Treatment response and clinical event-free survival in autoimmune hepatitis: A Canadian multicentre cohort study.

BACKGROUND & AIMS: Treatment outcomes for people living with autoimmune hepatitis (AIH) are limited by a lack of specific therapies, as well as limited well-validated prognostic tools and clinical trial endpoints. We sought to identify predictors of outcome for people living with AIH. METHODS: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis. RESULTS: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12 months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and IgG values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased the risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival. CONCLUSION: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose. IMPACT AND IMPLICATIONS: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, and uses continuous measurements over follow-up. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side effects.

Emergency Department Utilization and Outcomes Among Adults With Cirrhosis From 2008 to 2022 in the United States.

BACKGROUND & AIMS: Globally, emergency departments (ED) are experiencing rising costs and crowding. Despite its importance, ED utilization and outcomes among patients with cirrhosis are understudied. METHODS: We analyzed Optum's de-identified Clinformatics Data Mart Database, between 2008 and 2022, including adults with at least 180 days of enrollment. Liver transplant recipients were censored at the year of transplant. ED visits (stratified by liver vs non-liver related) were identified using validated billing code definitions. Linear regression was used to assess ED visits per year, and logistic regression was used to assess 90-day mortality rates and discharge dispositions, with models adjusted for patient- and visit-level characteristics. RESULTS: Among 38,419,650 patients, 198,439 were with cirrhosis (median age, 66 [interquartile range, 57-72 years]; 54% male; 62% White). In age-adjusted analysis, ED visits per person-year were 1.72 (95% confidence interval [CI], 1.71-1.74) with cirrhosis vs 0.46 (95% CI, 0.46-0.46) without cirrhosis, 1.66 (95% CI, 1.66-1.66) for congestive heart failure (CHF), and 1.22 (95% CI, 1.22-1.22) for chronic obstructive pulmonary disease (COPD). Age-adjusted 90-day mortality rates were 12.2% (95% CI, 12.1%-12.4%) with cirrhosis vs 4.8% [95% CI, 4.8%-4.8%) without cirrhosis, 6.9% (95% CI, 6.9%-6.9%) for CHF, and 6.3% (95% CI, 6.3%-6.4%) for COPD. Non-liver (vs liver-related) ED visits were more likely to lead to discharge home among patients with compensated (52.8%; 95% CI, 52.2%-53.5% vs 39.2%; 95% CI, 38.5%-39.8%) and decompensated (42.2%; 95% CI, 41.5%-42.8% vs 29.5%; 95% CI, 29.0%-30.1%) cirrhosis. In exploratory analysis, among patients who remained alive and were not readmitted for 30 days after ED discharge, those without any outpatient follow-up had higher 90-day mortality (22.0%; 95% CI, 21.0%-23.0%) than those with both primary care and gastroenterology/hepatology follow-up within 30-days (7.9%; 95% CI, 7.3%-8.5%). CONCLUSIONS: Patients with cirrhosis have higher ED utilization and almost 2-fold higher post-ED visit mortality than CHF and COPD. These findings provide impetus for ED-based interventions to improve cirrhosis-related outcomes.

Global Epidemiology of Cirrhosis in Women.

Recent epidemiological evidence indicates a significant rise in cirrhosis burden over the past two decades in all parts of the world, with cirrhosis incidence rates and related deaths escalating quickly. Women face unique risk factors and susceptibility to chronic liver diseases compared to men, underscoring the need for a sex-specific approach in early identification, reversal of causative factors, and complications prevention. This review aims to explore epidemiological trends and sex-specific factors contributing to the global epidemiology of cirrhosis among females today. While cirrhosis prevalence remains higher in males globally, the incidence rate from 2010 to 2019 grew faster among females. The female-to-male incidence ratio of metabolic-associated steatotic liver disease (MASLD) related cirrhosis globally in 2019 was 1.3, indicating a shifting trend towards new diagnoses among women now surpassing that of men. Alcohol-associated cirrhosis (AC) epidemiology is also changing, with trends towards equal incidence of AC between both sexes, particularly in industrialized nations with increased alcohol accessibility. Cirrhosis from viral hepatitis remains the main etiology among females in endemic regions. Sex differences in epidemiology are likely multifactorial, influenced by varying risk factors, susceptibility and behaviors between sexes. Further research is necessary to better understand these disparities and to tailor sex-specific interventions towards improved management and treatment strategies, ultimately enhancing outcomes for women with cirrhosis and providing better patient-centered care.

