214 results on '"Muir, AJ"'
Search Results
2. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial
- Author
-
Dore, GJ, Feld, JJ, Thompson, A, Martinello, M, Muir, AJ, Agarwal, K, Mullhaupt, B, Wedemeyer, H, Lacombe, K, Matthews, GV, Schultz, M, Klein, M, Hezode, C, Mercade, GE, Kho, D, Petoumenos, K, Marks, P, Tatsch, F, Dos Santos, AGP, Gane, E, Trinh, R, Erratt, A, Quiene, S, Shaw, I, Filep, E, Roberts, S, Foster, G, Curry, M, Warlow, J, Mauss, S, Stedman, C, Vachon, M-L, Christensen, S, Muir, A, Baker, D, Ramji, A, Cornberg, M, Bloch, M, Bourliere, M, Semmo, N, Cannon, M, Tam, E, Jacobson, I, Shaw, D, Levin, J, Tsoi, K, Cooke, G, Matthews, G, Feld, J, Borgia, SM, Baumgarten, A, Dore, GJ, Feld, JJ, Thompson, A, Martinello, M, Muir, AJ, Agarwal, K, Mullhaupt, B, Wedemeyer, H, Lacombe, K, Matthews, GV, Schultz, M, Klein, M, Hezode, C, Mercade, GE, Kho, D, Petoumenos, K, Marks, P, Tatsch, F, Dos Santos, AGP, Gane, E, Trinh, R, Erratt, A, Quiene, S, Shaw, I, Filep, E, Roberts, S, Foster, G, Curry, M, Warlow, J, Mauss, S, Stedman, C, Vachon, M-L, Christensen, S, Muir, A, Baker, D, Ramji, A, Cornberg, M, Bloch, M, Bourliere, M, Semmo, N, Cannon, M, Tam, E, Jacobson, I, Shaw, D, Levin, J, Tsoi, K, Cooke, G, Matthews, G, Feld, J, Borgia, SM, and Baumgarten, A
- Abstract
BACKGROUND & AIMS: Direct-acting antiviral (DAA) therapy for HCV has high efficacy and limited toxicity. We hypothesised that the efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule. METHODS: In this open-label multicentre phase IIIb trial, treatment-naïve adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300 mg-120 mg daily for 8 weeks administered with a simplified or standard monitoring strategy. Clinic visits occurred at baseline and post-treatment week 12 in the simplified arm, and at baseline, week 4, week 8, and post-treatment week 12 in the standard arm. Study nurse phone contact occurred at week 4 and week 8 in both arms. Participants requiring adherence support were not eligible, including those reporting recent injecting drug use. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12), with a non-inferiority margin of 6%. RESULTS: Overall, 380 participants (60% male, 47% genotype 1, 32% genotype 3) with chronic HCV were randomised and treated with glecaprevir-pibrentasvir in the simplified (n = 253) and standard (n = 127) arms. In the intention-to-treat population, SVR12 was 92% (95% CI 89%-95%) in the simplified and 95% (95% CI 92%-99%) in the standard arm (difference between arms -3.2%; 95% CI -8.2% to 1.8%) and did not reach non-inferiority. In the per-protocol population, SVR12 was 97% (95% CI 96%-99%) in the simplified and 98% (95% CI 96%-100%) in the standard arm. No treatment-related serious adverse events were reported. CONCLUSIONS: In patients with chronic HCV infection without cirrhosis, treatment with glecaprevir-pibrentasvir was safe and effective. In comparison to standard monitoring, a simplified monitoring schedule did not achieve non-inferiority. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03117569. LAY SUMMARY: Direct-acting
- Published
- 2020
3. NGM282 for Treatment of Patients With Primary Biliary Cholangitis: A Multicenter, Randomized, Double Blind Placebo Controlled Trial
- Author
-
Mayo, MJ, Wigg, AJ, Leggett, BA, Arnold, H, Thompson, AJ, Weltman, M, Carey, EJ, Muir, AJ, Ling, L, Rossi, SJ, Depaoli, AM, Mayo, MJ, Wigg, AJ, Leggett, BA, Arnold, H, Thompson, AJ, Weltman, M, Carey, EJ, Muir, AJ, Ling, L, Rossi, SJ, and Depaoli, AM
- Abstract
Patients with primary biliary cholangitis (PBC) who had an inadequate response to ursodiol have few treatment options. Alkaline phosphatase (ALP) and bilirubin levels correlate with the risk of liver transplant or death in PBC patients. Fibroblast growth factor (FGF) 19 is a hormone that acts directly in the liver to regulate bile acid synthesis. We evaluated NGM282, an engineered analogue of FGF19, for the treatment of PBC. In this 28-day, double-blind, placebo-controlled phase 2 trial, 45 PBC patients who had an inadequate response to ursodiol were randomly assigned 1:1:1 to receive subcutaneous daily doses of either NGM282 at 0.3 mg (n = 14), 3 mg (n = 16), or placebo (n = 15). The primary endpoint was a change in ALP from baseline after 28 days of treatment. At day 28, ALP was significantly reduced with NGM282 treatment at both 0.3 mg (least-squares mean -51.0 IU/L [standard error (SE) 15.4]) and 3 mg (-66.0 IU/L [SE 16.0]) versus placebo (3.3 IU/L [SE 14.8]), with least-squares mean differences of -54.3 IU/L (95% confidence interval -104.2 to -4.5; P = 0.0149) and -69.3 IU/L (95% confidence interval -120.5 to -18.3; P = 0.0030), respectively. Fifty percent (7 of 14) of patients receiving NGM282 0.3 mg and 46% (6 of 13) of those receiving NGM282 3mg achieved 15% or greater reduction in ALP levels from baseline, compared with 7% (1 of 15) of patients receiving placebo. NGM282 also significantly reduced serum concentrations of transaminases and immunoglobulins. Most adverse events were grade 1 (mild) to grade 2 (moderate) in severity, with gastrointestinal disorders more frequent in the NGM282 treatment groups. No worsening of pruritus was observed with NGM282 treatment. Conclusion: NGM282 administered for 28 days resulted in significant improvements in ALP and transaminase levels compared with placebo, with an acceptable safety profile in patients with PBC. (Hepatology Communications 2018; 00:000-000).
- Published
- 2018
4. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis
- Author
-
Kwo, PY, Poordad, F, Asatryan, A, Wang, S, Wyles, DL, Hassanein, T, Felizarta, F, Sulkowski, MS, Gane, E, Maliakkal, B, Overcash, JS, Gordon, SC, Muir, AJ, Aguilar, H, Agarwal, K, Dore, GJ ; https://orcid.org/0000-0002-4741-2622, Lin, CW, Liu, R, Lovell, SS, Ng, TI, Kort, J, Mensa, FJ, Kwo, PY, Poordad, F, Asatryan, A, Wang, S, Wyles, DL, Hassanein, T, Felizarta, F, Sulkowski, MS, Gane, E, Maliakkal, B, Overcash, JS, Gordon, SC, Muir, AJ, Aguilar, H, Agarwal, K, Dore, GJ ; https://orcid.org/0000-0002-4741-2622, Lin, CW, Liu, R, Lovell, SS, Ng, TI, Kort, J, and Mensa, FJ
- Abstract
Background & Aims Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4 A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1–6 infection. Methods SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1–6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying doses with or without ribavirin for 8 or 12 weeks. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at post-treatment week 12 (SVR12). Results Of the 449 patients who received varying doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1, 2, 3, and 4–6 infection, respectively. Twelve-week treatment achieved SVR12 in 97–100%, 96–100%, 83–94%, and 100% in genotypes 1, 2, 3, and 4–6, respectively. Eight-week treatment with 300 mg glecaprevir plus 120 mg pibrentasvir in genotype 1-, 2-, or 3-infected patients yielded 97–98% SVR12 with no virologic failures. Three (0.7%) patients discontinued treatment due to adverse events; most events were mild (grade 1) in severity. No post-nadir alanine aminotransferase elevations were observed. Conclusions Glecaprevir plus pibrentasvir was well tolerated and achieved high sustained virologic response rates in HCV genotypes 1–6-infected patients without cirrhosis following 8- or 12-week treatment durations. Lay summary The combination of direct-acting antivirals glecaprevir and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV genotype 1–6 infection. This article describes results from two phase II trials investigating a range of d
- Published
- 2017
5. Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis
- Author
-
Muir, AJ, Poordad, F, Lalezari, J, Everson, G, Dore, GJ ; https://orcid.org/0000-0002-4741-2622, Herring, R, Sheikh, A, Kwo, P, Hézode, C, Pockros, PJ, Tran, A, Yozviak, J, Reau, N, Ramji, A, Stuart, K, Thompson, AJ, Vierling, J, Freilich, B, Cooper, J, Ghesquiere, W, Yang, R, McPhee, F, Hughes, EA, Swenson, ES, Yin, PD, Muir, AJ, Poordad, F, Lalezari, J, Everson, G, Dore, GJ ; https://orcid.org/0000-0002-4741-2622, Herring, R, Sheikh, A, Kwo, P, Hézode, C, Pockros, PJ, Tran, A, Yozviak, J, Reau, N, Ramji, A, Stuart, K, Thompson, AJ, Vierling, J, Freilich, B, Cooper, J, Ghesquiere, W, Yang, R, McPhee, F, Hughes, EA, Swenson, ES, and Yin, PD
- Abstract
IMPORTANCE: Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus (HCV) infection and cirrhosis. OBJECTIVE: All-oral therapy with daclatasvir (nonstructural protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in patients with HCV genotype 1 infection and compensated cirrhosis. DESIGN, SETTING, AND PARTICIPANTS: The UNITY-2 study was conducted between December 2013 and October 2014 at 49 outpatient sites in the United States, Canada, France, and Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after completion of treatment. Adult patients with cirrhosis were enrolled in 2 cohorts: HCV treatment-naive or HCV treatment-experienced. Statistical analyses were based on historical controls; there were no internal controls. INTERVENTIONS: All patients received twice-daily treatment with the fixed-dose combination of daclatasvir (30 mg), asunaprevir (200 mg), and beclabuvir (75 mg). In addition, patients within each cohort were stratified according to HCV genotype 1 subtype (1a or 1b) and randomly assigned (1:1) to receive double-blinded weight-based ribavirin (1000-1200 mg/d) or matching placebo. MAIN OUTCOMES AND MEASURES: Sustained virologic response at posttreatment week 12 (SVR12). RESULTS: One hundred twelve patients in the treatment-naive group and 90 patients in the treatment-experienced group were treated and included in the analysis. Enrolled patients were 88% white with a median age of 58 years (treatment-naive group) or 60 years (treatment-experienced group); 74% had genotype 1a infection. SVR12 rates were 98% (97.5%CI, 88.9%-100%) for patients in the treatment-naive group and 93% (97.5% CI, 85.0%-100.0%) for those in the treatment-experienced group when ribavirin was included in the regimen. With the fixed-dose combination alone, response rates were 93% (97.5% CI, 85.
