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Background & Aims Coronavirus disease 2019 (COVID-19) pandemic lockdown and restrictions had significant disruption to patient care. We aimed to evaluate the impact of COVID-19 restrictions on hospitalizations of patients with alcoholic and nonalcoholic cirrhosis as well as alcoholic hepatitis (AH) in Alberta, Canada. Methods We used validated International Classification of Diseases (ICD-9 and ICD-10) coding algorithms to identify liver-related hospitalizations for nonalcoholic cirrhosis, alcoholic cirrhosis, and AH in the province of Alberta between March 2018 and September 2020. We used the provincial inpatient discharge and laboratory databases to identify our cohorts. We used elevated alanine aminotransferase or aspartate aminotransferase, elevated international normalized ratio, or bilirubin to identify AH patients. We compared COVID-19 restrictions (April–September 2020) with prior study periods. Joinpoint regression was used to evaluate the temporal trends among the 3 cohorts. Results We identified 2916 hospitalizations for nonalcoholic cirrhosis, 2318 hospitalizations for alcoholic cirrhosis, and 1408 AH hospitalizations during our study time. The in-hospital mortality rate was stable in relation to the pandemic for alcoholic cirrhosis and AH. However, nonalcoholic cirrhosis patients had lower in-hospital mortality rate after March 2020 (8.5% vs 11.5%; P = .033). There was a significant increase in average monthly admissions in the AH cohort (22.1/10,000 admissions during the pandemic vs 11.6/10,000 admissions before March 2020; P Conclusions Before and during COVID-19 monthly admission rates were stable for nonalcoholic and alcoholic cirrhosis; however, there was a significant increase in AH admissions. Because alcohol sales surged during the pandemic, future impact on alcoholic liver disease could be detrimental.

The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease.Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI3.2), prefrail (LFI 3.2-4.5), and frail (LFI4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis.Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

Purpose A high recurrence rate following ablative therapy of hepatocellular carcinoma (HCC) necessitates routine follow-up imaging (secondary surveillance) to facilitate early re-treatment. We evaluate our unique secondary surveillance algorithm (with use of alternating MRI and CEUS) by assessment of the relative diagnostic accuracy of MRI and CEUS in detection of residual/recurrent tumor. Potential benefits of alternating surveillance are compared to the use of MRI alone. Materials and methods This prospective observational IRB approved study included 231 patients with 354 treated tumors between January 2017 and June 2020. Treated lesions underwent secondary surveillance for a minimum of 7 months and up to 3 years, median follow-up 14 months. Secondary surveillance involved MRI performed at 1 month after treatment, followed by CEUS and MRI at alternate 3-month intervals (i.e., CEUS at month 4, MRI at month 7, etc.), for a total of 2 years. An equivocal finding on one imaging modality triggered expeditious evaluation with the alternate modality. Arterial phase hyperenhancement and washout comprise the classic features of recurrent tumor on both modalities. Results A total of 746 MRI and 712 CEUS examinations were performed, and a total of 184 tumor recurrences detected, MRI (n = 82) and CEUS (n = 102) (p = 0.19). There was no difference in the sensitivity (71.0–85.0% and 80.9–92.0%), specificity (97.4–99.2% and 98.5–99.9%), and area under the ROC curve (0.85–0.92 and 0.91–0.96) between MRI and CEUS, respectively. 23 of 82 recurrent tumors identified on MRI were equivocal and confirmed with expedited CEUS. 9 equivocal cases on MRI were disproved by expedited CEUS. On CEUS, 1 of the 102 recurrent tumors was equivocal and confirmed on MRI, and 2 equivocal CEUS cases were disproved by MRI. Conclusion MRI and CEUS performed similarly in our secondary surveillance algorithm for HCC in their ability to detect tumor recurrence, and showed no significant difference in their relative diagnostic test accuracy measures. Of greater interest, equivocal results on MRI (typically due to difficulty in distinguishing tumor recurrence from post-treatment change/shunting) were either confirmed or disproven by CEUS in all cases. Secondary surveillance of treated HCC with alternating MRI and CEUS shows equivalent performance of each modality. CEUS resolves equivocal MRI and optimally demonstrates APHE and washout in tumor recurrence. Graphic abstract

