SUN-519 Hypoparathyroidism after Harvoni Treatment for Hepatitis C

Background: Hepatitis C (Hep C) infection is one of the leading causes of end stage liver disease and hepatocellular carcinoma. Several advances have been made in the treatment of Hep C infection. Harvoni (ledipasvir and sofosbuvir) is one of the treatment options. There have been no case reports of hypocalcemia or hypoparathyroidism associated with Harvoni therapy. We report a case of hypocalcemia and permanent hypoparathyroidism that began after Harvoni therapy. Case Presentation: A 64-year old African American man presented with weight loss and was diagnosed to have Hep C. He was treated with 12 weeks course of Harvoni. He was first noted to have low calcium level at 8.4 (8.4 – 10.3 mg/dl), during the last week of Harvoni treatment. Several previous calcium levels were normal. Four months later, he presented to Emergency Department with numbness, palpitations, and muscle cramping. His calcium was then 6.6 mg/dl, albumin 4.3 (3.4 - 4.8 mg/dl), PTH 18 (15 - 65 pg/ml), 25-hydroxy vitamin D 11 (30 - 50 ng/ml), magnesium 2.2 (1.6 – 2.6 mg/dl), phosphorus 3.8 (2.3 - 4.7 mg/dl) and 24-hour urine calcium was less than 2. Oral calcitriol, ergocalciferol and calcium carbonate were initiated and his calcium normalized. His calcium remained normal on calcitriol and calcium carbonate, but twice he had to be treated in emergency department for symptomatic hypocalcemia after missing his medications. Recently, he began PTH (1-84) (NATPARA). He has been tolerating parathyroid hormone injections well. Discussion: Harvoni is a combination medication of Ledipasvir and Sofosbuvir. Ledipasvir is a NS5A inhibitor. NS5A is an RNA binding protein required for the activity of RNA polymerase of hepatitis C virus. Sofosbuvir is a viral RNA polymerase inhibitor. There have been no case reports of hypoparathyroidism occurring with Harvoni therapy in the literature. Hypoparathyroidism most commonly results after anterior neck surgery like thyroidectomy, parathyroidectomy, or anterior neck dissection. Other causes include neck irradiation, infections like HIV, infiltration of the glands by heavy metals such as iron or copper; genetic disorders of parathyroid gland development, parathyroid hormone synthesis and calcium sensing receptor mutations, and finally autoimmune etiologies. Our patient had none of the risk factors for developing hypoparathyroidism. Nevertheless, he developed permanent, symptomatic hypoparathyroidism towards the end of Harvoni treatment, making Harvoni as the most likely cause of his hypoparathyroidism. More long-term data on this drug is needed to assess the risk of hypoparathyroidism after Harvoni therapy. Conclusion: Hypoparathyroidism leading to hypocalcemia could be a potential complication of Harvoni treatment. Monitoring calcium and parathyroid hormone levels prior to initiation and periodically after completion of Harvoni treatment should be recommended for all patients.