Antivirals Reduce Liver Disease Progression in Hepatitis C patients

Whether the hepatitis C virus plays a direct role in causing hepatocellular carcinoma or an indirect one by fomenting inflammation and cirrhosis is unclear.

Direct-acting antivirals were effective at reducing the risk of tumor progression in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), a new study found.

Researchers at the Osaka City University Graduate School of Medicine in Osaka, Japan, discovered that, after patients received cancer treatment, the oral administration of direct-acting antivirals reduced the risk of tumor progression following recurrence of the liver disease.

The findings were published in the Journal of Viral Hepatitis. The direct-acting antivirals include Harvoni (ledipasvir and sofosbuvir), Zepatier (elbasvir and grazoprevir), and Mavyret (glecaprevir and pibrentasvir).

“DAA (direct-therapy antivirals) is effective at eradicating the hepatitis C virus, a major risk factor for HCC” said Norifumi Kawada, professor of the Department of Hepatology, in a news release. “While it is deemed low or inconclusive whether DAA therapy helps prevent HCC recurrence, little is known about how the antiviral therapy affects progression of the liver disease after cancer treatment.”

“Usually, cancer cells grow over long periods of time before they can be detected as a tumor,” said Hiroko Ikenaga, first author of the paper and with the Department of Hepatology Osaka City University Graduate School of Medicine. “Our study showed that eliminating the hepatitis C virus with DAA suppresses tumor progression, which we suggest contributes to overall patient survival.”

Several other studies have demonstrated the benefit of using direct-acting antivirals in HCC patients, researchers wrote in a Journal of Hepatology article published earlier this year. One study reported a significantly lower probability of liver transplantation linked to improved liver function in patients treated with direct-acting antivirals than in those not treated with them.

In another study published last year in PLOS One, HCC patients treated with direct-acting antivrals had longer overall survival time than the group that did not receive them. Wei-Chen Lin of Mackay Memorial Hospital and her colleagues noted that it remains controversial whether the hepatitis virus C plays a direct or indirect role in causing. Some mouse models have suggested a direct oncogenic effect of the virus. But it is also possible that the virus has an upstream role, causing chronic inflammation and cirrhosis.

Decisions about direct-acting antiviral treatment in HCC patients should be considered in light of the tumor stage, liver function, life expectancy, and patient preferences, the researchers said, and the optimal timing of HCV treatment in patients with HCC is debatable.

“Patients who have undergone potentially curative HCC management would not benefit from delayed DAA therapy. The AGA (American Gastroenterological Association) advises that the best timing for DAA therapy is 4 to 6 months after a complete response to HCC therapy,” they wrote.

In the Osaka University study, Kawada and colleagues analyzed data from 165 patients with early-stage HCC, who were also receiving curative HCC treatment. After treatment, 72 patients received direct-acting antiviral therapy while the remaining 93 did not.

There were 96 HCC recurrences, and around 75% of them were at an early stage.

A second multivariate adjusted time-varying Cox regression analysis showed a 72% reduction in tumor progression in the group treated wiuth direct-acting antivirals and an 88% reduction in risk of death from HCC.

In addition, the frequency of cancer treatments given before the cancer progressed declined by 59%, from 0.83 treatments per year in patients who did not receive DAA therapy to 0.24 treatments per year in patients who did.