Showing papers in "Digestive Diseases and Sciences in 2021"
TL;DR: This review will focus on how bile acids and their receptors mediate communications of intestinal microbiota with the intestinal immune system, describing dynamic changes of bile acid metabolism in IBD and the potential therapeutic application of targeting bile Acid signaling in these disorders.
Abstract: Bile acids are a group of chemically different steroids generated at the host/microbial interface. Indeed, while primary bile acids are the end-product of cholesterol breakdown in the host liver, secondary bile acids are the products of microbial metabolism. Primary and secondary bile acids along with their oxo derivatives have been identified as signaling molecules acting on a family of cell membrane and nuclear receptors collectively known as "bile acid-activated receptors." Members of this group of receptors are highly expressed throughout the gastrointestinal tract and mediate the bilateral communications of the intestinal microbiota with the host immune system. The expression and function of bile acid-activated receptors FXR, GPBAR1, PXR, VDR, and RORγt are highly dependent on the structure of the intestinal microbiota and negatively regulated by intestinal inflammation. Studies from gene ablated mice have demonstrated that FXR and GPBAR1 are essential to maintain a tolerogenic phenotype in the intestine, and their ablation promotes the polarization of intestinal T cells and macrophages toward a pro-inflammatory phenotype. RORγt inhibition by oxo-bile acids is essential to constrain Th17 polarization of intestinal lymphocytes. Gene-wide association studies and functional characterizations suggest a potential role for impaired bile acid signaling in development inflammatory bowel diseases (IBD). In this review, we will focus on how bile acids and their receptors mediate communications of intestinal microbiota with the intestinal immune system, describing dynamic changes of bile acid metabolism in IBD and the potential therapeutic application of targeting bile acid signaling in these disorders.
84 citations
TL;DR: For example, the authors found that non-Hispanic Black race was associated with nearly twice the odds of completing a phone visit instead of video visit, compared to non- Hispanic White patients, and being single or previously married (separated, divorced, widowed) is associated with increased odds of completion a phone compared to video visit compared to being married.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic resulted in a rapid expansion of telehealth services in hepatology. However, known racial and socioeconomic disparities in internet access potentially translate into barriers for the use of telehealth, particularly video technology. The specific aim of this study was to determine if disparities in race or socioeconomic status exist among patients utilizing telehealth visits during COVID-19. We performed a retrospective cohort study of all adult patients evaluated in hepatology clinics at Duke University Health System. Visit attempts from a pre-COVID baseline period (January 1, 2020 through February 29, 2020; n = 3328) were compared to COVID period (April 1, 2020 through May 30, 2020; n = 3771). On multinomial regression modeling, increasing age was associated with higher odds of a phone or incomplete visit (canceled, no-show, or rescheduled after May 30,2020), and non-Hispanic Black race was associated with nearly twice the odds of completing a phone visit instead of video visit, compared to non-Hispanic White patients. Compared to private insurance, Medicaid and Medicare were associated with increased odds of completing a telephone visit, and Medicaid was associated with increased odds of incomplete visits. Being single or previously married (separated, divorced, widowed) was associated with increased odds of completing a phone compared to video visit compared to being married. Though liver telehealth has expanded during the COVID-19 pandemic, disparities in overall use and suboptimal use (phone versus video) remain for vulnerable populations including those that are older, non-Hispanic Black, or have Medicare/Medicaid health insurance.
56 citations
TL;DR: These findings are the first to demonstrate the involvement of ferroptosis in SAP-associated renal damage and present ferroPTosis as a therapeutic target for effective treatment of SAP-induced AKI.
Abstract: Acute kidney injury (AKI) is a frequent complication of severe acute pancreatitis (SAP). Ferroptosis is involved in a range of diseases. However, the role of ferroptosis in SAP-induced AKI has yet to be elucidated. We aimed to investigate whether ferroptosis is induced in the kidney after SAP and whether inhibition of ferroptosis ameliorates AKI in a rat model of SAP. Sodium taurocholate (5%) was retrogradely perfused into the biliopancreatic duct to establish a model of SAP with AKI in rats. The levels of serum amylase, lipase, tumor necrosis factor (TNF)-α, interleukin (IL)-6, creatinine (Cr) and blood urea nitrogen (BUN) in rats were measured. We also determined the biochemical and morphological changes associated with ferroptosis in renal tissue, including iron accumulation, lipid peroxidation assays, and mitochondrial shrinkage. H&E staining was used to assess pancreatic and renal histological changes. Western blot analysis, RT-PCR, and immunofluorescence staining were performed to analyze the expression of ferroptosis-related proteins and genes. SAP-induced AKI was followed by iron accumulation, increased lipid peroxidation, and upregulation of ferroptosis-related proteins and genes. Twenty-four hours after SAP, TEM confirmed the presence of typical shrunken mitochondria. Furthermore, treatment with liproxstatin-1 lowered the levels of serum amylase, TNF-α, IL-6, Cr and BUN, decreased kidney lipid peroxidation and alleviated pancreatic and renal histopathology injury in SAP rats. Our findings are the first to demonstrate the involvement of ferroptosis in SAP-associated renal damage and present ferroptosis as a therapeutic target for effective treatment of SAP-induced AKI.
54 citations
TL;DR: A literature review of randomized controlled trials from 1973 to 2019 was used to compare the pooled efficacy of trials with a single strain versus the probiotic mixture with same matched strain within the same type of disease indication, finding that multi-strain mixtures were not significantly more effective than single-Strain probiotics.
