Abstract Background: This umbrella review synthesizes evidence from meta-analyses and reviews comparing transarterial chemoembolization (TACE) combined with sorafenib versus monotherapy for unresectable hepatocellular carcinoma. Methods: Following PRIOR guidelines, PubMed, Google Scholar, Web of Science, and Embase were searched from inception to December 2024. Outcomes included overall survival (OS), time to progression (TTP), disease control rate (DCR), and objective response rate (ORR). Corrected covered area (CCA) assessed overlap, and methodological quality was evaluated using AMSTAR-2. Results: Of 13,821 records, 9 meta-analyses were included, with substantial overlap (CCA: 49%). Eight reviews assessed OS; five reported a significant survival benefit (hazard ratio [HR] 0.62–0.74, p < 0.001), while two found no significant effect (HR 0.75–0.97, p > 0.05). Eight evaluated TTP; six showed a significant reduction in risk (HR 0.61–0.75, p < 0.05), while two reported non-significant findings (HR 0.74–0.77, p > 0.05). Four assessed DCR; two reported a significant benefit (odds ratio [OR] 0.52–4.72, p < 0.01), one showed a non-significant trend (OR: 1.57, p = 0.06), and one found no significant effect (relative risk [RR] 1.04, p = 0.57). Six assessed ORR; three reported a significant increase in response (OR 2.19–3.59, p < 0.01), one showed a significant reduction (OR 0.85, p < 0.001), one found no significant effect (RR 1.20, p = 0.26), and one reported a significant protective effect (OR 0.39, p = 0.008). Conclusions: TACE plus sorafenib improves TTP, ORR, and OS in unresectable HCC and highlights the need for personalized treatment and further research.
Abstract Background: Despite primary care's role in hepatitis C elimination, evidence of primary care providers’ involvement remains limited. To enhance our knowledge of health care use among hepatitis C–infected individuals, we described trends in hepatitis-related visits and patients’ characteristics by provider specialty in Quebec. Methods: We conducted a population-based cohort study using all hepatitis C cases in the Quebec Mandatory Reportable Disease database (1990–2018), linked with the provincial physician billing database. We described monthly rates of hepatitis-related medical visits using a generalized additive model across different provider specialties and stratified our results by at-risk populations. Results: Between 1990 and 2018, 37,251 patients were diagnosed with hepatitis C. Visit rates were lower for other specialties compared to gastroenterologists; rate ratios (RRs) were 0.73 (95% CI 0.67–0.79) for general practitioners/family physicians (GPs/FPs) and 0.24 (95% CI 0.21–0.26) for internal medicine physicians. The RR for GPs/FPs was 1.21(95% CI 1.05–1.39) among people who inject drugs (PWID), 0.76 (95% CI 0.71–0.82) among the 1945–1975 birth cohort, and 0.37 (95% CI 0.28–0.49) among immigrants, compared to gastroenterologists. Patients seen primarily by GPs/FPs were more likely to have a history of drug use and mental health disorders than those seen by specialists. Conclusions: Hepatitis C cases were more likely to be seen by gastroenterologists than by GPs/FPs in Quebec from 1990 to 2018. However, GPs/FPs had higher visit rates for PWID. Specialists more often managed immigrants and the 1945–1975 cohort. These findings suggest disparities in care access and emphasize GPs/FPs’ role in managing hepatitis C among marginalized populations.
