Health Care Utilization and Costs for Patients With End-Stage Liver Disease Are Significantly Higher at the End of Life Compared to Those of Other Decedents.

BACKGROUND & AIMS: Patients with end-stage liver disease (ESLD) have progressively complex medical needs. However, little is known about their end-of-life health care utilization or associated costs. We performed a population-based study to evaluate the end-of-life direct utilization and costs for patients with ESLD among health care sectors in the province of Ontario. METHODS: We used linked Ontario health administrative databases to conduct a population-based retrospective cohort study of all decedents from April 1, 2010, through March 31, 2013. Patients with ESLD were compared with patients without ESLD with regard to total health care utilization and costs in the last year and last 90 days of life. RESULTS: The median age at death was significantly lower for ESLD decedents (65 y; interquartile range, 56-75 y) than for individuals without ESLD (80 y; interquartile range, 68-88 y). The median cost in the last year of life was significantly greater for patients with ESLD ($51,235 vs $44,456 without ESLD) (P < .001). Median ESLD end-of-life care costs also significantly exceeded those associated with 4 of the 5 most resource-intensive chronic conditions ($69,040 for ESLD vs $59,088 for non-ESLD) (P < .001). Cost differences were most pronounced in the final 90 days of life. During this period, patients with ESLD spent 4.7 more days in the hospital (95% CI, 4.3-5.1 d) than patients without ESLD (P < .0001), had significantly higher odds of dying in an institutional setting (odds ratio, 1.8; 95% CI, 1.7-1.9) (P < .0001), and incurred an additional $4201 in costs (95% CI, $3384-$5019; P < .0001). CONCLUSIONS: In a population-based study in Canada, we found that patients with ESLD incur significantly higher end-of-life care costs than decedents without ESLD, predominantly owing to increased time in the hospital during the final 90 days of life.

Metabolic syndrome and liver steatosis occur at lower body mass index in US Asian patients with chronic hepatitis B.

We have previously shown that ultrasound identifies significant steatosis in patients with chronic HBV (CHB). However, the relationship between CHB, metabolic syndrome (MS) and steatosis is poorly understood. In this tertiary care, single-centre retrospective cohort study of 617 CHB patients, we examined the prevalence of MS and steatosis in a predominantly Asian US cohort. Patients were predominantly male (57%) with a mean age of 53 years, Asian (88%), on HBV therapy (64%) and had undetectable DNA (65%). 21% had MS, of which hypertension (41%), dyslipidemia (41%) and obesity (32%) were most common. Patients with MS were more likely to be older (60 vs 52 [P < 0.001]), have steatosis (40% vs 17% [P < 0.001]) and have a higher ALT (29 vs 25 [P = 0.003]). Of the 22% of patients with steatosis by ultrasound, a higher prevalence of MS (38% vs 16% [P < 0.001]) and higher ALT (31 vs 24 [P < 0.001]) was observed. Asian patients had a lower BMI than non-Asians (mean 24 vs 26 [P = 0.001]) but similar prevalence of MS risk factors and steatosis. Asian patients with a BMI between 25 and 30 and two other MS risk factors had steatosis at the same rate as patients with a BMI > 30 and at least two other MS risk factors. We found a strong association between MS, steatosis and elevated ALT in HBV patients. Asian HBV patients have lower BMI than non-Asians yet have the same prevalence of steatosis and other MS risk factors, supporting guidelines for lower BMI targets in Asians.

Moderate Alcohol Use Is Not Associated With Fibrosis Progression in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Women: A Prospective Cohort Study.

