Increased Risk of Subclinical Hepatic Injury in Children Exposed to Thiodiglycolic Acid

Abstract Background Nintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes. Methods We analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined. Results Fifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO) < 55% predicted, were associated with increased risk of hepatic injury (adjusted hazard ratio [aHR] was 3.46; 95% CI 1.13–10.60; p = 0.029 for KL-6, and 6.05; 95% CI 1.89–19.32; p = 0.002 for DLCO). Both factors also predicted severe and recurrent hepatic injury. Patients with baseline KL-6 ≥ 2.5 ng/mL also had a higher risk of AE-IPF (aHR 4.52; 95% CI 1.63–12.55; p = 0.004). For on-treatment mortality, baseline KL-6 ≥ 3.5 ng/mL and SPA ≥ 600 pg/mL were significant predictors (aHR 5.39; 95% CI 1.16–24.97; p = 0.031 for KL-6, and aHR 12.28; 95% CI 2.06–73.05; p = 0.006 for SPA). Results from subdistribution hazard regression and sensitivity analyses supported these findings. Patients with elevated baseline plasma KL-6 levels also exhibited a trend towards faster pulmonary function decline. Conclusions For patients with IPF who are receiving nintedanib, we have identified baseline predictors, in particular plasma KL-6 levels, for the risk of adverse outcomes. Patients with these predictors may require close monitoring for unfavourable responses during treatment. Our findings also support the prognostic role of molecular markers like KL-6 and may contribute to future formulation of more individualized therapeutic strategies for IPF.

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Urinary thiodiglycolic acid is associated with increased risk of non-alcoholic fatty liver disease in children living near a petrochemical complex

Environment International ◽

10.1016/j.envint.2019.104978 ◽

2019 ◽

Vol 131 ◽

pp. 104978 ◽

Cited By ~ 3

Author(s):

Chih-Wen Wang ◽

Hung-Yi Chuang ◽

Kai-Wei Liao ◽

Ming-Lung Yu ◽

Chia-Yen Dai ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Petrochemical Complex ◽

Thiodiglycolic Acid ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease

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An overview of COVID-19 induced gastrointestinal symptoms and liver dysfunction (Preprint)

10.2196/preprints.29648 ◽

2021 ◽

Author(s):

Obaid Rehman

Keyword(s):

Hepatic Injury ◽

Gastrointestinal Symptoms ◽

Prior History ◽

Rt Pcr ◽

Current Management ◽

Increased Risk ◽

Risk Of Progression ◽

History Of ◽

Polymerase Chain ◽

New Onset

UNSTRUCTURED The ongoing pandemic of COVID-19 beginning in December 2019 has caused widespread devastation to many individuals worldwide. Gastrointestinal manifestations and complications associated with SARS-CoV-2 are some of the less discussed implications of this virus. The initial gastrointestinal symptoms noted in COVID-19 patients are mainly diarrhea, nausea, poor appetite, anorexia, vomiting, diarrhea, and abdominal pain, as well as new onset of hepatic injury. Additionally, patients with a prior history of hepatic comorbidities have increased risk of progression to severe COVID-19. Presently, real-time reverse transcription polymerase chain reaction (RT-PCR), serological based tests, and imaging are used to achieve a definitive diagnosis. The current management of COVID-19 is supportive care along with antiviral, anti-inflammatory and analgesic therapy. The use of microbiota transplantation for COVID-19 management is also discussed. The importance of this article is to enlighten the overall understanding of COVID-19 induced gastrointestinal and liver pathophysiology, diagnosis, management, and prognosis.

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Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats

Journal of Toxicology ◽

10.1155/2017/6746989 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Star Khoza ◽

Ishmael Moyo ◽

Denver Ncube

Keyword(s):

Liver Injury ◽

Hepatic Injury ◽

Antifungal Agents ◽

Liver Enzymes ◽

Control Group ◽

Poor Correlation ◽

Histopathological Changes ◽

Increased Risk ◽

The Subject ◽

Oral Doses

Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p=0.0017) and AST levels (p=0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p<0.0001). The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.

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Factors independently associated with increased risk of pain development after ophthalmic surgery

European Journal of Anaesthesiology ◽

10.1017/s0265021504002042 ◽

2004 ◽

Vol 21 (2) ◽

pp. 101-106

Author(s):

D. Henzler ◽

R. Kramer ◽

U. H. Steinhorst ◽

S. Piepenbrock ◽

R. Rossaint ◽

...

Keyword(s):

Ophthalmic Surgery ◽

Increased Risk

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Site of Lysosome Production During Hepatic Injury

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100063652 ◽

1969 ◽

Vol 27 ◽

pp. 348-349

Author(s):

Nalin J. Unakar

Keyword(s):

Electron Microscopy ◽

Golgi Apparatus ◽

Mouse Liver ◽

Hepatic Injury ◽

Close Approximation ◽

Experimental Conditions ◽

Toxic Injury

The increased number of lysosomes as well as the close approximation of lysosomes to the Golgi apparatus in tissue under variety of experimental conditions is commonly observed. These observations suggest Golgi involvement in lysosomal production. The role of the Golgi apparatus in the production of lysosomes in mouse liver was studied by electron microscopy of liver following toxic injury by CCI4.

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