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author:("merit, Shahin")
1.  Adenoma detection rates in an opportunistic screening colonoscopy program in Iran, a country with rising colorectal cancer incidence 
BMC Gastroenterology  2014;14(1):196.
Data on the quality of colonoscopies in populations with rising colorectal cancer (CRC) incidence is scarce. We aimed to calculate the adenoma detection rates (ADR), and assess the quality of colonoscopies in an opportunistic screening colonoscopy program in Iran.
All the colonoscopy and pathology reports of asymptomatic adults over age 50 who underwent screening colonoscopy between June 2007 and March 2013 were reviewed. The colonoscopy quality indicators including ADR were calculated, and patient factors associated with the adenoma detection were determined.
A total of 713 asymptomatic adults aged 50 years and older who underwent their first-time screening colonoscopy were included in this study. ADR and advanced-ADR were 33.00% (95% CI: 29.52-36.54) and 13.18% (95% CI: 10.79-15.90), respectively. We observed a significantly higher rate of cecal intubation in patients with fair or better bowel preparation compared to those with poor prep, 90.00% vs. 70.45%, respectively (P < 0.001). Bowel preparation (adjusted OR: 2.49, 95% CI: 1.75-3.55), older age (≥60) (adjusted OR: 1.70, 95% CI: 1.22-2.36), and male gender (adjusted OR: 1.39, 95% CI: 1.01-1.92) were associated with the adenoma detection.
Our ADR in both genders meets and exceeds the recommended colonoscopy quality benchmarks. The polyp and adenoma detection rates in the current study are comparable to those reported from Western countries where the incidence of CRC is traditionally high. These data are in line with the epidemiologic transition of CRC in Iran.
PMCID: PMC4245784  PMID: 25404264
Screening colonoscopy; Colonic polyps; Colon cancers
2.  Cohort Profile: Golestan Hepatitis B Cohort Study- A Prospective Long Term Study in Northern Iran ​  
Hepatitis B virus (HBV) infection is the most common cause of end stage liver disease in Iran and in Golestan province. Large-scale population-based prospective cohort studies with long term follow-up are the method of choice to accurately understand the natural course of HBV infection. To date, several studies of HBV epidemiology, natural history, progression to cirrhosis and association with HCC have been reported from other countries. However, few of these are prospective and fewer still are population-based. Moreover, the underlying molecular mechanisms and immunogenetic determinants of the outcome of HBV infection especially in low and middle income countries remains largely unknown. Therefore, the hepatitis B cohort study (HBCS), nested as part of the Golestan Cohort Study (GCS), Golestan, Iran was established in 2008 with the objective to prospectively investigate the natural course of chronic hepatitis B with reference to its epidemiology, viral/host genetic interactions, clinical features and outcome in the Middle East where genotype D HBV accounts for >90% of infections. In 2008, a baseline measurement of HBV surface antigen (HBsAg) was performed on stored serum samples of all GCS participants. A sub-cohort of 3,505 individuals were found to be HBsAg positive and were enrolled in the Golestan HBCS. In 2011, all first degree relatives of HBsAg positive subjects including their children and spouses were invited for HBV serology screening and those who were positive for HBsAg were also included in the Golestan HBCS.
PMCID: PMC4208926  PMID: 25349681
3.  Characteristics of Colorectal Polyps and Cancer; a Retrospective Review of Colonoscopy Data in Iran 
Early diagnosis and endoscopic resection of adenomatous polyps is the main approach for screening and prevention of colorectal cancer (CRC). We aimed to assess polyp detection rate (PDR) and to characterize demographic, clinical, and pathological features of colorectal polyps in an Iranian population.
We retrospectively analyzed the data from 5427 colonoscopies performed during 2007-2012 at Masoud Clinic, the main endoscopy center associated with Sasan Alborz Biomedical Research Center, in Tehran, Iran.
