Broadening and strengthening the health providers caring for patients with chronic hepatitis C may improve continuity of care.

BACKGROUND: Direct-acting antiviral (DAA) therapies for hepatitis C virus infection (HCV) lead to excellent rates of sustained virological response (SVR). However, loss to follow-up (LTFU) for SVR testing remains a challenge. We examine factors associated with LTFU in a real-world setting. METHODS: Adults who received DAA therapy for HCV in one of 26 centers across Australia during 2016-2021 were followed up for 2 years. Data sources included the patient medical records and the national Pharmaceutical and Medicare Benefits Schemes. Linkage to Medicare provided utilization data of other health-care providers and re-treatment with DAAs. LTFU was defined as no clinic attendance for SVR testing by at least 52 weeks after DAA treatment commencement. Multivariable logistic regression assessed factors associated with LTFU. RESULTS: In 3619 patients included in the study (mean age 52.0 years; SD = 10.5), 33.6% had cirrhosis (69.4% Child-Pugh class B/C), and 19.3% had HCV treatment prior to the DAA era. Five hundred and fifteen patients (14.2%) were LTFU. HCV treatment initiation in 2017 or later (adj-OR = 2.82, 95% confidence interval [CI] 2.25-3.54), younger age (adj-OR = 2.63, 95% CI 1.80-3.84), Indigenous identification (adj-OR = 1.99, 95% CI 1.23-3.21), current injection drug use or opioid replacement therapy (adj-OR = 1.66, 95% CI 1.25-2.20), depression treatment (adj-OR = 1.49, 95% CI 1.17-1.90), and male gender (adj-OR = 1.31, 95% CI 1.04-1.66) were associated with LTFU. CONCLUSIONS: These findings stress the importance of strengthening the network of providers caring for patients with HCV. In particular, services targeting vulnerable groups of patients such as First Nations Peoples, youth health, and those with addiction and mental health disorders should be equipped to treat HCV.

Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study.

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients.

The Toronto Upper Gastrointestinal Cleaning Score: a prospective validation study.

BACKGROUND : Assessment of mucosal visualization during esophagogastroduodenoscopy (EGD) can be improved with a standardized scoring system. To address this need, we created the Toronto Upper Gastrointestinal Cleaning Score (TUGCS). METHODS : We developed the TUGCS using Delphi methodology, whereby an international group of endoscopy experts iteratively rated their agreement with proposed TUGCS items and anchors on a 5-point Likert scale. After each Delphi round, we analyzed responses and refined the TUGCS using an 80 % agreement threshold for consensus. We used the intraclass correlation coefficient (ICC) to assess inter-rater and test-retest reliability. We assessed internal consistency with Cronbach's alpha and item-total and inter-item correlations with Pearson's correlation coefficient. We compared TUGCS ratings with an independent endoscopist's global rating of mucosal visualization using Spearman's ρ. RESULTS : We achieved consensus with 14 invited participants after three Delphi rounds. Inter-rater reliability was high at 0.79 (95 %CI 0.64-0.88). Test-retest reliability was excellent at 0.83 (95 %CI 0.77-0.87). Cronbach's α was 0.81, item-total correlation range was 0.52-0.70, and inter-item correlation range was 0.38-0.74. There was a positive correlation between TUGCS ratings and a global rating of visualization (r = 0.41, P = 0.002). TUGCS ratings for EGDs with global ratings of excellent were significantly higher than those for EGDs with global ratings of fair (P = 0.01). CONCLUSION : The TUGCS had strong evidence of validity in the clinical setting. The international group of assessors, broad variety of EGD indications, and minimal assessor training improves the potential for dissemination.

Determination of hepatic extraction fraction with gadoxetate low-temporal resolution DCE-MRI-based deconvolution analysis: validation with ALBI score and Child-Pugh class.

INTRODUCTION: In this study, we aimed to investigate the feasibility of gadoxetate low-temporal resolution (LTR) DCE-MRI for voxel-based hepatic extraction fraction (HEF) quantification for liver sparing radiotherapy using a deconvolution analysis (DA) method. METHODS: The accuracy and consistency of the deconvolution implementation in estimating liver function was first assessed using simulation data. Then, the method was applied to DCE-MRI data collected retrospectively from 64 patients (25 normal liver function and 39 cirrhotic patients) to generate HEF maps. The normal liver function patient data were used to measure the variability of liver function quantification. Next, a correlation between HEF and ALBI score (a new model for assessing the severity of liver dysfunction) was assessed using Pearson's correlation. Differences in HEF between Child-Pugh score classifications were assessed for significance using the Kruskal-Wallis test for all patient groups and Mann-Whitney U-test for inter-groups. A statistical significance was considered at a P-value <0.05 in all tests. RESULTS: The results showed that the implemented method accurately reproduced simulated liver function; root-mean-square error between estimated and simulated liver response functions was 0.003, and the coefficient-of-variance of HEF was <20%. HEF correlation with ALBI score was r = -0.517, P < 0.0001, and HEF was significantly decreased in the cirrhotic patients compared to normal patients (P < 0.0001). Also, HEF in Child-Pugh B/C was significantly lower than in Child-Pugh A (P = 0.024). CONCLUSION: The study demonstrated the feasibility of gadoxetate LTR-DCE MRI for voxel-based liver function quantification using DA. HEF could distinguish between different grades of liver function impairment and could potentially be used for functional guidance in radiotherapy.

