TY - JOUR
T1 - Relationship between metabolic syndrome, alanine aminotransferase levels, and liver disease severity in a Multiethnic North American cohort with chronic Hepatitis B
AU - Khalili, Mandana
AU - Shuhart, Margaret C.
AU - Lombardero, Manuel
AU - Feld, Jordan J.
AU - Kleiner, David E.
AU - Chung, Raymond T.
AU - Terrault, Norah A.
AU - Lisker-Melman, Mauricio
AU - Sanyal, Arun
AU - Lok, Anna S.
N1 - Funding Information:
DK082919 to Daryl T.-Y. Lau, DK082923 to Richard K. Sterling, DK082927 to Steven-Huy B. Han, DK082943 to Robert C. Carithers, DK082944 to NorahA.Terrault);aninteragencyagreementwith NIDDK (A-DK-3002-001 to Lilia M. Ganova-Raeva); and support from the intramural program, NIDDK,NIH(toMarcG.Ghany).Additionalfunding to support this study was provided by the NIH/ NIDDK Center of Molecular Studies in Digestive and Liver Diseases (P30DK50306 to Kyong-Mi Chang, the Immunology Center) and a National Institutes of Health Public Health Service Research grant (M01-RR00040 to Kyong-Mi Chang, the Immunology Center); the National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR000058 to Richard K. Sterling); and Clinical and Translation Science Awards (grant nos. UL1TR000004 to Norah A. Terrault, UL1TR001111 to Michael W. Fried, and UL1RR024986 and U54TR001959 to Anna Suk-Fong Lok). Additional support was provided by Gilead Sciences, Inc., and Roche Molecular Systems through a Cooperative Research and Development Agreement through NIDDK. Duality of Interest. M.K. is a recipient of a research grant (to her institution) from Gilead Sciences, Inc.; Intercept Pharmaceuticals; and AbbVie, Inc.; and she has served on scientific advisory panels for Gilead Sciences, Inc., and Intercept Pharmaceuticals. J.J.F. is a recipient of a research grant (to his institution) or consults forAbbVie,Inc.;ContraVirPharmaceuticals;Gilead Sciences, Inc.; Janssen Pharmaceutica; Merck; and MedImmune. R.T.C. is a recipient of research grants (to his institution) from Gilead Sciences, Inc.; Janssen Pharmaceutica; and Bristol-Myers Squibb. N.A.T. is a recipient of research grants (to her institution) from Gilead Sciences, Inc., and Bristol-Myers Squibb. M.L.-M. serves on the speaker bureau and scientific advisory board for AbbVie, Inc., and the speaker bureau for Gilead Sciences, Inc.; Merck; and Simply Speaking, Inc. A.S. is president of Sanyal Biotechnology and has stockoptionsinGenfit,Akarna,TizianaLifeSciences, Indalo, and Durect; has served as a consultant to AbbVie, AstraZeneca, Nitto Denko, Ardelyx, Conatus, Nimbus, Amarin, Salix, Tobira, Takeda, FibroGen, Jannsen, Gilead, Boehringer Ingel-heim, Eli Lilly, Zafgen, Novartis, Pfizer, Immuron, Exalenz,andGenfit;hasbeenanunpaidconsultant toIntercept,Echosens,Immuron,Galectin,Fractyl, Synlogic, Novo Nordisk, Afimmune, ChemomAb, Nordic Bioscience, and Bristol-Myers Squibb; his institutionhasreceivedgrantsupportfromGilead, Salix, Tobira, Bristol-Myers Squibb, Shire, Intercept, Merck, AstraZeneca, Malinckrodt, Cumberland, and Novartis; and he receives royalties from Elsevier and UptoDate. A.S.L. is a recipient of research grants (to her institution) from Gilead Sciences, Inc., and Bristol-Myers Squibb. No other potential conflicts of interest relevant to this article were reported. Author Contributions. All authors designed the study concept, interpreted and analyzed the data and results, and critically reviewed and revised the manuscript. M.K., M.C.S., M.L., J.J.F., N.A.T., and A.S.L. drafted the manuscript. M.L. cleaned up the data. M.K. is the guarantor of this work and, as such, had full access to all the data in the study andtakesresponsibilityfortheintegrityofthedata and the accuracy of the data analysis.
