Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to...Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to their complex pathophysiology and tendency to relapse. A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers and achieve long-term goals such as mucosal healing. Lifelong medication is often necessary to manage the disease, maintain remission and prevent complications. The therapeutic landscape for IBD has evolved substantially; however, a ceiling on therapeutic efficacy remains and surgery is sometimes required (owing to uncontrolled disease activity or complications). Effective IBD management involves comprehensive care, including medication adherence and a collaborative clinician-patient relationship. This Review discusses current therapeutic options for IBD, detailing mechanisms of action, efficacy, safety profiles and guidelines for use of each drug class. We also explore emerging therapies and the role of surgery. Additionally, the importance of a multidisciplinary team and personalized care in managing IBD is emphasized, advocating for patient empowerment and involvement in treatment decisions. By synthesizing current knowledge and emerging trends, this Review aims to equip healthcare professionals with a thorough understanding of therapeutic options for IBD, enhancing informed, evidence-based decisions in clinical practice.
Coeliac disease is an autoimmune disease characterized by small intestinal villus atrophy and inflammation upon exposure to gluten. It has a global prevalence of approximately 1%. Although the gluten-free diet can be an...Coeliac disease is an autoimmune disease characterized by small intestinal villus atrophy and inflammation upon exposure to gluten. It has a global prevalence of approximately 1%. Although the gluten-free diet can be an effective treatment, this diet is burdensome with practical difficulties and frequent inadvertent gluten exposure. Moreover, there are a variety of potential complications and comorbidities of coeliac disease that might be related to malabsorption and/or chronic immune activation. Overall, individuals with coeliac disease have increased mortality compared with the general population, underscoring the severity of this common disease. Comorbidities and complications that have been associated with coeliac disease include poor growth, reproductive complications, kidney and liver diseases, respiratory disease (such as pneumonia) and infections (including sepsis). Furthermore, coeliac disease has been linked to other autoimmune disease and psychiatric disease, as well as certain cancers. Data suggest that mucosal healing on a gluten-free diet might protect against some, but not all, of these complications. In this Review, we present absolute and relative risks of coeliac-associated disorders. We discuss underlying mechanisms, the role of the gluten-free diet and mucosal healing, as well as implications for follow-up and non-dietary treatment of coeliac disease.
Two main stages are differentiated in patients with advanced chronic liver disease (ACLD), one compensated (cACLD) with an excellent prognosis, and the other decompensated (dACLD), defined by the appearance of complicati...Two main stages are differentiated in patients with advanced chronic liver disease (ACLD), one compensated (cACLD) with an excellent prognosis, and the other decompensated (dACLD), defined by the appearance of complications (ascites, variceal bleeding and hepatic encephalopathy) and associated with high mortality. Preventing the progression to dACLD might dramatically improve prognosis and reduce the burden of care associated with ACLD. Portal hypertension is a major driver of the transition from cACLD to dACLD, and a portal pressure of ≥10 mmHg defines clinically significant portal hypertension (CSPH) as the threshold from which decompensating events may occur. In recent years, innovative studies have provided evidence supporting new strategies to prevent decompensation in cACLD. These studies have yielded major advances, including the development of noninvasive tests (NITs) to identify patients with CSPH with reasonable confidence, the demonstration that aetiological therapies can prevent disease progression and even achieve regression of cirrhosis, and the finding that non-selective β-blockers can effectively prevent decompensation in patients with cACLD and CSPH, mainly by reducing the risk of ascites, the most frequent decompensating event. Here, we review the evidence supporting new strategies to manage cACLD to prevent decompensation and the caveats for their implementation, from patient selection using NITs to ancillary therapies.
In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common...In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood. This overlap has been shown to be of great relevance for DGBI. In addition, symptoms considered to be caused by a DGBI could have a detectable organic cause, and in patients with a diagnosed organic gastrointestinal disease, symptoms not clearly explained by the pathology defining this organic disease are common. Thus, the aims of this Rome Foundation Working Team Report were to review the literature on overlapping conditions among patients with paediatric and adult DGBI and, based on the available epidemiological and clinical evidence, make recommendations for the current diagnostic and therapeutic approach, and for future research. Specifically, we focused on other DGBI in the same or different gastrointestinal anatomical region(s), DGBI overlap with organic bowel diseases in remission, and DGBI overlap with non-gastrointestinal, non-structural conditions.
Hepatocellular carcinoma (HCC) represents a global health challenge, and ranks among one of the most prevalent and deadliest cancers worldwide. Therapeutic advances have expanded the treatment armamentarium for patients...Hepatocellular carcinoma (HCC) represents a global health challenge, and ranks among one of the most prevalent and deadliest cancers worldwide. Therapeutic advances have expanded the treatment armamentarium for patients with advanced HCC, but obstacles remain. Precision oncology, which aims to match specific therapies to patients who have tumours with particular features, holds great promise. However, its implementation has been hindered by the existence of numerous 'HCC influencers' that contribute to the high inter-patient heterogeneity. HCC influencers include tumour-related characteristics, such as genetic alterations, immune infiltration, stromal composition and aetiology, and patient-specific factors, such as sex, age, germline variants and the microbiome. This Review delves into the intricate world of HCC, describing the most innovative model systems that can be harnessed to identify precision and/or personalized therapies. We provide examples of how different models have been used to nominate candidate biomarkers, their limitations and strategies to optimize such models. We also highlight the importance of reproducing distinct HCC influencers in a flexible and modular way, with the aim of dissecting their relative contribution to therapy response. Next-generation HCC models will pave the way for faster discovery of precision therapies for patients with advanced HCC.
