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فهرست مطالب نویسنده:

shahin merat

  • Elham Jafari, Hossein Poustchi, Abbas Mohagheghi, Maryam Sharafkhah, Masoud Khoshnia, Alireza Nateghi, Shahin Merat, Reza Malekzadeh*
    Background

     While cardiovascular disease (CVD) polypills have demonstrated significant benefits in preventing CVD events by managing CVD risk factors and improving patient adherence, their effects on blood glucose levels, an important risk factor for CVD, remain unknown.

    Methods

     We analyzed data from the PolyIran-Liver trial, which involved 1,508 participants aged 50 and above. Of these, 787 were randomly assigned to receive a polypill (consisting of aspirin, atorvastatin, hydrochlorothiazide, and valsartan), while 721 received usual care as the control group over a five-year period. The aim was to determine whether there were any significant differences in fasting blood sugar (FBS) levels between the two groups at baseline, middle, and end of the study. The data analysis focused on three subgroups: participants with diabetes, those with metabolic syndrome (MetS) but without diabetes, and participants without diabetes or MetS.

    Results

     Of the total studied population, with a mean age of 59±6.7 years, 328(22%) were identified with diabetes, 371 (25%) with MetS but without diabetes, and 809 (54%) without diabetes or MetS. We observed a trend of rising FBS levels until month 30, followed by a subsequent decline at month 60. Participants in the polypill group exhibited lower FBS levels than the control group at both time points, with statistically significant differences in all three subgroups at month 30 and in the MetS-without diabetes at month 60 (mean difference: -9.3 mg/dl, 95% CI: 13.9 to -4.6).

    Conclusion

     The polypill used in this study may have the potential to delay the onset of diabetes in patients with MetS more effectively than in the general population. However, its beneficial effects on the blood sugar levels of diabetic individuals require further investigation.

    Keywords: Cardiovascular Disease, Diabetes Mellites, Fixed Dose Combination, Metabolic Syndrome, Polypill, Primary Prevention
  • Elham Jafari, Shahin Merat, Amir Anoushiravani, Amir Reza Radmard, Gholamreza Roshandel, Maryam Sharafkhah, Masoud Khoshnia, Alireza Nateghi, Abolfazl Shiravi Khuzani, Hossein Poustchi *, Reza Malekzadeh
    Background

    Metabolic dysfunction-associated fatty liver disease (MAFLD) is a rising global public health concern. It has been demonstrated that its prevalence and characteristics vary by region and racial/ethnicity. We aimed to investigate the prevalence of MAFLD and its characteristics among Turkmen and non-Turkmen ethnic groups in a multiethnic population region of Iran.

    Methods

    In this cross-sectional study, we analyzed baseline data for 1614 participants, aged above 50 years, from the PolyIran-Liver trial who were randomly selected from Gonabad city and determined the prevalence of MAFLD and its demographic and metabolic disorders for both the Turkmen and non-Turkmen ethnic groups. Multivariate binary logistic regressions were applied to identify MAFLD-associated factors for men and women separately for the Turkmen and non-Turkmen populations.

    Results

    The mean (SD) age of the participants was 59.1(6.7) years. Of the participants, 51.5% (n = 831) were men, and 52.9% (n = 854) were Turkmen. The prevalence of MAFLD among the overall study population was 39.8% (n = 614). It was more common among women (45.8% vs. 34.1% in men, P < 0.001), non-Turkmens (43.9% vs. 36.1% in Turkmens, P < 0.001), and at age 50-64 (41.5% vs.36.1% in age ≥ 65 P = 0.004). The fully adjusted multivariate analysis in sex strata exhibited an independent negative association between Turkmen ethnicity only among men but not among women. The increased waist circumference (WC) was the most common metabolic disorder, observed in more than 95.5% of patients with MAFLD (P < 0.001). Multivariate analysis in sex/ethnic strata with adjustment for potential confounders revealed an independent association of MAFLD with increased WC, insulin resistance, impaired fasting glucose/diabetes type 2, and high alanine aminotransferase (ALT) among women in both ethnic groups while with elevated triglyceride (TG) only among Turkmen and high body mass index (BMI) only among non-Turkmen women. Increased WC had the strongest independent association with MAFLD among women and the highest odds ratio (OR) with MAFLD in Turkmen women (OR: 6.10; 95% CI 1.56-23.86 vs. 4.80 in non-Turkmen women). Among men, MAFLD was independently associated with insulin resistance, high BMI, and high ALT in both ethnic groups and elevated TG only in non-Turkmen men (all P < 0.001). Insulin resistance had the strongest independent OR with MAFLD among men with similar size in both ethnic groups (4.68 [95% CI 2.56-8.55]) in non-Turkmen men and 4.37 (95% CI 2.27-8.42 in Turkmen men).

    Conclusion

    This study revealed the high prevalence of MAFLD with a sex and ethnic disparity in the middle-aged population of Gonabad city. Further research is needed to understand the factors contributing to the higher prevalence of MAFLD in this region, particularly in women. Furthermore, considering the diverse ethnic population of Iran, it is suggested that future investigations on the sex and ethnic aspects of MAFLD in the Iranian population be conducted to provide targeted prevention strategies better suited for the Iranian population.

    Keywords: MAFLD, NAFLD, Ethnicity, Genetic, Insulin Resistance, Iran
  • Sara Majd Jabbari*, Maryam Dibaie, Khadije Maajani, Shahin Merat, Sadaf Ghajarieh Sepanlou, Mohammad-Reza Rouini
    Background

    Sofosbuvir (SOF) is a revolutionary treatment for patients with hepatitis C virus (HCV). However, its efficacy and safety among patients with end-stage renal disease (ESRD) remains controversial. In this study, we examined the levels of SOF metabolite (GS-331007) (SOF-007) in human plasma of patients infected with HCV having ESRD using an optimized liquid chromatography-mass spectrometry (LC-MS) analytical method.

