Treatment of hepatitis C virus (HCV) infection is
associated with better glucose control and a lower likelihood of developing
diabetes, according to a report at the Conference on Retroviruses and
Opportunistic Infections (CROI 2019) this month in Seattle.
of diabetes was 52% lower among those treated with direct-acting antivirals (DAAs)
in a large study of US veterans, showing that treatment offers benefits beyond virological control, Dr Adeel Butt
of the Veterans Administration Pittsburgh Healthcare System reported.
It is well known that HCV infection is associated with a higher risk of
diabetes, although the underlying mechanism is not well understood. Determining the link would be a substantial increase in our medical knowledge,
Butt said, suggesting that inflammation could be a factor or HCV may have a
direct effect on glucose metabolism.
Something that has an
effect outside the liver, for example when viral hepatitis affects the kidneys
or causes depression.
- 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.
Studies during the interferon era produced mixed results, with some
showing that successful hepatitis C treatment reduced diabetes risk, while
others linked interferon and ribavirin to new-onset diabetes.
Newer DAAs are
highly active against HCV but have far fewer side-effects than interferon-based
therapy, including metabolic effects. Recent reports suggest that DAAs have a
beneficial short-term effect on glucose control, but to date no studies have
compared diabetes risk in untreated people with hepatitis C and those treated
with pegylated interferon/ribavirin or DAAs.
Butt and colleagues looked at the effect of HCV
treatment on the
risk and incidence of diabetes among more than 52,000 US veterans, using data
from the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a longitudinal national cohort of veterans with
After excluding people with HIV or
hepatitis B virus co-infection, those treated with both interferon-based
therapy and DAAs, and those missing follow-up HCV viral load data to determine
sustained virological response (SVR), the analysis included 4764 chronic
hepatitis C patients treated with pegylated interferon plus ribavirin and
21,279 treated with DAAs, along with the same number of matched untreated
study participants (96%) were men, as is typical of a veteran population, so
these findings cannot be generalised to women. About 54% were white, about 29%
were black and the median age was approximately 60 years. Around 20% had
advanced fibrosis or cirrhosis according to the non-invasive FIB-4 index. Among
the treated patients, 79% achieved SVR, or continued undetectable HCV RNA 12
weeks after finishing treatment, which is regarded as a cure.
the follow-up period, 1679 untreated veterans, 633 of those treated with
pegylated interferon/ribavirin and 255 of those treated with DAAs were
diagnosed with diabetes. The corresponding diabetes incidence rates were 20.6,
19.8 and 9.89, respectively, per 1000 person-years. HCV treatment was
associated with a larger reduction in diabetes incidence among people with more
advanced fibrosis or cirrhosis, Butt reported.
diabetes incidence did not differ significantly between untreated and
interferon-treated people, it was substantially lower among those treated
with DAAs. People who achieved SVR using either type of treatment were less
likely to develop diabetes than those without SVR (13.3 vs 19.2 per 1000
person-years). But the difference in diabetes risk was driven more by the type
of treatment than by presence or absence of SVR, according to Butt. DAAs
reduced the risk of diabetes by 52%, while achieving SVR lowered the risk by a
more modest 19%.
further reported that people treated with DAAs had longer diabetes-free
survival than either untreated people or those treated with pegylated
interferon/ribavirin, although there was no significant difference between
untreated people and those treated with interferon-based therapy.
significantly reduces the incidence and risk of subsequent diabetes, which
appears to be driven largely by DAA regimens," the researchers
of HCV with DAA regimens confer benefits beyond virologic control and may be
useful in controlling or mitigating some of the extrahepatic complications of