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

Background & Aims Acute pancreatitis is a common disease with significant associated morbidity and mortality. We performed a systematic review and meta-analysis of population-based studies to explore the changing temporal trends of acute pancreatitis incidence globally. Methods We performed a systematic literature search to identify population-based studies reporting the annual incidence of acute pancreatitis. Abstracts were independently assessed to identify applicable papers for full-text review and data extraction. Joinpoint temporal trend analyses were performed to calculate the average annual percent change (AAPC) with 95% confidence intervals (CI). The AAPCs were pooled in a meta-analysis to capture the overall and regional trends in acute pancreatitis incidence over time. Temporal data were summarized in a static map and an interactive, web-based map. Results Forty-four studies reported the temporal incidence of acute pancreatitis (online interactive map: https://kaplan-acute-pancreatitis-ucalgary.hub.arcgis.com/). The incidence of acute pancreatitis has increased from 1961 to 2016 (AAPC = 3.07%; 95% CI: 2.30, 3.84; n=34). Increasing incidence was observed in North America (AAPC = 3.67%; 95% CI: 2.76, 4.57; n=4) and Europe (AAPC = 2.77%; 95% CI: 1.91, 3.63; n=23). The incidence of acute pancreatitis was stable in Asia (AAPC = −0.28%; 95% CI: −5.03, 4.47; n=4). Conclusion This meta-analysis provides a comprehensive overview of the global incidence of acute pancreatitis over the last 56 years and demonstrates a steadily rising incidence over time in most countries of the Western world. More studies are needed to better define the changing incidence of acute pancreatitis in Asia, Africa, and Latin America.

Background Immune-related adverse events can occur after treatment with immune checkpoint inhibitors (ICI), limiting treatment persistence. We aimed to evaluate the clinical course of ICI-mediated hepatitis (IMH) associated with combination ipilimumab and nivolumab treatment. Methods A retrospective cohort study including consecutive patients with metastatic melanoma treated with ipilimumab and nivolumab between 2013 and 2018 was conducted at two tertiary care centres. IMH was defined by the Common Terminology Criteria for Adverse Events (CTCAE). We determined the proportion of patients developing IMH, and compared the duration, treatment patterns and outcomes, stratified by hepatitis severity. Kaplan–Meier survival analysis was used to evaluate time to hepatitis resolution, and a linear mixed-effects model was used to compare longitudinal outcomes by treatment. Results A total of 63 patients were included. Thirty-two patients (51%) developed IMH (34% Grade 1–2, 66% Grade 3–4), at a median of 34 days (IQR 20 to 43.5 days) after the first dose. Baseline FIB4 index ≥1.45 was associated with IMH (OR 3.71 [95% CI: 1.03 to 13.38], P = 0.04). Ninety-four per cent (30/32) of patients had liver enzyme normalization after a median duration of 43 days (IQR 26 to 70 days). Corticosteroid use was not associated with faster IMH resolution or less ICI discontinuation. A total of 24 patients died during the study; no deaths were attributable to hepatitis-related complications. Fifty-three per cent (17/32) of patients resumed anti-PD-1 monotherapy and three patients developed IMH recurrence. Conclusions Approximately half of the patients treated with combination ipilimumab and nivolumab developed IMH in this cohort. However, most patients experienced uncomplicated IMH resolution.

BACKGROUND AND AIMS The effect of major depression and antidepressant use on patient survival in chronic liver disease is unknown. We evaluated the impact of major depressive disorder (MDD) and antidepressants on survival among patients with alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS The Health Improvement Network database, the largest medical database in the United Kingdom, was used to identify incident ALD (n = 4148) and NAFLD (n = 19 053) in patients between 1986 and 2017. Our primary outcome was development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models as time-varying covariates. Models were adjusted for age, sex, socio-economic status and comorbidities. RESULTS MDD rate was higher among patients with ALD (22.8%) compared to those with NAFLD (16.1%), P

Due to shared modes of exposure, HIV-HBV co-infection is common worldwide. Increased knowledge of the demographic and clinical characteristics of the co-infected population will allow us to optimize our approach to management of both infections in clinical practice. The Canadian Hepatitis B Network Cohort was utilized to conduct a cross-sectional evaluation of the demographic, biochemical, fibrotic and treatment characteristics of HIV-HBV patients and a comparator HBV group. From a total of 5996 HBV-infected patients, 335 HIV-HBV patients were identified. HIV-HBV patients were characterized by older median age, higher male and lower Asian proportion, more advanced fibrosis and higher anti-HBV therapy use (91% vs. 30%) than the HBV-positive / HIV seronegative comparator group. A history of reported high-risk exposure activities (drug use, high-risk sexual contact) was more common in HIV-HBV patients. HIV-HBV patients with reported high-risk exposure activities had higher male proportion, more Caucasian ethnicity and higher prevalence of cirrhosis than HIV-HBV patients born in an endemic country. In the main cohort, age ≥60 years, male sex, elevated ALT, the presence of comorbidity and HCV seropositivity were independent predictors of significant fibrosis. HIV seropositivity was not an independent predictor of advanced fibrosis (adj OR 0.75 [95%CI: 0.34-1.67]). In conclusion, Canadian co-infected patients differed considerably from those with mono-infection. Furthermore, HIV-HBV-infected patients who report high-risk behaviours and those born in endemic countries represent two distinct subpopulations, which should be considered when engaging these patients in care.

BACKGROUND The burden of cirrhosis on the healthcare system is substantial and growing. Our objectives were to estimate the readmission rates and hospitalization costs as well as to identify risk factors for 90-day readmission in patients with cirrhosis. METHODS We conducted a weighted analysis of the 2014 Nationwide Readmission Database to identify adult patients with cirrhosis-related complications in the United States and assessed readmission rates at 30, 60 and 90 days post-index hospitalization. Predictors of 90-day readmissions were identified using weighted regression models adjusting for patient and hospital characteristics; the national estimate of hospitalization costs was also calculated. RESULTS Of the 58 954 patients admitted with cirrhosis-related complications in 2014, 14 910 (25%) were readmitted within 90 days because of cirrhosis-related complications. The main causes of readmission were ascites (56%), hepatic encephalopathy (47%) and bleeding oesophageal varices (9%). Independent predictors of 90-day readmissions were male sex (adjusted OR [aOR]: 1.08, 95% CI, 1.04-1.13), age

ObjectiveDepression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD.DesignThe Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn’s disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn’s disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA).ResultsWe identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC.ConclusionPatients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn’s disease and UC. These results may impact counselling and management of depression and IBD.

