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.

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.

Effectiveness of an injury prevention video on risky behaviours in youth snow sports: A randomized controlled trial.

Objectives: Ski and snowboard-related injuries are common among Canadian youth. Analyzing the role of risky behaviours that contribute to injury risk is essential for gaining an understanding of injury prevention opportunities. The objective was to determine if rates of risky behaviour seen at the ski hill were lower for children and adolescents exposed to an educational injury prevention video. Methods: This single-blinded cluster randomized controlled trial included students (ages 7-16) from 18 Calgary schools who were enrolled in novice levelled school-sanctioned ski and snowboard programs. Consenting schools were randomly assigned to the intervention or control. The control group followed standard preparation including watching a general ski hill orientation video that was created by the ski hill. The intervention group viewed the intervention video focussed on injury prevention. The Risky Behaviour and Actions Assessment Tool was used by blinded research assistants to observe and record students' risky behaviours at an Alberta ski hill. Results: In total, 407 observations estimated the rate of risky behaviour. The overall rate of risky behaviour was 23.31/100 person runs in the control group and 22.95/100 person runs in the intervention group. The most commonly observed risky behaviours in both groups were skiing too close to other skiers/snowboarders and near collision with an object/person. Conclusions: Both groups showed similar rates of risky behaviour and demonstrated the same most common type of behaviour. Practical applications: future work should focus on mitigating common risky behaviours.

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.

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.

Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study.

STUDY QUESTION: Is the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception? SUMMARY ANSWER: Infertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment. WHAT IS KNOWN ALREADY: Infertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear. STUDY DESIGN, SIZE, DURATION: This population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006-2014. Outcomes were assessed up to June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Linked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm <37 weeks) and neonatal adverse morbidity (absent or present). MAIN RESULTS AND THE ROLE OF CHANCE: The study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4-8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16-1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01-1.17) in the OI/IUI group and 1.12 (95% CI 1.04-1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males. LIMITATIONS, REASONS FOR CAUTION: Some mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Infertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study. STUDY FUNDING/COMPETING INTEREST(S): This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Outcomes of Pregnant Women With Cirrhosis and Their Infants in a Population-Based Study.

BACKGROUND & AIMS: The incidence of cirrhosis is increasing among women of childbearing age. Contemporary outcomes of pregnant women with cirrhosis and their infants, as well as liver-related complications, have not been described in North America, to our knowledge. We investigated the association between cirrhosis and perinatal outcomes and evaluated perinatal liver-related events. METHODS: We performed a retrospective cohort study using population-based administrative health care data from Ontario, Canada (2000-2017). We identified pregnant women with compensated cirrhosis (n = 2022) using validated case definitions and routine mother-infant linkage; the women were matched to 10,110 pregnant women in the general population (1:5) based on birth year and socioeconomic status. Maternal and infant outcomes up to 6 weeks postpartum and liver-related complications up to 1 year postpartum were evaluated by using multivariate log-binomial regression. RESULTS: After we adjusted for demographic and metabolic risk factors, cirrhosis was independently associated with intrahepatic cholestasis of pregnancy (relative risk [RR], 10.64; 95% confidence interval [CI], 7.49-15.12), induction of labor (RR, 1.15; 95% CI, 1.03-1.28), puerperal infections (RR, 1.32; 95% CI, 1.02-1.70), preterm birth (RR, 1.60; 95% CI, 1.35-1.89), infants who were large for gestational age (RR, 1.24; 95% CI, 1.05-1.46), and neonatal respiratory distress (RR, 1.20; 95% CI, 1.02-1.42). Fewer than 2% of pregnant women with cirrhosis had liver-related complications, but these occurred in a significantly higher proportion of women with a history of hepatic decompensation (13%) than women with compensated cirrhosis (1.2%) (P < .001). CONCLUSIONS: In a population-based study, we found that cirrhosis is an independent risk factor for adverse perinatal outcomes. However, liver-related complications are rare. Multidisciplinary teams are needed to coordinate care for pregnant women with cirrhosis during pregnancy and postpartum to optimize outcomes.

Physical fighting, fighting-related injuries and family affluence among Canadian youth.

