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Five nucleos(t)ide analogs are used to treat chronic hepatitis B. Ideal nucleos(t)ide analog therapy in chronic hepatitis B patients with kidney transplantation must ensure virological suppression and minimize renal injury. However, resistance to nucleos(t)ide analogs frequently results in virological breakthrough, hepatitis flare, and complicated deterioration of the transplanted kidney. Inappropriate rescue therapy for drug resistance may subsequently cause hepatitis B virus multidrug resistance. Currently, tenofovir is used to treat chronic hepatitis B patients with kidney transplantation. In the field, we first reported combination therapy with tenofovir plus entecavir in a kidney transplant chronic hepatitis B patient with nucleos(t)ide analog multidrug resistance.    Case presentation  A 50-year-old Chinese man with chronic hepatitis B and kidney transplantation received nucleos(t)ide analog therapy with sequential monotherapy and combination therapy. Virological parameters, hepatic enzymology and renal function were monitored. Drug-resistance mutations were detected by sequence analysis. Our patient received sequential nucleos(t)ide analog monotherapy and inappropriate combination therapy during 132 months, which caused multidrug resistance and renal functional injury. Entecavir plus adefovir was administered in month 106, resulting in decreased hepatitis B virus load, normal hepatic function, and stabilized creatinine clearance. As a result of rebounded viral load and significantly declining creatinine clearance, tenofovir plus entecavir was administered in month 133. After eight weeks, undetectable hepatitis B virus DNA, normal hepatic function and improved creatinine clearance were present. Compared with combination therapy with adefovir plus entecavir, tenofovir plus entecavir showed a potent antiviral effect for multidrug resistance and minimized renal injury.    Conclusions  In chronic hepatitis B patients with kidney transplantation, sequential monotherapy with antiviral agents with low barriers to resistance should be avoided, and initial therapy with entecavir is a better option. Combination therapy with tenofovir plus entecavir in this setting with multidrug resistance is safe and effective.

Efficacy and safety of tenofovir in a kidney transplant patient with chronic hepatitis B and nucleos(t)ide multidrug resistance: a case report