Background Electronic medical records (EMRs) contain large amounts of rich clinical information. Developing EMR-based case definitions, also known as EMR phenotyping, is an active area of research that has implications for epidemiology, clinical care, and health services research. Objective This review aims to describe and assess the present landscape of EMR-based case phenotyping for the Charlson conditions. Methods A scoping review of EMR-based algorithms for defining the Charlson comorbidity index conditions was completed. This study covered articles published between January 2000 and April 2020, both inclusive. Embase (Excerpta Medica database) and MEDLINE (Medical Literature Analysis and Retrieval System Online) were searched using keywords developed in the following 3 domains: terms related to EMR, terms related to case finding, and disease-specific terms. The manuscript follows the Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA) guidelines. Results A total of 274 articles representing 299 algorithms were assessed and summarized. Most studies were undertaken in the United States (181/299, 60.5%), followed by the United Kingdom (42/299, 14.0%) and Canada (15/299, 5.0%). These algorithms were mostly developed either in primary care (103/299, 34.4%) or inpatient (168/299, 56.2%) settings. Diabetes, congestive heart failure, myocardial infarction, and rheumatology had the highest number of developed algorithms. Data-driven and clinical rule–based approaches have been identified. EMR-based phenotype and algorithm development reflect the data access allowed by respective health systems, and algorithms vary in their performance. Conclusions Recognizing similarities and differences in health systems, data collection strategies, extraction, data release protocols, and existing clinical pathways is critical to algorithm development strategies. Several strategies to assist with phenotype-based case definitions have been proposed.

Background: Healthcare systems worldwide have adopted the electronic medical record (EMR). EMRs are an efficient method of interprofessional communication, and can improve data availability for secondary research purposes. The discharge summary (DS) is a crucial document for both interprofessional communication, and coding of data for research purposes. We aimed to assess the completeness of our EMRs by assessing the presence of a DS in the EMR. Additionally, we evaluated the presence of indicators for a missing DS. Method: A retrospective chart review was conducted on 3,011 inpatient charts from 3 hospitals in Calgary, Alberta Canada. 893 charts were missing an electronic DS. A 10% sample was drawn to assess for presence of a paper DS. A list of variables was compiled to assess for association between patient and hospital characteristics, patient comorbidities, and the absence of an electronic DS. A Chi-square test, Fisher’s test and logistic regression were conducted to assess for associations. Results: The univariate analyses showed that age, being a surgical patient, a Charlson Comorbidity Index (CCI) of

Background Liver cirrhosis is a leading cause of morbidity, premature mortality and acute care utilization in patients with digestive disease. In the province of Alberta, hospital readmission rates for patients with cirrhosis are estimated at 44% at 90 days. For hospitalized patients, multiple care gaps exist, the most notable stemming from i) the lack of a structured approach to best practice care for cirrhosis complications, ii) the lack of a structured approach to broader health needs and iii) suboptimal preparation for transition of care into the community. Cirrhosis Care Alberta (CCAB) is a 4-year multi-component pragmatic trial which aims to address these gaps. The proposed intervention is initiated at the time of hospitalization through implementation of a clinical information system embedded electronic order set for delivering evidence-based best practices under real-world conditions. The overarching objective of the CCAB trial is to demonstrate effectiveness and implementation feasibility for use of the order set in routine patient care within eight hospital sites in Alberta. Methods A mixed methods hybrid type I effectiveness-implementation design will be used to evaluate the effectiveness of the order set intervention. The primary outcome is a reduction in 90-day cumulative length of stay. Implementation outcomes such as reach, adoption, fidelity and maintenance will also be evaluated alongside other patient and service outcomes such as readmission rates, quality of care and cost-effectiveness. This theory-based trial will be guided by Normalization Process Theory, Consolidated Framework on Implementation Research (CFIR) and the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) Framework. Discussion The CCAB project is unique in its breadth, both in the comprehensiveness of the multi-component order set and also for the breadth of its roll-out. Lessons learned will ultimately inform the feasibility and effectiveness of this approach in “real-world” conditions as well as adoption and adaptation of these best practices within the rest of Alberta, other provinces in Canada, and beyond. Trial registration ClinicalTrials.gov: NCT04149223, November 4, 2019.

OBJECTIVES To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends. METHODS MEDLINE and EMBASE were searched for population-based studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time. RESULTS Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval [CI]: 13.7, 21.1) (I = 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I = 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I = 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I = 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I = 79.6%) per year over the past several decades. DISCUSSION Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.

Nonalcoholic fatty liver disease (NAFLD) is a rising epidemic worldwide and will be the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplant within the next decade. NAFLD is considered as the hepatic manifestation of metabolic syndrome. Behaviors, such as a sedentary lifestyle and consuming a Western diet, have led to substantial challenges in managing NAFLD patients. With no curative pharmaceutical therapies, lifestyle modifications, including dietary changes and exercise, that ultimately lead to weight loss remain the only effective therapy for NAFLD. Multiple diets, including low-carbohydrate, low-fat, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean (MD) diets, have been evaluated. NAFLD patients have shown better outcomes with a modified diet, such as the MD diet, where patients are encouraged to increase the consumption of fruits and vegetables, whole grains, and olive oil. It is increasingly clear that a personalized approach to managing NAFLD patients, based on their preferences and needs, should be implemented. In our review, we cover NAFLD management, with a specific focus on dietary patterns and their components. We emphasize the successful approaches highlighted in recent studies to provide recommendations that health care providers could apply in managing their NAFLD patients.