Abstract: The diversity of probiotic products makes choosing an appropriate probiotic challenging. One unanswered question is whether single-strain probiotics are more effective than multi-strain mixtures. The aim of this review is to account for both disease and strain specificity to determine whether single strains or multiple strains are equivalent or more effective. This literature review of randomized controlled trials from 1973 to 2019 was used to compare the pooled efficacy of trials with a single strain versus the probiotic mixture with same matched strain within the same type of disease indication. A total of 65 RCTs were included (41 with single strains, 22 multi-strain mixtures and 2 comparing single strain to mixture arms) for eight different disease indications (N = 10,863). Only three strains (L. rhamnosus GG, L. helveticus R52 and B. lactis Bb12) had corresponding trials with matching mixtures. Use of L. rhamnosus GG only was significantly more protective for necrotizing enterocolitis compared to two mixtures also containing different strains of B. lactis. The mixture of L. rhamnosus GG and B. lactis Bb12 was significantly more effective than L. rhamnosus GG alone for the eradication of H. pylori. In most cases, single strains were equivalent to mixtures. Choice of an appropriate probiotic should be based, not on the number of strains in the product, rather based on evidence-based trials of efficacy. In most cases, multi-strain mixtures were not significantly more effective than single-strain probiotics.
53 citations
TL;DR: Results suggest that DCA-induced gut dysbiosis may act as a key etiologic factor in intestinal inflammation, associated with bile acid metabolic disturbance and downregulation of the FXR–FGF15 axis.
Abstract: A Western diet is a risk factor for the development of inflammatory bowel disease (IBD). High levels of fecal deoxycholic acid (DCA) in response to a Western diet contribute to bowel inflammatory injury. However, the mechanism of DCA in the natural course of IBD development remains unanswered. The aim of this study is to investigate the effect of DCA on the induction of gut dysbiosis and its roles in the development of intestinal inflammation. Wild-type C57BL/6J mice were fed an AIN-93G diet, either supplemented with or without 0.2% DCA, and killed at 24 weeks. Distal ileum and colon tissues were assessed by histopathological analysis. Hepatic and ileal gene expression was examined by qPCR, and the gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. HPLC–MS was used for fecal bile acid quantification. Mice fed the DCA-supplemented diet developed focal areas of ileal and colonic inflammation, accompanied by alteration of the composition of the intestinal microbiota and accumulation of fecal bile acids. DCA-induced dysbiosis decreased the deconjugation of bile acids, and this regulation was associated with the repressed expression of target genes in the enterohepatic farnesoid X receptor–fibroblast growth factor (FXR–FGF15) axis, leading to upregulation of hepatic de novo bile acid synthesis. These results suggest that DCA-induced gut dysbiosis may act as a key etiologic factor in intestinal inflammation, associated with bile acid metabolic disturbance and downregulation of the FXR–FGF15 axis.
51 citations
TL;DR: CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with F MT with colonoscope and capsule are comparable.
Abstract: Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules. To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI. We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design. Twenty-six studies (1309 patients) were included in the study. FMT was administered using colonoscopy in 16 studies (483 patients), NGT in five studies (149 patients), enema in four studies (360 patients), and capsules in four studies (301 patients). The random effects of pooled FMT cure rates were colonoscopy 94.8% (CI 92.4–96.8%; I2 15.6%), capsule 92.1% (CI 88.6–95.0%; I2 7.1%), enema 87.2% (CI 83.4–90.5%; I2 0%), and NGT/NDT 78.1% (CI 71.6–84.1%; I2 0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%. CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.
41 citations
TL;DR: Disruption of the TJ-mediated paracellular barrier in the duodenum and jejunum is an early event in prediabetes development, which occurs in the absence of detectable endotoxemia/inflammation and may contribute to the HF diet-induced increase in intestinal permeability.
Abstract: A link between an impaired intestinal barrier, endotoxemia, and the pathogenesis of metabolic diseases, such as type 2 diabetes mellitus (T2DM), has been proposed. In previous work, we have demonstrated that the tight junction (TJ)-mediated intestinal barrier in ileum/colon was marginally changed in prediabetic mice; therefore, it does not seem to mainly contribute to the T2DM onset. In this study, the TJ-mediated epithelial barrier in the duodenum and jejunum was evaluated in mice during the development of type 2 prediabetes. HF diet induced prediabetes after 60 days associated with a significant rise in intestinal permeability to the small-sized marker Lucifer yellow in these mice, with no histological signs of mucosal inflammation or rupture of the proximal intestine epithelium. As revealed by immunofluorescence, TJ proteins, such as claudins-1, -2, -3, and ZO-1, showed a significant decrease in junctional content in duodenum and jejunum epithelia, already after 15 days of treatment, suggesting a rearrangement of the TJ structure. However, no significant change in total cell content of these proteins was observed in intestinal epithelium homogenates, as assessed by immunoblotting. Despite the changes in intestinal permeability and TJ structure, the prediabetic mice showed similar LPS, zonulin, and TNF-α levels in plasma or adipose tissue, and in intestinal segments as compared to the controls. Disruption of the TJ-mediated paracellular barrier in the duodenum and jejunum is an early event in prediabetes development, which occurs in the absence of detectable endotoxemia/inflammation and may contribute to the HF diet-induced increase in intestinal permeability.
37 citations
TL;DR: MSC-exosomal miR-3940-5p inhibits invasion and EMT of CRC cells as well as growth and metastasis of tumors through targeting ITGA6 and the following TGF-β1 inactivation.
Abstract: Exosomes are potential tools for disease control by regulating intercellular communication through carrying proteins and RNAs between cells or remote organs. Exosome activities have aroused wide concerns in cancer biology and malignancy control. This study was performed to explore the roles of mesenchymal stem cell (MSC)-derived exosomes in colorectal cancer (CRC) progression. MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed, and aberrantly expressed miRNAs in CRC tissues were obtained from the data available on the GEO database. Altered expression of miR-3940-5p was introduced to identify its role in CRC invasion and metastasis in both cell and animal models. The binding relationship between miR-3940-5p and Integrin alpha6 (ITGA6) was predicted on TargetScan and validated through a luciferase assay. The effects of ITGA6 on CRC were figured out. MSC-derived exosomes carried miR-3940-5p into CRC cells. Up-regulation of miR-3940-5p inhibited epithelial–mesenchymal transition (EMT) and invasion of CRC cells, and suppressed the tumor metastasis and growth in vivo. miR-3940-5p was found to directly bind to ITGA6. Overexpression of ITGA6 promoted CRC cell invasion and EMT and tumor progression through upregulating the transforming growth factor-beta1 (TGF-β1) signaling. A TGF-β1-specific antagonist, Disitertide, blocked the functions of ITGA6 both in vivo and in vitro. MSC-exosomal miR-3940-5p inhibits invasion and EMT of CRC cells as well as growth and metastasis of tumors through targeting ITGA6 and the following TGF-β1 inactivation. This study may provide novel insights into exosome-based treatment for CRC.