Our sample included 2928 (54%) women and 2499 (46%) men, with the mean age of 48.3 years (SD=16.1). The most common reasons for colonoscopy included screening in 25.0%, and gastrointestinal bleeding in 15.2%. Cecal intubation was successful in 86% of patients. The quality of bowel preparation was fair to excellent in 78.1% (n=4235) of colonoscopies. Overall PDR was 42.0% (95% CI: 40.6-43.3). The PDR in men (51.1%, 95% CI: 49.1-53.1) was significantly higher than women (34.2%, 95% CI: 32.4-35.9, p<0.001). Polyps were more frequently observed in patients after the 6th decade of life (F=3.2; p=0.004). CRC was detected in 2.9% (73/2499) of men and 1.9% (57/2928) of women (p=0.02). The mean age for patients with cancer was significantly higher than that for individuals with polyps, 60.9 (SD=13.4) year vs. 56.9 (SD=13.7) year, respectively (p=0.001). Almost 82.8% of the lesions were precancerous with tubular type predominance (62.3%) followed by tubulo-villous (10.3%), villous (6.6%), and serrated (3.6%). Hyperplastic/inflammatory polyps comprised 17.2% of lesions.
Distal colon was more prone to develop polyps and cancer than proximal colon in our series. These findings provide a great infrastructure for next preventive programs and have implications for colorectal cancer screening at population-level.
PMCID: PMC4119671  PMID: 25093062
Colon Cancer; Colonoscopy; Colonic Polyps
4.  Clinical and Pathological Features of Non-Functional Neuroendocrine Tumors of Pancreas: A Report from Iran 
Pancreatic neuroendocrine tumors (PNETs) are rare tumors with variable malignant potential, prognosis, and survival. We aimed to assess the characteristics of patients with non- functional PNET in our hospital.
From Nov 2010 to Nov 2013 , all patients who came to endosonography unit of Shariati hospital , Tehran , Iran , and had pancreatic lesions were assessed . Tumor samples were obtained through fine needle aspiration. Various characteristics of the non- functional PNET were recorded and patients were followed up to three years.
Twenty eight non func-PNET cases, aged 37-72 years were identified, 15 (53.6%) of whom were men. Fifteen (53.6%) tumors were located in the head and 5(17.8%) in the body of the pancreas. The mean tumor size was 3.9 Cm and 10.7% , 28.6%, 32.1%, and 28.6% of the patients were at stages I, II, III and IV, respectively. Of the patients, 12 (43%) underwent surgery, 3 (10.7%) received chemotherapy, and 13 (46.4%) received no treatment. During the mean follow-up of 16 months, the disease had progressed in 3 (10.7%) patients and 10 (35.7%) had died. In univariate analysis, tumor size>3Cm and Ki-67>20% were correlated with survival rate but not in multivariate analysis.
Iranian patients with non- functional PNET present similar characteristics to world patients. There is a need to establish efficacy of tumor samples which are obtaining through fine needle aspiration for assessing tumor grading.
PMCID: PMC4119672  PMID: 25093063
Neuroendocrine Tumors; Epidemiology; Survival
5.  Determinants of Gastroesophageal Reflux Disease, Including Hookah Smoking and Opium Use– A Cross-Sectional Analysis of 50,000 Individuals 
PLoS ONE  2014;9(2):e89256.
Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time.
We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn.
Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02–1.75) and opium use (OR 1.70, 95% CI 1.55–1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76–0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined).
GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.
PMCID: PMC3931722  PMID: 24586635
6.  Smoking water-pipe, chewing nass, and prevalence of heart disease – A cross-sectional analysis of baseline data from the Golestan Cohort Study, Iran 
Heart (British Cardiac Society)  2012;99(4):272-278.
Water-pipe and smokeless tobacco use have been associated with several adverse health outcomes. However, little information is available on the association between water-pipe use and heart disease (HD). Therefore, we investigated the association of smoking water-pipe and chewing nass (a mixture of tobacco, lime, and ash) with prevalent HD.
Cross-sectional study.
Baseline data (collected in 2004–2008) from a prospective population-based study in Golestan Province, Iran.
50,045 residents of Golestan (40–75 years old; 42.4% male).
Main outcome measures
ORs and 95% CIs from multivariate logistic regression models for the association of water-pipe and nass use with HD prevalence.
A total of 3051 (6.1%) participants reported a history of HD, and 525 (1.1%) and 3726 (7.5%) reported ever water-pipe or nass use, respectively. Heavy water-pipe smoking was significantly associated with HD prevalence (highest level of cumulative use versus never use, OR= 3.75; 95% CI 1.52 – 9.22; P for trend= 0.04). This association persisted when using different cutoff points, when restricting HD to those taking nitrate compound medications, and among never cigarette smokers. There was no significant association between nass use and HD prevalence (highest category of use versus never use, OR= 0.91; 95% CI 0.69 – 1.20).