Background Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Identifying high-risk patients is critical to best utilize limited health care resources. We established a community-based care pathway using 2D ultrasound shear wave elastography (SWE) to identify high risk patients with NAFLD. Our objective was to assess the cost-effectiveness of various non-invasive strategies to correctly identify high-risk patients. Methods A decision-analytic model was created using a payer’s perspective for a hypothetical patient with NAFLD. FIB-4 [≥1.3], NAFLD fibrosis score (NFS) [≥-1.455], SWE [≥8 kPa], transient elastography (TE) [≥8 kPa], and sequential strategies with FIB-4 or NFS followed by either SWE or TE were compared to identify patients with either significant (≥F2) or advanced fibrosis (≥F3). Model inputs were obtained from local data and published literature. The cost/correct diagnosis of advanced NAFLD was obtained and univariate sensitivity analysis was performed. Results For ≥F2 fibrosis, FIB-4/SWE cost $148.75/correct diagnosis while SWE cost $276.42/correct diagnosis, identifying 84% of patients correctly. For ≥F3 fibrosis, using FIB-4/SWE correctly identified 92% of diagnoses and dominated all other strategies. The ranking of strategies was unchanged when stratified by normal or abnormal ALT. For ≥F3 fibrosis, the cost/correct diagnosis was less in the normal ALT group. Conclusions SWE based strategies were the most cost effective for diagnosing ≥F2 fibrosis. For ≥F3 fibrosis, FIB-4 followed by SWE was the most effective and least costly strategy. Further evaluation of the timing of repeating non-invasive strategies are required to enhance the cost-effective management of NAFLD.

Background A subset of patients with ulcerative colitis (UC) will require colectomy within a few years of diagnosis. Thus, our aim was to determine the clinical predictors of early colectomy among patients with UC who are hospitalized with an acute flare. Methods Using population-based surveillance (1996-2009), all adults (≥18 years) hospitalized for UC within 3 years of diagnosis (n = 489) were identified. The primary outcome was a colectomy within 3 years of diagnosis. All medical charts were reviewed. A logistic regression model evaluated clinical variables that predicted colectomy within 3 years of diagnosis, and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Results Among patients admitted to hospital with UC within 3 years of diagnosis, 57.7% underwent colectomy, with the odds of colectomy decreasing by 12% per year. Early colectomy was more likely among patients aged 35 to 64 years versus 18 to 34 years (OR 2.18 [95% CI, 1.27-3.74]), males (OR 2.03 [95% CI, 1.24-3.34]), those with pancolitis (OR 5.38 [95% CI, 3.20-9.06]), and living in rural areas (OR 2.81 [95% CI, 1.49-5.29]). Prescription of infliximab before hospitalization increased odds of surgery (OR 5.12 [95% CI, 1.36-19.30]). Conclusions Patients hospitalized for UC have a high risk of early colectomy. This is particularly true in middle-aged men, those living in rural areas, and those without response to infliximab.

Malnutrition is an important predictor of morbidity and mortality among cirrhotic patients. Our objectives were to assess protein-calorie malnutrition (PCM) in cirrhotic pre-liver transplant patients and to study the correlation between subjective global assessment (SGA) and other objective measures of malnutrition.We recruited pre-liver transplant adult patients at our center between October 2012 and Oct 2015. Nutrition status was assessed via SGA. PCM was assessed by comparing recommended to actual protein and calorie intake. SGA was correlated with body mass index (BMI), dry BMI, handgrip strength by calibrated dynometer (HGS), and mid-arm circumference (MAC). We used non-parametric statistical methods in our analysis.Seventy patients were included in this study. Majority were males (n = 46, 66%) with a median age of 58 years (IQR: 50-61). Moderate to severe malnutrition was prevalent in our cohort (SGA-A: n = 15 (21.4%), SGA-B: n = 30 (42.9%) and SGA-C: n = 25 (35.7%). There was a significant difference in the recommended calories consumed between SGA groups (A 98.5% vs. C 79.2%, P = 0.03). A similar trend was observed for the recommended protein consumed (A 85.4%, C 62.5%; P = 0.09). SGA correlated with BMI (A = 26.4, C = 22.4; P0.01), Dry BMI (A = 25.9, C = 20.4; P0.01), HGS (A = 67.0, C = 47.0 PSI; P = 0.03), and MAC (A = 29.5 cm, C = 22.0 cm; P0.01). HGS and MAC were strongly correlated (Spearman correlation 0.49, P0.01).Cirrhotic patients have significant protein-calorie malnutrition. Multiple malnutrition tools including BMI, dry BMI, HGS and MAC were precisely able to assess malnutrition.

We would like to congratulate Mumtaz et al.1 for their important study attempting to develop and validate a risk score to predict 30-day hospital readmission in decompensated cirrhosis patients using the US nationwide readmission database (NRD). The identification of cirrhosis patients at high-risk for readmission is critical for developing processes to effectively address this problem. However, flaws in patient identification challenge the utility of the risk-score outlined in this study. This article is protected by copyright. All rights reserved.

Background & Aims In addition to monitoring adverse events (AEs) and post-colonoscopy colorectal cancers (PCCRC), indicators for assessing colonoscopy quality include adenoma detection rate (ADR) and cecal intubation rate (CIR). It is unclear whether there is an association between annual colonoscopy volume and ADR, CIR, AEs, or PCCRC. Methods We searched publication databases through March 2019 for studies assessing the relationship between annual colonoscopy volume and outcomes, including ADR, CIR, AEs, or PCCRC. Pooled odds ratios (ORs) were calculated using DerSimonian and Laird random effects models. Sensitivity analyses were performed to assess for potential methodological or clinical factors associated with outcomes. Results We performed a systematic review of 9235 initial citations, generating 27 retained studies comprising 11,276,244 colonoscopies. There was no association between procedural volume and ADR (OR, 1.00; 95% CI, 0.98–1.02 per additional 100 annual procedures). CIR improved with each additional 100 annual procedures (OR, 1.17; 95% CI, 1.08–1.28). There was a non-significant trend toward decreased overall AEs per additional 100 annual procedures (OR, 0.95; 95% CI, 0.90–1.00). There was considerable heterogeneity among most analyses. Conclusions In a systematic review and meta-analysis, we found higher annual colonoscopy volumes to correlate with higher CIR, but not with ADR or PCCRC. Trends toward fewer AEs were associated with higher annual colonoscopy volumes. There are few data available from endoscopists who perform fewer than 100 annual colonoscopies. Studies are needed on extremes in performance volumes to more clearly elucidate associations between colonoscopy volumes and outcomes.

