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Updates on the diagnosis and management of the most common hereditary porphyrias: AIP and EPP.

ABSTRACT: The porphyrias are a family of metabolic disorders caused by defects in the activity of one of the enzymes in the heme biosynthetic pathway. Acute intermittent porphyria (AIP), caused by autosomal dominant mutations in the gene encoding hydroxymethylbilane synthase, can lead to hepatocyte overaccumulation and systemic distribution of the proximal porphyrin precursors, 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA and PBG are toxic to neurons and extrahepatic tissue and cause the neurovisceral clinical manifestations of AIP. Management of AIP includes awareness and avoidance of triggering factors, infusions of hemin for severe acute attacks, and, if indicated for chronic suppressive therapy, maintenance treatment with hemin or givosiran, a small interfering RNA molecule that antagonizes ALA synthase 1 transcripts. Erythropoietic protoporphyria (EPP) is most commonly caused by autosomal recessive mutations in the gene encoding ferrochelatase (FECH), the heme pathway terminal enzyme. FECH deficiency leads to erythrocyte overaccumulation and high plasma levels of lipophilic protoporphyrins that photoactivate in the skin, causing burning pain and erythema. Protoporphyrins excreted in the bile can cause gallstones, cholestasis, fibrosis, and ultimately liver failure. Management of EPP includes skin protection and afamelanotide, an ?-melanocyte stimulating hormone analog that increases melanin pigment and reduces photoactivation. Liver transplantation may be necessary for severe EPP-induced liver complications. Because AIP and EPP arise from defects in the heme biosynthetic pathway, hematologists are often consulted to evaluate and manage suspected or proven porphyrias. A working knowledge of these disorders increases our confidence and effectiveness as consultants and medical providers.

SUBMITTER: Linenberger M

PROVIDER: S-EPMC7727547 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Updates on the diagnosis and management of the most common hereditary porphyrias: AIP and EPP.

Linenberger Michael M Fertrin Kleber Y KY

Hematology. American Society of Hematology. Education Program 20201201 1

The porphyrias are a family of metabolic disorders caused by defects in the activity of one of the enzymes in the heme biosynthetic pathway. Acute intermittent porphyria (AIP), caused by autosomal dominant mutations in the gene encoding hydroxymethylbilane synthase, can lead to hepatocyte overaccumulation and systemic distribution of the proximal porphyrin precursors, 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA and PBG are toxic to neurons and extrahepatic tissue and cause the neu ...[more]

PMID: 33275677

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Project description:IntroductionGlobally, the incidence, as well as mortality, related to hepatocellular carcinoma (HCC) is on the rise, owing to relatively few curative options. Underlying cirrhosis is the most common etiology leading to HCC, but risk factors of cirrhosis show great regional variability. Over the years, there has been a steady development in the diagnostic and therapeutic modalities of HCC, including the availability of a wide range of systemic chemotherapeutic agents. We aim to review the recent advancements in the diagnostic and therapeutic strategies for HCC.MethodologyThe literature search was done using databases PubMed, Cochrane, and Science Direct, and the latest relevant articles were reviewed.FindingsScreening of HCC is a pivotal step in the early diagnosis of the disease. Current guidelines recommend using ultrasound and alfa fetoprotein but various new biomarkers are under active research that might aid in diagnosing very small tumors, not picked up by the current screening methods. Treatment options are decided based upon the overall performance of the patient and the extent of the disease, as per the Barcelona classification. There are very few options that offer a cure for the disease, ranging from liver resection and transplantation to tumor ablation. Downstaging has proven to have a significant role in the course of the disease. An attempt to control the disease can be made via radiological interventions, such as transarterial chemoembolization, transarterial radioembolization, or radiation therapy. For advanced disease, sorafenib used to be the only option until a couple of years ago. Recently, many other systemic agents have received approval as first-line and second-line therapies for HCC. Genomics is an area of active clinical research as understanding the mutations and genomics involved in the evolution of HCC might lead to a breakthrough therapy.How to cite this articleRaees A, Kamran M, Özkan H, et al. Updates on the Diagnosis and Management of Hepatocellular Carcinoma. Euroasian J Hepato-Gastroenterol 2021;11(1):32-40.

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Updates on the diagnosis and management of the most common hereditary porphyrias: AIP and EPP.

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Updates on the diagnosis and management of the most common hereditary porphyrias: AIP and EPP.

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