Published online Sep 27, 2018. doi: 10.4254/wjh.v10.i9.612
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
Processing time: 174 Days and 13.4 Hours
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.
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.
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.
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.
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).
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.
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.