Physicians' knowledge and attitude towards fecal microbiota transplant in Iran

Fecal microbiota transplant [FMT] is employed to replace the 'unhealthy' microbiota of the patient with the 'healthy' microbiota of a pre-screened healthy donor. Given the growing importance of gut microbiota dysbiosis in the pathogenesis of intestinal or extraintestinal diseases; it is conceivable that FMT becomes integrated in the routine clinical practice. Our objective was to assess the knowledge and attitude of the Iranian physicians towards FMT. We surveyed the participants of Iranian gastroenterology and hepatology 2014 conference. Overall, 146 [68.5%] were familiar with FMT; of whom 132 [94.28%] were willing to accept FMT if scientifically and ethically approved and 115 [88.46%] were willing to refer their patients for FMT if indicated. In total, 42 [30.7%] had identified stool preparation as the most unappealing aspect of FMT, while 17 [11.6%] reported the therapeutic use of fecal material as the most unappealing and 39 [28.5%] indicated that both are equally unappealing. The doctors who had an overall positive opinion toward FMT reported less negative feelings towards FMT. Iranian physicians are willing to accept FMT as a therapeutic option if it is scientifically justified and ethically approved. Nevertheless, physicians prefer to skip the stool preparation phase; as they are more in favour of synthetic microbiota as opposed to fecal microbiota

Mean polyp per patient is an accurate and readily obtainable surrogate for adenoma detection rate: results from an opportunistic screening colonoscopy program

The incidence of colorectal cancer is rising in several developing countries. In the absence of integrated endoscopy and pathology databases, adenoma detection rate [ADR], as a validated quality indicator of screening colonoscopy, is generally difficult to obtain in practice. We aimed to measure the correlation of polyp-related indicators with ADR in order to identify the most accurate surrogate [s] of ADR in routine practice. We retrospectively reviewed the endoscopic and histopathological findings of patients who underwent colonoscopy at a tertiary gastrointestinal clinic. The overall ADR and advanced-ADR were calculated using patient-level data. The Pearson's correlation coefficient [r] was applied to measure the strength of the correlation between the quality metrics obtained by endoscopists. A total of 713 asymptomatic adults aged 50 and older who underwent their first-time screening colonoscopy were included in this study. The 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 good correlations between polyp detection rate [PDR] and ADR [r=0.93], and mean number of polyp per patient [MPP] and ADR [r=0.88] throughout the colon. There was a positive, yet insignificant correlation between advanced ADRs and non-advanced ADRs [r=0.42,p=0.35]. MPP is strongly correlated with ADR, and can be considered as a reliable and readily obtainable proxy for ADR in opportunistic screening colonoscopy programs

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

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

Efficacy of adding metformin to pegylated interferon and ribavirin in treatment naive 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 final analysis. 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.

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 microg 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 individuals with and without NASH.

[Antigen-specific IL-10 producing CD4[+], CD25[+] regulatory T cells in chronically infected HCV patients]

Background: the mechanism behind the apparent lack of effective antiviral immune response in patients with chronic hepatitis C virus [HCV] infection is poorly understood. Although multiple levels of abnormalities have been identified in innate and adaptive immunity, it is postulated that production of specific cytokines such as IL-10 may contribute to the induction and maintenance of HCV persistence. Production of IL-10 by CD4[+], CD25[+], and IL-10 [+] regulatory T cells with regulatory capacity [Tregs] appears to be one of the viral mechanisms that alter the antiviral immune response. As the first report, that attempts to mimic physiological forces that can occur during HCV infection, in this study we evaluate the ability of HCV-core antigens in increasing the frequency of CD4[+],CD25[+],IL-10[+] regulatory T cells

Materials and Methods: we analyzed peripheral blood mononuclear cells [PBMCs] from chronic HCV-infected patients [n=19] and normal controls [n=6] to determine the effect of the HCV-core antigen in the frequency of HCV-specific IL-10 production. PBMCs of different groups were isolated, cultured and stimulated with core antigen. Then, an in-house triple-stain flow cytometric method was used to investigate the frequency of CD4[+],CD25[+],IL-10 producing cells

Results: following incubation of PBMCs with HCV-core antigen, a population of CD4[+],CD25[+],IL-10[+] cells [regulatory T cells] increased. However we observed no increase in Tregs in the negative controls

Conclusion: the study supports the view that specific CD4[+],CD25[+],IL-10[+] T cells may be implicated in host immune tolerance during an HCV infection. It is likely that HCV vaccine candidates avoid epitopes that lead to strong IL-10 production

[Muscle cramps in cirrhotic patients: a cross-sectional study]

Background: muscle cramps are painful manifestations that occur in many cirrhotic patients. This study aims to evaluate the risk factors for developing muscle cramps

Materials and Methods: this cross-sectional study evaluated 24 cirrhotic patients [18 male, 6 female] during 15 months. Patients underwent careful examinations administered by the same person to determine the underlying cause of disease, presence of ascites, jaundice and encephalopathy as possible causes for muscle cramps. A specific questionnaire that contained demographic information, frequency, location, duration and time of muscle cramps was completed for each patient