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

BACKGROUND: First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection. METHODS: Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016-2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU. RESULTS: Compared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p < 0.001), morel likely to reside in most disadvantaged (p = 0.002) and in regional/remote areas (p < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%; p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p = 0.51) and 'good' adherence (90.0% vs. 86.9%, respectively; p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87-0.99) and treatment initiation in 2018-2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23-21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50-0.99). CONCLUSIONS: Our data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.

The present and future of gastroenterology and hepatology: an international SWOT analysis (the GASTROSWOT project).

GASTROSWOT is a strategic analysis of the current and projected states of the different subspecialties in gastroenterology that aims to provide guidance for research, clinical, and financial planning in gastroenterology. We executed a consensus-based international strengths, weaknesses, opportunities, and threats (SWOT) analysis. Four general coordinators, six field coordinators, and 12 experts participated in the study. SWOTs were provided for the following fields: neurogastroenterology, functional gastrointestinal disorders, and upper gastrointestinal diseases; inflammatory bowel disease; pancreatology and biliary diseases; endoscopy; gastrointestinal oncology; and hepatology. The GASTROSWOT analysis highlights the following in the current state of the field of gastroenterology: the incidence and complexity of several gastrointestinal diseases, including malignancies, are increasing; the COVID-19 pandemic has affected patient care on several levels; and with the advent of technical innovations in gastroenterology, a well trained workforce and strategic planning are required to optimise health-care utilisation. The analysis calls attention to the following in the future of gastroenterology: artificial intelligence and the use of big data will speed up discovery and smarter health-care provision in the field; the growth and diversification of gastroenterological specialties will improve specialised care for patients, but could promote fragmentation of care and health system inefficiencies; and furthermore, thoughtful planning is needed to reach an effective balance between the need for subspecialists and the value of general gastroenterology services.

Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia.

Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identifiable pathology. Psychological stress is a key factor associated with the onset of FD and locally acting hypothalamic-pituitary-adrenal (HPA) axis hormones have been implicated in GI motility and barrier dysfunction. Recent pre-clinical work has identified mechanistic pathways linking corticotropin-releasing hormone (CRH) with the innate epithelial immune protein NLRP6, an inflammasome that has been shown to regulate GI mucus secretion. We recruited twelve FD patients and twelve healthy individuals to examine whether dysregulation of hypothalamic-pituitary adrenal (HPA) axis hormones and altered NLRP6 pathways were evident in the duodenal mucosa. Protein expression was assessed by immunoblot and immunohistochemistry in D2 duodenal biopsies. Plasma HPA axis hormones were assayed by ELISA and enteroid and colorectal cancer cell line cultures were used to verify function. FD patients exhibited reduced duodenal CRH-receptor 2, compared to non-GI disease controls, indicating a dysregulation of duodenal HPA signalling. The loss of CRH-receptor 2 correlated with reduced NLRP6 expression and autophagy function, processes critical for maintaining goblet cell homeostasis. In accordance, duodenal goblet cell numbers and mucin exocytosis was reduced in FD patients compared to controls. In vitro studies demonstrated that CRH could reduce NLRP6 in duodenal spheroids and promote mucus secretion in the HT29-MTX-E12 cell line. In conclusion, FD patients exhibit defects in the NLRP6-autophagy axis with decreased goblet cell function that may drive symptoms of disease. These features correlated with loss of CRH receptor 2 and may be driven by dysregulation of HPA signalling in the duodenum of FD patients.

