Nucleotide analogues are associated in the long term with a risk of proximal tubular nephropathy (PT) with loss of phosphate, and, when compensatory mechanisms are overwhelmed, with osteopenia or osteoporosis. This toxicity has been particularly documented for tenofovir (TDF) in HIV disease, but its prevalence varies widely in the literature and is mainly associated with comorbidities: on average this prevalence is 0.39% after 48 weeks with exceptional cases of Fanconi syndrome described. In HBV monoinfection after 60 months of treatment with TDF, an 11% decrease of creatinine clearance (CreatCl) is observed. A single study showed a significant increase in creatinine level with entecavir (ETV) therapy, a second-generation nucleoside, hitherto not described as nephrotoxic. Furthermore, if the direct renal toxic effect characteristic of HIV in the kidney is well known, the role of HBV is less clear. Thus, HBV treatment appears to have a renal protective effect. The monitoring tools recommended by the SPC, CreatCl and plasma phosphorus level are late markers of tubular damage. The threshold of phosphate tubular reabsorption (TmPi/GFR) and the fractional excretion of uric acid (FEUA) are unexpensive early screening tools. However, the long-term evolution of this subclinical tubular involvement in HBV monoinfection is not known.

260 naive untreated patients, 220 patients treated with TDF and 220 patients treated with ETV and consecutively recruited in this interventional study, will have at baseline and every three months, a determination of phosphorus, creatinine, uric acid in plasma and urine samples for determination of TMPi / GFR and FEUA, and an evaluation of urinary calcium level. Depending on local opportunities, every six months, a urine sample will be stored in a declared biological collection to perform β2-microglobuline and cystatin dosage. A 25-OHD3 and PTH dosage will be conducted annually. A sample of genomic DNA will be collected after informed consent of the patient from a saliva sample (Saliva autocollection kits) in order to investigate genetic polymorphism in transporters responsible for the renal elimination of TDF and ETV. A serum sample will be stored at baseline, at one year and at endpoint for the retrospective dosage of bone markers (bone PAlk, PINP and CTX).

Inclusion Criteria:

• Age ≥ 18 years
• Patients with chronic HBV virus monoinfected
• For groups of patients treated: Patients with an indication of ETV or TDF
• For the group of naive patients: treatment-naive patients who have no indication of treatment (or do not want) for the duration of the study
• globular filtration rate (GFR) ≥ 50 ml / min / 1.73 m2 with no known cause of renal disease
• Patients who have given their informed and written informed consent
• Women of childbearing potential with an effective method of contraception without interruption for the duration of the research and during the 4 months after stopping treatment

Exclusion Criteria:

• Patients co-infected with HIV, hepatitis C or hepatitis Delta
• Patients who have already received the TDF in the group to receive the TDF and having already received ETV in the group to receive ETV
• Patient with a GFR <50 ml / min / 1.73 m2 or with known causes of renal disease
• Patient with hypophosphatemia <0.48 mmol / l
• Patients with hepatocellular carcinoma (diagnosed or suspected)

Patient with hepatitis B virus