Developing and validating clinical prediction models in hepatology - An overview for clinicians.

Prediction models are everywhere in clinical medicine. We use them to assign a diagnosis or a prognosis, and there have been continuous efforts to develop better prediction models. It is important to understand the fundamentals of prediction modelling, thus, we herein describe nine steps to develop and validate a clinical prediction model with the intention of implementing it in clinical practice: Determine if there is a need for a new prediction model; define the purpose and intended use of the model; assess the quality and quantity of the data you wish to develop the model on; develop the model using sound statistical methods; generate risk predictions on the probability scale (0-100%); evaluate the performance of the model in terms of discrimination, calibration, and clinical utility; validate the model using bootstrapping to correct for the apparent optimism in performance; validate the model on external datasets to assess the generalisability and transportability of the model; and finally publish the model so that it can be implemented or validated by others.

EASL Clinical Practice Guidelines on genetic cholestatic liver diseases.

Genetic cholestatic liver diseases are caused by (often rare) mutations in a multitude of different genes. While these diseases differ in pathobiology, clinical presentation and prognosis, they do have several commonalities due to their cholestatic nature. These Clinical Practice Guidelines (CPGs) offer a general approach to genetic testing and management of cholestatic pruritus, while exploring diagnostic and treatment approaches for a subset of genetic cholestatic liver diseases in depth. An expert panel appointed by the European Association for the Study of the Liver has created recommendations regarding diagnosis and treatment, based on the best evidence currently available in the fields of paediatric and adult hepatology, as well as genetics. The management of these diseases generally takes place in a tertiary referral centre, in order to provide up-to-date approaches and expertise. These CPGs are intended to support hepatologists (for paediatric and adult patients), residents and other healthcare professionals involved in the management of these patients with concrete recommendations based on currently available evidence or, if not available, on expert opinion.

Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS: A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS: A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION: Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.

Ineffective esophageal motility: Characterization and outcomes across pediatric neurogastroenterology and motility centers in the United States.

OBJECTIVES: Ineffective esophageal motility (IEM) on high-resolution manometry (HRM) is not consistently associated with specific clinical syndromes or outcomes. We evaluated the prevalence, clinical features, management, and outcomes of pediatric IEM patients across the United States. METHODS: Clinical and manometric characteristics of children undergoing esophageal HRM during 2021-2022 were collected from 12 pediatric motility centers. Clinical presentation, test results, management strategies, and outcomes were compared between children with IEM and normal HRM. RESULTS: Of 236 children (median age 15 years, 63.6% female, 79.2% Caucasian), 62 (23.6%) patients had IEM, and 174 (73.7%) patients had normal HRM, with similar demographics, medical history, clinical presentation, and median symptom duration. Reflux monitoring was performed more often for IEM patients (25.8% vs. 8.6%, p = 0.002), but other adjunctive testing was similar. Among 101 patients with follow-up, symptomatic cohorts declined in both groups in relation to the initial presentation (p > 0.107 for each comparison) with management targeting symptoms, particularly acid suppression. Though prokinetics were used more often and behavioral therapy less often in IEM (p ≤ 0.015 for each comparison), symptom outcomes were similar between IEM and normal HRM. Despite a higher proportion with residual dysphagia on follow-up in IEM (64.0% vs. 39.1%, p = 0.043), an alternate mechanism for dysphagia was identified more often in IEM (68.8%) compared to normal HRM (27.8%, p = 0.017). CONCLUSIONS: IEM is a descriptive manometric pattern rather than a clinical diagnosis requiring specific intervention in children. Management based on clinical presentation provides consistent symptom outcomes.

Adeno-associated viral vector gene therapy: Challenges for the paediatric hepatologist.

Hepatoxicity associated with recombinant adeno-associated virus gene therapy is being increasingly encountered by hepatologists in tertiary and quaternary referral units due to the recent increase of these therapies for neuromuscular and haematological disorders. The challenges in managing the condition stem from a lack of good-quality evidence on the appropriate protocols for immunosuppressants due to lack of representative animal models. There is a need for protocols for diagnosing and treating hepatotoxicity and this possible with further research to understand the problem and its management. The review also highlights the importance of a multidisciplinary team in managing hepatotoxicity and recommends further research to better identify at-risk individuals, define the extent of the problem and assess the long-term effects of liver injury and immunosuppressants.

Standardizing visual display of gastrointestinal pathology results for improved clinical interpretation.

