Clinical impact of the development of YMDD mutants in hepatitis B virus-associated glomerulonephritis

Background/Aims: Elimination of chronic viral infection with lamivudine (LAM) has recently been proposed to induce remission of HBV-associated glomerulonephritis (GN). However, prolonged LAM therapy can lead to the development of LAM-resistant HBV, causing viral breakthrough in serum. The present study evaluated the effect of the development of YMDD mutations on renal disease in HBV-associated GN patients. Methodology: The database and clinical records of 4 patients, who were diagnosed with biopsy-proven HBV-associated GN and had documented YMDD mutants following prolonged LAM therapy, were retrospectively reviewed. Results: The mean LAM treatment duration before the development of YMDD mutants was 25±9 months. Before YMDD mutants developed, LAM therapy lowered HBV DNA titers in serum and reduced the amount of proteinuria. With the development of YMDD mutations, viral breakthrough in serum occurred, and three patients experienced aggravation of proteinuria and/or progressive renal deterioration. Among them, one patient had a considerable amount of proteinuria and progressive renal deterioration even after HBV DNA titer fell under detectable levels with the switch to adefovir dipivoxil. Conclusions: YMDD mutant-related viral breakthrough after prolonged LAM therapy might lead to the aggravation of renal disease in HBV-associated GN patients.