37 citations
TL;DR: It is suggested that vonoprazan is non-inferior to PPIs as therapy for patients with GERD, and subgroup analysis indicates that vonopsion is more effective than PPIs for patientsWith severe erosive esophagitis.
Abstract: Gastroesophageal reflux disease (GERD) is a common disorder, and is typically treated with proton-pump inhibitors (PPIs) as the recommended first-line therapy. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. It is uncertain whether the standard dose of vonoprazan 20 mg is superior to that of PPIs for GERD, so a direct comparison of the therapeutic effects and adverse events between vonoprazan 20 mg and PPIs is needed. MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase were chosen as the literature sources. Randomized controlled trials for vonoprazan 20 mg and PPIs published in English were searched. Data from studies meeting the eligibility criteria were extracted individually by two researchers and compared to maintain consistency. Fifty-six articles were identified in the databases, and one study was manually searched and added to the analysis, ultimately yielding six eligible studies. For the main analysis, the risk ratios (RR) of efficacy and adverse events between vonoprazan and PPIs were 1.06 (0.99–1.13) and 1.08 (0.96–1.22), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher results for vonoprazan than lansoprazole, with an RR of 1.14 (1.06–1.22). Our findings suggest that vonoprazan is non-inferior to PPIs as therapy for patients with GERD. Subgroup analysis indicates that vonoprazan is more effective than PPIs for patients with severe erosive esophagitis. The safety outcomes for vonoprazan are similar to those for PPIs.
35 citations
TL;DR: The research and progress in immunotherapy for pancreatic cancer, including immune checkpoint inhibitors, vaccines, adoptive T cell therapy, oncolytic viruses, and immunomodulators are summarized and it is suggested that individualized, combination, and precise therapy should be the main direction of future immunotherapy in pancreaticcancer.
Abstract: Pancreatic cancer is a tumor with a high degree of malignancy, morbidity, and mortality. Immunotherapy is another important treatment for pancreatic cancer in addition to surgery and chemotherapy, but its application in pancreatic cancer is very limited, which is related to the unique biological behavior of pancreatic cancer and the tumor microenvironment. The immunosuppressive microenvironment of pancreatic cancer is highly heterogeneous and presents challenges for immunotherapy. The transformation of tumor immunosuppressive microenvironment contributes to the response to tumor immunotherapy, such that the tumor undergoes functional reprogramming to change from immunologically "cold" to immunologically "hot." In this review, we summarized the research and progress in immunotherapy for pancreatic cancer, including immune checkpoint inhibitors, vaccines, adoptive T cell therapy, oncolytic viruses, and immunomodulators, and suggest that individualized, combination, and precise therapy should be the main direction of future immunotherapy in pancreatic cancer.
35 citations
TL;DR: Significantly altered genes, microRNAs, and lncRNAs were identified, and a ceRNA regulatory network was constructed to explain the upregulation of METTL3 in HCC.
Abstract: N6-methyladenosine (m6A), the most prominent mRNA modification, plays a critical role in many physiological and pathological processes. However, the roles of m6A RNA modification in hepatocellular carcinoma (HCC) remain largely unknown. We investigated the mRNA expression and clinical significance of m6A-related genes using data from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma cohort. Mutation, copy number variation (CNV), methylation, differential expression, and gene ontology analyses, gene set enrichment analysis and the construction of a competing endogenous RNA (ceRNA) regulatory network were performed to investigate the underlying mechanisms of the aberrant expression of m6A-related genes. m6A-related genes were frequently dysregulated in cancers but with a cancer-specific pattern. METTL3, YTHDF2, and ZC3H13 were found to be independent prognostic factors of overall survival (OS); however, only METTL3 was found to be an independent prognostic factor of recurrence-free survival (RFS). Joint effects analysis showed the predictive capacity of combining METTL3, YTHDF2, and ZC3H13 for HCC OS. Then the potential mechanisms of METTL3 were further explored due to its prognostic role in both OS and RFS. CNV and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of METTL3 in HCC. Significantly altered genes, microRNAs, and lncRNAs were identified, and a ceRNA regulatory network was constructed to explain the upregulation of METTL3 in HCC. Our study identified several m6A-related genes, especially METTL3, that could be potential prognostic biomarkers in HCC.
TL;DR: In this database study of elderly patients coded with NAFLD no independent association with incident dementia was detected and risk assessment regarding dementia in patients withNAFLD should be carried out in the same way as for metabolic burdened patients.
Abstract: Dementia and NAFLD are two frequent conditions that share underlying risk factors mainly in the realm of metabolic disease. Additionally, an association between NAFLD and brain aging has been proposed. Therefore, we investigated the hypothesis if NAFLD is an independent risk factor for emerging dementia. In this population-based cohort study, elderly patients (≥ 65 years) with NAFLD diagnosed between 2000 and 2015 were matched 1:1 to a cohort without NAFLD based on ICD-10 coding in the Disease Analyzer database. Matching criteria were age, sex, physician, index year, and co-diagnoses associated with dementia. The primary outcomes of this study were all-cause dementia diagnoses, the incidence of vascular dementia, and antidementive drug prescription. A total of 22,317 patients with NAFLD were matched to 22,317 patients without NAFLD. Within 10 years of the index date, 16.0% of patients with NAFLD and 15.6% of the patients without NAFLD were diagnosed with dementia. On Cox regression analysis, there is no association between NAFLD and the incidence of all-cause dementia (HR 0.97, 95% CI 0.92–1.04), vascular dementia (HR 0.89, 95% CI 0.78–1.02), or the new prescription of antidementive therapy (HR 0.87, 95% CI 0.76–1.01). In sensitivity analyses, there was no association between NAFLD and dementia in different age-groups as well as men or women. In conclusion, in this database study of elderly patients coded with NAFLD no independent association with incident dementia was detected. Risk assessment regarding dementia in patients with NAFLD should be carried out in the same way as for metabolic burdened patients.
