[Click here for a timeline of discovery milestones]
By Rosanne Fohn
Joey Libby, 26, holds a job at a call center and does odd jobs for extra cash. While the outside work he does on weekends is demanding, especially as the temperatures rise, he does it willingly because for eight years—most of his teens and early 20s—his life was limited by a disease that few survived at that time.
Joey was just 15 when he was diagnosed with hepatitis C. The symptoms came quickly and were punishing.
“I wasn’t keeping any food down, not even water. It seemed to me that I had a stomach bug,” he said. “I tried medicine and I rested, but my mom had an instinct that she needed to take me to the hospital. She said, ‘Something’s just not right.’”
Joey went through a series of tests. Then the diagnosis was delivered—and the news that he was in liver failure.
“They told me that if I had not come to the hospital that day, I might have died,” Joey said.
Hepatitis C is a blood-borne virus that slowly destroys liver function. About 3.5 million people in the U.S. have chronic hepatitis C and 70 to 80 percent of them do not have symptoms until the disease has significantly progressed. According to the Centers for Disease Control and Prevention, more Americans die from hepatitis C than any other infectious disease. Hepatitis C also is a major cause of liver cancer.
Yet finding a cure for the disease that wasn’t even known or named until 1989 has been hailed as one of the biggest modern success stories in scientific research. In record time, scientists say, the virus has gone from unknown to almost 100 percent curable. It has claimed many lives in the process: In 2014, deaths associated with hepatitis C reached an all-time high of 19,659, surpassing the combined number of deaths from 60 other infectious diseases, including HIV, pneumococcal disease and tuberculosis.
But Joey wasn’t one of them. Instead, his path to recovery helped lead the way for researchers to find a cure.
It wasn’t an easy road.
It was 2007 when Joey was diagnosed with the disease. He was placed on the liver transplant list and started the standard hepatitis C treatment for that time—daily shots of an antiviral drug called interferon. The drug had severe side effects, with only 10 to 20 percent of patients being cured.
“When I was sick I couldn’t play sports, I couldn’t work out, I was depressed. For a while I even considered suicide. It was just too much,” he said.
Joey returned to school, but his eyes and skin turned yellow because of low liver function, and he was retaining fluid in his abdomen. As his condition worsened, he was homeschooled. He got a reprieve with a liver transplant on June 19, 2008; however, the good news was tempered.
“Unless the hepatitis C is cured, the virus continues circulating in their blood and infects the new liver, usually within a few months of transplant. One-third of them get cirrhosis again within five years,” said Fred Poordad, M.D., professor of medicine at UT Health San Antonio and chief of hepatology in the Liver Transplant Program at University Transplant Center, a partnership between UT Health San Antonio and University Health System.
It is unclear exactly how Joey contracted hepatitis C. Most people are diagnosed when they are age 50 or older, but both of his parents had the virus. Hepatitis C is found worldwide and is spread through contact with blood or semen, including using shared drug injection needles, inadequate sterilization of medical equipment, unscreened blood or blood products, accidental needle sticks and sexual intercourse with a person who has hepatitis C. The disease can also be spread from mothers to children during birth.
Baby boomers, those born between 1945 and 1965, are the most affected because of exposure during medical procedures after World War II, when injection and blood transfusion technology was not as safe. Many of these baby boomers unknowingly transmitted it to others.
A few years after Joey was diagnosed, his father died. His mother, Doris Libby, had learned she had the disease a few years before, but had refused treatment because fatigue was her only symptom.
Then she met liver specialist Eric Lawitz, M.D., a professor of medicine at UT Health San Antonio. Dr. Lawitz was conducting clinical trials through his medical practice, the Texas Liver Institute.
“I was in Dr. Lawitz’s office and I told him about Joey,” she said. “He told me about one of the trials, and the way he expressed it, he was bursting with enthusiasm and excitement. He wanted both of us to go on the study.”
The trial was for patients in two groups who had not benefitted from previous treatments—those, like Doris, with hepatitis C who had advanced liver disease, and patients like her son, who had received a liver transplant but whose liver disease had returned because of hepatitis C.
The year was 2014. By then, Dr. Lawitz had seen many treatments for hepatitis C come and go, with limited success.
But this one seemed different.
A long road
Dr. Lawitz was in medical school when hepatitis C was first discovered. The first standardized treatment—interferon—was approved by the Food and Drug Administration in 1991. As his medical training progressed, first in internal medicine and then with fellowships in gastroenterology and hepatology at Brooke Army Medical Center in San Antonio, he became involved in some of the early research to improve treatments.
