Biphasic effects of ethanol consumption on N,N-dimethylformamide-induced liver injury in mice.

N,N-Dimethylformamide (DMF) is a well-documented occupational hazardous material, which can induce occupational liver injury. The current study was designed to investigate whether ethanol consumption can affect DMF-induced hepatotoxicity and the potential underlying mechanisms involved. We found that a single dose of ethanol (1.25, 2.5, or 5 g/kg bw by gavage) significantly repressed the increase in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and alleviated the liver histopathological changes in mice challenged with 3 g/kg DMF. In contrast, long-term moderate drinking (2.5 g/kg bw) significantly aggravated the repeated DMF (0.7 g/kg bw) exposure-induced increase in the serum ALT and AST activities. Mechanistically, acute ethanol consumption suppressed DMF-induced activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome, while long-term moderate ethanol consumption promoted hepatocyte apoptosis in the mouse liver. Notably, cytochrome P4502E1 (CYP2E1) protein level and activity in mouse livers were not significantly affected by ethanol per se in the two models. These results confirm that regular drinking can increase the risk of DMF-induced hepatotoxicity, and suggest that DMF-handling workers should avoid consuming ethanol to reduce the risk of DMF-indued liver injury.

A Case of Liver Injury after Exposure to Isopropanol: A Challenging Diagnosis.

Drug-induced liver injury is hardly diagnosed, considering not only the wide range of hepatotoxic substances but also the diversity of associated phenotypes and the absence of specific biomarkers. Symptom chronology, drug or toxic exposure, and temporal association help to establish the diagnosis. Exposure to isopropanol has known but rare toxic effects. We report the clinical case of a 33-year-old female hairdresser admitted to the hospital with fatigue, epigastric pain, and jaundice. She presented the following values: aspartate aminotransferase, 485 U/L; alanine transaminase, 908 U/L; ALP, 240 U/L; GGT, 370 U/L; total bilirubin, 3.5 mg/dL; and direct bilirubin, 2.1 mg/dL. Albumin, platelet, and INR values were normal. Structural, infectious, immune, and vascular causes were excluded. Liver biopsy was suggestive of toxic hepatitis. A possible association with ibuprofen intake was considered. The patient resumed professional activity, with fatigue and jaundice relapse, as well as a new liver enzyme increase, despite ibuprofen withdrawal. It was concluded that a new hair product containing isopropanol had recently been introduced. As soon as its professional use was discontinued, there was no recurrence of the symptoms. Given the temporal association between the development of acute hepatitis and the use of an isopropanol-containing product, liver toxicity by exposure to isopropanol was assumed. This substance is metabolized in the liver and toxicity may occur by ingestion, skin exposure, or inhalation, and it is described in cases of occupational or accidental exposure. The treatment is symptomatic and comprises toxic suspension.

A lesão hepática induzida por tóxicos é um dos distúrbios de mais difícil diagnóstico, quer pela existência de múltiplos hepatotóxicos, quer pela diversidade de fenótipos associados e ausência de biomarcadores específicos. A cronologia dos sintomas, exposição a fármacos ou tóxicos e associação temporal auxilia o diagnóstico. A exposição a isopropanol tem efeitos tóxicos conhecidos e raros. Descrevemos o caso clínico de uma mulher de 33 anos, cabeleireira, admitida por fadiga, epigastralgias e icterícia. Apresentava AST 485 U/L, ALT 908 U/L, FA 240 U/L, GGT 370 U/L, bilirrubina total 3,5 mg/dL e bilirrubina direta 2,1 mg/dL; o doseamento sérico de albumina, plaquetas e o valor de INR eram normais. Foram excluídas lesões estruturais, causas infeciosas, imunes e vasculares. Biópsia hepática sugestiva de hepatite tóxica. Considerada possível associação a toma de ibuprofeno. Retomou atividade profissional, com recorrência de fadiga e icterícia, bem como elevação das enzimas hepáticas novamente, apesar de suspensão de ibuprofeno. Apurada exposição a tóxicos profissionais, percebendo-se que o quadro coincidiu com início da utilização de novo produto capilar contendo isopropanol. A doente retomou atividade profissional, não utilizando o produto, sem recorrência. Dada a relação temporal entre o desenvolvimento de hepatite aguda e a utilização de produtos contendo isopropanol, assumiu-se hepatotoxicidade por exposição profissional ao isopropanol. Esta substância é metabolizada no fígado e a toxicidade pode ocorrer por ingestão, exposição cutânea ou inalação, estando descrita em casos de exposição ocupacional ou acidental. O tratamento é sintomático e inclui a suspensão do tóxico.

EASL clinical practice guidelines for the management of occupational liver diseases.

The Clinical Practice Guidelines (CPG) on Occupational Liver Diseases (OLD) of the European Association for the Study of the Liver (EASL) have been developed to increase awareness, recognition and improve management of patients with OLD. Indeed, although workplace exposure has been associated with virtually the entire spectrum of acute and chronic liver diseases, data on the epidemiology of OLD are scarce. These diseases may be a result of high-level accidental exposure or prolonged lower level exposure to a variety of chemicals including solvents, pesticides, metals and other agents. While acute liver diseases related to OLD are uncommon and easily recognized, chronic liver diseases are relatively more frequent but often overlooked because of their asymptomatic course and an insidious onset which is often accompanied by comorbidities. Because of the absence of data in observational studies and meta-analyses or systematic reviews, the evidence and recommendations in these guidelines have been graded according to the Oxford Centre for Evidence-based Medicine, which assesses evidence according to diagnostic, prevalence, aetiological, prognostic or preventive categories. They can still generate grades of recommendation even when the evidence is inconclusive.