BACKGROUND: Physical fighting is an assaultive behaviour that can lead to injury. Family affluence is a health determinant that can influence injury. This study examines the relationship between family affluence and two outcomes: physical fighting and fighting-related injury in Canadian adolescents. Three measurements were used to represent family affluence and assess whether these measures demonstrated different associations with these outcomes. METHODS: Canadian data from the 2009/2010 Health Behaviour in School-aged Children Study were used. It consists of a nationally representative sample of 26,078 grade 6-10 students. A subset analysis of 10,429 grade 9-10 students was conducted to account for additional confounders. Modified Poisson regression was used to compare the risk of physical fighting and fighting-related injury in youth from different levels of family affluence. Three indicators were used to represent family affluence: self-perceived affluence, a family affluence scale (FAS), and area-level average household income. RESULTS: The overall prevalence was 35.6% for physical fighting and 2.7% for fighting-related injuries. Both outcomes were more frequent in males than females. An inverse gradient was present where risk for both outcomes increased with decreasing levels of affluence irrespective of the affluence measurement. The self-perceived affluence variable showed a significantly stronger gradient in girls than boys for both outcomes. For both outcomes, FAS showed a similar inverse gradient within females, but a threshold effect in males where there was a strong effect in the low FAS group, but a null effect in the moderate FAS group. The area-level income variable presented a significantly higher likelihood for physical fighting only in females (p = 0.001-0.075). For fighting-related injury, none of the area-level income models showed significant risk estimates with the exception of the bivariate association where low income females were twice as likely to report a fighting-related injury compared to higher income groups (p = 0.030). Post hoc power calculations indicate that there was not sufficient power to detect injury effects associated with the area level income measure. CONCLUSION: It appears that a socioeconomic gradient exists where lower affluence is associated with a higher risk of reporting a physical fight and fighting-related injury irrespective of the measure used. While the patterns were generally the same with all three measurements, the strength of this gradient varied across measures. This demonstrates that each indicator may measure different aspects of affluence. Further analyses are needed to explore concepts and mechanisms underlying each affluence measure.

Emergency Colorectal Surgery in Those with Cirrhosis: A Population-based Study Assessing Practice Patterns, Outcomes and Predictors of Mortality.

Background: Those with cirrhosis who require emergency colorectal surgery are at risk for poor outcomes. Although risk predictions models exists, these tools are not specific to colorectal surgery, nor were they developed in a contemporary setting. Thus, the objective of this study was to assess the outcomes in this population and determine whether cirrhosis etiology and/or the Model for End Stage Liver Disease (MELD-Na) is associated with mortality. Methods: This population-based study included those with cirrhosis undergoing emergent colorectal surgery between 2009 and 2017. All eligible individuals in Ontario were identified using administrative databases. The primary outcome was 90-day mortality. Results: Nine hundred and twenty-seven individuals (57%) (male) were included. The most common cirrhosis etiology was non-alcoholic fatty liver disease (NAFLD) (50%) and alcohol related (32%). Overall 90-day mortality was 32%. Multivariable survival analysis demonstrated those with alcohol-related disease were at increased risk of 90-day mortality (hazards ratio [HR] 1.53, 95% confidence interval [CI] 1.2-2.0 vs. NAFLD [ref]). Surgery for colorectal cancer was associated with better survival (HR 0.27, 95%CI 0.16-0.47). In the subgroup analysis of those with an available MELD-Na score (n = 348/927, 38%), there was a strong association between increasing MELD-Na and mortality (score 20+ HR 6.6, 95%CI 3.9-10.9; score 10-19 HR 1.8, 95%CI 1.1-3.0; score <10 [ref]). Conclusion: Individuals with cirrhosis who require emergent colorectal surgery have a high risk of postoperative complications, including mortality. Increasing MELD-Na score is associated with mortality and can be used to risk stratify individuals.

Impact of neighbourhood-level social determinants of health on healthcare utilisation and perinatal outcomes in pregnant women with NAFLD cirrhosis: a population-based study in Ontario, Canada.

