: 0-0.48%) by confirmatory test; frequency of RPR was 0 (0%, 95% CI: 0-0.30%). Despite excluding subjects with high-risk behaviors by standard interview and physical examination, still a few asymptomatic hepatitis B, hepatitis C, HIV-infected subjects existed among volunteer blood donors with demographic and biochemical findings similar to non-infected ones.