Dose escalation randomised study of efmarodocokin alfa in healthy volunteers and patients with ulcerative colitis
Conclusion
Efmarodocokin alfa had an adequate safety and pharmacokinetic profile in HVs and patients. Biomarker data confirmed IL-22R pathway activation in the colonic epithelium. Results support further investigation of this non-immunosuppressive potential inflammatory bowel disease therapeutic.
Trial registration number
NCT02749630. (Source: Gut)
Source: Gut - July 6, 2023 Category: Gastroenterology Authors: Wagner, F., Mansfield, J. C., Lekkerkerker, A. N., Wang, Y., Keir, M., Dash, A., Butcher, B., Harder, B., Orozco, L. D., Mar, J. S., Chen, H., Rothenberg, M. E. Tags: Open access, Gut Inflammatory bowel disease Source Type: research
Long versus short peroral endoscopic myotomy for the treatment of achalasia: results of a non-inferiority randomised controlled trial
Conclusions
Our study demonstrates non-inferiority of a shorter cut length of POEM as compared with the standard treatment, which saved some procedural time. GORD rate was not reduced by reducing cutting length.
Trial registration number
NCT03450928. (Source: Gut)
Source: Gut - July 6, 2023 Category: Gastroenterology Authors: Familiari, P., Borrelli de Andreis, F., Landi, R., Mangiola, F., Boskoski, I., Tringali, A., Perri, V., Costamagna, G. Tags: Gut Endoscopy Source Type: research
'Invisible immune checkpoint molecule causing resistance to anti-PD1 therapy in HCC
Immune checkpoint inhibitors targeting PD-1/PD-L1 have become standard of care as systemic first-line therapy for the treatment of hepatocellular carcinoma (HCC).1 As of today, only antibody-based treatments have been approved to block the PD-1/PD-L1 pathway. A recent study from Tan et al published in Gut2 describes the unexpected finding that lymphocytes from patients with HCC express an alternative spliced isoform of PD-1, which contains an in-frame deletion of 14-amino acids within the exon 2 of PD-1, 42PD-1. Importantly, 42PD-1 does not interact with PD-L1/L2 and most commercially available anti-PD-1 monoclonal antibod...
Source: Gut - July 6, 2023 Category: Gastroenterology Authors: Greten, T. F. Tags: Gut Commentary Source Type: research
Meltdown of the cold tumour microenvironment: a new 'translational approach to augment immunotherapy efficacy
Liver cancer represents a huge global burden as the third leading cause of cancer deaths. While hepatocellular carcinoma accounts for 80%–90% of primary liver cancer diagnoses, the incidence of intrahepatic cholangiocarcinoma (ICC) is increasing in most countries.1 Although the restoration of T cell functions by immune checkpoint inhibitors (ICIs) has achieved unprecedented clinical responses in various malignancies, the role for immunotherapy in ICC remains to be established.1 The heterogeneous ICI responsiveness is influenced by a range of tumour cell-intrinsic factors, tumour-stroma factors including the immunosup...
Source: Gut - July 6, 2023 Category: Gastroenterology Authors: Cheng, A. S.-L. Tags: Gut Commentary Source Type: research
Engineered IFN-{alpha} and anti-PDL1 containing compounds to target the liver and restore antiviral protection for HBV cure
Chronic HBV infection, with hepatic inflammation and viral genome persistence in the hepatocytes either in the form of cccDNA or partially integrated into the host nucleus, is one of the major causes of liver cirrhosis and hepatocellular carcinoma.1 Available therapies for chronic hepatitis B (CHB) include long-term administration of nucleos(t)ide analogues or a finite treatment with polyethylene-glycol (PEG)–interferon alpha (IFN-α) that rarely allow reaching a functional cure, defined as loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA in the serum.1 Thus, a major effort is currently devot...