    Methods

    In this case-control study, 10 clinically confirmed cases and five controls were enrolled. SOF-007 was extracted from plasma using methanol precipitation. The limit of detection (LOD) for the drug and its metabolite were 0.85 and 2.3, respectively. Such a wide range of quantification in a period of separation time shorter than 3.0 minutes (run time) allowed monitoring of the plasma concentration of analytes up to 4 hours (pre-dialysis and post-dialysis) for 12 weeks in non-cirrhotic patients with HCV infection undergoing dialysis.

    Results

    SOF-007 in the plasma of HCV patients with healthy kidneys showed no cumulative effect. An analysis comparing patients with ESRD and healthy participants showed that their behaviour was similar, followed by dialysis with a relatively small cumulative effect.

    Conclusion

    The plasma concentrations of SOF-007 decreased significantly after the 4-hour period of dialysis compared with the plasma concentrations hemodialysis of pre-dialysis in HCV patients with ESRD.

    Keywords: Sofosbuvir, SOF Metabolites, UPLC-MS, MS, Validation, Hepatitis C, Hemodialysis
  • Zahra Mohammadi, Hossein Poustchi*, Azita Hekmatdoost, Arash Etemadi, Sareh Eghtesad, Maryam Sharafkhah, Delisha Stewart, Reza Ghanbari, George Edward Chlipala, Faraz Bishehsari, Shahin Merat, Reza Malekzadeh
    Background

    The main composition of intestinal microbiota in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients has not yet been elucidated. In this, case?control study, we  dentified differences of intestinal microbiota in male patients with NAFLD, presumed NASH, and healthy controls.

    Materials and Methods

    We  ompared gut microbial composition of 25 patients with NAFLD, 13 patients with presumed NASH, and 12 healthy controls. Demographic information as well as clinical, nutritional, and physical activity data was gathered.  tool and blood samples were collected to perform the laboratory analysis. The taxonomic composition of gut microbiota was assessed using V4  egions of microbial small subunit ribosomal Ribonucleic acid genes sequencing of stool samples.

    Results

    Firmicutes, Actinobacteria, and Bacteroidetes were the most frequently phyla in all groups. Our results revealed that Veillonella was the only genus with significantly different  mounts in presumed NASH patients compared with patients with NAFLD (P = 2.76 × 10?6, q = 2.07 × 10?4, logFC = 5.52).

    Conclusion

    This pilot study was the first study to compare gut microbial composition in patients with NAFLD and presumed NASH in the Middle East. Given the potential effects of gut microbiota on the management and prevention of NAFLD,  arger, prospective studies are recommended to confirm this study’s findings.

    Keywords: Gut microbiota, nonalcoholic fatty liver disease, presumed nonalcoholic steatohepatitis
  • Zahra Mohammadi, Faraz Bishehsari, Sahar Masoudi, Azita Hekmatdoost, Delisha A. Stewart, Sareh Eghtesad, Maryam Sharafkhah, Hossein Poustchi *, Shahin Merat
    Background

    Disruptions in sleep related to mealtime may contribute to gut microbial imbalances, and put individuals at higher risk for metabolic diseases. The aim of this pilot study was to investigate the relationships between late-night eating habits and sleep quality and duration, with gut microbiota (GM) profiles.

    Methods

    In this cross-sectional study, 36 men referred to a clinic were enrolled. In addition to demographic information, each participant completed questionnaires regarding medical history, physical activity, late-night eating habits, sleep quality and sleep duration. The scores from these questionnaires were used to categorize study participants into the following groups: sleep quality (good or poor), late-night eating (yes or no) and sleep duration (<7 or ≥7 hours). Five grams of stool was also obtained from each participant for GM profiling analysis by sequencing.

    Results

    The mean age of the study population was 42.1 ± 1.6 years. Firmicutes and Actinobacteria were the two dominant phyla present in all participant samples. Differences in the relative abundance of GM at each taxonomic rank between study groups were insignificant. Only Erysipelotrichales at the order level were found to be significantly different between individuals who had late-night eating habits and those who did not (P & q < 0.05). No other parameter demonstrated a significant difference in GM profiles of participants.

    Conclusion

    In this pilot study, we found Erysipelotrichales to be more abundant in individuals with late-night eating habits. Studies with higher sample sizes are warranted to better delineate the possible effects of time of eating on microbial composition.

    Keywords: Dietary behavior, Gut microbiome Mealtime, Sleeping pattern
  • Nazgol Motamed-Gorji, Sareh Eghtesad, Maryam Sharafkhah, Sahar Masoudi, Maryam Darvishian, Layli Eslami, Abdolsamad Gharavi, Masoud Khoshnia, Gholamreza Roshandel, Amaneh Shayanrad, Sanam Hariri, Shahin Merat, Hossein Poustchi*, Reza Malekzadeh*
    Background

    While hepatitis B virus (HBV) is the most prevalent cause of adult liver transplants in Iran, the mortality rates and leading causes of death in HBV patients are not well-understood. This study aimed to investigate all-cause and cause-specific mortality among HBsAg positive individuals in a large Iranian cohort.

    Methods

    The Golestan Cohort Study includes 50045 individuals aged 40–75 residing in Iran’s Golestan province, enrolled during 2004–2008. HBsAg test was performed at baseline. For the present study, individuals with hepatitis C coinfection were excluded. All-cause mortality was considered as the primary outcome. The association between HBsAg and different mortality causes was evaluated using Cox proportional hazard models. P value<0.05 was considered significant.