- Published
- 2015
6. Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: Impaired viral kinetics and therapeutic response
- Author
-
Naggie, S, Osinusi, A, Katsounas, A, Lempicki, R, Herrmann, E, Thompson, AJ, Clark, PJ, Patel, K, Muir, AJ, McHutchison, JG, Schlaak, JF, Trippler, M, Shivakumar, B, Masur, H, Polis, MA, Kottilil, S, Naggie, S, Osinusi, A, Katsounas, A, Lempicki, R, Herrmann, E, Thompson, AJ, Clark, PJ, Patel, K, Muir, AJ, McHutchison, JG, Schlaak, JF, Trippler, M, Shivakumar, B, Masur, H, Polis, MA, and Kottilil, S
- Abstract
UNLABELLED: Recent studies have shown that a single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene plays a major role in predicting therapeutic response in hepatitis C virus (HCV)-infected patients treated with pegylated interferon (PEG-IFN)/ribavirin. We sought to investigate the mechanism of the IL28B polymorphism, specifically as it relates to early HCV viral kinetics, IFN pharmacokinetics, IFN pharmacodynamics, and gene expression profiles. Two prospective cohorts (human immunodeficiency virus [HIV]/HCV-coinfected and HCV-monoinfected) completing treatment with IFN/ribavirin were enrolled. Patients were genotyped at the polymorphic site rs12979860. In the HIV/HCV cohort, frequent serum sampling was completed for HCV RNA and IFN levels. DNA microarray of peripheral blood mononuclear cells and individual expression of IFN-stimulated genes (ISGs) were quantified on IFN therapy. The IL28B-favorable (CC) genotype was associated with improved therapeutic response compared with unfavorable (CT or TT) genotypes. Patients with a favorable genotype had greater first- and second-phase viral kinetics (P = 0.004 and P = 0.036, respectively), IFN maximum antiviral efficiency (P = 0.007) and infected cell death loss (P = 0.009) compared with unfavorable genotypes. Functional annotation analysis of DNA microarray data was consistent with depressed innate immune function, particularly of natural killer cells, from patients with unfavorable genotypes (P <0.004). Induction of innate immunity genes was also lower in unfavorable genotypes. ISG expression at baseline and induction with IFN was independent of IL28B genotype. CONCLUSION: Carriers of the IL28B-favorable genotype were more likely to have superior innate immune response to IFN therapy compared with unfavorable genotypes, suggesting that the unfavorable genotype has aberrant baseline induction of innate immune response pathways resulting in impaired virologic response. IL28B genotype is associated wit
- Published
- 2012
7. Telaprevir in Kombination mit Peginterferon alfa 2a und Ribavirin: Analyse von prädefinierten Subpopulationen in der Phase III-Studie
- Author
-
Marcellin, P, primary, Jacobsen, IM, additional, Zeuzem, S, additional, Bzowej, N, additional, Muir, AJ, additional, Reddy, R, additional, Adda, N, additional, Bengtsson, L, additional, Kauffmann, RS, additional, George, S, additional, and Bisceglie, AM, additional
- Published
- 2011
- Full Text
- View/download PDF
8. Telaprevir in Kombination mit Peginterferon und Ribavirin bei nicht vorbehandelten Patienten mit Genotyp-1 HCV: Endgültige Ergebnisse der Phase-III-Studie ADVANCE
- Author
-
McHutchison, JG, primary, Jacobson, IM, additional, Dusheiko, GM, additional, Di Biscegli, AM, additional, Reddy, R, additional, Bzowej, NH, additional, Marcellin, P, additional, Muir, AJ, additional, Bengtsson, L, additional, Dunne, AM, additional, Adda, N, additional, George, S, additional, Kauffman, R, additional, and Zeuzem, S, additional
- Published
- 2011
- Full Text
- View/download PDF
9. IL28B in the era of direct-acting antivirals for hepatitis C.
- Author
-
Muir AJ and Muir, Andrew J
- Published
- 2013
- Full Text
- View/download PDF
10. Using capsule endoscopy to identify GI tract lesions in cirrhotic patients with portal hypertension and chronic anemia.
- Author
-
Canlas KR, Dobozi BM, Lin S, Smith AD, Rockey DC, Muir AJ, Agrawal NM, Poleski MH, Patel K, and McHutchison JG
- Published
- 2008
- Full Text
- View/download PDF
11. In the clinic. Hepatitis C.
- Author
-
Jou JH, Muir AJ, Jou, Janice H, and Muir, Andrew J
- Published
- 2008
- Full Text
- View/download PDF
12. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites.
- Author
-
Muir AJ, Bornstein JD, Killenberg PG, Atlantic Coast Hepatitis Treatment Group, Muir, Andrew J, Bornstein, Jeffrey D, and Killenberg, Paul G
- Abstract
Background: Several small studies have reported a lower response rate to interferon alfa among black patients with chronic hepatitis C infection than among white patients. The increased prevalence of infection with hepatitis C virus (HCV) genotype 1, which has a lower response rate than other genotypes, has been suggested as the cause.Methods: We treated 100 black patients and 100 non-Hispanic white patients with chronic hepatitis C with peginterferon alfa-2b and ribavirin for 48 weeks. Enrollment was controlled so that the two groups had similar proportions of patients with genotype 1 infection. The primary end point was a sustained virologic response, which was defined as a negative test for serum HCV RNA six months after the completion of therapy.Results: In both cohorts, 98 percent of patients had genotype 1 infection. The rate of sustained virologic response was higher among non-Hispanic white patients than among black patients (52 percent vs.19 percent, P<0.001). The black patients also had significantly lower rates of virologic response at 12 weeks and at the end of treatment. Multivariable analyses examining sociodemographic and clinical characteristics found that black race was the only variable significantly associated with the difference in response rate.Conclusions: Black patients with chronic hepatitis C have a lower rate of response to treatment with peginterferon alfa-2b and ribavirin than non-Hispanic white patients, a difference that is not explained by differences in the viral genotype. [ABSTRACT FROM AUTHOR]- Published
- 2004
13. Overcoming barriers to care for hepatitis C.
- Author
-
Clark PJ and Muir AJ
- Published
- 2012
14. Treatment of chronic hepatitis C in blacks and non-Hispanic whites.
- Author
-
Aigner ES, Moriguchi H, Sato C, Muir AJ, and Aigner, Elmar S
- Published
- 2004
15. Treatment of acute hepatitis C with interferon alfa-2b.
- Author
-
Patel R, Germer JJ, Tocci G, Visco-Comandini U, Antonucci G, Muir AJ, Rockey DC, Seligman HK, Fox RK, Cornberg M, Jaeckel E, Manns MP, Muir, Andrew, and Rockey, Don C
- Published
- 2002
16. Barriers and Strategies to Effective Serious Illness Communication for Patients with End-Stage Liver Disease in the Intensive Care Setting.
- Author
-
Brown C, Khan S, Parekh TM, Muir AJ, and Sudore RL
- Abstract
Background: Patients with end-stage liver disease (ESLD) often require Intensive Care Unit (ICU) admission during the disease trajectory, but aggressive medical treatment has not resulted in increased quality of life for patients or caregivers. Methods: This narrative review synthesizes relevant data thematically exploring the current state of serious illness communication in the ICU with identification of barriers and potential strategies to improve performance. We provide a conceptual model underscoring the importance of providing comprehensible disease and prognosis knowledge, eliciting patient values and aligning these values with available goals of care options through a series of discussions. Achieving effective serious illness communication supports the delivery of goal concordant care (care aligned with the patient's stated values) and improved quality of life. Results: General barriers to effective serious illness communication include lack of outpatient serious illness communication discussions; formalized provider training, literacy and culturally appropriate patient-directed serious illness communication tools; and unoptimized electronic health records. ESLD-specific barriers to effective serious illness communication include stigma, discussing the uncertainty of prognosis and provider discomfort with serious illness communication. Evidence-based strategies to address general barriers include using the Ask-Tell-Ask communication framework; clinician training to discuss patients' goals and expectations; PREPARE for Your Care literacy and culturally appropriate written and online tools for patients, caregivers, and clinicians; and standardization of documentation in the electronic health record. Evidence-based strategies to address ESLD-specific barriers include practicing with empathy; using the "Best-Case, Worst Case" prognostic framework; and developing interdisciplinary solutions in the ICU. Conclusion: Improving clinician training, providing patients and caregivers easy-to-understand communication tools, standardizing EHR documentation, and improving interdisciplinary communication, including palliative care, may increase goal concordant care and quality of life for critically ill patients with ESLD., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
- View/download PDF
17. Inadequate Dietary Education and Poor Adherence to a High Protein, Low Sodium Diet in Cirrhosis: Mixed Methods Approach.