Our study suggests a significant association between HD and heavy water-pipe smoking. Although the existing evidence suggesting similar biological consequences of water-pipe and cigarette smoking make this association plausible, results of our study were based on a modest number of water-pipe users and need to be replicated in further studies.
PMCID: PMC3671096  PMID: 23257174
hookah; ischemic heart disease; nass; tobacco; water-pipe
7.  Oral Nitrate Reductase Activity Is Not Associated with Development of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Pilot Study 
NAFLD/NASH is a manifestation of metabolic syndrome and is associated with obesity/overweight. Not all obese/overweight individuals develop NASH. Gastro-esophageal reflux disease (GERD) is considered a gastrointestinal manifestation of the metabolic syndrome and is associated with obesity/overweight. Again not all obese/overweight individuals develop GERD. Recent data show association of dietary nitrate content and oral nitrate reductase activity (NRA) with GERD. Nitrates need to be converted to nitrite (done in human beings by nitrate reductase of oral bacteria exclusively) to be active in metabolic pathways.
To assess the relation between NASH/NAFLD and oral NRA.
Oral NRA was measured in individuals with NASH (compatible abdominal ultrasound and two elevated ALT/AST levels over six months) and was compared with that of those without NASH. Oral NRA was measured according to a previously reported protocol.
Eleven NASH patients and twelve controls were enrolled. Mean oral NRA activity were 2.82 vs. 3.51 μg nitrite-N formed per person per minute for cases and controls respectively (p=0.46).
According to our data, oral nitrite production is not different between individual swith and without NASH.
PMCID: PMC4005477  PMID: 24829701
NASH; NAFLD; GERD; Nitrate Reductase Activity; Oral Bacterial Flora
8.  Efficacy of Adding Metformin to Pegylated Interferon and Ribavirin in Treatment Naïve Patients with Chronic Hepatitis C: A Randomized Double-Blind Controlled Trial 
Evidence indicates that insulin resistance results in poor sustained viral response (SVR) in patients with chronic hepatitis C (CHC). Metformin is an oral hypoglycemic agent which improves insulin resistance.
We sought to determine if the addition of metformin to the treatment regimen could improve SVR in treatment-naïve CHC patients in a randomized, double-blind, placebo-controlled trial. We randomized 140 consecutive CHC patients to receive either metformin 500 mg three times a day or placebo in addition to pegylated interferon (PEG-IFN) and ribavirin (RBV). Only treatment-naïve subjects aged between 15 and 65 years of age were included. SVR was defined as no detectable HCV RNA six months after the end of treatment. Subjects who received at least one dose of PEG-IFN were included in the finala nalysis.
The SVR rate in the metformin group was 75% versus 79% in controls (intention-to-treat) which was not significantly different. Also, the difference between the placebo and metformin group was not significant in subsets of different genotypes or those with homeostasis model assessment of insulin resistance (HOMA-IR) levels greater than 2 or body mass index greater than 25. The most common complaint was gastrointestinal discomfort (13% in metformin group versus 4% in controls; p=0.002) that lead to discontinuation of metformin in 8 participants.
Although triple therapy with metformin, PEG-IFN and RBV is relatively well tolerated, the addition of metformin did not significantly improve viral response in CHC patients.
PMCID: PMC4005479  PMID: 24829699
Metformin; Hepatitis C; Insulin resistance
9.  Seroprevalence of Hepatitis A among Students Enrolled in Tehran University of Medical Sciences during 2011 
Hepatitis A is often asymptomatic in children, however it can become a serious disease in adults. For countries that do not have a universal vaccination strategy targeted vaccination for high risk groups is recommended. Health workers could be at a higher risk of infection with hepatitis A virus (HAV) compared to the general population. The aim of this study is to investigate the seroprevalence of hepatitis A among enrolled students in Tehran University of Medical Sciences in 2011.
This study included all students enrolled in Tehran University of Medical Sciences during 2011. We checked serum samples for anti-HAV antibody and participants completed a simple questionnaire.
From 1864 health sciences students enrolled in Tehran University of Medical Sciences, 1813 samples were analyzed for anti-HAV IgG antibody. The results showed that 970 (53.5%) were seronegative, 722 (39.8%) were seropositive, and 121 (6.7%) were equivocal. There were significantly higher seropositive results for males (54%) compared to females (37%; RR = 1.46; 95% CI: 1.31-1.62).
