Abstract：ObjectiveTo explore the clinical diagnostic features of Fanconi syndrome (FS) combined with hypophosphatemic osteomalacia (HO) induced by tenofovir dipifurate fumarate (TDF) in a patient with chronic hepatitis B (CHB). MethodsThe clinical data of a case of CHB with FS and HO admitted to the Jining No.1 People′s Hospital on May 3, 2022 were reviewed retrospectively, and the literature was reviewed. ResultsThe 66-year-old female had a history of more than 20 years of CHB treated with TDF for more than 5 years before she was admitted to hospital due to "recurrent pain of both lower limbs for more than 1 year". The patient had pain, numbness and discomfort in both lower limbs without obvious inducement 1 year ago, especially in the right lower limb. The pain was more severe, worsened after activity and could be alleviated after rest. Her serum potassium was 3.00mmol/L, calcium was 2.18mmol/L, phosphorus was 0.32mmol/L, and there was no abnomality in blood urea nitrogen and creatinine. Repeated urine tests showed urine glucose ±-2+, urine protein 0-2+ .The 24-hour total urinary phosphorus was 23.25mmol. Plain MRI scan of bilateral ankle joints showed multiple bone abnormalities in constituent, tarsal and metatarsal bones of both ankles, and false fracture lines were found. The diagnosis was secondary FS with HO caused by TDF. TDF was discontinued, and antiviral therapy was replaced with tenofovir alafenamide fumarate, vitamin D calcium chewable tablets, vitamin D2 softgel capsules, sodium glycerophosphate, and other medications to correct calcium and phosphorus metabolism disorders, and the patient′s symptoms improved significantly. ConclusionsPatients with CHB treated with TDF should be aware of the possibility of FS complicating with HO. Clinicians should monitor blood creatinine, blood phosphorus, urine glucose, and urine protein levels both before and during treatment.
［1］Garcia M， Le Moal G， Godet C， et al. First case report of renal improvement on tenofovir alafenamide in an HIV/hepatitis B virus-coinfected patient with adefovir-induced Fanconi′s syndrome［J］.AIDS，2016，30(9):1487-1488.DOI：10.1097/QAD.0000000000001059.
［2］中华医学会内分泌学分会，中华医学会骨质疏松和骨矿盐疾病分会.中国低血磷性佝偻病/骨软化症诊疗指南［J］.中华骨质疏松和骨矿盐疾病杂志，2022，15(2):107-125.DOI：10.3969/j.issn.1674-2591.2022.02.001.
［3］Tien C，Xu JJ，Chan LS，et al.Long-term treatment with tenofovir in Asian-American chronic hepatitis B patients is associated with abnormal renal phosphate handling［J］.Dig Dis Sci，2015，60(2):566-572.DOI：10.1007/s10620-014-3363-4.
［4］Gupta SK，Anderson AM，Ebrahimi R，et al.Fanconi syndrome accompanied by renal function decline with tenofovir disoproxil fumarate：a prospective，case-control study of predictors and resolution in HIV-infected patients［J］.PLoS One，2014，9(3):e92717.DOI：10.1371/journal.pone.0092717.
［5］Karris MY.Short communication：resolution of tenofovir disoproxil fumarate induced fanconi syndrome with switch to tenofovir alafenamide fumarate in a HIV-1 and hepatitis B coinfected patient［J］.AIDS Res Hum Retroviruses，2017，33(7):718-722.DOI：10.1089/AID.2016.0180.
［6］Post FA，Tebas P，Clarke A,et al.Brief report：switching to tenofovir alafenamide，coformulated with elvitegravir，cobicistat，and emtricitabine，in HIV-Infected adults with renal impairment：96-week results from a single-arm，multicenter，open-label phase 3 study［J］.J Acquir Immune Defic Syndr，2017,74(2):180-184.DOI：10.1097/QAI.0000000000001186.
［7］de Vries-Sluijs TE，Reijnders JG，Hansen BE，et al.Long-term therapy with tenofovir is effective for patients co-infected with human immunodeficiency virus and hepatitis B virus［J］.Gastroenterology，2010，139(6):1934-1941.DOI：10.1053/j.gastro.2010.08.045.
［8］Rao M， Dadey L， Glowa T， et al. Fanconi syndrome leading to hypophosphatemic osteomalacia related to tenofovir use［J］.Infect Dis Rep，2021，13(2):448-453.DOI：10.3390/idr13020044.
［9］刘恒丽,李侠,杨欣平,等.HIV感染/艾滋病患者富马酸替诺福韦二吡呋酯相关范可尼综合征临床特征分析［J］.药物不良反应杂志,2023,25(1)：21-27.DOI:10.3760/cma.j.cn114015-20220603-00491.
［10］Jafari A，Khalili H，Dashti-Khavidaki S.Tenofovir-induced nephrotoxicity：incidence，mechanism，risk factors，prognosis and proposed agents for prevention［J］.Eur J Clin Pharmacol，2014,70(9):1029-1040.DOI：10.1007/s00228-014-1712-z.
［11］Labarga P，Barreiro P，Martin-Carbonero L，et al.Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir［J］.AIDS，2009，23(6):689-696.DOI：10.1097/QAD.0b013e3283262a64.
［12］Woodward CL，Hall AM，Williams IG，et al.Tenofovir-associated renal and bone toxicity［J］.HIV Med，2009，10(8):482-487.DOI：10.1111/j.1468-1293.2009.00716.x.
［13］Sahoo RR，Wakhlu A.Clinical images：tenofovir-induced fanconi syndrome：an uncommon cause of hypophosphatemic osteomalacia［J］.ACR Open Rheumatol，2022，4(6):484-485.DOI：10.1002/acr2.11415.
［14］Jung WJ，Jang JY，Park WY，et al.Effect of tenofovir on renal function in patients with chronic hepatitis B［J］.Medicine (Baltimore)，2018，97(7):e9756.DOI：10.1097/MD.0000000000009756.
［15］郭李炜，李雪琴，卢正红，等.阿德福韦酯导致低磷骨软化症并Fanconi综合征1例［J］.中华全科医师杂志，2023，22(8):864-866.DOI：10.3760/cma.j.cn114798-20230114-00055.
［16］Korean Association for the Study of the Liver.KASL clinical practice guidelines：management of chronic hepatitis B［J］.Clin Mol Hepatol，2016，22(1):18-75.DOI：10.3350/cmh.2016.22.1.18.
［17］Kim S，Kim SW，Lee BC，et al.Adult-onset hypophosphatemic osteomalacia as a cause of widespread musculoskeletal pain：a retrospective case series of single center experience［J］.World J Clin Cases，2023，11(32):7785-7794.DOI：10.12998/wjcc.v11.i32.7785.
