Achieving SVR Improves Glycemic Control in Patients with Diabetes, HCV Infection

Bing Chen, MD

Credit: Bing Chen on X

Achieving sustained virologic response (SVR) with direct-acting antiviral (DAA) treatment leads to clinically significant improvements in glycemic control among patients with chronic hepatitis C virus (HCV) and type 2 diabetes, according to findings from a recent study.¹

Results of the systematic review and meta-analysis highlight the extrahepatic benefits of HCV eradication in patients with diabetes. Specifically, mean hemoglobin A1c (HbA1c) was significantly reduced after SVR and persisted during 3- and 6-month follow-up periods, and SVR was associated with notable reductions in fasting glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).¹

According to the World Health Organization, an estimated 50 million people have chronic HCV infection globally, with about 1 million new infections occurring per year. Although there is currently no effective vaccine against hepatitis C, the advent of DAAs has introduced a cure for more than 95% of persons with hepatitis C infection.2 Beyond HCV cure, achieving SVR with DAA therapy is thought to be associated with positive hypoglycemic effects in individuals with type 2 diabetes, but research thus far has yielded mixed results.¹

“Recent studies have provided evidence of improved glucose control and reduced reliance on hypoglycaemic medications in type 2 diabetes patients who achieved SVR with DAA regimens,” Bing Chen, MD, a GI fellow at Geisinger Medical Center, and colleagues wrote.¹ “However, the hypoglycaemic effect of eradication of HCV with DAA regimens in type 2 diabetes patients has not been consistent across all studies, nor has the magnitude of the effect.”

To assess the impact of SVR after treatment with DAA agents on glycemic control in patients with type 2 diabetes, investigators conducted a systematic review and meta-analysis of studies evaluating the association between eradication of HCV infection with DAAs and glycemic control. Embase, Scopus, and PubMed databases were searched from inception to March 26, 2023, to identify studies related to diabetes mellitus, hepatitis C, DAA agents, and glycemic control. The search was restricted to studies published in English but not limited by publication date or country.¹

For inclusion, studies were required to meet the following criteria: enrolled adult patients with concurrent hepatitis C and type 2 diabetes who were treated with DAA agents; reported data on glycemic control, including HbA1c, fasting glucose, or HOMA-IR; and measured glycemic control both before the initiation of the DAA and post-SVR. Reviews, editorials, or case reports/series with a patient sample size < 5 were excluded, as were studies where patients received interferon or ribavirin therapy, were pregnant, or had a solid organ transplant.¹

The primary outcome was the change in HbA1c after SVR with DAA agents. The secondary outcome was the alternation in fasting glucose and HOMA-IR levels after SVR compared to their levels before receiving DAA agents.¹

A total of 1731 articles were identified from Embase, Pubmed, and Scopus. After excluding 453 duplicate citations, 1278 articles were screened based on titles and abstracts. In total, 16 studies met the eligibility criteria and were included in the study. Of the included studies, 6 were prospective observational studies and 10 were retrospective observational studies involving a total of 4266 patients, all of whom had diabetes and achieved SVR after receiving treatment with interferon and ribavirin-free DAAs.¹

HbA1c (%) before treatment and post-SVR was reported in 15 studies, fasting blood glucose level was reported in 5 studies, and HOMA-IR was reported in 2 studies. Using the Newcastle Ottawa Questionnaire for Cohort Studies, investigators determined all 16 studies were good quality.¹

The mean HbA1c before treatment was 8.05% (95% CI, 7.79%–8.31%), which decreased to 7.19% (95% CI: 6.98%–7.39%) after treatment. Investigators pointed out there was a significant mean absolute reduction in HbA1c of 0.72% (95% CI, 0.52%–0.93%), although there was high heterogeneity between studies (I2 = 91.7%). Of note, the reduction in HbA1c remained significant in the subgroup analysis at 3 months follow up post SVR (0.74%; 95% CI, 0.57%–0.91%) and at least 6 months follow up (0.66%; 95% CI, 0.23%–1.10%).¹

Analysis of 4 studies that provided data for fasting glucose before and after DAA treatment showed the mean reduction in fasting glucose was 10.59 mg/dL (95% CI, 5.10 mg/dL-16.08 mg/dL) with an I2 of 19.2%. HOMA-IR before and after DAA treatment was reported in 2 studies. The first showed median HOMA-IR improved from 4.32 (3.42–5.63) at baseline to 3.19 (2.61–3.7) post-SVR (P <.0001), and the second also reported a significant improvement in mean HOMA-IR from 2.56 ± 0.47 to 2.23 ± 0.38 (P <.05).¹

Investigators acknowledged multiple limitations to these findings, including heterogeneity in the meta-analysis pertaining to HbA1c level; the retrospective design of most included studies; the limited data preventing sensitivity analysis to adjust for potential confounding; the significant presence of publication bias; and the insufficient number of studies to investigate the long-term effects of SVR on diabetic control.¹

“Our study has demonstrated a clinically significant improvement in glycemic control among patients with chronic hepatitis C infection and type 2 diabetes who achieved SVR through DAA therapies,” investigators concluded.¹ “These findings underscore a valuable extrahepatic advantage of HCV eradication. This discovery may potentially guide adjustments in hypoglycaemic agents for diabetic patients who completed DAA regimens.”

References

1. ^{Chen B, Iqbal U, Desai SK, et al. The role of treatment of hepatitis C with direct-acting antiviral agents on glycaemic control in diabetic patients: An updated systematic review and meta-analysis. Journal of Viral Hepatitis. https://doi.org/10.1111/jvh.13984}
2. ^{World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed July 30, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}