Source: Gut - July 6, 2023 Category: Gastroenterology Authors: Fisicaro, P. Tags: Gut Commentary Source Type: research
Comparative effects of non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease on risk of incident cardiovascular events: a meta-analysis of about 13 million individuals
We read with interest the report on comparative risks of liver-related and cardiovascular disease (CVD) outcomes among lean and obese patients with non-alcoholic fatty liver disease (NAFLD) by Younes et al.1 Recently, international experts proposed redefining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD).2 The impact of this name change on CVD risk prediction is not known. We performed a meta-analysis of observational cohort studies (by searching PubMed, Scopus and Web of Science from database inception to 30 June 2022) that simultaneously used the NAFLD and MAFLD definitions for examining the risk ...
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Mantovani, A., Csermely, A., Tilg, H., Byrne, C. D., Targher, G. Tags: Gut PostScript Source Type: research
Ageing trajectory of the gut microbiota is associated with metabolic diseases in a chronological age-dependent manner
We read with interest the recent article by Ng et al. (Gut, 2022; 71:910–8), who reported inhibition of the gut microbiota trajectory in patients with autism spectrum disorder.1 Similarly, the human gut microbiota ages in adults.2 3 Transplantation of gut microbes from elderly hosts, compared with their younger counterparts, deteriorates recipients’ age-related metabolic alternations.4 5 However, the gut microbiota in humans could differ in its pace of ageing, namely, accelerated or delayed microbiota ageing, even among those with similar chronological ages (figure 1A); this process is analogous to biological a...
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Fu, J., Qiu, W., Zheng, H., Qi, C., Hu, S., Wu, W., Wang, H., Wu, G., Cao, P., Ma, Z., Zheng, C., Ma, W.-J., Zhou, H.-W., He, Y. Tags: Open access, Gut PostScript Source Type: research
Single-cell gene expression links SARS-CoV-2 infection and gut serotonin
We read with great interest the paper by Ha et al1 demonstrating that circulating levels of serotonin (5-hydroxytryptamine, 5-HT) are increased in COVID-19 and correlate with disease severity and gastrointestinal symptoms such as diarrhoea. Another recent paper by Lin et al2 in this journal demonstrated that diarrhoea is the most common GI symptom in patients with COVID-19. Almost all 5-HT in our body is produced by enterochromaffin (EC) cells within the epithelium of the GI tract, which constitute approximately half of all enteroendocrine (EE) cells. Gut-derived 5-HT modulates gut peristalsis and exacerbates inflammatory ...
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Martin, A. M., Roach, M., Jones, L. A., Thorpe, D., Coleman, R. A., Allman, C., Edwards, R., Keating, D. J. Tags: Open access, Gut, COVID-19 PostScript Source Type: research
Unravelling the risk of developing gastric cancer in autoimmune gastritis
We read with interest the paper by Rugge et al,1 who performed a single-centre study looking at the incidence of gastric cancer in patients with ‘pure’ autoimmune gastritis (AIG). The study has several strengths. First, it aims to fill some gaps about the risk of gastric carcinogenesis with a precise selection of the patients by accurately excluding an active or previous Helicobacter pylori infection. Another point of strength is the relatively long follow-up period. However, despite its undoubted interest, some considerations should be made. The first point we would like to address relates to the natural histo...
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Lenti, M. V., Broglio, G., Di Sabatino, A. Tags: Gut PostScript Source Type: research
LAMS versus plastic stents for infected pancreatic walled off necrosis (WON): has the addition of the TENSION trial to the AXIOMA study eased the tension?
We read with interest a recently published comparative non-randomised study by Boxhoorn et al.1 The TENSION trial compared with the AXIOMA study found that when compared with double-pigtail plastic stents in patients with infected pancreatic walled off necrosis (WON), lumen opposing metallic stent (LAMS) did not reduce the need for endoscopic transluminal necrosectomy and the rate of bleeding complications were comparable. Infected pancreatic WON is the most common indication for drainage. It has always been a difficult task for gastroenterologist to choose between LAMS and plastic stents for drainage in order to achieve a...
