Exposure to Proton Pump Inhibitors is a Risk Factor for New Fractures in Hepatitis C Patients Following IFN/Ribavirin Therapy Irrespective of Virological Response

Abstract

Purpose: Overall incidence of bone fractures among HCV positive patients is higher in those who receive proton pump inhibitors (PPI) than in those who do not receive PPI. The purpose of this study is to determine whether the increased bone fracture incidence in hepatitis C patients associated with PPI is dependent upon viral clearance. Methods: A retrospective cohort study of the incidence of bone fractures after treatment with interferon/ribavirin (IFN/RIB) based therapy treated between 1/1999 and 1/2011 in 365 HCV antibody positive veterans was performed. The primary study endpoints were the number of bone fractures after therapy in HCV patients with a response (R), defined as an SVR or end of treatment response (ETR) or those with NR (defined as nonresponder or relapser). For both HCV groups (R and NR), the beginning and final date of the bone fracture observation period was defined as 6 months after IFN/RIB therapy and the study end date, respectively. Body mass index (BMI), calcium levels, ethnicity, tobacco, alcohol and PPI use were collected. Statistical differences in fracture incidence between groups were determined by Mann Whitney U and multivariable regression analysis. Results: Our cohort was 92.3% male, 70% W, 26% AA and 2% H with a mean age of 57.7 yrs. Response occurred in 44% of HCV patients, with significantly more AA in NR than R (34% vs 13%) but with no differences between groups in BMI, calcium levels, gender, alcohol, and PPI use. Among the study population with complete data analyzed (n=342), similar number of fractures were noted after IFN/RIB therapy in NR (n=7) and R (n=6) groups. After adjusting for ethnicity, gender, BMI, alcohol, tobacco and PPI use, there was no difference in new bone fracture incidence between R and NR in patients with chronic HCV. Of interest, more PPI users had fractures post IFN/Rib therapy than non PPI users (p = 0.003). Conclusion: In patients with chronic HCV, SVR did not confer a decreased risk of new bone fractures. Importantly, PPI were a risk factor for new fractures in Hepatitis C patients after IFN/Ribavirin therapy,irrespective of Hepatitis C viral clearance.