OBJECTIVES: Pathology is an essential component of disease diagnosis and management in pediatric gastroenterology. Pathology reports have not been standardized in some areas of pediatric gastrointestinal pathology and pathology reporting varies. Development of electronic medical record (EMR) pathology synoptic report templates (PSRT) enables pathology data collection in a specific format and can help standardize pathology reporting. We developed, implemented, and evaluated EMR PSRTs for eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD). METHODS: PSRTs were developed by a multidisciplinary team of pediatric experts of allergy, gastroenterology, and pathology for both EoE and IBD based on available literature and validated scales. Likert surveys (range 1 low acceptance to 5 high acceptance) based on the Technology Acceptance Model assessed user acceptance of the developed PSRTs. The use of PSRTs was monitored via control charts. RESULTS: Overall, evaluation questionnaires achieved >80% response rates. Clinicians and pathologists reported moderate-to-high levels of Perceived Usefulness (median (interquartile range) for EoE PSRT: clinicians 4.0 (4.0, 5.0) and pathologists 3.5 (3.5, 4.0); and IBD PSRT: clinicians 4.0 (3.0, 4.0) and pathologists 4.0 (4.0, 5.0)) and Perceived Ease of Use (EoE PSRT: clinicians 4.5 (4.0, 5.0) and pathologists 4.0 (4.0, 4.0); and IBD PSRT: clinicians 4.0 (4.0, 5.0) and pathologists 4.0 (4.0, 5.0)) of the developed PSRTs. Control charts demonstrated 100% utilization by 2-5 months from launch. CONCLUSIONS: We demonstrate successful implementation of synoptic reporting for both pediatric EoE and IBD pathology. EMR synoptic reporting provides standardization of pathology reporting and improved methods of pathology data presentation, which could potentially optimize provider efficiency, clinician interpretation of pathology results and disease trajectory, patient care, and clinician satisfaction.

Generative AI in Pediatric Gastroenterology.

PURPOSE OF REVIEW: The integration of digital technology into medical practice is often thrust upon clinicians, with standards and routines developed long after initiation. Clinicians should endeavor towards a basic understanding even of emerging technologies so that they can direct its use. The intent of this review is to describe the current state of rapidly evolving generative artificial intelligence (GAI), and to explore both how pediatric gastroenterology practice may benefit as well as challenges that will be faced. RECENT FINDINGS: Although little research demonstrating the acceptance, practice, and outcomes associated with GAI in pediatric gastroenterology is published, there are relevant data adjacent to the specialty and overwhelming potential as professed in the media. Best practice guidelines are widely developed in academic publishing and resources to initiate and improve practical user skills are prevalent. Initial published evidence supports broad acceptance of the technology as part of medical practice by clinicians and patients, describes methods with which higher quality GAI can be developed, and identifies the potential for bias and disparities resulting from its use. GAI is broadly available as a digital tool for incorporation into medical practice and holds promise for improved quality and efficiency of care, but investigation into how GAI can best be used remains at an early stage despite rapid evolution of the technology.

Yoga in Pediatric Gastroenterology.

PURPOSE OF REVIEW: Pediatric use of yoga as an integrative medicine modality has increased in prevalence over the last several decades. In this article, we review the available evidence for yoga in pediatric gastrointestinal disorders. RECENT FINDINGS: Evidence supports that in many pediatric disorders of gut brain interaction (DGBI), including irritable bowel syndrome, functional abdominal pain and functional dyspepsia, yoga decreases pain intensity and frequency and increases school attendance. Yoga has been shown to improve health-related quality of life and improve stress management as an effective adjunct to standard medical therapy in pediatric inflammatory bowel disease (IBD). Further studies are needed regarding optimal frequency, duration of practice and evaluation of the impact on IBD disease activity measures. Yoga may benefit pediatric gastroenterology patients with DGBIs and IBD through improving quality of life and reducing pain. Future yoga studies could investigate biomarkers and continued research will help integrate this modality into routine pediatric gastroenterology care.

Implementation of a Web-Based Outpatient Asynchronous Consultation Service: Mixed Methods Study.