The risk of suicide is higher for patients with colorectal cancer (crc) than for the general population. Given known differences in morbidity and sites of recurrence, we sought to compare the predictors of suicide for patients with colon cancer and with rectal cancer. Using the U.S. Surveillance, Epidemiology, and End Results database, adult patients with confirmed adenocarcinoma of the colon or rectum during 1973&ndash, 2009 were identified. Parametric and nonparametric tests were used to assess selected variables, and Cox proportional hazards regression models were used to determine predictors of suicide. The database identified 187,996 patients with rectal cancer and 443,368 with colon cancer. Compared with the rectal cancer group, the colon cancer group was older (median age: 70 years vs. 67 years, p < 0.001) and included more women (51% vs. 43%, p < 0.001). Suicide rates were similar in the colon and rectal cancer groups [611 (0.14%) vs. 337 (0.18%), p < 0.001]. On univariate analysis, rectal cancer was a predictor of suicide [hazard ratio (hr): 1.26, 95% confidence interval (ci): 1.10 to 1.43]. However, after adjusting for clinical and pathology factors, rectal cancer was not a predictor of suicide (hr: 1.05, 95% ci: 0.83 to 1.33). In the colon cancer cohort, independent predictors of suicide included older age, male sex, white race, and lack of primary resection. The aforementioned predictors, plus metastatic disease, similarly predicted suicide in the rectal cancer cohort. The suicide risk in crc patients is low (

Background Despite universal vaccination, chronic hepatitis B virus (HBV) infection remains a public health concern in North America owing to immigration. We aimed to characterize the number of people with a positive result of testing for HBV surface antigen (HBsAg) in Calgary, a large urban Canadian health care region, and to assess whether recommended laboratory tests and specialist consultation were done for those identified as HBsAg-positive. Methods Based on laboratory and Alberta Health Services administrative data, we identified all adults (age > 18 yr) with a positive HBsAg test result from Jan. 1 to Dec. 31, 2014 within the Calgary Zone. Demographic and relevant laboratory data were extracted within 6 months of a positive HBsAg test result, and referral to hepatology (2011-2014) was identified from data on referral to a centralized clinic. Parametric and nonparametric statistical methods were used for analyses. Results We identified 1214 HBsAg-positive people (584 women [48.1%]; median age 44 [interquartile range (IQR) 36-55] yr). A total of 1192 people (98.2%) had alanine aminotransferase testing (median level 23 [IQR 16-34] U/L; 117 [9.8%] with elevated levels), 682 (56.2%) had testing for HBV DNA (median level 2.8 [IQR 2.1-3.8] logIU/mL), 630 (51.9%) had HBV e antigen testing (negative result in 548 [87.0%]), and 145 (11.9%) had HBV e antibody testing (positive result in 111 [76.6%]). Overall, 144 people (11.9%) received anti-HBV treatment, and 390 (32.1%) were referred to a hepatologist. Interpretation Many HBsAg-positive people in Calgary did not receive the recommended laboratory assessments. The results highlight the necessity of continual public health efforts to screen for chronic HBV infection in Canada and to ensure adequate follow-up in order to reach the World Health Organization's goal of viral hepatitis elimination by 2030.

Background Modifications to the Model for End-Stage Liver Disease (MELD) have been proposed to improve prioritization of liver transplant (LT) candidates. Using a U.S. database, we derived a revised MELD including sodium and albumin [5-variable MELD (5vMELD)] that improved prediction of waiting list mortality. Our objectives were to confirm the association between hypoalbuminaemia and mortality and to externally validate 5vMELD in Canadian LT candidates. Methods Among adults registered on the LT waiting list at the University of Alberta (01/2000-10/2009), Cox regression determined the association between albumin and 1-year waiting list mortality. The discrimination of MELD, MELDNa and 5vMELD for predicting 1-year mortality were compared using c-statistics. Results Among 677 patients, 17% died and 51% underwent LT within 1 year of listing. Median serum albumin was 3.1 g/dl (IQR 2.6–3.6) and 70% of patients were hypoalbuminaemic (albumin

Rituximab, an anti-CD20 monoclonal antibody that selectively depletes B cells, has shown promise in autoantibody-associated, immune-mediated disorders. As ursodeoxycholic acid (UDCA) is not successful in all patients with primary biliary cirrhosis (PBC), additional treatment options are necessary. The objective of this study was to assess the safety and efficacy of rituximab in patients with PBC refractory to UDCA.Fourteen PBC patients refractory to UDCA received two rituximab infusions (1,000 mg) 2 weeks apart. The primary efficacy outcome was normalization and/or 25% improvement in serum alkaline phosphatase (ALP) concentration at 6 months.The median age was 53 years, and 92% were female and antimitochondrial antibody (AMA) positive. The median UDCA dosage was 15.3 mg/kg/day (interquartile range 14.5-17.8). Although rituximab was well tolerated, one patient withdrew due to an asthma exacerbation during the first infusion. Effective B-cell depletion was observed in the remaining 13 patients, including three that developed human anti-chimeric antibodies. ALP normalization and/or ≥ 25% improvement was observed in three patients (23%) at 6, 12, and 18 months. Significant reductions in median ALP (from 259 U/l at baseline to 213 U/l at 6 months; median decrease 16%), and serum IgM and AMA levels were observed at 6 months. Although fatigue was stable, pruritus improved in 60% of patients at 12 months (vs. 8% with worsening pruritus).Selective B-cell depletion with rituximab was safe and associated with a significant decrease in autoantibody production, but had limited biochemical efficacy in PBC patients with an incomplete response to UDCA.

Background High-throughput technologies have the potential to identify non-invasive biomarkers of liver pathology and improve our understanding of basic mechanisms of liver injury and repair. A metabolite profiling approach was employed to determine associations between alterations in serum metabolites and liver histology in patients with chronic hepatitis C virus (HCV) infection. Methods Sera from 45 non-diabetic patients with chronic HCV were quantitatively analyzed using 1H-NMR spectroscopy. A metabolite profile of advanced fibrosis (METAVIR F3-4) was established using orthogonal partial least squares discriminant analysis modeling and validated using seven-fold cross-validation and permutation testing. Bioprofiles of moderate to severe steatosis (≥33 %) and necroinflammation (METAVIR A2-3) were also derived. The classification accuracy of these profiles was determined using areas under the receiver operator curves (AUROCSs) measuring against liver biopsy as the gold standard. Results In total 63 spectral features were profiled, of which a highly significant subset of 21 metabolites were associated with advanced fibrosis (variable importance score >1 in multivariate modeling; R2 = 0.673 and Q2 = 0.285). For the identification of F3–4 fibrosis, the metabolite bioprofile had an AUROC of 0.86 (95 % CI 0.74–0.97). The AUROCs for the bioprofiles for moderate to severe steatosis were 0.87 (95 % CI 0.76–0.97) and for grade A2–3 inflammation were 0.73 (0.57–0.89). Conclusion This proof-of-principle study demonstrates the utility of a metabolomics profiling approach to non-invasively identify biomarkers of liver fibrosis, steatosis and inflammation in patients with chronic HCV. Future cohorts are necessary to validate these findings. Electronic supplementary material The online version of this article (doi:10.1186/s40169-016-0109-2) contains supplementary material, which is available to authorized users.

