TY  - JOUR
AU  - Bokan, Goran
AU  - Glamočanin, Tanja
AU  - Mavija, Zoran
AU  - Vidović, Bojana
AU  - Stojanović, Ana
AU  - Björnsson, Einar S.
AU  - Vučić, Vesna
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1341
AB  - Herb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity. Due to various biological activities, ashwagandha and its extracts became widespread as herbal supplements on the global market. Although it is generally considered safe, there are several reported cases of ashwagandha-related liver injury, and one case ended with liver transplantation. In this paper, we review all reported cases so far. Additionally, we describe two new cases of ashwagandha hepatotoxicity. In the first case, a 36-year-old man used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. In the second case, a 30-year-old woman developed pruritus after 45 days of using ashwagandha capsules (450 mg). In both cases, serum bilirubin and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were increased. The liver injury pattern was hepatocellular (R-value 11.1) and mixed (R-value 2.6), respectively. The updated Roussel Uclaf Causality Assessment Method (RUCAM) (both cases with a score of seven) indicated a “probable” relationship with ashwagandha. Clinical and liver function improvements were observed after the discontinuation of ashwagandha supplement use. By increasing the data related to ashwagandha-induced liver injury, these reports support that consuming ashwagandha supplements is not without its safety concerns.
PB  - Multidisciplinary Digital Publishing Institute (MDPI)
T2  - Pharmaceuticals
T2  - Pharmaceuticals
T1  - Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause
IS  - 8
VL  - 16
DO  - 10.3390/ph16081129
ER  - 

@article{
author = "Bokan, Goran and Glamočanin, Tanja and Mavija, Zoran and Vidović, Bojana and Stojanović, Ana and Björnsson, Einar S. and Vučić, Vesna",
year = "2023",
abstract = "Herb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity. Due to various biological activities, ashwagandha and its extracts became widespread as herbal supplements on the global market. Although it is generally considered safe, there are several reported cases of ashwagandha-related liver injury, and one case ended with liver transplantation. In this paper, we review all reported cases so far. Additionally, we describe two new cases of ashwagandha hepatotoxicity. In the first case, a 36-year-old man used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. In the second case, a 30-year-old woman developed pruritus after 45 days of using ashwagandha capsules (450 mg). In both cases, serum bilirubin and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were increased. The liver injury pattern was hepatocellular (R-value 11.1) and mixed (R-value 2.6), respectively. The updated Roussel Uclaf Causality Assessment Method (RUCAM) (both cases with a score of seven) indicated a “probable” relationship with ashwagandha. Clinical and liver function improvements were observed after the discontinuation of ashwagandha supplement use. By increasing the data related to ashwagandha-induced liver injury, these reports support that consuming ashwagandha supplements is not without its safety concerns.",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
journal = "Pharmaceuticals, Pharmaceuticals",
title = "Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause",
number = "8",
volume = "16",
doi = "10.3390/ph16081129"
}

Bokan, G., Glamočanin, T., Mavija, Z., Vidović, B., Stojanović, A., Björnsson, E. S.,& Vučić, V.. (2023). Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. in Pharmaceuticals
Multidisciplinary Digital Publishing Institute (MDPI)., 16(8).
https://doi.org/10.3390/ph16081129

Bokan G, Glamočanin T, Mavija Z, Vidović B, Stojanović A, Björnsson ES, Vučić V. Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. in Pharmaceuticals. 2023;16(8).
doi:10.3390/ph16081129 .

Bokan, Goran, Glamočanin, Tanja, Mavija, Zoran, Vidović, Bojana, Stojanović, Ana, Björnsson, Einar S., Vučić, Vesna, "Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause" in Pharmaceuticals, 16, no. 8 (2023),
https://doi.org/10.3390/ph16081129 . .