- Author
-
Brown C, Hernandez R, Ford T, Aksan N, DiVincenzo C, and Muir AJ
- Subjects
- Humans, Male, Female, Middle Aged, Patient Education as Topic methods, Diet, High-Protein, Caregivers, Aged, Malnutrition diet therapy, Malnutrition prevention & control, Malnutrition etiology, Liver Cirrhosis diet therapy, Liver Cirrhosis complications, Diet, Sodium-Restricted methods, Patient Compliance
- Abstract
Background: Malnutrition in cirrhosis is associated with poor outcomes, leading to guidelines for a high protein, low sodium diet; however, there is no guidance regarding the implementation of diet education in clinical practice., Methods: A mixed methods study enrolled 21 patients with cirrhosis and their caregivers. Semi-structured interviews on barriers and facilitators of dietary education and adherence were conducted. Demographic and clinical data were obtained, along with quantitative measures of dietary adherence, including 24-h food recall and spot urine sodium. Combined deductive and inductive coding was used to identify qualitative themes, along with a quantitative assessment of interviews. Quantitative data was reported using descriptive statistics with frequencies, mean and confidence intervals., Results: Participants were mostly male (16/21) with a mean age 57.8 years (SE 2.8) and MELD-Na 9 (SE 1.2). 4 themes emerged: 1. More than 50% of participants and caregivers endorsed no or inadequate diet education 2. They reported mostly negative experiences with dietary adherence with largest impact on social life 3. Facilitators of adherence included the presence of household support and fear of complications of cirrhosis 4. Overwhelmingly desired non-generic handouts and information. Dietary adherence was poor with only one participant meeting protein and sodium requirements based on food recall. Four participants who adhered to < 2000 mg sodium had inadequate daily caloric intake., Conclusions: Dietary education is inadequate, and adherence to dietary recommendations is poor in patients with cirrhosis. Future studies should use these barriers and facilitators for intervention development., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
18. Psychological processes and alcohol reduction in patients with chronic hepatitis C: Results from the HepART trial.
- Author
-
Evon DM, Yao J, Zimmer C, Muir AJ, Hendershot CS, and Proeschold-Bell RJ
- Abstract
Background: There is a lack of randomized controlled trials of behavioral interventions and process-level research related to alcohol reduction among patients with chronic liver disease (e.g., hepatitis C viral (HCV) infection). We conducted a process-level, secondary analysis of the Hepatitis C-Alcohol Reduction Treatment (HepART) trial to investigate the association between change in psychological processes posited by the Integrated Behavioral Model (IBM) and change in World Health Organization (WHO) drinking risk levels., Methods: Patients with HCV who consume alcohol were recruited from hepatology clinics and received provider-delivered SBIRT (Screening, Brief Intervention, Referral to Treatment) or SBIRT+ 6 months of co-located alcohol counseling. Treatment arms were combined for this analysis because no between-group differences were found. At baseline and 6 months, the timeline followback method was used to determine alcohol risk levels according to the 2000 WHO risk categories (based on average grams of alcohol per day). Changes in alcohol consumption and WHO risk levels were quantified and regressed on change in individual psychological processes (e.g., readiness, self-efficacy, motives, attitudes, and strategies) from baseline to 6 months., Results: At the baseline assessment, 162 participants were classified as abstinent (5%), low (47%), moderate (16%), high (19%), or very high (13%) WHO risk levels. At 6 months, 38% remained at the same risk level and 48% decreased by at least one level. In univariate analyses, changes in 7 of 12 psychological processes were associated with change in risk levels. Adjusted multivariate analyses demonstrated that change in four processes were significantly associated with change in risk levels, including SOCRATES Taking Steps, Ambivalence, and Recognition scores and alcohol reduction strategies., Conclusions: These findings demonstrate significant reductions in quantitative indices of alcohol consumption following opportunistic alcohol interventions in patients with HCV. However, results provided mixed support for associations between change in IBM psychological processes and alcohol consumption., (© 2024 Research Society on Alcohol.)
- Published
- 2024
- Full Text
- View/download PDF
19. Decreased Completion of Ordered Laboratories and Imaging in Telehealth Compared With In-person Hepatology Encounters.
- Author
-
Henson JB, Patel YA, Wall AH, and Muir AJ
- Abstract
Objective: To evaluate order completion after telehealth compared with in-person encounters., Background: Completion of ordered testing, including laboratories and imaging, is an important aspect of successful outpatient care of patients with liver disease. Whether the completion of orders from telehealth encounters differs from in-person visits is unknown., Materials and Methods: Completion of ordered laboratories and imaging from hepatology encounters at our center from 2021 to 2022 were evaluated and compared between video telehealth and in-person visits. Laboratory completion was evaluated at 14 days, 30 days, and 90 days, and imaging completion was assessed at 1 year., Results: Telehealth encounters were significantly less likely to have laboratories completed at all evaluated time points (14 d: 40.7% vs 90.9%; 30 d: 50.9% vs 92.2%; 90 d: 63.9% vs 94.3%, P< 0.001 for all). Among telehealth encounters, encounters in patients more remote from the center were less likely to have laboratories completed. Imaging ordered at telehealth encounters was also less likely to be completed within 1 year (62.5% vs 70.1%, P< 0.001), including liver ultrasounds (59.1% vs 67.6%, P= 0.001), which persisted when limited to encounters for cirrhosis (55.8% vs 66.4%, P= 0.01)., Conclusions: Telehealth encounters were significantly less likely to have ordered laboratories and imaging completed compared with in-person visits, which has important clinical implications for effective outpatient care of patients with liver disease. Further research is needed to better understand the barriers to order completion for telehealth visits and ways to optimize this to improve the effectiveness of this visit modality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
20. Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis.
- Author
-
Thorburn D, Leeming DJ, Barchuk WT, Wang Y, Lu X, Malkov VA, Ito KL, Bowlus CL, Levy C, Goodman Z, Karsdal MA, Muir AJ, and Xu J
- Subjects
- Humans, Male, Female, Prognosis, Adult, Middle Aged, Severity of Illness Index, Hyaluronic Acid blood, Liver pathology, Cholangitis, Sclerosing drug therapy, Cholangitis, Sclerosing blood, Cholangitis, Sclerosing pathology, Biomarkers blood, Liver Cirrhosis blood, Liver Cirrhosis drug therapy, Liver Cirrhosis etiology, Antibodies, Monoclonal, Humanized therapeutic use, Extracellular Matrix pathology, Disease Progression
- Abstract
Background: Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events., Methods: Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide of type IV collagen, propeptide of type V collagen), collagen degradation (type III collagen matrix metalloproteinase degradation product and type IV collagen matrix metalloproteinase degradation product), and fibrosis (enhanced liver fibrosis [ELF] score and its components [metalloproteinase-1, type III procollagen, hyaluronic acid]) were assessed in samples from baseline to week 96 in patients with PSC enrolled in a study evaluating simtuzumab (NCT01672853). Diagnostic performance for advanced fibrosis (Ishak stages 3-6) and cirrhosis (Ishak stages 5-6) was evaluated by logistic regression and AUROC. Prognostic performance for PSC-related clinical events and fibrosis progression was assessed by AUROC and Wilcoxon rank-sum test., Results: Among 234 patients, 51% had advanced fibrosis and 11% had cirrhosis at baseline. Baseline Pro-C3 and ELF score and its components provided moderate diagnostic ability for discrimination of advanced fibrosis (AUROC 0.73-0.78) and cirrhosis (AUROC 0.73-0.81). Baseline Pro-C3, ELF score, and type III procollagen provided a moderate prognosis for PSC-related clinical events (AUROC 0.70-0.71). Among patients without cirrhosis at baseline, median changes in Pro-C3 and ELF score to week 96 were higher in those with than without progression to cirrhosis (both p < 0.001)., Conclusions: Pro-C3 correlated with fibrosis stage, and Pro-C3 and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. The results support the clinical utility of Pro-C3 and ELF score for staging and as prognostic markers in PSC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
- Published
- 2024
- Full Text
- View/download PDF
21. Characterization of social determinants of health of a liver transplant referral population.
- Author
-
Henson JB, Chan NW, Wilder JM, Muir AJ, and McElroy LM
- Subjects
- Humans, Social Determinants of Health, Retrospective Studies, Referral and Consultation, Liver Transplantation adverse effects, Organ Transplantation
- Abstract
Disparities exist in referral and access to the liver transplant (LT) waitlist, and social determinants of health (SDOH) are increasingly recognized as important factors driving health inequities, including in LT. The SDOH of potential transplant candidates is therefore important to characterize when designing targeted interventions to promote equity in access to LT. Yet, it is uncertain how a transplant center should approach this issue, characterize SDOH, identify disparities, and use these data to inform interventions. We performed a retrospective study of referrals for first-time, single-organ LT to our center from 2016 to 2020. Addresses were geoprocessed and mapped to the corresponding county, census tract, and census block group to assess their geospatial distribution, identify potential disparities in referrals, and characterize their communities across multiple domains of SDOH to identify potential barriers to evaluation and selection. We identified variability in referral patterns and areas with disproportionately low referrals, including counties in the highest quartile of liver disease mortality (9%) and neighborhoods in the highest quintile of socioeconomic deprivation (17%) and quartile of poverty (21%). Black individuals were also under-represented compared with expected state demographics (12% vs. 18%). Among the referral population, several potential barriers to evaluation and selection for LT were identified, including poverty, educational attainment, access to healthy food, and access to technology. This approach to the characterization of a transplant center's referral population by geographic location and associated SDOH demonstrates a model for identifying disparities in a referral population and potential barriers to evaluation that can be used to inform targeted interventions for disparities in LT access., (Copyright © 2023 American Association for the Study of Liver Diseases.)
- Published
- 2023
- Full Text
- View/download PDF
22. Parental leave, childcare policies, and workplace bias for hepatology professionals: A national survey.
- Author
-
Feld LD, Sarkar M, Au JS, Flemming JA, Gripshover J, Kardashian A, Muir AJ, Nephew L, Orloff SL, Terrault N, Rabinowitz L, Volerman A, Arora V, Farnan J, and Villa E
- Subjects
- Pregnancy, Male, Child, Humans, Female, Cross-Sectional Studies, Parental Leave, Workplace, Child Care, Gastroenterology
- Abstract
Background: The presence of workplace bias around child-rearing and inadequate parental leave may negatively impact childbearing decisions and sex equity in hepatology. This study aimed to understand the influence of parental leave and child-rearing on career advancement in hepatology., Methods: A cross-sectional survey of physician members of the American Association for the Study of Liver Diseases (AASLD) was distributed through email listserv in January 2021. The 33-item survey included demographic questions, questions about bias, altering training, career plans, family planning, parental leave, and work accommodations., Results: Among 199 US physician respondents, 65.3% were women, and 83.4% (n = 166) were attendings. Sex and racial differences were reported in several domains, including paid leave, perceptions of bias, and child-rearing. Most women (79.3%) took fewer than the recommended 12 paid weeks of parental leave for their first child (average paid leave 7.5 wk for women and 1.7 for men). A majority (75.2%) of women reported workplace discrimination, including 83.3% of Black and 62.5% of Hispanic women. Twenty percent of women were asked about their/their partners' pregnancy intentions or child-rearing plans during interviews for training. Women were more likely to alter career plans due to child-rearing (30.0% vs. 15.9%, p = 0.030). Women were also more likely to delay having children than men (69.5% vs.35.9%)., Conclusions: Women reported sex and maternity bias in the workplace and during training interviews, which was more frequently experienced by Black and Hispanic women. As two-thirds of women had children during training, it is a particularly influential time to reevaluate programmatic support to address long-term gender disparities in career advancement., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
- Published
- 2023
- Full Text
- View/download PDF
23. The key role of hepatology providers in optimizing reproductive care in patients with liver disease: A call to action.