The prevalence and effects of anxiety on health-related quality of life and clinical outcomes in cirrhosis are not well understood. This is increasingly relevant during COVID-19. Our aim was to use the Mini-International Neuropsychiatric Interview (MINI) to determine the prevalence of anxiety, its association with clinical outcomes in cirrhosis and to develop a rapid cirrhosis-specific anxiety screening nomogram.Adults with a diagnosis of cirrhosis were prospectively recruited as outpatients at three tertiary care hospitals across Alberta and followed for up to 6 months to determine the association with unplanned hospitalization/death. The Hospital Anxiety and Depression scale (HADS) was used as a screening tool as it is free of influence from somatic symptoms. Anxiety was diagnosed using the MINI.Of 304 patients, 17% of patients had anxiety by the MINI and 32% by the HADS. Anxious patients had lower health-related quality of life as assessed by the chronic liver disease questionnaire (P 0.001) and EuroQol Visual Analogue Scale (P 0.001), and also had higher levels of frailty using the Clinical Frailty score (P = 0.004). Multivariable analysis revealed smoking and three HADS subcomponents as independent predictors of anxiety. These were used to develop a rapid screening nomogram.A formal diagnosis of anxiety was made in approximately one in five patients with cirrhosis, and it was associated with worse HrQoL and frailty. The use of a 4-question nonsomatic symptom-based nomogram requires validation but is promising as a rapid screen for anxiety in cirrhosis.

Background Choosing Wisely Canada (CWC) recommends not to perform gastroscopy for dyspepsia in otherwise healthy adults less than 55 years of age (2014). The aim of this study was to evaluate the use of gastroscopy in a young, healthy population with uncomplicated dyspepsia. Methods A retrospective review of gastroscopies completed during 3-month periods in 2015, 2016, and 2017 identified all patients undergoing gastroscopy for the primary indication of dyspepsia. Low-risk patients for dyspepsia were defined as adults, aged 18 to 54 years without alarm symptoms, comorbidities and/or abnormal imaging findings or laboratory values. Gastroscopy and pathology reports were reviewed to identify clinically actionable findings. Clinical outcomes were followed to December 31, 2018 including gastroenterology referrals, emergency room visitation and hospitalization. Results Among 1358 patients having a gastroscopy for dyspepsia, 480 (35%) were low-risk patients. Sixteen patients 3.3% (16/480) had a clinically actionable result found on gastroscopy or biopsy. No malignant lesions were detected. Low-risk patients were followed up for an average of 2.75 years, 8% (39/480) visited the emergency department (ED), 1% (3/480) of patients were admitted to hospital and 12% (59/480) of patients were re-referred for a dyspepsia-related concern. Interpretation A high rate of low yield, high cost, invasive endoscopic investigations were performed in this population of otherwise healthy patients under age 55 years. These data suggest limited uptake of current recommendations against the routine use of gastroscopy to investigate dyspepsia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the least deadly but most infectious coronavirus strain transmitted from wild animals. It may affect many organ systems. Aim of the current guideline is to delineate the effects of SARS-CoV-2 on the liver. Asymptomatic aminotransferase elevations are common in coronavirus disease 2019 (COVID-19) disease. Its pathogenesis may be multifactorial. It may involve primary liver injury and indirect effects such as "bystander hepatitis," myositis, toxic liver injury, hypoxia, and preexisting liver disease. Higher aminotransferase elevations, lower albumin, and platelets have been reported in severe compared with mild COVID-19. Despite the dominance of respiratory disease, acute on chronic liver disease/acute hepatic decompensation have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a higher risk of respiratory disease progression than those without MAFLD. Alcohol-associated liver disease may be severely affected by COVID-19-such patients frequently have comorbidities including metabolic syndrome and smoking-induced chronic lung disease. World Gastroenterology Organization (WGO) recommends that interventional procedures such as endoscopy and endoscopic retrograde cholangiopancreatography should be performed in emergency cases or when they are considered strictly necessary such as high risk varices or cholangitis. Hepatocellular cancer surveillance may be postponed by 2 to 3 months. A short delay in treatment initiation and non-surgical approaches should be considered. Liver transplantation should be restricted to patients with high MELD scores, acute liver failure and hepatocellular cancer within Milan criteria. Donors and recipients should be tested for SARS-CoV-2 and if found positive donors should be excluded and liver transplantation postponed until recovery from infection., NA

Hepatocellular carcinoma (HCC) is the second most common lethal cancer, and there is a need for effective therapies. Selective internal radiation therapy (SIRT) has been increasingly used, but is not supported by guidelines due to a lack of solid evidence. Determine the efficacy and safety of SIRT in HCC across the Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C. Consecutive patients that received SIRT between 2006 and 2016 at two centers in Canada were evaluated. We analyzed 132 patients, 12 (9%), 62 (47%), and 58 (44%) belonged to BCLC stages A, B, and C; mean age was 61.2 (SD ± 9.2), and 89% were male. Median survival was 12.4 months (95% CI 9.6–16.6), and it was different across the stages: 59.7 (95% CI NA), 12.8 (95% CI 10.2–17.5), and 9.3 months (95% CI 5.9–11.8) in BCLC A, B, and C, respectively (p = 0.009). Independent factors associated with survival were previous HCC treatment (HR 2.01, 95% CI 1.23–3.27, p = 0.005), bi-lobar disease (HR 2.25, 95% CI 1.30–3.89, p = 0.003), ascites (HR 1.77, 95% CI 0.99–3.13, p = 0.05), neutrophil-to-lymphocyte ratio (HR 1.11, 95% CI 1.02–1.20, p = 0.01), Albumin–Bilirubin (ALBI) grade-3 (HR 2.69, 95% CI 1.22–5.92, p = 0.01), tumor thrombus (HR 2.95, 95% CI 1.65–5.24, p

