Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C.
Cutaneous porphyrias
Direct-acting antivirals against hepatitis C
Harvoni
Ledipasvir/sofosbuvir
Sustained virological response
Uroporphyria
Journal
Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
29
11
2022
accepted:
28
01
2023
medline:
18
5
2023
pubmed:
23
2
2023
entrez:
22
2
2023
Statut:
ppublish
Résumé
Chronic hepatitis C [CHC] is a risk factor for porphyria cutanea tarda [PCT]. To assess whether ledipasvir/sofosbuvir is effective for treating both PCT and CHC, we treated patients with CHC + PCT solely with ledipasvir/sofosbuvir and followed them for at least 1 year to assess cure of CHC and remission of PCT. Between September 2017 and May 2020, 15 of 23 screened PCT + CHC patients were eligible and enrolled. All were treated with ledipasvir/sofosbuvir at recommended doses and durations, according to their stage of liver disease. We measured plasma and urinary porphyrins at baseline and monthly for the first 12 months and at 16, 20, and 24 mos. We measured serum HCV RNA at baseline, 8-12, and 20-24 mos. Cure of HCV was defined as no detectable serum HCV RNA ≥ 12 weeks after the end of treatment (EOT). Remission of PCT was defined clinically as no new blisters or bullae and biochemically as urinary uro- plus hepta-carboxyl porphyrins ≤ 100 mcg/g creatinine. All 15 patients, 13 of whom were men, were infected with HCV genotype 1. 2/15 withdrew or were lost to follow-up. Of the remaining 13, 12 achieved cure of CHC; 1 had complete virological response, followed by relapse of HCV after ledipasvir/sofosbuvir but was subsequently cured by treatment with sofosbuvir/velpatasvir. Of the 12 cured of CHC, all achieved sustained clinical remission of PCT. Ledipasvir/sofosbuvir [and likely other direct-acting antivirals] is an effective treatment for HCV in the presence of PCT and leads to clinical remission of PCT without additional phlebotomy or low-dose hydroxychloroquine treatment. ClinicalTrials.gov NCT03118674.
Sections du résumé
BACKGROUND AND AIMS
Chronic hepatitis C [CHC] is a risk factor for porphyria cutanea tarda [PCT]. To assess whether ledipasvir/sofosbuvir is effective for treating both PCT and CHC, we treated patients with CHC + PCT solely with ledipasvir/sofosbuvir and followed them for at least 1 year to assess cure of CHC and remission of PCT.
METHODS
Between September 2017 and May 2020, 15 of 23 screened PCT + CHC patients were eligible and enrolled. All were treated with ledipasvir/sofosbuvir at recommended doses and durations, according to their stage of liver disease. We measured plasma and urinary porphyrins at baseline and monthly for the first 12 months and at 16, 20, and 24 mos. We measured serum HCV RNA at baseline, 8-12, and 20-24 mos. Cure of HCV was defined as no detectable serum HCV RNA ≥ 12 weeks after the end of treatment (EOT). Remission of PCT was defined clinically as no new blisters or bullae and biochemically as urinary uro- plus hepta-carboxyl porphyrins ≤ 100 mcg/g creatinine.
RESULTS
All 15 patients, 13 of whom were men, were infected with HCV genotype 1. 2/15 withdrew or were lost to follow-up. Of the remaining 13, 12 achieved cure of CHC; 1 had complete virological response, followed by relapse of HCV after ledipasvir/sofosbuvir but was subsequently cured by treatment with sofosbuvir/velpatasvir. Of the 12 cured of CHC, all achieved sustained clinical remission of PCT.
CONCLUSIONS
Ledipasvir/sofosbuvir [and likely other direct-acting antivirals] is an effective treatment for HCV in the presence of PCT and leads to clinical remission of PCT without additional phlebotomy or low-dose hydroxychloroquine treatment.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03118674.
Identifiants
pubmed: 36811718
doi: 10.1007/s10620-023-07859-8
pii: 10.1007/s10620-023-07859-8
pmc: PMC9945827
doi:
Substances chimiques
ledipasvir, sofosbuvir drug combination
0
Sofosbuvir
WJ6CA3ZU8B
Antiviral Agents
0
ledipasvir
013TE6E4WV
Fluorenes
0
RNA
63231-63-0
Porphyrins
0
Banques de données
ClinicalTrials.gov
['NCT03118674']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2738-2746Subventions
Organisme : NIDDK NIH HHS
ID : U54 DK083909
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001420
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR029876
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Bonkovsky HL, Guo J-T, Hou W, Li T, Narang T, Thapar M. Porphyrin and heme metabolism and the porphyrias. Compr Physiol. 2013;3:365–401.
doi: 10.1002/cphy.c120006
pubmed: 23720291
Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med 2017;377:862–872.
doi: 10.1056/NEJMra1608634
pubmed: 28854095
Wang B, Rudnick S, Cengia B, Bonkovsky HL. Acute hepatic porphyrias: Review and recent progress. Hepatol Commun 2019;3:193–206.
doi: 10.1002/hep4.1297
pubmed: 30766957
Sixel-Dietrich F, Doss M. Hereditary uroporphyrinogen-decarboxylase deficiency predisposing porphyria cutanea tarda (chronic hepatic porphyria) in females after oral contraceptive medication. Arch Dermatol Res 1985;278:13–16.
