A Real-World Analysis of the Population with Hepatitis C Virus Infection Affected by Type 2 Diabetes in Italy: Patients’ Characteristics, Comorbidity Profiles and Treatment Patterns
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Source
2.2. Study Design and Selection Criteria
2.3. Patients’ Baseline Characteristics and Most Frequent Medications Used During Follow-Up
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
HCV+ Only (N = 1289), Included from 2019 | |||
---|---|---|---|
ATC Code (2nd Level) | Description | Untreated (N = 4170) | DAA-Treated (N = 2406) |
J01 | Antibacterials for systemic use | 185 (42.6%) | 370 (43.3%) |
C09 | Agents acting on the renin–angiotensin system | 178 (41.0%) | 325 (38.0%) |
A02 | Drugs for acid-related disorders | 163 (37.6%) | 325 (38.0%) |
M01 | Anti-inflammatory and antirheumatic products | 116 (26.7%) | 225 (26.3%) |
A11 | Vitamins | 91 (21.0%) | 189 (22.1%) |
C07 | Beta-blocking agents | 88 (20.3%) | 234 (27.4%) |
B01 | Antithrombotic agents | 88 (20.3%) | 177 (20.7%) |
H02 | Corticosteroids for systemic use | 77 (17.7%) | 142 (16.6%) |
R03 | Drugs for obstructive airway diseases | 57 (13.1%) | * |
C03 | Diuretics | 56 (12.9%) | 153 (17.9%) |
References
- Manns, M.P.; Buti, M.; Gane, E.; Pawlotsky, J.-M.; Razavi, H.; Terrault, N.; Younossi, Z. Hepatitis C virus infection. Nat. Rev. Dis. Primers 2017, 3, 17006. [Google Scholar] [CrossRef]
- Iversen, J.; Wand, H.; Chan, P.L.; Le, L.V.; Maher, L. Systematic review of hepatitis C virus prevalence in the WHO Western Pacific Region. Viruses 2022, 14, 1548. [Google Scholar] [CrossRef] [PubMed]
- Andriulli, A.; Stroffolini, T.; Mariano, A.; Valvano, M.R.; Grattagliano, I.; Ippolito, A.M.; Grossi, A.; Brancaccio, G.; Coco, C.; Russello, M.; et al. Declining prevalence and increasing awareness of HCV infection in Italy: A population-based survey in five metropolitan areas. Eur. J. Intern. Med. 2018, 53, 79–84. [Google Scholar] [CrossRef]
- Negro, F. Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseases. J. Hepatol. 2014, 61 (Suppl.), S69–S78. [Google Scholar] [CrossRef] [PubMed]
- Milner, K.L.; van der Poorten, D.; Trenell, M.; Jenkins, A.B.; Xu, A.; Smythe, G.; Dore, G.J.; Zekry, A.; Weltman, M.; Fragomeli, V.; et al. Chronic hepatitis C is associated with peripheral rather than hepatic insulin resistance. Gastroenterology 2010, 138, 932–941.e1–3. [Google Scholar] [CrossRef] [PubMed]
- Romero-Gómez, M.; Del Mar Viloria, M.; Andrade, R.J.; Salmerón, J.; Diago, M.; Fernández-Rodríguez, C.M.; Corpas, R.; Cruz, M.; Grande, L.; Vázquez, L.; et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology 2005, 128, 636–641. [Google Scholar] [CrossRef]
- Aghemo, A.; Prati, G.M.; Rumi, M.G.; Soffredini, R.; D’Ambrosio, R.; Orsi, E.; De Nicola, S.; Degasperi, E.; Grancini, V.; Colombo, M. Sustained virological response prevents the development of insulin resistance in patients with chronic hepatitis C. Hepatology 2012, 56, 1681–1687. [Google Scholar] [CrossRef]
- Arase, Y.; Suzuki, F.; Suzuki, Y.; Akuta, N.; Kobayashi, M.; Kawamura, Y.; Yatsuji, H.; Sezaki, H.; Hosaka, T.; Hirakawa, M.; et al. Virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C. Hepatology 2009, 49, 739–744. [Google Scholar] [CrossRef]
