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Much about the etiology, pathophysiology, natural course and optimal treatment of cystic disease of the biliary tree remains under debate. Gastroenterologists, surgeons and radiologists alike still strive to optimize their roles in the management of choledochal cysts. To that end, much has been written about this disease entity, and the purpose of this 3-part review is to organize the available literature and present the various theories currently argued by the experts. In part 3, we discuss the management of choledochal cysts, thus completing our comprehensive review. [ABSTRACT FROM AUTHOR]

Much about the etiology, pathophysiology, natural course and optimal treatment of cystic disease of the biliary tree remains under debate. Gastroenterologists, surgeons and radiologists alike still strive to optimize their roles in the management of choledochal cysts. To that end, much has been written about this disease entity, and the purpose of this 3-part review is to organize the available literature and present the various theories currently argued by the experts. In part 2, we explore the details surrounding diagnosis, describing the presentation and imaging of the disease. [ABSTRACT FROM AUTHOR]

Much about the etiology, pathophysiology, natural course and optimal treatment of cystic disease of the biliary tree remains under debate. Gastroenterologists, surgeons and radiologists alike still strive to optimize their roles in the management of choledochal cysts. To that end, much has been written about this disease entity, and the purpose of this 3-part review is to organize the available literature and present the various theories currently argued by the experts. In part 1, we discuss the background of the disease, describing the etiology, classification, pathogenesis and malignant potential of choledochal cysts. [ABSTRACT FROM AUTHOR]

In patients with jaundice and normal liver function, the cause of hyperbilirubinemia is an isolated disorder of bilirubin metabolism. In patients with hyperbilirubinemia who have abnormal liver enzyme levels, hepatocellular disease must be differentiated from cholestatic liver injury. In general, if the cause of jaundice is global hepatocellular dysfunction, the serum alanine aminotransferase and aspartate aminotransferase levels will be predominantly elevated. If the cause is cholestasis, the serum alkaline phosphatase and gamma-glutamyl peptidase levels will be elevated. In most patients, imaging studies will be needed. The initial workup should include abdominal ultrasonography, which can identify dilated intrahepatic and extrahepatic biliary ducts as well as findings that may suggest cirrhosis or signs of portal hypertension, including splenomegaly and ascites. [ABSTRACT FROM AUTHOR]

