Retrospective Cohort Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2016; 22(19): 4732-4740
Published online May 21, 2016. doi: 10.3748/wjg.v22.i19.4732
Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration
Christine M Hunt, Lauren A Beste, Elliott Lowy, Ayako Suzuki, Cynthia A Moylan, Hans L Tillmann, George N Ioannou, Joseph K Lim, Michael J Kelley, Dawn Provenzale
Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States
Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Durham VA Medical Center, Durham, NC 27705, United States
Lauren A Beste, George N Ioannou, Department of Medicine, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, United States
Lauren A Beste, Elliott Lowy, George N Ioannou, Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, United States
Lauren A Beste, George N Ioannou, Department of Medicine, University of Washington, Seattle, WA 98195, United States
Elliott Lowy, University of Washington School of Public Health, Seattle, WA 98195, United States
Ayako Suzuki, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
Ayako Suzuki, Division of Hepatology, Central Arkansas Veterans Heathcare System, Little Rock, AR 72205, United States
Hans L Tillmann, Department of Medicine, Eastern Carolina University, Greenville, NC 27858, United States
Joseph K Lim, Yale Liver Center, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520, United States
Michael J Kelley, Office of Patient Care Services, Department of Veterans Affairs, Washington, DC 20420, United States
Michael J Kelley, Hematology-Oncology Service, Durham Veterans Affairs Medical Center, Durham, NC 27705, United States
Dawn Provenzale, Cooperative Studies Program Epidemiology Center-Durham, Durham Veterans Affairs Medical Center, Durham, NC 27705, United States
Dawn Provenzale, Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Durham, NC 27710, United States
Author contributions: Hunt CM, Ioannou GN, Provenzale D, Kelley MJ, Suzuki A, Moylan CA and Tillmann HL designed the study; Hunt CM, Beste LA and Lowy E performed the research; Lowy E analyzed the data. Hunt CM, Beste LA, Ioannou GN, Lowy E, Provenzale D, Kelley MJ, Suzuki A, Moylan CA, Tillmann HL and Lim JK interpreted the data; Hunt CM drafted the paper; Hunt CM, Beste LA, Ioannou GN, Lowy E, Provenzale D, Kelley MJ, Suzuki A, Moylan CA, Tillmann HL and Lim JK made critical revisions, and approved the final version.
Supported by (in part) by resources from the Veterans Affairs (VA) Cooperative Studies Program Epidemiology Center-Durham, the Puget Sound VA Health Care System, and the VA Office of Public Health and Human Health Pathogens.
Institutional review board statement: The analysis was exempted from review by the Durham Veterans Affairs Medical Center Institutional Review Board, as it was performed for Veterans Health Administration quality improvement.
Informed consent statement: Informed consent was not needed as only anonymized patient information was used in this national quality improvement analysis.
Conflict-of-interest statement: Christine M. Hunt has received consultancy fees from Otsuka and Furiex. Ayako Suzuki has received consultancy fees from GlaxoSmithKline. Cynthia A. Moylan has received research funding from TaiwainJ, Genfit, Galmed, Arisaph, Immuron, Gilead and Bristol-Myers Squibb. Joseph K. Lim has received research funding and speaker’s fees from Bristol-Myers Squibb and Gilead.
Data sharing statement: No additional data are available for this quality improvement analysis.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Christine M Hunt, MD, MPH, Adjunct Associate Professor of Medicine, Department of Medicine, Duke University School of Medicine, Duke University, 00550 Hospital South, Durham, NC 27710, United States. christine.hunt@va.gov
Fax: +1-919-4165839
Received: January 19, 2016
Peer-review started: January 19, 2016
First decision: March 7, 2016
Revised: March 16, 2016
Accepted: March 30, 2016
Article in press: March 30, 2016
Published online: May 21, 2016
Processing time: 118 Days and 17.6 Hours
Abstract

AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement.

METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group.

RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up.

CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.

Keywords: Hepatitis B, Hepatitis B reactivation, Anti-CD20 antibody, Rituximab, Lymphoma, Chemotherapy, Hepatitis B antivirals, Vaccination, Veteran

Core tip: Prior to anti-CD20 antibody (Ab) treatment in 2014, 61%-73% of 19304 Veterans had hepatitis B virus (HBV) tests. Of these, 11% tested were positive for hepatitis B surface antigen or core antibody and at risk for reactivation; ≤ 37% of these HBV+ patients received HBV antivirals during anti-CD20 Ab and follow-up. HBV+ patients had significantly higher hepatitis rates than HBV-. Among pretreatment HBV- patients, about 1 in 300 tested suffered acute hepatitis during anti-CD20 Ab and 12 mo follow-up. Electronic health record algorithms to increase HBV testing, antiviral use and vaccination will likely improve outcomes with anti-CD20 Ab treatment.