Abstract Metabolic dysfunction–associated steatotic liver disease (MASLD) is a leading and increasingly prevalent cause of chronic liver disease, cirrhosis, hepatocellular carcinoma, and liver transplantation in Canada. This Canadian Association for the Study of the Liver clinical practice guidance provides pragmatic recommendations for MASLD assessment and management across Canadian health care settings. Guidance statements were developed by a multidisciplinary national steering committee using the best available evidence, targeted literature review, expert consensus, and a modified Delphi process. This document summarizes Canadian epidemiology and natural history, nomenclature, identification of populations at increased risk, screening and advanced fibrosis risk stratification, federal and provincial health policy, remote and community care delivery, and management across the MASLD disease spectrum. MASLD screening is recommended for adults with type 2 diabetes mellitus, obesity, cardiometabolic risk factors, hepatic steatosis, family history of MASLD cirrhosis, or persistently abnormal liver tests. A stepwise approach for at-risk populations, using simple blood-based tests, such as FIB-4, followed by imaging elastography or Enhanced Liver Fibrosis score, to rule advanced fibrosis in or out is appropriate. For children with MASLD, a multidisciplinary approach to management is recommended and should include lifestyle counselling, cardiometabolic risk reduction, treatment of obesity and type 2 diabetes mellitus, and approved therapy for non-cirrhotic MASLD as appropriate. The guidance also highlights gaps in Canadian population-level data in disease surveillance; Indigenous, ethnic-diverse, and equity-deserving cohorts; natural history, prevalence, and risk stratification for pediatric MASLD; epidemiology of MetALD; and varying provincial access to non-invasive tests and multidisciplinary care for persons with MASLD.
Abstract Introduction: We describe the association between cirrhosis and outcomes among patients treated for non-small cell lung cancer (NSCLC). Methods: NSCLC cases in 2007–2017 in Ontario, Canada, were reviewed. Cirrhosis was identified using validated coding. The association between cirrhosis and outcomes was evaluated using logistic regression, Kaplan–Meier curves, and adjusted survival models. Results: Among patients with stage 1–3 NSCLC receiving lung resection (n = 59,226), 3% had cirrhosis with higher 30-day (5% versus 2%, p < 0.001) and 90-day (8% versus 3%, p < 0.001) mortality. After multivariable logistic regression, cirrhosis was associated with higher mortality odds at 30 days (OR 2.35, 95% CI 1.39–3.99, p < 0.001) and 90 days (OR 2.10, 95% CI 1.38–3.21, p < 0.001); higher 90-day post-operative complications odds (OR 1.44, 95% CI 1.14–1.81, p = 0.002); and higher hospital readmission odds at 30 days (OR 1.90, 95% CI 1.41–2.56, p < 0.001) and 90 days (OR 1.63, 95% CI 1.27–2.10, p = 0.001). Among those with stage 4 NSCLC (n = 27,357), adjusted Cox regression showed cirrhosis was associated with higher mortality (HR 1.10, 95% CI 1.02–1.18, p = 0.016). However, when liver-related mortality was a competing event, association between cirrhosis and cancer-specific mortality was absent (sHR 1.04, 95% CI 0.95–1.13, p = 0.395). A lower proportion of patients with cirrhosis received systemic treatments (31% versus 40%, p < 0.001), and a greater proportion experienced post-treatment complications: electrolyte disturbances (10% versus 5%, p < 0.001), kidney injury (5% versus 2%, p = 0.012), and thrombocytopenia (7% versus 2%, p < 0.001). Conclusions: Cirrhosis is associated with increased morbidity and mortality in stage 1–3 NSCLC patients undergoing curative surgery. Stage 4 NSCLC patients with cirrhosis are less likely to receive palliative treatment and may experience more post-treatment complications.
BACKGROUND: Metabolic health significantly impacts long-term survival among liver transplant (LT) recipients. Emerg- ing evidence suggests that metabolic health in the general population is related to skeletal muscle quality. However, this has not been well investigated in the transplant patient population. While myosteatosis, characterized by fat infiltration into skeletal muscle, has been closely associated with metabolic health in the general population, it has not been thoroughly explored as a risk factor for outcomes in LT recipients. METHODS: In this retrospective cohort study of 503 adult LT recipients at the University Health Network, we evaluated the prognostic value of myosteatosis on post-transplant survival and cardiometabolic outcomes. Pre-transplant contrast-enhanced CT scans of LT recipients within 6 months prior to transplantation were analyzed using the nnU-Netv2 convolutional neural network, and myosteatosis was quantified by skeletal muscle radiation attenuation adjusted for BMI. RESULTS: The mean age of LT recipients was 56.89 years; patients with myosteatosis were significantly older (58.69 y) than those without (54.96 y). LT recipients were predominately male (75.9%). Cox proportional hazards models showed that myosteatosis independently predicted both all-cause mortality (HR 1.50 [95% CI 1.06-2.12]; P = 0.024 ) and the incidence of post-transplant metabolic dysfunction-associated steatotic liver disease (MASLDratio [HR] 2.25 [95% CI 1.28-3.98]; p = 0.0051). Notably, cardiovascular disease, diabetes mellitus, and malignancy did not differ significantly by myosteatosis status. CONCLUSIONS: The presence of myosteatosis could identify LT recipients at higher risk for metabolic complications. As a modifiable and non-invasive biomarker, the presence of myosteatosis could guide personalized interventions to improve long-term outcomes.