Objective: As metabolic dysfunction-associated steatotic liver disease (MASLD) becomes more prevalent worldwide, it is imperative to create more accurate technologies that make it easy to assess the liver in a point-of-care setting. The aim of this study is to test the performance of a new software tool implemented in Velacur (Sonic Incytes), a liver stiffness and ultrasound attenuation measurement device, on patients with MASLD. This tool employs a deep learning-based method to detect and segment shear waves in the liver tissue for subsequent analysis to improve tissue characterization for patient diagnosis., Methods: This new tool consists of a deep learning based algorithm, which was trained on 15,045 expert-segmented images from 103 patients, using a U-Net architecture. The algorithm was then tested on 4429 images from 36 volunteers and patients with MASLD. Test subjects were scanned at different clinics with different Velacur operators. Evaluation was performed on both individual images (image based) and averaged across all images collected from a patient (patient based). Ground truth was defined by expert segmentation of the shear waves within each image. For evaluation, sensitivity and specificity for correct wave detection in the image were calculated. For those images containing waves, the Dice coefficient was calculated. A prototype of the software tool was also implemented on Velacur and assessed by operators in real world settings., Results: The wave detection algorithm had a sensitivity of 81% and a specificity of 84%, with a Dice coefficient of 0.74 and 0.75 for image based and patient-based averages respectively. The implementation of this software tool as an overlay on the B-Mode ultrasound resulted in improved exam quality collected by operators., Conclusion: The shear wave algorithm performed well on a test set of volunteers and patients with metabolic dysfunction-associated steatotic liver disease. The addition of this software tool, implemented on the Velacur system, improved the quality of the liver assessments performed in a real world, point of care setting., Competing Interests: Conflict of interest M.H., J.L., and C.S. are employees of Sonic Incytes. N.W. is a consultant for Sonic Incytes. S.G.: Research grant support for Viking, Zydus, Sonic Incytes, DSM. R.L. Is the Co-founder of LipoNexus Inc. and was an investigator of clinical trials sponsored by Sonic Incytes. R.L. receives funding support from NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515), NHLBI (P01HL147835), John C Martin Foundation (RP124). A.R.: Advisor /consultant for Abbvie, Gilead, Intercept/ Advanz, Janssen, Novo-Nordisc. He was an investigator of clinical trials sponsored by Sonic Incytes. T.H.: Receives Grant/Research Support from AbbVie, Allergan, Amgen, Biolinq, Bristol-Myers Squibb, Cytodyn, Assembly, Astra Zeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, CARA, DURECT Corporation, Enanta, Escient, Fractyl, Galectin, Gilead, Grifols, HepQuant, Intercept, Janssen, Merck, Mirum, Novartis, Novo Nordisk, Nucorion, Pfizer, Provepharm, Regeneron, Salix Pharmaceuticals, Sonic Incytes, Terns Pharmaceuticals, Valeant. He was an investigator of clinical trials sponsored by Sonic Incytes. E.Y.: Dr. Eric Yoshida is an investigator of clinical research and clinical trials sponsored by: Sonic Incytes Inc, Pfizer Inc, Gilead Inc, Intercept Inc, Madrigal Inc, Novodisc Inc, Genfit Inc. He has also received a research grant from Paladin Laboratories. EP: None. MC has received research support from CareDx, Intercept and Sonic Incytes and consults for International Healthcare and Pfizer. He was an investigator of clinical trials sponsored by Sonic Incytes. N.A. has received consulting fees from Gilead, Glaxo Smith Kline, Jannsen, Sonic Incytes, Precision Biosciences, Intercept Pharmaceuticals. He has stock in Allurion. He is director, Liver Institute for Education and Research. He was an investigator of clinical trials sponsored by Sonic Incytes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Indigenous Peoples in Canada face healthcare inequities impacting access to solid organ transplantation. The experiences of Indigenous patients during the liver transplant process, and how transplant professionals perceive challenges faced by Indigenous Peoples, has not been studied. Thirteen semi-structured qualitative interviews were conducted via telehealth with Indigenous liver transplant patients ( n  = 7) and transplant care providers ( n  = 6) across British Columbia, Canada between April 2021-May 2022. Themes were identified to inform clinical approaches and transplant care planning and validated by Indigenous health experts. Among patient participants: transplants occurred between 1992-2020; all were women; and the mean age at the time of interview was 60 years. Among transplant care provider participants: roles included nursing, social work, and surgery; 83% were women; and the median number of years in transplant care was ten. Three broad themes were identified: Indigenous strengths and resources, systemic and structural barriers, and inconsistent care and cultural safety across health professions impact Indigenous patient care during liver transplantation. This study contributes insights into systemic barriers and Indigenous resilience in the liver transplant journey. Dismantling structural barriers to early linkage to care is needed, and training for transplant clinicians on Indigenous histories, cultural protocols, and cultural safety is strongly recommended.

Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada., Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population., Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively)., Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus., Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC)., Competing Interests: JDM and DJ are supported by the Canadian Network on Hepatitis C (CanHepC) Ph.D. fellowship, DJ is also supported by the CIHR Frederick Banting and Charles Best Doctoral Award. RLM received travel awards from the CIHR and the University of British Columbia but not related the current work. SB received grant/research support from Gilead Sciences and Abbvie. EY has received grant/research support from Paladin Laboratories, Pfizer Inc, Novodisc Inc, Genefit Inc, Intercept Inc, Madrigal Inc, Gilead Sciences, Merck Inc, Sonic Incytes. AR has received greant/research support from Abbvie, Assembly, Galmed, Gilead, Intercept, Janssen, Merck, Novartis, Novo-Nordisc, Pfizer. MK has received grant/research support from Roche, Merck, Siemens, Boehringer Ingelheim and Hologic. NZJ participated in advisory boards and has spoken for AbbVie, not related to current work. MB had no conflict of interest at the time of the study but is now an employee of AstraZeneca. SW, PAA, SB, GC, AY, MA, HS, HAVG, HHK, and YA have no conflicts of interest to declare., (© 2024 The Author(s).)

Competing Interests: EM Yoshida has been an investigator of clinical trials in non-alcoholic fatty liver disease sponsored by Genfit, Intercept Gilead.