BACKGROUND: Asynchronous outpatient patient-to-provider communication is expanding in UK health care, requiring evaluation. During the pandemic, Aberdeen Royal Infirmary in Scotland expanded its outpatient asynchronous consultation service from dermatology (deployed in May 2020) to gastroenterology and pain management clinics. OBJECTIVE: We conducted a mixed methods study using staff, patient, and public perspectives and National Health Service (NHS) numerical data to obtain a rounded picture of innovation as it happened. METHODS: Focus groups (3 web-based and 1 face-to-face; n=22) assessed public readiness for this service, and 14 interviews with staff focused on service design and delivery. The service's effects were examined using NHS Grampian service use data, a patient satisfaction survey (n=66), and 6 follow-up patient interviews. Survey responses were descriptively analyzed. Demographics, acceptability, nonattendance rates, and appointment outcomes of users were compared across levels of area deprivation in which they live and medical specialties. Interviews and focus groups underwent theory-informed thematic analysis. RESULTS: Staff anticipated a simple technical system transfer from dermatology to other receptive medical specialties, but despite a favorable setting and organizational assistance, it was complicated. Key implementation difficulties included pandemic-induced technical integration delays, misalignment with existing administrative processes, and discontinuity in project management. The pain management clinic began asynchronous consultations (digital appointments) in December 2021, followed by the gastroenterology clinic in February 2022. Staff quickly learned how to explain and use this service. It was thought to function better for pain management as it fitted preexisting practices. From May to September 2022, the dermatology (adult and pediatric), gastroenterology, and pain management clinics offered 1709 appointments to a range of patients (n=1417). Digital appointments reduced travel by an estimated 44,712 miles (~71,956.81 km) compared to the face-to-face mode. The deprivation profile of people who chose to use this service closely mirrored that of NHS Grampian's population overall. There was no evidence that deprivation impacted whether digital appointment users subsequently received treatment. Only 18% (12/66) of survey respondents were unhappy or very unhappy with being offered a digital appointment. The benefits mentioned included better access, convenience, decreased travel and waiting time, information sharing, and clinical flexibility. Overall, patients, the public, and staff recognized its potential as an NHS service but highlighted informed choice and flexibility. Better communication-including the use of the term assessment instead of appointment-may increase patient acceptance. CONCLUSIONS: Asynchronous pain management and gastroenterology consultations are viable and acceptable. Implementing this service is easiest when existing administrative processes face minimal disruption, although continuous support is needed. This study can inform practical strategies for supporting staff in adopting asynchronous consultations (eg, preparing for nonlinearity and addressing task issues). Patients need clear explanations and access to technical support, along with varied consultation options, to ensure digital inclusion.

The digital transformation of hepatology: The patient is logged in.

The rise in innovative digital health technologies has led a paradigm shift in health care toward personalized, patient-centric medicine that is reaching beyond traditional brick-and-mortar facilities into patients' homes and everyday lives. Digital solutions can monitor and detect early changes in physiological data, predict disease progression and health-related outcomes based on individual risk factors, and manage disease intervention with a range of accessible telemedicine and mobile health options. In this review, we discuss the unique transformation underway in the care of patients with liver disease, specifically examining the digital transformation of diagnostics, prediction and clinical decision-making, and management. Additionally, we discuss the general considerations needed to confirm validity and oversight of new technologies, usability and acceptability of digital solutions, and equity and inclusivity of vulnerable populations.

Health Care Transition for Adolescents and Young Adults With Pediatric-Onset Liver Disease and Transplantation: A Position Paper by the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

Advances in medical therapies and liver transplantation have resulted in a greater number of pediatric patients reaching young adulthood. However, there is an increased risk for medical complications and morbidity surrounding transfer from pediatric to adult hepatology and transplant services. Health care transition (HCT) is the process of moving from a child/family-centered model of care to an adult or patient-centered model of health care. Successful HCT requires a partnership between pediatric and adult providers across all disciplines resulting in a transition process that does not end at the time of transfer but continues throughout early adulthood. Joint consensus guidelines in collaboration with the American Society of Transplantation are presented to facilitate the adoption of a structured, multidisciplinary approach to transition planning utilizing The Six Core Elements of Health Care Transition TM for use by both pediatric and adult specialists. This paper provides guidance and seeks support for the implementation of an HCT program which spans across both pediatric and adult hepatology and transplant centers.

[Gastroenterology and hepatology: what's new in 2022]. / Gastroentérologie et hépatologie : ce qui a changé en 2022.

The field of gastroenterology and hepatology is evolving constantly. In 2022, numerous landmark studies have been published in all its subspecialities including hepatology, functional diseases, interventional endoscopy, and inflammatory bowel disease. Among the most significant advances are the antiviral treatment for hepatitis D, the new Chicago classification version 4 for esophageal motility disorders, the first biological treatment for eosinophilic esophagitis, a randomized controlled trial about the efficacy of screening colonoscopy, novel endoscopic techniques such as G-POEM or endoscopic sleeve gastrectomy, and emerging IBD therapies such as ozanimod, upadacitinib or anti-IL23 antibodies.