- Author
-
Kardashian A, Kushner T, Au JS, Flemming JA, Gripshover J, Muir AJ, Orloff SL, Villa E, and Sarkar M
- Subjects
- Humans, Gastroenterology, Liver Diseases therapy, Digestive System Diseases
- Published
- 2023
- Full Text
- View/download PDF
24. Safety and Sustained Efficacy of the Farnesoid X Receptor (FXR) Agonist Cilofexor Over a 96-Week Open-label Extension in Patients With PSC.
- Author
-
Trauner M, Bowlus CL, Gulamhusein A, Hameed B, Caldwell SH, Shiffman ML, Landis C, Muir AJ, Billin A, Xu J, Liu X, Lu X, Chung C, Myers RP, and Kowdley KV
- Subjects
- Humans, Male, Adult, Female, Ursodeoxycholic Acid therapeutic use, Liver, Bile Acids and Salts, Biomarkers, gamma-Glutamyltransferase, Alkaline Phosphatase, Cholangitis, Sclerosing drug therapy
- Abstract
Background & Aims: Primary sclerosing cholangitis (PSC) is a major unmet medical need in clinical hepatology. Cilofexor is a nonsteroidal farnesoid X receptor agonist being evaluated for the treatment of PSC. Here, we describe the safety and preliminary efficacy of cilofexor in a 96-week, open-label extension (OLE) of a phase II trial., Methods: Noncirrhotic subjects with large-duct PSC who completed the 12-week, blinded phase of a phase II study (NCT02943460) were eligible, after a 4-week washout period, for a 96-week OLE with cilofexor 100 mg daily. Safety, liver biochemistry, and serum markers of fibrosis, cellular injury, and pharmacodynamic effects of cilofexor (fibroblast growth factor 19, C4, and bile acids [BAs]) were evaluated., Results: Among 52 subjects enrolled in the phase II study, 47 (90%) continued in the OLE phase (median age, 44 years; 60% male patients, 60% with inflammatory bowel disease, and 45% on ursodeoxycholic acid [UDCA]). At OLE baseline (BL), the median serum alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were 368 U/L (interquartile range [IQR], 277-468 U/L) and 417 U/L (IQR, 196-801 U/L), respectively. Of the 47 subjects enrolled, 15 (32%) discontinued treatment prematurely (pruritus [n = 5], other adverse events [n = 5], subject decision/investigator discretion [n = 5]). At week 96, reductions in liver biochemistry parameters occurred, including serum ALP (median, -8.3% [IQR, -25.9% to 11.0%]; P = .066), GGT (-29.8% [IQR, -42.3% to -13.9%]; P < .001), alanine aminotransaminase (ALT) (-29.8% [IQR, -43.7% to -6.6%]; P = .002), and aspartate aminotransaminase (AST) (-16.7% [IQR, -35.3% to 1.0%]; P = .010), and rebounded after 4 weeks of untreated follow-up. ALP response (≥20% reduction from BL to week 96) was similar in the presence or absence of UDCA therapy (29% vs 39%; P = .71). At week 96, cilofexor treatment was associated with a significant reduction in serum 7α-hydroxy-4-cholesten-3-one (C4) (-29.8% [IQR, -64.3% to -8.5%]; P = .001). In subjects with detectable serum BAs at BL (n = 40), BAs decreased -23.9% (IQR, -44.4% to -0.6%; P = .006) at week 48 (n = 28) and -25.7% (IQR, -35.9% to 53.7%; P = .91) at week 96 (n = 26). Serum cytokeratin 18 (CK18) M30 and M65 were reduced throughout the OLE; significant reductions were observed at week 72 (CK18 M30, -17.3% [IQR, -39.3% to 8.8%]; P = .018; CK18 M65, -43.5% [IQR, -54.9% to 15.3%]; P = .096). At week 96, a small, but statistically significant absolute increase of 0.15 units in Enhanced Liver Fibrosis score was observed compared with BL (median, 9.34 vs 9.53; P = .028)., Conclusions: In this 96-week OLE of a phase II study of PSC, cilofexor was safe and improved liver biochemistry and biomarkers of cholestasis and cellular injury., Clinicaltrials: gov identifier: NCT02943460., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
25. Consider hospice in end-stage liver disease prognostic scale to open discussions regarding six-month mortality.
- Author
-
Brown C, Aksan N, and Muir AJ
- Abstract
Background and Aim: Hospice is underutilized in the management of patients with end-stage liver disease and may improve the patient experience at the end of life. This study aims to create a novel prognostic scale to accurately predict 6-month mortality to more comprehensively facilitate hospice referral., Methods: Sociodemographic, clinical, and laboratory variables associated with mortality from the United Network for Organ Sharing database were tested in univariate analysis followed by multivariate analyses with four predictor groups: Demographics, Diagnoses, Complexities, and Laboratory studies to develop the hospice in end-stage liver disease prognostic scale (HELP) scale (70% sample, N = 13 516) followed with replication in a 30% ( N = 5792) internal validation sample., Results: Only the predictor groups of Complexities and Laboratory studies met the c -statistic threshold of 0.70 for inclusion in the multivariate analyses. Backward elimination in the final logistic regression and validated weighted transformation procedure resulted in: HELP scale = (functional status × 11) + (ascites × 3) + (SBP × 3) + (HE × 4) + (dialysis × 5) + (TIPS × -3) + (albumin × -3) + (MELD-Na ≥ 21 × 20). HELP scale had a strong predictive value for six-month mortality with Area under the Receiver Operating Curve (AUROC) 0.816 and replicated in the validation sample., Conclusion: HELP scale is a novel prognostic score utilizing the strength of model of end-stage liver disease-sodium (MELD-Na), along with clinical factors, for a more nuanced assessment of six-month mortality. This scale can provide an individualized approach in opening discussions of hospice referral and may be better accepted by patients and providers given its contextualization of important clinical factors., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
26. Performance of the Pooled Cohort Equations in non-alcoholic fatty liver disease: The Multi-Ethnic Study of Atherosclerosis.
- Author
-
Henson JB, Budoff MJ, and Muir AJ
- Subjects
- Humans, Female, Risk Factors, Risk Assessment, Non-alcoholic Fatty Liver Disease epidemiology, Cardiovascular Diseases epidemiology, Atherosclerosis complications, Atherosclerosis epidemiology
- Abstract
Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of cardiovascular disease. Whether risk scores developed in the general population accurately assess cardiovascular risk in the NAFLD population is unknown. This study aimed to evaluate the performance of the Pooled Cohort Equations (PCE) in NAFLD., Methods: Individuals in the Multi-Ethnic Study of Atherosclerosis with baseline non-contrast cardiac computed tomography scans with sufficient data to determine the presence of hepatic steatosis were identified and assessed for the development of incident 10-year atherosclerotic cardiovascular disease. The discrimination and calibration of the PCE were evaluated, and the observed and expected events by risk category (<5%, 5-<7.5%, 7.5-<20%, ≥20%) were determined. Risk reclassification with the addition of NAFLD to the PCE was assessed., Results: Of 4014 participants included, 698 (17.4%) with NAFLD were identified, including 247 (35.3%) with moderate-to-severe steatosis. Discrimination of the PCE was suboptimal in NAFLD (c-statistic 0.69), particularly moderate-to-severe steatosis (0.65), and calibration was overall poor. While risk was overestimated in non-NAFLD, it was underestimated in NAFLD in lower/intermediate risk categories, predominantly in women (5-<7.5% observed/expected ratio = 1.67). The addition of NAFLD to the PCE improved risk classification in women., Conclusions: The PCE overall performed suboptimally in cardiovascular risk assessment in NAFLD, particularly in women and individuals with moderate-to-severe steatosis in clinically relevant risk categories. Primary prevention may need to be considered at a lower risk threshold in these groups, and further work is needed to improve risk stratification in this growing high-risk population., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
27. Rates of employment after liver transplant: A nationwide cohort study.
- Author
-
Henson JB, Cabezas M, McElroy LM, and Muir AJ
- Subjects
- Humans, Male, Adolescent, Young Adult, Adult, Middle Aged, Aged, Cohort Studies, Employment, Liver Transplantation adverse effects
- Abstract
Background: Employment outcomes after liver transplant (LT) over the past decade have not been described., Methods: LT recipients ages 18-65 from 2010-2018 were identified in Organ Procurement and Transplantation Network data. Employment within two years post-transplant was assessed., Results: Of 35,340 LT recipients, 34.2% were employed post-LT, including 70.4% who were working pre-transplant, compared to only 18.2% not working preLT. Younger age, male sex, educational attainment, and functional status were associated with returning to employment., Conclusion: Returning to employment is an important goal for many LT candidates and recipients, and these findings can be used to guide their expectations., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
- Published
- 2023
- Full Text
- View/download PDF
28. Evaluation of an Abnormal Liver Panel After Liver Transplantation.
- Author
-
Henson JB and Muir AJ
- Subjects
- Humans, Postoperative Complications diagnosis, Liver Function Tests, Tissue Donors, Liver diagnostic imaging, Liver pathology, Liver Transplantation adverse effects, Liver Transplantation methods
- Abstract
Abnormal liver tests are common after liver transplantation. The differential diagnosis depends on the clinical context, particularly the time course, pattern and degree of elevation, and donor and recipient factors. The perioperative period has distinct causes compared with months and years after transplant, including ischemia-reperfusion injury, vascular thrombosis, and primary graft nonfunction. Etiologies seen beyond the perioperative period include biliary complications, rejection, infection, recurrent disease, and non-transplant-specific causes. The evaluation begins with a liver ultrasound with Doppler as well as appropriate laboratory testing and culminates in a liver biopsy if the imaging and laboratory testing is unrevealing., Competing Interests: Disclosure JBH is supported by NIH grant 2T32DK007568-31A1., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
29. Access to technology to support telehealth in areas without specialty care for liver disease.
- Author
-
Henson JB, Wegermann K, Patel YA, Wilder JM, and Muir AJ
- Subjects
- Humans, Rural Population, Gastrointestinal Tract, Internet, Telemedicine, Liver Diseases therapy
- Abstract
Background and Aims: Telehealth may be a successful strategy to increase access to specialty care for liver disease, but whether the areas with low access to care and a high burden of liver-related mortality have the necessary technology access to support a video-based telehealth strategy to expand access to care is unknown., Approach and Results: Access to liver disease specialty care was defined at the county level as <160.9 km (100 miles) from a liver transplant (LT) center or presence of local gastroenterology (GI). Liver-related mortality rates were compared by access to care, and access to technology was compared by degree of access to care and burden of liver-related mortality. Counties with low access to liver disease specialty care had higher rates of mortality from liver disease, and this was highest in areas both >160.9 km from an LT center and without local GI. These counties were more rural, had higher poverty, and had decreased access to devices and internet at broadband speeds. Technology access was lowest in areas with low access to care and the highest burden of liver-related mortality., Conclusions: Areas with poor access to liver disease specialty care have a greater burden of liver-related mortality, and many of their residents lack access to technology. Therefore, a telehealth strategy based solely on patient device ownership and internet access will exclude a large proportion of individuals in the areas of highest need. Further work should be done at the local and state levels to design optimal strategies to reach their populations of need., (Copyright © 2022 American Association for the Study of Liver Diseases.)