BACKGROUND: Heavy alcohol use can lead to progressive liver damage, especially in individuals with chronic hepatitis C (HCV); however, the impact of nonheavy use is not clear. We studied long-term effects of modest alcohol use on fibrosis progression in a large cohort of women coinfected with human immunodeficiency virus (HIV)/HCV. METHODS: Alcohol intake was ascertained every 6 months and use categorized as abstinent, light (1-3 drinks/week), moderate (4-7 drinks/week), heavy (>7 drinks/week), and very heavy (>14 drinks/week). Fibrosis progression was defined as the change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) units per year using random-intercept, random-slope mixed modeling. RESULTS: Among 686 HIV/HCV-coinfected women, 46.0% reported no alcohol use; 26.8% reported light use, 7.1% moderate use, and 19.7% heavy use (6.7% had 8-14 drinks/week and 13.0% had >14 drinks/week) at cohort entry. Median FIB-4 at entry was similar between groups. On multivariable analysis, compared to abstainers, light and moderate alcohol use was not associated with fibrosis progression (0.004 [95% confidence interval {CI}, -.11 to .12] and 0.006 [95% CI, -.18 to .19] FIB-4 units/year, respectively). Very heavy drinking (>14 drinks/week) showed significant fibrosis acceleration (0.25 [95% CI, .01-.49] FIB-4 units/year) compared to abstaining, whereas drinking 8-14 drinks per week showed minimal acceleration of fibrosis progression (0.04 [95% CI, -.19 to .28] FIB-4 units/year). CONCLUSIONS: Light/moderate alcohol use was not substantially associated with accelerated fibrosis progression, whereas drinking >14 drinks per week showed increased rates of fibrosis progression. Women with HIV/HCV infection should be counseled against heavy alcohol consumption, but complete abstinence may not be required to prevent accelerated liver fibrosis progression.

Sonography Predicts Liver Steatosis in Patients With Chronic Hepatitis B.

OBJECTIVES: Liver inflammation and fibrosis may impair the ability of sonography to identify steatosis. We determined the accuracy of sonography in grading steatosis in patients with chronic hepatitis B compared to liver biopsy. METHODS: We conducted was a single-center retrospective study of all nontransplanted patients with chronic hepatitis B undergoing sonography and liver biopsy between 2004 and 2014 (n = 109). Steatosis was graded by sonography as none, mild, moderate, or severe. Liver histologic analysis graded steatosis (0, <5%; 1, <33%; 2, <66%; or 3, ≥66%) and staged fibrosis (F0-F4). Severe steatosis was defined as grade 2 or 3. Clinical variables within 6 months of liver biopsy were collected, and the association with steatosis was analyzed by univariate logistic regression. RESULTS: Patients were predominantly Asian (83%), male (62%), and hepatitis B e antigen negative (62%). Twenty-nine percent of patients were obese; 9% had diabetes mellitus; 23% had hypertension; and 31% had dyslipidemia. Forty-four percent of patients had steatosis on liver biopsy; 8% had severe steatosis. The presence of any steatosis on sonography correctly identified any steatosis on liver biopsy in 29 of 48 patients (60%). The absence of steatosis on sonography ruled out severe steatosis on biopsy (specificity, 100%). Severe steatosis on sonography correctly predicted the presence of severe steatosis on liver biopsy (89%; P < .001); however, it was not accurate at distinguishing between steatosis grades. Predictors of biopsy-proven steatosis on univariate analysis included diabetes (P < .001), hypertension (P = .03), hypercholesterolemia (P = .02), and body mass index (P < .001). CONCLUSIONS: Sonography had excellent accuracy in identifying patients with steatosis on biopsy. Abdominal sonography can be used to predict clinically important steatosis in patients with chronic hepatitis B.

Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/Hepatitis C Virus-coinfected Women.

BACKGROUND: Marijuana (hereafter "tetrahydrocannabinol [THC]") use has been associated with liver fibrosis progression in retrospective analyses of patients with chronic hepatitis C (HCV). We studied long-term effects of THC on fibrosis progression in women coinfected with human immunodeficiency virus (HIV)/HCV enrolled in the Women's Interagency HIV Study (WIHS). METHODS: Liver fibrosis was categorized according to FIB-4 scores as none, moderate, or significant. THC and alcohol use were quantified as average exposure per week. Associations between THC use and progression to significant fibrosis were assessed using Cox proportional hazards regression. RESULTS: Among 575 HIV/HCV-coinfected women followed for a median of 11 (interquartile range, 6-17) years, 324 (56%) reported no THC use, 141 (25%) less than weekly use, 70 (12%) weekly use, and 40 (7%) daily use at WIHS entry. In univariable analysis, entry FIB-4 score (hazard ratio [HR], 2.26 [95% confidence interval {CI}, 1.88-2.73], P < .001), log HCV RNA (HR, 1.19 [95% CI, 1.02-1.38], P = .02), tobacco use (HR, 1.37 [95% CI, 1.02-1.85], P = .04), CD4(+) count (risk per 100-cell increase: HR, 0.90 [95% CI, .86-.95], P < .001), and log HIV RNA (HR, 1.18 [95% CI, 1.05-1.32], P = .005) were associated with progression to significant fibrosis, as was cumulative alcohol use in follow-up (HR, 1.03 [95% CI, 1.02-1.04], P < .001). In multivariable analysis, entry FIB-4, entry CD4(+) count, and cumulative alcohol use remained significant. Cumulative THC use was not associated with fibrosis progression (HR, 1.01 [95% CI, .92-1.10], P = .83). CONCLUSIONS: In this large cohort of HIV/HCV-coinfected women, THC was not associated with progression to significant liver fibrosis. Alcohol use was independently associated with liver fibrosis, and may better predict fibrosis progression in HIV/HCV-coinfected women.