Szajewska H, Scott KP, de Meij T
… +9 more, Forslund-Startceva SK, Knight R, Koren O, Little P, Johnston BC, Łukasik J, Suez J, Tancredi DJ, Sanders ME
The disruptive effect of antibiotics on the composition and function of the human microbiota is well established. However, the hypothesis that probiotics can help restore the antibiotic-disrupted microbiota has been adva...The disruptive effect of antibiotics on the composition and function of the human microbiota is well established. However, the hypothesis that probiotics can help restore the antibiotic-disrupted microbiota has been advanced, with little consideration of the strength of evidence supporting it. Some clinical data suggest that probiotics can reduce antibiotic-related side effects, including Clostridioides difficile-associated diarrhoea, but there are no data that causally link these clinical effects to microbiota protection or recovery. Substantial challenges hinder attempts to address this hypothesis, including the absence of consensus on the composition of a 'normal' microbiota, non-standardized and evolving microbiome measurement methods, and substantial inter-individual microbiota variation. In this Review, we explore these complexities. First, we review the known benefits and risks of antibiotics, the effect of antibiotics on the human microbiota, the resilience and adaptability of the microbiota, and how microbiota restoration might be defined and measured. Subsequently, we explore the evidence for the efficacy of probiotics in preventing disruption or aiding microbiota recovery post-antibiotic treatment. Finally, we offer insights into the current state of research and suggest directions for future research.
Immunotherapy has changed the treatment landscape for patients with cancer in the past decade. Immune checkpoint inhibitor (ICI)-based therapies have proven effective in a range of malignancies, including liver and gastr...Immunotherapy has changed the treatment landscape for patients with cancer in the past decade. Immune checkpoint inhibitor (ICI)-based therapies have proven effective in a range of malignancies, including liver and gastrointestinal cancers, but they can cause diverse off-target organ toxicities. With the increasingly wider application of these drugs, immune-mediated liver injury from ICIs has become a commonly encountered challenge in clinical hepatology and gastroenterology. In this Review, we discuss the evidence from human and animal studies on the immunological mechanisms of immune-mediated liver injury from ICIs and summarize its clinical features and practical considerations for its management.
Liver cancer is the third leading cause of cancer-related deaths globally, with incident cases expected to rise from 905,700 in 2020 to 1.4 million by 2040. Hepatocellular carcinoma (HCC) accounts for about 80% of all pr...Liver cancer is the third leading cause of cancer-related deaths globally, with incident cases expected to rise from 905,700 in 2020 to 1.4 million by 2040. Hepatocellular carcinoma (HCC) accounts for about 80% of all primary liver cancers. Viral hepatitis and chronic excessive alcohol consumption are major risk factors for HCC, but metabolic dysfunction-associated steatotic liver disease is also becoming a dominant cause. The increasing numbers of cases of HCC and changes in risk factors highlight the urgent need for updated and targeted prevention strategies. Preventive interventions encompass strategies to decrease the burden of chronic liver diseases and their progression to HCC. These strategies include nutritional interventions and medications that have shown promise in preclinical models. Although prevailing approaches focus on treating chronic liver disease, leveraging a wider range of interventions represents a promising area to safeguard at-risk populations. In this Review, we explore existing evidence for preventive strategies by highlighting established and potential paths to reducing HCC risk effectively and safely, especially in individuals with chronic liver diseases. We categorize the preventive strategies by the mechanism of action, including anti-inflammatory, antihyperglycaemic, lipid-lowering, nutrition and dietary, antiviral, and antifibrotic pathways. For each category, we discuss the efficacy and safety information derived from mechanistic, translational, observational and clinical trial data, pinpointing knowledge gaps and directions for future research.
The classification of steatotic liver disease (SLD) has evolved, incorporating all conditions characterized by hepatic lipid accumulation. SLD represents a continuum of disorders that are shaped by the dynamic factors of...The classification of steatotic liver disease (SLD) has evolved, incorporating all conditions characterized by hepatic lipid accumulation. SLD represents a continuum of disorders that are shaped by the dynamic factors of alcohol intake and cardiometabolic risk factors. This updated classification has profound implications for both the management and research of SLD, especially with the new distinct category of patients with both metabolic and alcohol-related liver disease. In this Perspective, we highlight the pivotal role of alcohol within the SLD framework. We introduce the 'SLD burden paradox': a concept illustrating the disparity in which metabolic dysfunction-associated steatotic liver disease is more prevalent, yet individuals with SLD and excessive alcohol intake (such as in metabolic and alcohol-related liver disease and in alcohol-related liver disease) account for greater global liver-related morbidity and mortality. We explore strategies to mitigate the effect of SLD on morbidity and mortality, emphasizing the importance of early detection and reducing stigma associated with alcohol intake. Our discussion extends to methods for assessing and monitoring alcohol intake together with the critical role of managing cardiometabolic risk factors in patients across the SLD spectrum. Conclusively, we advocate for a coordinated care framework that adopts a person-centric approach when managing SLD, aiming to improve outcomes and patient care.