    Results

    The current study included 49667 participants. After 11.33 (median) follow-up years, there were 7,686 total deaths, with 635 deaths in the HBsAg positive group. In the multivariate Cox proportional hazard model, HBsAg positive individuals had higher all-cause (adjusted hazard ratio [aHR]=1.15, 95% CI: 1.06–1.24) and liver-related mortality risk (aHR=7.13; 5.19–9.79). Mortality from colorectal and pancreatic cancers was higher among male HBsAg positive participants (aHRs=2.41 and 2.22, respectively). Nevertheless, cardiovascular diseases (CVDs) and extrahepatic malignancies were the leading causes of death among both HBsAg positive and negative individuals, and liver-related deaths contributed to an overall 10% of deaths in HBsAg positive patients.

    Conclusion

    HBV is associated with significant mortality risk from different causes in Iranian adults. However, solely focusing on liver outcomes in Iranian HBV patients might result in overlooking non-liver events, especially CVD and extrahepatic cancers.

    Keywords: Cohort study, Hepatitis B virus, Iran, Mortality
  • Ayda Esmaeili, Mohssen Nasiri Toosi, Mohammad Taher, Shahin Merat, Jaleh Bayani, Zahra Fruzan. Karimian, Aysan Esmaeili, Bobak Moazzami, Soha Namazi *
    Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a negative impact on patient quality of life and potentially resulting in early liver transplants. Given the main role of the autotaxin enzyme in pruritus induced by CLD and the suppressive effects of melatonin on the expression of the autotaxin gene, this study was designed to evaluate the antipruritic effect of melatonin in patients with CLD. A double-blind, cross-over, randomized, placebo-controlled pilot trial was conducted on patients with CLD -induced pruritis. Patients were randomly assigned to two groups where they received melatonin 10-mg at night or placebo for 2 weeks. After a 2-week washout period, patients were then crossed over to the other group. The Visual Analog Scale (VAS) and the 12-Item Pruritus Severity Score (12-PSS) were used to assess patient response to therapy as the co-primary outcomes, while liver function tests were assayed too. Forty patients completed the study. The VAS score showed alleviation of 3.21 ± 2.24 (in pruritus) with melatonin (p-value <0.05). The study goal (a reduction of at least 20% in VAS) was achieved in 33 (82%) of study participants. In patients who received melatonin, the 12-PSS and Body Surface Area (BSA) affected by pruritus decreased on average 46.57% and 51.71%, respectively, with mood, sleep pattern and daily activity levels also demonstrating significant improvement (p-value < 0.05). Melatonin was found to be effective for managing pruritus in patients with CLD.
    Keywords: Melatonin, Pruritus, Chronic liver disease, Visual analog scale, 12-Item pruritus severity score
  • Sanam Hariri, Sabereh Davari, Zeinab Malekzadeh, Zahra Mohammadi, Sahar Masoudi, Abdullah Gandomkar, Sedigheh Amini Kafiabad, Mahtab Maghsoudloo, Shahin Merat, Hossein Poustchi, Fatemeh Malekzadeh*
    BACKGROUND

    Hepatitis B and C virus (HBV and HCV) infections rank among the most frequent infectious diseases with a rising worldwide burden. However, their epidemiology and risk factors are understudied in many regions, including Iran.

    METHODS

    This study was conducted as part of the Pars Cohort Study (PCS) in Valashahr district, Fars province (2012-2014). Participants received venipuncture for HBsAg and HCV antibody, followed by Polymerase Chain Reaction (PCR) testing. All infected people and their comparison groups completed a risk assessment questionnaire.

    RESULTS

    Overall, 9,269 people participated in the study; the majority were women and of Fars ethnicity. Prevalence of HBsAg and HCV antibody was 2.3% (n = 215) and 0.3% (n = 26), from whom 23% (n = 47) and 13% (n = 3) had indications for treatment, respectively. During follow-up, among HBsAg-positive individuals who were not on treatment, 62% tested negative for HBsAg, and in 2% HBV DNA had risen to treatment levels. Risk factors for HBV infection were illiteracy [OR = 3.43, 95% CI = 1.1, 10.3], and Turk ethnicity compared to Fars [OR = 1.58, 95% CI = 1.1, 2.3]. History of blood transfusion [OR = 2.00, 95% CI = 1.1, 3.5] and history of drug use [OR = 2.85, 95% CI = 1.1, 7.4] were associated with HCV infection, after adjustment.

    CONCLUSION

    Further epidemiological studies are needed to identify at-risk populations in different regions. Preventive interventions, including educational programs and transfusion safety strategies, are crucial for reducing the hepatitis burden.

    Keywords: Hepatitis B virus (HBV), Hepatitis C virus (HCV), Prevalence, Risk factors, Treatment, Iran
  • Fatemeh Malekzadeh, Abdullah Gandomkar, Zinab Malekzadeh, Hossein Poustchi, Mohsen Moghadami, MohammadReza Fattahi, Maryam Moini, Amir Anushiravani, Roozbeh Mortazavi, Shahrokh Sadeghi Boogar, Vahid Mohammadkarimi, Firoozeh Abtahi, Shahin Merat, Sadaf G. Sepanlou*, Reza Malekzadeh

    This corrects the article “Effectiveness of polypill for prevention of cardiovascular disease (PolyPars): protocol of a randomized controlled trial” published on 2020: Volume 23, Issue 08, Pages 548–556. Correction to: Arch Iran Med. 2020;23(8):548–556. doi: 10.34172/aim.2020.58. In the original version of this article, the recruitment period was wrongly reported to last from December 2014 to December 2015 in abstract and methods sections of the article. This is corrected into “from December 2015 to December 2016” in the PDF and HTML versions of the article. Also the “PolyIran” is changed to “PolyPars” in the last paragraph of the discussion section in the PDF and HTML versions of the article.

