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in category gastroenterology

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1: Clinical Features of COVID-19 Related Liver Damage
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Posted 27 Feb 2020

Clinical Features of COVID-19 Related Liver Damage
6,078 downloads medRxiv gastroenterology

Zhenyu Fan, Liping Chen, Jun Li, Cheng Tian, Yajun Zhang, Shaoping Huang, Zhanju Liu, Jilin Cheng

BACKGROUNDA recent outbreak of SARS-CoV-2 infection occurs mainly in China, with rapidly increasing the number of cases (namely COVID-19). Abnormal liver functions are frequently present in these patients, here we aimed to clarify the clinical features of COVID-19-related liver damage to provide some references for the clinical treatment. METHODSIn this retrospective, single-center study, we included all confirmed COVID-19 cases in Shanghai Public Health Clinical Center from January 20 to January 31, 2020. The outcomes were followed up until February 19, 2020. A total of 148 cases were analyzed for clinical features, laboratory parameters (including liver function tests), medications and the length of stay. FINDINGSOf 148 confirmed SARS-CoV-2-infected patients, 49.3% were females and 50.7% were males. The median age was 50.5 years (interquartile range, 36-64). Patients had clinical manifestations of fever (70.1%), cough (45.3%), expectoration (26.7%) at admission. 75 patients (50.7%) showed abnormal liver functions at admission, characterized by an increased of alt, ast, GGT, AKP . Patients (n = 75) who had elevated liver function index were more likely to have a moderate-high degree fever (44% vs 27.4%; p = 0.035) and significantly present in male patients (62.67% vs 38.36%; p = 0.005). The numbers of CD4+ and CD8+ T cells were significantly lower in abnormal liver function group than those in normal liver function group. There was no statistical difference in prehospital medications between normal and abnormal liver function groups, while the utilization rate of lopinavir/ritonavir after admission was significantly higher in patients with emerging liver injury than that in patients with normal liver functions. Importantly, the emerging abnormal liver functions after admission caused a prolonged length of stay INTERPRETATIONSARS-CoV-2 may cause the liver function damage and the Lopinavir/ritonavir should be applied carefully for the treatment of COVID-19. FUNDINGShanghai Science and Technology Commission Fund Project and National Science and Technology Major Project

2: Liver Function in Novel Coronavirus Disease (COVID-19): A Systematic Review and Meta-Analysis
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Posted 23 May 2020

Liver Function in Novel Coronavirus Disease (COVID-19): A Systematic Review and Meta-Analysis
5,014 downloads medRxiv gastroenterology

Mohammad Zahedi, Mohammad Yousefi, Mahdi Abounoori, Mohammad Malekan, Fatemeh Tajik, Keyvan Heydari, Parham Mortazavi, Monireh Ghazaeian, Fateme Sheydaee, Amirreza Nasirzadeh, Reza Alizadeh-Navaei

Introduction:The outbreak of new coronavirus has become a global public health challenge. Given a consequential liver function, and the high risk of death coming from liver disorders, the assessment of Novel Coronavirus Disease on liver function is importance. Hence, we carried out this meta-analysis to heightening insight into the occult features of COVID 19, which is likely to affect liver function. Method:This study was performed using databases of Web of Science, Scopus, and PubMed. We considered English cross-sectional and case-series papers, which reported available findings on the association between liver injury and COVID-19 infection. We used the STATA v.11 and random effect model for data analysis. Result:In this present meta-analysis, 52 papers, including 8,463 COVID-19 patients, were studied. The prevalence of increased liver enzymes among the patients, including Alanine aminotransferase, Aspartate aminotransferase, were 30% and 21% in non-severe patients, respectively, which were 38% and 48% in severe patients. The prevalence of increasing C-reactive protein, Lactate dehydrogenase, D-dimer, and Bilirubin were 55%, 39%, 28%, and 10% in non-severe patients respectively, which were 78%, 75%, 79% and 17% in sever patients.The prevalence of liver toxicity as a complication of COVID-19 was 20%.Also patients who have severe condition are 5.54, 4.22, 4.96, 4.13 and 4.34 times more likely to have elevated CRP, ALT, AST, LDH, D-dimer enzymes retrospectively. Conclusion:Elevation of some liver markers were higher in patients with severe COVID-19 infection. All to gather, we assumed that abnormal liver markers could act as a prognostic factor for a better survey of COVID-19.