Objective: The present study examined the effects of aqueous and methanolic extracts of palm dates (fruits and seeds) on diabetic nephropathy in a rat model of type 2 DM. Methods: Sixty male albino rats subdivided into a) normal control (NC) group, b) diabetic control (DM) group, c) aqueous fruit extract (AFE) group, d) methanolic fruit extract (MFE) group, e) aqueous seed extract (ASE) group and f) methanolic seed extract (ASE) group. Treatment with both extracts done for 15 weeks after induction of type 2 DM. by the end of experiment fasting blood glucose, serum lipid profile, creatinine, urea, uric acid, urinary albumin excretion, kidney tissue MDA, catalase, SOD, GSH were measured and kidney histopathological examination was done. Results: Diabetic untreated rats showed significant hyperglycemia and hyperlipidemia and deterioration in kidney functions and morphology with enhanced oxidative stress in kidney tissues. On other hand, rats treated with either aqueous or methanolic fruit or seed extracts showed significant improvement in all studied parameters compared to DM group (p

Background. Hospital outcome report cards are used to judge provider performance, including for liver transplantation. We aimed to determine the impact of the choice of risk adjustment method on hospital rankings based on mortality rates in cirrhotic patients. Material and methods. We identified 68,426 cirrhotic patients hospitalized in the Nationwide Inpatient Sample database. Four risk adjustment methods (the Charlson/Deyo and Elixhauser algorithms, Disease Staging, and All Patient Refined Diagnosis Related Groups) were used in logistic regression models for mortality. Observed to expected (O/E) death rates were calculated for each method and hospital. Statistical outliers with higher or lower than expected mortality were identified and rankings compared across methods. Results. Unadjusted mortality rates for the 553 hospitals ranged from 1.4 to 30% (overall, 10.6%). For 163 hospitals (29.5%), observed mortality differed significantly from expected when judged by one or more, but not all four, risk adjustment methods (25.9% higher than expected mortality and 3.6% lower than expected mortality). Only 28% of poor performers and 10% of superior performers were consistently ranked as such by all methods. Agreement between methods as to whether hospitals were flagged as outliers was moderate (kappa 0.51-0.59), except the Charlson/Deyo and Elixhauser algorithms which demonstrated excellent agreement (kappa 0.75). Conclusions. Hospital performance reports for patients with cirrhosis require sensitivity to the method of risk adjustment. Depending upon the method, up to 30% of hospitals may be flagged as outliers by one, but not all methods. These discrepancies could have important implications for centers erroneously labeled as high mortality outliers.

Background & Aims The severe depletion of muscle mass at the third lumbar vertebral level (sarcopenia) is a marker of malnutrition and is independently associated with mortality in patients with cirrhosis. Instead of monitoring sarcopenia by cross-sectional imaging, we investigated whether ultrasound-based measurements of peripheral muscle mass, measures of muscle function, along with nutritional factors, are associated with severe loss of muscle mass. Methods We performed a prospective study of 159 outpatients with cirrhosis (56% male; mean age, 58 ± 10 years; mean model for end-stage liver disease score, 10 ± 3; 60% Child-Pugh class A) evaluated at the Cirrhosis Care Clinic at the University of Alberta Hospital from March 2011 through September 2012. Lumbar skeletal muscle indices were determined by computed tomography or magnetic resonance imaging. We collected clinical data and data on patients' body composition, nutrition, and thigh muscle thickness (using ultrasound analysis). We also measured mid-arm muscle circumference, mid-arm circumference, hand grip, body mass index, and serum level of albumin; patients were evaluated using the subjective global assessment scale. Findings from these analyses were compared with those from cross-sectional imaging, for each sex, using logistic regression analysis. Results Based on cross-sectional imaging analysis, 43% of patients had sarcopenia (57% of men and 25% of women). Results from the subjective global assessment, serum level of albumin, and most nutritional factors were significantly associated with sarcopenia. We used multivariate analysis to develop a model to identify patients with sarcopenia, and developed a nomogram based on body mass index and thigh muscle thickness for patients of each sex. Our model identified men with sarcopenia with an area under the receiver operating characteristic curve value of 0.78 and women with sarcopenia with an area under the receiver operating characteristic curve value of 0.89. Conclusions In a prospective study of patients with cirrhosis, we found that the combination of body mass index and thigh muscle thickness (measured by ultrasound) can identify male and female patients with sarcopenia almost as well as cross-sectional imaging (area under the receiver operating characteristic curve values of 0.78 and 0.89, respectively). These factors might be used in screening and routine nutritional monitoring of patients with cirrhosis.

Background: Amoebic liver abscess (ALA) may be associated with significant morbidity and mortality, but nationwide American data is unavailable. Our objective was to describe ALA epidemiology and outcomes in USA from a population-based perspective. Methods: Patients hospitalized with ALA between 1993 and 2007 were identified using the Nationwide Inpatient Sample. Patient characteristics, interventions and outcomes including mortality were determined. The annual incidence of ALA and temporal trends were determined using the negative binomial regression models. Results: Between 1993 and 2007, 848 hospitalizations for ALA, corresponding to ∼4100 hospitalizations nationwide, were identified. The annual incidence was 1.38 per million population with a 2.4% [95% confidence interval (CI) 0–4.8%; P=0.06] average annual decline during this study. Most patients were hospitalized in western (54%) and southern states (27%), and 48% were Hispanic. Males (incidence rate ratio vs. females: 4.53; 95% CI 4.19–4.90) had the highest incidence rates. Percutaneous and surgical drainage was required in 48 and 7% of patients respectively. Although length of stay [median, 6 days; interquartile range (IQR) 4–10] and hospital charges (US$25 345; IQR US$15 030–42 275) were substantial, in-hospital mortality was rare (0.8%). Females [odds ratio (OR) 6.12; CI 1.39–26.8], patients ≥60 years (OR 13.3; 95% CI 2.5–71.5), and those with ≥3 comorbidities (OR 5.80; 95% CI 1.30–25.8), particularly malnutrition, had an increased risk of death. Conclusions: ALA is rare and the incidence has decreased in USA. Young, Hispanic males in southwestern states are most frequently affected. Mortality caused by ALA is lower than what was reported previously.