Maternal neighbourhood-level social determinants of health and their association with paediatric hepatitis C screening among children exposed to hepatitis C in pregnancy.

BACKGROUND: Current guidelines recommend HCV screening by 18 months of age for those exposed to HCV in utero; yet, screening occurs in the minority of children. OBJECTIVES: To evaluate the association between maternal neighbourhood-level social determinants of health (SDOH) and paediatric HCV screening in the general population in a publicly funded healthcare system in Canada. METHODS: Retrospective cohort study using administrative healthcare data held at ICES. Children born to individuals positive for HCV RNA in pregnancy from 2000 to 2016 were identified and followed for 2 years. Major SDOH were identified, and the primary outcome was HCV screening in exposed children (HCV antibody and/or RNA). Associations between SDOH and HCV screening were determined using multivariate Poisson regression models adjusting for confounding. RESULTS: A total of 1780 children born to persons with +HCV RNA were identified, and 29% (n = 516) were screened for HCV by age two. Most mothers resided in the lowest income quintile (42%), and most vulnerable quintiles for material deprivation (41%), housing instability (38%) and ethnic diversity (26%) with 11% living in rural locations. After adjustment for confounding, maternal rural residence (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.62, 1.07) and living in the highest dependency quintile (RR 0.83, 95% CI 0.65, 1.07) were the SDOH most associated with paediatric HCV screening. Younger maternal age (RR 0.98 per 1-year increase, 95% CI 0.97, 0.99), HIV co-infection (RR 1.69, 95% CI 1.16, 2.48) and GI specialist involvement (RR 1.18, 95% CI 1.00, 1.39) were associated with higher probabilities of screening. CONCLUSIONS: Among children exposed to HCV during pregnancy, rural residences and living in highly dependent neighbourhoods showed a potential association with a lower probability of HCV screening by the age of 2. Future work evaluating barriers to paediatric HCV screening among rural residing and dependent residents is needed to enhance the screening.

An evolutionary concept analysis: stigma among women living with hepatitis C.

BACKGROUND: Stigma is a complex social phenomenon that leads to marginalization and influences the course of illness. In the context of hepatitis C virus (HCV), stigma is a well-documented barrier to accessing care, treatment, and cure. In recent years, HCV rates among women have increased, resulting in an urgent need to address stigma and its harmful effects. The purpose of this concept analysis was to investigate stigma in the context of women living with HCV using Rodgers' evolutionary method. METHODS: PubMed, CINAHL, Scopus, Medline, PsycINFO, and Nursing and Allied Health were used to identify articles describing HCV stigma among women. Articles from peer-reviewed journals and geographic locations, published between 2002-2023, were included in the analysis. As specified in Rodgers' evolutionary method, articles were analyzed with a focus on the concept's context, surrogate and related terms, antecedents, attributes, examples, and consequences. RESULTS: Following screening, 33 articles were selected for inclusion in the analysis. Discrimination and marginalization were identified as surrogate and related terms to stigma; and antecedents of stigma were identified as limited knowledge, fear of diagnosis, and disclosure. Prevalent attributes of stigma in the literature were described as feelings of decreased self-worth, negative stereotyping, and fear of transmission. Importantly, HCV stigma among women is unique in comparison to other forms of infectious disease-related stigma, primarily due its impact on women's identity as mothers and caregivers. Stigmatization of women living with HCV resulted in negative consequences to personal relationships and healthcare access due to decreased health-seeking behaviours. Although access to HCV treatment has changed considerably over time, a temporal analysis could not be completed due to the limited number of articles. CONCLUSIONS: Stigma in the context of women living with HCV has its own unique antecedents, attributes, and consequences. This enhanced understanding of stigma among women living with HCV has the potential to inform improved and more effective approaches to care, which will be required to reach HCV elimination. Furthermore, this analysis identifies stigma layering and stigma in the direct-acting antiviral  treatment era as areas for more in-depth future inquiry.