3: Diarrhea may be underestimated: a missing link in 2019 novel coronavirus
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Posted 11 Feb 2020

Diarrhea may be underestimated: a missing link in 2019 novel coronavirus
3,299 downloads medRxiv gastroenterology

Weicheng Liang, Zhijie Feng, Shitao Rao, Cuicui Xiao, Ze-Xiao Lin, Qi Zhang, Qi Wei

The outbreak of pneumonia caused by the 2019 Novel Coronavirus (2019-nCoV) was reported in Wuhan City, China. However, the clinical symptoms varied in different reports. Based on results of inter-group difference test, we found that the incidence of diarrhea differed in three recent reports. As 2019-nCoV utilizes the same cell entry receptor ACE2 as severe acute respiratory syndrome coronavirus (SARS-CoV) and ACE2 tightly controls intestinal inflammation, to trace the route of infection mediated by 2019-nCoV, we used the single-cell RNA sequencing data for analysis. We found that the ACE2 mRNA was highly expressed in the healthy human small intestine rather than the lung. Besides, single-cell RNA sequencing data showed that ACE2 was significantly elevated in the proximal and distal enterocytes, where the small intestinal epithelium is exposed to the foreign pathogen. Thus, we suspect that ACE2-expressing small intestinal epithelium cells might be vulnerable to 2019-nCoV infection when people eat infected wild animals and diarrhea may serve as an indicator for infection, suggesting that clinicians should pay more attention to patients with diarrhea during the outbreak of pneumonia.

4: The influence of pH on SARS-CoV-2 infection and COVID-19 severity
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Posted 11 Sep 2020

The influence of pH on SARS-CoV-2 infection and COVID-19 severity
2,535 downloads medRxiv gastroenterology

Leandro Jimenez, Ana C Codo, Vanderson S Sampaio, Antonio E.R. Oliveira, Lucas KK Ferreira, Gustavo G Davanzo, Lauar B Monteiro, Joao V Virgilio-da-Silva, Mayla GS Borba, Gabriela F Souza, Nathalia Zini, Flora A Gandolfi, Stefanie P Murano, Jose L Proenca-Modena, Fernando A Val, Gisely C Melo, Wuelton M Monteiro, Mauricio L Nogueira, Marcus VG Lacerda, Pedro M. Moraes-Vieira, Helder I Nakaya

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect a broad range of human tissues by using the host receptor angiotensin-converting enzyme 2 (ACE2). Individuals with comorbidities associated with severe COVID-19 display higher levels of ACE2 in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression of ACE2. Here we showed that patients with Barrett's esophagus (BE) have a higher expression of ACE2 in BE tissues compared to normal squamous esophagus, and that the lower pH associated with BE may drive this increase in expression. Human primary monocytes cultured in reduced pH displayed increased ACE2 expression and viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of COVID-19 patients that previous use of proton pump inhibitors is associated with 2- to 3-fold higher risk of death compared to those not using the drugs. Our work suggests that pH has a great influence on SARS-CoV-2 Infection and COVID-19 severity.

5: Profiling ACE2 expression in colon tissue of healthy adults and colorectal cancer patients by single-cell transcriptome analysis
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Posted 23 Feb 2020

Profiling ACE2 expression in colon tissue of healthy adults and colorectal cancer patients by single-cell transcriptome analysis
2,524 downloads medRxiv gastroenterology

Haoyan Chen, Baoqin Xuan, Yuqing Yan, Xiaoqiang Zhu, Chaoqin Shen, Gang Zhao, Linhua Ji, Danhua Xu, Hua Xiong, TaChung Yu, Xiaobo Li, Qiang Liu, Yingxuan Chen, Yun Cui, Jie Hong, Jing-Yuan Fang

A newly identified novel coronavirus (2019-nCoV) has caused numerous acute respiratory syndrome cases in Wuhan China from December 2019 to Feb 2020. Its fast spreading to other provinces in China and overseas is very likely causing a pandemic. Since the novel coronavirus has been reported to be capable of endangering thousands of lives, it is extremely important to find out how the coronavirus is transmitted in human organs. Apart from fever and respiratory complications, gastrointestinal symptoms are observed in some patients with 2019-nCoV but the significance remains undetermined. The cell receptor angiotensin covering enzyme II (ACE2), which is the major receptor of SARS-nCoV, has been reported to be a cellular entry receptor of 2019-nCoV as well. Here, to more precisely explore the potential pathogen transmission route of the 2019-nCoV infections in the gastrointestinal tract, we analyzed the ACE2 RNA expression profile in the colon tissue of healthy adults and colorectal cancer patients of our cohort and other databases. The data indicates that ACE2 is mainly expressed in epithelial cells of the colon. The expression of ACE2 is gradually increased from healthy control, adenoma to colorectal cancer patients in our cohort as well as in the external Asian datasets. According to the expression profile of ACE2 in colon epithelial cells, we speculate adenoma and colorectal cancer patients are more likely to be infected with 2019-nCoV than healthy people. Our data may provide a theoretical basis for the classification and management of future 2019-nCoV susceptibility people in clinical application.

