Report Ties Antiviral Med to Exogenous Cushing’s

Chinese woman was taking antiviral Epclusa to treat hepatitis C virus

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A 49-year-old woman developed exogenous, or therapy-related, Cushing’s syndrome, after being treated with the antiviral Epclusa, which is approved to treat hepatitis C virus infections, a case study reported.

“To our knowledge, this is the first time that [Epclusa] has been linked to [exogenous Cushing’s],” the researchers wrote.

The study, “A rare case report of iatrogenic Cushing syndrome caused by direct anti-hepatitis C virus therapy with sofosbuvir/velpatasvir,” was published in the journal Medicine.

Exogenous Cushing’s syndrome is caused by excessive or long-term exposure to certain medications, usually glucocorticoids.

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Epclusa (sofosbuvir/velpatasvir), sold by Gilead, is a combination of anti-viral medications approved for treatment of the hepatitis C virus (HCV), which causes a liver disease called hepatitis C. Epclusa is approved for patients with or without compensated cirrhosis — liver scarring due to long-term damage.

Several studies demonstrated that Epclusa provides a higher sustained anti-viral response in patients with hepatitis C virus genotypes 1–6 — the major variants of this virus.

Now, researchers in China reported the case of a woman who developed Cushing’s after taking Epclusa.

The 49-year-old woman had been diagnosed with chronic hepatitis C for more than two years. She was infected with the HCV 3b variant, and had a viral load of 1.10 million international units per milliliter (IU/mL) of blood.

She had psoriasis — an autoimmune skin condition that causes flaky patches — but no history of heart disease, diabetes, or high blood pressure (hypertension). She denied any past history of infections, food or medication allergies, as well as no history of trauma or surgery.

Prescribed Epclusa

Before her hospital stay, she had never received antiviral treatment. At hospital admission, her viral load was 2.73 million IU/mL. She was prescribed treatment with Epclusa (400 mg daily) in March 2021.

After three months of treatment, she tested negative for HCV, but had swelling in the face (so-called “moon face”). This was accompanied by swelling in both lower legs that gradually worsened. These symptoms were followed by shortness of breath after physical activity, casual panic, and heart palpitations.

Clinical examination revealed a round face and mild facial puffiness, accompanied by fat accumulation in the upper neck. She also presented abdominal obesity, and high levels of red blood cells. Skin also showed alterations, including skin breakdown on both hands, and acne.  These signs led clinicians to suspect Cushing’s syndrome.

Bloodwork revealed she had low levels of adrenocorticotropic hormone (ACTH) (0.22 picomoles per liter, pmol/L; normal range: 1.6–13.9 pmol/L) across three time-points during the day (12 a.m., 8 a.m., 4 p.m.). Levels of cortisol at these times also were also lower than normal ( 11.2, 11.43, and 19.54 nanomoles per L, nmol)/L; normal cortisol levels range between 240–619 nmol/L from 12–8 a.m. and drop below 276 nmol/L after 4 p.m.). Additionally, her 24-hour urinary free cortisol was low (34.75 nmol/24-hour; normal range 108–961 nmol/24-hour).

These findings suggested the patient had exogenous, or therapy-related, Cushing’s syndrome.

Other extensive clinical exams were unremarkable, but an abdominal CT scan showed signs of liver cirrhosis and a slightly enlarged spleen.

Treating the liver

She received protective therapy for her liver with acetylcysteine and enzyme-lowering treatment with dicyclomine for approximately five days,  together with Epclusa. However, due to the risk of therapy-related Cushing’s syndrome, all three medications were discontinued.

One month later, the patient was referred to a more advanced hospital. Lab bloodwork showed circulating ACTH levels of 18.8 pg/L and cortisol of 0.7 micrograms per deciliter (mcg/dL) at 8 a.m., consistent with exogenous Cushing’s syndrome .

According to researchers, neither acetylcysteine nor dicyclomine could trigger Cushing’s syndrome.

“The patient had recently not taken glucocorticoids or unauthorized amounts of oral drugs, topical creams, sprays, or cosmetics. She developed medically induced Cushing syndrome after receiving direct anti-HCV treatment with [Epclusa]” , the researchers wrote.

To restore ACTH and cortisol levels, she was given oral hydrocortisone acetate tablets (10 mg, three times daily), a form of cortisol replacement therapy.

Symptoms eased

She was re-examined in September following one month of hydrocortisone. Her symptoms had eased markedly and circulating ACTH and cortisol levels had improved.

Hydrocortisone treatment was maintained, and on a second follow-up in December her circulating  ACTH and cortisol levels had nearly normalized.

On an endocrinologist consultation, treatment with hydrocortisone was advised to be discontinued and regularly reviewed.

Overall, this case-report “aims to improve early recognition of this rare adverse event by hepatologists and primary care physicians treating HCV, allowing early discontinuation of DAA [direct-acting antiviral] therapy if a similar adverse event recur,” the researchers wrote.