  • Fatemeh Malekzadeh, Abdullah Gandomkar, Zinab Malekzadeh, Hossein Poustchi, Mohsen Moghadami, Mohammad Reza Fattahi, Maryam Moini, Amir Anushiravani, Roozbeh Mortazavi, Shahrokh Sadeghi Boogar, Vahid Mohammadkarimi, Firoozeh Abtahi, Shahin Merat, Sadaf G. Sepanlou *, Reza Malekzadeh
    Background

    Cardiovascular diseases (CVDs) are the leading cause of death in Iran. A fixed-dose combination therapy (polypill) was proposed as a cost-effective strategy for CVD prevention, especially in lower-resource settings. We conducted the PolyPars trial to assess the effectiveness and safety of polypill for prevention of CVD.

    Methods

    The PolyPars trial is a pragmatic cluster randomized controlled trial nested within the Pars Cohort Study. Participants were randomized to an intervention arm and a control arm. Participants in the control arm received minimal non-pharmacological care, while those in the intervention arm received polypill in addition to minimal care. The polypill comprises hydrochlorothiazide 12.5 mg, aspirin 81 mg, atorvastatin 20 mg, and either enalapril 5 mg or valsartan 40 mg. The primary outcome of the study is defined as the first occurrence of acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, sudden cardiac death, new-onset heart failure, coronary artery revascularization procedures, transient ischemic attack, cerebrovascular accidents (fatal or non-fatal), and hospitalization due to any of the mentioned conditions. The secondary outcomes of the study include adverse events, compliance, non-cardiovascular mortality, changes in blood pressure, fasting blood sugar, and lipids after five years of follow-up.

    Results

    From December 2014 to December 2015, 4415 participants (91 clusters) were recruited. Of those, 2200 were in the polypill arm and 2215 in the minimal care arm. The study is ongoing. This trial was registered with ClinicalTrials.gov number NCT03459560.

    Conclusion

    Polypill may be effective for primary prevention of CVDs in developing countries.

    Keywords: Cardiovascular prevention, Non-communicable disease risk factors, Polypill
  • Javad Moayedi, Tayebeh Hashempour *, Zahra Musavi, Behzad Dehghani, Zahra Hasanshahi, Shahin Merat

    We aimed to investigate the association of pretreatment host and/or viral related factors with sustained virological response (SVR) rate in chronic hepatitis C (CHC) infected patients. This cohort study was performed on 200 IFN-naïve Iranian CHC patients who were treated with pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV). Pretreatment levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood sugar (FBS), HCV load and genotype were determined and the pattern of changes was monitored throughout the course of treatment. The baseline FBS value in the non-responder group was significantly higher than that of the SVR group. The SVR group showed a rapid and continuous decline of ALT/AST activity from the beginning of the treatment, while the ALT level was fluctuating in non-responder and relapse groups. Persistent normalization of transaminases during combination antiviral therapy was significantly associated with SVR rate. Besides, age and FBS level had the greatest impact on SVR.

    Keywords: Hepatitis C virus (HCV), Sustained virological response, Predictive marker, Transaminase
  • Shadi Kolahdoozan, Babak Mirminachi, Sadaf G. Sepanlou, Reza Malekzadeh, Shahin Merat, Hossein Poustchi *
    BACKGROUND

     Measuring serum alanine aminotransferase (ALT) enzyme is a routine clinical test commonly used to evaluate abnormalities in the body in general, and in the liver function in particular. Higher ALT levels are associated with some metabolic disorders. The upper limit normal (ULN) is considered as a reliable threshold for the definition of high ALT.

    OBJECTIVES

    To assess the existing evidence on the ULN for ALT in the general population.
    DATA SOURCE: PubMed (Medline), EMBASE, Scopus, and Web of Science (ISI) were searched using a specified search strategy.

    ELIGIBILITY CRITERIA

     We collected documents published from 1980 to 2018 in the English language, focusing on human samples at the population level and extracted the data after qualitative evaluation.

    METHODS

    We conducted this study in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. We used specific search terms and their combinations to find documents from relevant databases. We used a snowballing approach to find documents not captured in the main phase of the search. Two authors separately conducted the search, screened the articles, and selected documents that were qualified for data extraction based on the defined inclusion criteria. Finally, data extraction was conducted by two authors using PRISMA checklist. Reported ULNs for ALT and 95% confidence intervals (CIs) were documented in previously developed datasheets.

    RESULTS

    Out of 15242 studies, 47 articles were included for data extraction and analysis. Data were sparse and lacked the consistency to precisely estimate ULN for serum ALT. The ULN of ALT was significantly diverse across various geographical locations and sexes. The lowest value of ULN for ALT was 19 IU/L in Chinese children (age range: 7 to < 10 years), and the highest value of ULN for ALT was 55 IU/L in children from Ghana aged < 5 years. LIMITATIONS: The main limitation of the current systematic review was the scarcity of the reported measures for ULN of ALT.

    CONCLUSION

     Based on the results of the current systematic review, it is suggested that the normal range of ALT be redefined, but this redefinition should be done according to the localized data. In order to redefine the ULN for ALT, regional differences, methods used in ALT measurements, and ULN determination should be considered.

    Keywords: Alanine Transaminase, Alanine Aminotransferase, SGPT, ALT, Liver Enzymes
  • Shadi Kolahdoozan, Sadaf G. Sepanlou, Elaheh Shaker, Ameneh Shayanrad, Reza Malekzadeh, Shahin Merat*, Hossein Poustchi
    Background

    It is increasingly common to collect and store specimens for future unspecified research. However, the effects of prolonged storage on the stability and quality of analytes in serum have not been well investigated. We aimed to determine whether the stability of liver enzymes extracted from frozen bio-samples stored at the baseline is affected by storage conditions.

