Entecavir resistance in a patient with treatment-naïve HBV: A case report
Andrea Marino 1 , Federica Cosentino 1 , Manuela Ceccarelli 1 , Vittoria Moscatt 1 , Alessio Pampaloni 1 , Daniele Scuderi 1 , Flavia D'Andrea 2 , Emmanuele Venanzi Rullo 2 , Giuseppe Nunnari 2 , Francesco Benanti 1 , Benedetto Maurizio Celesia 1 , Bruno Cacopardo 1
Affiliations
Affiliations
1
Department of Clinical and Experimental Medicine, Division of Infectious Diseases, ARNAS Garibaldi Hospital, University of Catania, I-95122 Catania, Italy.
2
Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, University of Messina, I-98124 Messina, Italy.
Among nucleos(t)ide analogue therapies for hepatitis B virus (HBV) treatment, entecavir (ETV) and tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide are associated with the lowest rate of drug resistance. ETV is a drug requiring at least three substitutions in the reverse transcriptase (RT) domain to develop resistance, which is a rare occasion in treatment-naïve patients. However, pre-existing or acquired single mutations in the RT domain could lead to a virological breakthrough, after viral suppression. The present case report describes a 58-year-old female patient with hepatitis B virus (HBV) and high viral load who started HBV treatment with ETV. After 85 weeks of treatment, HBV-DNA declined to 0 IU/ml and remained undetectable for 3 years. However, after that period of time, the HBV-DNA rebounded, followed by the rise of liver enzymes (aspartate aminotransferase and alanine transaminase). Only the substitution M204I was detected in the HBV polymerase region. The patient was then switched to TDF treatment, achieving normalization of the liver enzymes and a decline in HBV-DNA levels. The present case report suggests that nucleoside-naïve patients should be cautiously monitored for resistance, even more than biochemically (transaminases, bilirubin) and virologically (HBV-DNA), even if complete HBV suppression is achieved.
在用于乙型肝炎病毒（HBV）治疗的核苷类似物疗法中，恩替卡韦（ETV）和替诺福韦富马酸替诺福韦酯（TDF）/替诺福韦阿拉芬酰胺的耐药率最低。 ETV是一种在逆转录酶（RT）域中至少需要三个取代基才能产生耐药性的药物，这在未接受过治疗的患者中很少见。然而，在病毒抑制后，RT域中先前存在或获得的单突变可能导致病毒学突破。本病例报告描述了一名58岁的乙型肝炎病毒（HBV）和高病毒载量的女性患者，他们开始使用ETV进行HBV治疗。治疗85周后，HBV-DNA降至0 IU / ml，并在3年内仍未检测到。然而，在那段时间之后，HBV-DNA反弹，随后是肝酶（天冬氨酸转氨酶和丙氨酸转氨酶）上升。在HBV聚合酶区域中仅检测到取代M204I。然后将患者转为TDF治疗，实现肝酶正常化和HBV-DNA水平下降。本病例报告建议，即使未完全抑制HBV，也应谨慎监测未接受过核苷治疗的患者的耐药性，甚至比生化检查（转氨酶，胆红素）和病毒学检查（HBV-DNA）还要严格。