Fabbri Gabriele, Mastrorosa Ilaria, Vergori Alessandra, Mazzotta Valentina, Pinnetti Carmela, Grisetti Susanna, Zaccarelli Mauro, Ammassari Adriana, Antinori Andrea
National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy.
BMC Infect Dis. 2017 Mar 1;17(1):182. doi: 10.1186/s12879-017-2287-y.
Reactivation of occult or inactive Hepatitis B virus (HBV) infection during immunosuppressant treatments is well known and widely described in literature. The same observation has been made in Hepatitis C (HCV)-infected patients previously exposed to HBV and treated with interferon-free DAA treatments. Because of common transmission routes, persons may have been exposed to HCV, HBV and HIV, but few cases have been reported in this scenario to date. Frequency of HBV reactivation in HIV/HCV co-infected patients previously exposed to HBV and treated with DAA remains unclear. Herein, we report an episode of HBV reactivation in an HIV/HCV co-infected patient prescribed with sofosbuvir/ledipasvir for HCV.
The patient is a Caucasian 54-years old female, with HIV/HCV co-infection (genotype 4), and a previous exposure to HBV, documented by negativity of HBsAg and positivity of HBsAb and HBcAb. Her medical history included: myocardial infarct, chronic kidney disease stage 3, chronic obstructive pulmonary disease, and mild pulmonary hypertension. HCV had not been treated with interferon (IFN)-based regimens and liver stiffness was 10.5 KPa (Metavir stage F3) at hepatic elastography. Because of CKD, she was prescribed with a nucleoside reverse transcriptase (NRTI)-sparing regimen including darunavir/ritonavir plus etravirine, and thereafter with sofosbuvir/ledipasvir for 12 weeks. Four weeks after DAA termination, the patient was hospitalized with symptoms of acute hepatitis. Blood tests showed HCV RNA <12 IU/ml, but positivity of HBAg, HBeAg, and of anti-core antibodies (IgM and IgG), while anti-HBs and anti-HBe antibodies were negative. HBV DNA was 6.06 Log IU/ml. Entecavir was started obtaining resolution of symptoms, normalization of liver enzymes, as well as reduction of HBV DNA and of quantitative HBV surface antigen.
This case-report highlights the risk of HBV reactivation with interferon-free DAA treatment in HIV/HCV co-infected patients previously exposed to HBV and who have contraindications for treatment with nucleoside/nucleotide reverse transcriptase Inhibitors because of comorbid conditions. In the setting of HIV infection, clinicians prescribing DAA should be aware of this risk, and HBV assessment at treatment start as well as virological monitoring during DAA treatment is recommended. Large epidemiological and virological studies are needed to investigate reactivation of occult HBV infection more in depth.
在免疫抑制治疗期间，隐匿性或非活动性乙型肝炎病毒（HBV）感染的重新激活是众所周知的，并且在文献中已有广泛描述。在先前感染过HBV并接受不含干扰素的直接抗病毒药物（DAA）治疗的丙型肝炎（HCV）感染患者中也观察到了同样的情况。由于常见的传播途径，人们可能同时接触过HCV、HBV和HIV，但迄今为止，这种情况下的病例报告很少。HIV/HCV合并感染且先前感染过HBV并接受DAA治疗的患者中HBV重新激活的频率仍不清楚。在此，我们报告一例接受索磷布韦/维帕他韦治疗HCV的HIV/HCV合并感染患者发生HBV重新激活的病例。
该患者为一名54岁的白种女性，合并HIV/HCV感染（4型基因型），既往有HBV暴露史，HBsAg阴性、HBsAb和HBcAb阳性可证实。她的病史包括：心肌梗死、慢性肾脏病3期、慢性阻塞性肺疾病和轻度肺动脉高压。HCV未接受过基于干扰素（IFN）的治疗方案，肝脏弹性成像显示肝脏硬度为10.5 KPa（梅塔维分级F3期）。由于患有慢性肾脏病，她接受了一种不含核苷类逆转录酶（NRTI）的治疗方案，包括达芦那韦/利托那韦加依曲韦林，此后接受索磷布韦/维帕他韦治疗12周。DAA治疗结束后四周，患者因急性肝炎症状住院。血液检查显示HCV RNA<12 IU/ml，但HBAg、HBeAg和抗核心抗体（IgM和IgG）呈阳性，而抗-HBs和抗-HBe抗体呈阴性。HBV DNA为6.06 Log IU/ml。开始使用恩替卡韦治疗后，症状得到缓解，肝酶恢复正常，HBV DNA和定量HBV表面抗原也有所下降。
本病例报告强调了在HIV/HCV合并感染、既往感染过HBV且因合并症而有核苷/核苷酸逆转录酶抑制剂治疗禁忌证的患者中，使用不含干扰素的DAA治疗存在HBV重新激活的风险。在HIV感染的情况下，开具DAA处方的临床医生应意识到这种风险，建议在治疗开始时进行HBV评估，并在DAA治疗期间进行病毒学监测。需要进行大规模的流行病学和病毒学研究，以更深入地调查隐匿性HBV感染的重新激活情况。