    Methods

    A total of four liver enzymes in the sera of 400 patients were examined following storage. After deter-mining the baseline measurements, the serum of each patient was aliquoted and stored at −70°C for three and six months, as well as one, two, and five years after collecting the original sample. The percent change from baseline measurements was calculated both statistically and clinically. Linear models were also used to correct the results of the samples based on the time they were frozen.

    Results

    In almost all samples, liver enzymes were detectable until two years after the baseline, while in a signifi-cant proportion of samples, enzymes were not ultimately detectable five years after the baseline. Linear regression analysis on log-transformed levels of enzymes shows that the performance is acceptable until one year after the baseline. The performance of the prediction model declines substantially two and five years after the baseline, except for GGT.

    Conclusion

    Long-term storage of serum samples significantly decreases the concentration of the liver enzymes from the baseline, except for GGT. It is not recommended to store samples for more than two years, as liver en-zymes are not detectable afterwards

    Keywords: Enzymes, Liver, Storage, Temperature, Time
  • Zahra Mohammadi, Hossein Poustchi, Nazgol Motamed Gorji, Sareh Eghtesad, Azita Hekmatdoost, Parastoo Saniee, Shahin Merat*
    Background

    With the increasing prevalence of obesity, non-alcoholic fatty liver disease (NAFLD), has become a frequent cause of chronic liver disease, often leading to cirrhosis. In recent decades, gut microbiota have been evaluated as an effective factor in NAFLD pathogenesis, causing steatohepatitis by involving the host immune system. The aim of this study is to evaluate gut microbiota dysbiosis in NAFLD/NASH patients in comparison to healthy controls.

    Methods

    We conducted a systematic search of published studies that have examined the composition of gut microbiota in relation to NAFLD. PubMed, Scopus and ISI Web of Science were searched. After the exclusion of irrelevant studies, 15 eligible studies were included and summarized.

    Results

    Overall, some studies reported the composition of microbiota at the phyla level, while others reported them at smaller subgroups; the results of studies were contradictory in some cases.

    Conclusion

    Overall, study findings indicate a relationship between microbial composition and NAFLD. Study methods and sequencing techniques influenced these results.

    Keywords: Fecal microbiota, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis
  • Mahdi Nalini, Maryam Sharafkhah, Hossein Poustchi, Sadaf G. Sepanlou, Akram Pourshams, Amir Reza Radmard, Masoud Khoshnia, Abdolsamad Gharavi, Sanford M. Dawsey, Christian C. Abnet, Paolo Boffetta, Paul Brennan, Masoud Sotoudeh, Arash Nikmanesh, Shahin Merat, Arash Etemadi, Ramin Shakeri, Reza Malekzadeh*, Farin Kamangar*
    Background
    It is unclear which anthropometric obesity indicator best predicts adverse health outcomes. This study aimed to investigate the association of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), and hip-adjusted WC with all-cause and cardiovascular mortality.
    Methods
    50045 people aged 40–75 (58% women, median BMI: 26.3 kg /m2 ) participated in the population-based Golestan Cohort Study. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for the association of obesity indicators with mortality. We also examined the association of these indicators with intermediate outcomes, including hypertension, blood glucose, dyslipidemia, carotid atherosclerosis, nonalcoholic fatty liver, and visceral abdominal fat.
    Results
    After a median follow-up of 10.9 years (success rate: 99.1%), 6651 deaths (2778 cardiovascular) occurred. Comparing 5th to the 1st quintile, HRs (95% CIs) for all-cause and cardiovascular mortality were 1.12 (1.02–1.22) and 1.59 (1.39–1.83) for BMI, 1.16 (1.07–1.27) and 1.66 (1.44–1.90) for WC, 1.28 (1.17–1.40) and 1.88 (1.63–2.18) for WHtR, 1.44 (1.32–1.58) and 2.04 (1.76–2.36) for WHR, and 1.84 (1.62–2.09) and 2.72 (2.23–3.32) for hip-adjusted WC, respectively. Hip-adjusted WC had the strongest associations with the intermediate outcomes.
    Conclusion
    Indicators of visceral adiposity (e.g., hip-adjusted WC) were much stronger predictors of overall and cardiovascular mortality than were indicators of general adiposity (e.g., BMI). The full-strength effect of visceral adiposity becomes apparent only when both WC, as a risk factor, and hip circumference, as a protective factor, are individually and simultaneously taken into consideration.
    Keywords: Body mass index, Cardiovascular, Hip circumference, Mortality, Obesity, Waist circumference
  • Fatemeh Kiaee, Naiimeh Tavakolinia, Leila Moradi, Samaneh Delavari, Kosar Abouhamzeh, Shiva Bayat, Pardis Anvari, Seyed Alireza Mahdaviani, Mohammad Nabavi, Shahin Merat, Fariborz Zandieh, Nima Parvaneh, Reza Malekzadeh
    Background/ objectives

    Primary antibody deficiencies (PADs) are the most common inherited immunodeficiencies, which can present wide clinical presentation including susceptibility to bacterial infections and gastric adenocarcinoma. Since Helicopter pylori (H.pylori) infection is associated with immune dysregulation and an increased risk of gastric carcinogenesis, we evaluated the prevalence of HP infection in patients with different forms of PAD.

    Methods

    Thirty-seven patients with common variable immunodeficiency (CVID), 23 patients with X-linked agammaglobulinemia (XLA), and eleven patients with hyper IgM syndrome (HIgM, age range 8-25; 47 males and 24 females) were screened for H.pylori infection by Urea breath test (UBT) and H.pylori stool antigen (HPSA). Subsequently, an upper gastrointestinal endoscopy was conducted only for patients who had UBT and HPSA positive results due to an established gastrointestinal indication.

