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Hepatology (Baltimore, Md.) Mar 2024
Evidence-based consensus guidelines for the diagnosis and management of protoporphyria-related liver dysfunction in erythropoietic protoporphyria and X-linked protoporphyria.
Topics: Humans; Protoporphyria, Erythropoietic; Liver Diseases; Ferrochelatase; Genetic Diseases, X-Linked; 5-Aminolevulinate Synthetase
PubMed: 37505211
DOI: 10.1097/HEP.0000000000000546 -
The Tohoku Journal of Experimental... Oct 2023Erythropoietic protoporphyria (EPP) is a very rare disease with an estimated prevalence of 1 in 200,000 individuals. Decreased ferrochelatase activity causes the... (Review)
Review
Erythropoietic protoporphyria (EPP) is a very rare disease with an estimated prevalence of 1 in 200,000 individuals. Decreased ferrochelatase activity causes the accumulation of protoporphyrin in the body, and light exposure results in the generation of active oxygen, causing photosensitivity. Liver damage has the greatest influence on the prognosis, and liver transplantation is the only treatment option for patients with decompensated liver cirrhosis. We report a case of living-donor liver transplantation for decompensated liver cirrhosis associated with EPP. The patient was a 52-year-old male who led a normal life except for mild photosensitivity. When the patient was 37-year-old, hepatic dysfunction was noticed. At 48-year-old, high erythrocyte protoporphyrin levels, skin biopsy, and genetic tests resulted in a diagnosis of EPP. The patient underwent living- donor liver transplantation because of decompensated liver cirrhosis. In the operating room and intensive care unit, a special light-shielding film was applied to all light sources to block light with harmful wavelengths during treatment. Due to the need for special measures, a lecture on patients with EPP was given before surgery to deepen understanding among all medical professionals involved in the treatment. As a result, no adverse events occurred during the perioperative period, and the patient was discharged on the 46th post-operative day. Currently, the transplanted liver is functioning extremely well, and the patient is alive 3 years post-transplant. Herein, we describe a case of living donor liver transplantation for EPP with a brief literature review.
Topics: Male; Humans; Middle Aged; Adult; Protoporphyria, Erythropoietic; Liver Transplantation; Living Donors; Protoporphyrins; Ferrochelatase; Liver Diseases; Liver Cirrhosis
PubMed: 37495523
DOI: 10.1620/tjem.2023.J061 -
Pharmacology & Therapeutics Aug 2023Protoporphyrin IX (PPIX) is an intermediate in the heme biosynthesis pathway. Abnormal accumulation of PPIX due to certain pathological conditions such as erythropoietic... (Review)
Review
Protoporphyrin IX (PPIX) is an intermediate in the heme biosynthesis pathway. Abnormal accumulation of PPIX due to certain pathological conditions such as erythropoietic protoporphyria and X-linked protoporphyria causes painful phototoxic reactions of the skin, which can significantly impact daily life. Endothelial cells in the skin have been proposed as the primary target for PPIX-induced phototoxicity through light-triggered generation of reactive oxygen species. Current approaches for the management of PPIX-induced phototoxicity include opaque clothing, sunscreens, phototherapy, blood therapy, antioxidants, bone marrow transplantation, and drugs that increase skin pigmentation. In this review, we discuss the present understanding of PPIX-induced phototoxicity including PPIX production and disposition, conditions that lead to PPIX accumulation, symptoms and individual differences, mechanisms, and therapeutics.
Topics: Humans; Endothelial Cells; Protoporphyrins; Protoporphyria, Erythropoietic; 5-Aminolevulinate Synthetase
PubMed: 37392940
DOI: 10.1016/j.pharmthera.2023.108487 -
The New England Journal of Medicine Jun 2023
Topics: Humans; Protoporphyria, Erythropoietic
PubMed: 37379151
DOI: 10.1056/NEJMc2305601 -
The New England Journal of Medicine Jun 2023
Topics: Humans; Protoporphyria, Erythropoietic; Erythropoiesis
PubMed: 37379150
DOI: 10.1056/NEJMc2305601 -
The New England Journal of Medicine Jun 2023
Topics: Humans; Protoporphyria, Erythropoietic; Erythropoiesis
PubMed: 37379149
DOI: 10.1056/NEJMc2305601 -
Nature Reviews. Endocrinology Sep 2023A large body of preclinical and clinical data shows that the central melanocortin system is a promising therapeutic target for treating various metabolic disorders such... (Review)
Review
A large body of preclinical and clinical data shows that the central melanocortin system is a promising therapeutic target for treating various metabolic disorders such as obesity and cachexia, as well as anorexia nervosa. Setmelanotide, which functions by engaging the central melanocortin circuitry, was approved by the FDA in 2020 for use in certain forms of syndromic obesity. Furthermore, the FDA approvals in 2019 of two peptide drugs targeting melanocortin receptors for the treatment of generalized hypoactive sexual desire disorder (bremelanotide) and erythropoietic protoporphyria-associated phototoxicity (afamelanotide) demonstrate the safety of this class of peptides. These approvals have also renewed excitement in the development of therapeutics targeting the melanocortin system. Here, we review the anatomy and function of the melanocortin system, discuss progress and challenges in developing melanocortin receptor-based therapeutics, and outline potential metabolic and behavioural disorders that could be addressed using pharmacological agents targeting these receptors.
