Antiviral medicines seen to resolve both hepatitis C and PCT

Over two-thirds of porphyria cutanea tarda patients have infections

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Among people with porphyria cutanea tarda (PCT) and chronic hepatitis C infection, treatment with modern antiviral medicines has been found to cure the infection and resolve PCT symptoms, according to a new study.

Specifically, a combination therapy of ledipasvir and sofosbuvir — sold by Gilead under the brand name Harvoni — was found to treat both of these often co-occurring conditions.

This is important, according to researchers, given that, in the U.S., more than two-thirds of people with PCT — the most common form of porphyria — have an underlying hepatitis C infection.

“The main finding of this work is that ledipasvir/sofosbuvir [Harvoni] alone is highly effective both for treatment and cure of [chronic hepatitis C infection] and of active PCT,” the investigators wrote.

The study, “Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C,” was published in the journal Digestive Diseases and Sciences. The work was funded by a grant from Gilead Sciences.

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Antiviral medicines effective for PCT plus hepatitis C

Porphyria cutanea tarda, known as PCT, is caused by the abnormally reduced activity of an enzyme called UROD, which leads to symptoms like sunlight sensitivity. Chronic infection with the hepatitis C virus is a well-established risk factor for PCT. In fact, a majority of PCT cases in the U.S. occur in people who also have an hepatitis C infection.

In decades past, treatment of hepatitis C was generally not very effective and could cause substantial side effects. As such, it became common practice to prioritize treating and managing the symptoms of PCT, rather than addressing that infection.

In recent years, new therapies that directly interfere with the replication of the hepatitis C virus have become available. These treatments are much more effective at clearing the infection and tend to cause far fewer side effects compared with older treatments.

Since the availability of these new antiviral therapies, there have been a few case reports describing patients with PCT whose symptoms resolved once the underlying hepatitis C infection was treated.

Now, scientists at Wake Forest University Health Sciences and other U.S. institutions conducted a small Phase 2 trial (NCT03118674) aiming to formally explore the efficacy of antiviral therapies as a first-line treatment for PCT arising in the setting of an hepatitis C infection.

The study enrolled 15 adults with both conditions. Most were current smokers and reported regularly consuming alcohol. Of the participants, one was Black, the rest were white, and 13 of them were men. They had a mean age of 58.9.

All were treated with a fixed-dose combination of the antiviral medicines ledipasvir and sofosbuvir. Gilead sells this combination under the brand name Harvoni; generic versions of the therapy also are available.

Two of the 15 participants were lost to follow-up in the first few months of the study. Among the 13 patients who were followed for at least three months, 11 were cured of hepatitis C infection.

Of the two patients who were not cured of hepatitis C following treatment with ledipasvir/sofosbuvir, one was subsequently cured after treatment with sofosbuvir and velpatasvir, another combination of modern antivirals sold under the brand name Epclusa.

In all patients, porphyrin levels tended to decrease following the start of antiviral treatment; so too did skin lesions. Porphyrins are molecules that tend to build up to toxic levels in different tissues and organs in people with porphyria.

Among those cured of hepatitis C, symptoms of PCT resolved following the treatment. The one patient who remained uncured of the viral infection continued to experience PCT symptoms.

The scientists noted that treatment was successful “even among those who continued to consume alcohol and to use tobacco” — also risk factors for PCT.

The main finding of this work is that ledipasvir/sofosbuvir [Harvoni] alone is highly effective both for treatment and cure of [chronic hepatitis C infection] and of active PCT.

While this study specifically focused on one modern antiviral therapy, the team noted similar results would be expected with other comparable medications that directly target the hepatitis C virus.

Because people with PCT can experience periods of remission in between symptom attacks, the researchers said they are still following patients where possible. The team also hope to assess how long-lasting the effects of treatment might be.

Additionally, while all patients cured of hepatitis C saw their symptoms resolve, the team noted that many still had abnormal porphyrin levels on laboratory tests. Normal lab tests “may require longer follow-up and/or may not be achieved in all patients,” they wrote.

A noted limitation of this study was the small number of participants. Researchers said they had originally planned to enroll nearly 50 participants, but enrollment slowed considerably in 2020 when the COVID-19 pandemic hit, and at the end of 2020 Gilead decided to close the study.