Resolution of Porphyria Cutanea Tarda in Patients With Hepatitis C Following Ledipasvir-Sofosbuvir Combination Therapy | Dermatology | JAMA Dermatology | JAMA Network
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Observation
December 2016

Resolution of Porphyria Cutanea Tarda in Patients With Hepatitis C Following Ledipasvir-Sofosbuvir Combination Therapy

Author Affiliations
  • 1Department of Dermatology, University of California, San Diego
  • 2Center For Clinical Studies, Houston, Texas
  • 3University of Texas Medical Branch, Galveston
  • 4Department of Dermatology, University of Texas Health Science Center at Houston
JAMA Dermatol. 2016;152(12):1393-1395. doi:10.1001/jamadermatol.2016.3036

Porphyria cutanea tarda (PCT) is the most common porphyria, caused by a decrease in uroporphyrinogen decarboxylase (UROD) activity.1 There is a strong association between the sporadic form of PCT and hepatitis C virus (HCV) infection. Depending on the country, 40% to 50% of patients with PCT have been found to be infected with HCV.2 Chronic hepatitis C infection unmasks the UROD enzyme deficiency in genetically predisposed patients by causing oxidative stress from iron overload.3 In addition, PCT occurs in the highest rates in patients with HCV-related liver cirrhosis, which suggests that cirrhosis may play a role in disease development.4

Report of Case

Previous HCV treatments, such as interferon, have shown mixed responses in the resolution of PCT.3 One case report demonstrated the resolution of PCT after HCV treatment with the direct-acting antiviral (DAA) agent boceprevir.5 Boceprevir, however, still requires interferon therapy in the treatment regimen, which may have contributed to PCT resolution. We describe 3 men with HCV who had resolution of their PCT manifestations months after completing an 8- or 12-week combination regimen of ledipasvir, 90 mg and sofosbuvir, 400 mg (Figure and Table).

Figure.  Clinical Images of Patient 1
Clinical Images of Patient 1

A, Bullae and erosions of porphyria cutanea tarda are seen in a patient with hepatitis C before treatment. B, Five months after completing an 8-week regimen of combination therapy with ledipasvir and sofosbuvir, the lesions are cleared.

Table.  Patient and Clinical Characteristics
Patient and Clinical Characteristics

Discussion

A literature search revealed 1 case report of successful PCT clearance following treatment with another DAA agent, boceprevir.5 This suggests that the marked improvement in PCT is likely related to the cure of HCV that can be achieved by DAA agents in general and not necessarily only ledipasvir-sofosbuvir combination therapy.

Hepatitis C is an infectious disease that primarily affects the liver potentially leading to cirrhosis and hepatic cancer. As many as 170 million people worldwide are infected with HCV chronically.6 The ushering of a greater understanding of the HCV genome has facilitated the dawn of a new age of treatments for hepatitis C capable of 95% sustained virologic response with DAA agents.6 Direct-acting antiviral agents target specific steps in HCV replication. The improvement of PCT following DAA treatment further suggests that viral activity is directly linked with disease severity and may provide important insight into therapeutics for HCV-associated PCT.

The development of DAA agents heralds a new direction for infectious diseases and hepatology in the fight against hepatitis C. Our case series highlights the potential secondary benefits in improving cutaneous skin diseases of hepatitis C with DAA agents. Further investigations are needed to corroborate our findings regarding PCT resolution in patients with HCV following DAA treatment. Hepatitis C also has known associations with other extrahepatic manifestations such as mixed cryoglobulinemia and lichen planus, which require further investigation.

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Article Information

Corresponding Author: Yun “Larry” Tong, MD, University of California San Diego, 8899 University Center Ln, Ste 350, San Diego, CA 92122 (larrytongmed@gmail.com).

Published Online: October 12, 2016. doi:10.1001/jamadermatol.2016.3036

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patients for granting permission to publish this information.

References
1.
Alla  V, Bonkovsky  HL.  Iron in nonhemochromatotic liver disorders.  Semin Liver Dis. 2005;25(4):461-472.PubMedGoogle ScholarCrossref
2.
Jadali  Z.  Dermatologic manifestations of hepatitis C infection and the effect of interferon therapy: a literature review.  Arch Iran Med. 2012;15(1):43-48.PubMedGoogle Scholar
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Ryan Caballes  F, Sendi  H, Bonkovsky  HL.  Hepatitis C, porphyria cutanea tarda and liver iron: an update.  Liver Int. 2012;32(6):880-893.PubMedGoogle ScholarCrossref
4.
Cacoub  P, Bourlière  M, Lübbe  J,  et al.  Dermatological side effects of hepatitis C and its treatment: patient management in the era of direct-acting antivirals.  J Hepatol. 2012;56(2):455-463.PubMedGoogle ScholarCrossref
5.
Aguilera  P, Laguno  M, To-Figueras  J.  Treatment of chronic hepatitis with boceprevir leads to remission of porphyria cutanea tarda.  Br J Dermatol. 2014;171(6):1595-1596.PubMedGoogle ScholarCrossref
6.
Tamori  A, Enomoto  M, Kawada  N. Recent advances in antiviral therapy for chronic hepatitis C. https://www.hindawi.com/journals/mi/2016/6841628/. Accessed September 7, 2016.
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