For a long time, treatments for patients with chronic hepatitis C virus infection were largely unsuccessful. But in the last two years, a landmark medical advance led to the approvals of new antiviral medications that can cure more than 95 percent of the millions of patients worldwide with the liver disease.
Now, Northwestern Medicine investigator Steven Flamm, MD, and colleagues are studying the best ways to treat patients with the most severe – and fatal – complication of hepatitis C, decompensated cirrhosis.
“Decompensated cirrhosis means that the liver disease process has advanced to the point that the patient is seriously ill and death is imminent without liver transplantation, unless the disease process can be reversed,” said Dr. Flamm, who is a professor of Medicine in the Division of Gastroenterology and Hepatology and a professor of Surgery.
In a recent phase III clinical trial published in the New England Journal of Medicine (NEJM), he helped show that patients with decompensated cirrhosis who received a new combination of antiviral drugs had a high rate of response and early improvements in liver function.
“For hepatitis C in general, but for decompensated disease in particular, there was a large unmet medical need for therapies that were safe, well-tolerated and efficacious,” Dr. Flamm said. “Now that we have a powerful standard treatment, we’re looking at the next iteration to incapacitate the virus even more effectively.”
According to the World Health Organization, 130 to 150 million people have chronic hepatitis C, most without experiencing any symptoms. But over a period of 20 to 30 years, about a third of these patients will develop extensive scar damage in the liver, called cirrhosis. Left untreated, that damage can progress and develop into decompensated cirrhosis with high mortality.
“In the early phases of cirrhosis, people have a lot of damage in the liver, yet they feel well still,” Dr. Flamm said. “As the problem worsens, patients start to experience complications from their sick liver, the decompensated disease.”
When direct-acting antiviral agents were approved for patients in 2013, they had not yet been assessed in the sickest patients, and clinicians didn’t know if the medications would work in this population. In the two years since, Dr. Flamm has been involved in several studies showing the drugs are safe and effectively fight hepatitis C virus in patients with decompensated cirrhosis. Previously, the only treatment for late-stage cirrhosis was liver transplantation, an option not available to everyone.
In the recent multicenter, randomized and open-label trial, 267 patients took a combination of the medications velpatasvir and sofosbuvir, with and without another drug called ribavirin, for 12 or 24 weeks. The drugs work together by attacking different targets of the hepatitis C virus.
“We found that this combination has a cure rate that is in general higher than drugs that are already out,” Dr. Flamm said. He anticipates that the new combination will be available to patients next summer.
The investigators measured patient responses 12 weeks after treatment, but they believe the drug can cure patients with hepatitis C for good. Ongoing trials are following patients over several years to find out for sure.
In future research, Flamm is interested in pursuing whether the velpatasvir-sofosbuvir drug combination can reverse liver complications, in addition to clearing the hepatitis C virus. He and colleagues will also continue to study new medications, shorter therapies and seek improved regimens with fewer drug-drug interactions for patients with hepatitis C.
This study was supported by Gilead Sciences, the manufacturer of the drugs tested. Dr. Flamm has received financial compensation from Gilead Sciences.
If you are interested in participating in research at Northwestern University, please call 1-855-NU-STUDY or visit https://registar-prod.nubic.northwestern.edu to sign up for Northwestern’s Research Registry.