Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury

Medina‐Cáliz, Inmaculada; Robles‐Díaz, Mercedes; García‐Muñoz, B.; Stephens, Camilla; Ortega‐Alonso, Aida; García‐Cortés, Miren; González-Jiménez, A.; Sanabria‐Cabrera, Judith; Moreno, Inmaculada; Fernández, M. Carmen; Romero–Gómez, Manuel; Navarro, José María; Barriocanal, A.; Montané, E.; Hallal, Hacibe; Blanco, Sonia; Soriano, Germán; Román, Eva; Gómez-Domínguez, Elena; Castiella, Agustín; Zapata, Eva; Jiménez‐Pérez, Miguel; Moreno, José María Ruiz; Aldea-Perona, Ana; Hernández‐Guerra, Manuel; Prieto, M.; Zoubek, Miguel Eugenio; Kaplowitz, Neil; Lucena, M. Isabel; Andrade, Raúl J.

doi:10.1016/j.jhep.2016.05.003

Cited by 128 publications

(157 citation statements)

References 42 publications

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“…In addition, ALP and TBIL levels in the second month can be a predictor of chronicity or very prolonged recovery . When defined as 12 months of chronicity, the incidence was 17% in another study . In the present study, 26 people recovered within 1 year.…”

Section: Discussionsupporting

confidence: 44%

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Prolonged interval of total bilirubin decline is an early independent predictive factor of chronic persistent drug‐induced liver injury

Zhu

Wang

Zhao

et al. 2019

Hepatology Research

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Aim Chronic drug‐induced liver injury (DILI) with persistent abnormal liver function tests (LFTs) >6 months after cessation of the insulting drugs could progress to cirrhosis. The aim of the present study was to identify the risk factors of chronic DILI for early recognition and better management. Methods History of drug intake and results of LFTs were retrospectively retrieved for patients with a discharge diagnosis of DILI for at least 1‐year follow up. The risk factors independently associated with chronic DILI were analyzed by multiple logistic regression analyses. Results A total of 33 of the 140 DILI patients had persistent abnormal LFTs >6 months, which were considered as chronic DILI. It was found that the time intervals of alanine aminotransferase and total bilirubin decline from the peak to their half peak (T0.5ALT, T0.5TBIL) were significantly longer in the chronic DILI group than that in the recovered group (P = 0.001 and P < 0.001). The risk factors associated with chronic DILI independently were T0.5TBIL (OR 1.315, 95% CI 1.038–1.668), longer period of insulting drug(s) intake (OR 1.018, 95% CI 1.003–1.033), mixed/cholestatic pattern (OR 97.159, 95% CI 1.866–5005.994). More importantly, receiver operating characteristic curve analysis showed that the prognostic value of T0.5TBIL for chronic DILI had a sensitivity of 60.0% at a specificity of 90.7% with the threshold of 16 days. Conclusions The time intervals of total bilirubin decline from its peak to half of its peak (T0.5TBIL) was an early independent predictive factor of chronic DILI, suggesting that T0.5TBIL might serve as an indicator for chronicity.

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Section: Discussionsupporting

confidence: 44%

“…proved that the best cut‐off time is 1 year. In addition, ALP and TBIL levels in the second month can be a predictor of chronicity or very prolonged recovery . When defined as 12 months of chronicity, the incidence was 17% in another study .…”

Section: Discussionmentioning

confidence: 93%

Prolonged interval of total bilirubin decline is an early independent predictive factor of chronic persistent drug‐induced liver injury

Zhu

Wang

Zhao

et al. 2019

Hepatology Research

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“…Besides the low incidence of DILI in statin users, these agents have been implicated in triggering drug-induced autoimmune hepatitis, and are among the top of the list of drugs implicated in chronic outcome after an acute episode of DILI [69•]. This fact is, added to the greater mortality of DILI episodes in patients with pre-existing chronic liver diseases [68•], a matter of particular concern [70].…”

Section: Clinical Studiesmentioning

confidence: 99%

Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects

Vargas

Arrese

Shah

et al. 2017

Curr Gastroenterol Rep

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Purpose of review The purpose of this study is to analyze the current evidence regarding the use of statins in patients with chronic liver disease and cirrhosis. Recent findings Chronic liver disease (CLD), cirrhosis, and its complications, including hepatocellular carcinoma (HCC), are significant public health problems. The use of statins in patients with CLD has been a matter of concern, and physicians are often reluctant to its prescription in these patients. This mainly relates to the potential occurrence of drug-induced liver injury. However, newer evidence from pre-clinical and clinical research has shown that statins are drugs with a potentially beneficial impact on the natural history of cirrhosis, on portal hypertension, and in HCC prevention. Summary In this review, we summarize current evidence regarding the influence of statins in endothelial dysfunction in CLD, their ability to modulate hepatic fibrogenesis, and their vasoprotective effects in portal hypertension; we also focus on existing data about the impact of statins in cirrhosis development, progression, and complications and critically assess the current concerns about its use in patients with CLD.

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“…Many risk factors predispose epileptic patients to idiosyncratic drug-induced mitochondrial dysfunction [155, 181, 182]. These risk factors are typically drug-specific and determination of clinical manifestations for diagnosis and prognosis of hepatotoxicity in a particular patient is difficult [183].…”

Section: Anti-epileptic Drug Hepatotoxicitymentioning

confidence: 99%

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

et al. 2018

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Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area.

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Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury

Cited by 128 publications

References 42 publications

Prolonged interval of total bilirubin decline is an early independent predictive factor of chronic persistent drug‐induced liver injury

Prolonged interval of total bilirubin decline is an early independent predictive factor of chronic persistent drug‐induced liver injury

Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

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