Gastroenterology and Hepatology from Bed to Bench

Aim: Present study aimed to systematically review and quantitatively synthesize published data about the prevalence of Hepatitis B
Virus (HBV) infection among high risk groups in Iran.
Background: Determining true burden of Hepatitis B Virus (HBV) infection among high-risk groups relies on knowledge of occurrence
measures such as prevalence rate. There is no conclusive and comprehensive data regarding to prevalence of HBV infection among
high risk groups in Iran.
Methods: Relevant studies were searched in PubMed, Scopus, Web of Knowledge and local databases. In addition, reference lists of
relevant studies were searched manually. Two independent authors reviewed the eligibility of retrieved studies and extracted the
required data. Studies reporting HBV infection among high risk groups were included in the meta-analysis using random effects models.
Meta regression and sub-group analysis were considered as additional analyses.
Results: The initial search yielded 566 citations. After the primary screen, 37 studies were selected for review. Meta-analysis results showed
that pooled prevalence of HBV infection among high risk groups in Iran was 4.8% (95% confidence interval: 3.6%-6.1%), with the highest
prevalence among in prisoners (5%; 3%-6%), and in central regions of Iran (7%; 4%-11%). Year of study may affect the observed heterogeneity
in the estimated prevalence of HBV infection among injection drug users (IDUs) and prisoners.
Conclusion: Our results indicate that prevalence of HBV infection among high risk groups was seemingly high in Iran. Health policy decision
makers should be aware of prevalence of HBV infection among different high risk groups and in different regions of Iran.
Keywords: Hepatitis B, Prevalence, Drug users, Sex workers, Prisoners, Meta-analysis, Iran.
(Please cite as: Almasi-Hashiani A, Ayubi E, Mansori K, Salehi-Vaziri M, Moradi Y, Gholamaliei B, et al. Prevalence
of hepatitis B virus infection among Iranian high risk groups: a systematic review and meta-analysis. Gastroenterol
Hepatol Bed Bench 2018;11(2):91-100).

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Lifestyle is identified as one of the most
important risk factors for CRC, especially in sporadic colorectal cancer. The natural composition of the gut microbiota changes
rapidly during the first decade of life. Maintaining homeostasis in the gut is essential as structural and metabolic functions of the
commensal microbiota inhibit gut colonization of pathogens. Dysbiosis, imbalance in function or structure of gut microbiota, has been
associated with a variety of diseases, such as colorectal cancer. The aim of this review was to investigate the possible links between
the dysbiosis in gut microbiota and colorectal cancer, and the potential role of anaerobic gut microbiota in the pathogenesis of
colorectal cancer. Based on this review, various studies have shown that some of the gut microbiota such as anaerobic bacteria
significantly increased in CRC patients, but we suggest more investigations are required to assess the importance of these bacteria and
their metabolites in the pathogenesis of CRC are required.
Keywords: Gut microbiota, Pathogenesis, Colorectal cancer.
(Please cite as: Jahani-Sherafat S, Alebouyeh M, Moghim Sh, Ahmadi-Amoli H, Ghasemian Safaei H. Role of gut
microbiota in the pathogenesis of colorectal cancer; a review article. Gastroenterol Hepatol Bed Bench
2018;11(2):101-109).

Aim: This study aims to predict survival rate of gastric cancer patients and identify the effective factors related to it, using artificial
neural network model.
Background: Gastric cancer is the most deadly disease in north and northeast provinces of Iran. A total of 430 patients with gastric
cancer who referred to Baghban clinic in Sari, from early November 2006 to late October 2013 were followed.
Methods: A historical cohort of patients who referred to Baghban Clinic, the cancer research center of Mazandaran University of
Medical Sciences in Sari, from early November 2006 to late October 2013 was studied. Three groups of variables (demographic,
biological and socio-economic) were studied. Survival rate and effective factors on survival time were calculated using Kaplan-Meier
methods and artificial neural networks and the best network structure were chosen using the mean square error and ROC curve. All
analyses were performed using SPSS v.18.0 and the level of significance was selected ?=0.05.
Results: In this research, the median survival time was 19±2.04 months. The 1 to 5-year survival rates for patients were 0.64, 0.44,
0.34, 0.24 and 0.19, respectively. The percentage of right predictions of the selected network and the area under the ROC curve were
92% and 94%, respectively. According to the results, the type of treatment, metastasis, stage of disease, histology grade, histology type
and the age of diagnosis were effective factors on survival period.
Conclusion: the 5 years survival rate of gastric cancer patients in Mazandaran is lower than other provinces which could be due to the
delay in diagnosis or patient’s referral. Therefore, the use of screening methods and early diagnosis could be influential for improving
survival rate of these patients.
Keywords: Gastric cancer, Survival analysis, Artificial neural network.
(Please cite as: Yazdani Charati J, Janbabaei G, Alipour N, Mohammadi S, Ghorbani Gholiabad S, Fendereski A.
predicting survival of gastric cancer patients by Artificial Neural Network model. Gastroenterol Hepatol Bed Bench
2018;11(2):110-117).

