Escaping 'MELD purgatory'
WASHINGTON – Treatment of hepatitis C infection with a direct-acting antiviral drug strongly linked with a rapid, 14% drop in the incidence of all nonhepatic cancers, based on analysis of data from more than 30,000 U.S. patients.
The data also showed compared with infected patients who had been treated with an interferon-based regimen during the period immediately preceding the availability of DAAs in late 2013. This included a 45% cut in lung cancers, a 49% cut in bladder cancer, a 62% relative risk reduction in leukemia, and a 29% drop in prostate cancer, Michael B. Charlton, MD, said at the annual Digestive Disease Week.®
The relative reductions in nonhepatic cancer incidence appeared soon after DAA treatment. The data Dr. Charlton reported reflected a median follow-up of 1 year for DAA-treated patients and 2.6 years for the hepatitis C–infected patients who had received interferon and did not get a DAA. A major difference between these two regimens is their efficacy, with DAA regimens producing sustained virologic response rates of 90% or better, while the interferon regimens produced substantially lower eradication rates.
“The most obvious hypothesis” to explain the observed effects is that “hepatitis C is a potent carcinogen,” possibly acting by inhibiting immune surveillance for new cancers in infected people, Dr. Charlton said in a video interview.
The study he reported used insurance-claims data from more than 146 million U.S. residents during 2007-2017 in the IQVIA PharMetrics Plus database, which included more than 367,000 adults infected with hepatitis C. Dr. Charlton and his associates pulled from this claims data on 10,989 of the infected patients who received interferon during January 2007-May 2011 (and followed through November 2013), and 22,894 infected patients treated with any type of DAA during December 2013 through March 2017. They used these two discrete time windows to completely separate the patients who received a DAA from those who did not.
The primary analysis calculated a hazard ratio for the development of any nonhepatic cancer after adjustment for a number of demographic and clinical covariates including age, smoking history, and weight, and also applied propensity-score weighting to the data. The Kaplan-Meier analysis of the data showed clear separation of the cancer-free survival curves of the two subgroups by 6 months of follow-up, and then showed steady further separation over time suggesting an ongoing carcinogenic effect from continued hepatitis C infection in patients who had received the less effective antiviral regimen. The analysis was able to reveal this effect because it had data from many thousands of treated hepatitis C patients, far more than had been enrolled in the pivotal trials for the DAAs, noted Dr. Charlton, professor and director of the Center for Liver Diseases at the University of Chicago.
The Centers for Disease Control and Prevention estimates that 3.5 million Americans have a chronic hepatitis C infection. Dr. Charlton believed the number today might be more like 1-2 million remaining chronic U.S. cases because of the strong impact of DAA treatment. These chronic infections largely remain because hepatitis C is mostly silent and many clinicians fail to act on screening recommendations. The new findings provide even greater incentive for more rigorous screening and treatment, Dr. Charlton suggested.
“As if you needed another reason to get rid of hepatitis C, lowering your cancer risk is now added to the list,” he said.