Case presentation

A 52-year-old man who had undergone kidney transplantation for chronic renal failure and complicated chronic hepatitis B was referred for multidrug resistance and renal functional injury. He had received nucleos(t)ide analog treatment with sequential monotherapy and combination therapy.

History

The patient had received sequential nucleos(t)ide analog monotherapy and inappropriate combination therapy during 134 months, which caused multidrug resistance and renal functional injury.

He had suffered from glomerulonephritis complicating renal failure without detectable hepatitis B virus (HBV) markers and underwent hemodialysis for 3 years. Eventually, kidney transplantation was performed. Post-surgery, he was given immunosuppression and anti-rejection therapy, following which, he developed type 2 diabetes mellitus as a side effect and was thus administered insulin.

Around 12 years back, he had active hepatitis B with increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but normal creatinine clearance (CC) levels. He was immediately started on lamivudine 100 mg daily monotherapy, and this time point was denoted as month 1. After 52 months, virological breakthrough and hepatitis flare were identified, and lamivudine resistance was detected by sequence analysis. Subsequently, a series of monotherapies were used, including adefovir 10 mg daily for 9 months, telbivudine 600 mg daily for 9 months, and entecavir 1 mg daily for 18 months. However, increased HBV load, positive HBeAg and fluctuating ALT levels were within 3 times the upper limit of normal during 3 years. Sequential monotherapy also led to virological breakthrough, resistance mutation, and partial virological response, hence combination therapy with lamivudine 100 mg plus entecavir 1 mg daily was administered in month 88. Although a decrease in viral load was noticed, it rebounded in the month 105. Moreover, resistance mutations with rtL180M and rtM204V were again detectable. Renal function showed that serum creatinine levels were at upper limit of normal and CC was 59.5ml/min. This was followed by administration of entecavir 1 mg plus adefovir 10mg daily in month 107. This treatment improved the viral load, normalized hepatic function and renal function but only for some time and rebounded in month 134.

Investigations

Virological parameters, hepatic enzymology and renal function were monitored.

Drug-resistance mutations were identified by sequence analysis.

Diagnosis

Multidrug resistance and renal functional injury due to sequential nucleos(t)ide analog monotherapy and inappropriate combination therapy.

Management

The patient was started on combination therapy comprising entecavir 0.5 mg and tenofovir 300 mg daily in month 134. A gradual reduction in viral load and serum creatinine was observed. Moreover, an increase in the level of CC was also seen. After 9 months of therapy, HBV DNA was undetectable (< 20 IU/ml), ALT and AST levels were normal and CC concentration improved. Thus, tenofovir plus entecavir combination therapy offered better therapeutic potential in terms of antiviral effect for multidrug resistance and minimized renal injury than adefovir plus entecavir.