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Free Access to Antivirals for Hep C Reduces Mortality Rate

Providing hepatitis C patients with free access to new antiviral medicines drastically reduces the risk for death, according to a study carried out by a team of researchers from the National School of Public Health at Carlos III Institute of Health. Experts have noted this correlation in recent years, and current research published in Hepatology backs it up with data. After analyzing data from 2001 to 2018, the researchers showed that the annual reduction in hepatitis C–related mortality in Spain went from 3.2% to 18.4% from 2015 — when the free-access became widespread in Spain — to 2018.

“There’s been a radical change in the disease since new treatments became available. The advances made in treating hepatitis C have been spectacular. It marks a historical change, and I feel honored to be a part of it,” said hepatologist José Luis Castro Urda, MD, head of digestive medicine at Severo Ochoa University Hospital in Madrid.

Direct-acting antivirals prevent the hepatitis C virus (HCV) from multiplying and have a cure rate of up to 97%. The drugs were approved by the European Medicines Agency (EMA) in 2014, and introduced in Spain a year later.

“With the latest generation of drugs, we’ve cured more than 160,000 people in Spain,” said Pedro Santamaría, a founder and current member of the Catalan Association of Liver Patients (ASSCAT). “At first, the experience was very difficult. But after the concerted efforts of associations, of professionals, and of the patients themselves, we succeeded in getting the medication offered free of charge.”

A Worldwide Public Health Issue

Hepatitis C is an asymptomatic viral disease that causes liver inflammation and that can lead to both liver dysfunction and liver failure. To this day, the disease continues to be a significant cause of hepatic morbidity and mortality in many countries and is considered to be a worldwide public health issue. The World Health Organization (WHO) estimates that 1.4 million deaths annually are due to acute hepatitis infection and hepatitis-related liver cancer and cirrhosis; 48% of these deaths are attributable to HCV.

For a few lucky people, the body is able to fight the infection and the virus goes away, but between 75% and 85% of acute infections develop into chronic hepatitis infections without adequate treatment.

“And in these cases, people who have had the infection for 30 years have a 30% chance of developing liver cancer,” explained Juan Antonio Pineda, MD, PhD, from the University Hospital of Valme in Seville, who is founder of the Study Group for Viral Hepatitis (HEPAVIR) of the Andalusian Society of Infectious Diseases (SAEI), which primarily focuses on research into HIV/HCV coinfection.

“Patients with cirrhosis secondary to HCV have a 2% to 4% annual risk of developing hepatocellular carcinoma,” added Castro Urda. “We have to keep in mind that, once cirrhosis has taken hold, curing the virus does not mean that the cirrhosis is cured; therefore, these patients have to be monitored and screened for hepatocellular carcinoma.”

Until the introduction of second-generation direct-acting antivirals in 2014, efforts to reduce the disease burden of hepatitis C had not been very effective, Santamaría recalled. Interferon and ribavirin were able to lower the viral load during treatment, but as soon as the treatment was stopped, the viral load returned to previous levels.

“When the new medication became available to us, it was like the discovery of penicillin: a miracle!” he said. “These new antivirals radically changed the outlook; patients now had a short-course, straightforward, well-tolerated treatment. Today’s medication is a daily pill that has no side effects.”

As the new study reports, more than 95% of hepatitis C patients treated with these new antivirals have undetectable HCV RNA levels in their blood specimens, suggesting a very significant increase in the cure levels for the disease.

A Strategic Plan

The emergence of these highly effective antivirals led to the development and publication of the Strategic Plan for Tackling Hepatitis C in the Spanish National Health System in April 2015. The plan was aimed at promoting adequate diagnosis and treatment for HCV as the disease had become the leading cause of infectious disease burden in Spain between 2000 and 2009. At that time, however, there was not a lot of evidence on the ability of the new treatments to reduce mortality related to hepatitis C.

After the new direct-acting antivirals came on the scene, there was a quite significant increase in the number of people cured in groups considered to be at very high risk (such as people who inject drugs).

“By and large, the patients are men over 40 who are former drug users or men and women over 60 who contracted the disease through medical equipment that was not properly sterilized,” said Pineda.

Santamaría is one of the latter. He became infected as a result of a blood transfusion that he received at a public hospital in February 1988.

“When I realized that my case was not unique, I started to look for others who found themselves in the same situation. First, we formed a support group, and then, in 2010, we decided to establish the association,” he said.

“Blood transfusions are the common denominator among people over 60 who have hepatitis C. And being infected in this way wasn’t due to carelessness. It was because no one knew that the sterilization methods being used didn’t prevent hepatitis infections,” Pineda said. “Moreover, hepatitis C had yet to be discovered. In Spain, we weren’t able to screen blood for HCV until 1991, at which point the virus had been identified.”

According to Castro Urda, “the patient profile has changed a lot. More and more now, we’re seeing patients who are coming from so-called difficult-to-treat populations — for example, patients with psychiatric disorders who may be on a number of central nervous system agents — and patients who have difficulties adhering to treatment, such as those who are homeless or incarcerated.”

Challenges During the Pandemic

Although the advances made toward a cure for hepatitis C are incredible, “and we can be pleased with the progress that has been made toward eradicating the virus, the pandemic has restricted people’s access to the treatments,” said Castro Urda. “This is especially true with respect to people in the most vulnerable populations.”

“We’ve seen outbreaks in healthcare centers, reduced access to healthcare services, and deleterious effects of lockdowns, for example, increasing mortality in patients with mental disorders. All of this has had a negative impact, as many HCV treatments are now behind,” he added.

“Although, during the pandemic, the rate of decline has been slower, the number of patients with active infection is continuously decreasing,” said Pineda. “While not many, there are some new diagnoses being made. Most of these cases are in men who have sex with men and drug users who share needles and other drug equipment.”

In 2019, an international study assessed progress toward eliminating HCV in 45 high-income countries. A review was done of each country’s action plan for eliminating the virus, and a model was developed to forecast annual HCV-infected populations. Spain was among those on track to meet the HCV elimination targets by 2030, second only to Iceland.

“Fortunately, Spain is one of the most advanced countries when it comes to the elimination of the virus. But, of course, there’s still a long way to go,” said Castro Urda. Given the current challenges, his focus is on “identifying people who have it and don’t know that they do. In other words, carrying out screenings and setting up micro-elimination programs.”

“There’s still a small percentage of people who have hepatitis C, but because they have no symptoms they lack a diagnosis,” explained Santamaría.

The number of patients diagnosed with HCV infection have gone up since Spain’s strategic plan was implemented, “as patients who were unaware that they’d been infected all those years ago are now being diagnosed. These are not cases of people being newly infected. And these patients, as soon as they are diagnosed, are treated. Therefore, the number of patients with active infection (who are the true carriers of the infection; the rest are past infections) is rapidly decreasing,” concluded Pineda.

Hepatology. Published online November 12, 2021. Abstract

This article originally appeared on Univadis Spain.

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