Javier A Cepeda1, David L Thomas2, Jacquie Astemborski3, Mark S Sulkowski2, Gregory D Kirk2,3, Shruti H Mehta3. 1. Division of Global Public Health, Department of Medicine, University of California, San Diego, La Jolla. 2. Division of Infectious Diseases, Johns Hopkins School of Medicine. 3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Abstract
BACKGROUND: Despite the availability of curative treatment for hepatitis C virus (HCV) infection, because of cost, treatment is often denied until liver fibrosis has progressed to at least moderate fibrosis and, in some cases, cirrhosis. That practice is justified on assumptions that there are no medical consequences to having moderate disease and that disease stage transitions can be anticipated. METHODS: We performed transient elastography on 964 people chronically infected with HCV with a history of injection drug use living in Baltimore, Maryland. Liver stiffness was evaluated semiannually from 2006 to 2014 using validated cutoffs for moderate fibrosis (8.0-12.3 kPa) and severe fibrosis/cirrhosis (>12.3 kPa). RESULTS: Among 964 persons, 62%, 23% and 15% had baseline measurements suggestive of no/mild fibrosis, moderate fibrosis, and severe fibrosis/cirrhosis, respectively. All-cause and nonaccidental mortality were elevated in persons with moderate fibrosis (adjusted hazard ratio [aHR], 1.42 [95% confidence interval {CI}, .96-2.11]; aHR, 1.66 [95% CI, 1.06-2.59], respectively) after adjustment for sociodemographics, substance use, and human immunodeficiency virus status. Despite the increased risk of mortality among those with moderate fibrosis, no combination of demographic, behavioral, and clinical factors, nor changes in stiffness measurements themselves could predict the transition from mild to moderate fibrosis with sufficiently high diagnostic accuracy (C-statistic = 0.72 for best-performing model). CONCLUSIONS: Delaying treatment for anyone chronically infected with HCV regardless of fibrosis stage may be detrimental given the increased risk of mortality even for those with moderate disease and the inability to predict the transition from mild to moderate disease.
BACKGROUND: Despite the availability of curative treatment for hepatitis C virus (HCV) infection, because of cost, treatment is often denied until liver fibrosis has progressed to at least moderate fibrosis and, in some cases, cirrhosis. That practice is justified on assumptions that there are no medical consequences to having moderate disease and that disease stage transitions can be anticipated. METHODS: We performed transient elastography on 964 people chronically infected with HCV with a history of injection drug use living in Baltimore, Maryland. Liver stiffness was evaluated semiannually from 2006 to 2014 using validated cutoffs for moderate fibrosis (8.0-12.3 kPa) and severe fibrosis/cirrhosis (>12.3 kPa). RESULTS: Among 964 persons, 62%, 23% and 15% had baseline measurements suggestive of no/mild fibrosis, moderate fibrosis, and severe fibrosis/cirrhosis, respectively. All-cause and nonaccidental mortality were elevated in persons with moderate fibrosis (adjusted hazard ratio [aHR], 1.42 [95% confidence interval {CI}, .96-2.11]; aHR, 1.66 [95% CI, 1.06-2.59], respectively) after adjustment for sociodemographics, substance use, and human immunodeficiency virus status. Despite the increased risk of mortality among those with moderate fibrosis, no combination of demographic, behavioral, and clinical factors, nor changes in stiffness measurements themselves could predict the transition from mild to moderate fibrosis with sufficiently high diagnostic accuracy (C-statistic = 0.72 for best-performing model). CONCLUSIONS: Delaying treatment for anyone chronically infected with HCV regardless of fibrosis stage may be detrimental given the increased risk of mortality even for those with moderate disease and the inability to predict the transition from mild to moderate disease.
Authors: M Schiavini; E Angeli; A Mainini; P Zerbi; P G Duca; G Gubertini; L Vago; P Fociani; R Giorgi; A Cargnel Journal: HIV Med Date: 2006-07 Impact factor: 3.180
Authors: Gregory D Kirk; Jacquie Astemborski; Shruti H Mehta; Chuck Spoler; Cedric Fisher; Danisha Allen; Yvonne Higgins; Richard D Moore; Nezem Afdhal; Michael Torbenson; Mark Sulkowski; David L Thomas Journal: Clin Infect Dis Date: 2009-04-01 Impact factor: 9.079
Authors: Shruti H Mehta; Becky L Genberg; Jacquie Astemborski; Ravi Kavasery; Gregory D Kirk; David Vlahov; Steffanie A Strathdee; David L Thomas Journal: J Community Health Date: 2008-06
Authors: Adriaan J van der Meer; Bart J Veldt; Jordan J Feld; Heiner Wedemeyer; Jean-François Dufour; Frank Lammert; Andres Duarte-Rojo; E Jenny Heathcote; Michael P Manns; Lorenz Kuske; Stefan Zeuzem; W Peter Hofmann; Robert J de Knegt; Bettina E Hansen; Harry L A Janssen Journal: JAMA Date: 2012-12-26 Impact factor: 56.272
Authors: Jack X Q Pang; Scott Zimmer; Sophia Niu; Pam Crotty; Jenna Tracey; Faruq Pradhan; Abdel Aziz M Shaheen; Carla S Coffin; Steven J Heitman; Gilaad G Kaplan; Mark G Swain; Robert P Myers Journal: PLoS One Date: 2014-04-22 Impact factor: 3.240
Authors: Mark S Sulkowski; David F Gardiner; Maribel Rodriguez-Torres; K Rajender Reddy; Tarek Hassanein; Ira Jacobson; Eric Lawitz; Anna S Lok; Federico Hinestrosa; Paul J Thuluvath; Howard Schwartz; David R Nelson; Gregory T Everson; Timothy Eley; Megan Wind-Rotolo; Shu-Pang Huang; Min Gao; Dennis Hernandez; Fiona McPhee; Diane Sherman; Robert Hindes; William Symonds; Claudio Pasquinelli; Dennis M Grasela Journal: N Engl J Med Date: 2014-01-16 Impact factor: 91.245
Authors: Eshan U Patel; Sunil S Solomon; Allison M Mcfall; Aylur K Srikrishnan; Amrose Pradeep; Paneerselvam Nandagopal; Oliver Laeyendecker; Aaron A R Tobian; David L Thomas; Mark S Sulkowski; M Suresh Kumar; Shruti H Mehta Journal: Int J Drug Policy Date: 2018-04-19
Authors: Brian Conway; Julie Bruneau; Curtis Cooper; Chris Steingart; Chris Fraser; Kris Stewart; Lucie Deshaies; Réjean Thomas; Duncan Webster; Gisela Macphail; Jeff Powis; Joseph Cox; Jordan J Feld; Mark E McGovern; Janie B Trepanier; Martine Drolet Journal: Can Liver J Date: 2020-11-17
Authors: Jason Grebely; Gregory J Dore; Sébastien Morin; Jürgen K Rockstroh; Marina B Klein Journal: J Int AIDS Soc Date: 2017-07-28 Impact factor: 5.396
Authors: Tea L Laursen; Thomas D Sandahl; Konstantin Kazankov; Jacob George; Henning Grønbæk Journal: World J Gastroenterol Date: 2020-06-14 Impact factor: 5.742