TL;DR: In a cohort of 342 patients, metabolic disease was highly prevalent including nearly 90% overweight, and HS was associated with increased transaminitis and need for intubation, dialysis, and vasopressors.
Abstract: Coronavirus disease-2019 (COVID-19) is a global pandemic. Obesity has been associated with increased disease severity in COVID-19, and obesity is strongly associated with hepatic steatosis (HS). However, how HS alters the natural history of COVID-19 is not well characterized, especially in Western populations. To characterize the impact of HS on disease severity and liver injury in COVID-19. We examined the association between HS and disease severity in a single-center cohort study of hospitalized COVID-19 patients at Michigan Medicine. HS was defined by either hepatic steatosis index > 36 (for Asians) or > 39 (for non-Asians) or liver imaging demonstrating steatosis > 30 days before onset of COVID-19. The primary predictor was HS. The primary outcomes were severity of cardiopulmonary disease, transaminitis, jaundice, and portal hypertensive complications. In a cohort of 342 patients, metabolic disease was highly prevalent including nearly 90% overweight. HS was associated with increased transaminitis and need for intubation, dialysis, and vasopressors. There was no association between HS and jaundice or portal hypertensive complications. In a sensitivity analysis including only patients with liver imaging > 30 days before onset of COVID-19, imaging evidence of hepatic steatosis remained associated with disease severity and risk of transaminitis. HS was associated with increased disease severity and transaminitis in COVID-19. HS may be relevant in predicting risk of complications related to COVID-19.
TL;DR: In E-CRC, obesity, DM2, HTN, HLD, and smoking are independent risk factors for CRC among men; obesity and HLD are independent risks for CRC in women; these subgroups may benefit from a personalized screening approach to detect early-onset CRC.
Abstract: The association between obesity and colorectal cancer (CRC) is well established in older individuals, but evidence is limited in the younger population. The study aims to analyze the relationship of obesity and its related comorbidities in early-onset CRC (E-CRC) and compare it to late-onset CRC (L-CRC). A retrospective, cross-sectional study was performed on average-risk individuals ≥ 20 years who were active patients in the commercial database, IBM Watson Health Explorys in the last 5 years. Individuals with CRC were compared to those without CRC across different age groups (20–39, 40–49, and 50–74 years). Individuals with CRC diagnosed < 50 years (E-CRC) were compared to those with CRC between 50 and 74 years (L-CRC). Variables included sex, smoking, obese BMI, diabetes mellitus type 2 (DM2), hypertension (HTN), and hyperlipidemia (HLD). Since Explorys aggregates population-level, de-identified data, approval from institutional review board was not required. Among 37,483,140 individuals, 162,150 cases of sporadic CRC were identified. Compared to the general population, obesity and HLD were independent risk factors for CRC across all age groups; DM2, HTN, and smoking were independent risk factors for CRC in men of all age groups and women with L-CRC. Compared to L-CRC, individuals with E-CRC had lower percentages of obesity-related comorbidities. In E-CRC, obesity, DM2, HTN, HLD, and smoking are independent risk factors for CRC among men; obesity and HLD are independent risk factors for CRC in women. These subgroups may benefit from a personalized screening approach to detect early-onset CRC.
TL;DR: Significant differences are found in the main components of the gut microbiome, with greater diversity in the STC group and differences between the groups in species composition at different classification levels, which may be valuable biomarkers for STC.
Abstract: Slow transit constipation (STC) is a type of functional constipation in which colon transit time is extended as a result of a reduction in the high amplitude of colon contraction activity. The utility of gut microbiome and metabolite characteristics in patients with STC is rarely studied. Short-chain fatty acids (SCFAs) enhance colonic fluid and sodium absorption and thus may aggravate the symptoms of STC. However, the content and role of SCFAs in constipation patients are not clear. We speculate that gut microbiome and SCFAs in the colon of STC patients may be abnormal and linked to the underlying mechanism of STC. This observational study is registered at ClinicalTrials.gov (NCT02984969). The high-throughput sequencing was used to analyze the diversity and composition of fecal microbial communities. Gas chromatography–mass spectrometry (GC–MS) was used to determine the properties and concentrations of the SCFAs in the two groups. The Shannon diversity and Simpson diversity of the gut microbiome were significantly greater in the STC group than the control group. The two groups also showed significant differences in the species composition of the gut microbiome at different classification levels. The results of GC–MS showed that the acetate concentrations in the STC group were significantly reduced compared with the control group, but the other five types of SCFAs and total SCFAs showed no significant difference between groups. ROC curve analyses revealed that the AUC of Acetate (AUC = 0.758) was higher than Propionate (AUC = 0.660). The largest AUC of gut microbiome for predicting STC was Prevotella (AUC = 0.807). Correlation analysis showed a positive correlation between the concentration of Ruminococcus and Disease history (rs = 0.519). Meanwhile, a positive correlation between the concentration of Roseburia and Acetate (rs = 0.606) or Butyrate (rs = 0.543) was found. We found significant differences between the STC and control groups in the main components of the gut microbiome, with greater diversity in the STC group and differences between the groups in species composition at different classification levels. These different microbiome and metabolite may be valuable biomarkers for STC.
TL;DR: Gastroenterologists who become aware of mast cell activation syndrome can dramatically improve the quality of life for their patients who previously have been labeled with a functional gastrointestinal disorder.
Abstract: Mast cell activation syndrome is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation. Gastrointestinal symptoms are frequently reported by these patients and are often mistaken by physicians as functional gastrointestinal disorders. This syndrome can be diagnosed by the medical history and measurable biomarkers. Gastroenterologists manage diseases associated with active inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils. The mast cell has only recently been recognized as a major player in our specialty. Gastrointestinal disorders from mast cell mediators often present with apparent irritable bowel syndrome, dyspepsia, chronic or cyclical nausea, and heartburn. Individuals with mast cell activation syndrome experience significant delays in diagnosis. The gastrointestinal symptoms are often refractory to symptom-targeted prescription medications. Beyond avoiding triggers, the best therapy is directed at modulating mast cell activation and the effects of the mediators. Many of these therapies are simple over-the-counter medications. In this article, we review mast cell function and dysfunction and the gastrointestinal symptoms, comorbid conditions, diagnosis, and management of mast cell activation syndrome. Gastroenterologists who become aware of this syndrome can dramatically improve the quality of life for their patients who previously have been labeled with a functional gastrointestinal disorder.