TY  - JOUR
AU  - Björnsson, Einar S.
AU  - Vučić, Vesna M.
AU  - Stirnimann, Guido
AU  - Robles-Díaz, Mercedes
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1216
AB  - Introduction: Apart from cessation of the implicated agent leading to drug-induced liver injury (DILI), there is no standard therapy for DILI. Corticosteroids have been used in DILI, although their efficacy is unclear. Published data showed either beneficial effects or no improvement associated with steroid therapy. The aim of the current study was to perform a systematic review of the role of corticosteroids in the treatment of DILI. Methods: A search was performed in PubMed, searching for the terms: “corticosteroids” and “drug-induced liver injury”. Observation studies were included, but case reports excluded. Results: A total of 24 papers were retrieved. Most of these were observational studies on the effects of corticosteroids in moderate/severe DILI (n = 8), reports on the corticosteroid treatment in patients with drug-induced autoimmune hepatitis (DI-AIH) (n = 5), and effects of corticosteroids in drug-induced fulminant acute liver failure (ALF, n = 2). Furthermore, treatment of corticosteroids in patients with liver injury due to check point inhibitors (CPIs) was addressed in nine studies. In moderate/severe DILI, six out of eight studies suggested steroid treatment to be beneficial, whereas two studies showed negative results. All five observational studies on the effects of corticosteroids in DI-AIH showed good therapeutic response with rapid and long lasting effects after discontinuation of corticosteroids and without evidence of relapse. Steroid therapy was not associated with improved overall survival in patients with drug-induced fulminant ALF. CPIs-induced liver injury was found to improve spontaneously in 33–50% without corticosteroids, and the rate of patients who were treated responded to steroids in 33–100% (mean 72%). Conclusions: The majority of studies analyzing the effects of corticosteroids in moderate/severe DILI have demonstrated beneficial effects. However, this was not the case in drug-induced fulminant ALF. Patients with DI-AIH had an excellent response to corticosteroids. The majority of those with CPIs-induced liver injury responded to corticosteroids; however, patients without treatment usually recovered spontaneously. The observational design and comparison with historical controls in these studies makes it very difficult to draw conclusions on the efficacy of corticosteroids in DILI. Therefore, there is a strong need for a randomized controlled trial to properly assess the role of corticosteroids in DILI.
PB  - Frontiers Media S.A.
T2  - Frontiers in Pharmacology
T1  - Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review
SP  - 820724
VL  - 13
DO  - 10.3389/fphar.2022.820724
ER  - 

@article{
author = "Björnsson, Einar S. and Vučić, Vesna M. and Stirnimann, Guido and Robles-Díaz, Mercedes",
year = "2022",
abstract = "Introduction: Apart from cessation of the implicated agent leading to drug-induced liver injury (DILI), there is no standard therapy for DILI. Corticosteroids have been used in DILI, although their efficacy is unclear. Published data showed either beneficial effects or no improvement associated with steroid therapy. The aim of the current study was to perform a systematic review of the role of corticosteroids in the treatment of DILI. Methods: A search was performed in PubMed, searching for the terms: “corticosteroids” and “drug-induced liver injury”. Observation studies were included, but case reports excluded. Results: A total of 24 papers were retrieved. Most of these were observational studies on the effects of corticosteroids in moderate/severe DILI (n = 8), reports on the corticosteroid treatment in patients with drug-induced autoimmune hepatitis (DI-AIH) (n = 5), and effects of corticosteroids in drug-induced fulminant acute liver failure (ALF, n = 2). Furthermore, treatment of corticosteroids in patients with liver injury due to check point inhibitors (CPIs) was addressed in nine studies. In moderate/severe DILI, six out of eight studies suggested steroid treatment to be beneficial, whereas two studies showed negative results. All five observational studies on the effects of corticosteroids in DI-AIH showed good therapeutic response with rapid and long lasting effects after discontinuation of corticosteroids and without evidence of relapse. Steroid therapy was not associated with improved overall survival in patients with drug-induced fulminant ALF. CPIs-induced liver injury was found to improve spontaneously in 33–50% without corticosteroids, and the rate of patients who were treated responded to steroids in 33–100% (mean 72%). Conclusions: The majority of studies analyzing the effects of corticosteroids in moderate/severe DILI have demonstrated beneficial effects. However, this was not the case in drug-induced fulminant ALF. Patients with DI-AIH had an excellent response to corticosteroids. The majority of those with CPIs-induced liver injury responded to corticosteroids; however, patients without treatment usually recovered spontaneously. The observational design and comparison with historical controls in these studies makes it very difficult to draw conclusions on the efficacy of corticosteroids in DILI. Therefore, there is a strong need for a randomized controlled trial to properly assess the role of corticosteroids in DILI.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Pharmacology",
title = "Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review",
pages = "820724",
volume = "13",
doi = "10.3389/fphar.2022.820724"
}

Björnsson, E. S., Vučić, V. M., Stirnimann, G.,& Robles-Díaz, M.. (2022). Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review. in Frontiers in Pharmacology
Frontiers Media S.A.., 13, 820724.
https://doi.org/10.3389/fphar.2022.820724

Björnsson ES, Vučić VM, Stirnimann G, Robles-Díaz M. Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review. in Frontiers in Pharmacology. 2022;13:820724.
doi:10.3389/fphar.2022.820724 .

Björnsson, Einar S., Vučić, Vesna M., Stirnimann, Guido, Robles-Díaz, Mercedes, "Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review" in Frontiers in Pharmacology, 13 (2022):820724,
https://doi.org/10.3389/fphar.2022.820724 . .