Angiotensin receptor blockers might be protective against hepatic steatosis after liver transplantation.

BACKGROUND: Hepatic steatosis is an increasing complication in liver transplant recipients. Currently, there is no pharmacologic therapy for treatment of hepatic steatosis after liver transplantation. The aim of this study was to determine the association between use of angiotensin receptor blockers (ARB) and hepatic steatosis in liver transplant recipients. METHODS: We conducted a case-control analysis on data from Shiraz Liver Transplant Registry. Liver transplant recipients with and without hepatic steatosis were compared for risk factors including use of ARB. RESULTS: A total of 103 liver transplant recipients were included in the study. Thirty five patients treated with ARB and 68 patients (66%) did not receive these medications. In univariate analysis, ARB use (P = 0.002), serum triglyceride (P = 0.006), weight after liver transplantation (P = 0.011) and etiology of liver disease (P = 0.008) were associated with hepatic steatosis after liver transplantation. In multivariate regression analysis, ARB use was associated with lower likelihood of hepatic steatosis in liver transplant recipients (OR = 0.303, 95% CI: 0.117-0.784; P = 0.014). Mean duration of ARB use (P = 0.024) and mean cumulative daily dose of ARB (P = 0.015) were significantly lower in patients with hepatic steatosis. CONCLUSION: Our study showed that ARB use was associated with reduced incidence of hepatic steatosis in liver transplant recipients.

Altered ARID1A expression in colorectal cancer.

BACKGROUND: ARID1A has been described as a tumor suppressor gene, participating in chromatin re-modeling, epithelial-mesenchymal-transition and many other cellular and molecular processes. It has been cited as a contribute in tumorigenesis. The role of ARID1A in CRC is not yet defined. AIM: To investigate the role of ARID1A methylation and CNV in its expression in CRC cell lines and to examine the relationship between ARID1A status with survival and clinicopathologic characteristics in patients with CRC. METHODS: We used RT-PCR to determine both CNV and expression of ARID1A from six CRC cell lines. We used MSP to evaluate methylation of ARID1A. IHC was used to assess ARID1A protein expression. We also evaluated MSI and EMAST status in 18 paired CRC and adjacent normal tissues. 5AzadC was used to assess effect of DNA demethylation on ARID1A expression. Statistical analysis was performed to establish correlations between ARID1A expression and other parameters. RESULTS: Among the 18 CRC tumors studied, 7 (38.8%) and 5 tumors (27.7%) showed no or low ARID1A expression, respectively. We observed no significant difference in ARID1A expression for overall patient survival, and no difference between clinicopathological parameters including MSI and EMAST. However, lymphatic invasion was more pronounced in the low/no ARID1A expression group when compared to moderate and high expression group (33% VS. 16.6% respectively. ARID1A promoter methylation was observed in 4/6 (66%) cell lines and correlated with ARID1A mRNA expression level ranging from very low in SW48, to more pronounced in HCT116 and HT-29/219. Treatment with the methyltransferase inhibitor 5-Azacytidine (5-aza) resulted in a 25.4-fold and 6.1-fold increase in ARID1A mRNA expression in SW48 and SW742 cells, respectively, while there was no change in SW480 and LS180 cells. No ARID1A CNV was observed in the CRC cell lines. CONCLUSION: ARID1A expression is downregulated in CRC tissues which correlates with it being a tumor suppressor protein. This finding confirms ARID1A loss of expression in CRC development. Our in-vitro results suggest high methylation status associates with reduced ARID1A expression and contributes to CRC tumorigenesis. However, there was no significant association between ARID1A loss of expression and clinicopathological characteristics. Future in-vivo analysis is warranted to further establish ARID1A role in colorectal neoplastic transformation.

Outcomes of patients with acute severe autoimmune hepatitis: Predictors of non-response to corticosteroids and need for liver transplantation.

