Background AMP kinase (AMPK) is an energy sensor implicated in regulation of lipid metabolism, inflammation, and insulin sensitivity. We aimed to assess efficacy and safety of PXL770, a novel direct AMPK activator, in patients with non-alcoholic fatty liver disease (NAFLD). Methods STAMP-NAFLD, a randomised, double-blind, placebo-controlled phase 2a study, was done across 15 US clinical sites. Patients

Background Studies have reported a significant association between non-alcoholic fatty liver disease (NAFLD) and increased incidence of cardiovascular disease (CVD). However, the magnitude of the risk and whether this risk changes with the severity of NAFLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of

Background The use of magnetically controlled capsules for gastroscopy is in the early stages of clinical adoption. We aimed to evaluate the safety and efficacy of a fully automated magnetically controlled capsule endoscopy (FAMCE) system in clinical practice for gastroscopy and small bowel examination. Methods We did a prospective, comparative study to evaluate the safety and efficacy of FAMCE. Patients

Background Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. Methods In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium)

Background Computer-aided detection (CADe) techniques based on artificial intelligence algorithms can assist endoscopists in detecting colorectal neoplasia. CADe has been associated with an increased adenoma detection rate, a key quality indicator, but the utility of CADe compared with existing advanced imaging techniques and distal attachment devices is unclear. Methods For this systematic review

Background Treatment options are sparse for patients with advanced cholangiocarcinoma after progression on first-line gemcitabine-based therapy. FGFR2 fusions or rearrangements occur in 10–16% of patients with intrahepatic cholangiocarcinoma. Infigratinib is a selective, ATP-competitive inhibitor of fibroblast growth factor receptors. We aimed to evaluate the antitumour activity of infigratinib in

Background BI 695501 is a biosimilar that has demonstrated similar efficacy, safety, and immunogenicity to adalimumab reference product in patients with rheumatoid arthritis and chronic plaque psoriasis. The VOLTAIRE-CD study aimed to compare the efficacy and safety of BI 695501 with adalimumab reference product in patients with Crohn's disease. Methods This phase 3, randomised, double-blind study

Restorative proctocolectomy with ileal pouch–anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae

Sleep is a complex, highly regulated process essential for human health and wellbeing. Increasingly, sleep–wake disturbance has been implicated in the pathogenesis of chronic liver disease, particularly the development and progression of non-alcoholic fatty liver disease and alcohol-related liver disease. Patients with cirrhosis also have a high burden of sleep abnormalities with substantial implications

The term non-alcoholic fatty liver disease (NAFLD), and its definition, have limitations for both adults and children. The definition is most problematic for children, for whom alcohol consumption is usually not a concern. This problematic definition has prompted a consensus to rename and redefine adult NAFLD associated with metabolic dysregulation to metabolic (dysfunction)-associated fatty liver

Sub-Saharan Africa, which has a population of more than 1 billion people, carries 24% of the global burden of disease and spends the least on health care of any region, relying heavily on international development assistance to deliver health care for HIV, tuberculosis, and malaria. The demographic and epidemiological transitions occurring in sub-Saharan Africa, with rising prevalences of obesity and

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and is estimated to affect approximately 25% of the world's population. Data about the prevalence and incidence of NAFLD in Africa are scarce, but the prevalence is estimated to be 13·5% for the general population. This is likely to be an underestimate considering the increasing burden of non-communicable

Background Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin analogues might decrease rebleeding rates, but the true effect size is unknown. We therefore aimed to investigate the efficacy of somatostatin analogues on red blood cell transfusion requirements of patients with gastrointestinal

Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable

Background White light endoscopy is a pivotal first-line tool for the detection of gastric neoplasms. However, gastric neoplasms can be missed during upper gastrointestinal endoscopy due to the subtle nature of these lesions and varying skill among endoscopists. Here, we aimed to evaluate the effect of an artificial intelligence (AI) system designed to detect focal lesions and diagnose gastric neoplasms

Background Colorectal cancer is one of the leading causes of cancer morbidity and mortality in Europe. We aimed to ascertain the economic burden of colorectal cancer across Europe using a population-based cost-of-illness approach. Methods In this population-based cost-of-illness study, we obtained 2015 activity and costing data for colorectal cancer in 33 European countries (EUR-33) from global and

Background RO7049389, a hepatitis B virus (HBV) core protein allosteric modulator being developed for the treatment of chronic HBV infection, was found to be safe and well tolerated in healthy participants (part 1 of this study). The objective of this proof-of-mechanism study (part 2) was to evaluate the safety, pharmacokinetics, and antiviral activity of RO7049389 in patients with chronic HBV infection

