Editorial: Risk of Incident Type 2 Diabetes and Prediabetes in Patients With Direct Acting Antiviral-Induced Cure of Hepatitis C Virus Infection—Authors' Reply

Abstract

We sincerely appreciate Drs. Tamaki and Kurosaki's insightful comments on our work regarding the clinical impact of incident type 2 diabetes (T2D) and prediabetes among patients with direct-acting antiviral (DAA)-induced viral clearance [1, 2]. While hepatitis C virus (HCV) infection can be eradicated using a short course of potent oral antiviral agents, the presence of T2D or prediabetes has been demonstrated to be adversely associated with liver-related outcomes, including hepatocellular carcinoma (HCC), hepatic decompensation and fibrosis progression [3-5]. Additionally, current evidence also shows that T2D and prediabetes are key driving cardiometabolic risk factors (CMRFs) in the development of metabolic dysfunction-associated steatotic liver disease (MASLD), which indirectly affects HCC development [4]. Because our findings reveal that the age-standardised incidence rates (ASIRs) of T2D and prediabetes among patients following DAA-induced viral cure remain substantial, early detection of incident T2D or prediabetes in at-risk populations, along with timely lifestyle, medical or surgical interventions for those diagnosed with T2D or prediabetes, is crucial to improving long-term health-related outcomes.

Among the HCV viremic carriers, both MASLD and old age are highly associated with hyperferritinemia [6]. This is consistent with a recent report demonstrating a strong link between MASLD, T2D and hyperferritinemia in non-HCV individuals [7]. Moreover, patients who achieve HCV cure through antiviral therapies exhibit a more favourable time-dependent trend in ferritin dynamics compared to those who do not achieve viral cure. This reflects the benefits of resolving hepatic inflammation and fibrosis following viral eradication [8]. The complex interplay among MASLD, hyperferritinemia, T2D/prediabetes, and age in influencing long-term hepatic and extrahepatic outcomes following HCV cure warrants further in-depth research.

In addition to early detection of T2D and prediabetes through rigorous surveillance, maintaining well-controlled glycemic status through various interventions is essential for patients diagnosed with T2D or prediabetes to achieve favourable hepatic and cardiovascular outcomes [9]. The use of glucagon-like peptide-1 receptor (GLP1R) agonists, alone or in combination with glucagon receptor (GCGR) or glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, may benefit glycemic control in these patients. Additionally, the effects of combining selective thyroid hormone receptor-beta (THR-β) or fibroblast growth factor 21 (FGF21) agonists in patients with significant hepatic fibrosis warrant further investigation [10].

Yu-Ping Chang: writing – review and editing, writing – original draft. Jia-Horng Kao: writing – review and editing, writing – original draft. Chen-Hua Liu: writing – original draft, writing – review and editing.

The authors' declarations of personal and financial interests are unchanged from those in the original article [2].

This article is linked to Chang et al papers. To view these articles, visit https://doi.org/10.1111/apt.70029 and https://doi.org/10.1111/apt.70060.