Decrease of Serum Angiotensin Converting Enzyme Levels Upon Telbivudine Treatment for Chronic Hepatitis B Virus Infection and Negative Correlations Between the Enzyme Levels and Estimated Glumerular Filtration Rates

BACKGROUND During antiviral therapy for chronic hepatitis B, renal function impairment could be a critical concern when oral nucleot(s)ide analogues were used. Paradoxically, long-term telbivudine treatment was associated with an increase of estimated glomerular filtration rate (eGFR) through unknown mechanisms. OBJECTIVES We aimed to investigate changes in serum protein abundances associated with renal function in response to antiviral treatments. MATERIALS AND METHODS Primarily, a transcriptomic assay was performed to identify differentially expressed genes in peripheral blood cells caused by the telbivudine treatment. Two genes coding angiotensin converting enzyme (ACE) and complement factor H (CFH) were screened from 14 candidate renal function-related genes. ACE and CFH production were further investigated using enzyme-linked immunoassays. RESULTS Verification studies showed no significant change of serum CFH levels, but there was a significant reduction of serum ACE levels by continuous telbivudine treatment for 330.00 ± 0.85 days (34 patients; paired t-test, P = 0.022). Serum HBV DNA and ALT levels also decreased (P = 0.008 and < 0.001, respectively). A significant increase in eGFR was found (33 patients, paired t-test, P = 0.002) at 708.64 ± 31.63 days. Patients' eGFRs were negatively correlated with serum ACE levels (r = -0.375, P = 0.002) but not with serum HBV DNA and ALT levels (P = 0.241 and 0.088 respectively). Significant decreases of the ACE levels were also observed upon entecavir treatment (20 patients; paired t-test, P = 0.020) at 412.88 ± 36.92 days. No significant correlation was found between serum ACE levels and eGFRs (r = -0.239, P = 0.138) in entecavir-treated patients. CONCLUSIONS We discovered a consistent reduction of serum ACE levels by two oral antiviral monotherapies, entecavir and telbivudine. Serum ACE levels were negatively correlated with eGFRs in telbivudine treated patients.