- Imazeki, F.; Yokosuka, O.; Fukai, K.; Kanda, T.; Kojima, H.; Saisho, H. Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: Comparison with hepatitis B virus-infected and hepatitis C virus-cleared patients. Liver Int. 2008, 28, 355–362. [Google Scholar] [CrossRef]
- Compagnoni, S.; Bruno, E.M.; Madonia, G.; Cannizzaro, M.; Madonia, S. Direct antiviral agents in hepatitis C virus related liver disease: Don’t count the chickens before they’re hatched. World J. Gastroenterol. 2021, 27, 2771–2783. [Google Scholar] [CrossRef]
- Kwon, S.Y.; Kim, S.S.; Kwon, O.S.; Kwon, K.A.; Chung, M.G.; Park, D.K.; Koo, Y.S.; Kim, Y.K.; Choi, D.J.; Kim, J.H. Prognostic significance of glycaemic control in patients with HBV and HCV-related cirrhosis and diabetes mellitus. Diabet. Med. 2005, 22, 1530–1535. [Google Scholar] [CrossRef] [PubMed]
- Rao, H.; Wei, L.; Li, H.; Yang, R.; Zhang, H.; Shang, J.; Chen, H.; Li, J.; Xie, Q.; Gao, Z.; et al. Prevalence of abnormal glycometabolism in treatment-naive patients with hepatitis C virus infection in a Chinese Han population. J. Gastroenterol. Hepatol. 2015, 30, 1049–1056. [Google Scholar] [CrossRef] [PubMed]
- Ciardullo, S.; Mantovani, A.; Ciaccio, A.; Carbone, M.; Invernizzi, P.; Perseghin, G. Hepatitis C virus infection and diabetes: A complex bidirectional relationship. Diabetes Res. Clin. Pract. 2022, 187, 109870. [Google Scholar] [CrossRef] [PubMed]
- Tang, L.; Marcell, L.; Kottilil, S. Systemic manifestations of hepatitis C infection. Infect. Agents Cancer 2016, 11, 29. [Google Scholar] [CrossRef]
- Soverini, V.; Persico, M.; Bugianesi, E.; Forlani, G.; Salamone, F.; Massarone, M.; La Mura, V.; Mazzotti, A.; Bruno, A.; Marchesini, G. HBV and HCV infection in type 2 diabetes mellitus: A survey in three diabetes units in different Italian areas. Acta Diabetol. 2011, 48, 337–343. [Google Scholar] [CrossRef]
- ISS; AISF; SIMIT PITER Collaborating. Clinical and virological profile of patients with diagnosed HCV chronic infection in Italy: Data from PITER cohort study. Dig. Liver Dis. 2016, 48 (Suppl. 1). [Google Scholar] [CrossRef]
- Mason, A.L.; Lau, J.Y.; Hoang, N.; Qian, K.; Alexander, G.J.; Xu, L.; Guo, L.; Jacob, S.; Regenstein, F.G.; Zimmerman, R.; et al. Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 1999, 29, 328–333. [Google Scholar] [CrossRef]
- Mangia, A.; Scaglione, F.; Toniutto, P.; Pirisi, M.; Coppola, N.; Di Perri, G.; Nieto, G.A.; Calabrese, S.; Hernandez, C.; Perrone, V.; et al. Drug-drug interactions in Italian patients with chronic hepatitis C treated with pangenotypic direct-acting agents: Insights from a real-world study. Int. J. Environ. Res. Public Health 2021, 18, 7144. [Google Scholar] [CrossRef]
- European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C: Final update of the series. J. Hepatol. 2020, 73, 1170–1218. [Google Scholar] [CrossRef]
- Borghi, C.; Ciancio, A.; Gentile, I.; Filardi, P.P.; Pasqualetti, P.; Brillanti, S. Evaluation of drug interactions in patients treated with DAAs for hepatitis C therapy with comorbidities and cardiovascular issues: A Delphi consensus project. J. Clin. Med. 2022, 11, 6946. [Google Scholar] [CrossRef]
- Valenti, L.; Pelusi, S.; Aghemo, A.; Gritti, S.; Pasulo, L.; Bianco, C.; Iegri, C.; Cologni, G.; Degasperi, E.; D’ambrosio, R.; et al. Dysmetabolism, diabetes and clinical outcomes in patients cured of chronic hepatitis C: A real-life cohort study. Hepatol. Commun. 2022, 6, 867–877. [Google Scholar] [CrossRef] [PubMed]