One of the challenges of finding a cure for hepatitis C is that there are six strains of the disease, based on the geographic location where the strain developed. In the U.S., genotype 1 is the most common type. Another variable is the extent of liver scarring called fibrosis, which when severe is called cirrhosis.
When Dr. Lawitz opened his private practice in 2004, it included cutting-edge liver disease research. Interferon, given to boost the body’s immune system and reduce the growth of cancer and viral cells, was the standard treatment for hepatitis B. But to treat the chronic and deadly hepatitis C, he knew it wasn’t enough.
Interferon has terrible side effects, including flu-like symptoms, fatigue and depression. While it helped the body recognize viruses and eliminate them, as soon as patients stopped taking it, the virus would come back.
“Back then with our research, we were just inching along, trying to squeeze another 5 percent cure rate out of interferon by changing the dose or duration of therapy,” Dr. Lawitz said.
Then doctors began adding an antiviral drug, ribavirin, to their treatment regimen. The pills seemed to work at preventing relapse and more than doubled cure rates from 10 or 20 percent to about 40 percent. But it also had adverse effects such as anemia, gastrointestinal issues and rash. Attempts to keep interferon in the bloodstream longer meant patients were given weekly long-acting injections of interferon and up to six pills daily for months.
While Joey endured these difficult regimens with limited success, the field of medicinal chemistry was beginning to blossom with a new approach. Instead of focusing on strengthening the body’s immune system to fight the virus using existing treatments, scientists began studying the use of direct-acting antivirals to target specific parts of the virus and prevent it from reproducing. These new drugs held the promise of a shortened treatment length, minimal side effects and, because they targeted the virus itself, improved response.
Several physician-researchers around the country were invited to evaluate the new drugs in clinical trials. Among them were Dr. Lawitz and Dr. Poordad, who at that time was chief of hepatology and liver transplantation at Cedars-Sinai Medical Center in Los Angeles.
“If they worked, we knew direct-acting antivirals would change the field forever,” Dr. Poordad said.
They were on the cusp of finding a cure for the disease that seemed unconquerable.
The first clinical trials of direct-acting antivirals began in 2008 by adding them to standard immune-building treatments. Amazingly, three short years later, the FDA approved the first two direct-acting antiviral therapies for genotype 1.
Cure rates escalated to 79 percent with some treatments.
“With these two regimens, we got high cure rates, but we still had significant adverse events, so it helped in one way but it wasn’t patient-friendly in the other,” Dr. Lawitz said.
So, the physician-scientists teamed up, and the work went on.
Having met at various professional research meetings, Dr. Lawitz invited Dr. Poordad to join his practice in 2012, when both also became professors of medicine at UT Health San Antonio.
Their academic backgrounds and clinical success provided them with opportunities to assist and advise pharmaceutical companies in the design and conduct of some of the major hepatitis C clinical trials, including Harvoni, now a common drug used in the treatment of hepatitis C, Dr. Lawitz said.
Then came the study that changed the lives of Joey and his mother.
In this clinical trial, patients received a 12-week course of a direct-acting antiviral drug combined with an inhibitor of a key viral protein found in hepatitis C.
The trial showed an overall cure rate of 94 percent for patients with a liver transplant and returning hepatitis C, like Joey, and a cure rate of 83 percent for patients with advanced cirrhosis, like his mom.
“The medicine didn’t make me feel bad and it was all pills, which was cool because I didn’t have to take shots,” Joey said.
The trial was a highlight of Dr. Poordad’s career, and he presented the results at the International Liver Congress of the European Association for the Study of the Liver. The combination therapy received FDA approval in 2015. But the study had a much more profound effect on the Libbys.
Both Joey and his mother were cured.
A game changer
In June 2016, the first agent to treat all six forms of hepatitis C in adults, called Epclusa, was approved. Drs. Lawitz and Poordad have investigated myriad drugs now approved by the FDA. Their work has appeared in premier research journals and helped shape guidelines in the treatment of hepatitis C.
The most recent drug approved by the FDA was Mavyret in 2017; it treats all genotypes of hepatitis C. Some of the drugs have also been approved for use in pediatric patients.
“The bottom line is that in a little more than a decade, we have conquered hepatitis C,” Dr. Lawitz said. “We now have many direct-acting, all-oral medications that cure 95 to 100 percent of patients in eight to 12 weeks of therapy with very minor side effects. Additionally, we can successfully re-treat 96 percent of [previous direct-acting antiviral] failures.”