Aim: Pathway analysis of gastric atrophy to find new molecular prospective of disease.
Background: Gastric atrophy as a process which is accompanied with “loss of glans” in stomach can be considered as a risk factor of
gastric cancer. Here, the correlated biochemical pathways to the disorder have been analyzed via protein-protein interaction (PPI)
network analysis.
Methods: The genes related to gastric atrophy were retrieved by STRING database and organized in a network by Cytoscape. Three
significant clusters were determined by ClusterONE plug-in of Cytoscape. The elements of cluster-2 which contained all central nodes
of the network were enriched by ClueGO and the biochemical pathways discussed in details.
Results: The number of seven central nodes (which are included in cluster-2); INS, TP53, IL6, TNF, SRC, MYC, and IL8 were
identified. The biochemical pathways related to the elements of cluster-2 were determined and clustered in nine groups. The pathways
were discussed in details.
Conclusion: Pathway analysis indicates that the introduced central genes of the network can be considered as biomarkers of gastric
atrophy.
Keywords: Gastric atrophy, Network analysis, Gene, Biochemical pathway, Central node.
(Please cite as: Rezaei Tavirani M, Rezaei Tavirani S, Tajik Rostami F. Biochemical pathway analysis of gastric
atrophy. Gastroenterol Hepatol Bed Bench 2018;11(2):118-124).

Aim: The aim of this study was to determine common factors leading to incomplete colonoscopy with a special interest in patient body
mass index (BMI), and also to determine most common second line investigation, its pick up rates for cancer and the success rate of
re-scoping.
Background: Wide availability of scope guide in all procedures may decrease failure rate.
Methods: We retrospectively reviewed 2891 colonoscopies performed at our institution from August 2015 to July 2016. The cohort
was composed of all incomplete procedures (148) during this time period and a second cohort (148) of complete examinations which
were randomly selected for relation of BMI only. The data in incomplete colonoscopy group included age, gender, BMI, causes of
failure, mode of referral, second line investigation. The success of re-scope to pick up a cancer was compared to other modalities i.e.
CT Colonography etc.
Results: Male to female ratio was 1:4.8. High incomplete colonoscopy rate was noted in females (81%). Mean age in failure group was
64 ±15. Average BMI was 28± 15.Most common mode of referral was urgent or suspected cancer (74%). Common cause of failure was
patient intolerance (30%). Most common anatomical site of failure was sigmoid colon (35%). Completion rate of re-scoping in
experienced hands was 95%. A lower BMI is related with higher chances of failure or vice versa.
Conclusion: Lower BMI has higher chance of failure, possibly due to less extra colonic fat leading to tortuous colon. Female sex is
second most common cause of failure due to low intolerance to pain. Using stronger pain relief and equal distribution of these
characteristics on different list will have least implications in busy cancer screening unit.
Keywords: BMI, Colonoscopy, Cancer.
(Please cite as: Qureshi A, BiBi S, Madhotra R. Body mass index & low CIR in colonoscopy!. Gastroenterol Hepatol
Bed Bench 2018;11(2):125-130).

