Intestinal strictures in Crohn's disease: An update from 2023.

Crohn's disease (CD) is a chronic inflammatory disease that leads to intestinal stricture in nearly 35% of cases within 10 years of initial diagnosis. The unknown pathogenesis, lack of universally accepted criteria, and absence of an effective management approach remain unconquered challenges in structuring CD. The pathogenesis of stricturing CD involves intricate interactions between factors such as immune cell dysbiosis, fibroblast activation, and microecology imbalance. New techniques such as single-cell sequencing provide a fresh perspective. Non-invasive diagnostic tools such as serum biomarkers and novel cross-sectional imaging techniques offer a precise understanding of intestinal fibrostenosis. Here, we provide a timely and comprehensive review of the worthy advancements in intestinal strictures in 2023, aiming to dispense cutting-edge information regarding fibrosis and to build a cornerstone for researchers and clinicians to make greater progress in the field of intestinal strictures.

Comparative analysis of [18F]F-FAPI PET/CT, [18F]F-FDG PET/CT and magnetization transfer MR imaging to detect intestinal fibrosis in Crohn's disease: A prospective animal model and human cohort study.

PURPOSE: Accurately and early detection of intestinal fibrosis in Crohn's disease (CD) is crucial for clinical management yet remains an unmet need. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising tool to assess fibrosis. We aimed to investigate the diagnostic capability of [18F]F-FAPI PET/CT in detecting intestinal fibrosis and compared it with[18F]F-FDG PET/CT and magnetization transfer MR imaging (MTI). METHODS: Twenty-two rats underwent TNBS treatment to simulate fibrosis development, followed by three quantitative imaging sessions within one week. Mean and maximum standardized uptake values (SUVmean and SUVmax) were calculated on[18F]F-FAPI and [18F]F-FDG PET/CT, along with normalized magnetization transfer ratio on MTI. Intestinal fibrosis was assessed pathologically, with MTI serving as imaging standard for fibrosis. The diagnostic efficacy of imaging parameters in fibrosis was compared using pathological and imaging standards. Ten patients with 34 bowel strictures were prospectively recruited to validate their diagnostic performance, using the identical imaging protocol. RESULTS: In CD patients, the accuracy of FAPI uptake (both AUCs = 0.87, both P ≤ 0.01) in distinguishing non-to-mild from moderate-to-severe fibrosis was higher than FDG uptake (both AUCs = 0.82, P ≤ 0.01) and comparable to MTI (AUCs = 0.90, P ≤ 0.001). In rats, FAPI uptake responded earlier to fibrosis development than FDG and MTI; consistently, during early phase, FAPI uptake showed a stronger correlation (SUVmean: R = 0.69) with pathological fibrosis than FDG (SUVmean: R = 0.17) and MTI (R = 0.52). CONCLUSION: The diagnostic efficacy of [18F]F-FAPI PET/CT in detecting CD fibrosis is superior to [18F]F-FDG PET/CT and comparable to MTI, exhibiting great potential for early detection of intestinal fibrosis.

Novel supramolecular deep eutectic solvent-enabled in-situ lignin protection for full valorization of all components of wheat straw.

Lignin is usually deemed as an inhibitor to enzymatic hydrolysis of cellulose due to its physical barrier, non-productive adsorption, and steric hindrance. Herein, a novel supramolecular deep eutectic solvent (SUPRADES), comprising ethylene glycol and citric acid in 5:1 M ratio, and ß-cyclodextrin (ß-CD) in a concentration of 3.5% (w/w), was developed to be efficient for pretreating wheat straw. The delignification rate, cellulose enzymatic digestibility, and hemicellulose removal reached 90.45%, 97.36% and 87.24%, respectively, which may be attributed to the introduction of ß-CD with superior ability of both adsorption and in-situ lignin protection to efficiently remove lignin with intact structure from cellulose surface. The mechanisms of high-efficiency lignin extraction/protection were systematically illustrated by adsorption kinetics. Moreover, Trichosporon cutaneum grown on the hemicellulose and cellulose fractions after pretreatment afforded 8.8 g total lipids from 100 g wheat straw. The green SUPARDES pretreatment strategy offers a new avenue for upgrading lignocellulose to biofuels.

Naringin Inhibits Colorectal Carcinogenesis by Inhibiting Viability of Colorectal Cancer Cells.