Only 1 in 1,000 patients in the hardest-to-treat categories cannot be cured.
“To me, the biggest surprise was how quickly the pace of development occurred,” Dr. Lawitz said. “The incremental steps from drug to drug and clinical trial to clinical trial were fairly big. To get from 40 percent to nearly 100 percent cure rate with only minor adverse effects in that short of a time is unheard of.”
However, it didn’t come without drawbacks.
“Liver disease has a high death rate. I’ve seen too many patients pass away. There is not one patient who stands out for me. I’d say that many stand out. They helped drive me and helped me remember why we do this work,” Dr. Poordad said. “We’re very thankful to the many patients along the way. Without them we wouldn’t have had these successes. They trusted us with their lives.”
While finding a cure happened in record time, the doctors know there is more work to be done. They want to see the fruits of their labor made available throughout the world to aid in total eradication of the disease. A vaccine could help achieve this goal.
For Joey, the journey to health was more than a decade-long process that unfortunately ended a year after his father died. Today, Joey is just glad to be able to lead a normal life, working two jobs and exercising regularly.
Doctors still routinely check his liver function “and I’m still doing well,” Joey said. “I’m just living my life.”
1989: Hepatitis C is identified for the first time. It has six types, or genotypes, based on the geographic location where the strain developed. Genotype 1 is the most common in the U.S.
1991: Interferon is approved by the FDA to treat hepatitis C. There are many classes of interferons, which are used to boost the immune system to fight viruses, not directly kill viral or cancerous cells. Cure rate: about 10-20 percent.
1992: Blood tests are perfected to screen for the hepatitis C virus. These tests effectively eliminated the virus from the blood transfusion supply.
1998: Ribavirin, an antiviral medication, is added to the standardized treatment of interferon. Cure rate: about 40 percent.
2001: Pegylated interferon is introduced to help interferon stay active in the bloodstream longer. Treatment regimens include injections and up to six ribavirin pills daily for six months. Cure rate: about 41 percent.
2003: A combination of interferon and ribavirin is approved for treating pediatric patients.
2005: Hepatitis C cells are grown in a lab for the first time, leading to the first study of the virus’ life cycle.
2006: A new class of oral drugs, called direct-acting antivirals, is developed. The drugs are aimed at directly stopping the spread of hepatitis C in the body by targeting specific steps in the virus’ life cycle.
2007: Sofosbuvir, an inhibitor of a key viral protein in hepatitis C, is designed to decrease the amount of hepatitis C virus in the body and shows promise when used with standardized treatment. A series of clinical trials showed a cure rate of more than 90 percent in 12 weeks for genotypes 1, 2 and 3.
2008: The first clinical trials of direct-acting antivirals begin.
2011: Direct-acting antivirals are approved by the FDA to treat hepatitis C. These include boceprevir, used in combination with pegylated interferon and ribavirin, for a cure rate of up to 66 percent in genotype 1 patients. Telaprevir also was approved in combination with pegylated interferon and ribavirin for a 79 percent cure rate of genotype 1.
2014: Ledipasvir, another direct-acting antiviral, used in combination with sofosbuvir, is approved by the FDA for genotypes 1, 4, 5 and 6. Known by its brand name Harvoni, the drug was the first hepatitis C treatment contained in one pill. Cure rate: 95 percent within eight weeks.
2015: The FDA approves a 12-week course of the direct-acting antiviral agent daclatasvir combined with sofosbuvir, with and without ribavirin, for genotypes 1 and 3. Overall cure rate: 94 percent for patients with a liver transplant and returning hepatitis C. Cure rate for patients with advanced cirrhosis: 83 percent.
2016: Epclusa, a combination of sofosbuvir and velpatasvir antiviral medications, is approved by the FDA to treat all six forms of hepatitis C in adults. Cure rate: 95 percent in 12 weeks.
2017: Mavyret, a combination of the viral inhibitor glecaprevir and the antiviral agent pibrentasvir, is approved by the FDA to treat all genotypes of hepatitis C. Cure rate: 92-100 percent in eight weeks.
Sources: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, the Hepatitis C Support Project, Eric Lawitz, M.D., Fred Poordad, M.D.
A wonderfully written article. Thank you, Drs. Poordad and Lawitz, for your skill, commitment, dedication and many hard hours of work to achieve this goal.
Wayne Gage MD
Class of 1971.