The seroprevalence of HAV among enrolled medical science students is considerably lower than previous reports from Iran. Targeted vaccination for health sciences students prior to exposure should be seriously considered.
PMCID: PMC3990182  PMID: 24829683
Hepatitis A; Vaccination; Seroepidemiologic Studies
10.  Development and Application of an In-house Line Probe Assay for Hepatitis C Virus Genotyping 
Hepatitis Monthly  2013;13(5):e6767.
Hepatitis C virus (HCV) is the major cause of chronic liver disease. HCV is a single stranded positive sense RNA of approximately 9.6 Kb. Because of high conservativeness of 5΄untranslated region of HCV genome, it is widely used for virus genotyping. Different methods are used for the virus genotyping, but all involve some difficulties.
The aim of the present study was to develop an in-house reverse hybridization method as a line probe assay, for HCV genotyping.
Materials and Methods
Sixty serum samples were collected with newly diagnosis of HCV infection. Genotyping process had already been performed for the samples using RT-PCR RFLP method. After total RNA extraction from the samples and cDNA synthesis, nested PCR method was applied for amplification of the target sequence on the 5΄UTR. In the nested PCR, biotinylated oligonucleotides were used as inner primers. Optimized concentrations of the biotinylated inner primers (as positive control), two universal and seven specific probes were spotted onto nylon membrane stripes in a defined pattern. Hybridization process was conducted between the probes and the denaturized biotin labeled PCR products. Finally, the stripes were developed by using streptavidin conjugated alkaline phosphate as a signal generating agent. To determine the diagnostic sensitivity and specificity of the home made LiPA, a panel containing 60 confirmed sera with positive results for HCV (and PCR-RFLP genotyped) was subjected to evaluate.
Agarose gel electrophoresis of the nested PCR products using the outer and inner primers showed 305 and 234 bp fragments respectively. After performing hybridization and detection processes on the prepared strips, the colored bands were formed for the positive control, universal probes and the corresponding genotypes. HCV genotype results were found to be in 100% concordance through studying 60 sera that were successfully typed by the two methods. P-value of 0.045 conveys that the two methods were the same and had no significant difference.
The most common genotyping method in Iran is RT-PCR RFLP. Given the results and advantages of this homemade technique, such as high specificity and sensitivity, ability for detection of most genotypes, it provides possibility of evaluating much of the isolates without needing electrophoresis stage.
PMCID: PMC3734896  PMID: 23922557
Hepatitis C Virus; Genotyping; LIPA Protein; Human
11.  Tea drinking habits and oesophageal cancer in a high risk area in northern Iran: population based case-control study 
Objective To investigate the association between tea drinking habits in Golestan province, northern Iran, and risk of oesophageal squamous cell carcinoma.
Design Population based case-control study. In addition, patterns of tea drinking and temperature at which tea was drunk were measured among healthy participants in a cohort study.
Setting Golestan province, northern Iran, an area with a high incidence of oesophageal squamous cell carcinoma.
Participants 300 histologically proved cases of oesophageal squamous cell carcinoma and 571 matched neighbourhood controls in the case-control study and 48 582 participants in the cohort study.
Main outcome measure Odds ratio of oesophageal squamous cell carcinoma associated with drinking hot tea.
Results Nearly all (98%) of the cohort participants drank black tea regularly, with a mean volume consumed of over one litre a day. 39.0% of participants drank their tea at temperatures less than 60°C, 38.9% at 60-64°C, and 22.0% at 65°C or higher. A moderate agreement was found between reported tea drinking temperature and actual temperature measurements (weighted κ 0.49). The results of the case-control study showed that compared with drinking lukewarm or warm tea, drinking hot tea (odds ratio 2.07, 95% confidence interval 1.28 to 3.35) or very hot tea (8.16, 3.93 to 16.9) was associated with an increased risk of oesophageal cancer. Likewise, compared with drinking tea four or more minutes after being poured, drinking tea 2-3 minutes after pouring (2.49, 1.62 to 3.83) or less than two minutes after pouring (5.41, 2.63 to 11.1) was associated with a significantly increased risk. A strong agreement was found between responses to the questions on temperature at which tea was drunk and interval from tea being poured to being drunk (weighted κ 0.68).
Conclusion Drinking hot tea, a habit common in Golestan province, was strongly associated with a higher risk of oesophageal cancer.