Agenesis of the left hepatic lobe: a cadaveric case report.

Agenesis of the left hepatic lobe is a rare anomaly described as the absence of liver tissue on the left side of the gallbladder fossa or falciform ligament. Here we report a case of agenesis of the left hepatic lobe identified during educational dissection of an 84-year-old male formalin-fixed cadaver. The gross anatomical characteristics, embryological origin, and clinical relevance of this rare variation are described in this report.

Platelet and INR Thresholds and Bleeding Risk in Ultrasound Guided Percutaneous Liver Biopsy: A Before-After Implementation of the 2019 Society of Interventional Radiology Guidelines Observational Quality Improvement Study.

Purpose: To evaluate if implementation of the 2019 Society of Interventional Radiology (SIR) guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy is associated with increased haemorrhagic adverse events, change in pre-procedural blood product utilization, and evaluation of guideline compliance rate at a single academic institution. Methods: Ultrasound guided percutaneous liver biopsies from (January 2019-January 2023) were retrospectively reviewed (n = 504), comparing biopsies performed using the 2012 SIR pre-procedural coagulation guidelines (n = 266) to those after implementation of the 2019 SIR pre-procedural guidelines (n = 238). Demographic, preprocedural transfusion, laboratory, and clinical data were reviewed. Chart review was conducted to evaluate the incidence of major bleeding adverse events defined as those resulting in transfusion, embolization, surgery, or death. Results: Implementation of the 2019 SIR periprocedural guidelines resulted in reduced guideline non-compliance related to the administration of blood products, from 5.3% to 1.7% (P = .01). The rate of pre-procedural transfusion remained the same pre and post guidelines at 0.8%. There was no statistically significant change in the incidence of bleeding adverse events, 0.8% pre guidelines versus 0.4% post (P = 1.0). Conclusion: Implementation of the 2019 SIR guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy did not result in an increase in bleeding adverse events or pre-procedural transfusion rates. The guidelines can be safely implemented in clinical practice with no increase in major adverse events.

Incidence of Cirrhosis Among Recent Immigrants and Refugees to Ontario, Canada.

The epidemiology of cirrhosis among immigrants to North America has not been described. Using population-level data from Ontario, Canada, recent immigrant and refugees with incident cirrhosis were identified and stratified by World Bank region of origin and cirrhosis etiology. Incidence rates were described based on region of origin and etiology and compared with those in Canadian-born/long-term residents. A total of 25,054 immigrants/refugees were identified with rates of cirrhosis lower compared with those in Canadian-born/long-term residents for all etiologies except hepatitis B virus likely explained by the healthy immigrant effect. Nonalcoholic fatty liver disease was the most common etiology of cirrhosis among immigrants and refugees.

Association between social determinants of health and rates of liver transplantation in individuals with cirrhosis.