TL;DR: The END-PAC model was validated in a cohort of patients with NOD using retrospectively collected data from a large integrated health maintenance organization and it is critical that prediction models are validated before they are implemented in various populations and clinical settings.
Abstract: The risk of pancreatic cancer is elevated among people with new-onset diabetes (NOD). Based on Rochester Epidemiology Project Data, the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) model was developed and validated. We validated the END-PAC model in a cohort of patients with NOD using retrospectively collected data from a large integrated health maintenance organization. A retrospective cohort of patients between 50 and 84 years of age meeting the criteria for NOD in 2010–2014 was identified. Each patient was assigned a risk score (< 1: low risk; 1–2: intermediate risk; ≥ 3: high risk) based on the values of the predictors specified in the END-PAC model. Patients who developed pancreatic ductal adenocarcinoma (PDAC) within 3 years were identified using the Cancer Registry and California State Death files. Area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated. Out of the 13,947 NOD patients who were assigned a risk score, 99 developed PDAC in 3 years (0.7%). Of the 3038 patients who had a high risk, 62 (2.0%) developed PDAC in 3 years. The risk increased to 3.0% in white patients with a high risk. The AUC was 0.75. At the 3+ threshold, the sensitivity, specificity, PPV, and NPV were 62.6%, 78.5%, 2.0%, and 99.7%, respectively. It is critical that prediction models are validated before they are implemented in various populations and clinical settings. More efforts are needed to develop screening strategies most appropriate for patients with NOD in real-world settings.
TL;DR: In this paper, the authors evaluated the prevalence of enteric infections among hospitalized patients with COVID-19 and found that patients who tested positive were less likely to test positive compared to patients who did not test positive (10% vs 22%, p < 0.01).
Abstract: Gastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown. This study assessed the prevalence of enteric infections among hospitalized patients with COVID-19. We evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing. Among 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p < 0.01). This trend was driven by lower rates of non-C.difficile infections (11% vs 22% in COVID-19 positive vs. negative, respectively, p = 0.04), but not C. difficile infection (5.1% vs. 8.2%, p = 0.33). On multivariable analysis, infection with COVID-19 remained significantly associated with lower odds of concurrent GI infection (aOR 0.49, 95% CI 0.24–0.97), again driven by reduced non-C.difficile infection. Testing for both C.difficile and non-C.difficile enteric infection decreased dramatically during the pandemic. Pathogens aside from C.difficile do not appear to be a significant contributor to diarrhea in COVID-19 positive patients.
TL;DR: Multivariate analysis revealed resection size > 40 mm and heparin bridge were the independent risk factor for post-ESD bleeding and Ulcer base closure using endoloop and endoclips did not prevent post- ESD bleeding in patients on antithrombotic therapy.
Abstract: Antithrombotic therapy is a well-known independent risk factor for bleeding after endoscopic submucosal dissection (ESD) of early gastric cancer (EGC). A novel method of ulcer base closure using an endoloop and endoclips has been reported. This study aimed to evaluate the effectiveness of endoscopic closure using an endoloop and endoclips in preventing post-ESD bleeding in patients undergoing gastric ESD on antithrombotic therapy. This was a single center, retrospective study. Patients on antithrombotic therapy who underwent gastric ESD were divided into two groups, the closure group and the non-closure group. We analyzed procedural outcomes, post-ESD bleeding rate and factors associated with post-ESD bleeding. Among 400 ESDs with EGCs in 311 patients, 131 ESDs in 110 patients were in the closure group, and 269 ESDs in 217 patients were in the non-closure group (16 patients were overlapped in both groups). Post-ESD bleeding rate was 11.5% (15/131) in the closure group, and 11.9% (32/269) in the non-closure group (p = 0.89). Total sustained closure rate during second look endoscopy was 47.8% (33/69). Post-ESD bleeding rate tended to be lower in the closure group than in the non-closure group for lesions located in the greater curvature (3.6% vs. 11.1%, p = 0.11). In addition, sustained closure rate was significantly higher in the greater curvature than in the lesser curvature (72.0% vs. 34.1%, p 40 mm and heparin bridge were the independent risk factor for post-ESD bleeding. Ulcer base closure using endoloop and endoclips did not prevent post-ESD bleeding in patients on antithrombotic therapy.
TL;DR: In this paper, the authors assessed the prevalence of frailty and factors associated with 30-day readmission and mortality among hospitalized IBD patients, and found older age to be associated with a lower risk of readmission.
Abstract: Although age is often used as a clinical risk stratification tool, recent data have suggested that adverse outcomes are driven by frailty rather than chronological age. In this nationwide cohort study, we assessed the prevalence of frailty, and factors associated with 30-day readmission and mortality among hospitalized IBD patients. Using the Nationwide Readmission Database, we examined all patients with IBD hospitalized from 2010 to 2014. Based on index admission, we defined IBD and frailty using previously validated ICD codes. We used univariable and multivariable regression to assess risk factors associated with all-cause 30-day readmission and 30-day readmission mortality. From 2010 to 2014, 1,405,529 IBD index admissions were identified, with 152,974 (10.9%) categorized as frail. Over this time period, the prevalence of frailty increased each year from 10.20% (27,594) in 2010 to 11.45% (33,507) in 2014. On multivariable analysis, frailty was an independent predictor of readmission (aRR 1.16, 95% CI: 1.14–1.17), as well as readmission mortality (aRR 1.12, 95% CI 1.02–1.23) after adjusting for relevant clinical factors. Frailty also remained associated with readmission after stratification by IBD subtype, admission characteristics (surgical vs. non-surgical), age (patients ≥ 60 years old), and when excluding malnutrition, weight loss, and fecal incontinence as frailty indicators. Conversely, we found older age to be associated with a lower risk of readmission. Frailty, independent of age, comorbidities, and severity of admission, is associated with a higher risk of readmission and mortality among IBD patients, and is increasing in prevalence. Given frailty is a potentially modifiable risk factor, future studies prospectively assessing frailty within the IBD patient population are needed.