PMCID: PMC3269898  PMID: 19325180
12.  Clinical Features and Long Term Outcome of 102 Treated Autoimmune Hepatitis Patients 
Hepatitis Monthly  2012;12(2):92-99.
There is limited data on the natural history of autoimmune hepatitis (AIH) and on the long-term follow-up of AIH patients who have been referred for regular medical attention.
We evaluated the clinical presentation and natural history of AIH in a large cohort of type I AIH patients from Iran.
Patients and Methods
Between 1997 and 2008, 102 patients were enrolled in the study. Patients were diagnosed using the International Autoimmune Hepatitis Group criteria and were followed up for an average of 60 months. Clinical and biochemical data were gathered from all the patients at both the beginning and the end of the follow-up period. Liver biopsy was performed in all patients before treatment, and the biopsies were performed in 28 patients after treatment.
Biochemical remission was achieved by 80 (79.4%) patients. Of these, 53 (66.5%) showed near-normal liver histology or liver function test results and sonogram. The remaining 27 (33.5%) patients also achieved clinical and biochemical remission, but developed compensated cirrhosis. After a period of remission, 24 patients (32.5%) relapsed. Among the 22 (21.6%) patients who showed ultimate treatment failure, 6 underwent orthotopic liver transplantation and 3 died of liver failure while awaiting a transplant. Sixteen (72.7%) of the 22 patients who did not respond to therapy were non-compliant with medications and had irregular follow-up. The overall 10-year survival rate in the cohort was 96%.
Long-term survival in AIH patients is very good. Prompt diagnosis and appropriate first-line and salvage therapy that includes close follow-up will make liver transplantation a rare necessity in the treatment of this disease.
PMCID: PMC3321327  PMID: 22509185
Hepatitis; Autoimmune; Natural History; Liver Cirrhosis; Hepatitis, Chronic; Iran
13.  Metformin in Nonalcoholic Steatohepatitis: A Randomized Controlled Trial 
Nonalcoholic steatohepatitis (NASH) is a common liver disease that can progress to cirrhosis or hepatocellular carcinoma. It is estimated that up to 3% of the Iranian population have this condition. Although the pathogenesis of NASH is incompletely understood, there is significant evidence pointing to the importance of insulin resistance. Metformin is an oral hypoglycemic agent known to improve insulin resistance. This study examines the effectiveness of metformin on biochemical and histological improvement among NASH patients in a randomized double-blind controlled trial.
This study enrolled 33 biopsy-proven NASH patients. Other causes of liver disorders were excluded. Subjects were randomized to receive either metformin, 500 mg twice daily, or an identical-looking placebo. Overweight patients were also instructed to lose weight. Treatment continued for 6 months. Patients were regularly visited and liver enzyme levels recorded. Compliance and any adverse drug effects were recorded.
In the metformin group, the mean aspartate aminotransferase (AST) level dropped from 61.2 IU/L to 32.7 IU/L and the mean alanine aminotransferase (ALT) level dropped from 85.1 IU/L to 50.8 IU/L. The mean AST level in the placebo group dropped from 54.3 IU/L to 37.9 IU/L, whereas the mean ALT level dropped from 111.8 IU/L to 55.4 IU/L in the placebo group. The decrease in liver enzymes was significant in both groups, but the magnitude of decrease was not significantly different.
The improvement observed in liver enzyme levels is totally attributable to weight loss. Metformin had no significant effect on liver enzyme levels.
PMCID: PMC4017700  PMID: 24829630
Nonalcoholic Steatohepatitis; Metformin; Nonalcoholic Fatty Liver Disease
14.  Pegaferon in hepatitis C: Results of a Multicenter Study 
Chronic hepatitis C (CHC) is a major contributor to cirrhosis and hepatocellular carcinoma and major global public health problem that causes mortality in both developed and developing countries.For the past decade, treatment with pegylated interferon (peg interferon α) and ribavirin (RBV) has been associated with rates of sustained virologic response of ≤ 66% among patients with hepatitis C virus (HCV) infection. In this study, we report the response rate of Iranian treatment-naïve CHC patients to Pegaferon, a locally developed pegylated interferon-α2a (PEG-IFNα2a).
Patients diagnosed with CHC who referred to two university based outpatient clinics in Tehran from December 2007 to May 2011 were enrolled in a single-group, open-labeled experimental design. Eligible patients were above 15 years of age and had HCV infection with evidence of chronic hepatitis. Exclusion criteria included the presence of a debilitating disease, decompensated cirrhosis or refusal to participate in the study. Patients were treated with 180μg Pegaferon weekly in addition to 800-1200 mg daily, weight-based RBV for 24 or 48 weeks depending on genotype. Viral response and adverse effects were recorded.