BACKGROUND AND AIMS: This study evaluated the association between neighborhood-level social determinants of health (SDOH) and liver transplantation (LT) among patients with cirrhosis who have universal access to health care. APPROACH AND RESULTS: This was a retrospective population-based cohort study from 2000-2019 using administrative health care data from Ontario, Canada. Adults aged 18-70 years with newly decompensated cirrhosis and/or HCC were identified using validated coding. The associations between five neighborhood level SDOH quintiles and LT were assessed with multivariate Fine-Gray competing risks regression to generate subdistribution HRs (sHRs) where death competes with LT. Overall, n = 38,719 individuals formed the cohort (median age 57 years, 67% male), and n = 2788 (7%) received LT after a median of 23 months (interquartile range 3-68). Due to an interaction, results were stratified by sex. After multivariable regression and comparing those in the lowest versus highest quintiles, individuals living in the most materially resource-deprived areas (female sHR, 0.61; 95% CI, 0.49-0.76; male sHR, 0.55; 95% CI, 0.48-0.64), most residentially unstable neighborhoods (female sHR, 0.61; 95% CI, 0.49-0.75; male sHR, 0.56; 95% CI, 0.49-0.65), and lowest-income neighborhoods (female sHR, 0.57; 95% CI, 0.46-0.7; male sHR, 0.58; 95% CI, 0.50-0.67) had ~40% reduced subhazard for LT (p < 0.01 for all). No associations were found between neighborhoods with the most diverse immigrant or racial minority populations or age and labor force quintiles and LT. CONCLUSIONS: This information highlights an urgent need to evaluate how SDOH influence rates of LT, with the overarching goal to develop strategies to overcome inequalities.

Ethnicity, disease severity, and survival in Canadian patients with primary biliary cholangitis.

BACKGROUND AND AIMS: We investigated associations between ethnicity, survival, and disease severity in a diverse Canadian cohort of patients with primary biliary cholangitis (PBC). APPROACH AND RESULTS: Patients with PBC were included from the Canadian Network for Autoimmune Liver Disease. Ethnicity was defined using a modified list adopted from Statistics Canada, and ethnicities with small samples were grouped. Clinical events were defined as liver decompensation, HCC, liver transplantation, or death. Clinical event-free and liver transplantation-free survival were analyzed using Cox regression. Trajectories of serum liver function tests were assessed over time using mixed-effects regression. Health-related quality of life was assessed using the Short Form 36, the PBC-40 questionnaire, and the 5-D Itch scale and analyzed using mixed-effects regression. The cohort included 1538 patients with PBC from six sites and was comprised of 82% White, 4.7% Indigenous, 5.5% East Asian, 2.6% South Asian, and 5.1% miscellaneous ethnicities. Indigenous patients were the only ethnic group with impaired liver transplant-free and event-free survival compared to White patients (HR, 3.66; 95% CI, 2.23-6.01; HR, 3.09; 95% CI, 1.94-4.92). Indigenous patients were more likely to have a clinical event before diagnosis (10%) than all other ethnic groups despite similar age at diagnosis. Indigenous patients presented with higher alkaline phosphatase, total bilirubin, and GLOBE scores than White patients; and these relative elevations persisted during follow-up. CONCLUSIONS: Indigenous Canadians with PBC present with advanced disease and have worse long-term outcomes compared to White patients.

Influence of hepatitis C viral parameters on pregnancy complications and risk of mother-to-child transmission.