Chronic hepatitis B virus (HBV) infection remains a major global health challenge, affecting over 300 million people worldwide and contributing substantially to liver-related morbidity and mortality. Despite the availability of effective vaccination, diagnostic tools, antiviral therapy, and surveillance strategies, progress toward the World Health Organization's hepatitis elimination targets has been slower than anticipated. HBV-related stigma has emerged as a critical and under-recognized barrier undermining efforts across the entire HBV care cascade. Stigma associated with HBV is multi-faceted, encompassing internalized, social, systemic, and health care-related forms, and is driven largely by misconceptions surrounding transmission, moral judgment, and disease prognosis. These stigmatizing beliefs negatively impact testing uptake, disclosure, linkage to care, treatment adherence, and long-term surveillance while also contributing to psychosocial distress and reduced quality of life among people living with HBV. This narrative review synthesizes current literature on the manifestations and consequences of HBV-related stigma, examines its impact on global hepatitis elimination efforts, and highlights strategies to mitigate stigma through targeted education, culturally sensitive interventions, and health care provider training.
Background: Frailty is a predictor of disease progression in cirrhotic patients. Prehabilitation programs are helpful interventions to reduce frailty and worsening sarcopenia. Methods: This was a single-group, pre-post feasibility study of a 6-week home pedometer-monitored program with the goal of achieving a weekly compound 5%-10% step increase and thereby decreasing frailty in cirrhotic patients. A review of patients was performed 3 years after the intervention to assess clinical status and walking levels. Results: Sixty-three cirrhotic patients were recruited and 71% completed the study. At the end of week 6, mean steps per day had increased by 37% from 3,394 at baseline to 4,500 (p < 0.001), with a mean weekly compound increase of 6.4%. For study completers, the mean Fried frailty index (FFI) score improved from 2.64 at baseline to 2.24 at the end of the intervention (p = 0.007). Patients with Model of End-Stage Liver Disease-Sodium (MELD-Na) scores <15 had significantly improved mean FFI scores, from 2.74 to 2.26 (p = 0.007); those with scores >= 15 did not have significant improvement. At the 3-year follow-up, 18% of patients had died, 13% had undergone liver transplantation, and 37% self-reported that they were walking more than before the intervention. Conclusions: These findings suggest the 6-week home pedometer-monitored program is feasible but is best suited for cirrhotic patients whose disease has not advanced to levels where they are considered for transplantation, as indicated by MELD-Na scores >= 15.
BACKGROUND: Hepatitis B virus (HBV) reactivation is a well-recognized complication of immunosuppressive therapy in patients with hematologic malignancies. It usually occurs in those with chronic or resolved HBV infection identified by positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc). Reactivation in patients who test negative for both markers is exceedingly rare and poses a diagnostic challenge. METHODS: We report on three patients with hematologic malignancies who developed HBV reactivation despite negative baseline serology. Cases were identified and managed at a tertiary liver centre in Canada. Clinical, virologic, and treatment data were reviewed, including HBV serology, viral load, chemotherapy exposure, and outcomes following antiviral therapy. RESULTS: All three patients originated from HBV-endemic regions and had received potent immunosuppressive regimens, including B cell-depleting agents or hematopoietic stem cell transplantation. Two were completely seronegative (HBsAg-/anti-HBc-/hepatitis B surface antibody [anti-HBs]-negative), and one had isolated anti-HBs positivity that was subsequently lost before reactivation. HBV DNA became detectable months to years after treatment initiation. All patients received antiviral therapy with entecavir or tenofovir, resulting in viral suppression and biochemical recovery. CONCLUSIONS: This case series highlights a critical limitation of current HBV screening strategies that rely solely on antibody-based testing. Loss of humoral immunity may obscure prior HBV exposure, leading to unrecognized reactivation risk. Clinicians should maintain a high index of suspicion and consider serial ALT and HBsAg monitoring in immunosuppressed patients with humoral (B cell) immune deficiencies, particularly those from HBV-endemic regions.