Background Identification of patients with nonalcoholic fatty liver disease (NAFLD) with advanced liver fibrosis in primary care remains an unmet need. Our primary objective was to implement a pathway driven by shear wave elastography (SWE) to facilitate risk stratification of patients with NAFLD within primary care and evaluate whether SWE assessment can reduce referrals of patients with NAFLD at low risk for fibrosis to hepatology. Methods A multidisciplinary NAFLD clinical care pathway was codeveloped by hepatologists, radiologists and primary care physicians in Calgary to provide access to SWE-based screening of patients with NAFLD risk factors in primary care. The study outcome measures were estimated NAFLD-related referrals to the hepatology service in Calgary after implementation of the NAFLD pathway and characteristics of patients with NAFLD at risk for advanced fibrosis. The NAFLD pathway was implemented in January 2018 and was made available to all primary care physicians in the Calgary Health Zone. Patients with NAFLD who had liver stiffness (SWE value ≥ 8.0 kPa) or an inconclusive assessment were referred to hepatology. A serum liver fibrosis score was also measured with the fibrosis-4 (FIB-4) index, and performance of an FIB-4 index score of 1.30 or greater to risk stratify patients with NAFLD was evaluated. Demographic, clinical and laboratory characteristics of study groups were compared. Results Between March and October 2018, 2084 patients with suspected NAFLD were evaluated. Nonalcoholic fatty liver disease was confirmed by ultrasonography in 1958 (94.1%). A majority of the cohort had elevated liver enzyme values (1028 [52.5%]) and obesity (body mass index ≥ 30) (1063/1764 [60.3%]). Most patients with NAFLD (1791 [91.5%]) had an SWE value less than 8.0 kPa and were not referred to hepatology. Sixty-seven patients (3.4%) had an SWE value of 8.0 kPa or more, and 100 (5.1%) had an inconclusive SWE; these patients were referred to hepatology. Using an FIB-4 index score cut-off of 1.30 would have led to hepatology referral of 396/1251 patients (31.6%). Interpretation Implementation of a primary care-accessible SWE pathway for patients with NAFLD facilitated fibrosis risk stratification and greatly reduced hepatology referrals. Using the FIB-4 index score alone would led to higher rates of referral of patients with NAFLD.

BACKGROUND: The management of gastrointestinal (GI) cancers is associated with high healthcare spending. We estimated trends in US healthcare spending for patients with GI cancers between 1996 and 2016, and developed projections to 2030. METHODS: We used economic data, adjusted for inflation, developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. Corresponding US age-adjusted prevalence of GI cancers were estimated from the Global Burden of Diseases Study. Prevalence-adjusted, temporal trends in the US healthcare spending in patients with GI cancers, stratified by cancer site, age, and setting of care were estimated using joinpoint regression, expressed as annual percent change (APC) with 95% confidence intervals. Autoregressive integrated moving average models were used to project spending to 2030. RESULTS: In 2016, total spending for GI cancers was primarily attributable to colorectal ($10.50 billion [95% CI $9.35, $11.70]) and pancreatic cancer ($2.55 billion [95% CI $2.23 billion, $2.82 billion]), and primarily for inpatient care (64.5%). Despite increased total spending, more recent per-patient spending for pancreatic (APC 2008–2016 −1.4% [95% CI −2.2%, −0.7%]), gallbladder/biliary tract (APC 2010–2016 −4.3% [95% CI −4.8%, −3.8%]), and gastric cancer (APC 2011–2016 −4.4% [95% CI: −5.8%, −2.9%]) decreased. Increasing price and intensity of care provision was the largest driver of higher expenditures. By 2030, it is projected over $21 billion annually will be spent on GI cancer management. CONCLUSIONS: Total spending for GI cancers in the US is substantial and projected to increase. Expenditures are primarily driven by inpatient care for colorectal cancer, although per-capita spending trends differ by GI cancer type.