- Published
- 2023
- Full Text
- View/download PDF
30. Patient-Predicted Outcomes Are Associated with Quality of Life in Patients with Primary Sclerosing Cholangitis.
- Author
-
Henson JB, Helzberg JH, and Muir AJ
- Subjects
- Humans, Quality of Life, Bile Ducts, Intrahepatic pathology, Cholangitis, Sclerosing complications, Cholangiocarcinoma diagnosis, Liver Diseases complications, Bile Duct Neoplasms complications
- Abstract
Background: Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease, and many patients ultimately require liver transplantation (LT). PSC also confers an increased risk of malignancies, including cholangiocarcinoma (CCA) and colorectal cancer., Aims: This study aimed to evaluate patient-perceived outcomes and the extent to which these impact health-related quality of life (HRQoL)., Methods: Patients with PSC completed a risk perception questionnaire, the Short Form-36 (SF-36), and the Chronic Liver Disease Questionnaire. Multivariable models were used to determine factors associated with patient-perceived risks of malignancy, LT, and life expectancy, as well as their relationship with HRQoL scores., Results: A total of 95 patients completed the risk perception questionnaire, and 73 returned the remaining instruments. The estimated risks varied widely. Half overestimated their one-year or lifetime CCA risk, while some predicted zero chance. Predicted LT risk was the only outcome concordant with disease severity. Pruritus was associated with higher predicted one-year risks and lower life expectancy. Lifetime CCA and LT risks were associated with the SF-36 physical component score, while perceived life expectancy was strongly associated with mental health domains, including the SF-36 mental component score., Conclusions: Predicted prognosis varies widely among patients with PSC and is influenced more by symptoms than objective disease severity. The psychological burden of shorter perceived life expectancy impacts mental HRQoL more than the risks of malignancy or LT. These findings highlight an opportunity for improved patient communication regarding these outcomes, as well as the importance of discussing them, as they may impact HRQoL., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
31. MELD-Na Accurately Predicts 6-Month Mortality in Patients With Decompensated Cirrhosis: Potential Trigger for Hospice Referral.
- Author
-
Brown C, Aksan N, and Muir AJ
- Subjects
- Bilirubin, Creatinine, Cross-Sectional Studies, Humans, Liver Cirrhosis complications, Liver Cirrhosis diagnosis, Liver Cirrhosis surgery, Prognosis, Referral and Consultation, Retrospective Studies, Severity of Illness Index, Sodium, End Stage Liver Disease complications, End Stage Liver Disease diagnosis, End Stage Liver Disease surgery, Hospices, Liver Failure, Acute, Liver Neoplasms complications
- Abstract
Goal: The goal of this study was to determine the accuracy of Model of End-stage Liver Disease-Sodium (MELD-Na) in predicting 6-month mortality for patients listed for liver transplantation on the United Network of Organ Sharing (UNOS) waitlist., Background: End-stage liver disease patients underutilize hospice services despite significant morbidity and mortality associated with advanced liver disease. A well-known barrier to hospice referral is clinician uncertainty in identifying patients with an expected survival of <6 months, a requirement for a referral., Methods: Retrospective cross-sectional analysis was performed from UNOS data spanning February 27, 2002, to September 30, 2019. Inclusion criteria of patients aged 18 years and above, diagnosis of cirrhosis, liver transplant eligible, and listed in the UNOS database. Exclusion criteria included fulminant hepatic failure, prior history of liver transplantation, diagnosis of hepatocellular carcinoma, receipt of liver transplant in <180 days, or removal from waiting list <180 days for a reason other than death., Measurement: Mortality by 180 days., Results: Of the 93,157 patients that met inclusion criteria, MELD-Na was calculated for all patients with sodium, total bilirubin, international normalized ratio, and creatinine available (N=79,611). The c -statistic with 95% confidence interval for MELD-Na for the predicted 6-month mortality was 0.83 (0.827-0.835). Mean MELD-Na of 28.2 was associated with ≤50% 6-month survival., Conclusion: MELD-Na is an objective, quick measure that can aid providers in identifying patients with increased 6-month mortality in time-constrained settings, and a score of 28 can trigger the discussion for hospice as a means of improving value-based health care., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
32. Recent updates in preemptive transjugular intrahepatic portosystemic shunt for acute variceal bleeding.
- Author
-
Helzberg JH, Henson JB, and Muir AJ
- Abstract
Content available: Author Interview and Audio Recording., Competing Interests: Nothing to report., (© 2022 American Association for the Study of Liver Diseases.)
- Published
- 2022
- Full Text
- View/download PDF
33. Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis.
- Author
-
Sanyal AJ, Anstee QM, Trauner M, Lawitz EJ, Abdelmalek MF, Ding D, Han L, Jia C, Huss RS, Chung C, Wong VW, Okanoue T, Romero-Gomez M, Muir AJ, Afdhal NH, Bosch J, Goodman Z, Harrison SA, Younossi ZM, and Myers RP
- Subjects
- Collagen metabolism, Fibrosis, Humans, Liver pathology, Liver Cirrhosis drug therapy, Liver Cirrhosis etiology, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease drug therapy, Non-alcoholic Fatty Liver Disease metabolism
- Abstract
Background and Aims: Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver-related complications in patients with NASH cirrhosis., Approach and Results: Patients with compensated cirrhosis due to NASH were enrolled in two placebo-controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH Clinical Research Network (CRN) and Ishak classifications and a machine learning (ML) approach, hepatic collagen and alpha-smooth muscle actin (α-SMA) expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (enhanced liver fibrosis [ELF], NAFLD fibrosis score [NFS], and Fibrosis-4 index [FIB-4]) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver-related clinical events. Among 1,135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow-up of 16.6 months, 71 (6.3%) had a liver-related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, α-SMA expression, ML-based fibrosis parameters, LS, ELF, NFS, and FIB-4. Cirrhosis regression observed in 16% (176/1,135) between BL and W48 was associated with a lower risk of events versus nonregression (1.1% [2/176] vs. 7.2% [69/957]; HR, 0.16; 95% CI, 0.04, 0.65 [p = 0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, α-SMA, ML-based fibrosis parameters, NFS, and LS were associated with an increased risk of events., Conclusions: In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver-related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis., (© 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
- Published
- 2022
- Full Text
- View/download PDF
34. AGA Technical Review on Systemic Therapies for Hepatocellular Carcinoma.
- Author
-
Altayar O, Shah R, Chang CY, Falck-Ytter Y, and Muir AJ
- Subjects
- Anilides therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Bevacizumab administration & dosage, Carcinoma, Hepatocellular physiopathology, Carcinoma, Hepatocellular secondary, Carcinoma, Hepatocellular surgery, Chemoembolization, Therapeutic, Chemotherapy, Adjuvant, Hepatectomy, Humans, Liver Neoplasms pathology, Liver Neoplasms physiopathology, Liver Neoplasms surgery, Liver Transplantation, Phenylurea Compounds therapeutic use, Pyridines therapeutic use, Quinolines therapeutic use, Retreatment, Sorafenib therapeutic use, Ramucirumab, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Published
- 2022
- Full Text
- View/download PDF
35. Racial disparities in transjugular intrahepatic portosystemic shunt procedure outcomes.
- Author
-
Helzberg JH, Parish A, Niedzwiecki D, Kim CY, Patel YA, Wilder JM, and Muir AJ
- Subjects
- Cohort Studies, Gastrointestinal Hemorrhage etiology, Humans, Esophageal and Gastric Varices epidemiology, Esophageal and Gastric Varices surgery, Hypertension, Portal complications, Hypertension, Portal surgery, Portasystemic Shunt, Transjugular Intrahepatic adverse effects
- Abstract
Objective: The transjugular intrahepatic portosystemic shunt (TIPS) procedure is an important intervention for management of complications of portal hypertension. The objective of this study was to identify predictors of mortality from the TIPS procedure with a focus on race and ethnicity., Design: TIPS procedures from 2012 to 2014 in the National Inpatient Sample were identified. Weighting was applied to generate nationally representative results. In-hospital mortality was the primary outcome of interest. χ
2 and Student's t-tests were performed for categorical and continuous variables, respectively. Predictors of mortality following TIPS were assessed by survey-weighted logistic regression., Results: 17 175 (95% CI 16 254 to 18 096) TIPS cases were identified. Approximately 71% were non-Hispanic (NH) white, 6% were NH black, 16% were Hispanic and 7% were other. NH black patients undergoing TIPS had an in-hospital mortality rate of 20.1%, nearly double the in-hospital mortality of any other racial or ethnic group. NH black patients also had significantly longer median postprocedure and total lengths of stay (p=0.03 and p<0.001, respectively). The interaction of race by clinical indication was a significant predictor of in-hospital mortality (p<0.001). NH black patients had increased mortality compared with other racial/ethnic groups when presenting with bleeding oesophageal varices (OR 3.85, 95% CI 2.14 to 6.95)., Conclusion: This cohort study presents important findings in end-stage liver disease care, with clear racial disparities in in-hospital outcomes following the TIPS procedure. Specifically, black patients had significantly higher in-hospital mortality and longer lengths of stay. Further research is needed to understand how we can better care for black patients with liver disease., Competing Interests: Competing interests: CYK has received consulting fees from Boston Scientific, BD, and Humacyte. YAP has received consulting fees from Intercept Pharmaceuticals. JMW has received research funding from Gilead, Sequana, Mirum Pharmaceuticals, and BMS. He has received consulting fees from Science 37, Gilead and Viral ED. AJM has received research funding from Abbvie, CymaBay, Gilead, Intercept, Novartis and Taiwan J. He has served on advisory boards for Abbvie, Gilead and Pilant. He has received consulting fees from Pfizer and High Tide., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2022
