A new study demonstrates that antiviral drugs for hepatitis C reduce liver-related deaths by nearly 50%


A new study from the UT Southwestern Simmons Comprehensive Cancer Center demonstrates that antiviral drugs for hepatitis C reduce liver-related deaths by nearly 50% in patients with a history of liver cancer.

The finding builds on a December 2018 study by the same researchers who found that antiviral drugs do not increase the risk of liver cancer recurrence, as was previously feared.

Dr. Amit Singal’s study was published in the journal Gastroenterology on July 30. Dr. Singal is an Associate Professor of Internal Medicine, Medical Director of the UT Southwestern Liver Tumor Program, and Clinical Chief of Hepatology.

He collaborated on these studies with Dr. Caitlin Murphy, Assistant Professor of Population and Data Sciences and Internal Medicine. They are both members of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Their studies overturn prior misconceptions that made doctors reluctant to prescribe direct-acting antivirals to treat hepatitis C in patients with a history of liver cancer.

Many doctors previously believed that hepatitis C, for all its harmfulness, activates the immune system when it infects the liver, and the immune system kept liver cancer recurrence at bay.

But this notion appears to be false. Drs. Singal and Murphy studied nearly 800 patients from 31 medical centers across the country and found that the drugs are not only safe, they decrease death from cirrhosis and liver cancer by 46%.

“Not only are these drugs safe in this patient population, but we have now demonstrated that they are helpful,” Dr. Singal said.

“Our study changes the paradigm from you could treat a patient’s hepatitis C to you should treat it.”

Dr. Carlos L. Arteaga, Director of the Simmons Cancer Center, said the study’s scope and impact are something that can only be produced by a National Cancer Institute-designated Comprehensive Cancer Center.

“Dr. Singal had more patients involved in the study than any other participating site. As an epidemiologist, Dr. Murphy brought rigor to the data that removes prior doubt on this issue,” he said.

Dr. Murphy said previous studies compounded the misunderstandings of direct-acting antiviral therapy because they, among other things, failed to account for the timing of therapy relative to liver cancer diagnosis, did not include a comparison group, or did not properly consider clinical differences among patients.

The new study is a significant contribution because it clears the path to beneficial drug treatment.

Hepatitis C therapy is so important because it provides a cure,” Dr. Singal said.

“You take oral medications for two or three months, with minimal to no side effects, and you’re done.

You’re cured of hepatitis C.

There’s less than a 1% chance of relapse if you’re cured of hepatitis C.”

Defeating hepatitis C is an important step because infection can otherwise lead to cirrhosis – scarring of the liver – which can be deadly.

Cirrhosis can increase the risk for liver cancer, which also may be fatal.

Curing hepatitis C with antivirals breaks the first link in a deadly chain of events and can lead to improvement in liver function among those who have previously developed cirrhosis.

Hepatitis C rapidly made its way into the American blood stream in the 1970s and 1980s when intravenous drug use spiked and blood products were not screened for the hepatitis C virus.

Hepatitis C infected 2 to 3% of the baby boomer population, the largest generation in U.S. history. Millions were affected.

The disease can lie dormant for 25 to 30 years and resurface as a life-threatening specter years after someone has stopped using drugs and turned to a healthy lifestyle.

Hepatologists saw an alarming spike in cirrhosis as baby boomers aged. By 2017, The New York Times called hepatitis C “an enormous public health problem.”

In 2018, the Centers for Disease Control and Prevention announced there were nearly 2.4 million people living with hepatitis C in the U.S.

“Dr. Singal’s and Dr. Murphy’s study reports a welcome, fact-based way to oppose the adverse effects of hepatitis C infection in various demographic groups,” Dr. Arteaga said.

“Their findings will have a global, lifesaving impact on how hepatitis C is treated. It is particularly important to Texas because the liver cancer incidence rate in Texas is the highest in the nation.”

Dr. Arteaga said the study is also important because liver cancer is highest among the Hispanic population in Texas, and research-based advances in reducing cancer in underserved groups are a Simmons Cancer Center priority.

Treatment with direct-acting antivirals (DAAs) appears to reduce the risk of death and liver cancer among patients with chronic hepatitis C virus (HCV) infection, including those with cirrhosis, new research shows.

In a prospective cohort study of more than 10,000 adult patients with HCV, risk of all-cause mortality, liver-related mortality, non-liver-related mortality, and hepatocellular carcinoma (HCC) was significantly reduced among those who received direct-acting antiviral (DAA) medications compared with those who did not, Fabrice Carrat, PhD, Sorbonne University, French National Institute of Health and Medical Research (INSERM), Paris, and colleagues report.

The study was published online February 11 in The Lancet.

And while decompensated cirrhosis was not significantly influenced by DAA treatment, patients with cirrhosis who achieved sustained virologic response with DAA treatment experienced similarly decreased mortality and cancer risk, the authors write.

Reports in the literature of a possible increase in the occurrence and recurrence of HCC related to DAA treatment in chronic HCV have spurred some controversy, the authors write.

Although previous observational studies have linked DAA treatment with reduced risk of mortality and liver cancer in chronic HCV patients, the heterogeneity of the study populations, variations in inclusion and exclusion criteria, follow-up time, and other considerations have lead researchers to seek more definitive answers, they note.

The current investigation, which the authors say is the first prospective longitudinal study addressing clinical outcomes in DAA-treated HCV, was designed to do just that.

The French ANRS CO22 Hepather study compared outcomes among patients treated with DAAs with an untreated control group, independent of their sustained viral response status.

The study enrolled 14,389 patients with antibodies against HCV between August 6, 2012, and December 31, 2015, including 11,870 with chronic HCV infection at entry.

After excluding patients with active hepatitis B virus co-infection at entry; a history of hepatocellular carcinoma; decompensated cirrhosis; a history of liver transplantation; or a history of receiving peginterferon and ribavirin with or without a first-generation protease inhibitor, along with patients for whom follow-up information was not available, 9895 patients were included in the final analysis.

Of these, 7344 patients were treated with DAAs and 2551 were not.

Compared with the untreated control group, patients in the DAA group were older, had more comorbidities, and more severe liver disease.

In adjusted multivariable analyses of outcomes over a median 33.4 months, exposure to DAAs significantly reduced all-cause mortality by 52% (hazard ratio [HR] 0.48, 95% confidence interval [CI], 0.33–0.70; P = .0001), liver-related mortality by 61% (HR, 0.39; 95% CI, 0.21–0.71; P = .0020), non-liver-related mortality by 40% (HR, 0.60, 95% CI, 0.36–1.00; P  = .048), and hepatocellular carcinoma by 34% (HR, 0.66; 95% CI, 0.46–0.93; P =.018). However, DAA treatment was not associated with a reduction in risk for decompensated cirrhosis (HR, 1.14; 95% CI, 0.57–2.27; P = .72).

When the authors stratified patients based on whether they achieved a sustained virologic response, they found that those who did had significantly reduced risk of all-cause mortality, liver-related mortality, non-liver-related mortality, and hepatocellular carcinoma, compared with untreated patients.

There was also a trend toward reduced risk of decompensated cirrhosis, but it did not reach statistical significance.

More information: Amit G. Singal et al. Direct-Acting Antiviral Therapy for HCV Infection is Associated with Increased Survival in Patients With a History of Hepatocellular Carcinoma, Gastroenterology (2019). DOI: 10.1053/j.gastro.2019.07.040

Journal information: Gastroenterology
Provided by UT Southwestern Medical Center


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