Efficacy of hepatic T2* MRI values and serum ferritin concentration in predicting thalassemia major classification for hematopoietic stem cell transplantation.

Liver biopsy has been performed for many decades for classifying the patients with TM. Meanwhile, using non-invasive methods such as T2* MRI technique has been recently much more considered to determine the hepatic iron overload. Ninety-three pediatric HSCT candidates with TM who underwent liver biopsy were included in this study. Hepatic T2* MRI values and serum ferritin concentrations were assessed to investigate and determine the useful method in detection of patients with TM class III whom received different conditioning regimens, in comparison with class I and II. Twenty (21.5%) patients were categorized as class III. Hepatic T2* MRI could detect TM class III patients with 60% sensitivity and 87.67% specificity (LR+: 4.867, accuracy: 81.72%), while predictive feature of ferritin values for distinguishing patients with TM class III was not statistically significant (p-value >0.01). Combination of T2*MRI with age (T2*-age) could detect TM class III with 85% sensitivity and 72.6% specificity (LR+: 3.1, accuracy: 75.27%).T2*-age may be considered as an alternative and non-invasive method to liver biopsy for differentiation and classification of patients with TM before transplantation.

Noninvasive measurement of liver fibrosis using transient elastography in pediatric patients with major thalassemia who are candidates for hematopoietic stem cell transplantation.

Although liver biopsy is an invasive procedure, it remains the gold standard technique for the evaluation of hepatic fibrosis in different patients, including those with major thalassemia (MT). Recently, noninvasive imaging techniques, such as transient elastography, have emerged. We investigated the effectiveness of TE, in comparison to liver biopsy, for the evaluation of liver fibrosis in pediatric patients with MT who were candidates for hematopoietic stem cell transplantation (HSCT). Eighty-three pediatric MT patients (48 boys and 35 girls), who were candidates for HSCT, were included in this study. The median age was 8 years. Liver stiffness was assessed for all patients, before transplantation, using both TE, measured in kilopascals (kPa) and liver biopsy, based on the Metavir score. The diagnostic accuracy of TE and liver biopsy were estimated using linear discriminated analysis (the area under the receiver operating characteristic curves [AUROCs]). The median TE score was 4.3 kPa (range, 3.5 to 5.2). The TE value did not differ among patients with different ferritin levels (P = .53). TE increased proportionally to Metavir fibrosis stages (P < .001) and the necro-inflammatory grade (P < .001). The TE score also correlated to liver iron content (P < .001), liver size (P < .003), and Lucarelli risk classification (LRC) (P < .001). ROC curve analysis revealed moderate accuracy of the TE score for the diagnosis of fibrosis (AUROC = 73%) and for distinguishing individuals with a LRC III from those classified as I and II (AUROC = 82%). The TE score was also superior to Fibrosis-4 (AUROC = 61%) for the assessment of liver fibrosis and LRC differentiation. The results of this study demonstrated that TE can be a valuable method for assessing liver fibrosis and differentiating LRC III from the other 2 classes in pediatric patients with MT who have been selected for HSCT.

The effects of dietary habits on Iranian students' school performance, a pilot cross-sectional study.

OBJECTIVE: To determine whether dietary habits in Iranian secondary school students have any effect on an individual's performance in school. METHODS: The observational, cross-sectional study was conducted in Tehran during the 2010-11 academic year. Standardised Graduate Point Average was used as school performance. A validated nationalised nutritional questionnaire, designed by an expert committee, was filled by each student. Data was analysed using SPSS 16. RESULTS: The age of the 96 male high school students ranged betweeen 16 and 17 years, with the mean of 16.65 +/- 0.3 years. Of the total, 50 (52.1%) students had negative and 46 (47.9%) had positive standardised GPA. The average score of the questionnaire for the students in the positive group was significantly higher than the others (26.3 vs. 21.04) (p<0.05). CONCLUSIONS: Poor school performance in Iranian secondary school students was in relation with poor dietary habits.

Screening colonoscopy in first-degree relatives of patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), one of the most important causes of morbidity and mortality, has earned the attention of healthcare systems widely. Screening programs are designed to detect patients at risk as effectively as possible. One of the major CRC risk factors is having a family member with diagnosed CRC. AIM: To investigate the association between presence of polyps on colonoscopy and family history of CRC. METHODS: This was a retrospective cohort study in which the data was collected from colonoscopy reports of patients with/without familial history of CRC in Masoud private clinic, Tehran, Iran from October 1, 2011 to October 1, 2012. The association between presence of colorectal polyps on colonoscopy and family history of CRC was then assessed. RESULTS: A total of 210 patients were included in the study, constituting two groups with/without familial history of CRC with a 1:1 ratio (105 subjects in each group). Compared to subjects with a negative family history of CRC, a 2.7-fold (CI 95%: 1.2-6.24) fold increase was observed in those with a positive family history to have colorectal polyps. In multivariate regression analysis, family history of CRC was the only independent variable associated with presence of colorectal polyps (odds ratio: 3.12, CI 95%:1.22-8). CONCLUSION: A positive family history of CRC is a risk factor for colorectal polyps.

