Introduction: Hepatitis C (HCV) remains a significant public health concern in the United States, with an estimated 2.4 million people living with chronic infection. Untreated HCV is a leading cause of chronic liver disease, and a major contributor to the development of cirrhosis, hepatic carcinoma and death. HCV management has been revolutionized by direct-acting antivirals (DAAs). Regimens such as sofosbuvir/velpatasvir (Epclusa™), glecaprevir/pibrentasvir (Mavyret™), ledipasvir/sofosbuvir (Harvoni™), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi™) achieve cure rates exceeding 95% with short, well-tolerated treatment courses.1Treatment success is assessed by sustained virologic response (SVR), assessed 4–12 weeks after therapy completion and indicated by an undetectable HCV RNA level. Treatment failure was a detectable HCV RNA during the same post-treatment assessment window.
A key consideration in DAA therapy, Mavyret excluded, is their requirement for an acidic gastric pH, raising concerns for patients prescribed acid-suppressive agents such as proton-pump inhibitors (PPI) and histamine-2-receptor antagonists (H2RA). Guidelines recommend modifying PPI dose when they exceed 20 mg of omeprazole or an equivalent, as pharmacokinetic studies demonstrate reduced DAA exposure at higher doses. H₂RAs have a less pronounced interaction, with coadministration permitted up to 40 mg twice daily of famotidine or an equivalent. Although the clinical impact is not fully established, reduced exposure may affect efficacy. PPIs remain among the most commonly prescribed medication classes in the United States, with many available over the counter, increasing the risk of unreported use and overlooked interactions. This study evaluates virologic response rates in patients treated for HCV with and without concurrent acid-suppressive therapy at Grady Memorial Hospital.
Study Design and Methods: A retrospective analysis was conducted to compare SVR achievement in patients who did and did not receive acid suppressive therapy during HCV treatment. Patients were included if they are ≥18 years of age, diagnosed with HCV, completed treatment and had a documented post-treatment HCV RNA level. Patients were excluded if they had an incomplete treatment course for HCV, were lost to follow up or had no documented viral load 4-12 weeks after completion of therapy. Patients were stratified by use of acid suppressive therapy. The primary outcome was the rate of SVR achievement after treatment of HCV between groups. Secondary outcomes include differences in SVR between PPI’s including the drug and dose, differences in SVR between PPI and H2RA and differences in SVR based on cirrhosis state. Descriptive statistics were utilized for baseline characteristics, and demographic information. Chi Square test was used to analyze the rates of SVR between groups. Results: Among 736 adults who completed HCV treatment and had follow-up viral load testing, 359 (48.8%) received concomitant acid-suppressant therapy and 377 (51.2%) did not. Baseline characteristics were similar between groups. SVR rates were high overall and did not differ significantly between the two groups (96% vs 95%; p = 0.578). SVR differed by specific acid-suppressant agent (p < 0.001). Among patients receiving acid suppression, SVR was highest in those receiving omeprazole (98%) and ranitidine (98%), followed by famotidine (97%) and pantoprazole (94%). Patients receiving esomeprazole had the lowest SVR rate at 87%, corresponding to a higher proportion of treatment failures (13%) compared with other agents (2–6%). Overall, cure rates remained above 90% for all agents except esomeprazole. Patients receiving guideline-recommended acid-suppressant dosing achieved higher SVR compared with those receiving non-recommended dosing (97% vs 74%; p < 0.001).
Conclusion: Concomitant acid-suppressant use was not associated with reduced SVR achievement, supporting current guideline recommendations that PPIs and H2RAs, when used at guideline recommended doses, can be safely continued during HCV therapy.