Background: As the prevalence of metabolic dysfunction-associated steatotic liver disease increases, it is imperative to have noninvasive alternatives to liver biopsy. Velacur offers a non-invasive, point-of-care ultrasound-based method for the assessment of liver stiffness and attenuation. The aim of this study was to perform a head-to-head comparison of liver stiffness and liver fat determined by Velacur and FibroScan using MRI-based measurements as the reference standard., Methods: This prospective cross-sectional study included 164 adult participants with well-characterized metabolic dysfunction-associated steatotic liver disease. Patients underwent a research exam including Velacur, FibroScan and contemporaneous magnetic resonance elastography, and magnetic resonance imaging proton density fat fraction (MRI-PDFF) scans. The primary outcome was the presence of advanced fibrosis (>F2) as measured by magnetic resonance elastography and the presence of liver fat (>5%) as measured by MRI-PDFF., Results: The mean age and body mass index were 57±12 years and 30.6±4.8 kg/m2, respectively. The mean liver stiffness on magnetic resonance elastography was 3.22±1.39 kPa and the mean liver fat on MRI-PDFF was 14.2±8%. The liver stiffness assessments by Velacur and FibroScan were similar for the detection of advanced fibrosis (AUC 0.95 vs. 0.97) and were not statistically different (p=0.43). Velacur was significantly better than FibroScan (AUC 0.94 vs. 0.79, p=0.01), for the detection of MRI-PDFF >5% (diagnosis of metabolic dysfunction-associated liver disease)., Conclusions: Velacur was superior to FibroScan for liver fat detection with MRI-PDFF as the reference. Velacur and FibroScan were not statistically different for liver stiffness assessment as defined by magnetic resonance elastography., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower health-related quality of life. To date, there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis (NASH). Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD., Aim: To investigate the efficacy and safety of semaglutide in patients with NAFLD., Methods: MEDLINE, CENTRAL, and EMBASE were searched from inception to May 1, 2023, to identify eligible randomized controlled trials (RCTs). Meta-analysis was performed using random effects model expressing continuous outcomes as mean differences (MD) or standardized MDs (SMD), and dichotomous outcomes as odds ratios (OR) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the Cochran's Q test and I 2 statistic., Results: Three RCTs involving 458 patients were included. Semaglutide increased the likelihood of NASH resolution (OR: 3.18, 95%CI: 1.70, 5.95; P < 0.001), improvement in steatosis (OR: 2.83, 95%CI: 1.19, 6.71; P = 0.03), lobular inflammation (OR: 1.81, 95%CI: 1.11, 2.96; P = 0.02), and hepatocellular ballooning (OR: 2.92, 95%CI: 1.83, 4.65; P < 0.001), but not fibrosis stage (OR: 0.71, 95%CI: 0.15, 3.41; P = 0.67). Radiologically, semaglutide reduced liver stiffness (SMD: -0.48, 95%CI: -0.86, -0.11; P = 0.01) and steatosis (MD: -4.96%, 95%CI: -9.92, 0.01; P = 0.05). It also reduced alanine aminotransferase (MD: -14.06 U/L, 95%CI: -22.06, -6.07; P < 0.001) and aspartate aminotransferase (MD: -11.44 U/L, 95%CI: -17.23, -5.65; P < 0.001). Semaglutide led to improved cardiometabolic outcomes, including decreased HgA1c (MD: -0.77%, 95%CI: -1.18, -0.37; P < 0.001) and weight loss (MD: -6.53 kg, 95%CI: -11.21, -1.85; P = 0.006), but increased the occurrence of GI-related side effects (OR: 3.72, 95%CI: 1.68, 8.23; P = 0.001). Overall risk of serious adverse events was similar compared to placebo (OR: 1.40, 95%CI: 0.75, 2.62; P < 0.29)., Conclusion: Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile. Future studies are required to evaluate its effects on fibrosis regression and different phases of NAFLD., Competing Interests: Conflict-of-interest statement: Zhu K, Kakkar R and Chahal D have no conflicts of interests to declare; Yoshida EM is an investigator of clinical trials sponsored by Gilead Sciences, Pfizer, Genfit, Intercept, Celgene, Allergan, and Madrigal; Yoshida EM has received research funding from Paladin Labs Inc; Hussaini T has received research funding from Transplant Research Foundation of BC, and Paladin Labs Inc., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The COVID-19 pandemic has resulted in significant worldwide morbidity and mortality. In this review, we examine the intricate relationships between COVID-19 and liver diseases. While respiratory manifestations of COVID-19 are well known, its impact and consequences in patients with liver diseases remain an area of ongoing investigation. COVID-19 can induce liver injury through various mechanisms and is associated with higher mortality in individuals with preexisting chronic liver disease. Mortality increases with the severity of chronic liver disease and the level of care required. The outcomes in patients with autoimmune hepatitis remain unclear, whereas liver transplant recipients are more likely to experience symptomatic COVID-19 but have comparable outcomes to the general population. Despite suboptimal immunological response, COVID-19 vaccinations are safe and effective in liver disease, although cases of autoimmune hepatitis-like syndrome have been reported. In conclusion, COVID-19 has significant implications in liver diseases; early recognition and treatments are important for improving patient outcomes., Competing Interests: K.Z., O.T., and D.C. have no conflicts of interests to declare. E.M.Y. is an investigator of clinical trials sponsored by Gilead Sciences, Pfizer, Genfit, Intercept, Celgene, Allergan, and Madrigal. E.M.Y. has received research funding from Paladin Labs Inc. T.H. has received research funding from Transplant Research Foundation of BC, and Paladin Labs Inc., (Thieme. All rights reserved.)

