Cardoso Mariana F, Carvalho Rita, Correia Fábio Pereira, Branco Joana C, Costa Mariana Nuno, Martins Alexandra
Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal.
GE Port J Gastroenterol. 2023 Aug 16;31(3):203-208. doi: 10.1159/000531773. eCollection 2024 Jun.
The association of hepatitis delta virus (HDV) infection with positive autoantibodies and autoimmune features has been known for decades. However, to date, very few cases of clinical autoimmune hepatitis (AIH) have been reported in association with HDV infection, most of them being in the context of treatment with peginterferon.
This case refers to a 46-year-old woman born in Guinea-Bissau who moved to Portugal in 2018 to investigate complaints of diffuse abdominal discomfort and nausea. Her initial work-up, including laboratory and liver histology, was consistent with type 1 AIH. She had HBe antigen-negative chronic hepatitis B virus infection with negative DNA and also a positive total anti-HDV antibody, with negative IgM and undetectable RNA. Therefore, after initiating prophylactic tenofovir difumarate, she was started on prednisolone followed by azathioprine, which was later stopped due to presumed hepatotoxicity. Repeated histology showed signs of viral superinfection, and she was treated with acyclovir due to a positive herpes simplex IgM, with HDV RNA remaining negative. A third flare in transaminases prompted the introduction of mycophenolate mofetil (MMF) after a thorough exclusion of additional causes of liver disease. About 6 months later, during another bout of hepatitis, HDV RNA was finally positive and classified as genotype 5. MMF was stopped, and, considering a contraindication to interferon, the patient was offered therapy with bulevirtide, which she refused for personal reasons as she is currently living in her home country.
This is a challenging case of autoimmune or "autoimmune-like" hepatitis, probably induced by chronic HDV infection. High suspicion of HDV was essential because, had the case been interpreted as refractory AIH, with escalation of immunosuppression, a more severe course of the viral infection might have ensued. Recently, HDV suppression with bulevirtide was shown to reverse autoimmune liver disease. We hypothesize that the same could have happened to our patient, had she accepted this treatment.
几十年来，人们已经知道丁型肝炎病毒（HDV）感染与自身抗体阳性及自身免疫特征有关。然而，迄今为止，与HDV感染相关的临床自身免疫性肝炎（AIH）病例报道极少，其中大多数是在聚乙二醇干扰素治疗的背景下出现的。
该病例为一名46岁女性，出生于几内亚比绍，2018年移居葡萄牙，因弥漫性腹部不适和恶心前来就诊。她的初步检查，包括实验室检查和肝脏组织学检查，与1型AIH相符。她患有HBe抗原阴性的慢性乙型肝炎病毒感染，DNA阴性，总抗HDV抗体阳性，IgM阴性且RNA检测不到。因此，在开始使用替诺福韦二吡呋酯进行预防后，她开始服用泼尼松龙，随后服用硫唑嘌呤，后者因推测的肝毒性后来停药。重复的组织学检查显示有病毒重叠感染的迹象，由于单纯疱疹病毒IgM阳性，她接受了阿昔洛韦治疗，HDV RNA仍为阴性。转氨酶第三次升高促使在彻底排除其他肝病原因后引入霉酚酸酯（MMF）。大约6个月后, 在另一次肝炎发作期间，HDV RNA最终呈阳性，被分类为5型。MMF停药，考虑到干扰素的禁忌证，为患者提供了布列韦肽治疗，但她因个人原因拒绝了，因为她目前居住在本国。
这是一例具有挑战性的自身免疫性或“自身免疫样”肝炎病例，可能由慢性HDV感染引起。高度怀疑HDV至关重要，因为如果该病例被解释为难治性AIH并增加免疫抑制，可能会导致病毒感染的更严重病程。最近，布列韦肽抑制HDV被证明可逆转自身免疫性肝病。我们推测，如果我们的患者接受这种治疗，可能也会出现同样的情况。
