Etiology and Outcome of Acute Liver Failure in Children—The Experience of a Single Tertiary Care Hospital from Romania

Rare diseases are a group of uncommon diseases in the world population. To date, about 7000 rare diseases have been documented. However, most of them do not have a known treatment. As a result of the relatively low demand for their treatments caused by their scarce prevalence, the pharmaceutical industry has not sufficiently encouraged the research to develop drugs to treat them. This work aims to analyse potential drug-repositioning strategies for this kind of disease. Drug repositioning seeks to find new uses for existing drugs. In this context, it seeks to discover if rare diseases could be treated with medicines previously indicated to heal other diseases. Our approaches tackle the problem by employing computational methods that calculate similarities between rare and non-rare diseases, considering biological features such as genes, proteins, and symptoms. Drug candidates for repositioning will be checked against clinical trials found in the scientific literature. In this study, 13 different rare diseases have been selected for which potential drugs could be repositioned. By verifying these drugs in the scientific literature, successful cases were found for 75% of the rare diseases studied. The genetic associations and phenotypical features of the rare diseases were examined. In addition, the verified drugs were classified according to the anatomical therapeutic chemical (ATC) code to highlight the types with a higher predisposition to be repositioned. These promising results open the door for further research in this field of study.

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“…Albendazole and fluconazole. Both drugs cause liver failure and can, therefore, trigger liver failure [ 54 ].…”

Section: Resultsmentioning

confidence: 99%

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

et al. 2022

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“…Furthermore, the symptoms described were quite similar to cases of pediatric acute liver failure (PALF), which have been reported in many countries over the past few years. 8 , 9 PALF can be precipitated by disparate etiologies that include drug-induced, metabolic and genetic, infectious, immune-mediated, hemodynamic, and oncologic injuries, depending on the age of the child, and geographic and socioeconomic factors, etc. A definitive diagnosis was not determined in up to 50% of cases.…”

Section: Clinical Settings and Pathology Characteristicsmentioning

confidence: 99%

Acute Hepatitis of Unknown Origin in Children: Early Observations from the 2022 Outbreak

Zhang¹,

Huang²,

Yue³

et al. 2022

J Clin Transl Hepatol

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Recent reports of acute hepatitis of unknown origin in previously healthy children have been increasing worldwide. The main characteristics of the affected children were jaundice and gastrointestinal symptoms. Their serum aminotransaminase levels were above 500 IU/L, with negative tests for hepatitis viruses A-E. By 31 May 2022, the outbreak had affected over 800 children under the age of 16 years in more than 40 countries, resulting in acute liver failure in approximately 10%, including at least 21 deaths and 38 patients requiring liver transplantation. There was still no confirmed cause or causes, although there were several different working hypotheses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adenovirus serotype 41, or SARS-CoV-2 superantigen-mediated immune cell activation. Here, we review early observations of the 2022 outbreak which may inform diagnosis, treatment, and prevention in the context of an overlapping COVID-19 pandemic.

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“…Notably, however, even a single dose treatment (for empirical or seasonal use) of albendazole (400 mg) could cause acute liver toxicity in adult patients [39,[314][315][316][317][318] as well as in children [319][320][321][322]. Such liver toxicity may be recurrent each time after administration of albendazole [317,318,320,321].…”

Section: Albendazolementioning

confidence: 99%

Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update

2021

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The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

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Etiology and Outcome of Acute Liver Failure in Children—The Experience of a Single Tertiary Care Hospital from Romania

Cited by 19 publications

References 24 publications

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

Acute Hepatitis of Unknown Origin in Children: Early Observations from the 2022 Outbreak

Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update

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