Background: Recreational cannabis was legalized in Canada in 2018. A controversial contraindication for liver transplantation is cannabis. There is currently no consensus regarding cannabis use in liver transplant candidates. We aim to investigate liver transplantation candidacy and outcomes among cannabis users., Methods: English peer-reviewed studies on PubMed and Google Scholar were searched on September 9, 2022, using keywords including "cannabis," "liver transplantation," and their synonyms. Titles and abstracts were screened, followed by full texts. Reference lists were reviewed. Studies that investigated liver transplantation candidacy and outcomes among cannabis users were included., Results: The proportion of patients listed for liver transplantation was significantly less among cannabis users than among non-users. Time to listing was longer for cannabis users than non-users. The incidence of delisting was similar. There is an inconsistency between transplant centres regarding transplantation candidacy for cannabis users. While only 14% of Canadian centres had a policy in place and preferred candidates to abstain or decrease cannabis use before transplantation, a third of Canadian centres rejected cannabis users. Observational studies failed to demonstrate significant differences in patient survival between pre-transplantation cannabis users and non-users. However, self-reported mental health ratings were worse in post-transplantation cannabis users than in non-users and former users., Conclusions: Current observational data do not support a link between cannabis use and poor patient survival post-transplantation. However, high-quality prospective studies are needed to better elucidate the impact of cannabis use on liver transplantation outcomes. Liver transplant candidacy should be evaluated through a multidisciplinary and comprehensive approach considering all relevant psychosocial factors., Competing Interests: T Hussaini has received a research grant in support of investigator-initiated research from Paladin Lab Incorporation. EM Yoshida has been an investigator on clinical trials sponsored by Gilead Sciences, AbbVie, Merck, Pfizer, Allergan, Madrigal, Intercept, Celgene, and Novodisc. EM Yoshida has received an unrestricted research grant from Paladin Laboratories, and has received honoraria for CME lectures from Intercept Canada., (© Canadian Association for the Study of the Liver, 2023.)

BACKGROUND: Albuminuria is a marker of chronic kidney disease (CKD) associated with an increased risk of end-stage kidney disease (ESKD) and mortality in the general population, but it is uncertain whether the same association exists in liver transplant (LT) recipients. This study examined the association between albuminuria and kidney failure and mortality in LT recipients. METHODS: Retrospective cohort study of 294 adults who received a LT between January 1, 1989, and December 31, 2011, in British Columbia, Canada. Cox multivariable regression was used to determine the association between ACR and a primary combined outcome of mortality, doubling of serum creatinine, or ESKD; and a secondary outcome of a decrease in estimated glomerular filtration rate (eGFR) ≥30%. RESULTS: At baseline, mean eGFR was 67 (SD 20.9) mL/min/1.73 m 2 , and 10% had severe albuminuria (ACR >30 mg/mmol). The primary outcome occurred in 20.4% (60) of patients and was associated with ACR >30 mg/mmol (HR 2.77, 95% CI 1.28-6.04; P = 0.01). A decline in eGFR ≥30% occurred in 21.8% (64) of patients, and was associated with ACR >30 mg/mmol (HR 4.77, 95% CI 2.31-9.86; P < 0.0001). CONCLUSIONS: Severe albuminuria (ACR >30 mg/mmol) was associated with an increased risk of loss of kidney function and mortality after LT. Prospective studies are needed to determine if specific interventions directed at reducing albuminuria can improve long-term outcomes in LT recipients., Competing Interests: The authors have nothing to disclose., (© Canadian Association for the Study of the Liver, 2023.)

The liver is considered the most immunotolerant organ among all solid-organ transplants. Liver transplant recipients have a lower incidence of rejection and better outcomes after episodes of rejection, with spontaneous operational tolerance developing in up to 20%. In multiorgan transplants, a protective effect of the liver allograft on simultaneously transplanted organs from the same donor has been demonstrated. We describe an unusual case of isolated liver allograft rejection in a patient with polycystic liver and kidney disease who received a combined liver-kidney transplant from the same donor. After initial discharge from the hospital, our patient had 2 episodes of biopsy-proven late acute cellular rejections, despite higher levels of immunosuppression required for her kidney allograft, which were addressed with pulsed steroid therapy. She had no evidence of ischemic cholangiopathy on imaging. Later, a subsequent liver biopsy demonstrated features consistent with chronic ductopenic rejection. She was eventually listed for liver retransplant and has recently received a second liver transplant while continuing to have no concerns with her kidney allograft function. Examination of the explanted liver confirmed graft loss from chronic ductopenic rejection. The exact reasons why our patient developed acute graft rejection progressing to chronic end-stage rejection of the liver allograft despite not developing graft rejection in the kidney allograft from the same donor remains elusive. Our experience demonstrates that graft tolerance in multiorgan transplant recipients can be organ specific and despite the belief of "immunologic privilege," isolated liver allograft rejection can occur in multiorgan transplant, resulting in graft loss., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series., Approach and Results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up., Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient., (© 2022 American Association for the Study of Liver Diseases.)