Background Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in Canada. They are effective for several upper GI-disorders, have a very favorable safety profile and therefore there are few barriers to prescribing. Concern about overuse of PPIs has been growing. Many patients do not need long term treatment. Patients starting PPI should receive short term therapy (e.g. 8 weeks) and if they respond the need for long term therapy needs to be determined. The usual starting dose is once a day for most indications. Evidence suggests a lack of ongoing indication for PPI in 40–55% of primary care patients.There are economic implications of overuse of PPIs. Public drug spending on PPIs in Canada totaled $288.3 million of $13.5 billion spent in 2017. Aims To analyze prescribing data for all PPI prescriptions in Alberta for the years 2017–18 and 2018–19 and 2019–2020, to document number of prescriptions >60 days, the number of new versus repeat prescriptions, proportion of new prescriptions at a greater than 1x daily dose, the proportion of prescriptions written by primary care physicians and to estimate the number of prescriptions targetted for deprescribing. Methods Data were obtained anonymously from the Pharmaceutical Information Network (PIN) database from community based pharmacies in Alberta. PPIs were identified using DIN numbers. Prescribed dose and duration were obtained, as well as data on repeat prescriptions. The number of prescriptions that could be targeted for deprescribing was also estimated. Results The results are shown in table 1. More than 10% of the population receives a prescription each year. Of these 25–31% were new prescriptions and 69–75% were refills. The percentage of patients who were prescribed PPIs for more than 60 days was 26–28%. Furthermore, 23% of all prescriptions had a defined daily dosage greater than the recommended standard dose of once a day therapy for most indications.75% of all prescriptions are written by family physicians. Conclusions Prescription rates of PPIs are very high in Alberta and 75% of patients are on longer term therapy. There likely is significant overprescribing of PPIs, estimated to be up to 40% of patients filling PPI prescriptions in Alberta. This represents a significant avoidable medication and system burden and patient costs. The starting dose of new prescriptions is also high, despite the fact that for most indications the daily dose should be 1x a day. A 20% reduction in prescribing would save at least $ 9 million in Alberta. A deprescribing project has been initiated by the Digestive Health Strategic Clinical Network, a multi-stakeholder network, which addresses important GI issues in Alberta. Funding Agencies None

Background The Hepatitis B virus (HBV) affects over 250 million people worldwide and can lead to cirrhosis and hepatocellular carcinoma. HBV surface antigen (HBsAg) quantification is increasingly used to predict disease activity and treatment response. As there is no virologic cure, clinicians are seeking a “functional cure”, or HBsAg loss, as a guide to safely stopping nucleos(t)ide analogue therapy. Tenofovir Disoproxil Fumarate (TDF) and Entecavir (ETV) are first line therapy but require prolonged treatment to achieve HBsAg clearance. Aims To assess the association between nucleos(t)ide therapy and decline in quantitative HBsAg (qHBsAg) in patients with HBV from Calgary, Alberta. Methods A retrospective review of adult patients with chronic HBV, followed at the University of Calgary Liver Clinic, was conducted between January 2012 and October 2020. Patients were excluded if treatment was discontinued or changed, only had a single qHBsAg measurement, or were co-infected with hepatitis C virus, hepatitis delta virus, or HIV. Patients were stratified according to therapy with TDF, ETV, or no treatment. To identify associations between mean changes in qHBsAg by medication exposure, one-way ANOVAs and t-tests were performed. Results were reported as means and 95% confidence intervals (CI). The median time from initial qHBsAg to most-recent was calculated. Results 187 patients were included in the final analysis (Table 1). 77 were excluded for being on more than one medication over the study period, 10 were excluded due to discontinuation of treatment, and 195 were excluded for single qHBsAg measurements. The mean qHBsAg decline was -750.04 IU/mL (95% CI -1311.58, -188.50) in the TDF group (n=45) and -309.20 IU/mL (95% CI -600.90, -17.50) in the ETV group (n=35) (p=0.20). In the no treatment group (n=107), the mean qHBsAg increased by 711.29 IU/mL (95% CI -600.78, 2023.80)(Figure 1). The median time from initial qHBsAg to most-recent was 980 days. Conclusions Quantitative HBsAg levels declined in patients on TDF and ETV, but increased in untreated patients. Although HBsAg levels showed a trend for greater decline in TDF-treated patients, results failed to reach statistical significance, and may be affected by overall treatment duration. Future studies will explore medication use as a time-varying covariate to identify how change in treatment influences changes in HBsAg over time. Funding Agencies None

