Middle East Journal of Digestive Diseases
Volume:6 Issue: 2, Apr 2014

The hepatic progenitor cell (HPC) niche is a special microenvironment composed of different cell types, extracellular matrix (ECM) components, growth factors and cytokines released by the niche cells that help to maintain the characteristics of HPCs and the balance between their activation, proliferation and differentiation. Composition of this special microenvironment, created in response to specific liver damage, together with critical interactions between different partners of the HPC niche can determine the fate decision and differentiation pathways of HPCs. A number of recent studies have shed light on factors and signals from the HPC niche that determines the choice of HPCs differentiation towards a specific cell type depending on the nature of the liver injury and resultant microenvironment created by this injury. This paper seeks to provide an in-depth review, through a literature review and the authors'' experiences, of the most recent findings on the role of the HPC niche in fate choice option of HPCs toward either hepatocytes or bile duct epithelial cells and its clinical relevance.

Only a few studies in Western countrieshave investigated the association between gastroesophageal reflux disease(GERD) and mortality at the general population level and they have shown mixedresults. This study investigated the association between GERD symptoms andoverall and cause-specific mortality in a large prospective population-based studyin Golestan Province, Iran. Baseline data on frequency, onset time,and patient-perceived severity of GERD symptoms were available for 50001participants in the Golestan Cohort Study (GCS). We identified 3107 deaths(including 1146 circulatory and 470 cancer-related) with an average follow-upof 6.4 years and calculated hazard ratios (HR) and 95% confidence intervals(CI) adjusted for multiple potential confounders. SSevere daily symptoms (defined assymptoms interfering with daily work or causing nighttime awakenings on a dailybases, reported by 4.3% of participants) were associated with cancer mortality(HR 1.48, 95% CI: 1.04-2.05). This increase was too small to noticeably affectoverall mortality. Mortality was not associated with onset time or frequency ofGERD and was not increased with mild to moderate symptoms. We have observed an association withGERD and increased cancer mortality in a small group of individuals that hadsevere symptoms. Most patients with mild to moderate GERD can be re-assuredthat their symptoms are not associated with increased mortality.

Colorectal cancer is a common, deadly disease with different incidence rates in different parts of the world. The present study aims to investigate the clinical presentations, colonoscopic findings, and family history of colorectal cancer in the city of Khorramabad, Iran.This cross-sectional study, conducted in 2013, included 112 patients diagnosed with colorectal cancer by colonoscopy with pathological confirmation in addition to 112 individuals matched with patients for age and gender. Controls were chosen from the outpatients admitted to the Skin and Eye Clinics of ShohadaAshayer Hospital in Khorramabad who had no gastrointestinal diseases. A self-generated questionnaire was used to assess family history of smoking and gastrointestinal cancer history in immediate relatives of subjects from both groups. Fisher''s exact test and odds ratios (OR) were used to analyze the data. Based on the findings of this study, the most common clinical presentation in the patients was abdominal pain (67.9%). The sigmoid colon (40%) was the most common anatomical site of the tumor in men; the rectum (34.6%) and sigmoid colon (34.6%) were the most common sites in women, which was not statistically significant (p=0.21). There were 11 (19.6%) patients and 2 (3.6%) individuals in the control group who reported a history of colorectal cancer in their immediate relatives, which was statistically significant (p=0.008).In this study, left-sided colon cancer was more common. Subjects with colon cancer had more positive FHx. This indicated that genetic factors, in addition to environmental factors, could increase the incidence of colorectal cancer in a community. A better identification of these factors would result in better control and management of this disease.

Hereditary hemochromatosis (HH) is a very rare disease in Iran and reported cases are all negative for HFE mutation. We report a family affected by severe juvenile hemochromatosis (JH) with a detailed molecular study of the family members. We studied a pedigree with siblings affected by juvenile HH and followed them for 3 years. Microsatellite and gene sequencing analysis was performed for all family members.Two siblings (the proband and his sister, aged 26 and 30 years, respectively) were found to have clinical findings of JH. The proband’s brother, who presented with hyperpigmentation, died of probable JH at the age of 24 years. Gene sequencing analysis showed that the proband has a homozygote c.265T>C (p.C89R) HJV mutation + a heterozygote c.884T>C (p.V295A) mutation of HFE. The affected proband’s sister presented with the same HJV c.265T>C (p.C89R) homozygote mutation. In addition, we found the HJV c.98-6C>G polymorphic variant in both the sister and proband (homozygote). Sequencing of hepcidin (HAMP), TfR2, and FPN revealed no mutation.We have shown that molecular analysis of the HH related gene is a powerful tool for reliable diagnosis of JH and, in conjunction with magnetic resonance imaging (MRI) and noninvasive liver stiffness measurement by elastography, is adequate tool for management and follow up of HH.

