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The increased use of immune checkpoint inhibitors (ICIs) across cancer programs has created the need for standardized monitoring and management of immune-related adverse events (irAEs). Delayed recognition without appropriate treatment can have serious and life-threatening consequences. The management of irAEs presents a unique set of challenges that must be addressed at a multidisciplinary level. Although various national and international guidelines and working groups provide high-level recommendations for the management of irAEs, practical guidance is lacking. Furthermore, timely collaboration between specialists requires institutional protocols that enable the early recognition, assessment, and treatment of irAEs. Such protocols should be developed by institution specialists and include algorithms for all healthcare providers involved in the care of patients treated with ICIs. At William Osler Health System in Brampton, Ontario, practical step-by-step multidisciplinary treatment approaches with recommendations for the management of irAEs were developed in collaboration with experts across Canada. Here, we provide an in-depth description of the approaches, outlining baseline investigations prior to the initiation of ICIs, as well as the monitoring and management of irAEs based on symptoms, severity, and involved organ systems. We encourage other centres to adapt and modify our approaches according to their specific needs and requirements. [ABSTRACT FROM AUTHOR]

Presenters Jane Zhao, MSc, Elizabeth Lee, MN, NP, CGN(C), Hemant Shah, MD, MScCH HPTE FAASLD, Jordan Feld, Morven Cunningham, PhD, MBBS, [...], CONTEXT: Nursing primary care providers (PCPs) are well-positioned to address central gaps in screening, linkage to care, and treatment of liver diseases within their teams. The Extension for Community Healthcare Outcomes (ECHO) Model[TM] is a telementoring education program that connects PC providers from underserved areas to an interprofessional specialist team. Each session includes a didactic lecture and a patient case presentation. ECHO Ontario Liver launched in 2017 with the goal of disseminating hepatology best practices appropriate for PC and improving PC providers' knowledge and self-efficacy. OBJECTIVE: This study aims to explore the impact of ECHO on nursing PCPs and their role in interprofessional liver care. STUDY DESIGN: We conducted a qualitative study with nursing PCPs who attended ECHO sessions from 2017 to 2021. Focus groups were conducted virtually, recorded, and transcribed. ANALYSIS: Transcripts were analyzed using thematic content analysis. Researchers met regularly to discuss themes until consensus was reached. SETTING: Ontario, Canada POPULATION STUDIED: Nursing professionals (nurse practitioners, NPs, registered nurses, RNs, and registered practical nurses, RPNs) INTERVENTION: ECHO Ontario Liver OUTCOME MEASURES: Focus group discussions explored PCPs' experience in ECHO, their role in liver care management (interprofessional collaboration), and impact of ECHO on practice. RESULTS: Three focus groups were conducted between November 2021 and January 2022. Six participants were NPs, four were RNs, and one was a RPN. Six (55%) providers practiced in rural communities. All were female. Nursing PCPs involved in different levels of liver management were interviewed. They played active management roles from coordinating appointments to providing wraparound patient services. ECHO allowed participants to access specialty knowledge and education they did not receive in their training. Though PCPs practiced on a team, these individuals become the point person on their team to attend ECHO, gaining advanced training in this disease area. Participants also used the ECHO patient case presentation and recommendations as a means of advocating for care on their clinical teams. CONCLUSIONS: Nursing PCPs play a variety of roles within the management of liver disease on their clinical teams. ECHO Ontario Liver increased participants' access to specialty liver knowledge and case presentations and recommendations were often used as a means of advocacy.

LINKED CONTENT: This article is linked to Riveiro‐Barciela et al paper. To view this article, visit https://doi.org/10.1111/apt.17898 [ABSTRACT FROM AUTHOR]