Background & Aims Treatment options remain limited for patients with autoimmune hepatitis (AIH), while there are still concerns over the consequences of long-term corticosteroid use. A few studies have suggested a role for B cell-driven autoimmune liver injury in AIH. This multicentre, international retrospective cohort study from the International Autoimmune Hepatitis Group aims to evaluate the clinical efficacy and safety of rituximab in difficult-to-manage AIH. Methods Clinical data from 22 patients who received rituximab between 2007 and 2017 were collected from centres in the United Kingdom, Germany and Canada. Clinical response was assessed using changes in biochemical and immunological parameters up to 24 months post-rituximab infusion. In addition, we compared the doses of prednisolone used 3 months before and 12 months after treatment, and assessed freedom from AIH flares over the post-treatment period. Results Twenty-two patients with type-1 AIH were included, with a median age of 40 years at diagnosis (range 19–79); 15/22 (68%) were female and 18/22 (82%) were Caucasian. The median period from diagnosis to the end of follow-up in these patients was 11 years (range 3–28). Values of alanine aminotransferase, aspartate aminotransferase and albumin improved significantly following rituximab therapy, and were sustained for up to 2 years (all p ≪0.001). Prednisolone doses were significantly reduced by 12 months post-treatment (p = 0.003), with 13/21 (62%) patients having a dose reduction. Over a median post-treatment follow-up period of 6 years (range 1–10), 5 patients developed AIH flares at a median of 22 months post-treatment, giving an estimated 71% freedom from AIH flare at 2 years. Four of these patients received a second course of treatment, of whom 2 had subsequent further flares. No serious adverse events attributable to rituximab were recorded. Conclusion In patients with difficult-to-manage AIH, rituximab appears to be clinically effective and well tolerated. Rituximab was associated with sustained improvements in serum liver tests, an absence of clinical disease flares, and a reduction in prednisolone dose. Controlled trials are warranted to further evaluate B cell-targeting therapies in patients with AIH. Lay summary Autoimmune hepatitis is an autoimmune condition of the liver, usually treated with medications that suppress the immune system, such as steroids. However, some patients do not respond to this treatment. We analysed the safety and efficacy of rituximab in patients who were not responding to first- or second-line therapies. Rituximab was safe and improved liver blood tests in 70% of patients over a 2-year follow-up period, while enabling steroid doses to be reduced in two-thirds of patients, which is a very positive clinical outcome., Graphical abstract Unlabelled Image, Highlights • Study of rituximab therapy in 22 patients with autoimmune hepatitis over a follow-up period of 24 months. • No serious adverse events were noted during follow-up in patients treated with rituximab. • Rituximab therapy improved liver enzymes significantly during the 2 years of follow-up. • Prednisolone dose reductions were seen in 62% of patients at 12-month follow-up. • A total of 71% of patients were free of AIH flares during the 24 months of follow-up.

Hepatocellular carcinoma (HCC) has a high incidence of recurrence following therapy. Therefore, secondary surveillance (scheduled follow-up imaging after treatment) is an important part of disease management. The recent approval in the United States for use of a microbubble-based contrast agent for US liver imaging promotes the increased use of contrast-enhanced US (CEUS) in patients with HCC. Although the criteria for the diagnosis of HCC at CEUS are well described, there is a paucity of published literature describing the role of CEUS in ablative therapy and secondary surveillance. In the setting of ablative therapy, CEUS can have vital roles, including patient selection, intraprocedural guidance, and immediate postprocedural assessment. Although CEUS is not widely used, the authors found that it can be used to accurately detect residual or recurrent tumor, characterize the geographic pattern of recurrence (intrazonal, extrazonal, segmental, or remote), and assess for tumor in vein. In addition, similar to primary surveillance, secondary surveillance includes assessment of the entire liver for evaluation of new nodules. Arterial phase hyperenhancement is the reference standard characteristic of disease recurrence at secondary surveillance with CEUS. ©RSNA, 2019 See discussion on this article by Rodgers.