6: Reduced expression of COVID-19 host receptor, ACE2 is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn's disease
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Posted 23 Apr 2020

Reduced expression of COVID-19 host receptor, ACE2 is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn's disease
1,845 downloads medRxiv gastroenterology

Alka A Potdar, Shishir Dube, Takeo Naito, Gregory Botwin, Talin Haritunians, Dalin Li, Shaohong Yang, Janine Bilsborough, Lee A. Denson, Mark J. Daly, Stephan R Targan, Phillip Fleshner, Jonathan Braun, Subra Kugathasan, Thaddeus S. Stappenbeck, Dermot P B McGovern

Angiotensin-Converting Enzyme 2 (ACE2) has been identified as the host receptor for SARS-coronavirus 2 (SARS-CoV-2) which has infected millions world-wide and likely caused hundreds of thousands of deaths. Utilizing transcriptomic data from four cohorts taken from Crohn's disease (CD) and non-inflammatory bowel disease (IBD) subjects, we observed evidence of increased ACE2 mRNA in ileum with demographic features that have been associated with poor outcomes in COVID-19 including age and raised BMI. ACE2 was downregulated in CD compared to controls in independent cohorts. Within CD, ACE2 expression was reduced in inflamed ileal tissue and also remarkably, from uninvolved tissue in patients with a worse prognosis in both adult and pediatric cohorts. In active CD, small bowel ACE2 expression was restored by anti-TNF therapy particularly in anti-TNF responders. Collectively our data suggest that ACE2 downregulation is associated with inflammation and worse outcomes in CD.

7: Prehospitalization Proton Pump Inhibitor (PPI) use and Clinical Outcomes in COVID-19
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Posted 14 Jul 2020

Prehospitalization Proton Pump Inhibitor (PPI) use and Clinical Outcomes in COVID-19
1,644 downloads medRxiv gastroenterology

Preethi Ramachandran, Abhilash Perisetti, Mahesh Gajendran, Farla Jean-Louise, Alok Kumar Dwivedi, Hemant Goyal

Introduction There is a concern that proton pump inhibitors (PPI) induced hypochlorhydria could potentially predispose to severe COVID-19. Methods We studied the association between prehospitalization PPI use and clinical outcomes among hospitalized COVID-19 patients. Results In our study, 15.6% of hospitalized COVID-19 patients were on PPI. Mortality among PPI-users was 2.3 times higher than non-users, along with 2.5 times higher risk of mechanical ventilation. This relationship existed even after adjusting for confounding variables. Discussion These results warrant further investigation to evaluate if PPI-induced hypochlorhydria is associated with a higher risk of GI symptoms and worse outcomes because of the omnipresence of ACE-2 in the gastrointestinal tract.

8: The prevention of nosocomial SARS-CoV2 transmission in endoscopy: a systematic review of recommendations within gastroenterology to identify best practice.
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Posted 20 Mar 2020

The prevention of nosocomial SARS-CoV2 transmission in endoscopy: a systematic review of recommendations within gastroenterology to identify best practice.
1,376 downloads medRxiv gastroenterology

John Ong, Gail Brenda Cross, Yock Young Dan

Endoscopy generates aerosol droplets and fomites, thereby increasing the risk of SARS-CoV2 transmission to healthcare workers and uninfected patients within endoscopy departments. Despite the sharp rise in the incidence of COVID-19, authoritative recommendations to limit the spread of SARS-CoV2 within gastrointestinal endoscopy units are lacking. Therefore, with the primary aim of identifying best practice and scrutinizing its supporting evidence, we conducted a systematic review of literature for articles published between 1 January 2002 and 15 March 2020 in five databases relating to both the current SARS-CoV2 and the previous SARS-CoV outbreaks. Official websites for gastroenterology and endoscopy societies in the 15 most affected countries were also searched. Unfortunately, a paucity of high quality data and heterogeneity of recommendations between countries was observed. Interestingly, not all countries advocated the postponement of non-urgent or elective procedures. Recommendations for patient screening and personal protective equipment were commonly featured in all recommendations but specifics varied. Only 32% (9/28) of all gastroenterology and endoscopy societies issued guidance on endoscopy in the COVID-19 pandemic. In conclusion, stronger evidence to inform current practice and robust guidelines are urgently needed to prevent the transmission of SARS-CoV2 in gastrointestinal endoscopy departments worldwide.