TL;DR: It is shown that lncRNA FAM230B might function to promote GC and functioned as a ceRNA by sponging miR-27a-5p and enhancing TOP2A expression.
Abstract: Long non-coding RNAs serve as key components of competing endogenous RNA (ceRNA) networks that underlie tumorigenesis. We investigated the pathogenic roles of lncRNA FAM230B and its molecular mechanism in gastric cancer (GC). The levels of FAM230B expression in five gastric cancer cell lines and in human gastric mucosal cells were compared by quantitative RT-PCR. To analyze the function of FAM230B in GC, we overexpressed FAM230B in AGS cells, silenced FAM230B in MGC-803 cells, and tested the effect of FAM230B on tumor growth in nude mice. The interaction between miR-27a-5p and FAM230B was predicted by a bioinformatics analysis and then verified with a dual-luciferase reporter assay. We also further investigated the role and mechanism of FAM230B by forcing overexpression of miR-27a-5p in MGC-803 gastric cancer cells. We found that FAM230B was highly expressed in gastric cancer cell lines and mainly located in the cytoplasm. FAM230B overexpression promoted the proliferation, migration, and invasion of AGS cells and repressed their apoptosis; it also facilitated tumor growth in vivo. In contrast, FAM230B knockdown suppressed the proliferation, migration, and invasion of MGC0803 cells, but enhanced their apoptosis and inhibited tumor growth in vivo. MiR-27a-5p expression was suppressed by FAM230B overexpression in AGS cells. MiR-27a-5p inhibited the proliferation, migration, and invasion of gastric cancer cells, and promoted the apoptosis of gastric cancer cells by reducing TOP2A (topoisomerase 2 alpha) expression. Our study showed that lncRNA FAM230B might function to promote GC. FAM230B functioned as a ceRNA by sponging miR-27a-5p and enhancing TOP2A expression.
TL;DR: The two-dose recombinant hepatitis B vaccine resulted in better seroconversion than the three-dose vaccine and was associated with a lower likelihood of achieving immunogenicity.
Abstract: The efficacy of the two-dose hepatitis B virus (HBV) vaccine (Heplisav-B®) in patients with chronic liver disease (CLD) is unknown. To compare the immunogenicity achieved with Heplisav-B and the conventional three-dose vaccine (Engerix-B®) in patients with CLD, and to identify factors that predict seroconversion. We retrospectively identified all adults who completed Heplisav-B or Engerix-B regimens from August 1, 2015, to January 31, 2019. Post-vaccination immunity was assessed by quantitative HBV surface antibody (HBsAb) measurement. We identified 166 patients (106 Engerix-B and 60 Heplisav-B) with chronic liver disease (mean age 59.0 ± 11.3 years, 52% male, 34% cirrhosis, mean MELD score of those with cirrhosis 10.1 ± 5.4) who had completed the vaccinations and had data available on post-vaccination HBsAb levels at least 2 months after completion of the vaccine regimen. Seroprotective HBsAb levels (> 10 mIU/ml) were achieved in 63% with Heplisav-B and in 45% with Engerix-B (p = 0.03). Univariable analysis showed that age (p = 0.01), insurance (p = 0.02), renal failure (p = 0.02), COPD (p = 0.05), and cirrhosis (p < 0.01) had a significant effect on achieving immunogenicity. On multivariable analysis, patients with cirrhosis (adjusted odds ratio [aOR]: 0.27, 95% CI 0.13–0.55), COPD (aOR: 0.06, 95% CI 0.01–0.56), or renal failure (aOR 0.36, 95% CI 0.14–0.93) had a lower likelihood of achieving immunity, and patients who received Heplisav-B® had a 2.7-fold greater likelihood of achieving immunity than those who received Engerix-B® (aOR: 2.74, 95% CI 1.31–5.71). The two-dose recombinant hepatitis B vaccine resulted in better seroconversion than the three-dose vaccine. Cirrhosis, COPD, and renal failure were associated with a lower likelihood of achieving immunogenicity.
TL;DR: It is suggested that various diagnostic modalities are accurate in diagnosing a disrupted pancreatic duct in patients with acute pancreatitis, and secretin-magnetic resonance cholangiopancreatography or magnetic resonance chlangiopANCreatography would be recommended as first diagnostic modality.
Abstract: Severe pancreatitis may result in a disrupted pancreatic duct, which is associated with a complicated clinical course Diagnosis of a disrupted pancreatic duct is not standardized in clinical practice or international guidelines We performed a systematic review of the literature on imaging modalities for diagnosing a disrupted pancreatic duct in patients with acute pancreatitis A systematic search was performed in PubMed, Embase and Cochrane library databases to identify all studies evaluating diagnostic modalities for the diagnosis of a disrupted pancreatic duct in acute pancreatitis All data regarding diagnostic accuracy were extracted We included 8 studies, evaluating five different diagnostic modalities in 142 patients with severe acute pancreatitis Study quality was assessed, with proportionally divided high and low risk of bias and low applicability concerns in 75% of the studies A sensitivity of 100% was reported for endoscopic ultrasound and endoscopic retrograde cholangiopancreatography The sensitivity of magnetic resonance cholangiopancreatography with or without secretin was 83% A sensitivity of 92% was demonstrated for a combined cohort of secretin-magnetic resonance cholangiopancreatography and magnetic resonance cholangiopancreatography A sensitivity of 100% and specificity of 50% was found for amylase measurements in drain fluid compared with ERCP This review suggests that various diagnostic modalities are accurate in diagnosing a disrupted pancreatic duct in patients with acute pancreatitis Amylase measurement in drain fluid should be standardized Given the invasive nature of other modalities, secretin-magnetic resonance cholangiopancreatography or magnetic resonance cholangiopancreatography would be recommended as first diagnostic modality Further prospective studies, however, are needed
TL;DR: In this non-randomized pilot study, FMT appears to be safe and potentially effective in terms of viral suppression and H beAg clearance in patients with HBeAg-positive CHB.