La gastroentérologie et l'hépatologie sont des disciplines variées et en pleine évolution. Durant l'année 2022, plusieurs études marquantes ont été publiées dans les domaines de l'hépatologie, des maladies fonctionnelles, de l'endoscopie et des maladies inflammatoires chroniques de l'intestin (MICI). Les avancées les plus importantes sont le traitement antiviral contre l'hépatite D, la nouvelle classification de Chicago version 4 pour les troubles moteurs œsophagiens, le traitement biologique de l'œsophagite à éosinophiles, l'efficacité de la coloscopie de dépistage, de nouvelles techniques endoscopiques comme le G-POEM ou la gastrectomie endoscopique et des nouveaux médicaments pour les MICI comme l'ozanimod, l'upadacitinib ou les anticorps anti-IL-23.

AGA Technical Review on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn's Disease.

The incidence and prevalence of Crohn's disease (CD) is rising globally. Patients with moderate to severe CD are at high risk for needing surgery and hospitalization and for developing disease-related complications, corticosteroid dependence, and serious infections. Optimal management of outpatients with moderate to severe luminal and/or fistulizing (including perianal) CD often requires the use of immunomodulator (thiopurines, methotrexate) and/or biologic therapies, including tumor necrosis factor-α antagonists, vedolizumab, or ustekinumab, either as monotherapy or in combination (with immunomodulators) to mitigate these risks. Decisions about optimal drug therapy in moderate to severe CD are complex, with limited guidance on comparative efficacy and safety of different treatments, leading to considerable practice variability. Since the last iteration of these guidelines published in 2013, significant advances have been made in the field, including the regulatory approval of 2 new biologic agents, vedolizumab and ustekinumab. Therefore, the American Gastroenterological Association prioritized updating clinical guidelines on this topic. To inform the clinical guidelines, this technical review was completed in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. The review addressed the following focused questions (in adult outpatients with moderate to severe luminal CD): overall and comparative efficacy of different medications for induction and maintenance of remission in patients with or without prior exposure to tumor necrosis factor-α antagonists, comparative efficacy and safety of biologic monotherapy vs combination therapy with immunomodulators, comparative efficacy of a top-down (upfront use of biologics and/or immunomodulator therapy) vs step-up treatment strategy (acceleration to biologic and/or immunomodulator therapy only after failure of mesalamine), and the role of corticosteroids and mesalamine for induction and/or maintenance of remission. Finally, in adult outpatients with moderate to severe fistulizing CD, this review addressed the efficacy of pharmacologic interventions for achieving fistula and the role of adjunctive antibiotics without clear evidence of active infection.

AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review.

BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for oncology, leading to durable remissions in a subset of patients, but also a broad range of potentially life-threatening inflammatory toxicities, many of which involve the gastrointestinal (GI) tract and liver. The purpose of this expert review was to update gastroenterologists on the gastrointestinal and hepatic toxicities of ICIs and provide best practice advice on their diagnosis and management. METHODS: The evidence reviewed in this work combines the expert clinical opinion of the authors with a comprehensive search of several English-language databases and a manual review of relevant publications.

AGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease, with global public health impact affecting more than 25% of the global population. NAFLD is associated with significant morbidity and mortality from cirrhosis, hepatocellular carcinoma, solid organ malignancies, diabetes mellitus, cardiovascular disease, and obstructive sleep apnea, resulting in significant health care resource use and decreased health-related quality of life. NAFLD cirrhosis is a leading indication for liver transplantation in the United States. Lifestyle modification to achieve weight loss remains a first-line intervention in patients with NAFLD. We summarize evidence-based interventions for lifestyle modification in the treatment of NAFLD and provided best practice advice statements to address key issues in clinical management.

AGA Clinical Practice Update on Medical Management of Colonic Diverticulitis: Expert Review.

Colonic diverticulitis is a painful gastrointestinal disease that recurs unpredictably and can lead to chronic gastrointestinal symptoms. Gastroenterologists commonly care for patients with this disease. The purpose of this Clinical Practice Update is to provide practical and evidence-based advice for management of diverticulitis. We reviewed systematic reviews, meta-analyses, randomized controlled trials, and observational studies to develop 14 best practices. In brief, computed tomography is often necessary to make a diagnosis. Rarely, a colon malignancy is misdiagnosed as diverticulitis. Whether patients should have a colonoscopy after an episode of diverticulitis depends on the patient's history, most recent colonoscopy, and disease severity and course. In patients with a history of diverticulitis and chronic symptoms, alternative diagnoses should be excluded with both imaging and lower endoscopy. Antibiotic treatment can be used selectively rather than routinely in immunocompetent patients with mild acute uncomplicated diverticulitis. Antibiotic treatment is strongly advised in immunocompromised patients. To reduce the risk of recurrence, patients should consume a high-quality diet, have a normal body mass index, be physically active, not smoke, and avoid nonsteroidal anti-inflammatory drug use except aspirin prescribed for secondary prevention of cardiovascular disease. At the same time, patients should understand that genetic factors also contribute to diverticulitis risk. Patients should be educated that the risk of complicated diverticulitis is highest with the first presentation. An elective segmental resection should not be advised based on the number of episodes. Instead, a discussion of elective segmental resection should be personalized to consider severity of disease, patient preferences and values, as well as risks and benefits.