Intraoperative tranexamic acid (TXA) is used to reduce blood loss and the need for transfusions following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Despite evidence in literature and local practice protocols supporting TXA as a part of standard of care for joint arthroplasty, TXA administration is underutilized. We aimed to use group-facilitated audit and feedback as the foundation of a knowledge translation strategy to increase TXA use for THA and TKA procedures.Anesthesiologists consented to receive two data reports summarizing their individual rates of TXA use and postoperative blood transfusions compared with site peers. Variables collected included patient demographics, TXA usage, and the frequency and volume of red blood cell transfusions administered in the 72-hr postoperative period. The facilitated feedback session discussed report findings and focused on factors contributing to local practice patterns and opportunities for change.Tranexamic acid use increased for THA procedures at the intervention site from 66.6 to 74.4% (absolute change, 7.9%; 95% confidence interval [CI], 2.4 to 13.3). Likewise, TXA use for TKA procedures increased from 62.4 to 82.3% (absolute change, 19.9%; 95% CI 15.0 to 25.0).Physicians and their teams were able to review their practice data on TXA utilization, reflect on differences compared with evidence-based guidelines, discuss findings with peers, and identify opportunities for improvement. The intervention increased the use of TXA for both TKA and THA and shifted the dosage to better align with evidence-based practice guidelines.RéSUMé: OBJECTIF : L’acide tranexamique (ATX) peropératoire est utilisé pour réduire les pertes sanguines et les besoins transfusionnels après les arthroplasties totales de la hanche (ATH) et du genou (ATG). Malgré les données probantes et les protocoles de pratique locaux appuyant l’utilisation d’ATX dans le cadre de la norme de soins en cas d’arthroplastie, l’administration de cet agent est sous-utilisée. Notre objectif était d’utiliser l’audit et la rétroaction facilités par le groupe comme base d’une stratégie d’application des connaissances afin d’accroître l’utilisation de l’ATX lors des ATH et ATG. MéTHODE: Les anesthésiologistes ont consenti à recevoir deux rapports de données résumant leurs taux individuels d’utilisation d’ATX et de transfusions sanguines postopératoires par rapport à leurs pairs au sein du même établissement. Les variables recueillies comprenaient les données démographiques des patients, l’utilisation d’ATX et la fréquence et le volume des transfusions d’érythrocytes administrées au cours d’une période postopératoire de 72 heures. La séance de rétroaction facilitée a porté sur les conclusions du rapport et s’est concentrée sur les facteurs contribuant aux habitudes de pratique locales et aux possibilités de changement. RéSULTATS: L’utilisation d’acide tranexamique a augmenté pour les procédures d’ATH au site d’intervention, passant de 66,6 % à 74,4 % (variation absolue, 7,9 %; intervalle de confiance [IC] à 95 %, 2,4 à 13,3). De même, l’utilisation d’ATX pour les procédures d’ATG est passée de 62,4 % à 82,3 % (variation absolue, 19,9 %; IC 95 %, 15,0 à 25,0). CONCLUSION: Les médecins et leurs équipes ont pu passer en revue leurs données de pratique sur l’utilisation d’ATX, réfléchir aux différences par rapport aux lignes directrices fondées sur des données probantes, discuter des résultats avec leurs pairs et identifier les possibilités d’amélioration. L’intervention a augmenté l’utilisation d’ATX pour l’ATG et l’ATH et a modifié la posologie pour mieux s’aligner sur les lignes directrices de pratique fondées sur des données probantes.

Background Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are chronic conditions with high acute care utilization. Disease-specific order sets were developed for patients with COPD or HF in Calgary to reduce total days in hospital for this population of patients. However, many patients have comorbidities which may contribute to hospital utilization; thus, disease-specific order sets may not be an optimal solution to reduce overall acute care utilization. Methods Inpatient data on Calgary hospitalizations for COPD or HF between April 1, 2017 - March 31, 2019 and associated diagnoses were identified. Outcomes included total days in hospital and length of stay for COPD and HF patients stratified by number of comorbidities. Results Total days in hospital increased with the number of comorbidities for both conditions. During the study period, 131 patients with COPD and no comorbidities had a median length of stay of three days (IQR: 3) compared to 3,911 COPD patients with one to five comorbidities with a median length of stay of seven days (IQR: 9). There were 47 patients with HF and no comorbidities with a median length of stay of four days (IQR: 5) compared to 6,273 HF patients with one to five comorbidities with a median length of stay of nine days (IQR: 12). Common comorbidities included hypertension, type 2 diabetes, and acute renal failure. COPD and HF are frequently comorbid. Conclusions Total days in hospital for patients with COPD or HF is positively correlated with the number of comorbidities. COPD or HF patients with between one to five comorbidities (compared to those with no comorbidities, and those with more than five comorbidities) represent the majority of total days in hospital, and the majority of patients. This highlights the importance of focusing on patients with comorbidities in efforts to reduce hospital utilization, and suggests that concurrent management of commonly occurring comorbidities for HF and COPD patients may be necessary to achieve this goal.

A high recurrence rate following ablative therapy of hepatocellular carcinoma (HCC) necessitates routine follow-up imaging (secondary surveillance) to facilitate early re-treatment. We evaluate our unique secondary surveillance algorithm (with use of alternating MRI and CEUS) by assessment of the relative diagnostic accuracy of MRI and CEUS in detection of residual/recurrent tumor. Potential benefits of alternating surveillance are compared to the use of MRI alone.This prospective observational IRB approved study included 231 patients with 354 treated tumors between January 2017 and June 2020. Treated lesions underwent secondary surveillance for a minimum of 7 months and up to 3 years, median follow-up 14 months. Secondary surveillance involved MRI performed at 1 month after treatment, followed by CEUS and MRI at alternate 3-month intervals (i.e., CEUS at month 4, MRI at month 7, etc.), for a total of 2 years. An equivocal finding on one imaging modality triggered expeditious evaluation with the alternate modality. Arterial phase hyperenhancement and washout comprise the classic features of recurrent tumor on both modalities.A total of 746 MRI and 712 CEUS examinations were performed, and a total of 184 tumor recurrences detected, MRI (n = 82) and CEUS (n = 102) (p = 0.19). There was no difference in the sensitivity (71.0-85.0% and 80.9-92.0%), specificity (97.4-99.2% and 98.5-99.9%), and area under the ROC curve (0.85-0.92 and 0.91-0.96) between MRI and CEUS, respectively. 23 of 82 recurrent tumors identified on MRI were equivocal and confirmed with expedited CEUS. 9 equivocal cases on MRI were disproved by expedited CEUS. On CEUS, 1 of the 102 recurrent tumors was equivocal and confirmed on MRI, and 2 equivocal CEUS cases were disproved by MRI.MRI and CEUS performed similarly in our secondary surveillance algorithm for HCC in their ability to detect tumor recurrence, and showed no significant difference in their relative diagnostic test accuracy measures. Of greater interest, equivocal results on MRI (typically due to difficulty in distinguishing tumor recurrence from post-treatment change/shunting) were either confirmed or disproven by CEUS in all cases. Secondary surveillance of treated HCC with alternating MRI and CEUS shows equivalent performance of each modality. CEUS resolves equivocal MRI and optimally demonstrates APHE and washout in tumor recurrence.