BACKGROUND AND AIMS: Acute severe autoimmune hepatitis (AS-AIH) is an evolving concept and the outcomes and optimal treatment have been less studied. In this study, we aimed to investigate the outcomes of patients with AS-AIH and predictors of non-response to corticosteroid therapy and need for liver transplantation. METHODS: In a retrospective cohort, we included patients with AS-AIH admitted to our liver center. We defined AS-AIH based on the international autoimmune hepatitis group score as acute presentation of AIH with an international normalized ratio (INR) ≥ 1.5 and without liver cirrhosis and hepatic encephalopathy. All patients received high dose corticosteroid therapy. Treatment response was defined as liver transplant free survival at 4 months after presentation. Factors associated with response to corticosteroids and survival of patients were studied. RESULTS: In total, 61 patients with AS-AIH were included. Forty-seven patients responded to corticosteroid therapy. In the multivariate regression model, baseline INR (odds ratio [OR]: 0.184; 95% confidence interval [CI]: 0.048-0.699; p = 0.013) and delayed versus early initiation of corticosteroid (after vs. before 5 days of presentation) (OR: 0.189; 95% CI: 0.039-0.919; p = 0.039) were independent predictors of clinical non-response to corticosteroid therapy. In the multivariable Cox regression model, baseline INR level (OR: 2.542; 95% CI: 1.188-5.440; p = 0.016) and delayed initiation of corticosteroids (OR: 3.578; 95% CI: 1.084-11.812; p = 0.036) were independent predictors of liver transplant free survival at 6 months after diagnosis. CONCLUSION: Delayed initiation of corticosteroid therapy might be predictive of clinical non-response to medical therapy and need for liver transplantation in patients with AS-AIH.

Anatomic Variations of the Cystic Duct in Magnetic Resonance Cholangiopancreatography in Shiraz: A Cross-Sectional Study.

BACKGROUND: Anatomic variations of the cystic duct (CD) are commonly encountered. Being aware of these variants will reduce complications subsequent to surgical, endoscopic, or percutaneous procedures. Magnetic resonance cholangiopancreatography (MRCP) is the least invasive and the most reliable modality for biliary anatomy surveys. This study aimed to determine the prevalence of cystic duct variations in the Iranian population. METHODS: In this retrospective cross-sectional study, MRCP images of 350 patients referred to Shiraz Faraparto Medical Imaging and Interventional Radiology Center from October 2017 to October 2018 were reviewed. The CD course and insertion site to the extrahepatic bile duct (EHBD) was determined and documented in 290 cases. Descriptive statistics and Chi square test were applied for data analysis via SPSS software. RESULTS: About 77% of cases revealed the classic right lateral insertion to the middle third of EHBD. The insertion of CD to the upper third and the right hepatic duct was 10%, and the insertion to the medial aspect of the middle third of EHBD from anterior or posterior was noted to be about 7.6%. From 2.8% of insertions to the lower third, 1% demonstrated parallel course, and finally, 0.3% of cases presented short CD. CONCLUSION: CD variations are relatively common, and MRCP mapping prior to the hepatobiliary interventions could prevent unexpected consequences.

Early Liver Transplant In Patients With Liver Cirrhosis Recovered From COVID-19 Infection.

OBJECTIVES: Coronavirus disease 2019 has resulted in significant morbidities and mortalities in nearly all parts ofthe world. There remain major concerns about management, timing, and safety of liver transplant in patients who have recovered from COVID-19. We aimed to study the clinical course and outcomes of patients with liver cirrhosis who recovered from COVID-19 and underwent liver transplant from deceased donors. MATERIALS AND METHODS: A retrospective study was conducted on liver transplant recipients who underwent liver transplant from April 1, 2020, to January 30, 2021. We evaluated all recipients of liver transplantfrom deceased donors during this period in the COVID-19 pandemic. RESULTS: There were 14 patients with decompensated liver cirrhosis who had recovered from COVID-19 as documented by reverse transcription-polymerase chain reaction test for SARS-CoV-2. Mean duration from COVID-19 to transplant surgery was 56.14 ± 29.96 days. Mortality occurred in 3 patients, and of whom 2 had been hospitalized and received medications for COVID-19 before transplant. Five patients had positive reverse transcription-polymerase chain reaction results for SARS-CoV-2 after liver transplant. CONCLUSIONS: This is a large reported series of patients with liver cirrhosis who have received liver transplant after recovery from COVID-19. We provided evidence that liver transplant from deceased donors should be considered in patients recovered from COVID-19, especially in those with deterioration of clinical status.

