Hepatitis C Treatment Slashes Risk of Cancer and Improves Life Expectancy, Study Finds

Illustration depicting the destruction of a hepatitis C virion.
Kateryna Kon/Science Photo Library via Getty

A major French study involving nearly 10,000 patients with hepatitis C found that treatment with the new generation of direct-acting antiviral (DAA) drugs decreases a patient's risk of liver cancer and increases life expectancy.

This fundamental study helps answer questions about the long-term benefit of DAAs such as sofosbuvir (Sovaldi) and daclatasvir (Daklinza), which boast 90% cure rates but have been criticized for sky-high price tags. The study, which was led by Fabrice Carrat, Ph.D., with the Sorbonne University in Paris, was published in The Lancet Feb. 11.

Though prior observational studies have indicated that patients treated with DAAs are less likely to develop hepatocellular carcinoma, the French study is the first large prospective study to compare outcomes among treated and untreated patients.

The study, which followed 7,344 treated and 2,551 untreated patients for nearly three years, found that DAA exposure was associated with a 34% drop in hepatocellular carcinoma and a 52% drop in all-cause mortality.

This study further supports the use of DAAs in all patients with chronic hepatitis C, rather than older reimbursement policies that prioritized treatment for the sickest patients. The research was funded by the French National Institute for Health and Medical Research and the French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS).

The study also received funding from the pharmaceutical companies Merck Sharp & Dohme, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche -- all of which have DAAs on the market.

Interpretation of Results

From 2012 to 2016, French researchers screened 10,166 patients with hepatitis C, ultimately following 9,895 for a median time period of 33.4 months. About three-fourths of the patients were treated with DAAs, while the remainder still hadn't started treatment by the time the study ended.

These distinct cohorts allowed researchers to compare outcomes for treated and untreated groups. Out of the 7,344 patients who were treated with DAAs, 129 had died by the end of the study -- a death rate of less than 2%. Conversely, out of the 2,551 untreated patients, 89 died -- a death rate of about 4%.

Meanwhile, 187 treated patients and 71 untreated patients developed hepatocellular carcinoma -- both at about a rate of 3%. However, the benefit of DAA treatment became truly apparent after researchers adjusted for dramatic differences in the overall health profiles of patients in the treated and untreated cohorts.

Study co-author Stanislas Pol, M.D., Ph.D., with Paris Descartes University, observed that hepatitis C treatment and reimbursement policies have only recently started to emphasize universal treatment. During the study, treatment in France was restricted to "priority" patients with extensive health problems such as severe fibrosis or cirrhosis.

"These patients have of course the highest risk of [hepatocellular carcinoma], and that is why we need to reduce the heterogeneities of both population[s]," Pol said. Researchers accounted for variables such as age, body mass index, infection route, fibrosis score, alcohol consumption, and other health conditions associated with worse hepatitis C outcomes.

To evaluate the data, researchers used a method called the "inverse probability of treatment weighting" and other statistical methods. Weighing the data in this manner allowed the researchers to produce a true comparison, akin to what you would see in a randomized trial, Pol explained.

It also allowed them to correct for the bias in the patient population related to the older treatment prioritization guidelines, Pol added.

Ultimately, treatment was associated with a decrease in all-cause mortality, with an adjusted hazard ratio of 0.48 (95% confidence interval [CI] 0.33-0.70), and a decrease in hepatocellular carcinoma, with a hazard ratio of 0.66 (95% CI 0.46-0.93). The study did not find an association between DAA treatment and decompensated cirrhosis, with a hazard ratio of 1.14 (95% CI 0.57-2.27).

The Changing Treatment Paradigm

About 1% of the world's population is living with hepatitis C, a viral infection that often leads to cirrhosis and hepatocellular carcinoma. Starting in 2013, the U.S. Food and Drug Administration and other drug regulators began approving a flurry of DAAs capable of curing most patients. The drugs were heralded as game-changing cures and opened up the possibility of eliminating hepatitis C in the foreseeable future.

But with wholesale prices approaching $100,000, private insurers and public payers balked, many adopting reimbursement strategies that amounted to medical triage. Meanwhile, a 2017 Cochrane review further confused the situation by questioning the lifesaving potential of DAAs, concluding in a meta-analysis that DAAs "do not have any clinical effect."

Ultimately, DAAs are still so new that their long-term effects on liver disease, cancer, and overall life expectancy have been difficult to discern. However, the recently published French study stands in stark contrast to the 2017 Cochrane analysis and offers new incentives for payers to treat even asymptomatic patients with chronic hepatitis C in the hope of preventing expensive complications later in life.

For study co-author Pol, the major implication of the study is that all patients with chronic hepatitis C should be treated regardless of the severity of their disease.