The purpose of this study was to determine whether morbidity and mortality in patients undergoing elective resection of colon cancer are associated with surgeon or hospital volume. Using the Nationwide Inpatient Sample database, we identified all adult patients who underwent elective resection for colon cancer as their primary procedure between 2003 and 2007. Cases were divided into three groups according to the mean number of resections performed annually by each surgeon: low volume (≤4/year), intermediate volume (5–9/year), or high volume (≥10/year). Annual hospital case-load was also categorized as low volume (≤30/year), intermediate volume (31–60/year), and high volume (≥61/year). Multiple logistic regression models were used to identify differences in morbidity and mortality. A total of 54,000 patients underwent resection of colon cancer by 7,313 surgeons in 1,398 hospitals. After adjusting for important covariates including hospital volume, colon cancer resection by high-volume surgeons was an independent predictor of decreased morbidity (odds ratio [OR], 0.91; 95% CI, 0.85–0.97) and mortality (OR, 0.75; 95% CI, 0.65–0.86). Mortality was lowest among patients operated on by high-volume surgeons in high-volume hospitals (2.2% vs. 3.9%; OR, 0.56; 95% CI, 0.46–0.68). In patients undergoing elective resection of colon cancer, procedures done by high-volume surgeons are associated with decreased morbidity and mortality.

Background Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients. Methods We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes. In a sensitivity analysis, the study population was restricted to PBC patients using ursodeoxycholic acid (UDCA). Results We identified 1,177 PBC patients during our study period. In our cohort, 86 patients (7.3%) had a depression diagnosis prior to PBC diagnosis, while 79 patients (6.7%) had a depression diagnosis after PBC diagnosis. Ten-year incidence of mortality, decompensated cirrhosis, and liver transplantation were 13.4%, 6.6%, and 2.0%, respectively. In our adjusted models, depression status was not a predictor of poor outcomes. After studying all classes of antidepressants, using the atypical antidepressant mirtazapine after PBC diagnosis was significantly protective (Adjusted HR 0.23: 95% CI 0.07–0.72) against poor liver outcomes (decompensation, liver transplant, mortality), which remained statistically significant in patients using UCDA (HR 0.21: 95% CI 0.05–0.83). Conclusions In our study, depression was not associated with poor clinical outcomes. However, using the antidepressant mirtazapine was associated with decreased mortality, decompensated cirrhosis and liver transplantation in PBC patients. These findings support further assessment of mirtazapine as a potential treatment for PBC patients.

Background: The outcomes of pregnancy in patients with cirrhosis are poorly described. Our objective was to assess obstetric outcomes in cirrhotic women and their infants from a population-based perspective. Methods: We analysed the 1993–2005 US Nationwide Inpatient Sample database to identify obstetric hospitalizations among patients with cirrhosis (n=339) and controls matched on age, hospital and year (n=6625). The effect of cirrhosis on maternal and fetal outcomes was evaluated using regression models with adjustment for patient and hospital factors. Results: Between 1993 and 2005, 114 antepartum and 225 delivery admissions in cirrhotic patients were identified. The estimated mean number of deliveries nationwide increased from 68 to 106 annually between 1993 and 1999 and 2000 and 2005 (P=0.0004). Patients with cirrhosis were more likely to deliver by caesarean [42 vs. 28%; adjusted odds ratio (OR) 1.41; 95% confidence interval (CI) 1.06–1.88]. Maternal (1.8 vs. 0%; P

BACKGROUND: Large-scale epidemiological studies of primary biliary cirrhosis (PBC) have been hindered by difficulties in case ascertainment.OBJECTIVE: To develop coding algorithms for identifying PBC patients using administrative data – a widely available data source.METHODS: Population-based administrative databases were used to identify patients with a diagnosis code for PBC from 1994 to 2002. Coding algorithms for confirmed PBC (two or more of antimitochondrial antibody positivity, cholestatic liver biochemistry and/or compatible liver histology) were derived using chart abstraction data as the reference. Patients with a recorded PBC diagnosis but insufficient confirmatory data were classified as ‘suspected PBC’.RESULTS: Of 189 potential PBC cases, 119 (60%) had confirmed PBC and 28 (14%) had suspected PBC. The optimal algorithm including two or more uses of a PBC code had a sensitivity of 94% (95% CI 71% to 100%) and positive predictive values of 73% (95% CI 61% to 75%) for confirmed PBC, and 89% (95% CI 82% to 94%) for confirmed or suspected PBC. Sensitivity analyses revealed greater accuracy among women, and with the use of multiple data sources and one or more years of data. Inclusion of diagnosis codes for conditions frequently misclassified as PBC did not improve algorithm performance.CONCLUSIONS: Administrative databases can reliably identify patients with PBC and may facilitate epidemiological investigations of this condition.