Data on the contribution of hepatitis B virus (HBV) infection and related comorbidities to liver-related mortality in Canada are limited. We assessed the concurrent impact of HBV infection, non-alcoholic fatty liver disease (NAFLD), and hepatitis C virus (HCV) coinfection on liver-related deaths in British Columbia (BC), Canada. We used data from the BC Hepatitis Testers Cohort (BC-HTC). We used Fine-Gray multivariable sub-distributional hazards models to assess the effect of HBV, NAFLD, and HCV coinfection on liver-related mortality, while adjusting for confounders and competing mortality risks. The liver-related mortality rate was higher among people with HBV infection than those without (2.57 per 1000 PYs (95%CI: 2.46, 2.69) vs. 0.62 per 1000 PYs (95%CI: 0.61, 0.64), respectively). Compared with the HBV negative groups, HBV infection was associated with increased liver-related mortality risk in almost all of the subgroups: HBV mono-infection (adjusted subdistribution hazards ratio (asHR) of 3.35, 95% CI 3.16, 3.55), NAFLD with HBV infection, (asHR 12.5, 95% CI 7.08, 22.07), and HBV/HCV coinfection (asHR 8.4, 95% CI 7.62, 9.26). HBV infection is associated with a higher risk of liver-related mortality, and has a greater relative impact on people with NAFLD and those with HCV coinfection. The diagnosis and treatment of viral and fatty liver disease are required to mitigate liver-related morbidity and mortality.

Background: Compared to other recreational substances in Canada, alcohol consumption incurs the highest healthcare costs. Liver transplant recipients are unique stakeholders as members of the general public with lived experiences of liver disease. We sought to explore their perspectives on the current state of public education on alcohol-related health effects., Methods: The most recent 400 liver transplant recipients at Vancouver General Hospital, Canada, were invited to participate in an anonymous online survey on alcohol-related health effects by mail, email, and phone., Results: Of 372 contacted patients, 212 (57%) completed the survey. Most patients were between 60-79 years, 63% were male, and 69% were Caucasian. The most common liver conditions leading to transplant were viral hepatitis (33%), alcohol-related liver disease (16%), autoimmune liver disease (14%), and non-alcoholic fatty liver disease (15%). Most patients knew that alcohol leads to liver failure (85%), but fewer knew about alcohol leading to cancer (54%), heart disease (50%), and damage to other organs (58%). Most common sources of information included public media (61%), family and friends (52%), and physicians (49%), with narrative comments about learning of alcohol-related health effects after liver diagnosis. Most patients believed that public health education at a middle/high school level would have long-term efficacy (72%) compared to health warning labels (33%) and safety messaging in commercials (39%). Current public education was felt to be adequate by only 20% of patients and 73% of patients supported health warning labels., Conclusions: Liver transplant patients reported a high, but not universal, awareness of alcohol-related health effects. A majority thought that current public health efforts were inadequate; it is critical to implement public health interventions to ensure consumers are able to make an informed decision on alcohol consumption., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jiang et al.)

BACKGROUND: The incidence of advanced unresectable hepatocellular carcinoma (HCC) is increasing in developed countries and the prognosis of advanced HCC remains poor. Real-world evidence of treatment patterns and outcomes can highlight the unmet clinical need. METHODS: We conducted a retrospective population-based cohort study of patients with advanced unresectable HCC diagnosed in Alberta, Canada (2008-2018) using electronic medical records and administrative claims data. A chart review was conducted on patients treated with systemic therapy to capture additional information related to treatment. RESULTS: A total of 1,297 advanced HCC patients were included of whom 555 (42.8%) were recurrent cases and the remainder were unresectable at diagnosis. Median age at diagnosis was 64 (range 21-94) years and 82.1% were men. Only 274 patients (21.1%) received first-line systemic therapy and, of those, 32 patients (11.7%) initiated second-line therapy. Nearly all of the patients received sorafenib (>96.4%) in first-line, and these patients had considerably higher median survival (12.23 months; 95% CI 10.72-14.10) compared with patients not treated with systemic therapy (2.66 months; 95% CI 2.33-3.12; log-rank p <0.001). Among patients treated with systemic therapy, overall survival was higher for recurrent cases, patients with Child-Pugh A functional status, and patients with HCV or multiple known HCC risk factors ( p <0.05). CONCLUSIONS: In a Canadian real-world setting, patients who received systemic therapy had greater survival than those who did not, but outcomes were universally poor. These results underscore the need for effective front-line therapeutic options., (Copyright © 2022 Canadian Association for the Study of the Liver.)

