Long-term Nucleotide Analogue Treatment Has Higher Levels of Renal Toxicities than Does Entecavir in Patients with Chronic Hepatitis B
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background/Aims: Renal toxicity is a concern in patients with chronic hepatitis B taking nucleotide analogues, such as adefovir (ADV) and tenofovir disoproxil fumarate (TDF). We sought to determine the long-term renal effects of nucleotide analogue treatment versus entecavir (ETV) treatment. Methods: In this retrospective single-center study, we selected 87 patients who were treated with ADV and subsequently with TDF from June 2008 to December 2013. ETV-treated patients were matched by treatment duration. We analyzed the creatinine increase over 0.5 mg/dL, glomerular filtration rate (GFR) decrease over 25%, phosphorus decrease under 2.0 mg/dL, and dose reduction of antiviral agents. Results: The median follow-up period was 60.0 months for both groups. The incidence of liver cirrhosis was higher in the ADV-TDF group than in the ETV group (32.2% vs 74.7%, p<0.01). Creatinine increased in both groups during follow-up, but the difference was not significant (5.7% and 2.3%, p=0.44). In addition, GFR decreased more often in the ADV-TDF group than in the ETV group (31.0% and 14.9%, p=0.01). After multivariate Cox regression analysis, ADV-TDF treatment was significantly associated with a GFR decrease over 25% (hazard ratio, 2.10; 95% confidence interval, 1.08 to 4.10; p=0.03) after adjusting for the baseline GFR decrease. Conclusions: Patients taking nucleotide analogues had a significantly higher number of renal events than did those taking ETV. Clinicians should be aware of the development of renal toxicity in this patient population. Further long-term studies are warranted.
Abstract
Background/Aims: Renal toxicity is a concern in patients with chronic hepatitis B taking nucleotide analogues, such as adefovir (ADV) and tenofovir disoproxil fumarate (TDF). We sought to determine the long-term renal effects of nucleotide analogue treatment versus entecavir (ETV) treatment. Methods: In this retrospective single-center study, we selected 87 patients who were treated with ADV and subsequently with TDF from June 2008 to December 2013. ETV-treated patients were matched by treatment duration. We analyzed the creatinine increase over 0.5 mg/dL, glomerular filtration rate (GFR) decrease over 25%, phosphorus decrease under 2.0 mg/dL, and dose reduction of antiviral agents. Results: The median follow-up period was 60.0 months for both groups. The incidence of liver cirrhosis was higher in the ADV-TDF group than in the ETV group (32.2% vs 74.7%, p<0.01). Creatinine increased in both groups during follow-up, but the difference was not significant (5.7% and 2.3%, p=0.44). In addition, GFR decreased more often in the ADV-TDF group than in the ETV group (31.0% and 14.9%, p=0.01). After multivariate Cox regression analysis, ADV-TDF treatment was significantly associated with a GFR decrease over 25% (hazard ratio, 2.10; 95% confidence interval, 1.08 to 4.10; p=0.03) after adjusting for the baseline GFR decrease. Conclusions: Patients taking nucleotide analogues had a significantly higher number of renal events than did those taking ETV. Clinicians should be aware of the development of renal toxicity in this patient population. Further long-term studies are warranted.
참고문헌 (25)
- Lee WM, "Hepatitis B virus infection", N Engl J Med, 337, pp.1733~1745 (1997)
- Cho EJ, "Current status and strategies for hepatitis B control in Korea", Clin Mol Hepatol, 23, pp.205~211 (2017)
- Lok AS, "Antiviral therapy for chronic hepatitis B viral infection in adults : a systematic review and meta-analysis", Hepatology, 63, pp.284~306 (2016)
- "Dailymed, archived drug label" (2018)[URL]
- Gish RG, "Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B", Clin Gastroenterol Hepatol, 10, pp.941~946 (2012)
- Hall AM, "Tenofovir-associated kidney toxicity in HIV-infected patients : a review of the evidence", Am J Kidney Dis, 57, pp.773~780 (2011)
- Hwang HS, "Tenofovir-associated Fanconi syndrome and nephrotic syndrome in a patient with chronic hepatitis B monoinfection", Hepatology, 62, pp.1318~1320 (2015)
- 조혜기, "Tenofovir-associated nephrotoxicity in patients with chronic hepatitis B: Two cases", Clinical and Molecular Hepatology, 22(2), pp.286~291 (2016), 대한간학회
- Tanji N, "Adefovir nephrotoxicity : possible role of mitochondrial DNA depletion", Hum Pathol, 32, pp.734~740 (2001)
- Gara N, "Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B", Aliment Pharmacol Ther, 35, pp.1317~1325 (2012)
- Monteagudo-Chu MO, "Renal toxicity of long-term therapy with tenofovir in HIV-infected patients", J Pharm Pract, 25, pp.552~559 (2012)
- Korean Association for the Study of the Liver, "KASL clinical practice guidelines : management of chronic hepatitis B", Clin Mol Hepatol, 22, pp.18~75 (2016)
- Terrault NA, "AASLD guidelines for treatment of chronic hepatitis B", Hepatology, 63, pp.261~283 (2016)
- Levey AS, "A new equation to estimate glomerular filtration rate", Ann Intern Med, 150, pp.604~612 (2009)
- Inker LA, "KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD", Am J Kidney Dis, 63, pp.713~735 (2014)
- Abdul Basit S, "Tenofovir alafenamide for the treatment of chronic hepatitis B virus infection", Expert Rev Clin Pharmacol, 10, pp.707~716 (2017)
- Wu D, "Toward a cure for hepatitis B virus infection : combination therapy involving viral suppression and immune modulation and long-term outcome", J Infect Dis, 216, pp.S771~S777 (2017)
- Koklu S, "Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B", Aliment Pharmacol Ther, 41, pp.310~319 (2015)
- Riveiro-Barciela M, "Effectiveness and safety of entecavir or tenofovir in a Spanish cohort of chronic hepatitis b patients : validation of the page-B score to predict hepatocellular carcinoma", Dig Dis Sci, 62, pp.784~793 (2017)
- Hartono JL, "Resolution of adefovir-related nephrotoxicity by adefovir dose-reduction in patients with chronic hepatitis B", Aliment Pharmacol Ther, 37, pp.710~719 (2013)
- Marengo A, "Letter : renal effects of tenofovir in adefovir dipivoxil-experienced HBV patients", Aliment Pharmacol Ther, 40, pp.324~ (2014)
- Tsai MC, "Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients : real world experience", Clin Microbiol Infect, 22, pp.95~ (2016)
- Kim YJ, "Frequency and risk factors of renal impairment during long-term adefovir dipivoxil treatment in chronic hepatitis B patients", J Gastroenterol Hepatol, 27, pp.306~312 (2012)
- Stewart AF, "Clinical practice. Hypercalcemia associated with cancer", N Engl J Med, 352, pp.373~379 (2005)
- Llovet JM, "Sorafenib in advanced hepatocellular carcinoma", N Engl J Med, 359, pp.378~390 (2008)