Topics: Humans; Melanocortins; Sexual Dysfunctions, Psychological; Obesity; Cachexia; Metabolic Diseases
PubMed: 37365323
DOI: 10.1038/s41574-023-00855-y -
Cureus Apr 2023Erythropoietic protoporphyria (EPP) is a rare inherited disorder of porphyrin metabolism that can cause liver damage and cholestatic hepatocellular failure. We report a...
Erythropoietic protoporphyria (EPP) is a rare inherited disorder of porphyrin metabolism that can cause liver damage and cholestatic hepatocellular failure. We report a case of EPP in a teenaged male who underwent liver biopsy for investigation of liver dysfunction of unknown cause. The diagnosis was not made until a re-biopsy approximately three years later, when the patient presented with recurrent skin lesions and elevated blood and urinary protoporphyrin levels. The liver biopsies contained brownish deposits that exhibited birefringence under polarized light and porphyrin fluorescence under fluorescence spectroscopy. EPP should be considered in young patients with unexplained liver dysfunction, skin symptoms, and seasonal changes in symptoms. Fluorescence spectroscopy of liver biopsy tissue can be a useful tool in the diagnosis of EPP.
PubMed: 37228562
DOI: 10.7759/cureus.38017 -
Journal of Hepatology Jun 2023Living donor liver transplantation (LDLT) is recognised as an alternative treatment modality to reduce waiting list mortality and expand the donor pool. Over recent... (Review)
Review
Living donor liver transplantation (LDLT) is recognised as an alternative treatment modality to reduce waiting list mortality and expand the donor pool. Over recent decades, there have been an increasing number of reports on the use of LT and specifically LDLT for familial hereditary liver diseases. There are marginal indications and contraindications that should be considered for a living donor in paediatric parental LDLT. No mortality or morbidity related to recurrence of metabolic diseases has been observed with heterozygous donors, except for certain relevant cases, such as ornithine transcarbamylase deficiency, protein C deficiency, hypercholesterolemia, protoporphyria, and Alagille syndrome, while donor human leukocyte antigen homozygosity also poses a risk. It is not always essential to perform preoperative genetic assays for possible heterozygous carriers; however, genetic and enzymatic assays must hereafter be included in the parental donor selection criteria in the aforementioned circumstances.
Topics: Child; Humans; Living Donors; Liver Transplantation; Siblings; Heterozygote; Liver Diseases; Treatment Outcome
PubMed: 37208102
DOI: 10.1016/j.jhep.2022.10.013 -
Allergologia Et Immunopathologia 2023Acute lung injury (ALI) is a common complication of critical diseases with high morbidity and mortality. This study explored the regulatory role and mechanism of high...
OBJECTIVE
Acute lung injury (ALI) is a common complication of critical diseases with high morbidity and mortality. This study explored the regulatory role and mechanism of high mobility histone box 1 protein (HMGB1) on pulmonary fibrosis (PF) after ALI in rats through nucleotide oligomerization domain-like receptor protein-3 (NLRP3) inflammasome.
METHODS
PF rat models after ALI were established by induction of bleomycin. Degree of fibrosis was assessed by Masson staining and Ashcroft scoring. Hydroxyproline (Hyp) contents in lung tissues and rat lung tissue morphology were detected by enzyme-linked-immunosorbent serologic assay (ELISA) and hematoxylin and eosin staining. The levels of NLRP3, major proteins of NLRP3 inflammasome (NLRP3/ASC/caspase-1), and downstream inflammatory cytokines interleukin (IL)-1 and IL-18 were determined using immunohistochemistry, Western blotting analysis, and ELISA. The nuclear/cytoplasmic nuclear factor erythroid 2-related factor 2 (Nrf2) levels and HO-1 levels were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis. Rats was injected with lentivirus carrying short hairpin (sh)-HMGB1 and zinc protoporphyria (ZNPP) (HO-1 inhibitor) to assess the effects of HMGB1 and HO-1 on PF and NLRP3 inflammasome activation.
RESULTS
Bleomycin induced PF after ALI in rats, manifested as patchy fibrosis, atelectasis, and excessive expansion, and increased Aschcroft score and Hyp content. Bleomycin treatment enhanced levels of NLRP3, ASC, caspase-1, IL-1, and IL-18 in rat lung tissues, which promoted activation of NLRP3 inflammasome. HMGB1 was up-regulated in bleomycin-induced rats. HMGB1 knockdown partially reversed NLRP3 inflammasome activation and PF progression. HMGB1 knockdown promoted Nrf2 nuclear translocation and up-regulated HO-1. Suppression of HO-1 partially reversed inhibition of HMGB1 knockdown on NLRP3 inflammasome activation and PF.
CONCLUSION
HMGB1 can activate NLRP3 inflammasomes and promote PF by inhibiting the Nrf2/HO-1 pathway.
Topics: Animals; Rats; Acute Lung Injury; Bleomycin; Caspases; HMGB1 Protein; Inflammasomes; Interleukin-18; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Pulmonary Fibrosis
PubMed: 37169561
DOI: 10.15586/aei.v51i3.668