We report the case of a 28-year-old woman who presented with acute liver failure from suspected drug-induced liver injury. She was not vaccinated against COVID-19 and expressed considerable reluctance to become vaccinated, prompting discussions within the transplant group regarding her candidacy. She received a liver transplant and acquired COVID-19 immediately post-operatively that was treated with sotrovimab. She recovered well and was discharged shortly following her transplant. This case suggests that unwillingness to receive COVID-19 vaccination pre-transplant should not represent an absolute contraindication to a life-saving liver transplantation., (Copyright © 2022 Canadian Association for the Study of the Liver.)

BACKGROUND: Prior studies have assessed risk factors and clinical outcomes in liver transplant (LT) recipients infected with COVID-19 globally; however, there is a paucity of Canadian data. Our multicentre study aims to examine the characteristics and clinical outcomes of LT patients with COVID-19 infection in Canada. METHODS: Adult LT recipients with reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19, from Canadian tertiary care centres between March 2020 and June 2021 were included. RESULTS: A total of 49 patients with a history of LT and COVID-19 infection were identified. Twenty-nine patients (59%) were male, median time from LT was 66 months (IQR 1-128), and median age was 59 years (IQR 52-65). At COVID-19 diagnosis, the median alanine transaminase (ALT) was 37 U/L (IQR 21-41), aspartate aminotransferase (AST) U/L was 34 (IQR 20-37), alkaline phosphatase (ALP) U/L was 156 (IQR 88-156), total bilirubin was 11 μmol/L (IQR 7-14), and international normalized ratio (INR) was 1.1 (IQR 1.0-1.1). The majority of patients (86%) were on tacrolimus (monotherapy or combined with mycophenolate mofetil); median tacrolimus level at COVID-19 diagnosis was 5.3 μg/L (IQR 4.0-8.1). Immunosuppression was modified in eight (16%) patients post-infection. Eighteen patients (37%) required hospitalization, and three (6%) required intensive care unit (ICU) admission and mechanical ventilation. Four patients (8%) died from complications related to COVID-19 infection. On univariate analysis, neither age, sex, comorbidities, nor duration post-transplant were associated with risk of hospitalization or ICU admission. CONCLUSIONS: LT recipients with COVID-19 have high rates of hospitalization but fortunately have low rates of ICU admission and mortality in this national registry., (Copyright © 2022 Canadian Association for the Study of the Liver.)

Abstract: Effective pharmacologic treatment of primary sclerosing cholangitis (PSC) remains elusive. Ursodeoxycholic acid (UDCA) is known to improve liver biochemistry, specifically serum alkaline phosphatase, in patients with PSC but has not been shown to favourably alter the natural history. Similarly, many immunomodulatory medications have been studied for the treatment of PSC, but none has been demonstrated to be of unequivocal benefit. In this issue of the Journal, a pilot study of a ursodeoxycholate berberine salt vs placebo is reported. Although improvement in serum alkaline phosphatase is reported, without a control arm with UDCA monotherapy, it is not possible to determine whether this study drug is beneficial over UDCA by itself. More study in the PSC therapeutic arena is needed., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis are heterogeneous among studies and have not been sufficiently determined yet., Methods: The PubMed, EMBASE, and Cochrane Library databases were searched. Eligible studies would explore the prevalence and/or incidence of PVT in liver cirrhosis without hepatocellular carcinoma or abdominal surgery. Pooled proportion with 95% confidence interval (CI) was calculated using a random-effect model. Factors associated with the presence/occurrence of PVT were also extracted., Results: Among the 8549 papers initially identified, 74 were included. Fifty-four studies explored the prevalence of PVT in liver cirrhosis with a pooled prevalence of 13.92% (95%CI=11.18-16.91%). Based on cross-sectional data, Child-Pugh class B/C, higher D-dimer, ascites, and use of non-selective beta-blockers (NSBBs) were associated with the presence of PVT in liver cirrhosis. Twenty-three studies explored the incidence of PVT in liver cirrhosis with a pooled incidence of 10.42% (95%CI=8.16-12.92%). Based on cohort data, Child-Pugh class B/C, higher model of end-stage liver disease score, higher D-dimer, lower platelets count, decreased portal flow velocity, ascites, use of NSBBs, and moderate or high-risk esophageal varices could predict the occurrence of PVT in liver cirrhosis., Conclusion: Approximately one seventh of cirrhotic patients have PVT, and one tenth will develop PVT. Progression of liver cirrhosis and portal hypertension seems to be in parallel with the risk of PVT. Prospective studies with detailed information about classification and extension of PVT in liver cirrhosis are needed., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest in this study., (Copyright © 2022. Published by Elsevier B.V.)