A total of 216 patients were enrolled in the study of which 83.3% were male and 16.7% were female. In 93 (43.1%) patients, the HCV RNA viral load was ≥ 800,000 IU/ml before starting treatment. “As-treated analysis” indicated that a total of 168 (77.8%) patients achieved sustained viral response (SVR, undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment).
This study, with a larger number of participants, confirms the results of a previous study by the authors that Pegaferon, a PEG-IFNα 2a locally produced in Iran, is effective in treatment-naïve CHC patients.
PMCID: PMC4154913  PMID: 25197541
Hepatitis C virus; Pegylated interferon; Pegaferon; Ribavirin
15.  Eosinophilic Gastroenteritis: A Case Series from Iran 
Eosinophilic gastroenteritis (EG) is a rare inflammatory disorder of the gastrointestinal (GI) tract. There have been several case series of patients with EG from the western world and East Asia. However, there has not been a report of patients with EG from the Middle East region. The aim of this study is to describe clinical characteristics and treatment response in a series of EG patients from Iran.
We retrospectively reviewed charts with a diagnosis of EG from 1997 to 2010 at Shariati Hospital and the private clinics of the authors. Clinical characteristics of the patients were evaluated, and the treatment response and relapse rate were assessed.
Twenty-two patients (9 male) with EG were identified. Mean age of the patients was 45.1±15.5 (range: 27-75) years. Median duration between symptom onset and diagnosis was 12 (range 1- 48) months. Twenty (90%) patients had mucosal involvement, one (5%) had muscular involvement and one (5%) had subserosal involvement.
Patients were followed for a median duration of 36.5 (range 4-123) months. Two patients had spontaneous remission with supportive care. The remaining 20 patients responded well to oral corticosteroid treatments. The relapse rate was 33%. Episodes of relapse were successfully controlled with a repeat course of corticosteroids. Two patients with several relapses required maintenance treatment with azathioprine.
The clinical characteristics and treatment responses of EG patients from Iran are similar to reports from other parts of the world. Patients need to undergo close follow up after treatment to detect early signs of relapse.
PMCID: PMC4154914  PMID: 25197542
Eosinophilic gastroenteritis; Esophagus; Small intestine; Eosinophils
16.  The Impact of Illicit Drug Use on Spontaneous Hepatitis C Clearance: Experience from a Large Cohort Population Study 
PLoS ONE  2011;6(8):e23830.
Background and Aims
Acute hepatitis C infection usually ends in chronic infection, while in a minority of patients it is spontaneously cleared. The current population-based study is performed on a large cohort in Golestan province of Iran to examine the demographic correlates of Spontaneous Hepatitis C Clearance.
Serum samples used in this study had been stored in biorepository of Golestan Cohort Study. These samples were evaluated for anti hepatitis C Virus by third generation Enzyme-linked immunosorbent assay (ELISA). Subjects who tested positive were then invited and tested by Recombinant Immunoblot Assay (RIBA) and Ribonucleic Acid Polymerase Chain Reaction test (PCR). If tested positive for RIBA, subjects were recalled and the two tests were re-done after 6 months. Those subjects who again tested positive for RIBA but negative for PCR were marked as cases of spontaneous clearance.
49,338 serum samples were evaluated. The prevalence of Chronic Hepatitis C Virus (CHCV) infection based on PCR results was 0.31%. Among those who had acquired hepatitis C, the rate of SC was 38%. In multivariate analysis, illicit drug use both Injecting Use (OR = 3.271, 95% CI: 1.784–6.000, p-value<0.001) and Non-Injecting Use (OR = 1.901, 95% CI: 1.068–3.386, p-value = 0.029) were significant correlates of CHCV infection versus SC.
Illicit drug use whether intravenous or non-intravenous is the only significant correlate of CHCV, for which several underlying mechanisms can be postulated including repeated contacts with hepatitis C antigen.
PMCID: PMC3161071  PMID: 21887326
17.  Prognostic Factors for Esophageal Squamous Cell Carcinoma—A Population-Based Study in Golestan Province, Iran, a High Incidence Area 
PLoS ONE  2011;6(7):e22152.