Aim: To determine the distribution of important mutations of the “a” determinant region in the HBV genome among patients in different
clinical phases of HBV infection.
Background: Variations in Hepatitis B infection not only change the outcome of the disease but also the symptoms from which the
chronic HBV patients are suffering.
Methods: We have meticulously selected a total of 40 chronic HBV patients from four different subclasses of chronic HBV clinical
phases including immune tolerant (IT), immune active (IA), inactive carrier (IC) and hepatitis B e antigen (HBeAg)-negative (ENEG);
10 samples per each phase. Mutations of the “a” determinant region were identified using PCR-Direct sequencing method.
Results: 17 amino-acid substitutions at 12 positions inside the “a” determinant were identified in all forty samples; 3 mutations in the
IT group, 6 mutations in the IA phase, 3 mutations in the IC patients and 5 mutations in the ENEG phase. Different substitutions were
observed in all four clinical phases. The IA phase was the most variant group with the highest number of amino-acid substitutions.
Conclusion: These results did not reveal a strong pattern to distinguish different clinical phases of Chronic HBV infection, but there
are some obvious differences regarding the number and position of mutations between these four clinical phases.
Keywords: “a” determinant region, Chronic hepatitis B infection, Clinical phases, Amino-acid substitution.
(Please cite as: Romani S, Hosseini SM, Mohebbi SR, Boonstra A, Hosseini Razavi A, Sharifian A. Characterization
of the “a” determinant region of the hepatitis B virus genome in Iranian patients at different clinical phases of
chronic infection. Gastroenterol Hepatol Bed Bench 2018;11(2):131-137).

 Aim: In this study, we investigated the prevalence of PARV4 virus among the healthy population and four other groups of HBV infected,

HCV infected, HIV infected and HIV/HCV co-infected individuals in Iran.
Background: Parvovirus 4 (PARV4) was first discovered in 2005, in a hepatitis B virus–infected injecting drug user (IDU). To date,
the best evidence about PARV4 transmission is parenteral roots which comes from IDU individuals. It seems that the prevalence of the
virus in the normal population is very low.
Methods: A total of 613 patients, including chronic HCV (n=103), HBV (n=193), HIV (n=180) infected individuals, HIV/HCV (n=34)
co-infected patients and 103 healthy controls, were studied by using nested-PCR and also real-time PCR techniques.
Results: Of those 180 samples were positive for HIV RNA, co-infection of PARV4 was detected in 3 cases (1.66%). All these three
patients were male with the age of 28, 32 and 36 years (mean: 32). No statistical differences were found between HIV positive group
and the healthy individuals. (P>0.05) The result of PARV4 PCR was negative in all other samples and healthy controls as well.
Conclusion: This study is the first to investigate the occurrence of PARV4 among these groups in Iran. The results show that the virus
is not significant in Iranian population, even in patients with blood born infections such as HCV, HBV or even HIV patients. Further
studies in other areas and various groups are required.
Keywords: Chronic infection, Hepatitis C virus, HBV, Parvoviridae, Parvovirus 4.
(Please cite as: Rastegarpouyani H, Mohebbi SR, Hosseini SM, Azimzadeh P, beyraghie S, Sharifian A, et al.
Detection of Parvovirus 4 in Iranian patients with HBV, HCV, HIV mono-infection, HIV and HCV co-infection.
Gastroenterol Hepatol Bed Bench 2018;11(2):138-144).

Aim: This study aimed to determine the seroprevalence and viremic infection of hepatitis delta virus (HDV) in Kermanshah.
Background: Hepatitis delta is one of the most complex viral infections of liver that along with hepatitis B virus could lead to fulminant
hepatitis, progressive chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
Methods: Referrals with positive HBs Ag were included and tested for HDV Ab using ELISA. Seropositives were subsequently
evaluated for viremia by assaying HDV RNA and HBV DNA using real-time PCR. Viremia-related variables were also assessed.
Results: From 1749 patients included, 30 had positive HDV Ab, which makes HDV seroprevalence 1.7%. Twenty-nine out of 30
seropositives were assayed for viremia. Fourteen cases (48.3%) had positive HDV PCR, 18 (62.1%) had positive HBV DNA. Eight
patients (27.6%) had simultaneous replication of HBV and HDV, six (20.7%) only had HDV replication, ten (34.5%) only had HBV
replication and five (17.2%) had no replication of either viruses.
Conclusion: Kermanshah seems to be a low prevalent area in Middle East. Viremic HDV infection was lower compared to Europe and
Africa, probably due to genetic variations of the hosts or the differences in genotypes or sub-types of hepatitis B and D viruses.
Keywords: Hepatitis D, Prevalence, Viremia, Iran.
(Please cite as: Sayad B, Naderi Y, Alavian SM, Najafi F, Janbakhsh A, Mansouri F, et al. Hepatitis D virus infection
in Kermanshah, west of Iran: seroprevalence and viremic infections. Gastroenterol Hepatol Bed Bench
2018;11(2):145-152).