- Full Text
- View/download PDF
36. Racial and Socioeconomic Disparities in Utilization of Telehealth in Patients with Liver Disease During COVID-19.
- Author
-
Wegermann K, Wilder JM, Parish A, Niedzwiecki D, Gellad ZF, Muir AJ, and Patel YA
- Subjects
- Aged, COVID-19 epidemiology, COVID-19 therapy, Cohort Studies, Female, Health Services Accessibility economics, Health Services Accessibility trends, Healthcare Disparities trends, Humans, Insurance Claim Reporting economics, Insurance Claim Reporting trends, Liver Diseases epidemiology, Liver Diseases therapy, Male, Middle Aged, Patient Acceptance of Health Care, Retrospective Studies, Telemedicine trends, COVID-19 economics, Healthcare Disparities economics, Liver Diseases economics, Racial Groups, Socioeconomic Factors, Telemedicine economics
- Abstract
Background and Aims: The coronavirus disease 2019 (COVID-19) pandemic resulted in a rapid expansion of telehealth services in hepatology. However, known racial and socioeconomic disparities in internet access potentially translate into barriers for the use of telehealth, particularly video technology. The specific aim of this study was to determine if disparities in race or socioeconomic status exist among patients utilizing telehealth visits during COVID-19., Methods: We performed a retrospective cohort study of all adult patients evaluated in hepatology clinics at Duke University Health System. Visit attempts from a pre-COVID baseline period (January 1, 2020 through February 29, 2020; n = 3328) were compared to COVID period (April 1, 2020 through May 30, 2020; n = 3771)., Results: On multinomial regression modeling, increasing age was associated with higher odds of a phone or incomplete visit (canceled, no-show, or rescheduled after May 30,2020), and non-Hispanic Black race was associated with nearly twice the odds of completing a phone visit instead of video visit, compared to non-Hispanic White patients. Compared to private insurance, Medicaid and Medicare were associated with increased odds of completing a telephone visit, and Medicaid was associated with increased odds of incomplete visits. Being single or previously married (separated, divorced, widowed) was associated with increased odds of completing a phone compared to video visit compared to being married., Conclusions: Though liver telehealth has expanded during the COVID-19 pandemic, disparities in overall use and suboptimal use (phone versus video) remain for vulnerable populations including those that are older, non-Hispanic Black, or have Medicare/Medicaid health insurance., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
37. Trends in statin utilisation in US adults with non-alcoholic fatty liver disease.
- Author
-
Henson JB, Patel YA, and Muir AJ
- Subjects
- Adult, Humans, Nutrition Surveys, Cardiovascular Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Non-alcoholic Fatty Liver Disease diagnosis, Non-alcoholic Fatty Liver Disease drug therapy, Non-alcoholic Fatty Liver Disease epidemiology
- Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) has high morbidity and mortality related to cardiovascular disease (CVD), but statins have been historically underutilised in these patients due to concern for hepatotoxicity., Aims: To characterise trends in statin use among individuals with NAFLD and to determine predictors of statin utilisation in this population., Methods: Individuals with NAFLD were identified from 2005 to 2018 continuous National Health and Nutrition Examination Survey. Trends in statin use over time were assessed, and predictors of statin under-utilisation for primary prevention were identified. The roles of a known diagnosis of liver disease and disease severity were examined., Results: We included 14 113 individuals; 34.6% had NAFLD, of whom 5.4% reported a liver disease diagnosis. There was a significant increase in statin use for primary prevention between 2005 and 2018 (18.1%-25.0%; P = 0.03), but guideline-indicated use for this purpose was low (54.5% between 2005 and 2012; 48.6% between 2013 and 2018). A known NAFLD diagnosis was a negative predictor of statin use during the earlier time period but not more recently. Utilisation did not decrease with increasing liver disease severity., Conclusions: In a nationally representative population with NAFLD, statin use for primary prevention has increased over time, but guideline-concordant use remains low. A known liver disease diagnosis was associated with lack of statin use in the earlier time period but not more recently, suggesting a changing perspective of underlying liver disease impacting statin utilisation. Further work to improve guideline-indicated statin use in this high-risk population is needed., (© 2021 John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
38. A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.
- Author
-
Sulkowski MS, Moon JS, Sherman KE, Morelli G, Darling JM, Muir AJ, Khalili M, Fishbein DA, Hinestrosa F, Shiffman ML, Di Bisceglie A, Rajender Reddy K, Pearlman B, Lok AS, Fried MW, Stewart PW, Peter J, Wadsworth S, Kixmiller S, Sloan A, Vainorius M, Horne PM, Michael L, Dong M, Evon DM, Segal JB, and Nelson DR
- Subjects
- 2-Naphthylamine administration & dosage, Administration, Oral, Adolescent, Adult, Aged, Aged, 80 and over, Anilides administration & dosage, Benzimidazoles administration & dosage, Benzofurans administration & dosage, Cyclopropanes administration & dosage, Drug Combinations, Drug Therapy, Combination methods, Female, Fluorenes administration & dosage, Follow-Up Studies, Genotyping Techniques, Hepacivirus genetics, Hepatitis C, Chronic blood, Hepatitis C, Chronic diagnosis, Hepatitis C, Chronic virology, Humans, Imidazoles administration & dosage, Lactams, Macrocyclic administration & dosage, Male, Middle Aged, Proline administration & dosage, Proline analogs & derivatives, Quinoxalines administration & dosage, RNA, Viral blood, Ribavirin administration & dosage, Sofosbuvir administration & dosage, Sulfonamides administration & dosage, Sustained Virologic Response, Treatment Outcome, Uracil administration & dosage, Uracil analogs & derivatives, Valine administration & dosage, Young Adult, Antiviral Agents administration & dosage, Hepacivirus isolation & purification, Hepatitis C, Chronic drug therapy
- Abstract
Background and Aims: Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable., Approach and Results: We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the "equivalence" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar. Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12., Conclusions: This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
- Published
- 2021
- Full Text
- View/download PDF
39. A retrospective longitudinal study and comprehensive review of adult patients with glycogen storage disease type III.
- Author
-
Hijazi G, Paschall A, Young SP, Smith B, Case LE, Boggs T, Amarasekara S, Austin SL, Pendyal S, El-Gharbawy A, Deak KL, Muir AJ, and Kishnani PS
- Abstract
Introduction: A deficiency of glycogen debrancher enzyme in patients with glycogen storage disease type III (GSD III) manifests with hepatic, cardiac, and muscle involvement in the most common subtype (type a), or with only hepatic involvement in patients with GSD IIIb., Objective and Methods: To describe longitudinal biochemical, radiological, muscle strength and ambulation, liver histopathological findings, and clinical outcomes in adults (≥18 years) with glycogen storage disease type III, by a retrospective review of medical records., Results: Twenty-one adults with GSD IIIa (14 F & 7 M) and four with GSD IIIb (1 F & 3 M) were included in this natural history study. At the most recent visit, the median (range) age and follow-up time were 36 (19-68) and 16 years (0-41), respectively. For the entire cohort: 40% had documented hypoglycemic episodes in adulthood; hepatomegaly and cirrhosis were the most common radiological findings; and 28% developed decompensated liver disease and portal hypertension, the latter being more prevalent in older patients. In the GSD IIIa group, muscle weakness was a major feature, noted in 89% of the GSD IIIa cohort, a third of whom depended on a wheelchair or an assistive walking device. Older individuals tended to show more severe muscle weakness and mobility limitations, compared with younger adults. Asymptomatic left ventricular hypertrophy (LVH) was the most common cardiac manifestation, present in 43%. Symptomatic cardiomyopathy and reduced ejection fraction was evident in 10%. Finally, a urinary biomarker of glycogen storage (Glc
4 ) was significantly associated with AST, ALT and CK., Conclusion: GSD III is a multisystem disorder in which a multidisciplinary approach with regular clinical, biochemical, radiological and functional (physical therapy assessment) follow-up is required. Despite dietary modification, hepatic and myopathic disease progression is evident in adults, with muscle weakness as the major cause of morbidity. Consequently, definitive therapies that address the underlying cause of the disease to correct both liver and muscle are needed., (© 2021 The Authors. Published by Elsevier Inc.)- Published
- 2021
- Full Text
- View/download PDF
40. Adaptive Challenges and Family Support: Patient Self-Management during Treatment for Chronic Hepatitis C.
- Author
-
Bailey DE Jr, Muir AJ, Cary MP Jr, Ammarell N, Seaver S, Scirica E, Mah'moud M, and Anderson RA
- Subjects
- Family, Humans, Hepatitis C, Chronic drug therapy, Self-Management
- Abstract
The authors describe a family's adaptive challenges and adaptive work during a family member's treatment for Chronic Hepatitis C. We audiorecorded index and final clinical visits and interviewed participants (patients and providers) following the visits. We interviewed by telephone and reviewed medical records over the course of treatment. Transcripts were analyzed using directed content analysis. Three themes were identified: family adaptive challenges, patient-described aspects of family members' adaptive challenges, and family adaptive work. There were four subthemes related to family adaptive work. The adaptive leadership framework for chronic illness provided direction for future family intervention.
- Published
- 2021
- Full Text
- View/download PDF
41. Proton pump inhibitor use is associated with increased rates of post-TIPS hepatic encephalopathy: Replication in an independent patient cohort.
- Author
-
Dai R, Sag AA, Martin JG, Befera NT, Pabon-Ramos WM, Suhocki PV, Smith TP, Kim CY, Muir AJ, and Ronald J
- Subjects
- Humans, Liver Cirrhosis, Male, Middle Aged, Proton Pump Inhibitors adverse effects, Retrospective Studies, Risk Factors, Hepatic Encephalopathy chemically induced, Hepatic Encephalopathy epidemiology, Portasystemic Shunt, Transjugular Intrahepatic
- Abstract
Purpose: Proton pump inhibitor (PPI) use is a potential risk factor for hepatic encephalopathy (HE), but few studies have examined the effect on post-TIPS HE. The purpose of this study was to determine whether PPIs are associated with increased rates of post-TIPS HE in an independent patient cohort., Materials and Methods: This single-institution retrospective study analyzed 86 patients (54 male, mean age 58.2) following TIPS from 1/1/2017 to 12/31/2019. Dates of PPI usage and episodes of new or worsening HE were recorded. Poisson regression with generalized estimating equations was used to test for association between PPI use and post-TIPS HE and to test for dose dependence. Post-TIPS HE was also analyzed using the Andersen-Gill survival model for recurrent events., Results: There were 1.88 episodes of new or worsening post-TIPS HE per person-year among 35 patients on uninterrupted PPIs therapy, 1.95 on PPIs and 0.94 off PPIs among 35 patients on intermittent therapy, and 0.47 among 16 patients never on PPIs. PPI use was significantly associated with post-TIPS HE in both univariable (incidence rate ratio (IRR) = 2.62; CI = 1.41-4.84; p = 0.002) and multivariable (IRR = 2.31; CI = 1.37-3.89; p = 0.002) regression. Analysis of only those patients on PPIs showed increased rates of HE with higher doses (IRR = 1.17 per 10 mg omeprazole equivalent; CI = 1.04-1.33; p = 0.011). Recurrent events survival analysis supported the association between PPI use and HE in univariable (hazard ratio (HR) = 2.17; CI = 1.19-3.95; p = 0.011) and multivariable (HR = 1.87; CI = 1.12-3.13; p = 0.017) analysis., Conclusion: In an independent patient cohort PPI use was associated with increased rates of new or worsening post-TIPS HE., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
42. Reduced Alcohol Use Is Sustained in Patients Provided Alcohol-Related Counseling During Direct-Acting Antiviral Therapy for Hepatitis C.