Golestan Province in northern Iran is an area with a high incidence of esophageal squamous cell carcinoma (ESCC). We aimed to investigate prognostic factors for ESCC and survival of cases in Golestan, on which little data were available. We followed-up 426 ESCC cases participating in a population-based case-control study. Data were analyzed using the Kaplan–Meier method and the Cox proportional hazard models. Median survival was 7 months. Age at diagnosis was inversely associated with survival, but the association was disappeared with adjustment for treatment. Residing in urban areas (hazard ratio, HR = 0.70; 95% CI 0.54–0.90) and being of non-Turkmen ethnic groups (HR = 0.76; 95% CI 0.61–0.96) were associated with better prognosis. In contrast to other types of tobacco use, nass (a smokeless tobacco product) chewing was associated with a slightly poorer prognosis even in models adjusted for other factors including stage of disease and treatment (HR = 1.38; 95% CI 0.99–1.92). Opium use was associated with poorer prognosis in crude analyses but not in adjusted models. Almost all of potentially curative treatments were associated with longer survival. Prognosis of ESCC in Golestan is very poor. Easier access to treatment facilities may improve the prognosis of ESCC in Golestan. The observed association between nass chewing and poorer prognosis needs further investigations; this association may suggest a possible role for ingestion of nass constituents in prognosis of ESCC.
PMCID: PMC3141005  PMID: 21811567
18.  Socio-economic status and oesophageal cancer: results from a population-based case–control study in a high-risk area 
Background Cancer registries in the 1970s showed that parts of Golestan Province in Iran had the highest rate of oesophageal squamous cell carcinoma (OSCC) in the world. More recent studies have shown that while rates are still high, they are approximately half of what they were before, which might be attributable to improved socio-economic status (SES) and living conditions in this area. We examined a wide range of SES indicators to investigate the association between different SES components and risk of OSCC in the region.
Methods Data were obtained from a population-based case–control study conducted between 2003 and 2007 with 300 histologically proven OSCC cases and 571 matched neighbourhood controls. We used conditional logistic regression to compare cases and controls for individual SES indicators, for a composite wealth score constructed using multiple correspondence analysis, and for factors obtained from factors analysis.
Results We found that various dimensions of SES, such as education, wealth and being married were all inversely related to OSCC. The strongest inverse association was found with education. Compared with no education, the adjusted odds ratios (95% confidence intervals) for primary education and high school or beyond were 0.52 (0.27–0.98) and 0.20 (0.06–0.65), respectively.
Conclusions The strong association of SES with OSCC after adjustment for known risk factors implies the presence of yet unidentified risk factors that are correlated with our SES measures; identification of these factors could be the target of future studies. Our results also emphasize the importance of using multiple SES measures in epidemiological studies.
PMCID: PMC2720396  PMID: 19416955
Oesophageal cancer; socio-economic status; case–control; epidemiology; Iran; factor analysis; correspondence analysis
19.  Tooth loss and lack of regular oral hygiene are associated with higher risk of esophageal squamous cell carcinoma 
We tested the association between tooth loss and oral hygiene and the risk of esophageal squamous cell carcinoma (ESCC) in people living in a high risk area of Iran. We used a case-control study of pathologically-confirmed ESCC cases (N=283) and controls (N=560) matched on sex, age, and neighborhood. Subjects with ESCC had significantly more decayed, missing, or filled teeth with a median (interquartile range) of 31 (23-32) compared to controls 28 (2-32) (P=0.0045). And subjects with ESCC were significantly more likely than controls to fail to practice regular oral hygiene, 78% versus 58%. In multivariate adjusted conditional logistic regression models having 32 decayed, missing, or filled teeth compared to ≤15 conferred an OR (95% CI) of 2.10 (1.19-3.70). Compared to daily tooth brushing, practicing no regular oral hygiene conferred an OR (95% CI) of 2.37 (1.42-3.97). Restricting the analysis to subjects that had never smoked tobacco did not materially alter these results. We found significant associations between two markers of poor oral hygiene, a larger number of decayed, missing, or filled teeth and lack of daily tooth brushing, and risk of ESCC in a population at high risk for ESCC where many cases occur in never smokers. Our results are consistent with several previous analyses in other high risk populations.
