UK national trainee survey of hepatology training, research and the future workforce.

Objective: The increasing prevalence of liver disease in the UK means there is a pressing need to expand the hepatology workforce. This survey aims to evaluate current hepatology training provision, and trainee attitudes towards future careers in hepatology. Method: An electronic survey was distributed to higher specialty gastroenterology and hepatology trainees in the UK between March and May 2022. Results: 138 trainees completed the survey covering all training grades and regions of the UK. 73.7% reported receiving adequate hepatology training currently, with 55.6% intending to become future hepatologists. Trainee preference for future hepatology consultant posts in specialist liver centres were almost threefold higher compared with district general hospitals (60.9% vs 22.6%). All trainees, irrespective of training grade reported high confidence in managing decompensated cirrhosis in both inpatient and outpatient settings. Senior trainees (grade ST6 and higher), without advanced training programme (ATP) experience reported significantly lower confidence in managing viral hepatitis, hepatocellular carcinoma and post-transplant patients compared with equivalent trainees with ATP experience. For junior trainees (IMT3-ST5), remaining in their current deanery was the most important factor when considering future hepatology training application. Conclusions: There is a significant need to deliver widely available training on the management of complex liver disease to improve non-ATP trainee confidence. Innovative job planning strategies are required to encourage trainees to pursue careers outside of specialist liver centres. Expansion of hepatology training networks with wider geographical coverage are needed to address the growing need for more hepatologists around the UK.

The Natural History of Advanced Chronic Liver Disease Defined by Transient Elastography.

BACKGROUND & AIMS: The clinical course of cirrhosis does not follow a predictable trajectory. Transient elastography (TE) is commonly used in clinical practice to diagnose liver fibrosis and increasingly to risk stratify patients. The aim of this study was to assess the natural history of advanced chronic liver disease (ACLD) defined by TE using electronic health record (EHR) data in a multistate framework. METHODS: TE data were collected between 2008 and 2019. Patients with a liver stiffness measurement (LSM) >10 kPa were included. Disease and procedure code information held in EHR was analyzed. Clinical events including decompensation, hepatocellular carcinoma (HCC), and death were identified. Outcomes were described in a multistate model using flexible parametric survival methods including LSM and the albumin bilirubin (ALBI) score. RESULTS: Three thousand and twenty eight patients were included. Median follow up was 3.1 years. LSM and ALBI were associated with the development of varices and decompensation, and ALBI, age, sex, and viral liver disease were associated with the development of HCC from the compensated state. The cumulative incidence of HCC before decompensation was low for patients with alcohol-related liver disease (3.8%) and nonalcoholic fatty liver disease (1.3%) at 5 years after TE. Importantly, death was predicted to occur before decompensation or HCC in most cases. CONCLUSIONS: Liver stiffness, ALBI score, and disease etiology are each associated with outcomes in a large contemporary cohort with ACLD. EHR data can be used to define clinical progression in these patients, facilitating large clinical effectiveness trials and cost-effectiveness analyses.

High rates of ineligibility for participation in trials of new therapies in non-alcoholic steatohepatitis: a systematic review.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease is common and there are a number of treatments in development. Patients with non-alcoholic steatohepatitis (NASH) and significant fibrosis are thought to be the population most in need of treatment. Identification of this group requires liver biopsy. The aim of this study was to identify the proportion of patients screened for phase 2 randomised controlled trials who subsequently entered these studies. METHODS: Large, multicentre, phase 2 randomised controlled trials of pharmacological therapies for NASH were identified by systematic review. The pooled proportion of potential participants who entered the trials was estimated by meta-analysis. The reasons for trial ineligibility were separately extracted and analysed. RESULTS: Thirteen reports of 14 trials were included. Overall, there were 4014 screened individuals included in the quantitative analyses and 53% were subsequently enrolled in a trial. Considering trials in which the entry criteria matched the current paradigm for treatment, that is, the presence of NASH and significant fibrosis, only 35% of screened individuals were eligible for trial entry. More than half of ineligible individuals were excluded on the basis of liver histology most often due to insufficient disease activity with or without insufficient fibrosis. CONCLUSION: The majority of patients considered at risk of NASH and fibrosis sufficient for treatment in randomised controlled trials are ineligible for trial entry. Most often, this is due to ineligible liver histology. These findings have implications for the design of future trials in NASH and for the applicability of treatments after licensing.

Global health systems partnerships: a mixed methods analysis of Mozambique's HPV vaccine delivery network actors.

BACKGROUND: Global health partnerships have expanded exponentially in the last two decades with Gavi, the Vaccine Alliance considered the model's pioneer and leader because of its vaccination programs' implementation mechanism. Gavi, relies on diverse domestic and international partners to carry out the programs in low- and middle-income countries under a partnership engagement framework (PEF). In this study, we utilized mixed methods to examine Mozambique's Gavi driven partnership network which delivered human papillomavirus (HPV) vaccine during the demonstration phase. METHODS: Qualitative tools gauged contextual factors, prerequisites, partner performance and practices while a social network analysis (SNA) survey measured the partnership structure and perceived added value in terms of effectiveness, efficiency and country ownership. Forty key informants who were interviewed included frontline Ministry of Health workers, Ministry of Education staff and supporting partner organization members, of whom 34 participated in the social network analysis survey. RESULTS: Partnership structure SNA connectivity measurement scores of reachability (100%) and average distance (2.5), were high, revealing a network of very well-connected HPV vaccination implementation collaborators. Such high scores reflect a network structure favorable for rapid and widespread diffusion of information, features necessary for engaging and handling multiple implementation scales. High SNA effectiveness and efficiency measures for structural holes (85%) and low redundancy (30%) coupled with high mean perceived effectiveness (97.6%) and efficiency (79.5%) network outcome scores were observed. Additionally, the tie strength average score of 4.1 on a scale of 5 denoted high professional trust. These are all markers of a collaborative partnership environment in which disparate institutions and organizations leveraged each entity's comparative advantage. Lower perceived outcome scores for country ownership (24%) were found, with participants citing the prominent role of several out-of-country partner organizations as a major obstacle. CONCLUSIONS: While there is room for improvement on the country ownership aspects of the partnership, the expanded, diverse and inclusive collaboration of institutions and organizations that implemented the Mozambique HPV vaccine demonstration project was effective and efficient. We recommend that the country adapt a similar model during national scale up of HPV vaccination.