Liver transplant recipients and their infants may have an increased risk of obstetric complications. Our objective was to describe pregnancy outcomes in women with a prior transplant from a population-based perspective. We analyzed the 1993–2005 US Nationwide Inpatient Sample database to identify obstetric hospitalizations among transplant recipients (n = 206) and controls matched by age, hospital, and year (n = 4060). The effect of prior transplantation on maternal and fetal outcomes was evaluated with regression models with adjustments for patient and hospital factors, including admission to a transplant center. Between 1993 and 2005, 146 delivery admissions among liver transplant recipients were identified. Cesarean deliveries were more common among transplant recipients (38% versus 24%; P = 0.0001); however, this difference was not significant after multivariate adjustment [OR (odds ratio) = 0.87; 95% confidence interval (CI) = 0.60–1.27]. Maternal mortality was similar among cases and controls (0% versus 0.02%; P = 1.00), but transplant patients had higher rates of fetal mortality (6.3% versus 2.0%; P = 0.0006), antepartum admission (OR = 2.27; 95% CI = 1.59–3.25), and maternal (OR = 2.63; 95% CI = 1.82–3.80) and fetal complications (OR = 2.49; 95% CI = 1.68–3.70). Gestational hypertension (30% versus 9%; P < 0.0001) and postpartum hemorrhage (8% versus 3%; P = 0.009) were more common among transplant recipients; their infants had higher rates of prematurity (27% versus 11%; P < 0.0001), distress (10% versus 5%; P = 0.005), and growth restriction (5% versus 2%; P = 0.05) but not congenital anomalies. Hospitalization in a transplant center (∼50%) was associated with similar obstetric outcomes. In conclusion, although most pregnancy outcomes are favorable, liver transplant recipients and their infants have an increased risk of obstetric complications. Additional studies evaluating mechanisms aimed at reducing these complications are necessary. Liver Transpl 16:56–63, 2010. © 2009 AASLD.

Background: The risk of cardiac surgery in patients with cirrhosis is poorly defined. Our objective was to describe outcomes of coronary artery bypass graft (CABG) surgery in cirrhotic patients from a population-based perspective. Methods: We analysed the 1998–2004 Nationwide In-patient Sample to identify patients hospitalized for CABG surgery. The effect of cirrhosis on mortality, complications, length of stay (LOS) and charges was evaluated using logistic regression models. Results: Between 1998 and 2004, there were 403 094 CABG admissions; 711 patients (0.2%) had cirrhosis. The average annual number of surgeries increased 4.2% [95% confidence interval (CI) 0.7–7.8] in cirrhotic patients, but decreased 5.5% (3.4–7.5) in non-cirrhotic patients. Patients with cirrhosis had an increased risk of mortality [17 vs. 3%; adjusted odds ratio (OR) 6.67; 95% CI 5.31–8.31], complications [43 vs. 28%; OR 1.99 (95% CI 1.72–2.30)] and greater LOS and charges (P

Risk-adjusted health outcomes are often used to measure the quality of hospital care, yet the optimal approach in patients with liver disease is unclear. We sought to determine whether assessments of illness severity, defined as risk for in-hospital mortality, vary across methods in patients with cirrhosis. We identified 258,731 patients with cirrhosis hospitalized in the Nationwide Inpatient Sample between 2002 and 2005. The performance of four common risk adjustment methods (the Charlson/Deyo and Elixhauser comorbidity algorithms, Disease Staging, and All Patient Refined Diagnosis Related Groups [APR-DRGs]) for predicting in-hospital mortality was determined using the c-statistic. Subgroup analyses were conducted according to a primary versus secondary diagnosis of cirrhosis and in homogeneous patient subgroups (hepatic encephalopathy, hepatocellular carcinoma, congestive heart failure, pneumonia, hip fracture, and cholelithiasis). Patients were also ranked according to the probability of death as predicted by each method, and rankings were compared across methods. Predicted mortality according to the risk adjustment methods agreed for only 55%–67% of patients. Similarly, performance of the methods for predicting in-hospital mortality varied significantly. Overall, the c-statistics (95% confidence interval) for the Charlson/Deyo and Elixhauser algorithms, Disease Staging, and APR-DRGs were 0.683 (0.680–0.687), 0.749 (0.746–0.752), 0.832 (0.829–0.834), and 0.875 (0.873–0.878), respectively. Results were robust across diagnostic subgroups, but performance was lower in patients with a primary versus secondary diagnosis of cirrhosis. Conclusion: Mortality analyses in patients with cirrhosis require sensitivity to the method of risk adjustment. Because different methods often produce divergent severity rankings, analyses of provider-specific outcomes may be biased depending on the method used. (HEPATOLOGY 2008.)

Acetaminophen overdose is the most common cause of acute liver failure in the U.S. and other Western countries. Unintentional overdoses, alcohol abuse, and underlying liver disease might increase the risk of hepatotoxicity. In this population-based study, we examined outcomes of acetaminophen overdose, with particular attention to these risk factors.Patients hospitalized for acetaminophen overdose between 1995 and 2004 were identified retrospectively by using administrative data. Comorbid conditions, suicidal intent, and hepatotoxicity were identified by using International Classification of Diseases-Ninth Revision-Clinical Modification and International Statistical Classification of Diseases and Health-Related Problems, 10th revision diagnostic codes.During the 10-year interval, 1543 patients were hospitalized for acetaminophen overdose; 34% were alcohol abusers, 3% had liver disease, and 13% overdosed unintentionally. Seventy patients (4.5%) developed hepatotoxicity. Unintentional overdoses (odds ratio [OR], 5.18; 95% confidence interval [CI], 3.00-8.95), alcohol abuse (OR, 2.21; 95% CI, 1.30-3.76), underlying liver disease (OR, 3.50; 95% CI, 1.57-7.77), and N-acetylcysteine treatment (OR, 6.75; 95% CI, 2.78-16.39) were independently associated with hepatotoxicity. Fifteen patients (1.0%) died in-hospital; risk factors included older age, unintentional overdoses, alcohol abuse, comorbidities including liver disease, and hepatotoxicity (14% vs 0.3%; P.0005). During a median follow-up of 5.2 years (range, 1 day-11.0 years), 79 patients (5.1%) died. Approximately half of these deaths were due to preventable conditions including suicide, substance abuse, and trauma.In this population-based study, acetaminophen overdose had a relatively benign short-term course but was associated with substantial long-term mortality caused by preventable conditions. Acetaminophen-related hepatotoxicity is more common in patients with unintentional overdoses, alcohol abuse, and underlying liver disease.