PMCID: PMC2586052  PMID: 18990747
Tooth loss; tooth brushing; esophagus; squamous; cancer
20.  Persistent alanine aminotransferase elevation among the general Iranian population: Prevalence and causes 
AIM: To determine the prevalence and causes of persistently elevated alanine aminotransferase (ALT) levels among the general population in northern Iran.
METHODS: A total of 2292 (1376 female, aged 18-75 year), were selected by systematic clustered random sampling from the cities and villages of Gonbad and Kalaleh in Golestan Province and invited to participate in the study. A comprehensive history regarding alcohol drinking and medication was taken. Body mass index (BMI), viral markers and ALT levels were measured. If ALT level was ≥ 40 U/L, it was rechecked twice within 6 mo. Those with ≥ 2 times elevation of ALT were considered as having persistently elevated ALT level. Non-alcoholic fatty liver disease (NAFLD) was diagnosed based on evidence of fatty liver upon sonography and excluding other etiology.
RESULTS: A total of 2049 (1351 female) patients participated in the study, 162 (7.9%) had elevated ALT level at the first measurement. Persistently elevated ALT level was detected in 64 (3.1%) participants, with 51 (79.6%) with no obvious etiology, six (9.3%) with Hepatitis B, four (6.2%) with Hepatitis C virus (HCV) infection and three (4.6%) with alcoholic hepatitis. The prevalence of NAFLD and alcoholic hepatitis was 2.04% (42 patients) and 0.1% (three), respectively. There was correlation between NAFLD and male gender, overweight, diabetes and living in an urban area [odds ratio = 3.03 (95% CI: 1.6-5.72), 4.21 (95% CI: 1.83-9.68), 2.86 (95% CI: 1.05-7.79) and 2.04 (95% CI: 1.00-4.16) respectively].
CONCLUSION: NAFLD is the most common cause of persistently elevated serum ALT level among the general population of Iran.
PMCID: PMC2710729  PMID: 18473412
Alanine aminotransferase; Iran; Non-alcoholic fatty liver disease; Viral hepatitis
21.  Epidemiology of upper gastrointestinal cancers in Iran: A sub site analysis of 761 cases 
AIM: To define the sub site distribution of upper gastrointestinal cancers in three provinces of Iran.
METHODS: The study was carried out in three provinces in Iran: Ardabil, Golestan, and Tehran. In Arbabil and Golestan, the data was collected from the sole referral center for gastrointestinal cancers and the local cancer registry. For Tehran province, data from two major private hospitals were used. All gastric and esophageal cancer patients diagnosed during the period from September 2000 and April 2002 were included in the study.
RESULTS: A total of 761 patients with upper gastrointestinal cancers were identified, 314 from Ardabil, 261 from Golestan, and 186 from Tehran. In Tehran, the relative rate of cancer increased from the upper esophagus to the distal stomach. In Golestan, the reverse pattern was observed. In Ardabil, the mid portion (distal esophagus and proximal stomach) was involved most frequently.
CONCLUSION: There were considerable variations in the sub site of upper gastrointestinal cancers in the three provinces studied. We cannot provide any explanation for this variation. Further research aimed at explaining the discrepancies in sub site distribution of upper gastrointestinal cancers may help identify important risk factors.
PMCID: PMC4171328  PMID: 17879408
Upper gastrointestinal tract; Gastrointestinal neoplasms; Iran
22.  Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population 
AIM: To investigate the relation of human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in Iranian patients as compared to normal controls.
METHODS: Using MY09/MY11 consensus primers, we compared the prevalence of a HPV L1 gene in tumor tissues from 38 ESCC cases and biopsied tissues from 38 endoscopically normal Iranian individuals. We also compared the presence of HPV16 and HPV18 in the same samples using type-specific E6/E7 primers.
RESULTS: Fourteen (36.8%) of the 38 ESCC samples but only 5 (13.2%) of the 38 control samples were positive for the HPV L1 gene (P = 0.02). Five (13.2%) of the ESCC samples but none of the control samples were positive for the HPV16 E6/E7 gene (P = 0.05). Three (7.9%) of the ESCC samples and 5 (13.2%) of the control samples were positive for the HPV18 E6/E7 gene (P = 0.71).
CONCLUSION: Our data are consistent with HPV DNA studies conducted in other high-risk areas for ESCC. HPV should be considered as a potential factor contributing to the high incidence of ESCC in Iran and other high-incidence areas of the world.
PMCID: PMC4250714  PMID: 15754405
Papillomavirus; Squamous cell carcinoma of esophagus; Population

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