Palmer Melissa, Seekins Daniel, Avigan Mark, Marcinak John, Rockey Don C, Regev Arie, Shastri Vineet K, Lewis James H, Dash Ajit
Liver Consulting LLC, New York, USA.
Patient Safety, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Drug Saf. 2025 Aug 5. doi: 10.1007/s40264-025-01591-0.
While the acute impact of the coronavirus disease 2019 (COVID-19) pandemic has waned, implications for clinical trials remain. In particular, guidance for evaluation of elevated liver tests due to COVID-19, its treatments, and COVID-19 vaccination is lacking. The IQ DILI Initiative, composed of experts from academia, regulatory agencies, and industry herein propose recommendations to address this gap. Extensive literature review was conducted and structured discussions were held between IQ DILI industry members, regulators, and academic experts in hepatology and DILI. Liver-related manifestations in nonhospitalized patients with COVID-19 are highly varied. Evidence of liver injury may occur after COVID-19 symptoms resolve and testing is negative. Treatments for COVID-19 may cause liver injury or alter pharmacokinetics. COVID-19 vaccination has been associated with rare but clear hepatotoxicity, typically consistent with drug-induced autoimmune-like hepatitis, although other presentations, severity, latency, and time to resolution have been reported. Liver injury occurred with mRNA and viral vector vaccines, and in individuals with and without underlying autoimmune or liver diseases. Drug developers and investigators should be aware of the potential liver-related manifestations related to COVID-19, its treatments, and COVID-19 vaccination, as this may impact study eligibility and causality assessment during a trial. COVID-19 testing should be considered part of DILI causality assessment, as a positive test may prevent premature termination of the investigational drug. Since clinical trial participants may not consider vaccinations in their medical history, specific inquiry about their receipt is important when liver tests are abnormal during screening and as part of DILI causality assessment.
虽然2019冠状病毒病（COVID-19）大流行的急性影响已经减弱，但对临床试验的影响依然存在。特别是，目前缺乏针对因COVID-19、其治疗方法以及COVID-19疫苗接种导致的肝功能检查结果升高的评估指南。由学术界、监管机构和行业专家组成的IQ DILI倡议在此提出建议以填补这一空白。开展了广泛的文献综述，并在IQ DILI行业成员、监管机构以及肝病学和药物性肝损伤领域的学术专家之间进行了结构化讨论。非住院COVID-19患者的肝脏相关表现差异很大。肝损伤证据可能在COVID-19症状缓解且检测呈阴性后出现。COVID-19的治疗方法可能会导致肝损伤或改变药代动力学。COVID-19疫苗接种与罕见但明确的肝毒性有关，通常与药物性自身免疫样肝炎一致，不过也有其他表现、严重程度、潜伏期和恢复时间的报道。mRNA疫苗和病毒载体疫苗均出现了肝损伤情况，且无论有无潜在自身免疫或肝脏疾病的个体都有发生。药物研发人员和研究人员应了解与COVID-19、其治疗方法以及COVID-19疫苗接种相关的潜在肝脏相关表现，因为这可能会影响试验期间的研究入选资格和因果关系评估。应将COVID-19检测视为药物性肝损伤因果关系评估的一部分，因为检测呈阳性可能会避免过早终止试验药物。由于临床试验参与者可能不会在病史中提及疫苗接种情况，因此在筛查期间肝功能检查结果异常时以及作为药物性肝损伤因果关系评估的一部分，专门询问他们是否接种过疫苗非常重要。