OBJECTIVE: To explore the therapeutic effect of naringin on colorectal cancer (CRC) and the related mechanism. METHODS: Cell counting kit-8 (CCK-8) assay and annexin V-FITC/PI assay were used to detect the effect of naringin (50-400 µg/mL) on cell proliferation and apoptosis of CRC cells, respectively. The scratch wound assay and transwell migration assay were used to assess the effect of naringin on CRC cell migration. Four-week-old male nude mice were injected with HCT116 cells subcutaneously to establish the tumor xenograft model. Naringin was injected intraperitoneally at 50 mg/(kg·d), with solvent and 5-fluorouracil treatment as control. The width and length of the tumors were measured and recorded every 6 days, and tumor tissues were photographed and weighed on the last day of the 24-d observation period. Immunohistochemical staining for caspase-3, proliferating cell nuclear antigen and TUNEL assay were used to evaluate the effect of naringin on cell proliferation and apoptosis in tumor tissues. The body weight, food and water intake of mice were recorded, and the major organs in different treatment groups were weighed on the last day and stained with hematoxylin and eosin for histological analysis. Meanwhile, the routine blood indicators were recorded. RESULTS: CCK-8 and annexin V-FITC/PI results confirmed that naringin (100, 200, and 400 µg/mL) could inhibit proliferation and promote apoptosis. The scratch wound assay and transwell migration assay results confirmed the inhibitory activity of naringin against CRC cells migration. In vivo results demonstrated the inhibitory effect of naringin on tumor growth with good bio-compatibility. CONCLUSION: Naringin inhibited colorectal carcinogenesis by inhibiting viability of CRC cells.

Cellular and Molecular Mechanisms of Intestinal Fibrosis.

Intestinal fibrosis associated stricture is a common complication of inflammatory bowel disease usually requiring endoscopic or surgical intervention. Effective anti-fibrotic agents aiming to control or reverse intestinal fibrosis are still unavailable. Thus, clarifying the mechanism underpinning intestinal fibrosis is imperative. Fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) proteins at the injured sites. Multiple cellular types are implicated in fibrosis development. Among these cells, mesenchymal cells are major compartments that are activated and then enhance the production of ECM. Additionally, immune cells contribute to the persistent activation of mesenchymal cells and perpetuation of inflammation. Molecules are messengers of crosstalk between these cellular compartments. Although inflammation is necessary for fibrosis development, purely controlling intestinal inflammation cannot halt the development of fibrosis, suggesting that chronic inflammation is not the unique contributor to fibrogenesis. Several inflammation-independent mechanisms including gut microbiota, creeping fat, ECM interaction, and metabolic reprogramming are involved in the pathogenesis of fibrosis. In the past decades, substantial progress has been made in elucidating the cellular and molecular mechanisms of intestinal fibrosis. Here, we summarized new discoveries and advances of cellular components and major molecular mediators that are associated with intestinal fibrosis, aiming to provide a basis for exploring effective anti-fibrotic therapies in this field.

Ulcerative colitis increases risk of hypertension in a UK biobank cohort study.

OBJECTIVE: Inflammatory bowel disease (IBD) is not only a chronic inflammatory disorder of the gastrointestinal tract but also accompanied by systemic inflammation. The onset of hypertension is closely related to systemic inflammation. However, the relationship between IBD and hypertension has not been investigated. We aimed to investigate the potential association between IBD and the incidence of hypertension. METHOD: We retrieved IBD onset and the incidence of hypertension from a public database UK Biobank. The association between the onset of IBD and subsequent incidence of hypertension was analyzed using a multivariate Cox regression analysis, and propensity score matching was performed for sensitivity analysis. RESULT: Of a total of 281,064 participants included in the study, 2376 (0.8%) were diagnosed with IBD at baseline, and 20,129 (7.2%) in the whole cohort developed hypertension with a median follow-up duration of 8.1 years (interquartile range [IQR] 7.3-8.8 years). Patients with IBD had a higher cumulative risk of hypertension compared with general population (10.9% in ulcerative colitis [UC], 7.7% in Crohn's disease [CD], and 9.3% in IBD unclassified [IBD-U] vs. 7.1% in non-IBD, p < 0.001). Multivariate Cox regression analysis identified that UC, rather than CD or IBD-U, was independently associated with subsequent occurrence of hypertension (HR 1.30, 95% CI: 1.11-1.52, p = 0.001). In propensity matching analysis, UC also showed its robustness as a risk factor for the prediction of hypertension (HR 1.56, 95% CI: 1.21-2.03, p = 0.001). CONCLUSION: In IBD patients, UC rather than CD is associated with a higher risk for the incidence of hypertension compared with general population. Close monitoring of hypertension might be required in clinical practice.