BACKGROUND & AIMS: With the World Health Organization plan for hepatitis C elimination by the year 2030, and recent guideline recommendations to screen all women during pregnancy for HCV, data on HCV in pregnancy are needed to determine the association of HCV viremia with adverse pregnancy outcomes and mother-to-child transmission (MTCT). METHODS: This retrospective cohort study was performed in Ontario, Canada, using population-based administrative healthcare data. Individuals were stratified based on whether they had active HCV viremia during pregnancy or resolved viremia at time of pregnancy. Peak HCV viral load was determined. Logistic regression was used to determine the association of viremia with adverse pregnancy outcomes; maternal HCV RNA levels were evaluated as a predictor of MTCT. RESULTS: We identified a total of 2,170 pregnancies in 1,636 women who were HCV RNA positive prior to pregnancy; 1,780 (82%) pregnancies occurred in women who were HCV RNA positive during pregnancy. Patients who were HCV RNA positive during pregnancy were more likely to have preterm delivery (18% vs. 12%, p = 0.002), intrahepatic cholestasis of pregnancy (4% vs. <2%, p = 0.003), and post-partum hemorrhage (9% vs. 5%, p = 0.013), and less likely to have gestational diabetes (6% vs. 10%, p = 0.008) than those with resolved infection. Only 511 (29%) infants had screening consistent with guidelines after birth; there was an estimated 3.5% risk of MTCT. HCV RNA ≥6.0 log10 IU/ml was significantly associated with MTCT (exact odds ratio 3.4, p = 0.04). CONCLUSION: Active HCV viremia among individuals with a history of HCV infection significantly increases adverse pregnancy outcomes. Few infants are screened for MTCT. Higher HCV RNA is associated with increased risk of MTCT. LAY SUMMARY: The prevalence of hepatitis C has increased in women of child-bearing age and has important implications for women who become pregnant and their infants. We evaluated the effect that hepatitis C has on pregnancy outcomes as well as the rate of hepatitis C transmission to infants in a large database with linked mother-infant records. We found that active hepatitis C during pregnancy increased the risk of pregnancy complications. We also identified very low rates of testing of infants born to mothers with hepatitis C, but found higher rates of hepatitis C transmission to infants in mothers with higher virus levels.

NAFLD Cirrhosis Is Rising Among Childbearing Women and Is the Most Common Cause of Cirrhosis in Pregnancy.

Rates of pregnancies affected by nonalcoholic fatty liver disease (NAFLD) in the United States have nearly tripled in the last decade and NAFLD confers increased perinatal risks, such as hypertensive complications, postpartum hemorrhage, and preterm birth.1 Rates of cirrhosis in pregnancy are also rising,2 although estimates specific to NAFLD cirrhosis are lacking. Whether NAFLD cirrhosis confers differential perinatal risks than other causes of cirrhosis in pregnancy is also unknown.

Increasing Incidence of Cirrhosis Over the Past 2 Decades Among Children in Ontario, Canada.

INTRODUCTION: We describe the incidence of cirrhosis in the general pediatric population. METHODS: This is a population-based study using health-care data from Ontario, Canada, between 1997 and 2017. Age-adjusted and sex-adjusted standardized incidence rates were described, and age-period-cohort modeling approach was used to estimate the independent effect of birth cohort. RESULTS: In total, 2,966 new diagnoses of cirrhosis among children were identified at a median age of 9 years. The incidence rate increased almost 4-fold over the study period (2.7/100,000 person-years in 1997 vs 10.6/100,000 person-years in 2017) with the highest increase seen in children younger than 1 year. DISCUSSION: In this first population-based study in children, the incidence of cirrhosis has increased dramatically over the past 2 decades.

Pregnancies With Cirrhosis Are Rising and Associated With Adverse Maternal and Perinatal Outcomes.

INTRODUCTION: Cirrhosis incidence in pregnancies from outside the United States (US) is rising, although contemporary data including maternal and perinatal outcomes within the United States are lacking. METHODS: Using discharge data from the racially diverse US National Inpatient Sample, temporal trends of cirrhosis in pregnancies were compared with noncirrhotic chronic liver disease (CLD) or no CLD. Outcomes included preterm birth, postpartum hemorrhage, hypertensive complications (preeclampsia, eclampsia, and/or hemolysis, elevated liver enzymes, and low platelets syndrome), and maternal or fetal death. Logistic regression was adjusted for age, race, multiple gestation, insurance status, and prepregnancy metabolic comorbidities. RESULTS: Among 18,573,000 deliveries from 2012 to 2016, 895 had cirrhosis, 119,875 had noncirrhotic CLD, and 18,452,230 had no CLD. Pregnancies with cirrhosis increased from 2.5/100,000 in 2007 to 6.5/100,000 in 2016 (P = 0.01). On adjusted analysis, cirrhosis was associated with hypertensive complications (vs no CLD, OR 4.9, 95% confidence intervals [CI] 3.3-7.4; vs noncirrhotic CLD, OR 4.4, 95% CI 3.0-6.7), postpartum hemorrhage (vs no CLD, OR 2.8, 95% CI 1.6-4.8; vs noncirrhotic CLD, OR 2.0, 95% CI 1.2-3.5), and preterm birth (vs no CLD, OR 3.1, 95% CI 1.9-4.9; vs noncirrhotic CLD, OR 2.0, 95% CI 1.3-3.3, P ≤ 0.01). Cirrhosis was statistically associated with maternal mortality, although rarely occurred (≤ 1%). DISCUSSION: In this racially diverse, US population-based study, pregnancies with cirrhosis more than doubled over the past decade. Cirrhosis conferred an increased risk of several adverse events, although maternal and perinatal mortality was uncommon. These data underscore the need for reproductive counseling and multidisciplinary pregnancy management in young women with cirrhosis.