Metabolic syndrome, hepatic fibrosis, and steatosis diagnosed by liver stiffness measurement and controlled attenuation parameter after liver transplantation: the impact on long-term survival.

BACKGROUND: Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) are used for diagnosis of liver fibrosis and steatosis. This study aimed to noninvasively evaluate hepatic steatosis and fibrosis in liver transplant recipients using CAP and LSM and the impact on survival of patients. METHODS: In a prospective study, adult liver transplant recipients were included. CAP and LSM obtained during transient elastography (TE) were used for assessment of hepatic steatosis and fibrosis. Patients were followed during 4 years for mortality as the main outcome after liver transplantation. RESULTS: From 296 patients, 24.7% and 25% of liver transplant recipients had liver steatosis and fibrosis in CAP and LSM, respectively. In multivariable Cox regression analysis, etiology of liver disease (NASH versus non-NASH) (HR: 3.125; 95% CI: 1.594-6.134; p = 0.001), and post-transplant diabetes mellitus (PTDM) (HR: 2.617; 95% CI: 1.396-4.926; p = 0.003) were associated with hepatic steatosis after liver transplantation.  In multivariable Cox regression analysis, liver fibrosis was an independent predictor of mortality after liver transplantation (HR: 4.926; 95%CI: 1.779-13.513; p = 0.002). CONCLUSION: CAP and LS measurement during TE are useful methods for diagnosis of hepatic steatosis and fibrosis in liver transplant recipients. LS measurement might predict long-term survival of patients.

Noninvasive Estimation of Hepatic Steatosis by Controlled Attenuation Parameter in Living Donor Liver Transplant.

OBJECTIVES: Estimation of liver fat among living donor candidates is necessary before living donor liver transplant. This study aimed to investigate the usefulness of the controlled attenuation parameter compared with liver biopsy for pretransplant estimation of hepatic steatosis in living liver donors. MATERIALS AND METHODS: In this retrospective study, we included all individuals who underwent transient elastography with controlled attenuation parameter and ultrasonography-guided liver biopsy as a part of donor evaluations before living donor liver transplant. Clinical and laboratory data of living donor candidates were reviewed and collected. RESULTS: Of 49 donor candidates included in this study, 21 (42.9%) had different degrees of hepatic macrosteatosis. Of the 21 donor candidates who had hepatic steatosis in liver biopsy, 13 individuals were diagnosed to have steatosis in transient elastography. Of the 28 donor candidates without hepatic steatosis in liver biopsy, 26 individuals showed no steatosis in transient elastography (odds ratio: 21.12; 95% CI, 3.91- 114.08; P < .001). Controlled attenuation parameter was useful in discriminating presence (P = .001) and grade of hepatic steatosis (P = .009) compared with liver biopsy with good sensitivity and specificity. CONCLUSIONS: The controlled attenuation parameter is a noninvasive method for detection of hepatic steatosis in living donor candidates and can be used as an adjunct to liver biopsy for screening of living donor candidates before liver transplant.

Efficacy of Rose Oil Soft Capsules on Clinical Outcomes in Ulcerative Colitis: A Pilot Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

BACKGROUND: Ulcerative colitis is the most common form of inflammatory bowel disease worldwide, which presents with superficial ulcers in the rectum and colon. The aim of this study was to assess the effectiveness of rose oil soft capsules over placebo on the clinical outcomes in moderate to severe ulcerative colitis. MATERIALS AND METHODS: This study was a pilot randomized, double-blind clinical trial, and the 40 patients were assigned into rose oil and placebo groups (n=20 per group). All patients were instructed to use their prescribed two soft capsules three times daily for two months. The clinical symptoms, quality of life the patients, and calprotectin level were evaluated via partial Mayo clinic score, irritable bowel disease questionnaire (IBDQ-9), and calprotectin kit as primary outcome measures. RESULTS: The mean age of the participants was 41±10 years. Most of them (53.6%) were male, and the remaining (46.4%) were female. The demographic and baseline data showed no differences between the two groups. Partial Mayo clinic scores decreased in both groups after the treatment, but the difference between the rose oil and placebo groups was not statistically significant (P=0.99). IBDQ-9 score also increased in both interventions before and after the treatment (P=0.012), though the differences between these two groups were not statistically significant (P=0.61). There were no significant differences between the two study groups either in terms of calprotectin level (P=0.219). CONCLUSION: This study showed that rose oil might improve ulcerative colitis clinical outcomes, but for a better evaluation, it is imperative to conduct experiments with a large sample size and longer follow-up observation.