Background: Steatotic liver disease (SLD) is increasingly common in patients with primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). We sought to determine the prevalence and clinical impact of SLD among Southeast Asian patients with PBC, AIH, and AIH/PBC overlap syndrome.Methods: We included all patients diagnosed with PBC, AIH and AIH/PBC overlap syndrome between 2000 and 2024. SLD was defined based on either radiological or histological evidence of hepatic steatosis. The primary outcomes were all-cause mortality, treatment response, liver-related events (LRE), and major adverse cardiovascular events (MACE).Results: Among 273 patients (PBC: 184, AIH: 69, AIH/PBC overlap syndrome: 20), one third had concomitant SLD. Patients with PBC/SLD were more likely to have a higher BMI (24.6 versus 22.6 kg/m2, p = 0.002) and less likely to have liver cirrhosis (36.7% versus 59.3%, p = 0.011) than PBC without SLD. AIH patients had a significantly higher risk of developing de novo SLD. Patients with PBC/SLD have a significantly lower risk of all-cause mortality (unadjusted HR 0.33, adjusted HR 0.18, p < 0.05 for both). Concomitant SLD did not influence the treatment response, occurrence of LRE, or MACE in patients with PBC, AIH, or AIH/PBC overlap syndrome.Conclusions: Concomitant SLD does not influence treatment response, liver-related events, or cardiovascular outcomes in patients with autoimmune liver disease.
Background:Electronic medical record (EMR)-based quality improvement (QI) tools for cirrhosis care require accurate patient identification. Combining administrative and EMR data may enhance cirrhosis identification. This study aims to validate the Alberta code set (a hybrid code set using both administrative and EMR data) for identifying patients with cirrhosis. Methods:Twelve high-performing ICD-10 codes (Alberta code set) were evaluated using a cohort of 719 chart review-confirmed cirrhosis patients. Validation was performed in an independent cohort of 913 consecutively admitted patients at four Albertan hospitals (two tertiary and two non-urban). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were obtained with a 95% CI. Two other code sets (Shearer and SoLiDaRity-10) were also validated using administrative-only, EMR-only, or hybrid data. Results:Using administrative data alone, the Alberta code set showed a sensitivity of 78.9%, specificity of 97.4%, PPV of 80.4%, and NPV of 97.2%. With hybrid data, sensitivity improved to 87.2% and NPV to 98.2%, while specificity (96.5%) and PPV (77.2%) remained similar. Urban sites showed higher sensitivity (86.2% and 91.7%) than non-urban sites (70% and 82.1%), likely attributed to coding practice variability. The Shearer and SoLiDaRity-10 code sets also demonstrated high sensitivity (86.2% and 83.5%, respectively) and similar specificity (96.6 and 97.1, respectively) when using hybrid data rather than either admin data or EMR data alone. Conclusions:A hybrid administrative and EMR-based approach effectively identifies in-patient cirrhosis cases across health care settings and holds promise to support QI and research for cirrhosis patients.
Background: Patient-partnered basic and translational research is the most productive and meaningful approach to developing informed research questions, generating high-quality data, and producing impactful work. While several organizations have published guidelines for patient-partnered research, few experiential reports in basic science are written from both the patient and researcher perspectives and comment on real-time practical challenges and approaches that ensure the establishment and maintenance of a non-tokenistic, organized, and successful research partnership with patient partners.Methods: We describe patient partners' and researchers' experiences working together in a basic science and translational research team studying the drivers of primary sclerosing cholangitis, a rare liver disease for which liver transplantation remains the only treatment to disrupt disease progression. We outline approaches used to support meaningful communication, collaboration, and shared output among project stakeholders, drawing on the perspectives of both basic science researchers and patient representatives involved in long-standing joint research projects.Results: Several practical elements support the success of patient partnership in basic and translational science, including structured communication, clear role definition, mutual respect, sustained engagement, and intentional mechanisms to support patient partners' meaningful contributions. We highlight challenges and strategies used to address them in real time, offering insight into how patient-researcher partnerships can be maintained in an organized, authentic, and non-tokenistic way.Conclusions: This review highlights a patient-partnered research team's experiential insights to bridge the gap between published guidance and real-world practice, reinforcing how authentic patient-researcher partnerships can drive more inclusive and impactful basic and translational science.
