Even without cure, treatment shows significant benefit.
By Benjamin Ryan
While researchers and clinicians have long presumed that antiviral treatment for hepatitis C lowers the risk of liver cancer, no data had produced solid proof to back that idea. Until now. A recent review of past research has shown that treatment for hepatitis C virus (HCV) may almost slash in half the rates of hepatocellular carcinoma (HCC). Also promising is the finding that, even in the absence of a cure—known as a sustained virological response (SVR)—hep C patients will likely experience a significantly lowered risk of cancer.
Praising the study, John Ward, MD, director of the division of viral hepatitis at the Centers for Disease Control and Prevention, said, “This report adds to the compelling body of evidence that hepatitis C testing, along with linkage to appropriate care and treatment, can save lives.”
While the study largely examined now-outdated treatments, some clinicians are ready to speculate that the findings may very well extend to the improved standard of care available today, and that the risk of liver cancer may drop even further with ever-improving SVR rates. These prospects are made all the more exciting considering the news coming out of the recent American Association for the Study of Liver Diseases meeting in Boston: Pharmaceutical companies announced that multiple therapies in the pipeline offer a groundbreaking promise of SVRs higher than 75 percent—some even approaching a 100 percent cure rate. Look for these antivirals to likely hit the market in the next three to five years.
Meanwhile, HCC is expected to see its rates peak sometime in the 2020s. It’s the fastest growing cancer in the United States, thanks to the ticking time bomb of an estimated 5.2 million Americans living with hepatitis C. The cancer is the result of the chronic inflammation the virus causes in the liver: Untreated, hep C can lead to fibrosis or cirrhosis, which in turn can cause liver cancer. About 20 to 30 percent of people with hepatitis C will develop cirrhosis two decades after infection—and those with cirrhotic livers experience a 1 to 4 percent annual incidence of HCC.
Published in BMJ Open, the new study was conducted by researchers at the Copenhagen University Hospital Hvidovre in Denmark. The scientists performed a meta-analysis of eight published randomized controlled trials that compared antiviral therapy—interferon or pegylated interferon as monotherapy or paired with ribavirin—to a placebo or no antiviral treatment. All told, the scientists examined data on 1,200 hep C patients, who were monitored for five to eight years after completing treatment, and compared their results to an untreated cohort of the same size.
Across the board, liver cancer rates dropped 47 percent thanks to antiviral treatment. While those who achieved an SVR saw a dramatic 85 percent drop in liver cancer rates, even those who didn’t rid their bodies of the virus still achieved a significant drop of 43 percent. The study’s findings, unfortunately, are difficult to apply to clinical practice because only two of the eight studies in the review used the current standard treatment of pegylated interferon rather than regular interferon, and most of the trials involved monotherapy. Their results are further clouded by the fact that today people with hepatitis C tend to be identified and treated earlier in the course of their disease, before the virus damages the liver as perilously.
Study author Nina Kimer, MD, a clinical researcher in the department of Medical Gastroenterology at Hospital Hvidovre, said that she and her colleagues chose to examine the older studies because they offered the best control groups—untreated patients—which in turn allowed them to yield most statistically significant results.
Another of the study’s limitations is that it could not provide information on whether antiviral treatment prevents or simply delays HCC. Nor does the paper produce solid results on the drugs’ effect on mortality or other complications such as cirrhosis and fibrosis.
Explaining the phenomenon that antivirals appear to reduce cancer rates irrespective of viral cure, Kimer said that “interferon must in some way have an anti-carcinogenic effect on the liver and not only an antiviral.” To that effect, the study theorizes that the “potential anti-carcinogenic effect of interferon could be related to its immunoregulatory and antitumoral [anti-tumor] effects” and notes that two previous research papers have found that prolonged interferon treatment reduces liver inflammation.
Calling the Danish study “excellent,” Douglas T. Dieterich, MD, director of outpatient hepatology at Mount Sinai School of Medicine in New York City, said that people with hep C who hope to hold out for the new drugs to hit the market in the mid- to late-2010s must carefully weigh their desire to put off treatment against progressing liver damage.
“Patients really need to be screened for their HCC,” Dieterich said. “That should be part of every discussion, every visit [with health care providers]. The guidelines say every six months. If they have advanced liver disease, I would screen them not just with an ultrasound, [but also] with a CAT scan or MRI—yearly, or alternating with an ultrasound.”
Even those who have been cured of HCV need to remain vigilant for liver cancer.
“We can’t let our guard down and stop screening,” Dieterich cautioned. “Patients who have had significant liver disease when we’ve treated them, even if they’re cured, if they have stage three or four disease, they really should be screened.” (Every six months is the gold standard.)
Tracy Swan, hepatitis/HIV project director at Treatment Action Group, said an HCV cure “is like quitting smoking: You’ve greatly lowered your risk of lung cancer, but you’re still going to be at higher risk than anyone who never smoked.”
Looking forward, David Bernstein, MD, chief of the division of hepatology at North Shore University Hospital in Manhasset, sees hope that the threat of liver cancer will diminish in the coming decade, should the current pharmaceutical development of promising new therapies pan out.
“I think as the newer therapies become available—first of all, they have far fewer side effects, so more and more people are going to be treated—you should be able to use them in the cirrhotic patients, or perhaps even in people with mild [liver] decompensation. And I think that this is going to lead to much higher cure rates. And hopefully that should translate into a significant decrease in the number of people who develop hepatocellular carcinoma.”
Focusing on the here and now, Dieterich said that “[t]he main messages [of the study] are that this is great news and it’s another argument to get tested and treated right away.” But he adds a caveat for anyone who has had advanced liver disease: “You can’t let your guard down and stop screening—even if you’re cured.”