False negative and false positive rates in common bile duct brushing cytology, a single center experience.

AIM: In this study we tried to find out the accuracy of biliary tract brushing cytology in our center as the largest referral center in the south of Iran. BACKGROUND: Common bile duct brushing cytology has been introduced as the method of choice for the diagnosis of pancreaticobiliary malignancies. However, there have been controversial reports about the sensitivity, specificity and overall accuracy of this method in the English literature. METHODS: During the study period (2012-2016) there has been 166 cases of common bile duct brushing cytology taken during endoscopic retrograde cholangiopancreatography (ERCP). One case has been excluded because of inadequate number of cells in the cytology smear. All the smears have been stained by routine cytologic stains and screened by cytotechnologists and diagnosed by expert cytopathologist. Final diagnosis by biopsy has been considered as the gold standard. RESULTS: According to the final histologic diagnosis as the gold standard, there were 22 false negative and 7 false positive cases. All of the false positive cases have been suspected cases in the background of primary sclerosing cholangitis. The most common final diagnosis of false negative cytologic diagnoses has been intrahepatic cholangiocarcinoma in which no malignant cell has been identified in the presence of adequate number of normal ductal epithelial cells. CONCLUSION: Common bile duct brushing cytology is the method of choice for the diagnosis of pancreaticobiliary tract malignancies; however, having high specificity (90%), the sensitivity is low (56%). Cytologic diagnosis of biliary tract malignancies should be made with caution in the patients with primary sclerosing cholangitis. Also it is important to know that high false negative rate is present in common bile duct brushing cytology especially in the cases of intrahepatic cholangiocarcinoma without extension into extrahepatic ducts.

Liver Transplantation Status in Iran: A Multi-center Report on the Main Transplant Indicators and Survival Rates.

BACKGROUND: Iran's experience with liver transplantation (LT) began more than two decades ago. The purpose of this article is to present the status of LT in Iran, review specific characteristics of the programs, their outcomes, and their growth to become one of the largest LT programs in the world. METHODS: A questionnaire, asking for data on the number of transplants performed and specifics of the recipients and type of donors with focus on indications and outcomes was sent to LT programs. RESULTS: During a period of 23 years, 4,485 LTs were performed at 6 centers in the country. Of these, 4106 were from deceased donors and 379 were from living donors. There were 3553 adults and 932 pediatric recipients. Hepatitis B and biliary atresia were the most common etiologies in adult and pediatric patients, respectively. Overall survival rates at 1, 5, and 10 years were 85%, 77%, and 71% for adults and 76%, 67% and 56% for pediatric patients, respectively. CONCLUSION: Approval of the brain death law in Iran and coordinated efforts by the transplant centers to build comprehensive LT programs has resulted in the ability to procure more than 700 deceased donors per year with acceptable long-term survival.

An unusual cause of thrombotic thrombocytopenic purpura in pregnancy.

Thrombotic thrombocytopenic purpura is a disseminated form of thrombotic microangiopathy. Although most cases are assumed to be idiopathic, its association with malignancy is well-recognized and it usually occurs at the terminal stage of cancer. The condition is characterized by microangiopathic hemolytic anemia and thrombocytopenia. It is generally idiopathic, and its association with adenocarcinomas is extremely rare.

Polymorphism of the promoter region of C-509T of transforming growth factor-beta1 gene and ulcerative colitis.

