Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland.
Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor.
JAMA. 2023 Dec 26;330(24):2376-2387. doi: 10.1001/jama.2023.23242.
Hepatitis D virus (HDV) infection occurs in association with hepatitis B virus (HBV) infection and affects approximately 12 million to 72 million people worldwide. HDV causes more rapid progression to cirrhosis and higher rates of hepatocellular carcinoma than HBV alone or hepatitis C virus.
HDV requires HBV to enter hepatocytes and to assemble and secrete new virions. Acute HDV-HBV coinfection is followed by clearance of both viruses in approximately 95% of people, whereas HDV superinfection in an HBV-infected person results in chronic HDV-HBV infection in more than 90% of infected patients. Chronic hepatitis D causes more rapidly progressive liver disease than HBV alone. Approximately 30% to 70% of patients with chronic hepatitis D have cirrhosis at diagnosis and more than 50% die of liver disease within 10 years of diagnosis. However, recent studies suggested that progression is variable and that more than 50% of people may have an indolent course. Only approximately 20% to 50% of people infected by hepatitis D have been diagnosed due to lack of awareness and limited access to reliable diagnostic tests for the HDV antibody and HDV RNA. The HBV vaccine prevents HDV infection by preventing HBV infection, but no vaccines are available to protect those with established HBV infection against HDV. Interferon alfa inhibits HDV replication and reduces the incidence of liver-related events such as liver decompensation, hepatocellular carcinoma, liver transplant, or mortality from 8.5% per year to 3.3% per year. Adverse effects from interferon alfa such as fatigue, depression, and bone marrow suppression are common. HBV nucleos(t)ide analogues, such as entecavir or tenofovir, are ineffective against HDV. Phase 3 randomized clinical trials of bulevirtide, which blocks entry of HDV into hepatocytes, and lonafarnib, which interferes with HDV assembly, showed that compared with placebo or observation, these therapies attained virological and biochemical response in up to 56% of patients after 96 weeks of bulevirtide monotherapy and 19% after 48 weeks of lonafarnib, ritonavir, and pegylated interferon alfa treatment.
HDV infection affects approximately 12 million to 72 million people worldwide and is associated with more rapid progression to cirrhosis and liver failure and higher rates of hepatocellular carcinoma than infection with HBV alone. Bulevirtide was recently approved for HDV in Europe, whereas pegylated interferon alfa is the only treatment available in most countries.
丁型肝炎病毒（HDV）感染与乙型肝炎病毒（HBV）感染相关，全球约有 1200 万至 7200 万人受到影响。HDV 导致肝硬化和肝细胞癌的发生率比 HBV 或丙型肝炎病毒更高。
HDV 需要 HBV 进入肝细胞并组装和分泌新的病毒颗粒。急性 HDV-HBV 合并感染后，约 95%的人会清除两种病毒，而 HBV 感染者的 HDV 超感染会导致超过 90%的感染者慢性 HDV-HBV 感染。慢性丁型肝炎比单独的 HBV 引起更快速的肝病进展。大约 30%至 70%的慢性肝炎 D 患者在诊断时已患有肝硬化，超过 50%的患者在诊断后 10 年内死于肝病。然而，最近的研究表明，进展情况各不相同，超过 50%的人可能病情较为隐匿。由于缺乏意识和获得可靠的 HDV 抗体和 HDV RNA 诊断检测的机会有限，只有大约 20%至 50%的感染 HDV 的人得到诊断。HBV 疫苗通过预防 HBV 感染来预防 HDV 感染，但没有疫苗可用于保护那些已患有 HBV 感染的人免受 HDV 感染。干扰素 alfa 抑制 HDV 复制，降低肝脏相关事件（如肝功能失代偿、肝细胞癌、肝移植或死亡率）的发生率，从每年 8.5%降至每年 3.3%。干扰素 alfa 的不良反应，如疲劳、抑郁和骨髓抑制，较为常见。HBV 核苷（酸）类似物，如恩替卡韦或替诺福韦，对 HDV 无效。丁型肝炎病毒进入肝细胞抑制剂 bulevirtide 和 HDV 组装抑制剂 lonafarnib 的 3 期随机临床试验表明，与安慰剂或观察相比，这些治疗方法在 bulevirtide 单药治疗 96 周后高达 56%的患者和 lonafarnib、ritonavir 和聚乙二醇干扰素 alfa 治疗 48 周后高达 19%的患者中达到了病毒学和生化应答。
HDV 感染影响全球约 1200 万至 7200 万人，与单独的 HBV 感染相比，它导致肝硬化和肝功能衰竭的进展更快，肝细胞癌的发生率更高。Bulevirtide 最近在欧洲获得 HDV 的批准，而聚乙二醇干扰素 alfa 是大多数国家唯一可用的治疗方法。
