Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 27, 2018; 10(9): 612-621
Published online Sep 27, 2018. doi: 10.4254/wjh.v10.i9.612
Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c
Tien S Dong, Elizabeth S Aby, Jihane N Benhammou, Jenna Kawamoto, Steven-Huy Han, Folasade P May, Joseph R Pisegna
Tien S Dong, Elizabeth S Aby, Jihane N Benhammou, Folasade P May, Joseph R Pisegna, the Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
Tien S Dong, Jihane N Benhammou, Jenna Kawamoto, Steven-Huy Han, Folasade P May, Joseph R Pisegna, Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
Steven-Huy Han, the Pfleger Liver Institute, Department of Surgery, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
Folasade P May, VA Health Services Research and Development Center for the Study of Healthcare Innovation Center for the Study of Healthcare Innovation, Implementation and Policy (CSHIIP), Los Angeles, CA 90073, United States
Folasade P May, Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, United States
Author contributions: Dong TS, Aby ES, Benhammou JN, Kawamoto J, Han SH, May FP and Pisegna JR contributed to the project design and writing of the manuscript; Dong TS, Aby ES and Benhammou JN collected data; Dong TS and May FP along with aid from the biostatistical department at UCLA performed the statistics.
Institutional review board statement: This study was approved by the VA Institutional Review Board and the Research and Development Committee at VA Greater Los Angeles Health System (VAGLAHS). ID Number 2016-100938.
Informed consent statement: Due to the retrospective nature of this study, an exempt for informed consent was approved by the VA institutional review board. ID Number 2016-100938.
Conflict-of-interest statement: All authors declare no conflicts of interest that might compromise the integrity of this study.
Data sharing statement: No additional data are available.
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: Tien S Dong, MD, Academic Fellow, the Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, 10945 Le Conte Ave, PVUB 2114 MC694907, Los Angeles, CA 90095, United States. tsdong@mednet.ucla.edu
Telephone: +1-310-2060449 Fax: +1-310-2671861
Received: April 5, 2018
Peer-review started: April 7, 2018
First decision: May 7, 2018
Revised: May 9, 2018
Accepted: May 23, 2018
Article in press: May 24, 2018
Published online: September 27, 2018
ARTICLE HIGHLIGHTS
Research background

Hepatitis C virus (HCV) infection is a major worldwide health problem. There are increasing reports indicating an association between HCV and type 2 diabetes mellitus (T2DM). Individuals with HCV are more likely to have risk factors to develop T2DM and patients with T2DM have at least a 2-fold greater risk of developing HCV infection than the general population. Previously standard therapy for HCV required the use of pegylated interferon-α (P-IFN) and ribavirin. However, these regimens had low sustained virologic response (SVR) rates and were poorly tolerated. During the era of P-IFN therapy, several studies showed that the presence of obesity and/or steatosis led to a reduction of SVR rate in HCV patients. In patients with diabetes and HCV who were treated with IFN-based therapies, HCV clearance was associated with improved insulin resistance and beta cell function.

Research motivation

In 2013 and 2014, approval of newer direct acting antiviral agents (DAA) created IFN-free regimens with SVR rates greater than 90%, radically changing HCV treatment. Due to the novelty of DAA regimen, research is being actively pursued in a variety of patient populations.

Research ojectives

We aim to determine if successful treatment with DAA is associated with improvements in hemoglobin A1c (HbA1c) and if the presence of T2DM or metabolic syndrome affects SVR rates.

Research methods

DAA were introduced to the VA Greater Los Angeles Healthcare System (VAGLAHS) at the beginning of April 2014. Therefore, we included all patients being treated with DAA between April 1st, 2014 and April 30th, 2016 for this study. We performed a retrospective analysis of all HCV patients at the VA Greater Los Angeles Healthcare System treated with DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment (SVR12). Patients with HCV were also included if they had diabetic medications on their medication list during the study period. Patients were excluded from the cohort if they did not have SVR12 data or a HbA1c one year after completion of DAA therapy.

Research results

A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2DM. Within that cohort, patients who achieved SVR12 had lower mean HbA1c pre-treatment (7.35 vs 8.60, P = 0.02), and lower mean HbA1c post-treatment compared to non-responders (6.55 vs 8.61, P = 0.01). The mean reduction in HbA1c after treatment was greater for those who achieved SVR12 than for non-responders (0.79 vs 0.01, P = 0.03). In adjusted models, patients that achieved SVR12 were more likely to have a HbA1c decrease of > 0.5 than those that did not achieve SVR12 (adjusted OR = 7.24, 95%CI: 1.22-42.94).

Research conclusions

In conclusion, this study of a diverse VA patient population demonstrates that HCV clearance with DAAs is associated with a clinically significant decrease in HbA1c. This change was consistent across all genotypes and treatment regimens. The change in HbA1c was independent of changes in BMI and DM medication requirements and so may represent a decrease in host insulin resistance or increased insulin sensitivity. This study substantiates similar studies during the pegylated-interferon era by showing that HCV clearance irrespective of treatment regimen and genotype leads to improved DM outcomes. However, unlike prior studies during the period of pegylated-interferon, we show that hypertension, hyperlipidemia, T2DM, obesity, and metabolic syndrome do not negatively affect SVR12 rates for DAA.

Research perspectives

Future prospective studies analyzing patient fasting blood glucose and serum insulin should be performed to validate these findings and to help elucidate the relationship between HCV, insulin sensitivity, and longer-term DM outcomes such as cardiovascular events.