Abstract: Intestinal flora plays a critical role in immunity against hepatitis B virus (HBV). Fecal Microbiota Transplantation (FMT) may be a potential immunomodulatory therapy in patients with chronic hepatitis B (CHB). We aimed to study role of FMT in hepatitis B e antigen (HBeAg)-positive CHB patients in terms of its effect on HBeAg, HBsAg, and HBV DNA. HBeAg-positive patients despite being on antiviral treatment for > 1 year were given six cycles of FMT via gastroscope (nasoduodenal route) at 4 weekly intervals along with antiviral therapy. Twelve out of 14 included patients in FMT arm completed six cycles. Another 15 HBeAg-positive patients who were on oral antivirals for > 1 year were taken as control—antiviral therapy (AVT) arm. Per-protocol analysis was done. The median (interquartile range) age in the FMT and AVT arm were 29 (25–35) and 29(24–38), respectively (P = 0.794). The median (interquartile range) duration of AVT prior to inclusion in the study was 80 (52–104) and 76 (52–114) months in FMT and AVT arm, respectively (P = 0.884). In the FMT arm, 16.7% (2/12) patients had HBeAg clearance in comparison to none in the AVT arm (P = 0.188). None of the patients in either arm had HBsAg loss. The FMT was tolerated well, 42.8% (6/14) patients reported one or more minor adverse events. In this non-randomized pilot study, FMT appears to be safe and potentially effective in terms of viral suppression and HBeAg clearance in patients with HBeAg-positive CHB. Further randomized controlled trials are needed in order to obtain robust conclusions.
TL;DR: LncRNA DLX6-AS1 regulated tumor growth and aerobic glycolysis in GC by targeting miR-4290 and PDK1, suggesting DLX 6- AS1 might serve as a novel potential therapeutic target for GC treatment from bench to clinic.
Abstract: Gastric cancer (GC) is one of the most commonly diagnosed malignancy worldwide. DLX6 antisense RNA 1 (DLX6-AS1) is a long noncoding RNA (lncRNA) that exhibits oncogenic effects on multiple human carcinomas. This study aimed to investigate the regulatory effect of DLX6-AS1 in GC progression. The expression of DLX6-AS1 in GC tissues and cell lines was examined. The cell viability, number of clones, and apoptosis, aerobic glycolysis, and mitochondrial respiration was assessed. The effect of DLX6-AS1 on tumor growth in nude mice was also evaluated. DLX6-AS1 was overexpressed in GC tissues and cell lines. DLX6-AS1 knockdown by short hairpin RNA (shRNA) significantly inhibited cell viability and colony formation, and induced apoptosis. DLX6-AS1 silencing impaired aerobic glycolysis but stimulated mitochondrial respiration in GC cells. miR-4290 was confirmed as a downstream target of DLX6-AS1, and their expression levels were inversely correlated. GC cells expressing sh-DLX6-AS1 showed significantly lower level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), a target of miR-4290, compared to cells expressing control shRNA. In addition, the suppressed GC cell malignancy upon DLX6-AS1 knockdown could be prominently reversed by PDK1 overexpression. Meanwhile, PDK1 overexpression enhanced aerobic glycolysis but repressed mitochondrial respiration under sh-DLX6-AS1 treatment. Furthermore, DLX6-AS1 knockdown significantly delayed the tumor growth in a mouse xenograft model inoculated with GC cells. LncRNA DLX6-AS1 regulated tumor growth and aerobic glycolysis in GC by targeting miR-4290 and PDK1, suggesting DLX6-AS1 might serve as a novel potential therapeutic target for GC treatment from bench to clinic.
TL;DR: The majority of BCS patients are now treated by endovascular intervention and anticoagulation which have improved survival in this disease, and surgical porto-systemic shunts are no longer done for BCS, liver transplantation is reserved for select indications.
Abstract: Budd–Chiari syndrome (BCS) is an uncommon condition, caused by obstruction to hepatic venous outflow. It is largely underdiagnosed, and a high index of suspicion is required for any patient with unexplained portal hypertension. The understanding of its etiology and pathology is improving with advances in diagnostic techniques. Recent studies reported an identifiable etiology in > 80% of cases. Myeloproliferative neoplasm (MPN) is the most common etiology, and genetic studies help in diagnosing latent MPN. Better cross-sectional imaging helps delineate the site of obstruction accurately. The majority of BCS patients are now treated by endovascular intervention and anticoagulation which have improved survival in this disease. Angioplasty of hepatic veins/inferior vena cava remains under-utilized at present. While surgical porto-systemic shunts are no longer done for BCS, liver transplantation is reserved for select indications. Some of the unresolved issues in the current management of BCS are also discussed in this review.
TL;DR: While nearly all subjects with NAFLD identify physical activity to be important and desire to be more active, only a few meet activity recommendations, and discordance is due to a perceived lack of resources and education, physical discomfort, and time constraints.
Abstract: Lifestyle changes, including physical activity, are the cornerstones of the treatment of nonalcoholic fatty liver disease (NAFLD). For unclear reasons, most NAFLD patients do not achieve the recommended amount of weekly activity. Our aim was to measure perceived barriers to physical activity and enablers to exercise intervention. Consecutive subjects aged 18–70 with NAFLD were prospectively enrolled. An exercise motivation questionnaire was administered to assess current behaviors and perceived barriers. Eighty-seven subjects (60% female) were enrolled with mean age 52 years and mean body mass index (BMI) 34.5 kg/m2. Metabolic comorbidities were common: 49% had hyperlipidemia, 42% hypertension, and 40% diabetes. The majority (75%) did not achieve ≥ 150 min/week of physical activity. Ninety-one percent agreed that activity was important in improving NAFLD; 88% desired to be more active. Lack of exercise resources and education from treating provider (47%), physical discomfort during exercise (44%), and time constraints (32%) were the most common barriers. Rates of fitness tracker (34%), gym (33%), exercise program (33%), and personal trainer (17%) use were low. While nearly all subjects with NAFLD identify physical activity to be important and desire to be more active, only a few meet activity recommendations. This discordance is due to a perceived lack of resources and education, physical discomfort, and time constraints. Better understanding of these barriers and behaviors are important to improve morbidity and mortality in NAFLD. Future behavioral research removing the identified barriers is of great importance to global public health and should be prioritized.