9: Gastrointestinal tract symptoms in coronavirus disease 2019: Analysis of clinical symptoms in adult patients
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Posted 27 Mar 2020

Gastrointestinal tract symptoms in coronavirus disease 2019: Analysis of clinical symptoms in adult patients
1,300 downloads medRxiv gastroenterology

Yong Zhang, Zuneng Lu, Bo Wang, Jinxing Cang, Yonggang Ma

ObjectiveTo investigate the clinical presentation of coronavirus disease 2019 (COVID-19), particularly the incidence of gastrointestinal tract symptoms. DesignWe enrolled adult COVID-19 patients from a mobile cabin hospital in Wuhan with a definitive diagnosis by SARS-CoV-2 nucleic acid testing. Face-to-face interviews were conducted in which the patient selected COVID-19-related symptoms and report the time of onset and duration of symptoms. ResultsA total of 212 adults were enrolled in this study, of which 127 (59.9%) were females, mean age was 48.50 {+/-}13.15 (range: 17-79) years, and mean disease course was 26.78{+/-}9.16 (3-60) days. Fever and cough were the most common and earliest clinical symptoms of COVID-19. Diarrhoea occurred in 43.8% (93/212) of patients, of which 86.0% (80/93) had mushy stools. Nausea and vomiting were also common (20.7%). Diarrhoea lasted for 4.00(2.00-8.85) days and mostly occurred 5.00(0.25-11.00) days after the emergence of the first symptoms. Multiple logistic regression analysis found that diarrhoea was significantly correlated with fatigue [OR2.900,95%CI (1.629-5.164), p<0.0001]. ConclusionsGastrointestinal tract symptoms are common in COVID-19 and most occur during the middle stage of the disease and lasts for a short period of time. Clinicians need to pay greater attention to gastrointestinal tract symptoms of COVID-19.

10: COVID-19 and Inflammatory Bowel Diseases: risk assessment, shared molecular pathways and therapeutic challenges
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Posted 01 May 2020

COVID-19 and Inflammatory Bowel Diseases: risk assessment, shared molecular pathways and therapeutic challenges
1,262 downloads medRxiv gastroenterology

Iolanda Valentina Popa, Mircea Diculescu, Catalina Mihai, Cristina Cijevschi-Prelipcean, Alexandru Burlacu

Background. The novel coronavirus SARS-CoV-2 causing COVID-19 disease is yielding a global outbreak with serious threats to public health. In this paper, we aimed to review the current knowledge about COVID-19 infectious risk status in inflammatory bowel disease (IBD) patients requiring immunosuppressive medication. Also, we focused on several molecular insights that could explain why IBD patients appear to not have higher risks of infection and worse outcome in COVID-19 than the general population, in attempt to provide scientific support for safer decisions in IBD patient care. Methods. PubMed electronic database was interogated for relevant articles involving data about common molecular pathways and shared treatment strategies between SARS-CoV-2, SARS-CoV-1, MERS-CoV and inflammatory bowel diseases. In addition, Neural Covidex, an artificial intelligence tool, was used to answer queries about pathogenic coronaviruses and possible IBD interactions using the COVID-19 Open Research Dataset (CORD-19). Discussions. Few molecular and therapeutic interactions between IBD and pathogenic coronaviruses were explored. First, we showed how the activity of soluble angiotensin-converting enzyme 2, CD209L alternate receptor and phosphorylated subunit of eukaryotic translation initiation factor 2 might exert protective impact in IBD in case of coronavirus infection. Second, IBD medication was discussed in the context of possible beneficial effects on COVID-19 pathogeny including "cytokine storm" prevention and treatment, immunomodulation, interferon signaling blocking, viral endocytosis inhibition. Conclusions. Using current understanding of SARS-CoV-2 as well as other pathogenic coronaviruses immunopathology, we showed why IBD patients should not be considered at an increased risk of infection or more severe outcomes. Whether our findings are entirely applicable to the pathogenesis, disease susceptibility and treatment management of SARS-CoV-2 infection in IBD must be further explored.