Hydrophobic species-enabled acid-base multi-catalysis for stereoselective access to renewable trans-anethole.

trans-Anethole (trans-AN) is widely applied in food, daily necessities, and pharmaceuticals and is typically available from inefficient natural oil extraction or complex organic transformations over mineral acid or noble metals. Here, a green and sustainable route was developed to stereoselectively produce trans-AN (ca. 90% selectivity) over an organic polymeric phosphonate-hafnium catalyst (PAS-Hf) through the cascade transfer hydrogenation and dehydration of biomass-based 4'-methoxypropiophenone (4-MOPP), with an environmental impact factor (E-factor) of 47.73. The porous structure and the enhanced hydrophobicity of the spherical catalyst PAS-Hf ensured the formation of more accessible and stable Lewis (Hf4+) and Brønsted (SO3H) acid active sites, which could be used for rapid conversion of biomass-based 4-MOPP to AN (100% conversion, 97.2% yield) in 0.5-2 h (TOF: 9.3 h-1). Density functional theory (DFT) calculations elucidated that the addition of PAS-Hf could remarkably facilitate the overall conversion process by decreasing the reaction energy barrier (151.33 to 48.27 kJ mol-1) of the rate-determining step. The good thermal stability and heterogeneity of the bifunctional catalyst were responsible for its constant activity during at least five consecutive cycles. The synergistic/relay catalysis of Lewis acid-base and Brønsted acid species could be extended to more than ten kinds of aldehydes and ketones. This acid-base multi-catalytic protocol has considerable potential in cascade biomass conversion via heterogeneous catalysis without any base additive.

Fibrosis in fat: From other diseases to Crohn's disease.

Creeping fat is a specific feature of Crohn's disease (CD) and is characterized by mesenteric fat wrapping around the intestine. It highly correlates with intestinal transmural inflammation, muscular hypertrophy, fibrosis, and stricture formation. However, the pathogenesis of creeping fat remains unclear. Molecular crosstalk exists between mesenteric fat and the intestine. Indeed, creeping fat contains different types of cells, including adipocytes and immune cells. These cell types can produce various cytokines, fatty acids, and growth factors, which affect the mesenteric fat function and modulate intestinal inflammation and immunity. Moreover, adipocyte progenitors can produce extracellular matrix to adapt to fat expansion. Previous studies have shown that fat fibrosis is an important feature of adipose tissue malfunction and exists in other diseases, including metabolic disorders, cancer, atrial fibrillation, and osteoarthritis. Furthermore, histological sections of CD showed fibrosis in the creeping fat. However, the role of fibrosis in the mesenteric fat of CD is not well understood. In this review, we summarized the possible mechanisms of fat fibrosis and its impact on other diseases. More specifically, we illustrated the role of various cells (adipocyte progenitors, macrophages, mast cells, and group 1 innate lymphoid cells) and molecules (including hypoxia-inducible factor 1-alpha, transforming growth factor-beta, platelet-derived growth factor, and peroxisome proliferator-activated receptor-gamma) in the pathogenesis of fat fibrosis in other diseases to understand the role of creeping fat fibrosis in CD pathogenesis. Future research will provide key information to decipher the role of fat fibrosis in creeping fat formation and intestinal damage, thereby helping us identify novel targets for the diagnosis and treatment of CD.

Research Progress on Lignocellulosic Biomass Degradation Catalyzed by Enzymatic Nanomaterials.

Lignocellulose biomass (LCB) has extensive applications in many fields such as bioenergy, food, medicines, and raw materials for producing value-added products. One of the keys to efficient utilization of LCB is to obtain directly available oligo- and monomers (e. g., glucose). With the characteristics of easy recovery and separation, high efficiency, economy, and environmental protection, immobilized enzymes have been developed as heterogeneous catalysts to degrade LCB effectively. In this review, applications and mechanisms of LCB-degrading enzymes are discussed, and the nanomaterials and methods used to immobilize enzymes are also discussed. Finally, the research progress of lignocellulose biodegradation catalyzed by nano-enzymes was discussed.

Intestinal strictures in Crohn's disease: a 2021 update.