Coronavirus disease 2019 (COVID-19) has challenged how care is delivered to patients with chronic liver disease (CLD). In an attempt to update Canadian health care practitioners taking care of individuals with CLD, the Canadian Association for the Study of the Liver (CASL) hosted a webinar on May 7, 2020, with more than 120 participants. The resultant article is a partnership between members of CASL’s executive and education committees to provide best practice management principles on liver disease during COVID-19 to the broader hepatology community.

Chronic Hepatitis B Virus (HBV) infection poses a significant global health burden. Although, effective treatment and vaccinations against HBV are available, challenges still exist, particularly in the development of curative therapies. The dynamic nature and unique features of HBV such as viral variants, integration of HBV DNA into host chromosomes, and extrahepatic reservoirs are considerations towards understanding the virus biology and developing improved anti-HBV treatments. In this review, we highlight the importance of these viral characteristics in the context of treatment and oncogenesis. Viral genotype and genetic variants can serve as important predictive factors for therapeutic response and outcomes in addition to oncogenic risk. HBV integration, particularly in coding genes, is implicated in the development of hepatocellular carcinoma. Furthermore, we will discuss emerging research that has identified various HBV nucleic acids and infection markers within extrahepatic sites (lymphoid cells). Intriguingly, the presence of hepatocellular carcinoma (HCC)-associated HBV variants and viral integration within the lymphoid cells may contribute towards the development of extrahepatic malignancies. Improved understanding of these HBV characteristics will enhance the development of a cure for chronic HBV infection.

The challenges of managing varices during the COVID-19 pandemic are reviewed, and a treatment algorithm is presented to best manage patients with advanced liver disease during periods of limited access to endoscopy.

Transplantation of hepatitis C virus (HCV)-positive organs has undergone a paradigm shift because of the advent of direct-acting antivirals. We present the case of a 57-year-old man successfully treated initially with pegylated interferon and ribavirin after HCV recurrence postliver transplantation. He subsequently developed end-stage renal disease and received a genotype 1a HCV-positive kidney transplant. A 12-week course of ledipasvir/sofosbuvir and low-dose ribavirin was initiated and sustained virologic response was achieved. This constitutes the first reported case of a patient successfully treated for HCV a second time after receiving an HCV-positive organ.

Evidence ranging from behavioural adaptations to neurocognitive theories has made significant advances into our understanding of feedback-based learning. For instance, over the past twenty years research using electroencephalography has demonstrated that the amplitude of a component of the human event-related brain potential - the reward positivity - appears to change with learning in a manner predicted by reinforcement learning theory (Holroyd and Coles, 2002; Sutton and Barto, 1998). However, while the reward positivity (also known as the feedback related negativity) is well studied, whether the component reflects an underlying learning process or whether it is simply sensitive to feedback evaluation is still unclear. Here, we sought to provide support that the reward positivity is reflective of an underlying learning process and further we hoped to demonstrate this in a real-world medical education context. In the present study, students with no medical training viewed a series of patient cards that contained ten physiological readings relevant for diagnosing liver and biliary disease types, selected the most appropriate diagnostic classification, and received feedback as to whether their decisions were correct or incorrect. Our behavioural results revealed that our participants were able to learn to diagnose liver and biliary disease types. Importantly, we found that the amplitude of the reward positivity diminished in a concomitant manner with the aforementioned behavioural improvements. In sum, our data support theoretical predictions (e.g., Holroyd and Coles, 2002), suggest that the reward positivity is an index of a neural learning system, and further validate that this same system is involved in learning across a wide range of contexts.

Introduction and aim. Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status. Material and methods. A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status. Results. 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported. Conclusions. SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list.