11: Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
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Posted 05 Sep 2020

Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
1,258 downloads medRxiv gastroenterology

Graham J Britton, Alice Chen-Liaw, Francesca Cossarini, Alexandra E Livanos, Matthew P Spindler, Tamar Plitt, Joseph Eggers, Ilaria Mogno, Ana S. Gonzalez-Reiche, Sophia Siu, Michael Tankelevich, Lauren Grinspan, Rebekah E. Dixon, Divya Jha, Adriana van de Guchte, Zenab Khan, Gustavo Martinez-Delgado, Fatima Amanat, Daisy A Hoagland, Benjamin R. tenOever, Marla C Dubinsky, Miriam Merad, Harm van Bakel, Florian Krammer, Gerold Bongers, Saurabh Mehandru, Jeremiah J Faith

We sought to characterize the role of the gastrointestinal immune system in the pathogenesis of the inflammatory response associated with COVID-19. We measured cytokines, inflammatory markers, viral RNA, microbiome composition and antibody responses in stool from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.

12: Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients
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Posted 23 Apr 2020

Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients
1,234 downloads medRxiv gastroenterology

Elisabetta Buscarini, Guido Manfredi, Gianfranco Brambilla, Fernanda Menozzi, Claudio Londoni, Saverio Alicante, Elena Iiritano, Samanta Romeo, Marianna Pedaci, Giampaolo Benelli, Ciro Canetta, Giuseppe Lapiana, Alessandro Scartabellati, Guido Merli, Giovanni Vigano, Roberto Sfogliarini, Giovanni Melilli, Roberto Assandri, Daniele Cazzato, Davide Sebastiano Rossi, Susanna Usai, Irene Tramacere, Germano Pellegata, Giuseppe Lauria

Objective To assess the prevalence of gastrointestinal symptoms and their correlation with need of non-invasive ventilatory support, intensive care unit admission and death in hospitalized SARS-CoV-2 patients. Design Since February 21th 2020, all individuals referred to our emergency department for suspected SARS-CoV-2 underwent a standardized assessment of body temperature and pulse oximetry, hematological screening, chest X-ray and/or computed tomography (CT), and SARS-CoV-2 assay on nasopharyngeal swab. Medical history and GI symptoms including nausea, vomit, diarrhea, and abdominal pain were recorded. Results GI symptoms were the main presentation in 42 (10.2%) of 411 patients, with a mean onset 4.9 +/-... days before admission. In 5 (1.2%) patients GI symptoms have not been associated with respiratory symptoms or fever. We found an inverse trend for ICU admission and death as compared with patients without GI symptoms. Conclusions GI symptoms can be an early and not negligible feature of Covid-19, and might be correlated with a more benign disease course.

13: Prevalence of Chronic Hepatitis B and C in Malaysia- results from a community-based screening campaign
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Posted 05 May 2020

Prevalence of Chronic Hepatitis B and C in Malaysia- results from a community-based screening campaign
1,234 downloads medRxiv gastroenterology

Zhuo-zhi Lim, Jau-shya Teo, Ah choon Tan, Teck Onn Lim

Introduction The epidemiology of hepatitis, which is apparently endemic in Asia, is still poorly documented in Malaysia. Available statistics are modelled estimates based on expert input or estimated from small studies on special populations. We therefore determined the prevalence of chronic hepatitis B and C in Malaysia based on a large sample data from a screening campaign. Methods A total of 10,914 subjects participated in the hepatitis screening campaign in 2018 and 2019. A low-cost Point-of-care test, which has previously been validated, was used to screen for HBsAg and anti-HCV. All screen positive subjects were recalled to undergo confirmatory serology tests and nucleic acid tests. Results We estimated 1.17% or 238,971 Malaysian adults aged 20 or older had chronic HBV, while only 0.74% or 151,144 adults had chronic HCV. Young adults below age 30 years had very low prevalence of HBV (0.09%). Women had lower prevalence of HBV and HCV, Chinese had the highest prevalence of HBV while Malay had the highest prevalence of HCV. Conclusion Young adults seems to be protected from HBV perhaps owing to the introduction of universal HBV vaccination since 1989. Chronic HBV however remains prevalent in older adults especially among the Chinese. Chronic HCV is uncommon in Malaysia.

14: Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for Covid-19.
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Posted 02 Sep 2020

Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for Covid-19.
1,100 downloads medRxiv gastroenterology

Carolyn Bramante, Christopher J. Tignanelli, Nirjhar Dutta, Emma Jones, Leonardo Tamariz, Jeanne M Clark, Michael Usher, Genevieve Metlon-Meaux, Sayeed Ikramuddin

