Hepatitis C virus eradication by direct-acting antiviral agents improves glucose tolerance

Eradication of hepatitis C virus (HCV) by direct-acting antiviral (DAA) agents improves glucose tolerance in pre-diabetic cirrhotic patients infected with genotype 1, according to a new study.

Genotype 1 chronic HCV infection is associated with impaired glucose homoeostasis, especially among patients with advanced stages of the disease. “A previous study showed that glucose tolerance is an independent predictor of overall mortality and hepatic decompensation in patients with HCV cirrhosis. HCV impairs insulin sensitivity, triggers insulin resistance, and thereby leads to diabetes onset. Our study is now the first to show that HCV clearance enhances glucose tolerance,” lead author Federico Salomone, MD, PhD of Acireale Hospital in Catania, Italy, told Medical Economics. 

The researchers published their results in July 2018 issue of Liver International.

Salomone and colleagues performed a prospective study assessing the effects of DAA treatment in nondiabetic patients with compensated cirrhosis due to genotypes 1a/1b. “These genotypes are also those associated with more incidence of diabetes. We decided to study pre-diabetic patients because these patients are not treated pharmacologically, and thus the effect to be observed was not influenced by any drug,” said Salomone. 

Glucose tolerance was evaluated through a 75-gm oral glucose tolerance test. Impaired glucose tolerance was diagnosed by 2-hour plasma glucose between 140 and 199 mg/dL, as recommended by the American Diabetes Association.

From an initial cohort of 100 patients, 32 patients with compensated Child A cirrhosis displayed impaired glucose tolerance without other relevant comorbidities, including HBV, HIV, hepatocellular carcinoma, or alcohol abuse, which would influence glucose tolerance, he said.

All patients achieved a sustained virological response following DAA treatment. After viral eradication, there was no observed change in fasting plasma glucose, but 2-hour plasma glucose was markedly reduced in all patients, and most of them returned to normal glucose tolerance.

“These effects were observed in spite of no change of body weight,” said Salomone. “Interestingly, HCV eradication also reduced glycated hemoglobin and post–load insulin resistance, both important parameters of glycemic control.”

Impaired glucose tolerance precedes overt diabetes. “For this reason, we may speculate that with the advent of second-generation DAAs we will observe not only a reduction of liver-related outcomes, such as portal hypertension and cancer, but also of metabolic outcomes, such as diabetes and its complications. This appears relevant to the single patient and to the community because of the high cost of diabetes treatment,” said Salomone.

The researchers concluded that “our novel findings shed light on an early beneficial effect of HCV eradication on glucose tolerance that conceivably may lead to a reduction in type 2 diabetes incidence in the long term. Furthermore, post–load hyperglycemia was shown to predict hepatocellular carcinoma onset in chronic hepatitis C.”

They suggest that next studies will take into account the effect of HCV eradication on the incidence of type 2 diabetes and its complications as a main outcome in the long term.