Intestinal strictures remain one of the most intractable and common complications of Crohn's disease (CD). Approximately 70% of CD patients will develop fibrotic strictures after 10 years of CD diagnosis. Since specific antifibrotic therapies are unavailable, endoscopic balloon dilation and surgery remain the mainstay treatments despite a high recurrence rate. Besides, there are no reliable methods for accurately evaluating intestinal fibrosis. This is largely due to the fact that the mechanisms of initiation and propagation of intestinal fibrosis are poorly understood. There is growing evidence implying that the pathogenesis of stricturing CD involves the intricate interplay of factors including aberrant immune and nonimmune responses, host-microbiome dysbiosis, and genetic susceptibility. Currently, the progress on intestinal strictures has been fueled by the advent of novel techniques, such as single-cell sequencing, multi-omics, and artificial intelligence. Here, we perform a timely and comprehensive review of the substantial advances in intestinal strictures in 2021, aiming to provide prompt information regarding fibrosis and set the stage for the improvement of diagnosis, treatment, and prognosis of intestinal strictures.

Prophylactic Antitubercular Therapy Is Associated With Accelerated Disease Progression in Patients With Crohn's Disease Receiving Anti-TNF Therapy: A Retrospective Multicenter Study.

INTRODUCTION: Prophylactic antitubercular therapy (ATT) is widely prescribed in patients with Crohn's disease (CD) receiving antitumor necrosis factor (anti-TNF) treatment. However, antitubercular agents have been demonstrated to possess profibrotic effects. We aimed to evaluate whether ATT accelerated disease progression in patients with CD receiving anti-TNF treatment. METHODS: A retrospective, multicenter study was performed in CD patients presented with inflammatory behavior (B1) and treated with anti-TNF agents. Disease progression was defined as the development of a stricturing (B2) or penetrating (B3) phenotype. ATT users were propensity score-matched with non-ATT users. Survival and multivariable Cox analyses were used to identify factors associated with disease progression. RESULTS: We enrolled 441 patients, including 295 ATT users and 146 non-ATT users, with a median follow-up of 3.15 years (interquartile range: 1.6-4.7). The cumulative rates of disease progression in the ATT group were constantly higher than those in the non-ATT group after 1-, 3-, 5-, and 10-year follow-ups, respectively (P = 0.031). Multivariable Cox analysis identified ATT as an independent risk factor for disease progression using both the whole (hazard ratio = 2.22; 95% confidence interval: 1.11-4.48; P = 0.025) and propensity score-matched cohorts (hazard ratio = 2.35; 95% confidence interval: 1.07-5.14; P = 0.033). In subgroup analysis, patients receiving ATT ≥4.5 months had a significantly higher rate of disease progression compared with patients receiving ATT <4.5 months (P = 0.005) and non-ATT treatment (P = 0.036). DISCUSSION: Prophylactic ATT with duration over 4.5 months was associated with disease progression in patients with CD receiving anti-TNF treatment.

Role of Telemedicine in Inflammatory Bowel Disease: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Telemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear. OBJECTIVE: This systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD. METHODS: We systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis. RESULTS: A total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference -0.71, 95% CI -1.07 to -0.36; P<.001). Subgroup analysis showed that adolescents in the telemedicine group had significantly higher IBD-specific QoL than those in the standard care group (standard mean difference 0.42, 95% CI 0.15 to 0.69; I2=0; P.002), but there was no significant difference between adults in the 2 groups. There were no significant differences in disease activity, remission rate, patient satisfaction, depression, self-efficacy, generic QoL, and medication adherence outcomes between the telemedicine and standard care groups. CONCLUSIONS: Telemedicine intervention showed a promising role in improving IBD-specific QoL among adolescents and decreased the number of clinic visits among patients with IBD. Further research is warranted to identify the group of patients with IBD who would most benefit from telemedicine.

Synthetic biology promotes the capture of CO2 to produce fatty acid derivatives in microbial cell factories.