TL;DR: FLC presents with a bimodal distribution in both early and elderly individuals and has a higher recurrence rate but better survival outcome compared to HCC.
Abstract: In the USA, fibrolamellar hepatocellular carcinoma (FLC) accounts for 1–2% of all cases of hepatocellular carcinoma. FLC remains poorly understood. We aim to investigate the incidence, demographics, tumor characteristics, treatment, and prognosis of patients with FLC. Data on FLC between 2000 and 2016 were extracted from the SEER database and analyzed. A total of 300 patients with FLC were identified where 126 were male. Median age at diagnosis was 27 ± 22 years. The overall age-adjusted incidence of FLC between 2000 and 2016 was 0.02 per 100,000 per year. A bimodal distribution was observed where the highest incidences occurred between 15–19 years and 70–74 years. Most tumors on presentation were moderately differentiated (20.7%), while the most common stage at presentation was stage 1 (21.7%) followed by stages 3 and 4 (20.0% and 20.3%, respectively); 50.3% of these tumors were surgically resected, while 8.0% received radiation and 45.3% received chemotherapy. One- and 5-year cause-specific survival for FLC was 72.0% and 32.9%, respectively, with a median survival of 32.9 months. HCC had a median survival time of 11.7 months. Patients who were not treated with surgical intervention had about 3 times increased risk for death (HR 2.8, 95% CI 1.68–4.72, P = 0.000). Radiation and chemotherapy did not significantly affect outcomes. FLC presents with a bimodal distribution in both early and elderly individuals. Compared to HCC, FLC has a higher recurrence rate but better survival outcome. Surgical intervention is superior to chemotherapy and radiation.
TL;DR: GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues from GC patients.
Abstract: How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established The present study therefore aims to investigate the microbial communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients These changes were evident in both tumor and paracancerous tissues from GC patients Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp abundance Importantly, these MDI values were readily able to discriminate between GC and SG patient samples Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues Differences in the relative abundance of Helicobacter spp may be the primary driver of gastric dysbiosis in GC patients
TL;DR: The diagnosis and work-up of elevated liver enzymes in patients with COVID-19 provides a timely glimpse into the difficulties encountered caring for these patients, and results should be interpreted in the context of potential limitations.
Abstract: Coronavirus Disease 2019 (COVID-19), due to infection with the virus termed SARS-CoV-2, has complicated the evaluation of elevated liver enzymes. Elevated liver enzymes occur in a median of 15% [1] and up to 58% [2] of patients with COVID-19. Though the most common patterns of liver enzyme abnormalities in patients with SARS-CoV-2 include elevated aminotransferases, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) typically 1–2 times the upper limit of normal [2], the prognostic significance of abnormal liver biochemistries remains uncertain. There are many potential contributing etiologies to elevated liver enzymes in patients with SARS-CoV-2 including direct liver injury, associated inflammatory responses, congestive hepatopathy, hepatic ischemia, drug-induced liver injury (DILI), and muscle breakdown [3, 4]. In one meta-analysis, an estimated 3% of patients had recognized chronic liver disease at the time of COVID-19 infection [5]. As a result, consultations for abnormal liver biochemistries in patients with COVID-19 are likely common and difficult to resolve. Clarifying a diagnosis is further complicated by the desire to limit exposure of staff assisting with or performing diagnostic testing (e.g., abdominal ultrasound or liver biopsy). In this context, there is need for more information on how best to evaluate these patients. In the current issue of Digestive Diseases and Sciences, Bloom et al. [6] demonstrate the diagnostic difficulties of evaluating elevated liver enzymes in patients with COVID19. The authors identified twenty adult inpatients at Massachusetts General and Brigham and Women’s Hospitals who were PCR-positive for SARS-CoV-2 and received inpatient hepatology consultations for abnormal liver biochemistries. Laboratory and clinical data were retrospectively reviewed by three senior hepatologists who assigned a rank-order list of the top three potential etiologies, providing recommendations for additional evaluations. Patients with COVID-19 in this study were middle-aged (median 46 years), 90% male, 55% Hispanic, and 40% had underlying chronic liver disease. Most had a hepatocellular (64%) or cholestatic (29%) pattern of liver biochemistries. Blood chemistries reflective of liver synthetic function were generally normal. The most common diagnoses for these patients were COVID-related liver injury and DILI, but agreement on the most likely diagnosis was low among the three hepatologists and the original consultant (κ agreement 0.10). Conversely, all were in general agreement with the diagnostic work-up, which included liver enzyme monitoring for all patients. Abdominal ultrasound was recommended for a minority and was often discouraged. Similarly, cross-sectional imaging and liver biopsy were not recommended for any patients. This investigation of the diagnosis and work-up of elevated liver enzymes in patients with COVID-19 provides a timely glimpse into the difficulties encountered caring for these patients. However, study results should be interpreted in the context of potential limitations. This study included a small patient sample, and results may lack generalizability to other settings given that it was conducted at a large academic medical center early in the US COVID-19 epidemic (March–April 2020), when understanding of the hepatic effects of SARS-CoV-2 was limited. Furthermore, restricting this cohort to patients with a hepatology consultation may have selected for more complex patients, which could account for the large proportion of included patients with chronic liver disease. Lastly, without follow-up data in these patients, it is impossible to evaluate the accuracy of the ranked diagnoses. These potential limitations do not diminish the immediate clinical implications of this study. These results underscore the immense diagnostic challenge of elevated liver enzymes in COVID-19, given the large degree of disagreement among * Andrew M. Moon Andrew.Moon@unchealth.unc.edu