By Wendy S. Meyer
Sitting in his office in the Hepatology and Transplant Center on the seventh floor of University Hospital, Professor Greg Everson, MD, FACP, mentions his plans to retire this summer. For most, this is naturally the time to reflect on 40 years of productive work and activity. In Everson’s case, however, his career in research and medicine has literally made history.
In 1979 when Dr. Everson came to the University of Colorado as a Gastroenterology Fellow, the viral infection called hepatitis C had not yet been identified. In the 1980s, researchers discovered this virus and in 1989 the FDA approved a test for it. Up until a few years ago, doctors could treat hepatitis C but they could not cure it in most cases and the treatments had considerable side effects. The disease is widespread: each year in the US, nearly 20,000 people are infected and an estimated 3.2 million people have chronic hepatitis C. Yet today, 98 percent of all patients can be cured.
What role does Dr. Everson play in this timeline? A significant one. Dr. Everson and his colleagues at CU helped to discover the
disease in the 1980s. For more than 30 years, he studied and treated hepatitis C in thousands of patients. And through his work as Principal Investigator of many hundreds of studies and clinical trials at the CCTSI’s Clinical and Translational Research Center (CTRC), he made major contributions to the testing and evolution of the drugs that led to the cures for hepatitis C.
“Because of Greg’s insight and tireless work at the CTRC over the years, we now have a cure for hepatitis C. His leadership and contributions to the study design and testing of these drugs cannot be overstated,” said CCTSI Director Ron Sokol, MD.
One of the seminal studies Everson conducted in the CTRC was the HALT-C Study, which started in 1999. The CTRC was one of 11 centers that participated in this NIH funded study. At that time, patients with hepatitis C were treated with interferon, which worked for only about 30-40 percent of those infected. The HALT-C study sought to see if low dose maintenance levels of interferon would suppress the advancement of the disease.
“Unfortunately, the treatment did not work,” Everson said. “But 75 original publications came out of that. And those 11 centers enrolled over 1,300 patients; we followed them for 10 years. There was a very low dropout rate because the university and the CTRC were basically a beacon of light for these people.” Those 75 publications were the beginning of a proliferation of research activity and findings that would actively continue until a cure was developed.
A few years later, Everson was one of 30 or so hepatologists at a pharmaceutical company advisory board meeting aimed at eradicating the disease. It was there he stood up and said, “You can get away without interferon. This virus has no sanctuary. It’s not like HIV. If you can shut down replication of it, you can stop it.”
In 2011, he led trials of Telaprevir and Boceprevir at the CTRC. Cure rates jumped from 30 percent to 70 percent, but unfortunately, the drugs were quite toxic. They were used with interferon and ribavirin. He said, “A lot of patients tolerated the treatment, but there was a lot of misery. Most of what we were doing as doctors was treating side effects of interferon.”
In that same year, Everson led an annual review at a national hepatology meeting. The point of the review was to discuss what was coming down the pike in terms of treatment for the disease. “Between 2010 and 2011 there was a huge burst of activity. There had been about 900 papers published in that time!” he said. “I reviewed what I could before the talk. I picked out some new drugs [to discuss] that looked promising." He referred to that talk as his “horizon talk” because so much data was coming out on new promising therapeutics.
Dozens of trials later, and just five years down the road, doctors continued to refine the treatments. Because the disease has six
genotypes, and subtypes under that, each patient may require a treatment that is tailored to their unique disease type. However, the last 3-4 years has seen the development of drugs that are good against all six types.
Today, if you have hepatitis C, you can theoretically come in to a clinic, make sure you have the active virus, take your particular combination of pills for 8 or 12 weeks, and come back after the end of treatment—and 98 percent of all patients treated will be cured.
“From trial to trial, Greg’s steady pursuit of the best therapeutics to treat hepatitis C contributed repeatedly and successfully to the curative therapy we have today,” said Professor Robert Eckel, former CTRC Director. “We're all proud of that history and thank Greg and his team for their efforts and perseverance."