COVID-19 and Canadian Gastroenterology Trainees.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted endoscopy services and education worldwide. This study aimed to characterize the impact of COVID-19 on gastroenterology trainees in Canada. METHODS: An analysis of Canadian respondents from the international EndoTrain survey, open from April 11 to May 2 2020 and distributed by program directors, trainees, and national and international gastroenterology societies' representatives, was completed. The survey included questions on monthly endoscopy volume, personal protective equipment availability, trainee well-being and educational resources. The primary outcome was change in procedural volume during the COVID-19 pandemic. Secondary outcomes included trainee's professional and personal concerns, anxiety and burnout. RESULTS: Thirty-four Canadian trainees completed the survey. Per month, participants completed a median of 30 esophagogastroduodenoscopies (interquartile range 16 to 50) prior to the pandemic compared to 2 (0 to 10) during the pandemic, 20 (8 to 30) compared to 2 (0 to 5) colonoscopies and 3 (1 to 10) compared to 0 (0 to 3) upper gastrointestinal bleeding procedures. There was a significant decrease in procedural volumes between the pre-COVID-19 and COVID-19 time periods for all procedures (P < 0.001). Thirty (88%) trainees were concerned about personal COVID-19 exposure, 32 (94%) were concerned about achieving and/or maintaining clinical competence and 24 (71%) were concerned about prolongation of training time due to the pandemic. Twenty-six (79%) respondents experienced some degree of anxiety, and 10 (31%) experienced some degree of burnout. CONCLUSION: The COVID-19 pandemic has substantially impacted gastroenterology trainees in Canada. As the pandemic eases, it important for gastrointestinal programs to adapt to maximize resident learning, maintain effective clinical care and ensure development of endoscopic competence.

Hepatitis B-related hepatocellular carcinoma: surveillance strategy directed by immune-epidemiology.

Hepatitis B infection (HBV) is one of the most common causes of hepatocellular carcinoma (HCC) worldwide. The age of occurrence, prognosis and incidence vary dramatically depending on the region of the world. This geographic variation is largely dependent on the contrasting incidence of HBV, age of transmission of the virus, the timing of integration into the human genome, and different HBV genotypes, as well as environmental factors. It results in a wide difference in viral interaction with the immune system, genomic modulation and the consequent development of HCC in an individual. In this review, we describe many factors implicated in HCC development, provide insight regarding at-risk populations and explain societal recommendations for HCC surveillance in persons living with HBV in different continents of the world.

Delayed Bleeding After Endoscopic Resection of Colorectal Polyps: Identifying High-Risk Patients.

Delayed post-polypectomy bleeding (DPPB) is a potentially severe complication of therapeutic colonoscopy which can result in hospital readmission and re-intervention. Over the last decade, rates of DPPB reported in the literature have fallen from over 2% to 0.3-1.2%, largely due to improvements in resection technique, a shift towards cold snare polypectomy, better training, adherence to guidelines on periprocedural antithrombotic management, and the use of antithrombotics with more favourable bleeding profiles. However, as the complexity of polypectomy undertaken worldwide increases, so does the importance of identifying patients at increased risk of DPPB. Risk factors can be categorised according to patient, polyp and personnel related factors, and their integration together to provide an individualised risk score is an evolving field. Strategies to reduce DPPB include safe practices relevant to all patients undergoing colonoscopy, as well as specific considerations for patients identified to be high risk. This narrative review sets out an evidence-based summary of factors that contribute to the risk of DPPB before discussing pragmatic interventions to mitigate their risk and improve patient safety.

Roadmap to resuming care for liver diseases after coronavirus disease-2019.

The global pandemic of coronavirus disease-2019 (COVID-19) has led to significant disruptions in healthcare delivery. Patients with chronic liver diseases require a high level of care and are therefore particularly vulnerable to disruptions in medical services during COVID-19. Recent data have also identified chronic liver disease as an independent risk factor for COVID-19 related hospital mortality. In response to the pandemic, national and international societies have recommended interim changes to the management of patients with liver diseases. These modifications included the implementation of telehealth, postponement or cancelation of elective procedures, and other non-urgent patient care-related activities. There is concern that reduced access to diagnosis and treatment can also lead to increased morbidity in patients with liver diseases and we may witness a delayed surge of hospitalizations related to decompensated liver disease after the COVID-19 pandemic has receded. Therefore, it is paramount that liver practices craft a comprehensive plan for safe resumption of clinical operations while minimizing the risk of exposure to patients and health-care professionals. Here, we provide a broad roadmap for how to safely resume care for patients with chronic liver disease according to various phases of the pandemic with particular emphasis on outpatient care, liver transplantation, liver cancer care, and endoscopy.

Impact of COVID-19 on endoscopy trainees: an international survey.