Environmental problems such as greenhouse effect, the consumption of fossil energy, and the increase of human demand for energy are becoming more and more serious, which force researcher to turn their attention to the reduction of CO2 and the development of renewable energy. Unsafety, easy to lead to secondary environmental pollution, cost inefficiency, and other problems limit the development of conventional CO2 capture technology. In recent years, many microorganisms have attracted much attention to capture CO2 and synthesize valuable products directly. Fatty acid derivatives (e.g., fatty acid esters, fatty alcohols, and aliphatic hydrocarbons), which can be used as a kind of environmentally friendly and renewable biofuels, are sustainable substitutes for fossil energy. In this review, conventional CO2 capture techniques pathways, microbial CO2 concentration mechanisms and fixation pathways were introduced. Then, the metabolic pathway and progress of direct production of fatty acid derivatives from CO2 in microbial cell factories were discussed. The synthetic biology means used to design engineering microorganisms and optimize their metabolic pathways were depicted, with final discussion on the potential of optoelectronic-microbial integrated capture and production systems.

Advances in Pretreatment of Straw Biomass for Sugar Production.

Straw biomass is an inexpensive, sustainable, and abundant renewable feedstock for the production of valuable chemicals and biofuels, which can surmount the main drawbacks such as greenhouse gas emission and environmental pollution, aroused from the consumption of fossil fuels. It is rich in organic content but is not sufficient for extensive applications because of its natural recalcitrance. Therefore, suitable pretreatment is a prerequisite for the efficient production of fermentable sugars by enzymatic hydrolysis. Here, we provide an overview of various pretreatment methods to effectively separate the major components such as hemicellulose, cellulose, and lignin and enhance the accessibility and susceptibility of every single component. This review outlines the diverse approaches (e.g., chemical, physical, biological, and combined treatments) for the excellent conversion of straw biomass to fermentable sugars, summarizes the benefits and drawbacks of each pretreatment method, and proposes some investigation prospects for the future pretreatments.

Impact of COVID-19 outbreak on the care of patients with inflammatory bowel disease: A comparison before and after the outbreak in South China.

BACKGROUND AND AIMS: Epidemics pose a great challenge to health care of patients. However, the impact of unprecedented situation of COVID-19 outbreak on health care of inflammatory bowel disease (IBD) patients in real-world setting has seldom been investigated. METHODS: We performed an observational study in a tertiary referral IBD center in China. The mode of health care and medication use was compared before and after COVID-19 outbreak. Electronic questionnaire surveys were performed among gastroenterologists and IBD patients to investigate the impact of COVID-19 outbreak on their attitudes towards telemedicine. RESULTS: COVID-19 outbreak resulted in substantial decrease of patients participating in standard face-to-face visit during 1 month post-outbreak (n = 51) than pre-outbreak (n = 249), whereas the participation in telemedicine was significantly higher than comparable period in 2019 (414 vs 93). During the 1 month after COVID-19 outbreak, 39 (39/56, 69.6%) patients had their infliximab infusion postponed with the mean delay of 3 weeks. The immunomodulator use was similar between pre-outbreak and post-outbreak. Six elective surgeries were postponed for a median of 43 days. In post-outbreak period, 193 (193/297, 64.98%) of the surveyed physicians have used telemedicine with an increase of 18.9% compared with 46.13% (137/292) in the pre-outbreak period (P < 0.001); 331 (331/505, 65.54%) of the surveyed IBD patients supported that the use of telemedicine should be increased in future health care. CONCLUSION: COVID-19 outbreak resulted in a great change in health-care access among IBD patients including decrease in standard face-to-face visit and delay of biologics use. There was an increased use and need of telemedicine after COVID-19 outbreak.

One-step upgrading of bio-based furfural to γ-valerolactone via HfCl4-mediated bifunctional catalysis.

γ-Valerolactone (GVL) is an attractive biomass-derived platform molecule that plays an important role in the production of biofuels and biopolymers. The synthesis of GVL from renewable biomass and its derivatives has great application prospects but also presents challenges due to the multiple conversion steps involved. Here, a HfCl4-mediated acid-base bifunctional catalytic system was developed, which was demonstrated to be efficient for upgrading furfural (FF) to GVL in a single pot with unprecedented performance. The Lewis acidity of Hf4+ and moderate basicity of HfO(OH)2·xH2O, and strong Brønsted acidity of HCl in situ generated from HfCl4 hydrolysis were found to play a synergistic role in the cascade reaction processes, mainly contributing to the pronounced catalytic activity. The effects of the key reaction parameters, such as the catalyst dosage, reaction time, and temperature, on GVL production were optimized by response surface methodology. It is worth mentioning that the recovered catalyst after thermal treatment could be directly used for the hydrogen transfer processes, like FF-to-furfuryl alcohol conversion. This catalytic strategy opens a new avenue for the selective conversion of biomass feedstocks involving multiple steps and complex processes.