Introduction. Quantitative hepatitis B surface antigen (qHBsAg) combined with HBV DNA may be useful for predicting chronic hepatitis B (CHB) activity and nucleoside analogue (NA) response.Material and methods. In this retrospective cohort study we evaluated qHBsAg levels according to CHB disease phase and among patients on treatment. Random effect logistic regression analysis was used to analyze qHBsAg change with time in the NA-treated cohort.Results. 545 CHB carriers [56% M, median age 48 y (IQR 38-59), 73% Asian] had qHBsAg testing. In the untreated group (44%), 8% were classified as immune tolerant, 10% immune clearance, 40% inactive, and 43% had HBeAg- CHB and the median HBsAg levels were 4.6 (IQR 3.4-4.9), 4.0 (IQR 3.4-4.5), 2.9 (IQR 1.4-3.8), and 3.2 log IU/mL (IQR 2.6-4.0), respectively; p < 0.001. In the NA-treated group (28% entecavir, 68% tenofovir, 4% lamivudine), no significant change in qHBsAg levels occured with time. However, 19% of patients on long-term NA had sustained qHBsAg < 2 log10 IU/mL.Conclusion. qHBsAg titers were associated with CHB phase and remained stable in those on long-term NA. A significant number of treated patients had low-level qHBsAg, of which some may be eligible for treatment discontinuation without risk of flare.

Recent studies suggest that withdrawal of hepatitis B immune globulin (HBIG) and nucleos(t)ide analogues (NA) prophylaxis may be considered in HBV surface antigen (HBsAg)-negative liver transplant (LT) recipients with a low risk of disease recurrence. However, the frequency of occult HBV infection (OBI) and HBV variants after LT in the current era of potent NA therapy is unknown. Twelve LT recipients on prophylaxis were tested in matched plasma and peripheral blood mononuclear cells (PBMCs) for HBV quasispecies by in-house nested PCR and next-generation sequencing of amplicons. HBV covalently closed circular DNA (cccDNA) was detected in Hirt DNA isolated from PBMCs with cccDNA-specific primers and confirmed by nucleic acid hybridization and Sanger sequencing. HBV mRNA in PBMC was detected with reverse-transcriptase nested PCR. In LT recipients on immunosuppressive therapy (10/12 male; median age 57.5 [IQR: 39.8-66.5]; median follow-up post-LT 60 months; 6 pre-LT hepatocellular carcinoma [HCC]), 9 were HBsAg-. HBV DNA was detected in all plasma and PBMC tested; cccDNA and/or mRNA was detected in the PBMC of 10/12 patients. Significant HBV quasispecies diversity (ie 143-2212 nonredundant HBV species) was noted in both sites, and single nucleotide polymorphisms associated with cirrhosis and HCC were detected at varying frequencies. In conclusion, OBI and HBV variants associated with severe liver disease persist in LT recipients on prophylaxis. Although HBV control and cccDNA transcriptional silencing may occur despite immunosuppression, complete virological eradication does not occur in LT recipients with a history of HBV-related end-stage liver disease.

SummaryBackground Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first-line treatments for chronic hepatitis B (CHB). Studies suggest lipid lowering effect of TDF in human immunodeficiency virus positive (HIV+) individuals, but the effect on lipids and cardiovascular disease (CVD) risk in CHB is unknown. Aim To compare TDF vs ETV effects on lipid levels in CHB. Methods In this retrospective cohort study, data on serum lipids and CVD risk factors at baseline and ~1 year on TDF or ETV were collected from CHB carriers. We used propensity score matched models to assess the effect on total cholesterol (TC), LDL-C, HDL and triglycerides (TGL). Results In 348 patients, median age was 57 (IQR: 47-65 years), 63% were male, 77% were Asian, 19% were cirrhotic, 25% were HBeAg positive at baseline, and 72% received TDF vs 28% ETV. ETV-treated patients were older (median age: 60 vs 55, P

The hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC), partly driven by viral integration and specific oncogenic HBV variants. However, the biological significance of HBV genomes within lymphoid cells (i.e., peripheral blood mononuclear cells, PBMCs) is unclear. Here, we collected available plasma, PBMC, liver, and tumor from 52 chronic HBV (CHB) carriers: 32 with HCC, 19 without HCC, and one with dendritic cell sarcoma, DCS. Using highly sensitive sequencing techniques, next generation sequencing, and AluPCR, we demonstrate that viral genomes (i.e., HBV DNA, RNA, and cccDNA), oncogenic variants, and HBV-host integration are often found in all sample types collected from 52 patients (including lymphoid cells and a DCS tumor). Viral integration was recurrently identified (n = 90 such hits) in genes associated with oncogenic consequences in lymphoid and liver cells. Further, HBV genomes increased in PBMCs derived from 7 additional (treated or untreated) CHB carriers after extracellular mitogen stimulation. Our study shows novel HBV molecular data and replication not only liver, but also within 63.8% of lymphoid cells analysed (including a representative lymphoid cell malignancy), that was enhanced in ex vivo stimulated PBMC.