Current Applications of Telemedicine in Gastroenterology.

Telemedicine generally refers to the use of technology to communicate with patients and provide health care from a distance. Advances in technology, specifically computers, cellphones, and other mobile devices, have facilitated healthcare providers' growing ability to virtually monitor and mentor patients. There has been a progressive expansion in the use of telemedicine in the field of gastroenterology (GI), which has been accelerated by the COVID-19 pandemic. In this review, we discuss telemedicine-its history, various forms, and limitations-and its current applications in GI. Specifically, we focus on telemedicine in GI practice in general and specific applications, including the management of inflammatory bowel disease, celiac disease, and colorectal cancer surveillance and its use as an aid in endoscopic procedures.

Hepatobiliary Organoids and Their Applications for Studies of Liver Health and Disease: Are We There Yet?

Organoid culture systems have emerged as a frontier technology in liver and biliary research. These three-dimensional (3D) cell cultures derived from pluripotent and adult hepatobiliary cells model organ structure and function. Building on gastrointestinal organoid establishment, hepatobiliary organoid cultures were generated from mouse leucine-rich repeat-containing G-protein-coupled receptor 5-positive liver progenitor cells. Subsequently, 3D hepatobiliary organoid cultures were developed from hepatocytes and cholangiocytes to model human and animal hepatobiliary health and disease. Hepatocyte organoids have been used to study Alagille syndrome, fatty liver disease, Wilson disease, hepatitis B viral infection, and cystic fibrosis. Cholangiocyte organoids have been established to study normal cholangiocyte biology and primary sclerosing cholangitis and to test organoid potential to form bile ducts and gallbladder tissue in vitro. Hepatobiliary cancer organoids, termed tumoroids, have been established from frozen and fresh human tissues and used as a drug-testing platform and for biobanking of cancer samples. CRISPR-based gene modifications and organoid exposure to infectious agents have permitted the generation of organoid models of carcinogenesis. This review summarizes currently available adult cell-derived hepatobiliary organoid models and their applications. Challenges faced by this young technology will be discussed, including the cellular immaturity of organoid-derived hepatocytes, co-culture development to better model complex tissue structure, the imperfection of extracellular matrices, and the absence of standardized protocols and model validation.

Application of Artificial Intelligence for the Diagnosis and Treatment of Liver Diseases.

Modern medical care produces large volumes of multimodal patient data, which many clinicians struggle to process and synthesize into actionable knowledge. In recent years, artificial intelligence (AI) has emerged as an effective tool in this regard. The field of hepatology is no exception, with a growing number of studies published that apply AI techniques to the diagnosis and treatment of liver diseases. These have included machine-learning algorithms (such as regression models, Bayesian networks, and support vector machines) to predict disease progression, the presence of complications, and mortality; deep-learning algorithms to enable rapid, automated interpretation of radiologic and pathologic images; and natural-language processing to extract clinically meaningful concepts from vast quantities of unstructured data in electronic health records. This review article will provide a comprehensive overview of hepatology-focused AI research, discuss some of the barriers to clinical implementation and adoption, and suggest future directions for the field.

A Guide to Establishing a Pediatric Neurogastroenterology and Motility Program.

ABSTRACT: The purpose of this document is to provide guidance for establishing a pediatric neurogastroenterology and motility (PNGM) program, including considerations for personnel, equipment, and physical space requirements, and business planning, from members of the neurogastroenterology and motility (NGM) Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) who have developed PNGM programs at various institutions. A business plan defining the needs for required personnel, dedicated physical space, procedures, clinical care, and equipment storage is a prerequisite. Thoughtful logistical planning should address provider schedules, clinical visits, procedure coordination, and prior authorization processes. A business-plan outlining equipment purchase with projected costs, revenue generation, and goals for future growth is desirable for obtaining institutional support, which is imperative to building a successful PNGM program.