Abstract
Background
Fatigue is a common symptom of liver disease but not well characterized in patients with chronic hepatitis B virus (HBV).
Aims
We assessed the rate of fatigue using a validated instrument in patients with HBV and identified demographic, virologic, and clinical features associated with fatigue in a cross-sectional cohort study from the Hepatitis B Research Network.
Methods
Participants were English- and Spanish-speaking adults with chronic HBV who were not pregnant nor on treatment. Fatigue was measured using the PROMIS® Fatigue 7-item Short Form.
Results
The sample included 948 adults: median age 42; 51 % female; 71 % Asian; 74 % college educated; 77 % employed; 41 % inactive HBV carriers; 36 % with active chronic disease; and 2 % with advanced fibrosis, defined as AST–platelet ratio index (APRI) > 1.50. Patients with chronic HBV had a mean fatigue T-score of 46.8 ± SD = 7.9, compared to a mean fatigue T-score of 50.0 ± 10 in the US general population (p < .0001). In univariate analyses, greater fatigue was associated with demographic and clinical features such as female sex, lower income, more comorbidities, higher APRI score, and poorer mental health (p < 0.05). In multivariate analysis, female sex (p < .001), poorer mental health (p < .001), APRI score (p = .005), and history of diabetes (p = .039) were the strongest independent predictors.
Conclusions
The frequency of fatigue in this large cohort of North American chronic HBV patients may be equal to or lower than that reported in the US general population. Patients with advanced fibrosis, more comorbidities, and poorer mental health report worse fatigue.
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Abbreviations
- HBRN:
-
Hepatitis B Research Network
- PROMIS:
-
Patient Reported Outcomes Measurement Information System
- APRI:
-
AST–platelet ratio index
- HBV:
-
Hepatitis B virus
- NIH:
-
National Institutes of Health
- SD:
-
Standard deviation
- ALT:
-
Alanine aminotransferase test
- BMI:
-
Body mass index
- MOS SF-36:
-
Medical Outcomes Study 36-item Short Form
- HrQOL:
-
Health-related quality of life
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Acknowledgments
The HBRN: Harvard Consortium: Daryl T-Y Lau, MD, MPH (Beth Israel Deaconess Medical Center, Boston, MA), Raymond T. Chung, MD (Massachusetts General Hospital, Boston MA). Minnesota Alliance for Research in Chronic Hepatitis B Consortium Lewis R. Roberts, MB, ChB, PhD (Mayo Clinic Rochester, Rochester, MN), Coleman I. Smith, MD (University of Minnesota, Minneapolis, MN). Midwest Hepatitis B Consortium: Adrian M. Di Bisceglie, MD (Saint Louis University School of Medicine, St Louis, MO). University of Toronto Consortium: Harry L. A. Janssen, MD, PhD (Toronto Western and General Hospitals, Toronto, Ontario), David K. Wong, MD (Toronto Western and General Hospitals, Toronto, Ontario), Joshua Juan, MD (Toronto Western and General Hospitals, Toronto, Ontario), Jordan Feld, MD, MPH (Toronto Western and General Hospitals, Toronto, Ontario), Colina Yim (Toronto Western and General Hospitals, Toronto, Ontario), Jenny Heathcote, MD (Toronto Western and General Hospitals, Toronto, Ontario). HBV CRN North Texas Consortium: William M. Lee, MD (Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas), Robert Perrillo, MD (Baylor University Medical Center, Dallas, TX), Son Do, MD (University of Texas Southwestern, Dallas, TX). Los Angeles Hepatitis B Consortium: Steven-Huy B. Han, MD (David Geffen School of Medicine, UCLA, Los Angeles, CA), Tram T. Tran, MD (Cedars Sinai Medical Center, Los Angeles, CA). San Francisco Hepatitis B Research Group Consortium: Norah A. Terrault, MD, MPH (University of California, San Francisco), Stewart L. Cooper, MD (California Pacific Medical Center, Research Institute and Sutter Pacific Medical Foundation, Division