BACKGROUND: Transforming growth factor-beta is a regulatory protein that plays a key role in inflammatory, fibrotic, and immunological events in the intestinal mucosa. Recently, attention has been focused on the role of transforming growth factor-beta in the etiopathogenesis of inflammatory bowel disease. Enhanced expression of transforming growth factor-beta mRNA in the lamina propria and a disordered expression pattern of transforming growth factor-beta1 receptors I and II in epithelial cells have been documented in the colonic mucosa of patients with ulcerative colitis and Crohn's disease. Based on these associations, we report in this study, the restriction fragment length polymorphism-polymerase chain reaction and allele frequencies of the transforming growth factor-beta gene polymorphisms in a population of Iranian patients with ulcerative colitis and healthy controls. We analyzed whether these two polymorphisms are related with the disease characteristics. METHODS: One hundred fifty-seven (75 males and 82 females) unrelated patients with ulcerative colitis attending the Departments of Gastroenterology, Nemazi and Faghihi Hospitals, affiliated to Shiraz University of Medical Sciences, Shiraz, Iran were enrolled into this study. Ninety-four age- and sex-matched healthy volunteers with no history of chronic bloody diarrhea and abdominal pain (41 males and 53 females) served as the control group. The change at position -509 (C/T) of the transforming growth factor-beta1 gene was studied using restriction fragment length polymorphism-polymerase chain reaction in this study. RESULTS: The mean age of patients was 36.4 (range: 23 - 51) years. The genotype at position -509 (C/T) in 58 (37%) patients with ulcerative colitis, and 39 (41.5%) normal subjects, were homozygous as CC. In addition, 65 (41.5%) patients and 44 (47%) normal individuals were heterozygous as CT. Thirty-four (21.5%) of 157 patients, and 11 (11.5%) of 94 normal individuals, were homozygous as TT. There was no statistically significant difference between patients and normal female individuals in respect to genotype distribution and allele frequency at the said position (P = 0.138). CONCLUSION: No association could be found between transforming growth factor-beta1 -509 (C/T) promoter gene polymorphism and patients with ulcerative colitis.

Association of H pylori cagA and vacA genotypes and IL-8 gene polymorphisms with clinical outcome of infection in Iranian patients with gastrointestinal diseases.

AIM: To find out if a functional promoter polymorphism in the IL-8 gene along with cagA status and polymorphisms in vacA gene influence the type of diseases in Iranian patients infected by H pylori. METHODS: IL-8 -251 A/T polymorphism was genotyped by oligonucleotide allele specific PCR (ASO-PCR) in a sample of 233 patients with H pylori infection undergoing upper gastrointestinal endoscopy. The presence of cagA gene and polymorphisms in vacA gene was also determined by PCR. Association of these genetic polymorphisms with the development of gastritis, peptic ulcers as well as gastric cancer was tested. RESULTS: When the patients with different clinical manifestations were compared according to the presence of cagA gene or various vacA genotypes, only the vacA genotypes were significantly different among gastritis, peptic ulcer and gastric cancer patients (chi 2 = 17.8; P = 0.001). Furthermore, there was a significant difference in the frequency of IL-8 -251 A/T genotypes between patients with gastric cancer and benign diseases (chi 2 = 10.47; P = 0.005). CONCLUSION: The IL-8 -251 A/T polymorphism and the polymorphisms in H pylori vacA gene are involved in limiting the infection outcome to gastritis and peptic ulcer or in favoring cancer onset in Iranian patients.

High rate of A2142G point mutation associated with clarithromycin resistance among Iranian Helicobacter pylori clinical isolates.

This study aimed to investigate the clarithromycin resistance and its associated molecular mechanisms among Helicobacter pylori isolates from dyspeptic patients in Shiraz, Iran. From January to May 2014, 100 H. pylori strains were isolated from patients with gastroduodenal disorders. The resistance to clarithromycin was quantitatively evaluated, using Epsilometer (E-test) method. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on all the isolates to detect A2143G and A2142G mutations in 23S rRNA gene. The H. pylori isolation rate was found to be 31.4%. E-test showed that 20% of isolates were resistant to clarithromycin (MIC ≥ 1 mg/L). MIC of clarithromycin ranged between 0.016 and 24 mg/L. Findings of PCR-RFLP showed that the A2142G was the most (90%) frequently point mutation, followed by the A2143G (10%). No statistically significant difference was found between H. pylori clarithromycin resistance point mutations and patients' gender or age. To the best of our knowledge, this is the first report of high frequency of A2142G point mutation in Iran and probably in other regions of the world. Considering the increasing trend of H. pylori resistance to clarithromycin due to these mutations, it is crucial to investigate the new therapeutic approaches against H. pylori infection.