Background and aims: Immune checkpoint inhibitors (ICI) are increasingly used in cancer therapy. Elevated liver enzymes frequently occur in patients treated with ICI but evaluation is poorly described. We sought to better understand causes of liver enzyme elevation, investigation and management. Methods: Patients treated with anti-PD-1, PDL-1 or CTLA-4 therapy in Phase I/II clinical trials between August 2012 and December 2018 were included. Clinical records of patients with significant liver enzyme elevations were retrospectively reviewed. Results: Of 470 ICI-treated patients, liver enzyme elevation occurred in 102 (21.6%), attributed to disease progression (56; 54.9%), other drugs/toxins (7; 6.9%), other causes (22; 21.6%) and ICI immunotoxicity (17; 16.7%; 3.6% of total cohort). Immunotoxicity was associated with higher peak ALT than other causes of enzyme elevation (N = 17; M = 217, 95% CI 145–324 for immunotoxicity, N = 103; M = 74, 95% CI 59–92 for other causes; ratio of means 0.34, 95% CI 0.19–0.60, p = <0.001) and higher ALT:AST ratio (M = 1.27, 95% CI 0.78–2.06 for immunotoxicity, M = 0.69, 95% CI 0.59–0.80 for other causes, ratio of means 0.54, 95% CI 0.36–0.82, p = 0.004). Immunotoxicity was more often seen in patients with prior CPI exposure (41.2% of immunotoxicity vs 15.9% of patients without, p = 0.01), anti-CTLA-4 –containing ICI treatments (29.4% of immunotoxicity vs 6.8% of patients without, p = <0.001) and other organ immunotoxicity (76.5% of immunotoxicity vs 19.2% of patients without, p = <0.001). Cause for enzyme elevation was established in most patients after non-invasive investigation. Liver biopsy was reserved for four patients with atypical treatment response. Conclusions: Liver enzyme elevation is common in patients receiving ICI, but often has a cause other than immunotoxicity. A biochemical signature with higher ALT and ALT/AST ratio, a history of prior ICI exposure and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity. Liver biopsy can be safely deferred in most patients. We propose an approach to diagnostic evaluation in patients with liver enzyme elevations following ICI exposure. [ABSTRACT FROM AUTHOR]

Background & Aims: Primary sclerosing cholangitis (PSC) is associated with an increased risk of gallbladder cancer (GBC). Gallbladder polyps potentially harbour malignancy and thus international guidelines recommend prophylactic cholecystectomy for gallbladder polyps of any size in patients with PSC. To best inform patient care we sought to quantify the malignant risk of gallbladder polyps in patients with PSC. Methods: A retrospective cohort study of patients followed in secondary and tertiary care settings in two large PSC clinics in North America was performed. Results: In total, 453 patients were included with a median (IQR) follow‐up time of 7.7 (4.1‐12) years. A gallbladder polyp was radiographically detected in 16% (n = 71) with median size (range) of 4 (2‐18) mm. In this group, post‐cholecystectomy histology (n = 17) reported benign or no polyp in 77% (n = 13), dysplasia in 5.9% (n = 1) and malignancy in 18% (n = 3). The GBC rate was 8.8 (95% CI 1.8‐25.7) per 1000 person‐years in patients with a radiographically detected gallbladder polyp. GBC was associated with polyps >10 mm, interval growth or mass‐like lesions on pre‐operative imaging. In patients who did not have cholecystectomy (n = 50), the polyp was only transiently seen in 80% (n = 40), remained stable or decreased in size in 10% (n = 5) and increased in size in 6% (n = 3). The majority of gallbladder polyps did not show significant growth over time (0.041 mm/year [95% CI −0.017 to 0.249]). Conclusions: Most gallbladder polyps in patients with PSC are benign. Short‐term surveillance imaging may be considered prior to recommending immediate cholecystectomy in patients with PSC without high‐risk imaging features. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C infection represents a significant and growing health problem worldwide. Patients with genotype 1 hepatitis C respond poorly to the current standard of care, pegylated interferon and ribavirin, which is frequently associated with unpleasant side effects. Consequently new agents with improved efficacy and tolerability are needed. The efficacy and safety of the direct-acting antiviral agent telaprevir in the treatment of genotype 1 hepatitis C infection have been demonstrated in a number of clinical trials. The addition of telaprevir to standard therapy considerably improves response rates and allows response-guided shortening of treatment duration in a substantial number of treatment-naïve patients. Side effects associated with telaprevir therapy include rash, anaemia, gastrointestinal disturbance and anorectal discomfort. Telaprevir-resistant variants have been identified in patients who have failed telaprevir-containing therapy, and whether selection of these variants will compromise future therapeutic options is currently unknown. The efficacy and safety of telaprevir in the treatment of the most challenging patients, including those with recurrent hepatitis C following liver transplantation and those co-infected with HIV, remains to be established. [ABSTRACT FROM PUBLISHER]