Recovery From Dialysis-Treated Acute Kidney Injury in Patients With Cirrhosis: A Population-Based Study.

RATIONALE & OBJECTIVE: The decision to initiate kidney replacement therapy (KRT) for acute kidney injury (AKI) in cirrhosis remains controversial because it is unclear which patients will benefit. We sought to characterize factors associated with recovery from KRT-treated AKI in patients with cirrhosis to inform shared clinical decision-making. STUDY DESIGN: Population-based retrospective cohort study. SETTING & PARTICIPANTS: Adult patients from Ontario, Canada, identified using administrative data to have cirrhosis at the time of hospital admission with AKI (based on serum creatinine level) who were treated with KRT (January 1, 2009, to December 31, 2016) and followed up until the end of 2017. EXPOSURES: Demographic characteristics and comorbidities before admission. OUTCOMES: Kidney recovery defined as the absence of KRT for at least 30 days. ANALYTICAL APPROACH: The cumulative incidences of kidney recovery, death, and liver transplant were calculated at 1, 3, 6, and 12 months, and independent predictors of kidney recovery were evaluated using Fine and Gray competing risk regression models that generated subdistribution hazards ratios (sHRs). RESULTS: Overall, 722 patients were included (median age, 61 [interquartile range, 54-68] years; Model for End-Stage Liver Disease (MELD)-Na score, 26 [interquartile range, 22-34]; 66% were male; 52% had viral hepatitis, 25% nonalcoholic fatty liver disease, 18% alcohol-associated liver disease). The cumulative incidences of kidney recovery at 1, 3, 6, and 12 months were 3%, 22%, 25%, and 26%, respectively. Higher MELD-Na score (sHR per 5 units greater, 0.72 [95% CI, 0.65-0.80]), acute-on-chronic liver failure (sHR, 0.61 [95% CI, 0.43-0.86]), and sepsis (sHR, 0.57 [95% CI, 0.41-0.81]) were associated with a lower hazard of kidney recovery, whereas those on a liver transplant waitlist (sHR, 3.10 [95% CI, 1.96-4.88]) and who were admitted to a teaching hospital (sHR, 1.48 [95% CI, 1.05-2.08]) were more likely to experience kidney recovery. LIMITATIONS: Observational design, AKI etiology not identified. CONCLUSIONS: Kidney recovery from KRT occurred in only one quarter of patients and was very unlikely after 3 months. These findings provide information regarding prognosis that may guide decisions regarding KRT initiation and continuation.

NAFLD and Alcohol-Associated Liver Disease Will Be Responsible for Almost All New Diagnoses of Cirrhosis in Canada by 2040.

