Hepatitis C Virus Eradication with New Interferon‐Free Treatment Improves Metabolic Profile in Hepatitis C Virus‐Related Liver Transplant Recipients

Abstract

Interferon (IFN)-free, direct-acting antiviral (DAA) therapy agents provide a safe and efficacious treatment for liver transplant recipients with recurrent hepatitis C virus (HCV) infection. The aim of this study is to evaluate the impact of HCV eradication on the metabolic factors in liver transplant recipients. We completed a retrospective single-center study on HCV-related liver transplant recipients treated with IFN-free DAAs including both treatment-naive and treatment-experienced patients. IFN-free DAAs impact on the metabolic profile were assessed at baseline and sustained virological response (SVR) between 24 and 48 weeks. In total, 91 liver transplant recipients with recurrent HCV infection received IFN-free DAA treatment, 62 patients had IFN-based treatment failure, and 29 were treatment-naïve, of whom 87 (96%) achieved SVR. Eradication of recurrent HCV infection was associated with reduction in the treatment of diabetes and hypertension by 38% and 22% from the baseline respectively. Hemoglobin A1c (HbA1c) levels declined from mean 35.5 ± 4.3 mmol/mol to 33.3 ±3.6 mmol/mol at 44 weeks posttreatment (P = 0.03). Total cholesterol levels increased from 3.8 ± 0.9 mmol/L to 4.9 ± 0.9 mmol/L at 41 weeks posttreatment (P < 0.0001), reflecting a significant increase in serum low-density lipoprotein (LDL) levels (2.0 ± 0.8 to 2.9 ± 0.8; P < 0.0001). Estimated glomerular filtration rate (eGFR) levels increased from 64.9 ± 20 mL/minute to 69.6 ± 20 mL/minute at 24 weeks posttreatment (P = 0.0004). Glucose, lipid profile, and eGFR changes were independent of weight changes and immunosuppression dosage and trough levels. In conclusion, eradication of recurrent HCV infection by DAA therapy has beneficial impacts on glucose metabolism and renal profile and reverses the hypolipidemic effect of HCV in liver transplant recipients. These extrahepatic effects of DAA therapy need to be validated by larger prospective studies.

Direct‐acting antivirals for HCV treatment in older patients: A systematic review and meta‐analysis

“…It has been recently shown that DAAs improve metabolic balance in CHC patients by exerting beneficial effects on fasting glucose, glycated haemoglobin and hypertension …”

The Effect of Viral Clearance Achieved by Direct-Acting Antiviral Agents on Hepatitis C Virus Positive Patients with Type 2 Diabetes Mellitus: A Word of Caution after the Initial Enthusiasm

“…The effect of antiviral therapy with DAAs on diabetic patients has also been studied in the liver transplant setting [24,29,30]. Beig and colleagues [24] observed a significant decrease of HbA1c levels (from 35.5 ± 4.3 mmol/mol to 33.3 ± 3.6 mmol/mol, p = 0.03) at 44 weeks from the end of treatment in 91 liver transplant recipients with recurrent HCV infection treated with DAAs. Unfortunately, it is not possible to establish from the reported data the HbA1c reduction in the 26 diabetic patients treated and cured by DAAs, even though the authors report a 40% decrement of DM treatment.…”

“…In addition to the uncertainty about how viral eradication would act on glycemic dysmetabolism, there is a lack of prospective studies with appropriate follow-up on the outcomes of diabetic patients achieving SVR. With the advent of DAAs and consequent high SVR rates, several observational studies [14][15][16][17][18][19][20][21][22][23][24][25][26][27] and one meta-analysis [28] suggested a significant clinical impact of SVR on DM outcomes; however, two of them [18,19], despite reporting significant initial amelioration, did not observe long-term improvement in glycemic control and some other studies [29][30][31][32][33] failed to find any significant glycometabolic changes. Controversies still exist regarding the post-SVR outcome of DM; current data are not sufficient to determine whether the acquired effect observed at SVR (significant decrease in fasting glycemia and glycated hemoglobin, HbA1c) persists over time and if it induces relevant variations regarding antidiabetic therapy.…”

Hepatitis C virus infection is associated with hepatic and adipose tissue insulin resistance that improves after viral cure

“…[10][11][12] Directly acting antiviral agents (DAAs) have recently become the standard of care with high rates of cure >90%. [13][14][15] Curing HCV infection with DAA or interferonbased therapies improves the metabolic profile [16][17][18] ; however, none of these studies investigated the tissue-specific effects of HCV infection on IR.…”