The impact of a successful treatment of hepatitis C virus on glyco-metabolic control in diabetic patients: a systematic review and meta-analysis

  • Carla Carnovale
  • Marco Pozzi
  • Alice Dassano
  • Francesca D’Addio
  • Marta Gentili
  • Carlo Magni
  • Emilio Clementi
  • Sonia Radice
  • Paolo Fiorina
Original Article



The effect of HCV eradication following the use of direct-acting antiviral drugs (DAAs) on the glyco-metabolic control is unknown. Through a meta-analysis of available clinical studies, we investigated whether eradication of HCV infection with interferon-free DAAs is associated with improved glyco-metabolic control in diabetic patients.


We searched the PubMed, MEDLINE and Embase, up to 08th June 2018, for all studies evaluating whether eradication of HCV infection with DAAs is associated with changes in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels from baseline in human subjects, without restrictions for study type and language. Data were independently extracted by two researchers using pre-specified forms. Random effects meta-analyses were conducted on HbA1c and FPG levels before/after HCV eradication.


We found a significant mean reduction in HbA1c levels of − 0.45% (95% CI − 0.60 to − 0.30%; P < 0.001) and in FPG levels of − 22.03 mg/dL (95% CI − 41.61 to − 2.44 mg/dL; P = 0.03), with high heterogeneity between studies (χ2 = 20.4, P < 0.001, I2 = 80% and χ2 = 35.8, P = 0.001, I2 = 94%, respectively). The number of available manuscripts did not allow conducting a meta-regression to elucidate the role of sustained virological response and other confounders in determining the effect of direct-acting antiviral agents on HbA1c reduction.


We found a significant improvement in glyco-metabolic control after HCV eradication (in terms of glycated haemoglobin and fasting plasma glucose levels reduction) following direct-acting antiviral treatment in patients with established diabetes, including a consequent positive impact on anti-diabetic therapies.


Glyco-metabolic control HbA1c FPG Direct-acting antiviral agents Hepatitis C 



Hepatitis C virus


Sustained virological response


Haemoglobin A1c, A1C, glycosylated haemoglobin, glycated haemoglobin, glycol-haemoglobin


Direct-acting antiviral




Newcastle–Ottawa Scale


Clinical trial


Fasting plasma glucose


Confidence interval


Author contributions

CC and MP conceptualized and designed the study, carried out the data extraction and statistical analyses, drafted the manuscript and the summary tables, revised and approved the final manuscript as submitted. AD and FD contributed to literature extraction and manuscript revision and approved the final manuscript as submitted. MG and CM participated in the conceptualization and design of the study, participated in the analysis of the data, revised the article, and approved the final article as submitted. EC and SR participated in the conceptualization and design of the study, participated in the analysis and interpretation of the data, revised the article, and approved the final article as submitted. PF contributed to concept and design of the study, participated in the analysis and interpretation of the data, coordinated and supervised data collection, critically reviewed the manuscript and approved the final manuscript as submitted. PF is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.


The financial support by the Agenzia Italiana del Farmaco (AIFA), by the Centre of Pharmacovigilance of Regione Lombardia (MEAP project, Monitoraggio degli Eventi Avversi nelle Popolazioni a Rischio, to EC), by the Italian Ministry of Health (RC 2017 to EC) and the Italian Ministry of Health (Ricerca Corrente 2018, to MP) is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human or animal subjects performed by the any of the authors.

Informed consent

For this type of study formal consent is not required.

Supplementary material

592_2018_1257_MOESM1_ESM.docx (323 kb)
Supplementary material 1 (DOCX 322 KB)


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  • Carla Carnovale
    • 1
  • Marco Pozzi
    • 2
  • Alice Dassano
    • 3
  • Francesca D’Addio
    • 3
  • Marta Gentili
    • 1
  • Carlo Magni
    • 4
  • Emilio Clementi
    • 1
    • 2
  • Sonia Radice
    • 1
  • Paolo Fiorina
    • 3
    • 5
    • 6
  1. 1.Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, “Luigi Sacco” University HospitalUniversità di MilanoMilanItaly
  2. 2.Scientific Institute IRCCS Eugenio MedeaBosisio PariniItaly
  3. 3.International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. SaccoUniversità di MilanoMilanItaly
  4. 4.1st Division of Infectious DiseasesASST Fatebenefratelli-SaccoMilanItaly
  5. 5.Nephrology Division, Boston Children’s HospitalHarvard Medical SchoolBostonUSA
  6. 6.Division of EndocrinologyASST Fatebenefratelli-SaccoMilanItaly

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