Utility of MRCP in surveillance of primary sclerosing cholangitis associated hepatobiliary malignancy: 15 year experience at a single institution in Ontario, Canada.

OBJECTIVE: Magnetic resonance cholangiopancreatography (MRCP) is used for the surveillance of primary sclerosing cholangitis (PSC) and its associated complications. The time interval gap for subsequent follow-up MRCP is variable depending on clinical practice patterns, therefore this study was done to assess the MRCP follow-up strategy used in our institution for screening PSC-associated hepatobiliary malignancies. MATERIALS AND METHODS: This retrospective observational cohort included MRCP studies in adult patients, with clinical and radiological diagnosis of PSC over the past 15-year period between January 1, 2003 to December 31, 2018. The study population was grouped based on the presence and absence of PSC-associated malignancy. The frequency of MRCP follow-up was compared between the groups to look for MRI ordering trends in surveillance for PSC-associated complications. RESULTS: The overall median interval follow-up with MRCP was 14 months. The median follow-up interval in cases with PSC-associated malignancy was 6.0 months, compared to 13.1 months in the PSC group without malignancy (p 0.013). During the study period, the PSC-associated malignancy group had a median number of 7.5 scans, while the no malignancy group had a median number of 4 scans. Three patients (3/10, 30%) developed hepatobiliary malignancies within the first year of clinical diagnosis of PSC. The most common malignancy associated with PSC was cholangiocarcinoma (4.6%,7/10). Other PSC-associated malignancies included carcinoma gallbladder (1.3%,2/10), and hepatocellular carcinoma (0.6%,1/10). The median age of PSC associated malignancies was 56 (IQR 15) and higher compared to median age of PSC group without malignancies 46 (IQR 25.5), p 0.035. CONCLUSION: The median interval for subsequent follow-up MRCP in our study cohort was 14 months. One-third of PSC-associated hepato-biliary malignancies developed within the first year of clinical diagnosis of PSC, and the risk of PSC-associated hepato-biliary malignancy is constant after the first year.

Reduced immune responses to hepatitis B primary vaccination in obese individuals with nonalcoholic fatty liver disease (NAFLD).

Obesity and cirrhosis are associated with poor hepatitis B virus (HBV) vaccine responses, but vaccine efficacy has not been assessed in nonalcoholic fatty liver disease (NAFLD). Sixty-eight HBV-naïve adults with NAFLD were enrolled through the Canadian HBV network and completed three-dose HBV or HBV/HAV vaccine (Engerix-B®, or Twinrix®, GlaxoSmithKline). Anti-HBs titers were measured at 1-3 months post third dose. In 31/68 subjects enrolled at the coordinating-site, T-cell proliferation and follicular T-helper cells (pTFH) were assessed using PBMC. Immune response was also studied in NAFLD mice. NAFLD patients were stratified as low-risk-obesity, BMI < 35 (N = 40) vs. medium-high-risk obesity, BMI > 35 (N = 28). Anti-HBs titers were lower in medium/high-risk obesity, 385 IU/L ± 79 vs. low-risk obesity class, 642 IU/L ± 68.2, p = 0.02. High-risk obesity cases, N = 14 showed lower vaccine-specific-CD3+ CD4+ T-cell response compared to low-risk obesity patients, N = 17, p = 0.02. Low vaccine responders showed dysfunctional pTFH. NAFLD mice showed lower anti-HBs levels and T-cell response vs. controls. In conclusion, we report here that obese individuals with NAFLD exhibit decreased HBV vaccine-specific immune responses.