BACKGROUND: Cirrhosis is rising in North America, driven partly by the epidemic of non-alcoholic fatty liver disease (NAFLD), most in women of reproductive age. Little is known about factors that impact perinatal outcomes and healthcare utilisation in pregnant women with NAFLD cirrhosis. OBJECTIVES: We investigated the association between population-level social determinants, health outcomes and healthcare utilisation. METHODS: We retrospectively analysed healthcare utilisation and perinatal outcomes in a cohort of pregnant women with NAFLD cirrhosis from Ontario, Canada from 2000 to 2016 and followed for 90 days postdelivery. We compared utilisation and health outcomes according to income, residential instability, material deprivation, dependency and ethnic diversity. A Cochran-Armitage test for trend was done to assess whether utilisation patterns were linear across quintiles. RESULTS: 3320 pregnant women with NAFLD cirrhosis formed the study cohort. Decreasing income quintile associated with a higher proportion of women with at least one emergency department (ED) visit. Increasing residential instability, material deprivation and dependency were associated with a higher frequency of ED visitation, with no compelling differences in the rates of perinatal complications or adverse outcomes in pregnant women with NAFLD cirrhosis. Using multiple population-level proxies for social determinants of health, this study demonstrates an association between marginalisation and increased ED visitation. CONCLUSIONS: As the incidence rate of pregnancies among women with NAFLD cirrhosis continues to rise, understanding how this population uses healthcare services will help coordinate care for these patients.

Cause-specific mortality among patients with cirrhosis in a population-based cohort study in Ontario (2000-2017).

BACKGROUND: Although patients with cirrhosis are at increased risk of death, the exact causes of death have not been reported in the contemporary era. This study aimed to describe cause-specific mortality in patients with cirrhosis in the general population. METHODS: Retrospective cohort study using administrative health care data from Ontario, Canada. Adult patients with cirrhosis from 2000-2017 were identified. Cirrhosis etiologies were defined as HCV, HBV, alcohol-associated liver disease (ALD), NAFLD, or autoimmune liver disease/other with validated algorithms. Patients were followed until death, liver transplant, or end of study. Primary outcome was the cause of death as liver-related, cardiovascular disease, non-hepatic malignancy, and external causes (accident/self-harm/suicide/homicide). Nonparametric analyses were used to describe the cumulative incidence of cause-specific death by cirrhosis etiology, sex, and compensation status. RESULTS: Overall, 202,022 patients with cirrhosis were identified (60% male, median age 56 y (IQR 46-67), 52% NAFLD, 26% alcohol-associated liver disease, 11% HCV). After a median follow-up of 5 years (IQR 2-12), 81,428 patients died, and 3024 (2%) received liver transplant . Patients with compensated cirrhosis mostly died from non-hepatic malignancies and cardiovascular disease (30% and 27%, respectively, in NAFLD). The 10-year cumulative incidence of liver-related deaths was the highest among those with viral hepatitis (11%-18%) and alcohol-associated liver disease (25%), those with decompensation (37%) and/or HCC (50%-53%). Liver transplant occurred at low rates (< 5%), and in men more than women. CONCLUSIONS: Cardiovascular disease and cancer-related mortality exceed liver-related mortality in patients with compensated cirrhosis.

Colorectal Cancer in Individuals with Cirrhosis: A Population-Based Study Assessing Practice Patterns, Outcomes, and Predictors of Survival.

Those with cirrhosis who develop colorectal cancer (CRC) are an understudied group who may tolerate treatments poorly and are at risk of worse outcomes. This is a retrospective cohort study of 842 individuals from Ontario, Canada, with a pre-existing diagnosis of cirrhosis who underwent surgery for CRC between 2009 and 2017. Practice patterns, overall survival, and short-term morbidity and mortality were assessed. The most common cirrhosis etiology was non-alcoholic fatty liver disease (NAFLD) (52%) and alcohol-associated liver disease (29%). The model for end-stage liver disease score (MELD-Na) was available in 42% (median score of 9, IQR7-11). Preoperative radiation was used in 62% of Stage II/III rectal cancer patients, while postoperative chemotherapy was used in 42% of Stage III colon cancer patients and 38% of Stage II/III rectal cancer patients. Ninety-day mortality following surgery was 12%. Five-year overall survival was 53% (by Stages I-IV, 66%, 55%, 50%, and 11%, respectively). Those with alcohol-associated cirrhosis (HR 1.8, 95% CI 1.5-2.2) had lower survival than those with NAFLD. Those with a MELD-Na of 10+ did worse than those with a lower MELD-Na score (HR 1.9, 95% CI 1.4-2.6). This study reports poor survival in those with cirrhosis who undergo treatment for CRC. Caution should be taken when considering aggressive treatment.

Rising Healthcare Costs and Utilization among Young Adults with Cirrhosis in Ontario: A Population-Based Study.