Background Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous

With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of

Inflammatory bowel diseases, principally Crohn's disease and ulcerative colitis, are multifactorial chronic conditions. Alterations in gut microbial patterns partly affect disease onset and severity. Moreover, the evolution of dietary patterns, and their effect on gut microbial behaviour, have been shown to play a crucial role in disease processes. This Viewpoint reviews the role of dietary patterns

Background Biologic treatment options are limited for children with ulcerative colitis. The aim of this study was to assess the safety and efficacy of adalimumab in children with moderate-to-severe ulcerative colitis. Methods The double-blind ENVISION I study was done at 24 hospitals in ten countries. Children (4–17 years) with moderate-to-severe ulcerative colitis despite stable doses of concurrent

Background WHO has set targets to eliminate hepatitis C virus (HCV) infection as a global health threat by 2030 through a 65% reduction in HCV-related deaths and 80% reduction in HCV incidence. To achieve these goals, WHO set service coverage targets of 90% of the infected population being diagnosed and 80% of eligible patients being treated. In February, 2016, Iceland initiated a nationwide HCV elimination

Background Functional constipation is a common functional bowel disorder in the community, which has a varying prevalence across cross-sectional surveys. We did a contemporaneous systematic review and meta-analysis of studies using comparable methodology and all iterations of the Rome criteria to estimate the global prevalence of functional constipation. Methods In this systematic review and meta-analysis

Background Hepatocellular carcinoma is the third-leading cause of cancer-related death worldwide. Preservation of health-related quality of life (HRQOL) during treatment is an important therapeutic goal. The aim of this study was to evaluate the effect of treatment with lenvatinib versus sorafenib on HRQOL. Methods REFLECT was a previously published multicentre, randomised, open-label, non-inferiority

Transmural healing is associated with substantial improvements in disease-related outcomes for patients with Crohn's disease, but there is no single validated definition of transmural healing to date. We did a systematic review to summarise the available definitions and to evaluate the effect of transmural healing on disease-related outcomes for patients with Crohn's disease by searching PubMed, Cochrane

Diabetes represents a group of diseases involving persistent hyperglycaemia. Exocrine disorders of the pancreas are increasingly recognised to cause or precede the onset of diabetes, which in this context is referred to as pancreatogenic or type 3c diabetes. Diabetes, as a sequela of acute pancreatitis, is observed across the spectrum of severity in acute pancreatitis and can be associated with other

Background Limited empirical evidence exists for the effectiveness of hepatitis C virus (HCV) treatment-as-prevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study aimed to assess the effect of HCV treatment-as-prevention in the prison setting. Methods SToP-C was a prospective study, including a before-and-after analysis, within a cohort of people incarcerated in two

Background Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods In this systematic review and individual participant data meta-analysis,

Background Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma

Background Laparoscopic surgery has been widely used for rectal cancer; however, its long-term outcomes remain controversial. This study aimed to assess the long-term oncological safety of laparoscopic surgery for rectal cancer using 10-year follow-up data of the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial. Methods The

Non-alcoholic fatty liver disease (NAFLD) is a public health problem worldwide. This narrative Review provides an overview of the current literature to support the notion that NAFLD is a multisystem disease. Convincing evidence shows a strong association between NAFLD and the risk of developing multiple extrahepatic complications such as type 2 diabetes, cardiovascular disease (ie, the predominant

Increased knowledge of the intricate pathogenesis of ulcerative colitis has triggered an advance in drug development during the past two decades, resulting in the advent of several biological agents and small-molecule therapies. Although the increase in therapeutic options is positive, remission rates of patients with ulcerative colitis given new therapeutic agents in induction trials remain at a modest

Background Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients with ulcerative colitis in remission. We therefore aimed

Background The benefit and safety of laparoscopic pancreatoduodenectomy (LPD) for the treatment of pancreatic or periampullary tumours remain controversial. Studies have shown that the learning curve plays an important role in LPD, yet there are no randomised studies on LPD after the surgeons have surmounted the learning curve. The aim of this trial was to compare the outcomes of open pancreatoduodenectomy

Background In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir

Background Clinical trials in irritable bowel syndrome are associated with high placebo response rates. We aimed to identify the magnitude of the placebo response and the contributing factors to this occurrence. Methods We did a systematic review and meta-analysis with a search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials between April 1, 1959, and April 30, 2020. We included

Background The only established treatment for preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) is colectomy, which greatly reduces patient quality of life. Thus, an alternative method is warranted. In this trial, we aimed to clarify the individual and joint effects of low-dose aspirin and mesalazine on the recurrence of colorectal polyps in Japanese patients with FAP

The majority of patients with Crohn's disease and a proportion of patients with ulcerative colitis will ultimately require surgical treatment despite advances in diagnosis, therapy, and endoscopic interventions. The surgical procedures that are most commonly done include bowel resection with anastomosis, strictureplasty, faecal diversion, and ileal pouch. These surgical treatment modalities result