of Hepatology, San Francisco, CA). Michigan Hawaii Consortium: Anna Suk-Fong Lok, MD (University of Michigan, Ann Arbor, MI), Naoky Tsai, MD (The Queen’s Medical Center, University of Hawaii, Honolulu, HI). Chapel Hill, NC Consortium: Michael W. Fried, MD (University of North Carolina at Chapel Hill, Chapel Hill, NC), Keyur Patel, MD (Duke University Medical Center, Durham, NC). PNW/Alaska Clinical Center Consortium: Robert C Carithers, MD (University of Washington Medical Center, Seattle WA), Margaret Shuhart, MD (Harborview Medical Center, Seattle WA), Kris V Kowdley, MD (Virginia Mason Medical Center, Seattle WA), Chia C Wang, MD (Virginia Mason Medical Center, Seattle WA). Virginia Commonwealth University Medical Center: Richard K. Sterling, MD, MSc (Virginia Commonwealth University Health System, Richmond, VA). Liver Diseases Branch, NIDDK: Marc G. Ghany, MD, MHsc (National Institutes of Health, Bethesda, MD), T. Jake Liang, MD (National Institutes of Health, Bethesda, MD). Liver Diseases Research Branch, NIDDK: Edward Doo, MD (National Institutes of Health, Bethesda, MD). Immunology Center: Kyong-Mi Chang, MD (University of Pennsylvania Perelman School of Medicine, Philadelphia, PA), Jang-June Park, PhD (University of Pennsylvania Perelman School of Medicine, Philadelphia, PA). Data Coordinating Center: Steven H. Belle, PhD, MScHyg (Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA), Yona Cloonan, PhD (Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA). Central Pathology: David Kleiner, MD, PhD (Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD). In addition to the authors, the HBRN would like to acknowledge the contributions of the following: Harvard Consortium: Nezam Afdhal, MD, Asad Javaid, MBBS, Jianghe Niu, Johanna Han, Imad Nasser, MD (Beth Israel Deaconess Medical Center, Boston, MA). Minnesota Alliance for Research in Chronic Hepatitis B: Alisha C. Stahler, Linda Stadheim, RN (Mayo Clinic Rochester, Rochester, MN), Mohamed Hassan, MD (University of Minnesota, Minneapolis, MN). Midwest Hepatitis B Consortium: Kathryn Rushing, RN, Rosemary A. Nagy, RDN, LD, MBA, Jacki Cerkoski, RN, MSN (Saint Louis University School of Medicine, St Louis, MO), Debra DeMarco Shaw, RN, BSN, Lisa Kessels, RN, Michael K. Klebert, PhD, RN, ANP-BC (Washington University, St. Louis, MO). University of Toronto Consortium: Seham Noureldin, PhD, Danie La, RN, Lucie Liu, MSc, CCRP, Diana Kaznowski, RN, Jiayun Chen, Doinita Vladutu, Orlando Cerocchi (Toronto Western and General Hospitals, Toronto, Ontario). HBV CRN North Texas Consortium: Stacey Minshall, RN, BSN (Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas), Sheila Bass (University of Texas Southwestern, Dallas, TX), Ethel Sauceda, BS (Baylor University Medical Center, Dallas, TX). Los Angeles Hepatitis B Consortium: Samuel French, MD, Velma Peacock, RN (David Geffen School of Med, UCLA, Los Angeles, CA). San Francisco Hepatitis B Research Group Consortium: Ashley Ungermann, MS, Claudia Ayala, MS, Emma Olson, BS, Ivy Lau, BS (University of California, San Francisco), Veronika Podolskaya, BS, NCPT, Nata DeVole, RN (California Pacific Medical Center, Research Institute). Michigan Hawaii Consortium: Barbara McKenna, MD, Kelly Oberhelman, PAC, Sravanthi Kaza, Bpharm, Cassandra Rodd, BS (University of Michigan, Ann Arbor, MI), Leslie Huddleston, NP, Peter Poerzgen, PhD (The Queen’s Medical Center, University of Hawaii, Honolulu, HI). Chapel Hill, NC Consortium: Jama M. Darling, MD, A. Sidney Barritt, MD, Tiffany Marsh, BA, Vikki Metheny, ANP, Danielle Cardona, PA-C (University of North Carolina at Chapel Hill, Chapel Hill, NC). Virginia Commonwealth University Medical Center: Velimir A. Luketic, MD, Paula G Smith, RN, BSN, Charlotte Hofmann, RN (Virginia Commonwealth University Health System, Richmond, VA). PNW/Alaska Clinical