Published online Mar 28, 2015. doi: 10.3748/wjg.v21.i12.3657
Peer-review started: September 19, 2014
First decision: October 29, 2014
Revised: November 10, 2014
Accepted: January 21, 2015
Article in press: January 21, 2015
Published online: March 28, 2015
AIM: To evaluate urine β2-microglobulin (β2-M), retinol-binding protein (RBP) excretion, and renal impairment with adefovir dipivoxil (ADV) for chronic hepatitis B.
METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy (n = 90) or ADV plus lamivudine combination therapy (n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate (eGFR) at the initiation of antiviral therapy and every 6 mo for a period of five years.
RESULTS: Urine β2-M abnormalities were observed in patients during the first (n = 3), second (n = 7), third (n = 11), fourth (n = 16), and fifth (n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first (n = 2), second (n = 8), third (n = 12), fourth (n = 15), and fifth (n = 22) year of ADV treatment. eGFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in eGFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and eGFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment.
CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.
Core tip: Identifying a reliable and sensitive biomarker of early renal dysfunction would be helpful for facilitating early intervention and evaluating the effectiveness of treatments for chronic hepatitis B. Urinary β2-microglobulin and retinol-binding protein are early markers of nephrotoxicity induced by nephrotoxic substances, cardiac surgery, diabetes mellitus, or hypertension. This study shows that long-term adefovir dipivoxil therapy in patients with chronic hepatitis B results in renal impairment that correlates with abnormalities in these markers.