PDF(Pubmed)
Abstract：
BACKGROUND: An outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 was subsequently linked to infections with adenovirus-associated virus 2 and other \'helper viruses\', including human adenovirus. It is possible that evidence of such an outbreak could be identified at a population level based on routine data captured by electronic health records (EHR).
METHODS: We used anonymised EHR to collate retrospective data for all emergency presentations to Oxford University Hospitals NHS Foundation Trust in the UK, between 2016-2022, for all ages from 18 months and older. We investigated clinical characteristics and temporal distribution of presentations of acute hepatitis and of adenovirus infections based on laboratory data and clinical coding. We relaxed the stringent case definition adopted during the AS-Hep-UA to identify all cases of acute hepatitis with unknown aetiology (termed AHUA). We compared events within the outbreak period (defined as 1st Oct 2021-31 Aug 2022) to the rest of our study period.
RESULTS: Over the study period, there were 903,433 acute presentations overall, of which 391 (0.04%) were classified as AHUA. AHUA episodes had significantly higher critical care admission rates (p < 0.0001, OR = 41.7, 95% CI:26.3-65.0) and longer inpatient admissions (p < 0.0001) compared with the rest of the patient population. During the outbreak period, significantly more adults (≥ 16 years) were diagnosed with AHUA (p < 0.0001, OR = 3.01, 95% CI: 2.20-4.12), and there were significantly more human adenovirus (HadV) infections in children (p < 0.001, OR = 1.78, 95% CI:1.27-2.47). There were also more HAdV tests performed during the outbreak (p < 0.0001, OR = 1.27, 95% CI:1.17-1.37). Among 3,707 individuals who were tested for HAdV, 179 (4.8%) were positive. However, there was no evidence of more acute hepatitis or increased severity of illness in HadV-positive compared to negative cases.
CONCLUSIONS: Our results highlight an increase in AHUA in adults coinciding with the period of the outbreak in children, but not linked to documented HAdV infection. Tracking changes in routinely collected clinical data through EHR could be used to support outbreak surveillance.
METHODS: We used anonymised EHR to collate retrospective data for all emergency presentations to Oxford University Hospitals NHS Foundation Trust in the UK, between 2016-2022, for all ages from 18 months and older. We investigated clinical characteristics and temporal distribution of presentations of acute hepatitis and of adenovirus infections based on laboratory data and clinical coding. We relaxed the stringent case definition adopted during the AS-Hep-UA to identify all cases of acute hepatitis with unknown aetiology (termed AHUA). We compared events within the outbreak period (defined as 1st Oct 2021-31 Aug 2022) to the rest of our study period.
RESULTS: Over the study period, there were 903,433 acute presentations overall, of which 391 (0.04%) were classified as AHUA. AHUA episodes had significantly higher critical care admission rates (p < 0.0001, OR = 41.7, 95% CI:26.3-65.0) and longer inpatient admissions (p < 0.0001) compared with the rest of the patient population. During the outbreak period, significantly more adults (≥ 16 years) were diagnosed with AHUA (p < 0.0001, OR = 3.01, 95% CI: 2.20-4.12), and there were significantly more human adenovirus (HadV) infections in children (p < 0.001, OR = 1.78, 95% CI:1.27-2.47). There were also more HAdV tests performed during the outbreak (p < 0.0001, OR = 1.27, 95% CI:1.17-1.37). Among 3,707 individuals who were tested for HAdV, 179 (4.8%) were positive. However, there was no evidence of more acute hepatitis or increased severity of illness in HadV-positive compared to negative cases.
CONCLUSIONS: Our results highlight an increase in AHUA in adults coinciding with the period of the outbreak in children, but not linked to documented HAdV infection. Tracking changes in routinely collected clinical data through EHR could be used to support outbreak surveillance.
摘要：
背景：2022年期间儿童急性重症病因不明肝炎（AS-Hep-UA）的爆发随后与腺病毒相关病毒2和其他“辅助病毒”的感染有关，包括人类腺病毒。根据电子健康记录（EHR）捕获的常规数据，有可能在人群水平上识别这种爆发的证据。
方法：我们使用匿名的EHR来整理向英国牛津大学医院NHS基金会信托基金提供的所有急诊报告的回顾性数据，在2016年至2022年之间，适用于18个月及以上的所有年龄。我们根据实验室数据和临床编码调查了急性肝炎和腺病毒感染的临床特征和时间分布。我们放宽了AS-Hep-UA期间采用的严格病例定义，以识别所有病因不明的急性肝炎病例（称为AHUA）。我们将爆发期（定义为2021年10月1日至2022年8月31日）内的事件与我们研究期的其余部分进行了比较。
结果：在研究期间，总共有903433次急性表现，其中391人（0.04%）被归类为AHUA。与其他患者人群相比，AHUA发作的重症监护入院率明显更高（p<0.0001，OR=41.7，95％CI：26.3-65.0），住院时间更长（p<0.0001）。在爆发期间，诊断为AHUA的成年人（≥16岁）显着增加（p<0.0001，OR=3.01，95％CI：2.20-4.12），儿童中人类腺病毒（HadV）感染明显增多（p<0.001，OR=1.78，95％CI：1.27-2.47）。在爆发期间也有更多的HAdV测试（p<0.0001，OR=1.27，95％CI：1.17-1.37）。在3,707名接受HAdV测试的人中，179（4.8%）为阳性。然而,与阴性病例相比,在HadV阳性病例中,没有证据显示更多急性肝炎或疾病严重程度增加.
结论：我们的研究结果突出表明，成人中AHUA的增加与儿童中的爆发时期相吻合，但与记录的HAdV感染无关。通过EHR跟踪常规收集的临床数据的变化可用于支持爆发监测。
方法：我们使用匿名的EHR来整理向英国牛津大学医院NHS基金会信托基金提供的所有急诊报告的回顾性数据，在2016年至2022年之间，适用于18个月及以上的所有年龄。我们根据实验室数据和临床编码调查了急性肝炎和腺病毒感染的临床特征和时间分布。我们放宽了AS-Hep-UA期间采用的严格病例定义，以识别所有病因不明的急性肝炎病例（称为AHUA）。我们将爆发期（定义为2021年10月1日至2022年8月31日）内的事件与我们研究期的其余部分进行了比较。
结果：在研究期间，总共有903433次急性表现，其中391人（0.04%）被归类为AHUA。与其他患者人群相比，AHUA发作的重症监护入院率明显更高（p<0.0001，OR=41.7，95％CI：26.3-65.0），住院时间更长（p<0.0001）。在爆发期间，诊断为AHUA的成年人（≥16岁）显着增加（p<0.0001，OR=3.01，95％CI：2.20-4.12），儿童中人类腺病毒（HadV）感染明显增多（p<0.001，OR=1.78，95％CI：1.27-2.47）。在爆发期间也有更多的HAdV测试（p<0.0001，OR=1.27，95％CI：1.17-1.37）。在3,707名接受HAdV测试的人中，179（4.8%）为阳性。然而,与阴性病例相比,在HadV阳性病例中,没有证据显示更多急性肝炎或疾病严重程度增加.
结论：我们的研究结果突出表明，成人中AHUA的增加与儿童中的爆发时期相吻合，但与记录的HAdV感染无关。通过EHR跟踪常规收集的临床数据的变化可用于支持爆发监测。
