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Gut and Liver https://doi.org/10.5009/gnl18474 Long-term Nucleotide Analogue Treatment Has Higher Levels of Renal Toxicities than Does Entecavir in Patients with Chronic Hepatitis B
Author Information
Young Youn Cho1,2, Young Chang1, Joon Yeul Nam1, Hyeki Cho1, Eun Ju Cho1, Jeong-Hoon Lee1, Su Jong Yu1, Jung-Hwan Yoon1, and Yoon Jun Kim1
1Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, and 2Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea

Yoon Jun Kim
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-2072-3081, Fax: +82-2-743-6701, E-mail: yoonjun@snu.ac.kr
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

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.
Keywords: Hepatitis B, chronic; Kidney diseases; Guanine; Antiviral agents
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.
Keywords: Hepatitis B, chronic; Kidney diseases; Guanine; Antiviral agents
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