Aim: To determine the impact of obesity on development of portal vein thrombosis in cirrhotic patients.
Background: Cirrhosis is a known risk factor for portal vein thrombosis (PVT). Evidence also points to obesity as being a risk factor
for venous thromboembolism. Limited information is available on how obesity impacts the development of PVT in cirrhotic patients.
Methods: This was a retrospective cohort study using the 2013 National Inpatient Sample. Patients older than 18 years with an ICD-9
CM code for any diagnosis of liver cirrhosis were included. There was no exclusion criteria. The primary outcome was the impact of
obesity on development of PVT. Obesity was also sub-classified according to body-mass index (BMI). Secondary outcomes were inhospital
mortality, ICU admission, shock, TPN use, and resource utilization. Odds ratios (OR) and means were adjusted for age, gender,
and ethnicity.
Results: We included 69,934 obese cirrhotics of which, 1,125 developed PVT (mean age 59 years, 35% female). Overall in-hospital
mortality rates were 9% (11% with PVT vs 5% without PVT). On multivariate analysis, obesity was not associated with a significantly
different adjusted OR for development of PVT compared to non-obese. When stratifying by obesity subtype, class 1 obesity was
associated with increased odds of PVT (OR: 1.45, 95%CI: 1.06-1.96, p=0.02), while class 3 obesity was associated with a decreased
odds of PVT (OR: 0.72, 95%CI: 0.58-0.88, p<0.01) compared to non-obese.
Conclusion: Obesity is not associated with increased odds of PVT.
Keywords: Obesity, Portal vein thrombosis, Cirrhosis, ICD-9.
(Please cite as: Zakko A, Kroner PT, Nankani R, Karagozian R. Obesity is not associated with an increased risk of
portal vein thrombosis in cirrhotic patients. Gastroenterol Hepatol Bed Bench 2018;11(2):153-158).

Aim: The present study designed to evaluate the toxic effect of anatase TiO2 NPs on BALF biochemical changes and liver alteration
in rats.
Background: Titanium dioxide (TiO2) nanoparticles (NPs) are utilized in food color additives and cosmetics worldwide. Humans
uptake these nanoparticulate by different routes and may exhibit potential side effects, lags behind the rapid development of
nanotechnology.
Methods: Sixty-three mats rats were used. Included by the control group and the experimental groups treated twice a week with 0.5, 5,
50, 1.5, 15, 150 mg/kg of nano-TiO2 (size 21 nm), for four consecutive weeks. Animals were sacrificed at 4 days, a month and three
months post-instillation. The levels of tumor necrosis factor - ? (TNF-?) and macrophage inflammatory protein- 2 (MIP-2) were
measured in the lung homogenate and in the bronchoalveolar lavage fluid (BALF) supernatants by enzyme-linked immunosorbent assay
(ELISA) and histopathological examination of liver tissue was performed.
Results: The results showed that TiO2 NP induces many alterations in the liver structure after 4 days, a month and reduced after 3
months from intratracheal instillation. This included liver heavy infiltration of inflammatory cells, an increase of collagen density in
portal triads, beginning of fibrosis formation and Glisson capsule thickness increase and TiO2 NPs reached the liver tissue after a month
from exposure at all doses especially low doses (0.5, 1.5, 5) mg/kg of TiO2 NPs.
Conclusion: The immune system was strongly responded in the groups treated with high doses (15, 50, 150) mg/kg of TiO2 NP leading
to raising the concentration of ?-TNF, and MIP-2 in BALF while they decrease in tissue homogenate.
Keywords: Titanium dioxide effects, Liver histopathological alteration, MIP-2 changes, TiO2 effects on TNF-?.
(Please cite as: Suker DK, Jasim FA. Liver histopathological alteration after repeated intra-tracheal instillation of
titanium dioxide in male rats. Gastroenterol Hepatol Bed Bench 2018;11(2):159-168).

A 28-month-old boy with hematochezia for 10 hours was admitted into our hospital. Colonoscopy was performed for the patient in
which a mass-like lesion was seen with marron color. The mass suspected intussusception; thus, colonoscopy was interrupted and
patient was sent to operation room. After 1 month the patient was good with no abdominal pain or defecation difficulty.
Keywords: Children, Rectum, Intussusception, Case report.
(Please cite as: Tajik P, Goudarzian AH. Intussusception of the rectum in children: a rare case report. Gastroenterol
Hepatol Bed Bench 2018;11(2):169-171).

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