Center Consortium: Alycia Wolfstone, RN, MN (University of Washington Medical Center, Seattle WA), Jody Mooney, Lupita Cardona-Gonzalez (Virginia Mason Medical Center, Seattle WA). Liver Diseases Branch, NIDDK, NIH: Nancy Fryzek, RN, BSN, Elenita Rivera, BSN, Nevitt Morris, Vanessa Haynes-Williams. Liver Disease Research Branch, NIDDK, NIH: Jay H. Hoofnagle, MD, Averell H. Sherker, MD, Edward Doo, MD, Rebecca J. Torrance, RN, MS, Sherry R. Hall, MS. Immunology Center: Mary E. Valiga, RN, Keith Torrey, BS, Danielle Levine, BS, James Keith, BS, Michael Betts, PhD (University of Pennsylvania, Philadelphia, PA), Luis J. Montaner, DVM, DPhil (Wistar Institute, Philadelphia, PA). Data Coordinating Center: Michelle Danielson, PhD, Tamara Haller, Geoffrey Johnson, MS, Stephanie Kelley, MS, Sharon Lawlor, MBA, Joan M. MacGregor, MS, Andrew Pelesko, BS, Donna Stoliker, Ella Zadorozny, MS (Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA).
Declaration of funding interest
The HBRN was funded by a U01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases to the following investigators Lewis R. Roberts, MB, ChB, PhD (DK 082843), Anna Suk-Fong Lok, MD (DK082863), Steven H. Belle, PhD, MScHyg (DK082864), Kyong-Mi Chang, MD (DK082866), Michael W. Fried, MD (DK082867), Adrian M. Di Bisceglie, MD (DK082871), William M. Lee, MD (U01 DK082872), Harry L. A. Janssen, MD, PhD (DK082874), Daryl T-Y Lau, MD, MPH (DK082919), Richard K. Sterling, MD, MSc (DK082923), Steven-Huy B. Han, MD (DK082927), Robert C. Carithers, MD (DK082943), Norah A. Terrault, MD, MPH (U01 DK082944), an interagency agreement with NIDDK: Lilia M. Ganova-Raeva, PhD (A-DK-3002-001), and support from the intramural program, NIDDK, NIH: Marc G. Ghany, MD. Additional funding to support this study was provided to Kyong-Mi Chang, MD, the Immunology Center (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01-RR00040), Richard K. Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Norah A. Terrault, MD, MPH (CTSA Grant Number UL1TR000004), Michael W. Fried, MD (CTSA Grant Number UL1TR001111), and Anna Suk-Fong Lok (CTSA Grant Number UL1RR024986). Additional support was provided by Gilead Sciences, Inc., and Roche Molecular Systems via a CRADA through the NIDDK.
Author contributions
Donna Evon, Souvik Sarkar, and Jay Hoofnagle developed the study concept and design. Geoffrey Johnson and Abdus Wahed conducted the statistical analyses. All authors, including Mandana Khalili, Robert Fontana, and Mauricio Lisker-Melman, were involved in data acquisition and interpretation and drafting and critically revising the manuscript for interpretation and important intellectual content. All authors have made substantial contributions to the research design, data acquisition, analysis and interpretation, and drafting and revising the manuscript and have given approval of the submitted final versions and authorship list.
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Mandana Khalili, Geoffrey Johnson, Wahed Abdus, Souvik Sarkar, and Jay Hoofnagle have no conflict of interests to disclose. Donna Evon has served as a consultant for Gilead. Robert Fontana has received research funding from BMS, Vertex, Gilead and Janssen, and has served as a consultant for GSK and Tibotec. Mauricio Lisker-Melman is on the Speaker’s Bureau for Gilead and Simply Speaking.
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For the Hepatitis B Research Network (HBRN).
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Evon, D.M., Wahed, A.S., Johnson, G. et al. Fatigue in Patients with Chronic Hepatitis B Living in North America: Results from the Hepatitis B Research Network (HBRN). Dig Dis Sci 61, 1186–1196 (2016). https://doi.org/10.1007/s10620-015-4006-0
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DOI: https://doi.org/10.1007/s10620-015-4006-0