Secular Trends in Severe Idiosyncratic Drug-Induced Liver Injury in North America: An Update From the Acute Liver Failure Study Group Registry

Rao, Ashwin; Rule, Jody; Hameed, Bilal; Ganger, Daniel; Fontana, Robert J.; Lee, William M.

doi:10.14309/ajg.0000000000001655

Cited by 19 publications

(23 citation statements)

References 49 publications

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“…In the present study, the pooled incidence curve for ATLI showed a clear upward trend worldwide, which is consistent with other research findings [ 44 , 45 ]. In recent years, with the extensive use of drugs and the accelerated research of novel drugs, the different types of clinical drugs have been continuously increasing, and the incidence of DILI has been rising year by year [ 46 ], and ATLI is no exception.…”

Section: Discussionsupporting

confidence: 93%

Incidence and Temporal Trend of Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis

Wang

Chen

Hao

et al. 2022

Journal of Tropical Medicine

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Background and Aim. Antituberculosis (anti-TB) drug-induced liver injury (ATLI) is a common and serious adverse drug reaction of tuberculosis treatment, and the incidence of ATLI has been reported to vary from 2.0% to 28.0%. This study aims to estimate the incidence of ATLI in patients who receive anti-TB treatment and describe its temporal trend in the world. Methods. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed, and the protocol was registered in PROSPERO (CRD42020200077). Five electronic databases were searched to identify eligible studies published between 1990 and 2022. Search terms included anti-TB treatment and drug-induced liver injury. Studies that reported the incidence of ATLI or provided sufficient data to calculate the incidence of ATLI were included, and duplicate studies were excluded. Meta-analysis was conducted on the basis of logit-transformed metrics for the incidence of ATLI with 95% confidence intervals (CIs), followed by a predefined subgroup meta-analysis. Temporal trend analyses were performed to describe the change in pooled incidence over time. A random effects metaregression was conducted to explore the source of heterogeneity. All statistical analyses were carried out using R 4.0.1. Results. A total of 160 studies from 156 records with 116147 patients were included in the meta-analysis. Based on the random effects model, the pooled incidence of ATLI was 11.50% (95% CI: 10.10%–12.97%) and showed an upward trend over time ( P < 0.001 ). Patients who received first-line anti-TB drugs, patients in South America, and patients with hepatitis B and C virus coinfection had a higher incidence of ATLI (13.66%, 18.16%, and 39.19%, respectively). Sensitivity analyses also confirmed this robust incidence after the exclusion of some studies. The metaregression showed that different anti-TB regimens and geographical regions were important explanatory factors of the heterogeneity between studies. Conclusions. The present systematic review provided a basis for estimating the incidence of ATLI worldwide, which varied among patients with different anti-TB regimens in different geographical regions and with different coinfections and had an upward trend. Regular liver function monitoring is imperative for patient safety during the anti-TB treatment course.

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Section: Discussionsupporting

confidence: 93%

Incidence and Temporal Trend of Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis

Wang

Chen

Hao

et al. 2022

Journal of Tropical Medicine

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“…Previously, most of them had advanced coma grade ≥2 (68%) (117). Newer data suggest a reversal in this trend, with most (66.4%) presenting with lower-grade encephalopathy (118). Most patients have deep jaundice, with bilirubin levels generally >15 mg/dL.…”

Section: Etiology-specific Managementmentioning

confidence: 99%

Acute Liver Failure Guidelines

et al. 2023

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Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.

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“…12 Within the overall DILI group, the mix of drugs implicated has evolved; antibiotics remain the most common overall group, but the incidence of HDSs has doubled in the past decade from 10 to 20%. 13 Overall, ALF due to HDS are associated with worse overall outcomes than other forms of DILI and will be discussed in more detail below. Certain agents are less commonly used and thus less frequently implicated.…”

Section: Section I: Etiologies and Diagnosismentioning

confidence: 99%

“…Medications that are declining in use/incidence include phenytoin, isoniazid, nitrofurantoin, and the early and toxic highly active antiretroviral agents. 13…”

Section: Section I: Etiologies and Diagnosismentioning

confidence: 99%

“…Medications that are declining in use/incidence include phenytoin, isoniazid, nitrofurantoin, and the early and toxic highly active antiretroviral agents. 13 In summary, evolution of different etiologies over the past two decades has been relatively minimal for overall groups (APAP, DILI, AIH) while changes within the groups have been seen. We are not aware of differing trends in etiologies worldwide over this same time period.…”

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confidence: 97%

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Management of Acute Liver Failure: Update 2022

2022

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Abbreviated pathogenesis and clinical course of the acute liver failure syndrome. The pathogenesis and clinical course of the syndrome of acute liver failure (ALF) differs depending upon the etiology of the primary liver injury. In turn, the severity of the liver injury and resulting synthetic failure is often the primary determinant of whether a patient is referred for emergency liver transplantation. Injuries by viral etiologies trigger the innate immune system via pathogen-associated molecular patterns (PAMPs), while toxin-induced (and presumably ischemia-induced) injuries do so via damage-associated molecular patterns (DAMPs). The course of the clinical syndrome further depends upon the relative intensity and composition of cytokine release, resulting in an early proinflammatory phenotype (SIRS) and later compensatory anti-inflammatory response phenotype (CARS). The outcomes of overwhelming immune activation are the systemic (extrahepatic) features of ALF (cardiovascular collapse, cerebral edema, acute kidney injury, respiratory failure, sepsis) which ultimately determine the likelihood of death.Acute liver failure (ALF) continues to carry a high risk of mortality or the need for transplantation despite recent improvements in overall outcomes over the past two decades. Optimal management begins with identifying that liver failure is indeed present and its etiology, since outcomes and the need for transplantation vary widely across the different etiologies. Most causes of ALF can be divided into hyperacute (ischemia and acetaminophen) and subacute types (other etiologies), based on time of evolution of signs and symptoms of liver failure; the former evolve in 3 to 4 days and the latter typically in 2 to 4 weeks. Both involve intense release of cytokines and hepatocellular contents into the circulation with multiorgan effects/consequences.Management involves optimizing fluid balance and cardiovascular support, including the use of continuous renal replacement therapy, vasopressors, and pulmonary ventilation. Early evaluation for liver transplantation is advised particularly for acetaminophen toxicity, which evolves so rapidly that delay is likely to lead to death.Vasopressor support, high-grade hepatic encephalopathy, and unfavorable (subacute) etiologies heighten the need for urgent listing for liver transplantation. Prognostic scores such as Kings Criteria, Model for End-Stage Liver Disease, and the Acute Liver Failure Group prognostic index take these features into account and provide reasonable but imperfect predictive accuracy. Future treatments may include liver support devices and/or agents that improve hepatocyte regeneration.

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Secular Trends in Severe Idiosyncratic Drug-Induced Liver Injury in North America: An Update From the Acute Liver Failure Study Group Registry

Cited by 19 publications

References 49 publications

Incidence and Temporal Trend of Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis

Incidence and Temporal Trend of Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis

Acute Liver Failure Guidelines

Management of Acute Liver Failure: Update 2022

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