Acid-Reducing Agents and HCV Treatment
Some direct acting antivirals (DAAs) used for the treatment of hepatitis C virus (HCV), including ledipasvir (in Harvoni), require an acidic environment in the stomach for maximal absorption. However, in general, many people, including some with HCV, routinely take acid-reducing agents such as the following:
- pills or liquids that contain calcium and/or magnesium
- a class of drugs called H2 blockers -- commonly used examples include cimetidine (Tagamet) and ranitidine (Zantac)
- PPIs (proton pump inhibitors) -- esomeprazole (Nexium, Vimovo), omeprazole (Losec, Prilosec) and pantoprazole (Pantoloc)
It is possible that acid-reducing agents could reduce the absorption of ledipasvir and, therefore, its ability to help cure HCV infection. An observational study called Target has reported an association between the use of acid-reducing agents and decreased effectiveness of Harvoni (sofosbuvir-ledipasvir). In Target, participants who used PPIs had a cure rate of 93% vs. a cure rate of 98% in people who did not use PPIs.
Associations are just that; they are not conclusive. As a result of Target's findings, researchers at the Ottawa Hospital sought to analyse their database of patients who received interferon-free regimens of DAAs. The researchers also assessed their patients' use of acid-reducing agents, specifically H2 blockers and PPIs. A total of 168 people took part in this study.
Prior to initiating DAA therapy, 24% of participants in the Ottawa Hospital study took PPIs and 2% took H2 blockers. The researchers found that among 168 participants, those with severe scarring of the liver (cirrhosis) were most likely to use H2 blockers or PPIs. In total, among the participants who were taking PPIs prior to initiating therapy with DAAs, 93% continued to take PPIs (once daily) while on DAA therapy. There was no difference in cure rates between people who took PPIs and those who did not take these or other acid-reducing agents.
The average profile of the 168 participants in the Ottawa Hospital study was as follows:
- age -- 56 years
- 63% men, 37% women
- common strains of HCV -- genotypes 1a and 1b
- doctors had diagnosed cirrhosis in 45% of participants
During the course of the study, the following regimens were used:
- sofosbuvir + ledipasvir (with or without ribavirin) -- 51%
- sofosbuvir + ribavirin -- 15%
- sofosbuvir + simeprevir (with or without ribavirin) -- 31%
- other (unspecified) regimens -- 3%
Cure rates were generally high in this group of participants -- greater than 90%. There was no statistically significant impact of acid-reducing agents on the cure rate of DAA-based regimens. When subgroups of participants were assessed -- such as those with the difficult-to-treat genotype 1a or those who had cirrhosis or those who only received sofosbuvir + ledipasvir -- there was also no significant impact on cure rates caused by acid-reducing agents.
For the Future
To minimize any possible risk that acid-reducing agents might have on cure rates, the Ottawa researchers suggest that the dosing of these medicines be limited to once daily. Furthermore, they encourage doctors who care for people with HCV to reassess their patients' need for acid-reducing agents.
DeVreese L, Giguère P, Cooper C. Influence of proton pump inhibitors and H2 receptor antagonists on direct-acting antiviral HCV sustained virologic response. The International Liver Congress, 13-17 April 2017, Barcelona, Spain. Abstract SAT-200.