Objectives: Chronic diseases account for the majority of healthcare spending. Cirrhosis is a chronic disease whose burden is rising, especially in young adults. This study aimed at describing the direct healthcare costs and utilization in young adults with cirrhosis compared to other chronic diseases common to this age group. Methods: Retrospective population-based study of routinely collected healthcare data from Ontario for the fiscal years 2007-2016 and housed at ICES. Young adults (aged 18-40 years) with cirrhosis, inflammatory bowel disease (IBD), and asthma were identified based on validated case definitions. Total and annual direct healthcare costs and utilization were calculated per individual across multiple healthcare settings and compared based on the type of chronic disease. For cirrhosis, the results were further stratified by etiology and decompensation status. Results: Total direct healthcare spending from 2007 to 2016 increased by 84% for cirrhosis, 50% for IBD, and 41% for asthma. On a per-patient basis, annual costs were the highest for cirrhosis ($6,581/year) compared to IBD ($5,260/year), and asthma ($2,934/year) driven by acute care in cirrhosis and asthma, and drug costs in IBD. Annual costs were four-fold higher in patients with decompensated versus compensated cirrhosis ($20,651/year vs. $5,280/year). Patients with cirrhosis had greater use of both ICU and mental health services. Conclusion: Healthcare costs in young adults with cirrhosis are rising and driven by the use of acute care. Strategies to prevent the development of cirrhosis and to coordinate healthcare in this population through the development of chronic disease prevention and management strategies are urgently needed.

Pregnancy Is Not Associated with an Increased Risk of Decompensation, Transplant, or Death in Compensated Cirrhosis.

Background and Aims: Childbirth in women with cirrhosis is increasing and associated with a higher risk of perinatal outcomes compared to the general population. Whether pregnancy influences the risk of liver-related events compared to nonpregnant women with cirrhosis is unclear. This study evaluates the association between pregnancy and liver-related outcomes in women with compensated cirrhosis. Approach and Results. Population-based retrospective matched cohort study in Ontario, Canada, using routinely collected healthcare data. Pregnant women with compensated cirrhosis and without prior history of decompensation between 2000 and 2016 were identified and matched to nonpregnant women with compensated cirrhosis on age, etiology of cirrhosis, and socioeconomic status in a 1 : 2 ratio. The association between pregnancy and the composite outcome of nonmalignant decompensation, liver transplant (LT), and death up to two years after cohort entry was estimated using the multivariate Cox proportional hazard regression adjusting for potential confounders. Overall, 5,403 women with compensated cirrhosis were included (1,801 pregnant; 3,602 nonpregnant; median age 31 years (IQR 27-34); 60% nonalcoholic fatty liver disease, 34% viral hepatitis). After two years of follow-up, only 19 (1.1%) pregnant women had a liver-related event compared to 319 (8.9%) nonpregnant women. Pregnant women with compensated cirrhosis had a lower hazard of a liver-related event compared to nonpregnant women (aHR 0.14, 95% CI 0.09-0.22, P < .001). Conclusions: Pregnancy in women with compensated cirrhosis is not associated with increased liver-related events compared to nonpregnant women. These results can facilitate counselling women with cirrhosis of child-bearing age and suggests that pregnancy may not accelerate liver disease progression.

Infertility treatment and postpartum mental illness: a population-based cohort study.

BACKGROUND: Subfertility and infertility treatment can be stressful experiences, but it is unknown whether each predisposes to postpartum mental illness. We sought to evaluate associations between subfertility or infertility treatment and postpartum mental illness. METHODS: We conducted a population-based cohort study of individuals without pre-existing mental illness who gave birth in Ontario, Canada, from 2006 to 2014, stratified by fertility exposure: subfertility without infertility treatment; noninvasive infertility treatment (intrauterine insemination); invasive infertility treatment (in vitro fertilization); and no reproductive assistance. The primary outcome was mental illness occurring 365 days or sooner after birth (defined as ≥ 2 outpatient visits, an emergency department visit or a hospital admission with a mood, anxiety, psychotic, or substance use disorder, self-harm event or other mental illness). We used multivariable Poisson regression with robust error variance to assess associations between fertility exposure and postpartum mental illness. RESULTS: The study cohort comprised 786 064 births (mean age 30.42 yr, standard deviation 5.30 yr), including 78 283 with subfertility without treatment, 9178 with noninvasive infertility treatment, 9633 with invasive infertility treatment and 688 970 without reproductive assistance. Postpartum mental illness occurred in 60.8 per 1000 births among individuals without reproductive assistance. Relative to individuals without reproductive assistance, those with subfertility had a higher adjusted relative risk of postpartum mental illness (1.14, 95% confidence interval 1.10-1.17), which was similar in noninvasive and invasive infertility treatment groups. INTERPRETATION: Subfertility or infertility treatment conferred a slightly higher risk of postpartum mental illness compared with no reproductive assistance. Further research should elucidate whether the stress of infertility, its treatment or physician selection contributes to this association.