Emerging Epidemic of Inflammatory Bowel Disease in a Middle Income Country: A Nation-wide Study from Iran.

BACKGROUND: The burden of inflammatory bowel disease (IBD) hasn't been reported in Iran. We aimed to estimate the prevalence and incidence of IBD and its trend in Iran at national and subnational level from 1990 to 2012. METHODS: We conducted a systematic review of English and Persian databases about the epidemiology of IBD. We also collected outpatient data from 17 provinces of Iran using almost all public and private referral gastroenterology clinics. Prevalence and incidence rate was calculated at national and subnational levels. The Kriging method was used to extrapolate provinces with missing data and GPR model to calculate time trends of rates at subnational level. RESULTS: We found 16 case series, two population-based studies, and two review articles. We collected 11,000 IBD cases from outpatient databases. Among them, 9,269 (84.26%) had ulcerative colitis (UC), 1,646 (14.96%) had Crohn's disease (CD), and 85 had intermediate colitis (IC). A total of 5,452 (49.56%) patients were male. Mean age at diagnosis was 32.80 years (CI: 13 - 61) for UC and 29.98 years (CI: 11 - 58) for CD. Annual incidences of IBD, UC, and CD in 2012 were 3.11, 2.70, and 0.41 per 100,000 subjects respectively. Prevalence of IBD, UC, and CD in 2012 were 40.67, 35.52, and 5.03 per 100,000 subjects respectively. The incidence of UC and CD showed a significant increase during the study period (P for trend < 0.05). CONCLUSIONS: The incidence and prevalence of IBD are increasing in Iran. Establishing a national IBD registry seems necessary for comprehensive care of IBD patients in Iran.

Esophageal melanocytosis in oral opium consumption.

Esophageal melanocytosis is a rare and benign condition, characterized by melanocytic proliferation of the esophageal squamous epithelium with heavy melanin deposition. The etiology and pathogenesis has not been exactly known but it seems to be a chronic stimulus such as gastroesophageal reflux. This condition is very rare and about 35 cases have been reported so far, most of which have been from India and Japan. Herein, we present a case of esophageal melanocytosis in a patient with long history of oral opium consumption. To the best of our knowledge, such a history has not been reported.

IL-1ß (+3953 C/T) and IL-8 (-251 A/T) gene polymorphisms in H. pylori mediated gastric disorders.

BACKGROUND: Previous studies imply that IL-1 and IL-8 gene variations may play a crucial role in the genetic predisposition to different gastric disorders upon H. pylori infection. OBJECTIVE: The aim of this study was to determine the potential association between the prevalence of certain polymorphic sites and the risk of gastric disorders in Iranian population. METHODS: One hundred and forty three unrelated individuals with different gastric disorders and 374 normal individuals with no gastric disorders and with a negative serology test for H. pylori (control group) were studied for the association between IL-1ß (+3953 C/T) and IL-8 (-251 A/T) gene polymorphisms and H. pylori-mediated gastritis and gastric ulcer. An analysis of genotype frequency for these genes was performed using RFLP-PCR. RESULTS: Based on the data obtained from culture and pathologic findings, the patients were classified into three subpopulations: H. pylori(+) non-ulcerative gastritis(+), H. pylori(+) ulcerative gastritis(+) and H. pylori(-) non-ulcerative gastritis(+). A significantly higher frequency of TT genotype (p=0.02) in IL-1ß +3953 in H. pylori(+) ulcerative gastritis(+) was revealed compared to the control group. There were no significant differences among other subpopulations. No significant differences in allele and genotype frequencies of IL-8 (-251A/T) were found among the patients. CONCLUSION: The data suggest that TT genotype in IL-1ß +3953 may be a major contributing genetic risk factor for H. pylori induced gastric ulcer. Moreover, the role of other bacterial and host response factors, such as bacterial adherence peptides, host chemokines, and genes involved in gastric acid secretion, must be further investigated in different ethnic populations.