BACKGROUND AND AIMS: Although coronavirus disease 2019 (COVID-19) has affected endoscopy services globally, the impact on trainees has not been evaluated. We aimed to assess the impact of COVID-19 on procedural volumes and on the emotional well-being of endoscopy trainees worldwide. METHODS: An international survey was disseminated over a 3-week period in April 2020. The primary outcome was the percentage reduction in monthly procedure volume before and during COVID-19. Secondary outcomes included potential variation of COVID-19 impact between different continents and rates and predictors of anxiety and burnout among trainees. RESULTS: Across 770 trainees from 63 countries, 93.8% reported a reduction in endoscopy case volume. The median percentage reduction in total procedures was 99% (interquartile range, 85%-100%), which varied internationally (P < .001) and was greatest for colonoscopy procedures. Restrictions in case volume and trainee activity were common barriers. A total of 71.9% were concerned that the COVID-19 pandemic could prolonged training. Anxiety was reported in 52.4% of respondents and burnout in 18.8%. Anxiety was independently associated with female gender (odds ratio [OR], 2.15; P < .001), adequacy of personal protective equipment (OR, 1.75; P = .005), lack of institutional support for emotional health (OR, 1.67; P = .008), and concerns regarding prolongation of training (OR, 1.60; P = .013). Modifying existing national guidelines to support adequate endoscopy training during the pandemic was supported by 68.9%. CONCLUSIONS: The COVID-19 pandemic has led to restrictions in endoscopic volumes and endoscopy training, with high rates of anxiety and burnout among endoscopy trainees worldwide. Targeted measures by training programs to address these key issues are warranted to improve trainee well-being and support trainee education.

Overview of guidance for endoscopy during the coronavirus disease 2019 pandemic.

From its beginning in December 2019, the coronavirus disease 2019 outbreak has spread globally from Wuhan and is now declared a pandemic by the World Health Organization. The sheer scale and severity of this pandemic is unprecedented in the modern era. Although primarily a respiratory tract infection transmitted by direct contact and droplets, during aerosol-generating procedures, there is a possibility of airborne transmission. In addition, emerging evidence suggests possible fecal-oral spread of the virus. Clinical departments that perform endoscopy are faced with daunting challenges during this pandemic. To date, multiple position statements and guidelines have been issued by various professional organizations to recommend practices in endoscopic procedures. This article aims to summarize and discuss available evidence for these practices, to provide guidance for endoscopy to enhance patient safety, avoid nosocomial outbreaks, protect healthcare personnel, and ensure rational use of personal protective equipment. Responses adapted to national recommendations and local infection control guidelines and tailored to the availability of medical resources are imminently needed to fight the coronavirus disease 2019 pandemic.

Oesophageal food bolus obstruction and eosinophilic oesophagitis.

Eosinophilic oesophagitis (EoE) is now a well-recognised cause of dysphagia and food bolus obstruction (FBO). The diagnosis requires histologic confirmation, and the yield is greatest when at least 4 to 6 oesophageal biopsies are taken from different sites. Previous case reports of FBO have demonstrated a low biopsy rate, and as such cases of EoE may have been missed. In this review, the medical records of 123 patients aged 18 years or older, who had presented with FBO over a 2 year period, were reviewed. EoE was the most common diagnosis, and was found in 81.3% of patients with FBO aged 40 years or less. 45.5% of patients with FBO were biopsied, and of those, 33.9% were confirmed to have had at least 4 biopsies. EoE is a common cause of FBO and requires appropriate oesophageal sampling to confirm the diagnosis. Cases of EoE may otherwise be missed.

Real-world efficacy and safety of ritonavir-boosted paritaprevir, ombitasvir, dasabuvir ± ribavirin for hepatitis C genotype 1 - final results of the REV1TAL study.

BACKGROUND: Limited data exist on the outcomes of ritonavir-boosted paritaprevir with ombitasvir and dasabuvir (PrOD) ± ribavirin in a real-world setting. The aim of this study was to compare the efficacy and safety of PrOD-based therapy in hepatitis C genotype 1 patients with and without cirrhosis, and to explore pre-treatment factors predictive of sustained viral response (SVR) and serious adverse events (SAEs) on treatment. METHODS: 451 patients with hepatitis C genotype 1 treated in 20 centres across Australia were included. Baseline demographic, clinical and laboratory information, on-treatment biochemical, virological and haematological indices and details on serious adverse events were collected locally. RESULTS: Cirrhosis was present in 340 patients (75.4%). Overall SVR was 95.1% with no differences in SVR between the cirrhosis and non-cirrhosis groups (94.7% versus 96.4%). SVR in subgenotypes 1a and 1b was 93.1% and 99.2%, respectively. On multivariate analysis, baseline bilirubin level and early treatment cessation predicted SVR. SAEs occurred in 10.9% of patients including hepatic decompensation (2.7%) and hepatocellular carcinoma (1.8%). On multivariate analysis of factors predictive of SAEs in the overall group, Child-Turcotte-Pugh (CTP) B was the only significant factor, while in those with cirrhosis, baseline albumin and creatinine levels were significant. CONCLUSIONS: In this large real-world cohort of HCV genotype 1 subjects, treatment with PrOD was highly effective and similar to clinical trials. Important determinants of reduced SVR include early cessation of therapy and baseline bilirubin concentration. SAEs were not infrequent with CTP B patients being at greatest risk.