    Results

    Although almost all patients were under prophylactic antibiotic therapy, H.pylori infection was detected in 28% (n=20) of the patients; among different forms of PAD, 29% (n=11) of CVID patients, 30% (n=7) of XLA, and 18% (n=2) of HIgM patients were infected. Among patients with H.pylori infection, the rate of parasite infections was higher, while the prevalence of autoimmunity and autoinflammatory disorders increased in patients without H.pylori infection.

    Conclusions

    Despite regular immunoglobulin replacement therapy and antibiotic prophylaxis, one-fourth of PAD patients had a persistent H.pylori infection though without severe gastrointestinal manifestations. Long-term follow-up of these selected patients is essential to evaluate its association with gastric cancers.

    Keywords: Ataxia telangiectasia, immune deficiency, specific antibody response, anti-peptide anti-body, polypeptide vaccine, humoral immune defect
  • Luma Al, Bayati, Bahar Nayeri Fasaei*, Shahin Merat, Alireza Bahonar
    Background
    The normal colonic microbiota is associated with the etiology of ulcerative colitis (UC). Several bacterial species are associated with the initiation and amplification of disease process. However, the etiology and mechanism of UC are poorly understood. The present study aimed to investigate, characterize, and compare the main composition of the mucosa-associated intestinal microflora in colonoscopic biopsy specimens of UC and non-UC patients.
    Methods
    Aerobic and facultative-anaerobic mucosa-associated bacteria were isolated and diagnosed from colonoscopic biopsy specimens of 40 UC patients and 40 patients without UC. Patients were selected as control from the same centers and colonoscopy was carried out for other reasons (mainly colorectal screening). Isolation and characterization for aerobic and facultative-anaerobic intestinal bacteria were carried out by conventional culture techniques. DNA extraction from biopsies and polymerase chain reaction (PCR) amplification of bacterial 16S rRNA with gene-targeted and species-specific primers was performed for detection of anaerobic bacterial species.
    Results
    Several species of mucosa-associated aerobic and facultative anaerobic bacteria were found in biopsy specimens and there were no significant differences between UC patients and non-UC patients. Our investigation for detection of the anaerobic intestinal flora showed Faecalibacterium prausnitzii, Prevotella, and Peptostreptococcus productus were the predominant microflora in controls and have significant differences (P = 0.002, 0.025 and 0.039, respectively).
    Conclusion
    This is the first investigation of the intestinal mucosa-associated microflora in patients with UC in Iran. These results, although limited by sample size, allow a better understanding of changes in mucosa-associated bacterial flora in these patients, showing that decrease of Faecalibacterium prausnitzii, Provetella, and Peptostreptococcus productus in the intestinal tract may translate into a reduction in the important role of this beneficial bacterial species, which can lead to reduced protection of the gut mucosa and UC development.
    Keywords: Inflammatory bowel disease, Polymerase chain reaction, Ribosomal RNA, Ulcerative colitis
  • جواد مویدی*، طیبه هاشمپور، زهرا موسوی، مهرداد حلاجی، خانم فرزانه قصابی، ارغوان حاج شیخ الاسلامی، شاهین مرآت
    مقدمه
    درمان عفونت مزمن ویروس هپاتیت C (Hepatitis C virus; HCV) با استفاده از ترکیب دارویی اینترفرون آلفا(Interferon-α IFN-α) و ریباویرین(Ribavirin; RBV) صورت می گیرد. عوامل مختلفی در میزان پاسخ به درمان بیماران آلوده به HCV نقش دارند که ژنوتیپ و میزان بار ویروس، سن، نژاد، چاقی، مقاومت به انسولین، میزان فیبروز و پلی مورفیسم های ژن اینترلوکین 28B (Interleukin 28B; IL-28B) مهم ترین آن ها هستند. در سال های اخیر مشخص شده است که چندین پلی مورفیسم تک نوکلئوتیدی(Single nucleotide polymorphism; SNP) در نزدیکی ژنIL-28B با میزان پاسخ به درمان ترکیبی در ارتباط می باشد که از میان فاکتورهای پیشگویی کننده درمان، پلی مورفیسم های IL-28B در رسیدن به پاسخ پایدار ویروسی نقش مهم تری را نسبت به بقیه ایفا می کنند. در این مطالعه فراوانی ژنوتیپی پلی مورفیسم نقطه rs8099917 ژن اینترلوکین 28B در دو گروه افراد ایرانی سالم و آلوده به هپاتیت C از تهران بررسی شده است.
    مواد و روش ها
    فراوانی ژنوتیپی پلی مورفیسم نقطه rs8099917 در 105 فرد سالم و 105 فرد آلوده به HCV که در فاز مزمن بیماری قرار داشتند با استفاده از تکنیک PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) بررسی شد و نتایج به دست آمده توسط نرم افزار SPSS vol.15 و آزمون χ2 مورد بررسی و تجزیه و تحلیل آماری قرار گرفت.
    یافته های پژوهش: فراوانی ژنوتیپی این پلی مورفیسم در افراد سالم 1=GG، 7/25=GT و 3/73=TT درصد و در افراد آلوده به هپاتیت C نیز 1/58=GT و 9/41=TT درصد است. ژنوتیپ GG در افراد آلوده به HCV تشخیص داده نشد.
    بحث و نتیجه گیری
    در این مطالعه فراوانی ژنوتیپ های نقطه پلی مورفیسم rs8099917 بین دو جمعیت سالم و آلوده به HCV ایرانی از اختلاف معنی داری برخوردار است و فراوانی ژنوتیپ مطلوب TT در گروه افراد سالم بیشتر است.
    کلید واژگان: ویروس هپاتیت C، اینترلوکین 28، PCR، RFLP، پلی مورفیسم
    Javad Moayedi*, Tayebeh Hashempour, Zahra Musavi, Mehrdad Hallaji, Farzaneh Ghasabi, Arghavan Haj-Sheykholeslami, Shahin Merat
    Introduction
    Combination of interferon-alpha (IFN-α) and Ribavirin (RBV) drugs is used for treatment of hepatitis C virus (HCV) chronic infection. Various factors play role in the response rate of HCV infected patients to treatment. HCV genotype along with viral load, age, race, obesity, insulin resistance, fibrosis and interleukin 28B gene (IL-28B) polymorphisms are considered the most important ones. In recent years, it has been claimed that some polymorphisms close to IL-28B gene play a significant role in response to combined therapy among which IL-28B polymorphisms have a more important role in sustained virological response (SVR). In this study, frequency of genotypes of rs8099917 polymorphism of interleukin 28B gene in 2 groups of Iranian healthy individuals and HCV infected patients living in Tehran was compared.