BACKGROUND AND AIMS: Mortality secondary to cirrhosis in North America is increasing. We describe the incidence of cirrhosis stratified by birth cohort and cirrhosis etiology and project disease burden to 2040. APPROACH AND RESULTS: This is a retrospective cohort study in Ontario, Canada, using population-based administrative health care data. Individuals with incident cirrhosis (2000-2017) were identified, and etiology was defined as HCV, HBV, NAFLD, alcohol-associated liver disease (ALD), or autoimmune liver disease/other using validated case definitions. Annual age/sex-adjusted cirrhosis incidence rate per 100,000 person-years was calculated with incidence projection to 2040 using age-period-cohort modeling along with average annual percent change (AAPC) in cirrhosis incidence stratified by birth cohort and etiology. In total, 159,549 incident cases of cirrhosis were identified. Incidence increased by 26% with an AAPC of 2%/year (95% CI, 1.6-2.4; P < 0.001). The largest increases were for HCV (AAPC, 4.1%/year; 95% CI, 2.6-5.7; P < 0.001) and NAFLD (AAPC, 3.3%/year; 95% CI, 2.6-4.1%; P < 0.001). ALD and HCV cirrhosis in those born >1980 increased by 11.6%/year (95% CI, 9.3-13.9; P < 0.001) and 9.5%/year (95% CI, 6.2-13.0; P < 0.001), respectively. However, by 2040, cirrhosis incidence is projected to continue to increase, driven mostly by NAFLD, especially in postmenopausal women, and ALD in individuals born >1980. CONCLUSIONS: Cirrhosis incidence will continue to increase over the next two decades secondary to NAFLD with a worrisome rapid rise in ALD cirrhosis among young adults. Public education, policy, and intervention targeting NAFLD risk factors and alcohol use in young adults are urgently needed.

Predictors of Postoperative Liver Decompensation Events After Resection in Patients with Cirrhosis and Hepatocellular Carcinoma: A Population-Based Study.

BACKGROUND: Appropriate patient selection for liver resection in hepatocellular carcinoma (HCC) is critical to mitigation of major liver-related postoperative complications. Currently, no standard prognostic tool exists to predict the risk of postoperative liver decompensation events (POLDEs) after partial hepatectomy for patients with cirrhosis and HCC. This study aimed to identify independent preoperative predictors of POLDEs for future development of prognostic tools to improve surgical decision-making. METHODS: This population-based, retrospective cohort study investigated patients with cirrhosis and incident HCC between 2007 and 2017, identified using administrative health data from Ontario, Canada. The occurrence of a POLDE or death within 2 years after surgery was described. Multivariable Cox regression identified independent predictors of POLDE-free survival, as well as cause-specific hazards for POLDEs and death. RESULTS: Among 611 patients with cirrhosis and HCC who underwent liver resection, 160 (26.2%) experienced at least one POLDE, and 189 (30.9%) died within 2 years after surgery. Diabetes, cirrhosis etiology, major liver resection, and previous non-malignant decompensation were independent predictors of POLDE-free survival. Except for extent of resection, the same risk factors were associated with POLDEs in the cause-specific analysis. In contrast, only age and history of previous non-malignant decompensation were independent predictors of mortality. CONCLUSIONS: Among patients with cirrhosis undergoing resection for HCC, patient and disease-related factors are associated with POLDEs and POLDE-free survival. These factors can be used both to inform clinical practice and to advance the development of preoperative prognostic tools, which may lead to improved outcomes for this population.

Real-world colorectal cancer diagnostic pathways in Ontario, Canada: A population-based study.