- Author
-
Patel YA, Yao J, Proeschold-Bell RJ, Niedzwiecki D, Goacher E, and Muir AJ
- Subjects
- Alcohol Abstinence psychology, Alcohol Abstinence statistics & numerical data, Directive Counseling methods, Female, Humans, Male, Middle Aged, Motivational Interviewing, Risk Reduction Behavior, United States epidemiology, Alcohol Drinking adverse effects, Alcohol Drinking prevention & control, Alcoholism diagnosis, Alcoholism epidemiology, Alcoholism psychology, Alcoholism therapy, Antiviral Agents therapeutic use, Cognitive Behavioral Therapy methods, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic epidemiology, Liver Cirrhosis diagnosis, Liver Cirrhosis virology
- Abstract
Background: Patients with chronic hepatitis C and risky/harmful alcohol use experience poor outcomes. Granular data evaluating whether alcohol counseling during hepatitis C treatment impacts longitudinal alcohol consumption are lacking., Aims: To evaluate whether provider-delivered counseling in the context of direct-acting antiviral hepatitis C treatment associates with decreased longitudinal alcohol consumption., Methods: We performed secondary data analysis from the Hep ART study including adults with hepatitis C who underwent provider-delivered counseling during direct-acting antiviral treatment between October 2014 and September 2017. Demographics and disease characteristics were summarized. Alcohol consumption, abstinence, and heavy drinking were evaluated in periods before, during, and after direct-acting antiviral treatment. Multivariate regression analyses were performed to evaluate the association of alcohol consumption with each 12-week time period for all patients and a subsample with cirrhosis., Results: One hundred twenty-three patients were included; 41 had cirrhosis. Most patients were male (74.0%) and Black (58.5%). Alcohol consumption improved during direct-acting antiviral treatment and was notably sustained (< 12 weeks before treatment 32.5 g/day; during treatment 20.0 g/day; and 12-24 weeks after treatment 23.7 g/day). Multivariable analyses showed significantly improved alcohol consumption metrics during and after antiviral treatment compared to < 12 weeks before treatment (during treatment 13.04 g/day less, p = 0.0001; > 24 weeks after treatment 15.29 g/day less, p = 0.0001). The subsample with cirrhosis showed similar results (during treatment 13.21 g/day less, p = 0.0001; > 24 weeks after treatment 7.69 g/day less, p = 0.0001)., Conclusions: Patients with chronic HCV and risky/harmful alcohol use given provider-delivered alcohol-related counseling during HCV treatment sustain decreased alcohol consumption patterns during and after treatment., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2021
- Full Text
- View/download PDF
43. Socioeconomic Status Is Associated with the Risk of Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation.
- Author
-
Helzberg JH, Dai R, Muir AJ, Wilder J, Lee TH, Martin JG, Kim CY, and Ronald J
- Subjects
- Aged, Humans, Male, Middle Aged, Retrospective Studies, Severity of Illness Index, Social Class, United States, End Stage Liver Disease, Hepatic Encephalopathy etiology, Portasystemic Shunt, Transjugular Intrahepatic adverse effects
- Abstract
Purpose: To determine whether socioeconomic status (SES) is associated with hepatic encephalopathy (HE) risk after transjugular intrahepatic portosystemic shunt (TIPS) creation., Materials and Methods: This single-institution retrospective study included 368 patients (mean age = 56.7 years; n = 229 males) from 5 states who underwent TIPS creation. SES was estimated using the Agency for Healthcare Research and Quality SES index, a metric based on neighborhood housing, education, and income statistics. Episodes of new or worsening HE after TIPS creation, defined as hospitalization for HE or escalation in outpatient medical therapy, were identified from medical records. Multivariable ordinal regression, negative binomial regression, and competing risks survival analysis were used to identify factors associated with SES quartile, the number of episodes of new or worsening HE per unit time after TIPS creation, and mortality after TIPS creation, respectively., Results: There were 83, 113, 99, and 73 patients in the lowest, second, third, and highest SES quartiles, respectively. In multivariable regression, only older age (β = 0.04, confidence interval [CI] = 0.02-0.05; P < .001) and white, non-Hispanic ethnicity (β = 0.64, CI = 0.07-1.21; P = .03) were associated with higher SES quartile. In multivariable regression, lower SES quartile (incidence rate ratio [IRR] = 0.80, CI = 0.68-0.94; P = .004), along with older age, male sex, higher model for end-stage liver disease score, nonalcoholic steatohepatitis, and proton pump inhibitor use were associated with higher rates of HE after TIPS creation. Ethnicity was not associated with the rate of HE after TIPS creation (IRR = 0.77, CI = 0.46-1.29; P = .28). In multivariable survival analysis, neither SES quartile nor ethnicity predicted mortality after creation of a TIPS., Conclusion: Lower SES is associated with higher rates of new or worsening HE after TIPS creation., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
44. Inter- and Intra-individual Variation, and Limited Prognostic Utility, of Serum Alkaline Phosphatase in a Trial of Patients With Primary Sclerosing Cholangitis.
- Author
-
Trivedi PJ, Muir AJ, Levy C, Bowlus CL, Manns MP, Lu X, Crans G, Chung C, Subramanian GM, Myers RP, Goodman Z, Chalasani N, Vierling JM, Guha IN, and Hirschfield GM
- Subjects
- Biomarkers, Humans, Prognosis, Prospective Studies, Alkaline Phosphatase, Cholangitis, Sclerosing diagnosis
- Abstract
Background & Aims: Serum alkaline phosphatase (ALP) and the enhanced liver fibrosis (ELF) score are used as endpoints in trials of patients with primary sclerosing cholangitis (PSC). We aimed to quantify inter- and intra-individual variation in levels of ALP and the ELF score over time, and evaluated their association with fibrosis progression., Methods: We analyzed data from 234 patients with large-duct PSC enrolled in a 2-year, phase 2b placebo-controlled trial of simtuzumab. Participants were assessed by laboratory tests every 4 weeks, and liver biopsies collected at time of screening, week 48, and week 96., Results: Serum levels of ALP and ELF scores did not differ significantly between simtuzumab and placebo groups, so the data were pooled. Median per-patient variations in ALP between clinic visits were approximately 12% over 12 weeks, 20% over 48 weeks, and 20% over 96 weeks. Reductions, unrelated to study intervention, of more than 40% in ALP were observed in 10.9% of patients with baseline activity greater than 2-fold the upper limit of normal (ULN) and 12.5% of patients with more than 3-fold the ULN at 1 year. At 2 years, reductions of more than 40% in ALP were observed in 15.8% of patients with baseline activity greater than 2-fold the ULN and 17.9% of patients with more than 3-fold the ULN. Among the 209 patients with Ishak fibrosis stage 0-4 at baseline, serum ALP activity did not associate with development of cirrhosis or with a 2-point increase in fibrosis stage at 2 years. In contrast, the median per-patient variation in ELF scores between clinic visits was approximately 3% over 12 weeks, 4% over 48 weeks, and 4% over 96 weeks. Elevated ELF scores at baseline and at weeks 12, 24 and 48, each associated with development of cirrhosis at 2 years (odds ratio >2.75; P < .01 for all timepoints). ELF scores at baseline and weeks 12, 24 and 48, also associated with a 2-point increase in fibrosis stage at 2 years (odds ratios all greater than 2; P < .01 for all timepoints)., Conclusions: In an analysis of data from patients with large-duct PSC enrolled in a prospective trial, we found large interindividual and intraindividual variations in serum ALP activity. Serum ALP activity did not associate with disease progression over a 2-year period. Variations in ELF score were smaller, and scores determined at multiple timepoints associated with fibrosis progression and development of cirrhosis., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
45. Diagnosis of LI-RADS M lesions on gadoxetate-enhanced MRI: identifying cholangiocarcinoma-containing tumor with serum markers and imaging features.
- Author
-
Jiang H, Song B, Qin Y, Chen J, Xiao D, Ha HI, Liu X, Oloruntoba-Sanders O, Erkanli A, Muir AJ, and Bashir MR
- Subjects
- Contrast Media, Gadolinium DTPA, Humans, Magnetic Resonance Imaging, Retrospective Studies, Sensitivity and Specificity, Bile Duct Neoplasms diagnostic imaging, Carcinoma, Hepatocellular diagnostic imaging, Cholangiocarcinoma diagnostic imaging, Liver Neoplasms diagnostic imaging
- Abstract
Objectives: The LI-RADS M (LR-M) category describes hepatic lesions probably or definitely malignant, but not specific for hepatocellular carcinoma in at-risk patients. Differentiation among LR-M entities, particularly detecting cholangiocarcinoma-containing tumors (M-CCs), is essential for treatment and prognosis. Thus, we aimed to develop diagnostic models on gadoxetate disodium-enhanced MRI comprising serum tumor markers and LI-RADS imaging features for M-CC., Methods: Consecutive at-risk patients with LR-M lesions exclusively (no co-existing LR-4 and/or LR-5 lesions) were retrieved retrospectively from a prospectively collected database spanning 3 years. Intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (c-HCC-CCA) were classified together as M-CC. LI-RADS features determined by three independent radiologists and clinically relevant serum tumor markers were used to generate M-CC diagnostic models through logistic regression analysis against histology. Per-patient performance was evaluated using area under the receiver operating curve (AUC), sensitivity, and specificity., Results: Forty-five patients were included, 42.2% (19/45) with hepatocellular carcinoma, 33.3% (15/45) with ICC, 13.3% (6/45) with c-HCC-CCA, and 11.1% (5/45) with other hepatic lesions. Carbohydrate antigen (CA)19-9 > 38 U/mL, α-fetoprotein (AFP) > 4.8 ng/mL, and absence of the LI-RADS feature "blood products in mass" were significant predictors of M-CC. Combining three predictors demonstrated AUC of 0.862, sensitivity of 76%, and specificity of 88%. The risk of M-CC with all three criteria fulfilled was 98% (AUC, 0.690; sensitivity, 38%; specificity, 100%)., Conclusions: In at-risk patients with LR-M lesions, integrating CA19-9, AFP, and the LI-RADS feature "blood products in mass" achieved high diagnostic performance for M-CC. When all three criteria were fulfilled, the specificity for M-CC was 100%., Key Points: • In at-risk patients who had LR-M lesions exclusively (no concomitant LR-4/5 lesions), a model with carbohydrate antigen > 38 U/mL, α-fetoprotein > 4.8 ng/mL, and absence of the LI-RADS feature "blood products in mass" achieved high accuracy for diagnosing cholangiocarcinoma-containing tumors. • In patients of whom all three criteria were fulfilled, the specificity for M-CC was 100%, which might reduce or eliminate the need for biopsy confirmation.