    Materials and Methods
    Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to compare the frequency of genotypes of rs8099917 polymorphism between 105 healthy individuals and 105 chronic HCV infected patients. The results were analyzed with SPSS version 15 using χ2 test.
    Findings: The genotype frequency of this polymorphism in the healthy individuals was demonstrated as GG: 1%, GT: 25.7% and TT: 73.3%, while in HCV infected patients, it was shown as GT: 58.1% and TT: 41.9%.. No GG genotype was detected in the patients infected with HCV.
    Discussion &
    Conclusion
    Our investigation came to the conclusion that a significant difference existed between the 2 groups of Iranian healthy and HCV infected individuals regarding the frequency of rs8099917 genotypes and frequency of favorable TT genotype, because it was higher among the healthy individuals than that of the patients infected with HCV
    Keywords: hepatitis C virus_interlukin_28_PCR_RFLP_rs8099917 polymorphism_Tehran
  • Tayebeh Hashempoor, Amir Mohammad Alborzi, Javad Moayedi, Mehdi Ajorloo, Taravat Bamdad, Amir Houshang Sharifi, Jean Pierre Lavergne, Arghavan Haj-Sheykholeslami, Shahin Merat *
    Background
    Hepatitis C virus (HCV) causes one of the major chronic liver diseases (CLD). Hepatitis C virus- core encoding sequence possesses an overlapping open reading frame (ORF) that expresses a protein called F or core.
    Objectives
    The current study aimed at assessing the presence and titer of anti-core antibody (Ab) in 70 Iranian patients infected with HCV-1a, responder and non-responder groups, under combination therapy with pegylated interferon-α (PegIFN-α) plus ribavirin (RBV) using an enzyme-linked immunosorbent assay (ELISA).
    Methods
    In the current cohort study, HCV-1a core gene was amplified and cloned into vector followed by expressing in Escherichia coli and then, purified by ion exchange chromatography. The antibody titer of patients was evaluated before, during (12, 24, and 48 weeks), and 6 months after the end of therapy (ETR).
    Results
    The seroprevalence of anti-core Ab was 75.7% in pretreatment sera. The combination therapy could induce a decline in the level of anti-core Ab in both groups of responders and non-responders. These changes were significant only in the responders (P = 0.003). The seroprevalence of anti-core Ab had no correlation with the outcome of treatment.
    Conclusions
    According to the current study results, HCV core protein elicit a specific antibody response other than the anti-core protein antibodies. The current study data also suggested that the level of anti-core antibody might be affected by the combination therapy and associated with sustained virological response (SVR). The data implied that the declining trend of anti-core Abs during the treatment might be an alternative representation of the therapeutic response in Iranian population infected with HCV.
    Keywords: Hepatitis C Virus_Core+1_Sustained Virological Response
  • Hamideh Salimzadeh, Faraz Bishehsari, Catherine Sauvaget, Mohammad Amani, Gholamreza Hamzehloo, Ali Nikfarjam, Shahin Merat, Alireza Delavari*, Reza Malekzadeh
    Background
    Colorectal cancer (CRC) is the third most common cancer in Iran, where there is no mass screening for the disease yet. We aimed to measure the feasibility of a pilot CRC screening program based on fecal immunochemical test (FIT) in Iranian population and the implications for scaling-up at the national level.
    Methods
    A single quantitative FIT was offered by health navigators to individuals aged between 45 and 75 years in primary health centers in rural and urban areas in Tehran. Participants who had a positive FIT were referred for colonoscopy.
    Results
    A total of 1044 asymptomatic average-risk individuals were enrolled. The mean age (SD) was 54.1 ± 7.0 years and nearly 63.0% (n = 657) were female. Only a small fraction of the participants had a prior screening practice (2.2%) and were aware of colon cancer (13.7%). In sum, 1002 returned the FIT kit, of whom the stool sample was unsatisfactory for testing in six participants (0.6%). The FIT uptake was 96.0%, positivity rate was 9.1% and the detection rates were 11.9% for adenomas and 7.1% for advanced adenomas. No cancer was detected. The positive predictive value (PPV) of the FIT was about 17% for any colonic neoplasms.
    Conclusion
    This is the first study that reports minimal quality metrics within a CRC screening process. FIT modality as a test of choice for colon cancer screening in average-risk people is a safe and highly acceptable method of screening in Iranian people. The results of the current study may not be limited to Iranians, and could have implications to other developing countries with similar trends of CRC epidemic.
    Keywords: Colorectal cancer, feasibility studies, patient navigation, population screening
  • Behzad Hajarizadeh *, Bita Mesgarpour, Mohammad Javad Nasiri, Seyed Moayed Alavian, Shahin Merat, Hossein Poustchi, Reza Malekzadeh, Abbas Sedaghat, Ali Akbar Haghdoost
    Context: Accurate and updated data describing hepatitis B virus (HBV) epidemiology is crucial for development of national policies to control HBV infection in each country. This study was conducted to estimate the prevalence of HBV infection and exposure in Iran, using the available provincial data.
    Methods