Funding Information:
The authors also acknowledge the HBRN pathology committee members for their contri-butiontohistologicevaluationoftheliverbiopsies. TheHBRNpathologycommitteemembersareAtul K. Bhan, MBBS, MD (Massachusetts General Hospital, Boston, MA); Michael S. Torbenson, MD (Mayo Clinic Rochester, Rochester, MN); Barbara McKenna, MD (University of Michigan, Ann Arbor, MI); Elizabeth Brunt, MD (Washington UniversitySchoolofMedicineinSt.Louis,St.Louis, MO); Sandra Fischer, MD (Toronto General Hospital, Toronto, Ontario, Canada); Samuel French, MD (David Geffen School of Medicine at UCLA, Los Angeles, CA); Rageshree Ramachandran, MD, PhD (University of California, San Francisco, San Francisco, CA); Cynthia D. Guy, MD (Duke University Medical Center, Durham, NC); Mathew M. Yeh, MD, PhD (University of Washington Med-icalCenter,Seattle,WA);LanPeng,MD(University of Texas Southwestern Medical Center at Dallas, Dallas, TX); Michael Idowu, MD, MPH (Virginia Commonwealth University Health System, Richmond, VA); Robert Anders, MD, PhD (Johns Hopkins University, Baltimore, MD); Michael A. Nalesnik, MD (University of Pittsburgh Medical Center, Pittsburgh, PA); and David Kleiner, MD, PhD (NIH, Bethesda, MD). Funding. The HBRN was funded by a U01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (DK082843 to Lewis R. Roberts, DK082863 to Anna Suk-Fong Lok, DK082864 to Steven H. Belle, DK082866 to Kyong-Mi Chang, DK082867 to Michael W. Fried, DK082871 to Adrian M. Di Bisceglie, DK082872 to William M. Lee, DK082874 to Harry L. A. Janssen,
Publisher Copyright:
© 2018 by the American Diabetes Association.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - OBJECTIVE Metabolic syndrome (MS) is prevalent and is associated with adverse outcomes of liver disease.We evaluated the prevalence of MS and its influence on alanine aminotransferase (ALT) levels and fibrosis, as estimated by the aspartate aminotransferase- to-platelet ratio index (APRI), in a large, multiethnic North American cohort with chronic hepatitis B (HBV) infection. RESEARCH DESIGN AND METHODS Adultswith chronicHBVfrom21centerswithintheU.S.andCanadawereevaluatedat baseline and for up to 5 years (median 3.7 years) of follow-up. MSwas defined as the presenceofatleast threeoffivecriteriaincludingwaist circumference,bloodpressure, glucose, triglyceride, and HDL levels. RESULTS Analysis included 777 participants, ofwhom171 (22%) hadMS. Participants with MS (vs. those without MS) were older (median age 54.4 vs. 40.2 years), more oftenmale (61%vs. 51%), and born in the U.S./Canada or had immigrated >20 years ago (60% vs. 43%).MSwasnotassociatedwithALTorAPRIatbaseline.Uponadjustedmultivariable analysis of serial ALT values, ALTwas significantly higher (mean 12%; P = 0.02) among those withMS at baseline and even higher (mean 19%; P = 0.003) among those with persistent MS compared with those with persistent absence of MS. MS was not associated with serial APRI on follow-up. CONCLUSIONS MS was prevalent in this HBV cohort and was independently associated with higher ALT levels longitudinally. These findings highlight the importance of screening forMS and the potential for MSto influence ALT and its interpretation in the context of HBV treatment decisions.
AB - OBJECTIVE Metabolic syndrome (MS) is prevalent and is associated with adverse outcomes of liver disease.We evaluated the prevalence of MS and its influence on alanine aminotransferase (ALT) levels and fibrosis, as estimated by the aspartate aminotransferase- to-platelet ratio index (APRI), in a large, multiethnic North American cohort with chronic hepatitis B (HBV) infection. RESEARCH DESIGN AND METHODS Adultswith chronicHBVfrom21centerswithintheU.S.andCanadawereevaluatedat baseline and for up to 5 years (median 3.7 years) of follow-up. MSwas defined as the presenceofatleast threeoffivecriteriaincludingwaist circumference,bloodpressure, glucose, triglyceride, and HDL levels. RESULTS Analysis included 777 participants, ofwhom171 (22%) hadMS. Participants with MS (vs. those without MS) were older (median age 54.4 vs. 40.2 years), more oftenmale (61%vs. 51%), and born in the U.S./Canada or had immigrated >20 years ago (60% vs. 43%).MSwasnotassociatedwithALTorAPRIatbaseline.Uponadjustedmultivariable analysis of serial ALT values, ALTwas significantly higher (mean 12%; P = 0.02) among those withMS at baseline and even higher (mean 19%; P = 0.003) among those with persistent MS compared with those with persistent absence of MS. MS was not associated with serial APRI on follow-up. CONCLUSIONS MS was prevalent in this HBV cohort and was independently associated with higher ALT levels longitudinally. These findings highlight the importance of screening forMS and the potential for MSto influence ALT and its interpretation in the context of HBV treatment decisions.
UR - http://www.scopus.com/inward/record.url?scp=85047447413&partnerID=8YFLogxK
U2 - 10.2337/dc18-0040
DO - 10.2337/dc18-0040
M3 - Article
C2 - 29599296
AN - SCOPUS:85047447413
VL - 41
SP - 1251
EP - 1259
JO - Diabetes Care
JF - Diabetes Care
SN - 0149-5992
IS - 6
ER -