response to hepatitis C virus (HCV) therapy does not result in long-term improvements in glucose
metabolism for people with type 2 diabetes, according to US research
published in Liver International.
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 people who had an SVR
after receiving treatment with direct-acting antivirals (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
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
The present research
underlines the importance of monitoring and treating type 2 diabetes in
people with HCV, even if they have an 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 people with
type 2 diabetes, an 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.
limitations and conflicting findings in mind, investigators from the US Chronic
Hepatitis Cohort Study designed a study involving people with chronic HCV
infection and type 2 diabetes, comparing changes in HbA1c levels according to SVR
status (SVR vs untreated/unresponsive patients).
population consisted of 384 people,
half untreated, the other half with SVR or treatment failure. Median age was
approximately 57 years and 35% were women. The participants were racially diverse
(11%, African American; 41-45%, white; 44-48%, other). Cirrhosis was present in
between 11 and 15% of people, 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).
untreated people was timed from HCV diagnosis. In treated people, 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 body mass index (BMI).
duration of follow-up was 30 months.
stable in untreated people and also in people 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
analysis of the 73 people who had an 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.
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.”