A successful response to HCV therapy does not result in long-term improvements in glucose metabolism for patients with type-2 diabetes, according to US research published in Liver International.
A sustained virological response (SVR) was associated with a short-term improvement in a key marker of glucose control, but these improvements were not sustained in the longer-term and within three years glucose control was comparable between SVR patients and individuals who did not receive any HCV therapy or who had an unsuccessful treatment response. The investigators found the same results when they restricted their analysis to patients who had a SVR after receiving treatment with direct-acting agents (DAAs).
“A number of studies have reported significant decreases in HbA1c [glycosolated haemoglobin] immediately after SVR. In contrast, a recent report found that reductions in HbA1c immediately following successful treatment were not sustained after a mean duration of 2.5 years,” write the authors. “A strength of our longitudinal analysis is that our results allow us to reconcile these apparently conflicting reports.”
The present research underlines the importance of monitoring and treating type-2 diabetes in patients with HCV, even in patients even if they have a SVR to therapy.
It’s well known that chronic HCV infection directly impairs glucose metabolism and contributes to insulin resistance. Some research has suggested that among patients with type-2 diabetes, a SVR to HCV therapy is accompanied by improved glycemic control and insulin sensitivity. But these studies are limited by their small sample sizes and relatively short follow-up periods (a maximum of 15 months after SVR). Moreover, a recent report suggested that any improvements were not sustained in the longer-term.
With these limitations and conflicting findings in mind, investigators form the US Chronic Hepatitis Cohort Study designed a study involving patients with chronic HCV infection and type-2 diabetes, comparing changes in HbA1c levels according to SVR status (SVR vs. untreated/unresponsive patients).
The study population consisted of 384 patients, half untreated, the other half with SVR or treatment failure. Median age was approximately 57 years and 35% were women. The patients were racially diverse (11%, African American; 41-45%, White; 44-48%, Other). Cirrhosis was present in between 11% of 15% of patients, a third were hypertensive, a fifth had hyperlipidemia and just short of two-thirds were taking statins.
Baseline HbA1c was comparable (untreated, 8.0 vs. treated, 7.8).
Follow-up for untreated patients was timed from HCV diagnosis. In treated patients, follow-up was from date of starting HCV therapy. Results were adjusted to take into account demographic and other risk factors for type-2 diabetes, especially BMI.
The median duration of follow-up was 30 months.
HbA1c remained stable in untreated patients and also in patients who had an unsuccessful response to HCV treatment.
Among the SVR patients, there were three distinct HbA1c phases. A significant fall was observed in the first 90 days (-5.4%, p < 0.001). Levels increased over the next 90 days (+1.5%, p = 0.003) and stabilised (+0.5%) thereafter. By the end of follow-up, HbA1c was comparable between SVR patients and untreated/unsuccessfully treated patients.
A sub-group analysis of the 73 patients who had a SVR after DAA therapy found the same trajectory in HbA1c. There was a significant 5.7% fall in the first six months after treatment (p < 0.001). But this was followed by an increase of 3.9% every 90 days (p = 0.019), up to 15 months of follow-up.
“Our analysis shows that SVR to HCV treatment does not improve long-term glycemic control. Clinicians should be aware that in patients with type-2 diabetes, HbA1 decreases dramatically shortly after successful treatment, but these decreases are not sustained,” conclude the authors. “Less than three years after SVR, HbA1c rebounds to levels similar to untreated/treatment failure patients, and higher than recommended for type-2 diabetic maintenance.”
By Michael Carter
Li J et al. Sustained virological response does not improve long-term glycemic control in patients with type 2 diabetes and chronic hepatitis C. Liver Int, doi: 10.1111/liv.14031 (2018).