Biliary tract cancer (BTC) is a group of rare and aggressive malignancies with a dismal prognosis. There is currently a significant lack in effective treatment options for BTC, with gemcitabine-cisplatin remaining the first-line standard of care treatment for over a decade. A wave of investigational therapies, including new chemotherapy combinations, immunotherapy, and biomarker-driven targeted therapy have demonstrated promising results in BTC, and there is hope for many of these therapies to be incorporated into the Canadian treatment landscape in the near future. This review discusses the emerging therapies under investigation for BTC and provides a perspective on how they may fit into Canadian practice, with a focus on the barriers to treatment access.

Background: Primary biliary cholangitis (PBC) is a rare, chronic autoimmune, cholestatic liver disease affecting approximately 318 per million Canadians. There is limited information regarding the characterization of this patient population in Canada. Consequently, we aim to describe a cohort of PBC patients managed across liver centres serving this type of population., Methods: A cross-sectional examination of 1,125 PBC patient charts at 15 liver centres across Canada was conducted between January 2016 and September 2017., Results: Data from 1,125 eligible patients were collected from 7 Canadian provinces. The patient population was largely female (90.2%), had a median overall age of 61.3 years, and a median overall time since diagnosis of 6.4 years. Of the patients included in the study, 89% were on ursodeoxycholic acid (UDCA) therapy at a median dose of 14.0 mg/kg/day and 4.4% were previously treated with UDCA, whereas 6.6% were never treated with UDCA. Of the patients with available data (n = 1067), 289 (27.1%) presented with alkaline phosphatase (ALP) levels ≥200 IU/L and/or total bilirubin levels ≥21 µmol/L. Assessment of UDCA treatment response revealed that 26.6% and 38.3% of patients were inadequate responders according to the Toronto and Paris-II criteria, respectively. Mortality occurred in 1.2% (14) of patients, with liver-related adverse outcomes being more commonly observed in patients who discontinued UDCA compared to those who are currently on treatment (36.3% and 19.6%, respectively)., Conclusion: This study showed that Canadian PBC patients present with demographics and features commonly reported in the literature for this disease. Over one third of PBC patients had inadequate response to UDCA treatment or were not currently being treated with UDCA. Consequently, there is a significant unmet therapeutic need in this Canadian PBC population., Competing Interests: EM Yoshida has received an unrestricted research grant from Paladin Laboartories and clinical trials sponsorship from Gilead Sciences, Intercept, Abbvie, Merck, Genfit, Pfizer, Celgene, Allergan, and Madrigal. He has also received honoraria for CME/Ad Board lectures from Intercept, Gilead, and Merck. He is President of the Vancouver Medical Dental Allied Staff Association; C Tsien received grants/contracts from Lupin, and payment or honoraria for lectures, presentations, speaker bureaus, or educational events from Abbvie and Intercept; MG Swain received grants/contracts for research studies from Gilead, Intercept, CymaBay, Genkyotex, GSK, Genfit, Novartis, Pfizer, Celgene, AstraZeneca, AbbVie, and Novo Nordisk, payment or honoraria for lectures and presentations from Gilead, Intercept, and AbbVie, and participated on the advisory boards for Gilead, Novartis, and Intercept; KM Peltekian participated on the advisory board for Intercept and has held a leadership or fiduciary role on the Canadian Liver Foundation board; MA Puglia has received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Intercept as well as support from them for attending meetings and/or travel and participating on their advisory board; M Elkhashab has received consulting fees and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AbbVie, Gilead, and Merck, as well as participated on the advisory boards for AbbVie, Gilead, and Merck; M O’Brien has received payment or honoraria for lectures, presentations, speaker bureaus, or educational events from Intercept; HH Ko has received payment or honoraria for lectures, presentations, speaker bureaus, or educational events from Intercept and has held a leadership or fiduciary role on the Intercept advisory board; E Tam has received consulting fees from Intercept as well as payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Intercept; A Ramji has received grants/contracts from AbbVie, Allergan, Assembly, Galmed, Gilead, Janssen, Intercept, Novartis, and Merck, as well as payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AbbVie, Allergan, Amgen, Celgene, Gilead, Intercept, Amgen, Janssen, Novartis, and Merck. He has participated on advisory board for AbbVie, Gilead, Janssen, Intercept, Novartis, Merck, and Novo Nordisk; the other authors have nothing to disclose., (Copyright © 2022 Canadian Association for the Study of the Liver.)