Intravenous Albumin in Patients With Cirrhosis: Evaluation of Practice Patterns and Secular Trends of Usage in Ontario 2000 to 2017.

BACKGROUND: Intravenous (IV) albumin has evidence-based indications in cirrhosis that are limited in most guidelines to spontaneous bacterial peritonitis (SBP), type 1 hepatorenal syndrome (HRS) and large volume paracentesis (LVP).This study aimed to describe the trends of IV albumin usage in patients with cirrhosis at the population level and evaluate indications for IV albumin in the hospital setting. METHODS: A retrospective study identified albumin infusions in health care data from Ontario, Canada between 2000 and 2017 in those with and without cirrhosis. Annual rates of IV albumin by cirrhosis status were calculated per 10,000 person-years (PY) and described using Poisson regression and rate ratios. Secondly, patients with cirrhosis receiving IV albumin while hospitalized at Kingston Health Sciences Centre (KHSC) in 2017 were identified and underwent detailed chart abstraction to determine the reason for IV albumin administration. RESULTS: The overall rate of provincial IV albumin usage doubled over the study period (2000: 8.4/10,000 PY versus 2017: 16.3/10,000 PY; rate ratio 1.94, 95% confidence interval 1.90 to 1.99, P <0.001). The majority of albumin was used during hospitalization (88%) and 22% was used in patients with cirrhosis. At KHSC, there were134 admissions where a patient with cirrhosis received IV albumin. Of these, 49% of prescriptions were for evidence-based indications (LVP 30%, type 1 HRS 10%, SBP 10%), whereas other indications included non-HRS renal failure, hypovolemia and sepsis. CONCLUSION: IV albumin use has doubled over two decades and is frequently used in hospitalized patients with cirrhosis with only 50% being prescribed for evidence-based indications. These results highlight the impact of cirrhosis on albumin use and highlight potential quality improvement opportunities.

Validation of a hierarchical algorithm to define chronic liver disease and cirrhosis etiology in administrative healthcare data.

BACKGROUND AND AIMS: Chronic liver disease (CLD) and cirrhosis are leading causes of death globally with the burden of disease rising significantly over the past several decades. Defining the etiology of liver disease is important for understanding liver disease epidemiology, healthcare planning, and outcomes. The aim of this study was to validate a hierarchical algorithm for CLD and cirrhosis etiology in administrative healthcare data. METHODS: Consecutive patients with CLD or cirrhosis attending an outpatient hepatology clinic in Ontario, Canada from 05/01/2013-08/31/2013 underwent detailed chart abstraction. Gold standard liver disease etiology was determined by an attending hepatologist as hepatitis C (HCV), hepatitis B (HBV), alcohol-related, non-alcoholic fatty liver disease (NAFLD)/cryptogenic, autoimmune or hemochromatosis. Individual data was linked to routinely collected administrative healthcare data at ICES. Diagnostic accuracy of a hierarchical algorithm incorporating both laboratory and administrative codes to define etiology was evaluated by calculating sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and kappa's agreement. RESULTS: 442 individuals underwent chart abstraction (median age 53 years, 53% cirrhosis, 45% HCV, 26% NAFLD, 10% alcohol-related). In patients with cirrhosis, the algorithm had adequate sensitivity/PPV (>75%) and excellent specificity/NPV (>90%) for all etiologies. In those without cirrhosis, the algorithm was excellent for all etiologies except for hemochromatosis and autoimmune diseases. CONCLUSIONS: A hierarchical algorithm incorporating laboratory and administrative coding can accurately define cirrhosis etiology in routinely collected healthcare data. These results should facilitate health services research in this growing patient population.