This study aimed to explore demographic characteristics and clinical presentations of celiac disease (CD) in Northeastern Iran. This was a cross-sectional retrospective study of 193 adults with CD who presented to Mashhad University Gastroenterology Clinic between 2008 and 2013. Patient data that included mode of presentation and the presence of any concomitant illnesses were collected. Intestinal biopsy and serum anti-tissue transglutaminase (anti-tTG) were used for diagnosis. Mucosal lesions were classified according to modified Marsh classification. Overall, 132 females and 61 males, with a mean age at diagnosis of 32.6 ± 13.2 years were included. The patient’s chief complaints in order of decreasing frequency were dyspepsia (24.6%), diarrhea (20%), anemia (12.8%), and flatulence (7.2%). Bone disease was seen (osteopenia, osteoporosis) in 30% of patients. A positive family history of CD was found in 17.9% of cases. There were 64% who had serum anti-tTG >200 units/ml and 78% had a Marsh classification grade 3 on duodenal biopsy. The histology grade (Marsh) did not show any correlation with anti-tTG serum levels, age, body mass index (BMI) or hemoglobin levels. In Northeastern Iran, CD was seen more commonly in females and with non-diarrheal presentations. Abdominal discomfort, anemia and bone disease were most common primary presentations in this area. Histology grade showed no significant correlation with level of anti-tTG, BMI or hemoglobin levels. We suggest screening for CD in unexplained abdominal discomfort, bone disease and anemia.

Celiac disease presents with a wide spectrum of symptoms. This study clarifies different aspects of celiac disease along with the most common patterns of celiac presentation in Khuzestan Province, Iran. Patients'' information was obtained by evaluation of their files from the archives of the Khuzestan Celiac Society and records at gastroenterologists’ offices in this province.Overall, there were 103 (40 males, 63 females) patients included in this study. Patients’ mean ages were 33 ± 11 years (males) and 31.6 ± 11.7 years (females). In terms of geographic distribution, 54.1% resided in the center of the province followed by 26.5% who were residents of the northern area. The rate of employment among men was 70.6% whereas it was 8.3% for women. In terms of education, 21.9% of men and 33.3% of women had academic educations. The rate of matrimony was 80.6% (n=29) for men, 65.4% (n=38) for women and 3.4% (n=2) who were divorced. Mean height was 164 ± 14 cm in men and 157.5 ± 10 cm in women. Mean BMI at the time of presentation was 22.7 in men and 22.6 in women. The most common gastrointestinal (GI) complaints in male patients were diarrhea (35%), reflux (20%), bloating (17.5%), abdominal pain (15%), vomiting (15%) and constipation (7.5%). Female patients experienced diarrhea (49.2%), abdominal pain (31.7%), bloating (31.7%), vomiting (19%), constipation (9.5%) and reflux (7.9%). The most common concomitant non-GI disorders among male patients were anemia (17.1%), thyroid disease (14.3%), and weight loss (14.3%); women experienced anemia (33.9%), thyroid disease (12.5%), and weight loss (7.1%). Approximately half of the patients exhibited symptoms for more than five years prior to diagnosis and 90% were diagnosed by gastroenterologists. Of these, 43% had normal endoscopy results. The most common serologic markers were anti-TTG (69.9%), anti-EMA (27.7%). Physicians, prior to attributing patients’ symptoms to irritable bowel syndrome (IBS), should be aware that patients who present with long-term nonspecific symptoms might possibly have celiac disease. During endoscopy, the threshold for obtaining biopsies should be low.

Viral hepatitis and toxins comprise most common causes of fulminate hepatic failure that are often diagnosed with standard laboratory tests. Herein we discuss a rare, difficult to diagnosis etiology of acute liver failure (ALF). A 62-year-old man presented with a two-week history of fever and fatigue. At four days before admission he became lethargic. His past medical and drug histories were unremarkable. Physical examination revealed generalized jaundice, fever and loss of consciousness. Laboratory tests showed elevated liver transaminases with direct hyper-bilirubinemia. Abdominal ultrasonography and CT scan showed hepatosplenomegaly and para-aortic abdominal lymphadenopathy. A further work-up included liver biopsy. The histopathology and imunohistochemistry was compatible with diffuse large B-cell lymphoma. He underwent high dose glucocorticoid therapy but his condition deteriorated rapidly and he died eight days after admission. ALF, as an initial manifestation of malignant hepatic infiltration is extremely rare yet should be considered in all patients with unknown hepatic failure that are highly suspicious for malignant neoplasm.

The human intestinal tract is home to a complex ecosystem of commensal bacteria that live in a mutually beneficial state with the host. The study of the intestinal microbiota has gained considerable attention in recent years as it has been found to contribute to intestinal and extraintestinal diseases.