Background: The frequency with which patients with high Model for End-Stage Liver Disease (MELD) scores undergo liver transplantation has been increasing. Canadian literature regarding the outcomes of liver transplantation in recipients with high MELD scores is limited. The primary objective of this study was to assess patient and graft survival among recipients with high (> 35) and low (≤ 35) MELD scores. Secondary objectives were to potentially identify independent predictors of graft failure and patient mortality., Methods: We conducted a retrospective chart review of patients undergoing liver transplantation at a single Canadian centre from 2012 to 2017., Results: A total of 332 patients were included in the study: 280 patients had a MELD score of 35 or lower, and 52 had a MELD score above 35. Patients with high MELD scores had higher rates of pretransplant acute kidney injury and dialysis ( p < 0.001), admission to the intensive care unit (ICU) or intubation ( p < 0.001), intraoperative blood product transfusions ( p < 0.001) and post-transplantation acute kidney injury and dialysis ( p < 0.001), as well as longer ICU ( p < 0.001) and hospital stays ( p = 0.002). One- and 3-year patient survival in recipients with MELD scores of 35 or lower was 93.1% and 84.9% versus 85.0% and 80.0% in recipients with MELD scores above 35 ( p = 0.37). One- and 3-year graft survival in recipients with MELD scores of 35 or lower was 91.7% and 90.9% versus 77.2% and 72.8% in recipients with MELD scores above 35 ( p < 0.001). Prior liver transplant was an independent predictor of patient mortality, and no independent predictors of graft failure were identified. When MELD was replaced with D-MELD (donor age × recipient MELD), it predicted graft failure but not patient survival., Conclusion: No difference in patient mortality was found between MELD groups. Graft survival was significantly lower in recipients with MELD scores above 35. D-MELD may potentially be used as an adjunct in determining risk of graft failure in recipients with high MELD scores., Competing Interests: Competing interests: V. Marquez has received personal fees from Abbott Laboratories and Intercept Pharmaceuticals and support for attending meetings and/or travel from Intercept Pharmaceuticals. He has participated on a data safety monitoring board or advisory board for AbbVie, Paladin Labs, Eisai and Lupin Pharma. E. Yoshida has been an investigator for clinical trials sponsored by Gilead Sciences, AbbVie, Merck, Genfit, Pfizer, Intercept Pharmaceuticals, Calgene, Novo Nordisk, Allergan and Madrigal Pharmaceuticals. He has received an unrestricted research grant from Paladin Labs and speaker fees from Gilead Sciences Canada, AbbVie Canada and Merck Canada. S. Chartier-Plante has received consulting fees from Paladin Labs. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Alcohol is consumed by approximately three-quarters of Canadians. Alcohol causes acquired liver disease, increases the risk of cancer, has detrimental effects on mental health, and leads to adverse pregnancy outcomes. Alcohol-related morbidity and mortality are high, and urgent public health measures are warranted to prevent and control these. Tobacco safety labels have been shown in numerous studies to reduce tobacco consumption. Much can be learned from the design of tobacco safety labels in creating promising alcohol safety labels that can possibly help reduce alcohol consumption. The aim of this paper is to review the efficacy of tobacco safety labels in reducing tobacco consumption and the design of tobacco safety labels and to propose a promising design for alcohol safety labels based on our findings. English peer-reviewed papers published in western countries since 2000 were searched on PubMed and Google Scholar. Keywords and synonyms were used to search pertinent papers, which were subsequently screened by title and abstract and fully reviewed if relevant. Findings from studies comparing designs of safety labels on alcohol and tobacco products are similar. Graphics, higher emotion content, and greater size are associated with greater attention, awareness, negative emotions, intention to quit, and reduction in consumption. Mixed results are found for testimonials containing safety labels on tobacco products. It is unclear whether testimonials on alcohol safety labels reduce alcohol consumption or not. Safety labels with specific information, such as tobacco-related costs and alcohol-related cancer risks, are more effective in reducing tobacco consumption. In conclusion, preliminary alcohol safety labels show promise. Large safety labels with graphics and high emotional content appear to be most effective and may reduce alcohol consumption., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Yau et al.)