- Nava, F.A.; Mangia, A.; Riglietta, M.; Somaini, L.; Foschi, F.G.; Claar, E.; Maida, I.; Ucciferri, C.; Frigerio, F.; Hernandez, C.; et al. Analysis of patients’ characteristics and treatment profile of people who use drugs (PWUDs) with and without a co-diagnosis of viral hepatitis C: A real-world retrospective Italian analysis. Ther. Clin. Risk Manag. 2023, 19, 645–656. [Google Scholar] [PubMed]
- Fagiuoli, S.; Toniutto, P.; Coppola, N.; Ancona, D.D.; Andretta, M.; Bartolini, F.; Ferrante, F.; Lupi, A.; Palcic, S.; Rizzi, F.V.; et al. Italian real-world analysis of the impact of polypharmacy and aging on the risk of multiple drug-drug interactions in HCV patients treated with pangenotypic direct-acting antivirals. Ther. Clin. Risk Manag. 2023, 19, 57–65. [Google Scholar]
- Perrone, V.; Giacomini, E.; Veronesi, C.; Ancona, D.D.; Andretta, M.; Bartolini, F.; Chinellato, A.; Procacci, C.; Serena, M.; Bonora, E.; et al. Analisi del consumo di risorse sanitarie e costi diretti sostenuti dal Servizio Sanitario Nazionale nei pazienti con diabete in terapia insulinica in relazione al diverso monitoraggio della glicemia. ClinicoEconomics 2022, 17, 89–106. [Google Scholar]
- Zoratti, M.J.; Siddiqua, A.; Morassut, R.E.; Zeraatkar, D.; Chou, R.; van Holten, J.; Xie, F.; Druyts, E. Pangenotypic direct-acting antivirals for the treatment of chronic hepatitis C virus infection: A systematic literature review and meta-analysis. EClinicalMedicine 2020, 18, 100237. [Google Scholar] [CrossRef]
- Charlson, M.E.; Pompei, P.; Ales, K.L.; MacKenzie, C.R. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J. Chronic Dis. 1987, 40, 373–383. [Google Scholar] [CrossRef]
- Hammerstad, S.S.; Grock, S.F.; Lee, H.J.; Hasham, A.; Sundaram, N.; Tomer, Y. Diabetes and Hepatitis C: A Two-Way Association. Front. Endocrinol. 2015, 6, 134. [Google Scholar] [CrossRef]
- Songtanin, B.; Nugent, K. Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis C Virus Infection. Biology 2022, 12, 23. [Google Scholar] [CrossRef]
- Isfordink, C.J.; Boyd, A.; Sacks-Davis, R.; van Santen, D.K.; Smit, C.; Martinello, M.; Stoove, M.; Berenguer, J.; Wittkop, L.; Klein, M.B.; et al. Reasons for not commencing direct-acting antiviral treatment despite unrestricted access for individuals with HIV and hepatitis C virus: A multinational, prospective cohort study. Lancet Public Health 2023, 8, e294–e304. [Google Scholar] [CrossRef]
- Angel, M.; Petrosyan, Y.; Doyle, M.A.; Cooper, C. HCV infection characteristics, treatment uptake and outcomes in patient with diabetes mellitus. BMC Endocr. Disord. 2022, 22, 277. [Google Scholar] [CrossRef]
- Zhuang, L.; Li, J.; Zhang, Y.; Ji, S.; Li, Y.; Zhao, Y.; Li, B.; Li, W.; Quan, M.; Duan, Y.; et al. Real-World Effectiveness of Direct-Acting Antiviral Regimens against Hepatitis C Virus (HCV) Genotype 3 Infection: A Systematic Review and Meta-Analysis. Ann. Hepatol. 2021, 23, 100268. [Google Scholar] [CrossRef] [PubMed]
- Quan, H.; Li, B.; Saunders, L.D.; Parsons, G.A.; Nilsson, C.I.; Alibhai, A.; Ghali, W.A.; for the IMECCHI Investigators. Assessing validity of ICD-9-CM and ICD-10 administrative data in recording clinical conditions in a unique dually coded database. Health Serv. Res. 2008, 43, 1424–1441. [Google Scholar] [CrossRef] [PubMed]