Background: Liver biopsy is an important tool in the management of patients with liver disease. Because biopsy practices may be changing, we studied patterns of use in a large Canadian Health Region. We aimed to describe trends in biopsy utilization and the incidence and costs of complications from a population-based perspective. Methods: Administrative databases were used to identify percutaneous liver biopsies performed between 1994 and 2002. Significant complications were identified by reviewing medical records of patients hospitalized within 7 days of a biopsy and those with a diagnostic code indicative of a procedural complication. Analyses of biopsy rates employed Poisson regression. Results: Between 1994 and 2002, 3627 patients had 4275 liver biopsies (median 1 per patient; range 1–12). Radiologists performed the majority (90%), particularly during the latter years (1994 vs. 2002: 73 vs. 98%; P

Accurately staging hepatitis C virus (HCV)-related fibrosis is crucial for treatment decisions and prognostication. Our objective was to systematically review studies describing the accuracy of serum marker panels for predicting fibrosis in HIV/HCV-coinfected patients.Studies comparing serum marker panels with biopsy in HIV/HCV-coinfected patients were identified. Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) examined test accuracy for detecting significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression.Five studies (n = 574) including four fibrosis measures (APRI [n = 4 studies], Forns' [n = 2], FibroTest [n = 1], SHASTA [n = 1]) met the inclusion criteria. The prevalence of significant fibrosis and cirrhosis were 51% and 16%, respectively. For the prediction of significant fibrosis, the summary AUC was 0.82 (95% CI 0.78-86) and diagnostic odds ratio was 7.8 (5.1-11.9). For cirrhosis, these figures were 0.83 (0.69-0.97) and 11.0 (4.6-26.2), respectively. Meta-regression including study factors (methodological quality and biopsy adequacy), patient characteristics (age, gender, CD4 count), and fibrosis measure failed to identify important predictors of accuracy.Available fibrosis marker panels have acceptable performance for identifying significant fibrosis and cirrhosis in HIV/HCV-coinfected patients but are not yet adequate to replace liver biopsy. Additional studies are necessary to identify the optimal measure.

BACKGROUND: Nearly 1% of Canadians are infected with the hepatitis C virus (HCV). Simulation analyses have suggested that HCV will place an increasing burden on the health care system as the infected population ages, but supportive clinical data are limited.OBJECTIVES: To study temporal trends in HCV-related hospitalizations and predictors of increased health care utilization from a Canadian population-based perspective.METHODS: An administrative hospitalization database from the Calgary Health Region was used to identify patients who were admitted for HCV between 1994 and 2004. The primary outcomes were liver-related HCV hospitalizations, length of stay, hospital costs and in-hospital mortality. Average annual growth rates in outcomes were calculated and subgroup analyses were conducted according to age, sex and HIV/HCV coinfection status.RESULTS: Between 1994 and 2004, there were 4002 HCV-related hospitalizations; 22% were liver-related. Liver-related hospitalizations, lengths of stay and in-hospital mortality increased approximately fourfold or an average of 15% to 18% annually (PCONCLUSIONS: The present studies’ findings confirm the growing burden of HCV on the Canadian health care system. Strategies to prevent HCV infection and maximize the dissemination and most effective use of potentially curative antiviral therapies are necessary to reduce these trends.

An increasingly wide variety of extrahepatic manifestations have been reported in patients with chronic hepatitis C virus (HCV) infection. Many are immunologic in nature and may be precipitated by interferon-based therapy. Among these associations, mixed cryoglobulinemia is the most prevalent and best characterized. Additional HCV-related immunologic complications include autoantibody production, rheumatologic disorders, immune-mediated cytopenias, and lymphoproliferative disorders; the certainty of association varies for many of these conditions. The mechanisms through which HCV induces these complications are incompletely understood. In this review, we discuss the immunologic complications of HCV infection, focusing on their epidemiology, pathogenesis, and treatment.

BACKGROUND: Surveys originating from universities appear to have higher response rates than those from commercial sources. In light of the growing scrutiny placed on physician-industry relations, the present study aimed to determine the impact of the pharmaceutical industry versus university sponsorship on response to a postal survey completed by Canadian hepatitis C virus (HCV) care providers.PATIENTS AND METHODS: In the present controlled trial, 229 physicians and nurses involved in HCV treatment were randomly assigned to receive a survey with sponsorship from a pharmaceutical company or university. The primary outcome was the proportion of completed surveys returned. The secondary outcomes included the response rate after the first mailing and the number of days taken to respond.RESULTS: One hundred fifteen participants were randomly assigned to receive the pharmaceutical industry survey and 114 were assigned to receive the university survey. The final response rate was 72.9% (167 of 229), which did not differ between the industry and university groups (RR=0.91; 95% CI 0.78 to 1.07). Nurses (OR=2.20; 95% CI 1.08 to 4.48) and participants from an academic centre (OR=3.14; 95% CI 1.64 to 6.00) were more likely to respond. The response rate after the first mailing (RR=0.85; 95% CI 0.68 to 1.07) and the median number of days taken to respond (21 days in both groups; P=0.20) did not differ between the industry and university groups.CONCLUSIONS: Pharmaceutical industry sponsorship does not appear to negatively impact response rates to a postal survey completed by Canadian HCV care providers.

Background: Family history (FHx) of premature coronary artery disease (CAD) is an established cardiovascular risk factor. However the impact of FHx on outcomes of patients with CAD is unclear. Methods & Results: The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) Program is an inclusive prospective registry of patients undergoing coronary angiography. Between April 2002 and Mar 2013, 99,667 patients were enrolled. 30,030 (30%) patients reported FHx, defined as a first degree relative with premature CAD (males Compared to those without FHx, those with FHx were younger (60.1 vs 64.0 years, p Overall, FHx was associated with reduced 1-year mortality in fully adjusted models (odds ratio [OR] 0.56, 95% CI 0.51 to 0.62). This protective association was present in patients with and without a previous CAD event (OR 0.66 [95% CI 0.60 to 0.78] vs 0.53 [95% CI 0.47 to 0.59], respectively), and in patients with and without an ACS (OR 0.56 [95% CI 0.50 to 0.63] vs 0.56 [95% CI 0.48 to 0.65], respectively). There was slight attenuation of association with age, but FHx remained protective even in those aged 80 or more (OR 0.72, 95% CI 0.57 to 0.90). Conclusion: In patients with angiographic CAD, a family history of premature CAD is associated with lower mortality, independent of clinical characteristics, mode of presentation, and extent of disease. Further investigation of potential patient- and system-level mediators of this seemingly paradoxical relationship is required.

Background Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease. Methods In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation). The performance of LSM to predict complications was determined using the c-statistic. Results Among 2,052 patients (median age 51 years, 65% with hepatitis B or C), 87 patients (4.2%) died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0–23.5 months). Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P