Prophylactic endotracheal intubation in critically ill patients with upper gastrointestinal bleed: A systematic review and meta-analysis.

BACKGROUND AND AIM: Prophylactic endotracheal intubation for airway protection prior to endoscopy for the management of severe upper gastrointestinal bleeding (UGIB) is controversial. The aim of this meta-analysis is to examine the clinical outcomes and costs related to prophylactic endotracheal intubation compared to no intubation in UGIB. METHODS: EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were used to identify studies through June 2017. Data regarding mortality, total hospital and intensive care unit length of stay (LOS), pneumonia, and cardiovascular events were collected. The DerSimonian-Laird random effects models were used to calculate the inverse variance-based weighted, pooled treatment effect across studies. RESULTS: Seven studies (five manuscripts and two abstracts) were identified (5662 total patients). Prophylactic intubation conferred an increased risk of death (odds ratio [OR], 2.59, 95% confidence interval [CI]: 1.01-6.64), hospital LOS (mean difference, 0.96 days, 95% CI: 0.26-1.67), and pneumonia (OR 6.58, 95% CI: 4.91-8.81]) compared to endoscopy without intubation. The LOS-related cost was greater when prophylactic intubation was performed ($9020 per patient, 95% CI: $6962-10 609) compared to when it was not performed ($7510 per patient, 95% CI: $6486-8432). There was no difference in risk of cardiovascular events after sensitivity analysis. CONCLUSION: Prophylactic intubation in severe UGIB is associated with a greater risk of pneumonia, LOS, death, and cost compared to endoscopy without intubation. Randomized trials examining this issue are warranted.

An Assessment of the Clinical Accuracy of Ultrasound in Diagnosing Cirrhosis in the Absence of Portal Hypertension.

Ultrasound is an invaluable tool for the diagnosis of hepatocellular carcinoma and portal hypertension. However, the accuracy of ultrasound in diagnosing cirrhosis in the absence of portal hypertension has not been well studied. Using the specific terms cirrhosis or nodular(ity), a retrospective evaluation was conducted on abdominal ultrasounds performed between 2008 and 2013. Patients with evidence of portal hypertension were excluded from the evaluation. Charts were reviewed for evidence of cirrhosis on liver biopsy performed within 1 year of the ultrasound. Of the 69 patients whose ultrasound findings reported cirrhosis without portal hypertension who underwent liver biopsy, 47 (68%) had histologic evidence of cirrhosis. When patients with advanced fibrosis (F3 or F4) on liver biopsy were included, the sensitivity of the ultrasound improved to 80%. One in 5 biopsies showed only mild to moderate or no fibrosis (F0-F2). Sonographic assessment by experts may falsely suggest or overestimate cirrhosis. In the absence of objective evidence of portal hypertension, caution should be taken in diagnosing cirrhosis based on sonographic interpretation alone.

Reconcilable differences: a cross-sectional study of the relationship between socioeconomic status and the magnitude of short-acting beta-agonist use in asthma.

STUDY OBJECTIVE: To assess the association between socioeconomic status (SES) and short-acting (SA) beta-agonist use, controlling for asthma severity. DESIGN: Cross-sectional study. SETTING: Vancouver, BC, Canada. PARTICIPANTS: Two hundred two asthmatics between 19 years and 50 years of age and residing in the greater Vancouver regional district. MEASUREMENTS: The quantity of SA beta-agonist used in the previous year was collected by self-report; pulmonary function and beta-receptor genotype were measured on each participant. SES was measured at both the individual and population levels. Five methods of adjustment for asthma severity were used, as follows: the Canadian Asthma Consensus Guidelines, three previously developed asthma-severity scores, and forward stepwise multiple regression modeling. Polychotomous logistic regression was used to assess all relationships. RESULTS: Independent of the method used to measure SES or adjust for asthma severity, lower SES was consistently and significantly associated with the use of greater amounts of SA beta-agonist. Adjusting for severity using the multivariate model explained the most variance of SA beta-agonist use (R(2) adjusted, 0.35 to 0.37). In this model, social assistance recipients were more likely to use greater amounts of SA beta-agonist (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.7 to 6.5). An inverse relationship between SA beta-agonist use and both annual household income (> $50,000; OR, 0.28; 95% CI, 0.13 to 0.60; and $20,000 to $50,000; OR, 0.44; 95% CI, 0.21 to 0.96; relative to <$20,000) and education (completing a bachelor's degree vs no formal education; OR, 0.25; 95% CI, 0.14 to 0.71). Participants living in a neighborhood with higher median household income (OR, 0.91; 95% CI, 0.84 to 0.98 per $1,000 increase) or a higher prevalence of having attained a bachelor's degree (OR, 0.96; 95% CI, 0.84 to 0.98 per 1% increase) were also less likely use greater amounts of SA beta-agonist. Results were consistent for neighborhood unemployment rate. CONCLUSIONS: The social gradient in asthma-related outcomes may be at least partially attributable to poorer asthma control in lower-SES asthmatics.

