Abstract：
OBJECTIVE: Cancer immunotherapy has firmly established itself as a pillar of cancer care due to its advantages over traditional anti-tumor therapy but also carries limitations due to potential for severe adverse reactions. This review highlights the current understanding and management of patients with autoimmune and viral hepatitis immune in the setting of immune checkpoint inhibitor (ICI) therapy.
METHODS: A literature search was conducted on PubMed, Scopus, Google Scholar SEER*Stat databases (from inception to December 2022) using search terms: \"immune checkpoint inhibitor\", \"autoimmune hepatitis\", \"viral hepatitis\", \"HBV pathogenesis\", \"HCV pathogenesis\", \"HBV reactivation\", \"HCV reactivation\", \"cancer immunotherapy\", \"immune related adverse events\", \"immune related hepatitis\".
UNASSIGNED: Pre-existing autoimmune disease (AD), whether active or inactive, can predispose patients receiving ICI therapy to develop autoimmune disease flares or immune-related adverse events (irAEs). Thus, patients with AD have routinely been excluded from clinical trials and data on safety of ICI therapy are limited. Hepatic irAE can be seen in ICI therapy and is a distinct entity from autoimmune hepatitis (AIH). ICI therapy alters the immune environment in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Patients who had prior exposure to HBV are at risk for viral reactivation. However, the prevalence of viral hepatitis in patients receiving immunotherapy is under-recognized and can lead to increases in liver biochemical tests as well as deterioration of liver function ultimately limiting treatment.
CONCLUSIONS: The high morbidity and mortality associated with immune-related hepatitis emphasizes the need for screening of underlying diseases, including autoimmune and viral hepatitis, prior to initiation of ICI. Presence of AIH or chronic viral hepatitis is the most important risk factor for hepatic adverse events in ICI therapy. Screening for AIH, HBV and HCV is paramount in patients who will undergo ICI therapy.
METHODS: A literature search was conducted on PubMed, Scopus, Google Scholar SEER*Stat databases (from inception to December 2022) using search terms: \"immune checkpoint inhibitor\", \"autoimmune hepatitis\", \"viral hepatitis\", \"HBV pathogenesis\", \"HCV pathogenesis\", \"HBV reactivation\", \"HCV reactivation\", \"cancer immunotherapy\", \"immune related adverse events\", \"immune related hepatitis\".
UNASSIGNED: Pre-existing autoimmune disease (AD), whether active or inactive, can predispose patients receiving ICI therapy to develop autoimmune disease flares or immune-related adverse events (irAEs). Thus, patients with AD have routinely been excluded from clinical trials and data on safety of ICI therapy are limited. Hepatic irAE can be seen in ICI therapy and is a distinct entity from autoimmune hepatitis (AIH). ICI therapy alters the immune environment in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Patients who had prior exposure to HBV are at risk for viral reactivation. However, the prevalence of viral hepatitis in patients receiving immunotherapy is under-recognized and can lead to increases in liver biochemical tests as well as deterioration of liver function ultimately limiting treatment.
CONCLUSIONS: The high morbidity and mortality associated with immune-related hepatitis emphasizes the need for screening of underlying diseases, including autoimmune and viral hepatitis, prior to initiation of ICI. Presence of AIH or chronic viral hepatitis is the most important risk factor for hepatic adverse events in ICI therapy. Screening for AIH, HBV and HCV is paramount in patients who will undergo ICI therapy.
摘要：
目的：癌症免疫疗法由于其优于传统抗肿瘤疗法的优势，已经牢固地确立了自己作为癌症治疗的支柱，但由于可能出现严重的不良反应，也存在局限性。这篇综述强调了在免疫检查点抑制剂（ICI）治疗的背景下，对自身免疫性和病毒性肝炎免疫患者的当前理解和管理。
方法：在PubMed上进行了文献检索，Scopus,GoogleScholarSEER*Stat数据库（从成立到2022年12月）使用搜索词：“免疫检查点抑制剂”，“自身免疫性肝炎”，“病毒性肝炎”，“HBV发病机理”，“HCV发病机理”，“HBV再激活”，“HCV再激活”，“癌症免疫治疗”，“免疫相关不良事件”，“免疫相关肝炎”。
■预先存在的自身免疫性疾病（AD），无论是活动的还是非活动的，可能会使接受ICI治疗的患者发生自身免疫性疾病耀斑或免疫相关不良事件（irAEs）。因此，AD患者通常被排除在临床试验之外,关于ICI治疗安全性的数据有限.肝irAE可以在ICI治疗中看到，并且是与自身免疫性肝炎（AIH）不同的实体。ICI治疗改变慢性乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染患者的免疫环境。以前接触过HBV的患者有病毒再激活的风险。然而,在接受免疫治疗的患者中,病毒性肝炎的患病率未得到充分的认识,并可能导致肝脏生化检查的增加以及肝功能的恶化,最终限制治疗.
结论：与免疫相关性肝炎相关的高发病率和死亡率强调需要筛查基础疾病，包括自身免疫性肝炎和病毒性肝炎,在ICI开始之前。在ICI治疗中，AIH或慢性病毒性肝炎的存在是肝不良事件的最重要危险因素。AIH筛查，HBV和HCV在接受ICI治疗的患者中至关重要。
方法：在PubMed上进行了文献检索，Scopus,GoogleScholarSEER*Stat数据库（从成立到2022年12月）使用搜索词：“免疫检查点抑制剂”，“自身免疫性肝炎”，“病毒性肝炎”，“HBV发病机理”，“HCV发病机理”，“HBV再激活”，“HCV再激活”，“癌症免疫治疗”，“免疫相关不良事件”，“免疫相关肝炎”。
■预先存在的自身免疫性疾病（AD），无论是活动的还是非活动的，可能会使接受ICI治疗的患者发生自身免疫性疾病耀斑或免疫相关不良事件（irAEs）。因此，AD患者通常被排除在临床试验之外,关于ICI治疗安全性的数据有限.肝irAE可以在ICI治疗中看到，并且是与自身免疫性肝炎（AIH）不同的实体。ICI治疗改变慢性乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染患者的免疫环境。以前接触过HBV的患者有病毒再激活的风险。然而,在接受免疫治疗的患者中,病毒性肝炎的患病率未得到充分的认识,并可能导致肝脏生化检查的增加以及肝功能的恶化,最终限制治疗.
结论：与免疫相关性肝炎相关的高发病率和死亡率强调需要筛查基础疾病，包括自身免疫性肝炎和病毒性肝炎,在ICI开始之前。在ICI治疗中，AIH或慢性病毒性肝炎的存在是肝不良事件的最重要危险因素。AIH筛查，HBV和HCV在接受ICI治疗的患者中至关重要。