Impact of COVID-19 on the Healthcare of Patients With Inflammatory Bowel Disease: A Comparison Between Epicenter vs. Non-epicenter Areas.

Background and Aims: The COVID-19 pandemic poses a great challenge to healthcare. We aimed to investigate the impact of COVID-19 on the healthcare of patients with inflammatory bowel disease (IBD) in epicenter and non-epicenter areas. Methods: Patients with IBD from Hubei province (the epicenter of COVID-19) and Guangdong province (a non-epicenter area), China were surveyed during the pandemic. The questionnaire included change of medications (steroids, immunomodulators, and biologics), procedures (lab tests, endoscopy, and elective surgery), and healthcare mode (standard healthcare vs. telemedicine) during 1 month before and after the outbreak of COVID-19. Results: In total, 324 IBD patients from Guangdong province (non-epicenter) and 149 from Hubei province (epicenter) completed the questionnaire with comparable demographic characteristics. Compared to patients in Guangdong province (non-epicenter), significantly more patients in Hubei (epicenter) had delayed lab tests/endoscopy procedures [61.1% (91/149) vs. 25.3% (82/324), p < 0.001], drug withdrawal [28.6% (43/149) vs. 9.3% (30/324), p < 0.001], delayed biologics infusions [60.4% (90/149) vs. 19.1% (62/324), p < 0.001], and postponed elective surgery [16.1% (24/149) vs. 3.7% (12/324), p < 0.001]. There was an increased use of telemedicine after the outbreak compared to before the outbreak in Hubei province [38.9% (58/149) vs. 15.4% (23/149), p < 0.001], while such a significant increase was not observed in Guangdong province [21.9% (71/324) vs. 18.8% (61/324), p = 0.38]. Approximately two-thirds of IBD patients from both sites agreed that telemedicine should be increasingly used in future medical care. Conclusions: Our patient-based survey study in a real-world setting showed that COVID-19 resulted in a great impact on the healthcare of patients with IBD, and such an impact was more obvious in the epicenter compared to the non-epicenter area of COVID-19. Telemedicine offers a good solution to counteract the challenges in an unprecedented situation such as COVID-19.

Involvement of digestive system in COVID-19: manifestations, pathology, management and challenges.

The pandemic of novel coronavirus disease (COVID-19) has developed as a tremendous threat to global health. Although most COVID-19 patients present with respiratory symptoms, some present with gastrointestinal (GI) symptoms like diarrhoea, loss of appetite, nausea/vomiting and abdominal pain as the major complaints. These features may be attributable to the following facts: (a) COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in GI epithelial cells, providing a prerequisite for SARS-CoV-2 infection; (b) SARS-CoV-2 viral RNA has been found in stool specimens of infected patients, and 20% of patients showed prolonged presence of SARS-CoV-2 RNA in faecal samples after the virus converting to negative in the respiratory system. These findings suggest that SARS-CoV-2 may be able to actively infect and replicate in the GI tract. Moreover, GI infection could be the first manifestation antedating respiratory symptoms; patients suffering only digestive symptoms but no respiratory symptoms as clinical manifestation have also been reported. Thus, the implications of digestive symptoms in patients with COVID-19 is of great importance. In this review, we summarise recent findings on the epidemiology of GI tract involvement, potential mechanisms of faecal-oral transmission, GI and liver manifestation, pathological/histological features in patients with COVID-19 and the diagnosis, management of patients with pre-existing GI and liver diseases as well as precautions for preventing SARS-CoV-2 infection during GI endoscopy procedures.

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates. FINDINGS: We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2-5; range 0-15; I2=74%). The pooled prevalence of digestive symptoms was 15% (10-21; range: 2-57; I2=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9-32; range 1-53; I2=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of abdominal pain (odds ratio [OR] 7·10 [95% CI 1·93-26·07]; p=0·003; I2=0%) and abnormal liver function including increased ALT (1·89 [1·30-2·76]; p=0·0009; I2=10%) and increased AST (3·08 [2·14-4·42]; p<0·00001; I2=0%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4-19; range 3-23; I2=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22-5·48]; p=0·030; I2=73%). Patients with gastrointestinal involvement tended to have a poorer disease course (eg, acute respiratory distress syndrome OR 2·96 [95% CI 1·17-7·48]; p=0·02; I2=0%). INTERPRETATION: Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. FUNDING: None.