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

Abstract

Introduction: 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.

Figure 1

Alanine aminotransferase and creatinine clearance levels during nucleos(t)ide analog therapy. Because various physicians in various hospitals have separately participated in nucleos(t)ide analog therapy in different phases, parameters of liver enzymes, renal function and DNA load from month 1 to month 60 have not been recorded. Fluctuating alanine amino transferase levels showed during nucleos(t)ide analog therapy. Two bottom of creatinine clearance were present in month 104 and in month 133. The box showed the nucleos(t)ide analog-resistant mutations by sequence analysis. LVD, lamivudine; ETV, entecavir; ADV, adefovir; LdT, telbivudine; TDF, tenofovir; wt,wild-type.

Figure 2

Hepatitis B virus DNA and hepatitis B e antigen levels during nucleos(t)ide analog therapy. Viral load rebound presented in month 104 and in month 133. Combination therapy with entecavir 1mg plus adefovir 10mg daily was applied to inhibit viral load in month 106. Multidrug resistance mutations, namely rtL180M, rtM204V, rtA181T 30%/V 20%/wt 50% and rt T184G 40%/wt 60%, were identified in month 133. Thus, combination treatment with entecavir 0.5mg plus tenofovir 300mg daily was immediately selected in this time point. Viral load gradually decreased, and creatinine clearance correspondingly increased.