- Cole, S.A.; Laviada-Molina, H.A.; Serres-Perales, J.M.; Rodriguez-Ayala, E.; Bastarrachea, R.A. The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins? Pathogens 2020, 9, 389. [Google Scholar] [CrossRef]
- Tramonti Fantozzi, M.P.; Ceccarelli, L.; Petri, D.; De Vita, E.; Agostini, A.; Colombatto, P.; Stasi, C.; Rossetti, B.; Brunetto, M.; Surace, L.; et al. Hepatitis C epidemiology and treatment outcomes in Italy: Impact of the DAA era and the COVID-19 pandemic. J. Viral Hepat. 2024, 31, 623–632. [Google Scholar] [CrossRef] [PubMed]
Overall HCV+ (N = 7803) | T2D-HCV+ (N = 1227) | HCV+ Only (N = 6576) | T2D Only (N = 236,026) | p-Value | |
---|---|---|---|---|---|
Age at index date, years, mean (±SD) | 67.3 (±9.3) | 69.8 (±9.1) | 66.9 (±9.3) | 72.3 (±9.6) | <0.001 |
Age classes | |||||
55–64 years, N (%) | 3606 (46.2%) | 412 (33.6%) | 3194 (48.6%) | 56,195 (23.8%) | |
65–74 years, N (%) | 2126 (27.2%) | 378 (30.8%) | 1748 (26.6%) | 81,878 (34.7%) | |
75–84 years, N (%) | 1789 (22.9%) | 382 (31.1%) | 1407 (21.4%) | 70,564 (29.9%) | |
≥85 years, N (%) | 282 (3.6%) | 55 (4.5%) | 227 (3.5%) | 27,389 (11.6%) | |
Male gender, N (%) | 3966 (50.8%) | 716 (58.4%) | 3250 (49.4%) | 122,624 (52.0%) | <0.001 |
Charlson comorbidity index, mean (±SD) | 0.5 (±1.0) | 1.4 (±1.2) | 0.3 (±0.8) | 1.3 (±0.9) | <0.05 |
0, N (%) | 5315 (68.1%) | 149 (12.1%) | 5166 (78.6%) | 12,612 (5.3%) | |
1, N (%) | 1685 (21.6%) | 732 (59.7%) | 953 (14.5%) | 160,882 (68.2%) | |
≥2, N (%) | 803 (10.3%) | 346 (28.2%) | 457 (6.9%) | 62,532 (26.5%) |
T2D-HCV+ (N = 1227) | HCV+ Only (N = 6576) | |||||
---|---|---|---|---|---|---|
Untreated (N = 745) | DAA-Treated (N = 482) | p-Value | Untreated (N = 4170) | DAA-Treated (N = 2406) | p-Value | |
Age at index date, years, mean (±SD) | 69.1 (±8.85) | 70.9 (±9.39) | <0.001 | 66.4 (±9.00) | 67.65 (±9.66) | <0.001 |
Age classes | ||||||
55–64 years, N (%) | 269 (36.11%) | 143 (29.67%) | 2078 (49.83%) | 1116 (46.38%) | ||
65–74 years, N (%) | 246 (33.02%) | 132 (27.39%) | 1159 (27.79%) | 589 (24.48%) | ||
75–84 years, N (%) | 201 (26.98%) | 181 (37.55%) | 806 (19.33%) | 601 (24.98%) | ||
≥85 years, N (%) | 29 (3.89%) | 26 (5.39%) | 127 (3.05%) | 100 (4.16%) | ||
Male gender, N (%) | 444 (59.60%) | 272 (56.43%) | 0.272 | 2082 (49.93%) | 1168 (48.55%) | 0.280 |
Charlson comorbidity index, mean (±SD) | 1.29 (±1.10) | 1.57 (±1.31) | <0.001 | 0.29 (±0.73) | 0.45 (±1.01) | <0.001 |
0, N (%) | 104 (13.96%) | 45 (9.34%) | 3364 (80.67%) | 1802 (74.90%) | ||
1, N (%) | 459 (61.61%) | 273 (56.64%) | 577 (13.84%) | 376 (15.63%) | ||
≥2, N (%) | 182 (24.43%) | 164 (34.02%) | 229 (5.49%) | 228 (9.48%) |
ATC Code (2nd Level) | Description | T2D-HCV+ (N = 1227) | HCV+ Only (N = 6576) | T2D Only (N = 236,026) | p-Value |
---|---|---|---|---|---|
C09 | Agents acting on renin–angiotensin system | 744 (60.6%) | 2514 (38.2%) | 156,387 (66.3%) | <0.001 |
A02 | Drugs for acid-related disorders | 702 (57.2%) | 2487 (37.8%) | 121,345 (51.4%) | <0.001 |
J01 | Antibacterials for systemic use | 694 (56.6%) | 3029 (46.1%) | 129,100 (54.7%) | <0.001 |
B01 | Antithrombotic agents | 560 (45.6%) | 1462 (22.2%) | 127,375 (54.0%) | <0.001 |
C07 | Beta-blocking agents | 488 (39.8%) | 1437 (21.9%) | 84,981 (36.0%) | <0.001 |
