Antivirals Seen to Prevent Porphyria Cutanea Tarda in Hepatitis C Patients

Antiviral treatment can prevent the onset of porphyria cutanea tarda (PCT) in people with hepatitis C and urine abnormalities indicating this form of porphyria, a study found.

The study, “Resolution of subclinical porphyria cutanea tarda after hepatitis C eradication with direct‐acting anti‐virals,” was published in the journal Alimentary Pharmacology and Therapeutics.

PCT is caused by low levels of the enzyme uroporphyrinogen decarboxylase (UROD), which is required for the production of heme — a molecule essential for red blood cells to transport oxygen and break down compounds in the liver.

The disease can be caused by mutations in the UROD gene, or by such non-genetic factors as alcohol consumption, excessive iron in the liver, or infection by the hepatitis C virus (HCV).

With an estimated prevalence of 20%–79% among PCT patients, HCV is recognized in extensive research as one of the main causes of PCT.

However, a small percentage of HCV-infected individuals (1%–4%) also experience symptoms typical of PCT, such as sunlight sensitivity, blisters, or skin crusts. As such, additional factors may also play a role in PCT onset in patients with hepatitis C.

Recent studies have found that antiviral treatments for HCV are effective against PCT.

Investigators at the University of Barcelona carried out a study to evaluate the prevalence of PCT among hepatitis C patients who were being treated with direct-acting antivirals, and of how antiviral therapy affected PCT symptoms.

Their study included data on 84  people with HCV infection (median age, 56) being followed at the Liver Unit of Hospital Clinic Barcelona. All started taking antivirals after Jan. 1, 2018, and none had any skin manifestations typical of PCT.

Direct-acting antivirals were given for eight to 12 weeks without ribavirin, and in different combinations, such as glecaprevir/pibrentasvir (64%), sofosbuvir/velpatasvir (27%), and Zepatier (grazoprevir/elbasvir, 2%). All these patients achieved sustained virologic response, meaning no detectable viral RNA in the blood.

They were then screened for abnormal urine levels of porphyrins — heme precursors that tend to accumulate in PCT and are disease hallmarks. Patients with unusual amounts of porphyrins at baseline (study start) were tested again at 12 and 48 weeks after the antiviral treatment and showing no signs of HCV.

Five patients (6%) had an abnormal urinary porphyrin profile at baseline, with three showing high levels of porphyrins — above 200 nanomol (nmol)/mmol creatinine — that are normally associated with PCT. The other two had types of abnormalities that indicated a lack of UROD activity.

Tests at 12 weeks showed significantly lower urinary porphyrins  — under 40 nmol/mmol creatinine — in the three people with high baseline levels.

A final assessment at 48 weeks post-treatment showed normal levels of porphyrins in the urine — under 30 nmol/mmol creatinine — in all three patients.

Likewise, follow-up evaluations showed a normal urinary porphyrin profile after antiviral treatment in the two people with other types of abnormalities.

“This work confirms the existence of a relevant number of cases (6%) with uroporphyrinuria and full PCT profiles without dermatological involvement among a cohort of viremic hepatitis C-monoinfected patients receiving DAA [direct-acting antivirals] therapy,” the researchers wrote.

“Anti‐viral therapy with DAAs may be considered as the sole definite cure of PCT, since all our patients recuperated from their porphyrin abnormalities in a short time period in line with the rapid viral disappearance,” they added.