- Published
- 2021
- Full Text
- View/download PDF
46. Why do patients with chronic hepatitis C drink alcohol? An examination of pain, depression and drinking motives.
- Author
-
Wilder JM, Evon DM, Proeschold-Bell RJ, Yao J, Sohail MM, Niedzwiecki D, Makarushka C, Hodge T, and Muir AJ
- Subjects
- Alcohol Drinking, Depression epidemiology, Humans, Middle Aged, Pain, Hepatitis C, Chronic complications, Motivation
- Abstract
Alcohol consumption in the setting of chronic HCV is associated with accelerated progression towards cirrhosis, increased risk of hepatocellular carcinoma and higher mortality. This analysis contextualizes how sociodemographic factors, chronic pain and depression relate to the motivations of individuals with chronic HCV to consume alcohol. We conducted a secondary analysis of baseline data from the Hep ART trial of behavioural interventions on alcohol use among patients with HCV. Alcohol consumption was measured using the Drinking Motives Questionnaire and a novel 6-item measure of pain-related drinking motives. Statistical analyses performed included ANOVA for bivariate analyses and multivariable ordinary least-squares linear regression. At study baseline, 181 participants had an average age of 55 years; the majority (66.7%) reported beyond-minor pain; and a third (37%) met criteria for depression; drinking motives were higher for individuals with beyond-minor pain (means 9.9 vs. 4.6, p < .001) and who met criteria for depression (means 10.9 vs. 6.4, p < .001) when using the pain-related drinking motives items. Average pain(coef = 1.0410067141 < .001) was significantly associated with increased motives to drink to relieve pain in the full baseline model specification controlling for all covariates using ordinary at least squares; depression (coef = 7.06; 95% CI 1.32, 12.81; p = .016) was significantly associated with increased non-pain-related motives to drink. From baseline to 3-month follow-up, compared to participants who had mean average pain scores among the sample, motives to drink to relieve pain decreased in participants who had higher average pain scores (coef = -0.30; 95% CI -0.59, -0.01; p = .40). Physical pain and depression are associated with increased motives to consume alcohol. Patients with chronic liver disease should be screened for chronic pain and depression and, if present, referred to pain specialists or co-managed in partnership with pain specialists in hepatology clinics., (© 2021 John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
47. A Fibrosis-Independent Hepatic Transcriptomic Signature Identifies Drivers of Disease Progression in Primary Sclerosing Cholangitis.
- Author
-
Gindin Y, Chung C, Jiang Z, Zhou JZ, Xu J, Billin AN, Myers RP, Goodman Z, Landi A, Houghton M, Green RM, Levy C, Kowdley KV, Bowlus CL, Muir AJ, and Trauner M
- Subjects
- Bile Acids and Salts chemistry, Biomarkers analysis, Biopsy, Cholangitis, Sclerosing metabolism, Disease Progression, Female, Gene Expression Profiling, Humans, Interleukin-8 analysis, Liver metabolism, Liver pathology, Liver Cirrhosis pathology, Male, Middle Aged, Principal Component Analysis, Cholangitis, Sclerosing pathology, Liver Cirrhosis metabolism, Transcriptome
- Abstract
Background and Aims: Primary sclerosing cholangitis (PSC) is a heterogeneous cholangiopathy characterized by progressive biliary fibrosis. RNA sequencing of liver tissue from patients with PSC (n = 74) enrolled in a 96-week clinical trial was performed to identify associations between biological pathways that were independent of fibrosis and clinical events., Approach and Results: The effect of fibrosis was subtracted from gene expression using a computational approach. The fibrosis-adjusted gene expression patterns were associated with time to first PSC-related clinical event (e.g., cholangitis, hepatic decompensation), and differential expression based on risk groups and Ingenuity Pathway Analysis were performed. Baseline demographic data were representative of PSC: median age 48 years, 71% male, 49% with inflammatory bowel disease, and 44% with bridging fibrosis or cirrhosis. The first principle component (PC1) of RNA-sequencing data accounted for 18% of variance and correlated with fibrosis stage (ρ = -0.80; P < 0.001). After removing the effect of fibrosis-related genes, the first principle component was not associated with fibrosis (ρ = -0.19; P = 0.11), and a semisupervised clustering approach identified two distinct patient clusters with differential risk of time to first PSC-related event (P < 0.0001). The two groups had similar fibrosis stage, hepatic collagen content, and α-smooth muscle actin expression by morphometry, Enhanced Liver Fibrosis score, and serum liver biochemistry, bile acids, and IL-8 (all P > 0.05). The top pathways identified by Ingenuity Pathway Analysis were eukaryotic translation inhibition factor 2 (eIF2) signaling and regulation of eIF4/p70S6K signaling. Genes involved in the unfolded protein response, activating transcription factor 6 (ATF6) and eIF2, were differentially expressed between the PSC clusters (down-regulated in the high-risk group by log-fold changes of -0.18 [P = 0.02] and -0.16 [P = 0.02], respectively). Clinical events were enriched in the high-risk versus low-risk group (38% [12/32] vs. 2.4% [1/42], P < 0.0001)., Conclusions: Removing the contribution of fibrosis-related pathways uncovered alterations in the unfolded protein response, which were associated with liver-related complications in PSC., (© 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
- Published
- 2021
- Full Text
- View/download PDF
48. Change in Alcohol Use and Association with Positive and Negative Emotions: Results from an Alcohol Treatment Study with Hepatitis C Patients.
- Author
-
Muhammad Sohail M, Yao J, Evon DM, Muir AJ, and Proeschold-Bell RJ
- Abstract
Few studies exist on the change over time in positive and negative emotions during treatment for alcoholism disorders. We aimed to evaluate relationship between alcohol reduction and change in positive and negative emotions. Chronic HCV patients (n=174) with alcohol use received brief alcohol counseling. Participants completed the PANAS-Short Form, MHC-Short Form, and the Alcohol Timeline Follow back at baseline and 3, 6, and 12 months. Decreases in alcohol use were related to decreased negative emotions from baseline to 3 months, baseline to 6 months and baseline to 12 months. Decreases in alcohol use were associated with increased positive emotions from baseline to 12 months but not sooner., Competing Interests: Disclosure Statement No potential conflict of interest was reported by the author.
- Published
- 2021
- Full Text
- View/download PDF
49. Direct-Acting Antivirals and Organ Transplantation: Is There Anything We Can't Do?
- Author
-
Kappus MR, Wolfe CR, and Muir AJ
- Subjects
- Clinical Trials as Topic, Donor Selection, Hepatitis C complications, Humans, Immunocompromised Host, United States, Antiviral Agents therapeutic use, Hepatitis C drug therapy, Organ Transplantation adverse effects, Tissue Donors statistics & numerical data
- Abstract
The opioid epidemic has resulted in an increase in organ donors with hepatitis C virus (HCV) infection in the United States. With the development of direct-acting antiviral regimens that offer high sustained virologic response rates even in the setting of immunosuppression after transplantation, these HCV-viremic organs are now being offered to transplant candidates with or without preexisting HCV infection. Strategies for HCV treatment with HCV-viremic organs have included delayed and preemptive approaches. This review will discuss key studies in the different solid organ transplants, recent reports of adverse events, and ethical and regulatory considerations. The efficacy of current HCV therapies has created this important opportunity to improve survival for patients with end-organ failure through greater access to organ transplantation and decreased waitlist mortality rate., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2020
- Full Text
- View/download PDF
50. Impact of Malnutrition on Outcomes in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt Insertion.
- Author
-
Chiang RS, Parish A, Niedzwiecki D, Kappus MR, and Muir AJ
- Subjects
- Female, Hospital Charges statistics & numerical data, Humans, Length of Stay statistics & numerical data, Male, Malnutrition mortality, Middle Aged, Retrospective Studies, Skilled Nursing Facilities statistics & numerical data, Liver Cirrhosis complications, Malnutrition complications, Portasystemic Shunt, Transjugular Intrahepatic
- Abstract
Background: Malnutrition is common in patients with cirrhosis and is associated with poor outcomes after hepatic resection and liver transplantation. Transjugular intrahepatic portosystemic shunt (TIPS) is performed for complications of cirrhosis., Aim: To assess the impact of malnutrition on TIPS outcomes., Methods: A retrospective analysis was performed using the Healthcare Cost and Utilization Project: National Inpatient Sample database for TIPS procedures from 2005 to 2014. The primary end point was in-hospital mortality. The association of specific malnutrition diagnostic codes and race-ethnicity on mortality was evaluated with survey-weighted logistic regression adjusted for age, gender, admission type, insurance payer, hospital region, comorbidities, and length of stay (LOS)., Results: From 2005 to 2014, an estimated 53,207 (95% CI 49,330-57,085) admissions with TIPS occurred. A diagnosis of malnutrition was present in 11%. In-hospital death post-TIPS occurred in 15.0% versus 10.7% (p value < 0.001) of patients with and without malnutrition, respectively. Patients with malnutrition had longer post-procedural LOS (median 6.7 vs. 2.9 days, p value < 0.001) and greater total hospital charges (median $144,752 vs. $79,781, p value < 0.001) and were more likely to be discharged to a skilled nursing facility (21.6% vs. 9.7%) than patients without malnutrition. Patients with malnutrition had increased odds of mortality (OR 1.31, 95% CI 1.07, 1.59) compared to patients with no malnutrition., Conclusion: Malnutrition was associated with worse outcomes after TIPS. Further research is needed to understand the mechanism of malnutrition in post-procedure outcomes and the ability of interventions for nutritional optimization to improve outcomes.
- Published
- 2020
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.