Validation of an algorithm using inpatient electronic health records to determine the presence and severity of cirrhosis in patients with hepatocellular carcinoma in England: an observational study.

OBJECTIVES: Outcomes in hepatocellular carcinoma (HCC) are determined by both cancer characteristics and liver disease severity. This study aims to validate the use of inpatient electronic health records to determine liver disease severity from treatment and procedure codes. DESIGN: Retrospective observational study. SETTING: Two National Health Service (NHS) cancer centres in England. PARTICIPANTS: 339 patients with a new diagnosis of HCC between 2007 and 2016. MAIN OUTCOME: Using inpatient electronic health records, we have developed an optimised algorithm to identify cirrhosis and determine liver disease severity in a population with HCC. The diagnostic accuracy of the algorithm was optimised using clinical records from one NHS Trust and it was externally validated using anonymised data from another centre. RESULTS: The optimised algorithm has a positive predictive value (PPV) of 99% for identifying cirrhosis in the derivation cohort, with a sensitivity of 86% (95% CI 82% to 90%) and a specificity of 98% (95% CI 96% to 100%). The sensitivity for detecting advanced stage cirrhosis is 80% (95% CI 75% to 87%) and specificity is 98% (95% CI 96% to 100%), with a PPV of 89%. CONCLUSIONS: Our optimised algorithm, based on inpatient electronic health records, reliably identifies and stages cirrhosis in patients with HCC. This highlights the potential of routine health data in population studies to stratify patients with HCC according to liver disease severity.

Cyclic vomiting syndrome: a case series and review of the literature.

OBJECTIVE: Cyclic vomiting syndrome (CVS) is under-recognised. Treatment is difficult as the pathophysiology is incompletely understood. We report our experience of treating patients with amitriptyline, and review the literature to summarise symptoms and associated features, epidemiology, potential pathophysiological mechanisms, differential diagnoses and treatment. DESIGN: Consecutive adult patients with CVS were identified during a 5-year period from January 2010 until December 2015. Medical records were reviewed retrospectively, and age and sex of the patient, symptoms, associated features and response to treatment with amitriptyline were recorded. SETTING: A luminal gastroenterology clinic at a teaching hospital. RESULTS: Seventeen patients were identified (mean age 29.8 years, 13 (76.5%) female). Five had a history of cannabis use. Duration of symptoms prior to diagnosis ranged from 5 months to 15 years. Fourteen patients commenced amitriptyline, and in eight (57.1%) symptoms either ceased entirely or improved. Review of the literature suggested the prevalence of CVS was 0.5%. Symptoms are stereotypical, with acute episodes of nausea and vomiting, interspersed by periods when the patient is symptom-free. Proposed pathophysiologies include neuroendocrine dysfunction, mutations in mitochondrial DNA and re-intoxication effects from cannabis stored in fat tissues. Treatment during the acute phase is supportive, with rehydration, sedation and antiemetics. Prophylaxis to prevent future attacks with antihistamines, antimigraine drugs, antiepileptics and tricyclic antidepressants may be beneficial. Complete cessation of cannabis smoking should be advised. CONCLUSIONS: Diagnosis of CVS is often delayed in adults. Once identified, patients respond well to amitriptyline.

Evaluating Global Health Partnerships: A Case Study of a Gavi HPV Vaccine Application Process in Uganda.

BACKGROUND: Global health partnerships have grown rapidly in number and scope, yet there has been less emphasis on their evaluation. Gavi, the Vaccine Alliance, is one such public-private partnership; in Gavi-eligible countries partnerships are dynamic networks of immunization actors who work together to support all stages and aspects of Gavi support. This paper describes a conceptual framework - the partnership framework - and analytic approach for evaluating the perceptions of partnerships' added value as well as the results from an application to one case in Uganda. METHODS: We used a mixed-methods case study design embedded in the Gavi Full Country Evaluations (FCE) to test the partnership framework on Uganda's human papillomavirus (HPV) vaccine application partnership. Data from document review, interviews, and social network surveys enabled the testing of the relationships between partnership framework domains (context, structure, practices, performance, and outcomes). Topic guides were based on the framework domains and network surveys identified working together relationships, professional trust, and perceptions of the effectiveness, efficiency, and legitimacy of the partnership's role in this process. RESULTS: Data from seven in-depth interviews, 11 network surveys and document review were analyzed according to the partnership framework, confirming relationships between the framework domains. Trust was an important contributor to the perceived effectiveness of the process. The network was structured around the EPI program, who was considered the leader of this process. While the structure and composition of the network was largely viewed as supporting an effective and legitimate process, the absence of the Ministry of Education (MoE) may have had downstream consequences if this study's results had not been shared with the Ministry of Health (MoH) and acted upon. The partnership was not perceived to have increased the efficiency of the process, perhaps as a result of unclear or absent guidelines around roles and responsibilities. CONCLUSION: The health and functioning of global health partnerships can be evaluated using the framework and approach presented here. Network theory and methods added value to the conceptual and analytic processes and we recommend applying this approach to other global health partnerships to ensure that they are meeting the complex challenges they were designed to address.