Hepatitis C treatment reduces risk of diabetes

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.

The incidence 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.

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 hepatitis C.

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 control subjects.

Most 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.

During 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.

While 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%.

Butt 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.

"HCV treatment significantly reduces the incidence and risk of subsequent diabetes, which appears to be driven largely by DAA regimens," the researchers concluded." Treatment of HCV with DAA regimens confer benefits beyond virologic control and may be useful in controlling or mitigating some of the extrahepatic complications of HCV."