Background: Covid-19 disease causes significant morbidity and mortality through increase inflammation and thrombosis. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are states of chronic inflammation and indicate advanced metabolic disease. We sought to understand the risk of hospitalization for Covid-19 associated with NAFLD/NASH. Methods: Retrospective analysis of electronic medical record data of 6,700 adults with a positive SARS-CoV-2 PCR from March 1, 2020 to Aug 25, 2020. Logistic regression and competing risk were used to assess odds of being hospitalized. Additional adjustment was added to assess risk of hospitalization among patients with a prescription for metformin use within the 3 months prior to the SARS-CoV-2 PCR result, history of home glucagon-like-peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by gender and race. Results: A history of NAFLD/NASH was associated with increased odds of admission for Covid-19: logistic regression OR 2.04 (1.55, 2.96, p<0.01), competing risks OR 1.43 (1.09-1.88, p<0.01); and each additional year of having NAFLD/NASH was associated with a significant increased risk of being hospitalized for Covid-19, OR 1.86 (1.43-2.42, p<0.01). After controlling for NAFLD/NASH, persons with obesity had decreased odds of hospitalization for Covid-19, OR 0.41 (0.34-0.49, p<0.01). NAFLD/NASH increased risk of hospitalization in men and women, and in all racial/ethnic subgroups. Mediation treatments for metabolic syndrome were associated with non-significant reduced risk of admission: OR 0.42 (0.18-1.01, p=0.05) for home metformin use and OR 0.40 (0.14-1.17, p=0.10) for home GLP-1RA use. MBS was associated with a significant decreased risk of admission: OR 0.22 (0.05-0.98, p<0.05). Conclusions: NAFLD/NASH is a significant risk factor for hospitalization for Covid-19, and appears to account for risk attributed to obesity. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.

15: Variants in MARC1 and HSD17B13 reduce severity of NAFLD in children, perturb phospholipid metabolism, and suppress fibrotic pathways
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Posted 07 Jun 2020

Variants in MARC1 and HSD17B13 reduce severity of NAFLD in children, perturb phospholipid metabolism, and suppress fibrotic pathways
1,060 downloads medRxiv gastroenterology

Christian A Hudert, Anna Alisi, Quentin M. Anstee, Annalisa Crudele, Laura G Draijer, EU-PNAFLD investigators, Samuel Furse, Jan G. Hengstler, Benjamin Jenkins, Kylie Karnebeek, Deirdre A Kelly, Bart G Koot, Albert Koulman, David Meierhofer, Stuart G. Snowden, Indra van Mourik, Anita Vreugdenhil, Susanna Wiegand, Jake P Mann

Background & aims: Genome-wide association studies in adults have identified variants in HSD17B13 and MARC1 as protective against NAFLD. It is not known if they are similarly protective in children and, more generally, whether the peri-portal inflammation of pediatric NAFLD and lobular inflammation seen in adults share common genetic influences. Therefore, we aimed to: establish if these variants are associated with NAFLD in children, and to investigate the function of these variants in hepatic metabolism using metabolomics. Methods: 960 children (590 with NAFLD, 394 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MARC1. Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of samples. In silico tools were used to model the effect of rs2642438G>A (p.Ala165Thr) on MARC1. Results: rs72613567T>TA in HSD17B13 was associated with lower odds of NAFLD diagnosis (OR 0.7 (95%CI 0.6-0.9) and lower grade of portal inflammation (P<0.001) whilst rs2642438G>A in MARC1 was associated with lower grade of hepatic steatosis (P=0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective allele, whereas MARC1 levels were not affected by genotype. Both variants showed downregulation of hepatic fibrotic pathways, upregulation of retinol metabolism and perturbation of phospholipid species. Modelling suggests that p.Ala165Thr would disrupt the stability and metal-binding of MARC1. Conclusions: There are shared genetic mechanisms between pediatric and adult NAFLD, despite their differences in histology. MARC1 and HSD17B13 are involved in phospholipid metabolism and suppress fibrosis in NAFLD.

16: Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients
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Posted 24 Sep 2020

Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients
1,052 downloads medRxiv gastroenterology