T2(∗) MRI changes in the heart and liver of ex-thalassemic patients after hematopoietic stem cell transplantation.

BACKGROUND: Non-invasive methods like MRI-based techniques have been considered recently for assessment of liver and heart status in patients with thalassemia major (TM). The purpose of this study is to examine the alterations of hepatic and myocardial T2(∗) MRI values in TM patients after hematopoietic stem cell transplantation (HSCT) just before starting chelation therapy. PROCEDURE: The study included fifty-two TM patients with mean age of 7.6years who were referred to our center for HSCT. Before HSCT, patients underwent liver biopsy to determine fibrosis stage based on the Lucarelli classification. Hepatic and myocardial T2(∗) values before and 6months after transplantation were measured and analyzed. RESULTS: There was not a statistically significant increase in myocardial T2(∗) values after HSCT (p-value=0.35). Hepatic T2(∗) values significantly decreased after HSCT (p-value <0.001), showing the liver status has been worsened. In subgroup analysis, post-HSCT hepatic T2(∗) values (adjusted for baseline values) were significantly higher in patients with graft-versus-host disease (GvHD) compared to non-GvHD patients (p-value=0.04). CONCLUSIONS: The issue of iron overload is still remained as the main problem in ex-thalassemic patients after HSCT. We found T2(∗) MRI technique a quite beneficial method for following up the patients after transplantation. Obviously, planning large controlled trials associated with liver biopsy results after transplantation is required.

Diagnostic value of fecal calprotectin in patient with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by recurrent episodes of inflammation limited to the mucosal layer of the colon. Calprotectin is a zinc and calcium binding protein derived from neutrophils and monocytes. It is easily detectable in tissue samples, body fluids, and stools, which makes it a potentially valuable marker of inflammation. The aim of the current study is to evaluate the value of fecal calprotectin (FC) as a marker of disease activity in patients with UC. METHODS: Seventy three eligible subjects underwent ileocolonoscopy and multiple biopsies were obtained from different parts of the colon and terminal ileum. All patients underwent blood and stool sampling as well as an interview to assess the disease severity utilizing ulcerative colitis activity index (UCAI), subjectively. The diagnostic value of the FC in comparison with Mayo disease activity index as the gold standard technique, was then evaluated. RESULTS: Mean FC level increased linearly according to Mayo disease activity index (r=0.44, p<0.001) and was significantly different between levels of Mayo disease activity index (p=0.003). In multivariate analysis, Mayo disease activity index, positive CRP and ESR were associated with FC level. FC level > 21.4 ng/ml was able to discriminate between active and inactive phases of UC according to Mayo disease activity index>2 with 72.3% sensitivity and 73.1% specificity. The combination of FC > 21.4 ng/ml and UCAI score of 7 had a 46.8% sensitivity and 88% specificity to diagnose Mayo disease activity index >2. Furthermore, FC level <21.4 ng/ml in combination with UCAI score of <3 showed a highly considerable specificity of 98% to discriminate the remission phase of UC (Mayo disease activity index <2), although with a low sensitivity (31%). CONCLUSION: FC appears to be a non-invasive biomarker with moderate accuracy to discriminate the active phase of inflammatory bowel disease (IBD). The value of FC especially in combination with UCAI is highly considerable to rule out the Mayo disease activity index >2.

The Possible Role of TLR2 in Chronic Hepatitis B Patients with Precore Mutation.

Recognition mechanisms of innate immune response help to improve immunotherapeutic strategies in HBeAg-negative chronic hepatitis B (CHB). Toll-like receptor 2 (TLR2) is an important component of innate immunity. In this study, the frequency of precore mutations of the hepatitis B virus (HBV) and serum TLR2 were evaluated in CHB patients. Fifty-one patients with chronic hepatitis B, negative for HBeAg and detectable HBV DNA, were examined for the presence of mutations in pre-core region of HBV genome by direct sequencing. Serum TLR2 was measured by enzyme-linked immunosorbent assay. Interactions of truncated HBeAg and TLR2 proteins were evaluated with molecular docking software. The G1896A pre-core mutation were detected in 29 (57%) which was significantly associated with higher concentration of serum TLR2 in comparison with patients without this mutation (4.8 ± 2.9 versus 3.4 ± 2.2 ng/mL, P = 0.03). There was also a significant correlation between serum ALT and TLR-2 (r = 0.46; P = 0.01). Docking results illustrated residues within the N-terminus of truncated HBeAg and TLR2, which might facilitate the interaction of these proteins. These findings showed the dominance of G1896A pre-core mutation of HBV variants in this community which was correlated with serum TLR2. Moreover TLR2 is critical for induction of inflammatory cytokines and therefore ALT elevation.

