Results Summary
What was the research about?
Hepatitis C is a virus that damages the liver. Previously, patients took medicines called antivirals to treat the health problem. These medicines took six months to a year to work and were not always effective. A new type of medicine to treat hepatitis C, called direct-acting antivirals, or DAAs, takes only two to three months for treatment and has higher success rates. But some research has suggested that DAAs might have worse adverse events, like liver failure or stroke, than previously thought.
In this study, the research team looked at health records for patients with hepatitis C to see if patients who started DAAs had more adverse events compared with patients who didn’t receive—or had not yet received—DAAs.
What were the results?
DAAs weren’t linked with patients having more adverse events. Overall, compared with patients who hadn’t received DAAs, patients who received DAAs had lower rates of
- Death
- Reduced liver function
- Acute-on-chronic liver event, a type of liver failure
- Arrhythmia, or when the heart beats too slow or fast or with an irregular pattern
- Multiple organ failure
- Hospital or emergency room visits
The rates of heart attack, stroke, kidney failure, cancer, and a return of previously controlled hepatitis C did not differ between those who received DAAs and those who did not.
Who was in the study?
The study included health records from 33,808 patients diagnosed with hepatitis C. Of these, 55 percent were white, 19 percent were black, 5 percent were Asian or Pacific Islander, 1 percent were American Indian or Alaska Native, and 20 percent were other or unknown races. In addition, 20 percent were age 65 or older, and 61 percent were men. All received care at one of three healthcare systems in California and Florida.
What did the research team do?
The research team reviewed patient health records collected between January 1, 2012, and December 31, 2017. The team looked at whether patients who received DAAs had higher rates of adverse events within six months than those who had not received DAAs.
What were the limits of the study?
Doctors were more likely to prescribe DAAs to patients without multiple health problems, which could explain the lower rates of adverse events among those who received DAAs.
Future research could explore whether DAAs have different results for patients of different ages, genders, or with other health problems.
How can people use the results?
Doctors and patients can use these results when considering treatment for hepatitis C.
| How this project fits under PCORI’s Research Priorities The research reported in this results summary was conducted using PCORnet®, the National Patient-Centered Clinical Research Network. PCORnet® is intended to improve the nation’s capacity to conduct health research, particularly comparative effectiveness research (CER), efficiently by creating a large, highly representative network for conducting clinical outcomes research. PCORnet® has been developed with funding from the Patient-Centered Outcomes Research Institute® (PCORI®). |
Professional Abstract
Objective
To determine the safety of direct-acting antivirals (DAAs) used to treat hepatitis C by comparing patients who filled a prescription for DAAs to those who did not fill—or had not yet filled—a prescription for DAAs
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | EHR data from 33,808 patients with a diagnosis of active hepatitis C virus in 3 healthcare systems |
| Interventions/ Comparators |
|
| Outcomes | Primary: acute myocardial infarction, ischemic or hemorrhagic stroke, acute kidney failure, acute-on-chronic liver event, multiple organ failure, death Secondary: hepatic decompensation, hospitalization, ED visit, arrhythmia, liver cancer, non-liver cancer, hepatitis B reactivation |
| Timeframe | 6-month follow-up for primary outcomes |
This retrospective observational cohort study evaluated the safety of DAAs by analyzing the rates of adverse events in patients who filled prescriptions for DAAs for hepatitis C compared with patients who did not fill—or had not yet filled—prescriptions for DAAs.
The study included electronic health record (EHR) data from 33,808 patients with a diagnosis of active hepatitis C virus receiving care from one of three healthcare systems in California and Florida. Of these patients, 55% were white, 19% were black, 5% were Asian or Pacific Islander, 1% were American Indian or Alaska Native, and 20% were other or unknown races. In addition, 20% were age 65 or older, and 61% were male.
The research team reviewed patient EHR data collected between January 1, 2012, and December 31, 2017. The team examined whether patients developed adverse events within 180 days following the initiation of DAA treatment. Using a time-varying-exposure design, patients were in the untreated group until they received or filled a prescription for DAAs. Once patients received or filled a prescription for DAAs, they moved to the treated group. During the study, 54% of patients did not receive treatment. In comparisons between the treated and untreated groups, the team controlled for potentially confounding factors such as age, gender, race, body mass index, smoking status, healthcare utilization, laboratory results, general comorbidities, and hepatitis C virus-specific comorbidities.
Results
Compared with patients who had not received DAAs, those who received DAAs had significantly lower odds of an acute-on-chronic liver event, multiple organ failure, arrhythmia, and death (all p<0.01). They also had lower odds of hepatic decompensation and having to go to the emergency department (ED) or hospital (both p<0.01).
The odds of having the other outcomes did not differ between those who received DAAs and those who had not received DAAs.
Limitations
The research team found that doctors were more likely to prescribe DAAs to patients without multiple chronic conditions. The difference in prescribing could explain the lower rates of adverse events among those who received DAAs.
Conclusions and Relevance
In this study, DAAs were not associated with higher odds of adverse events.
Future Research Needs
Future research could investigate how patients of different ages, genders, and with other comorbidities respond to DAAs.
| How this project fits under PCORI’s Research Priorities The research reported in this results summary was conducted using PCORnet®, the National Patient-Centered Clinical Research Network. PCORnet® is intended to improve the nation’s capacity to conduct health research, particularly comparative effectiveness research (CER), efficiently by creating a large, highly representative network for conducting clinical outcomes research. PCORnet® has been developed with funding from the Patient-Centered Outcomes Research Institute® (PCORI®). |
Final Research Report
View this project's final research report.
Journal Citations
Article Highlight: Earlier this decade, the use of direct-acting antivirals—which stop a virus from making copies of itself—was a breakthrough in the treatment of hepatitis C virus. But little research exists on possible side effects of the antivirals, especially among large, real-world populations. This study, which used PCORnet data, found that patients who took the antivirals were no more likely to experience adverse events than those who didn’t take them. The researchers published their findings in JAMA Network Open.
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers asked for the extent of missing data in the study and how the researchers handled missing data. They also asked what analyses the researchers performed to determine that missing data did not influence the conclusions. The researchers responded that the three health systems that participated in the study are highly experienced in using data for research and routinely consider the appropriate use of data. The researchers noted that the patterns of data availability were a result of system use, rather than failure to capture data. The researchers also explained how they conducted sensitivity analyses to account for missing data.
- The reviewers expressed concern about the possibility of bias in the study sample that could be created if the different exposure groups were followed for different lengths of time on average. This could occur because the health outcomes the researchers were following might vary over the course of the disease. The researchers referred to Appendix 7, where they detailed their sensitivity analyses looking at length of follow-up time for the study participants in different groups. The researchers noted that they also truncated observations after 365 days for both those treated with direct acting antivirals (DAAs) and those not receiving DAAs to produce comparable exposure periods. They found that this adjustment made little difference in the adverse event rate estimates.
- The reviewers asked that the report include a distribution list of the specific DAAs prescribed for the exposed group of patients, and what restrictions existed related to patient access to specific medications. The researchers responded that their data systems did not permit disclosure of specific medications within a drug class, so they were unable to estimate the number of each medication prescribed. They did, however, include a list of all medications that they had included in this class and noted that there were almost no restrictions on patient access to these medications.
Conflict of Interest Disclosures
Project Information
Key Dates
Study Registration Information
^This project was previously titled: Rapid-Cycle Research: Hepatitis C (Observational Study)