doi: 10.1007/BF00412489
pubmed: 4096525
Weiss Y, Chen B, Yasuda M, Nazarenko I, Anderson KE, Desnick RJ. Porphyria cutanea tarda and hepatoerythropoietic porphyria: Identification of 19 novel uroporphyrinogen III decarboxylase mutations. Mol Genet Metab 2019;128:363–366.
doi: 10.1016/j.ymgme.2018.11.013
pubmed: 30514647
Pallet N, Karras A, Thervet E, Gouya L, Karim Z, Puy H. Porphyria and kidney diseases. Clin Kidney J 2018;11:191–197.
doi: 10.1093/ckj/sfx146
pubmed: 29644058
pmcid: 5888040
Singal AK, Kormos-Hallberg C, Lee C et al. Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Clin Gastroenterol Hepatol 2012;10:1402–1409.
doi: 10.1016/j.cgh.2012.08.038
pubmed: 22985607
pmcid: 3501544
Caballes FR, Sendi H, Bonkovsky HL. Hepatitis C, porphyria cutanea tarda and liver iron: an update. Liver Int 2012;32:880–893.
doi: 10.1111/j.1478-3231.2012.02794.x
pmcid: 3418709
Singal AK, Venkata KVR, Jampana S, Islam F-U, Anderson KE. Hepatitis C treatment in patients with porphyria cutanea tarda. Am J Med Sci 2017;353:523–528.
doi: 10.1016/j.amjms.2017.03.007
pubmed: 28641714
pmcid: 5484053
Dietz C, Maasoumy B. Direct-acting antiviral agents for hepatitis C virus infection—From drug discovery to successful implementation in clinical practice. Viruses 2022;14:1325.
doi: 10.3390/v14061325
pubmed: 35746796
pmcid: 9231290
Rojo E, Chaparro M, García-Buey L. Efficacy and safety of glecaprevir/pibrentasvir in a patient with HCV-induced porphyria cutanea tarda receiving vedolizumab for Crohn’s disease. J Crohns Colitis 2020;14:567–568.
doi: 10.1093/ecco-jcc/jjz159
pubmed: 31602458
Sastre L, To-Figueras J, Lens S et al. Resolution of subclinical porphyria cutanea tarda after hepatitis C eradication with direct-acting anti-virals. Aliment Pharmacol Ther 2020;51:968–973.
doi: 10.1111/apt.15703
pubmed: 32294804
Aguilera P, Laguno M, To-Figueras J. Treatment of chronic hepatitis with boceprevir leads to remission of porphyria cutanea tarda. Br J Dermatol 2014;171:1595–1596.
doi: 10.1111/bjd.13376
pubmed: 25154788
Tong Y, Song YK, Tyring S. Resolution of porphyria cutanea tarda in patients with hepatitis C following ledipasvir-sofosbuvir combination therapy. JAMA Dermatol 2016;152:1393–1395.
doi: 10.1001/jamadermatol.2016.3036
pubmed: 27732687
Takata K, Shakado S, Sakamoto K et al. Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C. Clin J Gastroenterol 2017;10:459–463.
doi: 10.1007/s12328-017-0772-x
pubmed: 28884440
Bruzzone B, Magnani O, Sticchi L et al. Resolution of porphyria cutanea tarda in HIV and mixed HCV coinfection after direct-acting antiviral (DAA) therapy. J Antimicrob Chemother 2017;72:2955–2958.
doi: 10.1093/jac/dkx222
pubmed: 29091216
Drago F, Gasparini G, Marenco S, Picciotto A, Parodi A. Porphyrin elevation in a patient on treatment with simeprevir: could it be a possible explanation for simeprevir-associated photosensitivity? Am J Gastroenterol 2016;111:1368.
doi: 10.1038/ajg.2016.291
pubmed: 27580792
Bonkovsky H, Rudnick S, Faust D, et al. Direct-acting antivirals [DAA] are effective as sole treatment of porphyria cutanea tarda [PCT] with chronic hepatitis C [CHC]. Abstract D0490. Annual Meeting of the American College of Gastroenterology; Oct 21–26, 2022; Charlotte, NC.
Gilead. Harvoni: highlights of prescribing information. In:2020 Harvoni package insert.
Egger NG, Goeger DE, Payne DA, Miskovsky EP, Weinman SA, Anderson KE. Porphyria cutanea tarda: multiplicity of risk factors including HFE mutations, hepatitis C, and inherited uroporphyrinogen decarboxylase deficiency. Dig Dis Sci 2002;47:419–426.
doi: 10.1023/A:1013746828074
pubmed: 11855561
Stölzel U, Köstler E, Schuppan D et al. Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda. Arch Dermatol 2003;139:309–313.
doi: 10.1001/archderm.139.3.309
pubmed: 12622622
Rudnick S, Phillips J, Bonkovsky H. Porphyrias consortium of the rare diseases clinical research network. Familial porphyria cutanea tarda. In: Adam M, Everman D, Mirzaa G, Pagon R, Wallace S, eds. GeneReviews®[Internet]. Seattle (WA): University of Washington, Seattle 2013 Jun 6 [Updated 2022 Jun 9].
Phillips JD, Bergonia HA, Reilly CA, Franklin MR, Kushner JP. A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda. Proc Natl Acad Sci USA 2007;104:5079–5084.
doi: 10.1073/pnas.0700547104
pubmed: 17360334
pmcid: 1820519
Bonkovsky H, Rudnick S. Porphyria cutanea tarda. Merck Manual Web site. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/porphyrias/porphyria-cutanea-tarda#v15718555 . Published 2020. Updated Dec 2020. Accessed 2022.