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Tiwari, A., Shah, A., Singh, J. Tags: Gut PostScript Source Type: research
GI highlights from the literature
Basic scienceGood-sleep diet: effects on sleep mediated by gut-to-brain direct interactions in modified diets Titos I, Juginović A, Vaccaro A, et al. A gut-secreted peptide suppresses arousability from sleep. Cell 2023;1867:1382–1397.e21. doi: 10.1016/j.cell.2023.02.022. To ensure sleep is deep and restorative, external stimuli have to be suppressed. Across species, ‘good sleep’ is influenced by multiple genes. External factors, like diet, have been recognised to impact on sleep quality. Titos et al identified a gut signalling pathway that suppresses arousability in flies and mice models. Using inc...
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Smith, P. J. Tags: Gut JournalScan Source Type: research
Fungi and cancer
The microbiome may impact cancer development, progression and treatment responsiveness, but its fungal components remain insufficiently studied in this context. In this review, we highlight accumulating evidence suggesting a possible involvement of commensal and pathogenic fungi in modulation of cancer-related processes. We discuss the mechanisms by which fungi can influence tumour biology, locally by activity exerted within the tumour microenvironment, or remotely through secretion of bioactive metabolites, modulation of host immunity and communications with neighbouring bacterial commensals. We examine prospects of utili...
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Saftien, A., Puschhof, J., Elinav, E. Tags: GUT Recent advances in basic science, Gut Source Type: research
Diagnostic accuracy of FibroScan-AST (FAST) score for the non-invasive identification of patients with fibrotic non-alcoholic steatohepatitis: a systematic review and meta-analysis
Conclusion
The results of our meta-analysis show that the FAST score has a good performance for non-invasive diagnosis of fibrotic NASH. Therefore, this score can be used to efficiently identify patients who should be referred for a conclusive liver biopsy and/or consideration for treatment with emerging pharmacotherapies.
PROSPERO registration number
CRD42022350945. (Source: Gut)
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Ravaioli, F., Dajti, E., Mantovani, A., Newsome, P. N., Targher, G., Colecchia, A. Tags: Gut Hepatology Source Type: research
Randomised phase 2 study (JADE) of the HBV capsid assembly modulator JNJ-56136379 with or without a nucleos(t)ide analogue in patients with chronic hepatitis B infection
Conclusions
In patients with non-cirrhotic CHB, JNJ-56136379+NA showed pronounced reductions in HBV DNA and HBV RNA, limited HBsAg or HBeAg declines in patients who are NCT HBeAg positive, and was well tolerated, but no clear benefit with regards to efficacy of JNJ-56136379 over NA was observed. (Source: Gut)
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Janssen, H. L. A., Hou, J., Asselah, T., Chan, H. L. Y., Zoulim, F., Tanaka, Y., Janczewska, E., Nahass, R. G., Bourgeois, S., Buti, M., Lampertico, P., Lenz, O., Verbinnen, T., Vandenbossche, J., Talloen, W., Kalmeijer, R., Beumont, M., Biermer, M., Shuk Tags: Open access, Gut Hepatology Source Type: research
S100A10 promotes HCC development and progression via transfer in extracellular vesicles and regulating their protein cargos
Conclusion
Altogether, our results uncovered that S100A10 promotes HCC progression significantly via its transfer in EVs and regulating the protein cargoes of EVs. EV-S100A10 may be a potential therapeutic target and biomarker for HCC progression. (Source: Gut)
Source: Gut - June 7, 2023 Category: Gastroenterology Authors: Wang, X., Huang, H., Sze, K. M.-F., Wang, J., Tian, L., Lu, J., Tsui, Y.-M., Ma, H. T., Lee, E., Chen, A., Lee, J., Wang, Y., Yam, J. W. P., Cheung, T.-T., Guan, X., Ng, I. O.-L. Tags: Open access, Gut Hepatology Source Type: research
