Kwong Sara, Lu Xiangping, Liu Xiuli, Lai Jinping
Department of Pathology and Laboratory Medicine, University of California, Davis-School of Medicine, Sacramento, CA, USA.
Department of Pathology and Laboratory Medicine, Kaiser Permanente San Leandro Medical Center, San Leandro, CA, USA.
Gastroenterology Res. 2020 Apr;13(2):81-84. doi: 10.14740/gr1283. Epub 2020 Apr 22.
Diagnosis of Epstein-Barr virus (EBV)-associated hepatitis, chronic active EBV infection, and EBV-associated lymphoproliferative diseases, is always challenging due to the overlapping symptoms and lack of diagnostic criteria. We report such a case of a 40-year-old man with unremarkable past medical history. He presented with fever of unknown origin for 1 month with jaundice for 2 days. Physical exams were unremarkable with body temperature at 98.6 °F. His liver function tests were elevated with alanine transaminase (ALT) 559 U/L, aspartate transaminase (AST) 892 U/L, alkaline phosphatase 319 U/L and total bilirubin 4.4 mg/dL. Computed tomography of his chest, abdomen and pelvis did not show lymphadenopathy or hepatosplenomegaly. A liver biopsy showed moderately acute hepatitis with hemophagocytosis, positive Epstein-Barr virus encoding RNA (EBER) hybridization in CD3 and CD4-positive T cells and CD56-positive natural killer (NK) cells. CD20 was negative. The pathology diagnosis was consistent with reactivation of EBV hepatitis but NK-cell lymphoma needs to be excluded. Steatohepatitis with mild activity was present. His blood EBV DNA was 846,000 copies/mL and continued to increase to 2,000,000 copies/mL. Flow cytometric analysis of his bone marrow revealed an increased NK-cell activity but no T/NK-cell lymphoma was identified. Initial treatment with rituxan, etoposide and/or ruxolitinib/acyclovir failed or only had limited effect. However, subsequent valganciclovir greatly improved his conditions. In his 3 months follow-up, the patient was doing well with almost normal liver function tests except mildly elevated ALT (95 U/L) that was due to mild steatohepatitis. EBV DNA PCR was 2,009 copies/mL. To the best of our knowledge, this is the first documented case with reactivation of EBV hepatitis mimicking NK-cell lymphoma in the English literature. With appropriate anti-EBV viral treatments, the patient eventually became asymptomatic and was able to return to his routine life.
由于症状重叠且缺乏诊断标准，诊断爱泼斯坦 - 巴尔病毒（EBV）相关肝炎、慢性活动性EBV感染和EBV相关淋巴增殖性疾病一直具有挑战性。我们报告了这样一例病例，一名40岁男性，既往病史无特殊。他出现不明原因发热1个月，伴有黄疸2天。体格检查无异常，体温98.6°F。他的肝功能检查结果升高，丙氨酸转氨酶（ALT）559 U/L，天冬氨酸转氨酶（AST）892 U/L，碱性磷酸酶319 U/L，总胆红素4.4 mg/dL。胸部、腹部和骨盆的计算机断层扫描未显示淋巴结病或肝脾肿大。肝活检显示中度急性肝炎伴噬血细胞增多，EBV编码RNA（EBER）在CD3和CD4阳性T细胞以及CD56阳性自然杀伤（NK）细胞中杂交阳性。CD20为阴性。病理诊断与EBV肝炎再激活一致，但需要排除NK细胞淋巴瘤。存在轻度活动性脂肪性肝炎。他的血液EBV DNA为846,000拷贝/mL，并持续增加至2,000,000拷贝/mL。对他的骨髓进行流式细胞术分析显示NK细胞活性增加，但未发现T/NK细胞淋巴瘤。最初使用利妥昔单抗、依托泊苷和/或鲁索替尼/阿昔洛韦治疗失败或仅产生有限效果。然而，随后的缬更昔洛韦极大地改善了他的病情。在3个月的随访中，患者情况良好，肝功能检查几乎正常，除了由于轻度脂肪性肝炎导致ALT轻度升高（95 U/L）。EBV DNA PCR为2,009拷贝/mL。据我们所知，这是英文文献中首例记录的类似NK细胞淋巴瘤的EBV肝炎再激活病例。通过适当的抗EBV病毒治疗，患者最终无症状并能够恢复正常生活。