Background:Sarcopenia is associated with increased mortality in patients with cirrhosis, but this association remains unclear when adjusted for portal hypertension. We investigated the association of muscle mass and portal hypertension on liver-related events. Methods:This retrospective study (2012-2022) included adult patients with cirrhosis and available hepatic venous pressure gradient (HVPG). Total cross-sectional skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI) at the third lumbar vertebrae (L3) were measured at the time of HVPG using CT imaging. Sarcopenia is defined as L3-SMI <39 cm2/m2 in female and <50 cm2/m2 in male patients. Logistic regression analyses assessed sarcopenia predictors; Cox regression analyses assessed liver-related events and mortality predictors. Results:A total of 121 patients were included (sarcopenia: 46%, female: 62%, mean age: 58.3 years, MASLD: 34%, median HVPG: 10 mmHg, median MELD score: 13, prior decompensation: 55%). Sarcopenia was more likely in patients with prior decompensation (70% versus 43%, p < 0.003), lower alanine aminotransferase (ALT) (21 versus 40 U/L, p < 0.001), and lower SATI (37.4 versus 76.4 cm2/m2, p < 0.001). After age, prior decompensation, and ALT adjustments, SATI remained an independent predictor of sarcopenia (adjusted odds ratio aOR 0.98 [95% CI 0.97-0.99]). Over a median follow-up of 14.5 months, 59% had liver-related events and 29% died. After HVPG and MELD adjustments, which were significant factors, L3-SMI remained a predictor of liver-related events (adjusted hazard ratio [aHR] 0.98 [95% CI 0.95-0.99]) and mortality (aHR 0.96 [95% CI 0.92-0.99]). Conclusions:Our study demonstrates that low muscle mass predicts liver-related events and mortality independently of portal hypertension and liver disease severity.
Background: Canada has committed to eliminating hepatitis C virus (HCV) by 2030. Despite highly effective treatments, screening and treatment uptake remains suboptimal. Immigrants from HCV-endemic countries account for 35% of HCV cases and face distinct barriers to care. This study explored health care providers’ perspectives on barriers and facilitators to providing HCV screening and treatment among immigrant populations. Methods: We conducted a qualitative descriptive study guided by the Theoretical Domains Framework (TDF). Semi-structured interviews were performed with health care providers in two Canadian cities. Transcripts were independently coded by two researchers, and key themes were identified. Results: Twelve health care providers (7 female, 5 male) were interviewed, including eight family doctors, two infectious disease specialists, one nurse, and one social worker. Participants identified multiple barriers including limited familiarity with immigrants’ specific clinical guidelines, low confidence in managing HCV, and difficulty addressing culturally sensitive issues. Providers perceived patient-related barriers, such as stigma, limited awareness, and competing life priorities, as factors that may hinder engagement with HCV care. Language and communication challenges frequently interfered with care. System-level issues, including fragmented services, long wait times, and shortages of family physicians, further constrained access. Conclusion: This study underscores the complex barriers health care providers face in delivering HCV care to immigrant populations in Canada. While some challenges reflect broader health care system gaps, they are compounded for immigrants by linguistic and cultural differences. Strengthening provider capacity, improving system coordination, and embedding culturally and linguistically responsive approaches are essential to advancing HCV elimination.
