Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

Abstract

Background and Aims Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C. Methods We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals. Results We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis. Conclusion We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Clearance of HCV infection with DAA therapy can improve hepatic function and thereby affect the safety and efficacy of some concomitantly administered medications. Real‐world data indicate an association between DAA therapy and reduced glycemia, particularly among people with diabetes . Patients taking diabetes medication(s) should be informed of the potential for symptomatic hypoglycemia during and after DAA therapy.…”

“…Real-world data indicate an association between DAA therapy and reduced glycemia, particularly among people with diabetes. (141)(142)(143)(144) Patients taking diabetes medication(s) should be informed of the potential for symptomatic hypoglycemia during and after DAA therapy. Glucose monitoring during and after DAA treatment is recommended; dosage adjustments of diabetes medication(s) may be needed.…”

“…(92,294,295) Additionally, on-treatment and posttreatment glucose monitoring for hypoglycemia in children and adolescents with diabetes and INR monitoring in those taking warfarin is recommended due to potential alterations in doseresponse relationships associated with DAA-related HCV viral clearance. (141)(142)(143)(144)(145)(146)…”

Management of Diabetes Mellitus in Patients with Chronic Liver Diseases

“…Mounting evidence indicated that chronic HCV infection can elicit a series of extrahepatic reactions, such as endocrine disturbances, abnormal autoimmunity, and turbulence of metabolic disorders, inducing hypobetalipoproteinemia, steatosis, IR, impaired glucose tolerance, thyroid disease, gonadal dysfunction, and even tumors like mixed cryoglobulinemia and B-cell NHLs [30]. Among these complications, DM and IR are the general manifestations related to fibrosis development and similarly HCC with HCV infection, which further affect the morbidity and mortality of patients [30][31][32].…”

“…The growing frequency of T2DM and fasting blood glucose (FBG) is associated with the degree of hepatic cirrhotic lesions with HCV infection. HCV infection is the leading predictor of T2DM, along with the fibrosis-4 (FIB4) category, elder age, and greater BMI [32].…”