Hypoglycemia in a diabetic patient during hepatitis C therapy

We read with interest the article from Simon and Chung in which universal treatment of hepatitis C virus (HCV) infection is defended. The authors acknowledge that HCV disease is a systemic condition that, beyond the liver, is associated with diabetes, cardiovascular disease, psychiatric disorders, renal dysfunction, and rheumatological conditions. Therefore, treatment should not be deferred in patients with null-minimal liver fibrosis. In agreement with the recently updated recommendations from the AASLD/IDSA guidelines (www.hcvguidelines. org), they supported that all HCV-infected persons should be treated. Herein, we would like to provide a unique example of systemic consequences of HCV infection unveiled once successful treatment is prescribed. A 53-year-old male with chronic hepatitis C known since 1991 presented in 2014 with cirrhosis, as measured using elastometry (19.4 KPa). He was infected with HCV genotype 1a and his plasma HCV RNA was 3,950,000 IU/mL. The patient harbored IL28B CT alleles. He had failed a previous course of pegylated interferon/ribavirin in 2007. Type 2 diabetes had been diagnosed in 2008. He soon required subcutaneous insulin for well controlling sugar levels. During the last year, he was using 18 units of slow insulin once-daily, supplemented with 4-8 units of rapid insulin every 6 hours depending on glycemic values. The patient was compliant with his medication and generally exhibited fasting glucose values below 140 mg/dL and serum HbA1c below 6.5%. In April 2015, treatment with sofosbuvir-ledipasvir was prescribed. Unexpectedly, since day 7 of therapy, dosing requests for rapid insulin declined and in fact were no longer needed since day 21. At day 18, he even suffered an episode of symptomatic hipoglycemia with fasting serum glucose of 50 mg/dL. Despite halting rapid insulin supplementation completely, steady declines in serum glucose levels forced him to further reduce slow insulin down to 14 units/day. Metabolic changes run in parallel with complete suppression of serum HCV RNA along with normalization of liver enzymes since the first 2 weeks on sofosbuvir-ledipasvir therapy. A link between diabetes and chronic HCV infection is well established. Up to 15%-25% of chronic hepatitis C patients will develop lifelong diabetes. Although the underlying mechanism is still unclear, it appears to be the result of HCV interference with the insulin receptor substrate 1 tyrosine phosphorylation pathway. The release of proinflammatory cytokines, such as tumor necrosis factor alpha, might also interfere with insulin signaling. The link between HCV and diabetes is also supported by the observation that HCV clearance after antiviral therapy reduces the risk of developing type 2 diabetes. To our knowledge, this is the first documentation of a direct time-frame correlation between suppression of HCV replication and insulin requests. Given that no drug-drug interactions are expected between subcutaneous insulin and either oral sofosbuvir or ledipasvir, we postulate that suppression of HCV replication led to a rapid improvement of insulin sensitivity in our patient. Therefore, diabetic patients on insulin treated for hepatitis C with new oral potent regimens should be informed of the potential risk of hypoglycemic episodes.