The contribution of the microbiota to disease progression and treatment efficacy is often neglected when determining who is at the highest risk of developing gastrointestinal cancers or designing treatment strategies for patients. We reviewed the current literature on the effect of the human microbiota on cancer risk, prognosis, and treatment efficacy. We highlight emerging research that seeks to identify

Background Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration

Background Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut–brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this

Background Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement

Background The COVID-19 pandemic has led to a substantial reduction in gastrointestinal endoscopies, creating a backlog of procedures. We aimed to quantify this backlog nationally for England and assess how various interventions might mitigate the backlog. Methods We did a national analysis of data for colonoscopies, flexible sigmoidoscopies, and gastroscopies from National Health Service (NHS) trusts

Hepatitis C virus (HCV) is a global public health problem in correctional settings. The International Network on Health and Hepatitis in Substance Users–Prisons Network is a special interest group committed to advancing scientific knowledge exchange and advocacy for HCV prevention and care in correctional settings. In this Review, we highlight seven priority areas and best practices for improving HCV

The frequent co-occurrence of irritable bowel syndrome and the common mental disorders of anxiety and depression is well established. A range of biological and psychosocial disease mechanisms are common to both disorders, many of which contribute to a dysregulated gut–brain axis. Clinical and subthreshold psychological comorbidity adds to the functional impairment and disease burden in individuals

Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome

Background Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but has inherent risks. Microbial Ecosystem Therapeutic 2 (MET-2) is an oral encapsulated formulation of 40 lyophilised bacterial species initially isolated from stool of a healthy donor, but subsequently manufactured independently of donors, eliminating potential risks introduced

Background Patients with advanced oesophageal cancer have a median survival of 3–6 months, and most require intervention for dysphagia. Self-expanding metal stent (SEMS) insertion is the most typical form of palliation in these patients, but dysphagia deterioration and re-intervention are common. This study examined the efficacy of adjuvant external beam radiotherapy (EBRT) compared with usual care

Background Colorectal cancer screening programmes worldwide have been disrupted during the COVID-19 pandemic. We aimed to estimate the impact of hypothetical disruptions to organised faecal immunochemical test-based colorectal cancer screening programmes on short-term and long-term colorectal cancer incidence and mortality in three countries using microsimulation modelling. Methods In this modelling

Autoimmune hepatitis is an immune-mediated disorder characterised by hypergammaglobulinaemia, autoantibodies, and interface hepatitis. The mainstay of treatment is non-specific immunosuppression, consisting of steroids with or without azathioprine. Although most patients respond satisfactorily to steroid and thiopurine-based treatment regimens, up to 40% relapse and 10% undergo liver transplantation

Anal squamous cell carcinoma is the most common type of anal cancer and is largely associated with anal human papillomavirus infection. The incidence of anal squamous cell carcinoma is increasing, and although still uncommon in the general population, a high incidence has been noted in specific population groups (eg, patients with HIV, men who have sex with men [MSM], recipients of solid organ transplants

Background Treatment for infection with hepatitis C virus (HCV) during pregnancy has not yet been approved; however, interventions specifically targeting women, especially those of childbearing age (15–49 years), could prevent vertical transmission and community spread. To assess the impact of such interventions, improved prevalence estimates in this group are needed. We aimed to estimate the global

Background Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic

Background There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England. Methods Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer

Background Findings of preclinical and clinical trials in colorectal cancer have shown promising antitumour effects of the co-formulation trifluridine/tipiracil and VEGF inhibition. We aimed to investigate the safety and activity of trifluridine/tipiracil and ramucirumab for previously treated advanced gastric cancer. Methods We did an open-label, single-arm, two-cohort, phase 2 study at eight centres

SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions

Linked to the growing obesity epidemic, demand for bariatric and metabolic surgery has increased, the most common procedures being sleeve gastrectomy and Roux-en-Y gastric bypass. Originally, bariatric procedures were described as purely restrictive, malabsorptive, or combined restrictive–malabsorptive procedures limiting food intake, nutrient absorption, or both. Nowadays, anatomical alterations are

Obesity and the corresponding burden of related diseases is a major public health issue worldwide that is reaching pandemic proportions. Bariatric surgery is the only intervention that has been shown to result in substantial and lasting weight loss, and a decrease in overall mortality for patients with severe obesity. Consequently, the population of patients having undergone this procedure is increasing

Background Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving

Background In 2016, of the estimated 257 million people living with chronic hepatitis B virus (HBV) infection worldwide, only a small proportion was diagnosed and treated. The insufficiency of information on the proportion of people infected with HBV who are eligible for treatment limits the interpretation of global treatment coverage. We aimed to estimate the proportion of people with chronic HBV