    MEDLINE, Web of Science, Scopus, Google Scholar, and Scientific Information Database were searched for studies assessing the prevalence of hepatitis B surface antigen (HBs Ag) or hepatitis B core antibody (anti-HBc Ab) among the general population between 2006 and 2016 in at least one city of Iran. National prevalence was estimated by two methods. Method 1 used only prevalence estimates of provinces with available survey data. In method 2, all provinces were classified based on the risk of HBV infection among blood donors. HBV prevalence in provinces with missing data was extrapolated from the provinces with available data, and with comparable risk of HBV infection among blood donors. In both methods, national prevalence was estimated using pooled provincial prevalence estimates, weighted by the province population size.
    Results
    Thirteen studies from 12 provinces were included. The prevalence of HBs Ag and anti-HBc Ab varied markedly across provinces. Provincial HBs Ag prevalence ranged from 0.76% to 5.10% (I-square = 91.7%) and provincial anti-HBc Ab prevalence ranged from 4.17% to 36.90% (I-square = 99.3%). Using method 1, the national prevalence of HBs Ag and anti-HBc Ab was estimated as 1.84% (95%CI: 1.61%, 2.09%), and 13.59% (95%CI: 12.92%, 14.29%), respectively. Using method 2, the national prevalence of HBs Ag was estimated as 1.79% (95% uncertainty range: 1.67%, 1.91%), equating to 1,347,000 (1,253,000 - 1,434,000) individuals living with chronic HBV infection in Iran. The prevalence of HBs Ag and anti-HBc Ab was higher among men compared to women.
    Conclusions
    HBV prevalence in Iran is low, and has decreased over past decades. However, the risk of HBV infection varies across provinces with some provinces having high HBV prevalence. More detailed data of the HBV epidemiology and transmission in provinces where HBV infection is endemic could support designing the appropriate interventions to control HBV epidemics.
    Keywords: Hepatitis B, Prevalence, Iran, HBs Ag, Anti, HBc Ab, Epidemiology, Systematic Review
  • Mahmood Naderi, Abdolreza Pazouki, Ehsan Arefian, Seyed Mahmoud Hashemi, Fatemeh Jamshidi Adegani, Omid Gholamalamdari, Sara Soudi, Kayhan Azadmanesh, Siamak Mirab Samiee, Shahin Merat, Mohammad Gholami Fesharaki, Mahdieh Mondanizadeh, Mohammad Vasei *
    Background
    Expression of miR-122 is highly specific to hepatocytes of the liver. This miRNA is involved in lipid hemostasis of the tissue; however, there is no comprehensive understanding of its function in lipid hemostasis.
    Materials And Methods
    Since hepatocytes are responsible for part of Triacylglycerol (TAG) synthesis in the body, we hypothesized that miR-122, as the most abundant miRNA in the tissue, might regulate TAG metabolism by targeting key enzymes that are involved in its production pathway. A systematic computational analysis of putative targets of miR-122 identified CTDNEP1 and LPIN1 genes in the TAG pathway. We used dual-luciferase reporter assay, quantitative RT-PCR as well as western blot to confirm the repressive effect of miR-122 on CTDNEP1 and LPIN1 in TAG pathway.
    Results
    Real time PCR on liver needle biopsies with hepatosteatosis showed that miR-122 is up-regulated in hepatosteatosis. Surprisingly, the protein and RNA level of identified targets of miR-122 are also up-regulated in clinical samples, probably as a disproportionate feedback response to the high level of miR-122.
    Conclusion
    Our findings suggest that up-regulation of miR-122 can trigger the compensatory response of LPIN1 and CTDNEP1 in hepatosteatosis.
    Keywords: Lipid metabolism, miR, 122, NAFLD, triglycerides
  • Babak Mirminachi, Zahra Mohammadi, Shahin Merat, Afarin Neishabouri, Amir Houshang Sharifi, Seyed Hoda Alavian, Hosein Poustchi *, Reza Malekzadeh
    Background
    One of the most important global public health concerns is chronic hepatitis C virus (HCV) infection, causing liver-related morbidity and mortality with a significant prevalence rate. Cirrhosis caused by hepatitis C is one of the most common causes of liver transplantation. Therefore, determining the prevalence of HCV infection and its geographical distribution is essential..
    Objectives
    The aim of this study was to estimate the point prevalence of HCV infection among Iranian general population..
    Methods
    Published studies reporting the prevalence of HCV infection in the Iranian general population were identified by a comprehensive literature search. Studies assessing and reporting HCV Ab positivity were evaluated in this review. Furthermore, an additional grey-literature search was performed to obtain other relevant studies..
    Results
    Twelve studies were eligible for inclusion in this review. The overall seroprevalence of HCV was 0.6% (95% CI: 0.4% to 0.8%). The seroprevalence of HCV infection varied considerably among different provinces ranging from 0.08% to 1.6%. Hormozgan province was reported to have the highest HCV Ab seropositivity rate while Mazandaran province had the lowest rate. The overall prevalence of actual viremia was 0.4% (range = 0.05 - 0.87), based on the results of five studies using PCR for confirmation of HCV diagnosis..
    Conclusions
    Our results demonstrated that the seroprevalence of HCV among Iranian general population is lower compared to other countries in the middle-east. However, the significant heterogeneity across included studies limits this conclusion. Therefore, to reduce the existing heterogeneity in the literature and strengthen the current evidence on the prevalence of HCV infection among Iranian general population, further high quality studies are required..
    Keywords: Hepatitis C, Iran, General Population, Systematic Review
  • Shahin Merat, Amir Houshang Sharifi, Arghavan Haj Sheykholeslami, Hossein Poustchi, Babak Fattahi, Alireza Nateghi Baygi, Seyed Moayed Alavian, Reza Malekzadeh*
    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..
    Keywords: Hepatitis C, Sofosbuvir, Daclatasvir, Sovodak
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