Results: patients' mean ages were 45.1 years for females and 48.3 years for males. The frequency of muscles cramps was 37.5% [6 males, 3 females]. The most frequent time for the occurrence of cramps was at night and when patients were at rest [88%]. The calf muscle [77%] was the most involved muscle group that experienced cramping. Patients with muscle cramps had lower serum albumin level [p<0.01] and higher PT [p<0.05] compared to those who did not experience cramps

Conclusion: lower serum albumin level as well as increased PT was associated with muscle cramps in cirrhotic patients. However further studies are mandatory to confirm the findings of this study

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

Sampling error in histopathology findings of nonalcoholic fatty liver disease: a post mortem liver histology study

Many clinical trials and natural history studies on nonalcoholic fatty liver disease [NAFLD] and nonalcoholic steatohepatitis [NASH] rely heavily on liver histology to define their endpoints. There are many indications that the liver is not uniformly involved in NAFLD thus sampling error is a major concern. This study aims to evaluate the uniformity of various histologic features in livers affected with NAFLD. Samples from a forensic autopsy series were studied and subjects with NAFLD identified. We took specimens from three different parts of each liver and recorded the degrees of steatosis, hepatocyte ballooning, lobular inflammation, portal inflammation, and fibrosis. A NASH activity index [NAI] which is the sum of scores of histologic features was also calculated. The agreement between the 3 samples from each liver was studied. There were 945 autopsies performed; 896 were suitable for histologic evaluation and 283 had NAFLD. Of these, 146 livers were available to our study from which 438 samples were taken. Fibrosis [intra-class correlation [ICC] = 0.87], lobular inflammation [kappa = 0.83], and portal inflammation [kappa = 0.83] were fairly uniformly distributed in the damaged liver. Steatosis was less uniform [kappa = 0.64], and hepatocyte ballooning was least uniformly distributed [kappa = 0.57]. The ICC for NAI was 0.86, which indicated good agreement. The individual histologic features of NAFLD and NASH are not uniformly distributed in the liver. Hepatocyte ballooning is especially non-uniform. Such non-uniformity should be taken into account when interpreting results of studies that rely on paired biopsies. A summary score such as NAI is less affected by sampling error

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

Rapid low-cost detection of hepatitis C virus RNA in HCV-infected patients by real-time RT-PCR using SYBR green I

We intend to design and validate a low-cost assay for the detection of hepatitis C virus [HCV] RNA using rapid-cycle RT-PCR. The procedure is performed in a closed system with little risk of contamination allowing PCR and product identification to be performed within one or two hours. A SYBR Green-based real-time RT-PCR for rapid detection of HCV. Amplicon synthesis was monitored continuously by SYBR Green I, which binds to double stranded DMA during PCR. The PCR products were identified by melting curve analysis. Standard sera with known concentrations of HCV RNA and 150 clinical samples were used to validate our assay. The minimum detection level of our assay was less than 50 ID/mL. The results on 100 plasma samples were comparable with commercial assays. This method is useful for rapid qualitative detection of HCV infection and particularly suitable for routine diagnostic applications

Familial aspects of colorectal cancers in southern littoral of Caspian sea

About 50,000 new cancer cases occur annually in Iran, of which gastrointestinal [GI] cancers are the most common Colorectal cancers [CRC] account for the third and fourth most prevalent cancers amongst Iranian men and women, respectively. Since CRC has some well-known hereditary forms with differences in their prevalence according to regional heterogeneity, we designed a study to assess familial aspects of this cancer in subjects who reside in Mazandaran Province, Iran. We interviewed all CRC patients who attended a private GI clinic during 1999-2007, with histologically confirmed diagnoses of colorectal adenocarcinoma, about their family histories of CRC and age at diagnosis. Pedigrees were drawn up to second-degree relatives. A total of 293 CRC cases were enrolled in the study, of which 152 were male and 141 were female. The mean age of patients was 52.6 +/- 15.2 years. Of these, 98 patients [33.5%] were under the age of 45. A total of 66 cases [22.5%] had familial histories of CRC, being significantly more prevalent in younger subjects [11.2% vs. 44.9%, P<0.0001]. Thirty-two patients [10.9%] fulfilled the criteria for hereditary non-polyposis colon cancer. In addition, right-sided colon cancers were more prevalent in those with positive familial histories [P<0.05]. Due to the frequency of early-onset CRC and familial syndromes, a more intense screening protocol for early detection of CRC should be developed for this population

Bell's palsy associated with chronic HCV infection before and during peginterferon alfa and ribavirin therapy

Neuropsychiatric side effects of peginterferon-alpha [EG-IFN-alpha] therapy consist of a large spectrum of symptoms. Organic personality syndrome, organic affective syndrome, psychotic manifestations and seizures are more common side effects of PEG-IFN-alpha whereas cranial neuropathy and movement disorders are less common. Bell's palsy is often idiopathic, but has been linked to some viral infections, particularly with herpes viruses. Other infections, such as human immunodeficiency virus infection and Lyme disease, may also lead to idiopathic facial paralysis. Neither acute nor chronic Hepatitis C infection has been implicated previously in Bell's palsy, but PEG-IFN- alpha may play a role. Two patients with CHC who developed Bell's palsy before and during treatment with PEG-IFN- alpha and Ribavirin are presented here

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 alpha] ribavirin [RBV] has been associated with rates of sustained virologic response of /= 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-IFN alpha 2a locally produced in Iran, is effective in treatment-na‹ve CHC patients

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 [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