Background: Alcohol-associated liver disease (ALD) is a growing health care concern, with alcohol use disorder (AUD) being a contributor to liver-related morbidity and mortality. This study examines the practices, perspectives, and challenges faced by Canadian health care providers in managing AUD within the context of ALD. Methods: A nationally representative survey was conducted among health care providers involved in ALD management. The survey evaluated practices related to AUD screening, prescribing pharmacotherapy, addiction services referral, and perceived barriers. Results: Alcohol use screening was common (75%), but standardized tools were rarely used (<10%), with barriers including time constraints (61%) and resource limitations (60%). Less than 15% of patients received AUD pharmacotherapy, with lack of training identified as a key barrier. Notably, 47% of providers had never prescribed AUD pharmacotherapy due to low comfort levels (78%). Early and mid-career providers were more likely to prescribe AUD pharmacotherapy compared to their senior counterparts (71% versus 61%, p = 0.02). Acamprosate and naltrexone were the most frequently prescribed medications. Behavioural therapy referrals were reported by 57% of respondents, although patient reluctance (70%) and financial barriers (53%) hindered access. Knowledge gaps regarding AUD pharmacotherapies were prevalent. Conclusions: This study reveals significant gaps in AUD management within ALD care, marked by insufficient screening, underuse of pharmacotherapies, and limited referrals to addiction services. Addressing these issues requires urgent attention through enhanced provider education, integration of addiction care, and systemic reforms. Collaborative efforts among all health care providers are essential to improving care delivery and outcomes for individuals with ALD and AUD.
Background:Patients with primary sclerosing cholangitis (PSC) are at risk for developing gallbladder neoplasia (GBN) and biliary neoplasia, including cholangiocarcinoma (CCA), because of chronic inflammation and an underlying field effect. However, the risk of CCA after GBN detection in those with PSC remains poorly understood. We aimed to determine if the incidence of CCA is higher in those with GBN. Methods:We conducted a retrospective review of adult patients with large-duct PSC seen at Mayo Clinic between January 1, 1995, and December 31, 2019. Incidence rates for CCA development were calculated. Cox regression analyses were performed to determine features associated with CCA development beginning at the time of PSC diagnosis. Results:Our study included 1,829 patients with PSC. CCA and GBN developed in 334 (18.26%) and 71 individuals (3.88%), respectively. Among those with GBN, 14 (19.72%) developed CCA. The annual incidence of CCA was nearly twofold higher in patients with GBN (4.34% versus 2.21%). GBN was associated with CCA in an unadjusted analysis (hazard ratio 2.14 [95% CI 1.16-3.94]). When adjusting for other predictors of CCA, an association between GBN and CCA may remain. Conclusions:While few patients with PSC develop GBN, this subgroup is more likely to develop CCA. Consequently, once GBN is detected, clinicians should consider more intensive screening for CCA.
Introduction: Liver transplantation (LT) is vital for patients with end-stage cirrhosis, but survival is compromised by recurrent graft cirrhosis in 25% of recipients due to de novo or recurrent disease. This study aims to understand the trajectory, predisposing factors, and complications of graft cirrhosis to improve management in this patient population.Methods: We retrospectively reviewed 454 LT recipients diagnosed with graft cirrhosis from January 1, 1985, to December 31, 2019. We collected demographic, clinical, laboratory, imaging, endoscopic, and histological data. Statistical analysis was done with univariate and multivariate analyses.Results: Graft cirrhosis was frequently due to recurrent primary disease, with hepatitis C (49.2%) and graft rejection (9.6%) being primary contributors. Signs of decompensation, including primarily ascites, were seen in 12% of patients, with an 18% mortality rate at first decompensation. MELD-Na >15 was found in 62% of patients, driven by creatinine levels. Of note, 42% experienced portal hypertensive complications before deterioration in their synthetic function. Predictors of mortality included lower serum sodium, elevated aspartate transaminase, and older donor age. Only two patients developed de novo hepatocellular carcinoma (HCC). The Baveno VII criteria for varices needing treatment showed high sensitivity (100%) with moderate specificity (46.7%).Conclusions: Portal hypertensive complications often precede synthetic dysfunction in graft cirrhosis patients. Clinicians should screen for portal hypertensive complications, de novo HCC, and biochemical decompensation following graft cirrhosis. Early intervention can improve outcomes and prolong survival in LT recipients with graft cirrhosis.