Azza Shoaibi, Stephen Fortin, Rachel Weinstein, Jesse Berlin, Patrick Ryan

Background: Famotidine has been posited as a potential treatment for COVID-19. We compared the incidence of COVID-19 outcomes (i.e., death; and death or intensive services use) among hospitalized famotidine users vs. proton pump inhibitors (PPIs) users, hydroxychloroquine users or famotidine non-users separately. Methods: We constructed a retrospective cohort study using data from COVID-19 Premier Hospital electronic health records. Study population were COVID-19 hospitalized patients aged 18 years or older. Famotidine, PPI and hydroxychloroquine exposure groups were defined as patients dispensed any medication containing one of the three drugs on the day of admission. The famotidine non-user group was derived from the same source population with no history of exposure to any drug with famotidine as an active ingredient prior to or on the day of admission. Time-at-risk was defined based on the intention-to-treat principle starting 1 day after admission to 30 days after admission. For each study comparison group, we fit a propensity score (PS) model through large-scale regularized logistic regression. The outcome was modeled using a survival model. Results: We identified 2193 users of PPI, 5950 users of the hydroxychloroquine, 1816 users of famotidine and 26,820 non-famotidine users. After PS stratification, the hazard ratios for death were as follows: famotidine vs no famotidine HR 1.03 (0.89-1.18); vs PPIs: HR 1.14 (0.94-1.39); vs hydroxychloroquine:1.03 (0.85-1.24). Similar results were observed for the risk of death or intensive services use. Conclusion: We found no evidence of a reduced risk of COVID-19 outcomes among hospitalized COVID-19 patients who used famotidine compared to those who did not or compared to PPI or hydroxychloroquine users.

17: Digestive Manifestations in Patients Hospitalized with COVID-19
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Posted 09 Jul 2020

Digestive Manifestations in Patients Hospitalized with COVID-19
1,028 downloads medRxiv gastroenterology

B. Joseph Elmunzer, Rebecca L. Spitzer, Lydia D. Foster, Ambreen A. Merchant, Eric F. Howard, Vaishali A. Patel, Mary K. West, Emad Qayad, Rosemary Nustas, Ali Zakaria, Marc S. Piper, Jason R Taylor, Lujain Jaza, Nauzer Forbes, Millie Chau, Luis F. Lara, Georgios I. Papachristou, Michael L. Volk, Liam G. Hilson, Selena Zhou, Vladimir M. Kushnir, Alexandria M. Lenyo, Caroline G. McLeod, Sunil Amin, Gabriela N. Kuftinec, Dhiraj Yadav, Charlie Fox, Jennifer M. Kolb, Swati Pawa, Rishi Pawa, Andrew Canakis, Christopher Huang, Laith H. Jamil, Andrew M. Aneese, Benita K. Glamour, Zachary L. Smith, Katherine A. Hanley, Jordan Wood, Harsh K Patel, Janak N. Shah, Emil Agarunov, Amrita Sethi, Evan L. Fogel, Gail McNulty, Abdul Haseeb, Judy A. Trieu, Rebekah E. Dixon, Jeong Yun Yang, Robin B. Mendelsohn, Delia Calo, Olga C. Aroniadis, Joseph F. LaComb, James M. Scheiman, Bryan G. Sauer, Duyen T. Dang, Cyrus R. Piraka, Eric D. Shah, Heiko Pohl, William M. Tierney, Stephanie Mitchell, Ashwinee Condon, Adrienne Lenhart, Kulwinder S. Dua, Vikram S. Kanagala, Ayesha Kamal, Vikesh K. Singh, Maria Ines Pinto-Sanchez, Joy M. Hutchinson, Richard S. Kwon, Sheryl J. Korsnes, Harminder Singh, Zahra Solati, Amar R. Deshpande, Don C. Rockey, Teldon B. Alford, Valerie Durkalski, Field F. Willingham, Patrick S. Yachimski, Darwin L. Conwell, Evan Mosier, Mohamed Azab, Anish Patel, James Buxbaum, Sachin Wani, Amitabh Chak, Amy E. Hosmer, Rajesh N. Keswani, Christopher J. DiMaio, Michael S. Bronze, Raman Muthusamy, Marcia I. Canto, V. Mihajlo Gjeorgjievski, Zaid Imam, Fadi Odish, Ahmed I. Edhi, Molly Orosey, Abhinav Tiwari, Soumil Patwardhan, Nicholas G. Brown, Anish A. Patel, Collins O. Ordiah, Ian P. Sloan, Lilian Cruz, Casey L. Koza, Uchechi Okafor, Thomas Hollander, Nancy Furey, Olga Reykhart, Natalia H. Zbib, John A. Damianos, James Esteban, Nick Hajidiacos, Melissa Saul, Melanie Mays, Gulsum Anderson, Kelley Wood, Laura Mathews, Galina Diakova, Molly Caisse, Lauren Wakefield, Haley Nitchie

Background: The prevalence and significance of digestive manifestations in COVID-19 remain uncertain. Methods: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were manually abstracted from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. Results: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were elevated to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio 0.93, 95% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death. Conclusions: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common but the majority were mild and their presence was not associated with a more severe clinical course.