The TNF-α -308 Promoter Gene Polymorphism and Chronic HBV Infection.

Background and Aims. TNF-α -308 allele promoter polymorphism has been known to be a potential prognostic factor in patients with chronic HBV infection. We tried to determine how TNF-α -308 allele promoter polymorphism would affect the prognosis in patients with chronic HBV infection. Methods. We searched MEDLINE, EMBASE, and reference lists of relevant review articles related to the association between "TNF-α G-308A promoter polymorphism" with "chronic HBV infection". We only focused on searching -308 locus in published studies. We reviewed 21 original articles about TNF-α -308 allele polymorphism and its effect on prognosis in patients with chronic HBV infection and discussed the results. Results. conflicting results were observed. The results were divided into 3 groups including neutral, negative, and positive associations between TNF-α -308 allele polymorphism and prognosis in patients with chronic HBV infection. We summarized the primary data as a table. Conclusions. Authors concluded that although there is an upward trend in evidence to claim that there is a positive relation between TNF-α G-308A promoter polymorphisms and resolution of chronic HBV infection, due to many biases and limitations observed in reviewed studies, an organized well-designed study is needed for clarifying the real association.

Hepatitis B virus genome asymmetry in hepatocellular carcinoma.

BACKGROUND: The association between hepatitis B virus (HBV) mutations and hepatocarcinogenesis were reported in the literature. Preference for G over C in the leading DNA strand has been reported to account for the asymmetry in nucleotide (nt) composition. The aim of this study was to analyze the complete genome sequence and compositional asymmetry of HBV in different stages of hepatitis B. METHODS: Full genome sequencing of 24 patients with chronic hepatitis B, some of whom also had cirrhosis and hepatocellular carcinoma (HCC) was performed. Mutations analysis was implemented in a comparison with a HBV genotype D reference from an international DNA database. CpGProD, a web-based application, was used to evaluate CG content and predict CpG islands. RESULTS: All strains were 3182 base pairs (bp) in length, except for two cases of HCC in which 9 and 21 nt, respectively, were deleted in preS2. The genetic relatedness of these isolates was 97%-100%. There were common CpG-rich regions in all 24 isolated full genome sequences, however a strong negative GC skew for forming a CpG island in the minus strand were exhibited in overlap with enhancer I in three HCC patients, a cirrhotic patient and three with chronic hepatitis. CONCLUSION: The high percentage of sequence identity between HBV isolates in our patients demonstrates that genomic factors, except for genotype, are involved in hepatocarcinogenesis. Variations in GC content which were caused by a different spectrum of mutations may affect DNA compositional asymmetry and epigenetic modification of HBV DNA in HCC.

The potential role of APOBEC3G in limiting replication of hepatitis B virus.

BACKGROUND AND STUDY AIMS: Recent findings introduced APOBEC3G (A3G) as a host factor that blocks viral replication. It induces G to A hypermutations in viral DNA at the step of reverse transcription and in response to interferon. This study aimed to investigate the expression of liver A3G protein in association with both replication of hepatitis B virus (HBV) and frequency of G to A mutations in BCP (basal core promoter)-PC (pre-core) region. PATIENTS AND METHODS: Fifty-one liver biopsies of naïve chronic hepatitis B (CHB) patients enrolled for the expression of A3G were done by immunohistochemistry (IHC) standard method. The presence of HBV DNA and sequences of BCP-PC region at the time of liver biopsy was investigated in all patients. RESULTS: Among 34 patients with detectable HBV DNA, 31 carried 1-5 G to A mutations in the BCP-PC region. IHC results showed that the expression level of A3G in CHB patients' liver was very low. Of all patients, A3G is expressed in three undetectable HBV DNA subjects and a patient with 2.24×10(4) copies ml(-1) of HBV DNA. G to A mutated residues were indicated at positions 1727, 1757 and 1896 of the HBV genome of this patient. CONCLUSION: This study indicates that despite very low levels of both A3G in liver and the number of positive subjects, A3G has a potential role to restrict the in vivo replication of HBV.