Hepatitis C antiviral treatment outcomes are comparable between clinical trial participants and recipients of standard-of-care therapy: an analysis of trial effect.

BACKGROUND: Trial effect refers to the impact of clinical trial participation on treatment outcomes. Little literature exists evaluating the magnitude and direction of trial effect in hepatitis C virus (HCV). METHODS: A single-center, retrospective study on HCV antiviral therapy recipients was conducted. Sustained virologic response (SVR), virologic response at treatment weeks 4 and 12, dose interruptions, and adverse events were compared between clinical trial participants and standard-of-care antiviral recipients between September 2000 and November 2011. RESULTS: A total of 449 patients were evaluated (trial: 89, nontrial: 360). Patients were matched for age (trial: 47 years, nontrial: 45 years), sex (male: trial, 74%; nontrial, 72%), and ethnicity (white: trial, 87%; nontrial, 78%). The groups differed in the incidence of genotype 1 infection (trial: 83%, nontrial 53%; P<0.001), liver biopsy rates (trial: 98%, nontrial: 66%; P<0.001), and history of psychiatric illness (trial: 30%, nontrial: 53%; P<0.001). On intent-to-treat analysis, SVR rates were found to be similar (trial: 51%, nontrial: 54%; P=0.86), even when stratified for genotype (G1: trial, 47%; nontrial, 47%; P=0.78). Interferon dose reductions (trial: 18%, nontrial: 6%; P<0.01) were more likely in trial patients, whereas treatment discontinuation because of side effects (trial: 8%, nontrial: 18%; P<0.02) was less likely in them. No differences in safety issues were identified. CONCLUSION: Overall, a trial effect resulting in improved or diminished SVR rates was not identified. Other potential positive and negative variables should be focused upon for HCV patients deliberating between clinical trial participation and receiving standard-of-care treatment.

Bipolar patients can safely and successfully receive interferon-based hepatitis C antiviral treatment.

AIM: Patients with bipolar disease are often not considered for hepatitis C virus (HCV) antiviral treatment and are excluded from clinical trials because of the risk of interferon-induced exacerbation of their underlying mood disorder. As this risk has not been well quantified in bipolar patients, we evaluated the safety and efficacy of HCV treatment in this population. METHODS: A retrospective analysis of HCV patients evaluated at The Ottawa Hospital between January 2000 and February 2008 (n=910) was carried out. Information on demographics, psychiatric history and treatment, baseline liver biopsy and blood work, treatment initiation, adherence, and therapeutic outcomes was collected. This was compared between bipolar patients (B), those with a history of depression (D), and those with no mental health disorders (N). RESULTS: Of 38 bipolar patients (4.2%), 16 (42.1%) initiated HCV treatment, a rate similar to that in patients with a history of depression (41.4%) and in those without psychiatric illness (32.6%). On-treatment psychiatric complications were comparable between the bipolar and depression groups (B=68.8%, D=54.8%; P=0.29) and were higher than in those without psychiatric illness (N=37.1%; P=0.01). Manic episodes were rare. [B=2 (12.5%), D=1 (0.9%), N=1 (0.7%)]. Interferon dose reduction or discontinuation rates for psychiatric complications (B=12.5%, D=7.9%, N=7.4%; P=NS), completion rates (B=50%, D=69%, N=58%), and sustained virologic response rates (genotype 1: B=33%, D=45%, N=49%) were similar between the groups. CONCLUSION: Stable bipolar patients have similar rates of on-treatment psychiatric complications as patients with a history of depression. With pharmacologic intervention and close clinical monitoring, well-selected bipolar patients can successfully complete treatment and achieve outcomes comparable to those in nonbipolar patients.