18: Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines
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Posted 28 Mar 2021

Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines
961 downloads medRxiv gastroenterology

Nick A Kennedy, Simeng Lin, James R. Goodhand, Neil Chanchlani, CLARITY IBD Contributors, Nick Powell, Tariq Ahmad

Background Delayed second-dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single-dose of a SARS-CoV-2 vaccine. Methods Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared to a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin a4B7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations 3-10 weeks after vaccination in patients without evidence of prior infection. Secondary outcomes were seroconversion rates, and antibody responses following past infection or a second dose of the BNT162b2 vaccine. Findings Geometric mean [SD] anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL [5.9] vs 28.8 U/mL [5.4] P<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL [4.9]) vs 13.8 U/mL [5.9] P<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab- compared to vedolizumab-treated patients who received the BNT162b2 (fold change [FC] 0.29 [95% CI 0.21, 0.40], p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 [95% CI 0.30, 0.51], p<0.0001) vaccines. In both models, age > 59 years, immunomodulator use, Crohn's disease, and smoking were associated with lower, whilst non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single-dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine. Interpretation Infliximab is associated with attenuated immunogenicity to a single-dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. Funding Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts. Unrestricted educational grants: F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea) and Galapagos NV (Belgium).

19: Questionnaire assessment helps the self-management of patients with inflammatory bowel disease during the outbreak of Coronavirus Disease 2019
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Posted 27 Mar 2020

Questionnaire assessment helps the self-management of patients with inflammatory bowel disease during the outbreak of Coronavirus Disease 2019
937 downloads medRxiv gastroenterology

Meiping Yu, Zhenghao Ye, Yu Chen, Tingting Qin, Jiguang Kou, De’an Tian, Fang Xiao

Background and AimsThe outbreak of Coronavirus Disease 2019 (COVID-19) may affect the disease status of patients with inflammatory bowel disease (IBD). This study aimed to assess the disease status of IBD patients in Hubei province by questionnaire online and guide to the self-management of IBD patients during this epidemic. MethodsA questionnaire was designed containing the Harvey-Bradshaw Index (HBI), the Partial Mayo Score (PMS), the short inflammatory bowel disease questionnaire (SIBDQ) and distributed to Hubei IBD patients online within one month of traffic control after the outbreak of COVID-19. This questionnaire also included some questions about patients self-report disease conditions and their epidemiological history of COVID-19. ResultsA total of 102 eligible questionnaires were included in the analysis. No patient reported infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in our study. Our result showed that 69.64% of patients with ulcerative colitis (UC) and 80.44% of patients with Crohns disease (CD) were in remission. There was not a statistically significant difference in the proportion of the active disease stage between the two types of disease (p=0.103). The majority of patients (85.29%) had a good health-related quality of life (HRQoL) (SIBDQ[&ge;]50). The reduction in physical exercise is a risk factor for worsening in conditions (OR=17.593, 95%CI 2.035 to 152.097, p=0.009). ConclusionsThe outbreak of COVID-19 might not have a significant impact on most Hubei IBD patients within one month after the traffic control. The patients disease condition could be assessed by our questionnaires. Doctors utilized the information and advised for IBD patients about self-management during the period of COVID-19.

20: Fecal microbiota transplantation in ulcerative colitis, a retrospective microbiome analysis
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Posted 30 Mar 2020

Fecal microbiota transplantation in ulcerative colitis, a retrospective microbiome analysis
844 downloads medRxiv gastroenterology

Marcel A. de Leeuw, Manuel X. Duval

BackgroundInflammatory bowel disease (IBD)is a set of conditions characterized by non-infectious chronic inflammation of the gastrointestinal tract. These primarily include Crohns disease (CD), ulcerative colitis (UC) and indeterminate colitis. Fecal microbiota transplantation (FMT) has proven to be an effective treatment for some patients with active UC. However, factors contributing to the individual response to FMT therapy remain to be uncovered. There is currently no procedure allowing to predict the patients response and to select the most adequate donor(s). MethodsThe first available UC FMT microbiome data sets were reanalyzed, with focus on species level changes in the microbiota, using state-of-the-art and in part proprietary 16S analysis routines. ResultsWe found the microbiomes of UC and CD patients to have paucity of obligate anaerobes, which could be a consequence of oxidative stress. Microbiomes of UC FMT responders and responder donors have higher phylogenetic diversity and a higher proportion of aerobes and facultative anaerobes as compared to non-responders and non-responder donors. We found Proteobacteria to account for the major part of species found in increased relative abundance in responders. Sphingolipid producers were found among these species. ImplicationsOur findings contribute to the establishment of selection criteria for UC FMT donor samples and composition guidelines for future synthetic microbial communities. Instead of replenishing missing obligate anaerobes, our results suggest that oxidative stress resistant Proteobacteria are important for successful UC FMT therapy.

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