OBJECTIVE: This study aimed to identify colorectal cancer (CRC) diagnostic pathways and describe patients in those pathway groups. METHODS: This was a cross-sectional study of CRC patients in Ontario, Canada, diagnosed 2009-2012 that used linked administrative data at ICES. We used cluster analysis on 11 pathway variables characterising patient presentation, symptoms, procedures and referrals. We assessed associations between patient- and disease-related characteristics and diagnostic pathway group. We further characterised the pathways by diagnostic interval and number of related physician visits. RESULTS: Six diagnostic pathways were identified, with three adhering to provincial diagnostic guidelines: screening (N = 4494), colonoscopy (N = 10,066) and imaging plus colonoscopy (N = 3427). Non-adherent pathways were imaging alone (N = 2238), imaging and emergency presentation (N = 2849) and no pre-diagnostic workup (N = 887). Patients in adherent pathways were younger, had fewer comorbidities, lived in less deprived areas and had earlier stage disease. The median diagnostic interval length varied across pathways from 12 to 126 days, correlating with the number of CRC-related visits. CONCLUSIONS: This study demonstrated substantial variations in real-world CRC diagnostic pathways and 25% were diagnosed through non-adherent pathways. Those patients were older, had more comorbid disease and had higher stage cancer. Further research needs to identify and describe the reasons for divergent diagnostic processes.

Surgical practice patterns and outcomes in T2 and T3 gallbladder cancer: a population-based study.

BACKGROUND: The extent of resection required in advanced gallbladder cancer is controversial. We aimed to describe the management and outcomes in patients with resected stage T2 and T3 gallbladder cancer. METHODS: In this population-based study, all T2 and T3 gallbladder cancer cases from Jan. 1, 2002, to Mar. 31, 2012, were identified from the Ontario Cancer Registry; pathology reports were linked and abstracted. The type of resection was classified as extended (cholecystectomy + liver resection, with or without bile duct resection) or simple (cholecystectomy only). We used Kaplan-Meier survival analysis to model time to death and evaluated factors associated with overall survival using the Cox proportional hazards regression model. RESULTS: A total of 370 patients were included, 232 with T2 disease and 138 with T3 disease. The proportions who underwent extended resection were 24.1% (56/232) and 37.0% (51/138), respectively. The unadjusted 5-year overall survival rates for simple and extended resection were 39.7% and 49.5%, respectively, for T2 disease (p = 0.03), and 13.5% and 22.8%, respectively, for T3 disease (p = 0.05). In adjusted analysis, extended resection significantly improved overall survival among patients with T2 disease (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.97), whereas higher grade of differentiation, presence of lymphovascular invasion and positive lymph nodes led to worse survival. Extended resection was not associated with improved survival in the T3 group; however, in subgroup analysis stratified by lymph node status, a trend toward improved overall survival with extended resection was seen in node-negative patients (HR 0.20, 95% CI 0.03-1.06). CONCLUSION: Extended resection improved overall survival in T2 disease regardless of nodal status but appeared most beneficial in node-negative T3 disease. The finding that extended resection was offered only to a small proportion of eligible patients highlights the need for improved knowledge translation at national surgical meetings.

Awareness, management, and practice patterns of pediatric NAFLD by primary care physicians.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Primary-care physicians (PCPs) play a key role in identifying patients requiring specialist referral. In this study, we aim to determine PCPs' practice patterns for paediatric NAFLD, as knowledge gaps have been reported for adult NAFLD. Methods: A survey was sent to 60 PCPs in the Eastern Ontario Network from July 2019 to January 2020. Results: Thirty-seven (62%) PCPs responded to the survey. Twenty-one incorrectly considered the prevalence of paediatric NAFLD to be ≤10%. The majority (35/36) cared for less than five paediatric NAFLD patients. Thirty-four (92%) were only 'slightly familiar' or 'not familiar at all' with paediatric NAFLD. Only one PCP routinely screens for NAFLD. Only one PCP was aware of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) clinical guidelines for paediatric NAFLD. Twenty-five (68%) correctly selected lifestyle modifications as a treatment option. Lack of confidence in the knowledge of NAFLD was the most common barrier for managing paediatric cases. Conclusion: The majority of PCPs are not screening for paediatric NAFLD and are not familiar with its clinical spectrum, citing a lack of knowledge regarding NAFLD as the greatest barrier. This may cause delays in diagnosis and a presentation with advanced fibrosis at the time of specialist referral. Dissemination and implementation of clinical guidelines have the potential to improve knowledge and screening rates for NAFLD in children at the primary-care level.