M01 | Anti-inflammatory and antirheumatic products | 411 (33.5%) | 1681 (25.6%) | 92,791 (39.3%) | <0.001 |
C03 | Diuretics | 407 (33.2%) | 939 (14.3%) | 66,439 (28.1%) | <0.001 |
C10 | Lipid-modifying agents | 391 (31.9%) | 740 (11.3%) | 124,353 (52.7%) | <0.001 |
C08 | Calcium channel blockers | 311 (25.3%) | 845 (12.8%) | 56,264 (23.8%) | <0.001 |
L01 | Antineoplastic agents | 19 (1.5%) | 75 (1.1%) | 2615 (0.1%) | 0.331 |
Overall HCV+ (N = 7803) | T2D-HCV+ (N = 1227) | HCV+ Only (N = 6576) | p-Value | |
---|---|---|---|---|
C—Anti-hypertensives/cardiac therapy, N (%) | 213 (2.7%) | 55 (4.5%) | 158 (2.4%) | <0.001 |
Enalapril | 109 (1.4%) | 19 (1.5%) | 90 (1.4%) | |
Verapamil | 52 (0.7%) | 14 (1.1%) | 38 (0.6%) | |
Ranolazine | 52 (0.7%) | 21 (1.7%) | 31 (0.5%) | |
C—Statins/Fibrates, N (%) | 963 (12.3%) | 305 (24.9%) | 658 (10.0%) | <0.001 |
Atorvastatin | 591 (7.6%) | 186 (15.2%) | 405 (6.2%) | |
Simvastatin | 217 (2.8%) | 79 (6.4%) | 138 (2.1%) | |
Rosuvastatin | 110 (1.4%) | 31 (2.5%) | 79 (1.2%) | |
B—Anticoagulants, N (%) | 428 (5.5%) | 97 (7.9%) | 331 (5.0%) | <0.001 |
Warfarin | 209 (2.7%) | 49 (4.0%) | 160 (2.4%) | |
Rivaroxaban | 104 (1.3%) | 19 (1.5%) | 85 (1.3%) | |
Apixaban | 71 (0.9%) | 15 (1.2%) | 56 (0.9%) | |
N—CNS drugs, N (%) | 212 (2.7%) | 56 (4.6%) | 156 (2.4%) | <0.001 |
Quetiapine | 75 (1.0%) | 17 (1.4%) | 58 (0.9%) | |
Fentanyl | 76 (1.0%) | 27 (2.2%) | 49 (0.7%) | |
Risperidone | 22 (0.3%) | 6 (0.5%) | 16 (0.2%) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Giannini, E.G.; Mangia, A.; Morisco, F.; Toniutto, P.; Avogaro, A.; Fagiuoli, S.; Borghi, C.; Frigerio, F.; Nugnes, M.; Veronesi, C.; et al. A Real-World Analysis of the Population with Hepatitis C Virus Infection Affected by Type 2 Diabetes in Italy: Patients’ Characteristics, Comorbidity Profiles and Treatment Patterns. Medicina 2025, 61, 614. https://doi.org/10.3390/medicina61040614
Giannini EG, Mangia A, Morisco F, Toniutto P, Avogaro A, Fagiuoli S, Borghi C, Frigerio F, Nugnes M, Veronesi C, et al. A Real-World Analysis of the Population with Hepatitis C Virus Infection Affected by Type 2 Diabetes in Italy: Patients’ Characteristics, Comorbidity Profiles and Treatment Patterns. Medicina. 2025; 61(4):614. https://doi.org/10.3390/medicina61040614
Chicago/Turabian StyleGiannini, Edoardo Giovanni, Alessandra Mangia, Filomena Morisco, Pierluigi Toniutto, Angelo Avogaro, Stefano Fagiuoli, Claudio Borghi, Francesca Frigerio, Marta Nugnes, Chiara Veronesi, and et al. 2025. "A Real-World Analysis of the Population with Hepatitis C Virus Infection Affected by Type 2 Diabetes in Italy: Patients’ Characteristics, Comorbidity Profiles and Treatment Patterns" Medicina 61, no. 4: 614. https://doi.org/10.3390/medicina61040614
APA StyleGiannini, E. G., Mangia, A., Morisco, F., Toniutto, P., Avogaro, A., Fagiuoli, S., Borghi, C., Frigerio, F., Nugnes, M., Veronesi, C., Cappuccilli, M., Andretta, M., Bacca, M., Barbieri, A., Bartolini, F., Chinellato, G., Ciaccia, A., Lombardi, R., Mancini, D., ... Ponziani, F. R. (2025). A Real-World Analysis of the Population with Hepatitis C Virus Infection Affected by Type 2 Diabetes in Italy: Patients’ Characteristics, Comorbidity Profiles and Treatment Patterns. Medicina, 61(4), 614. https://doi.org/10.3390/medicina61040614