Dataset Information

Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B.

ABSTRACT: To investigate the predictors of proximal kidney tubular dysfunction (PKTD) induced by adefovir dipivoxil (ADV) treatment for chronic hepatitis B.Seventy-nine patients (age at the evaluation of PKTD: 56.9±10.7 years) with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited. PKTD was defined by the presence of at least two of the following five abnormalities: phosphate diabetes, nondiabetic glucosuria, metabolic acidosis, ?2-microglobulinuria, or renal hypouricemia. The single-nucleotide polymorphisms (SNPs) in the SLC22A6 gene encoding human organic anion transporter 1 (hOAT1) and ABCC2 encoding multidrug resistance protein 2 (MRP2) were analyzed using the TaqMan Allelic Discrimination Demonstration Kit.Nine (30.0%) of the 30 ADV-treated patients were diagnosed with PKTD, while no patients without ADV developed PKTD (P<0.001). Three patients with ADV were diagnosed with symptomatic osteomalacia. Among the patients who took ADV, those with PKTD were of higher age at initiation, had significantly longer treatment duration, and had a significantly lower body mass index than those without PKTD. The incidence of PKTD dramatically increased after 96 mo from the start of ADV administration. In contrast, the SNPs were not correlated with PKTD. Logistic regression analysis extracted older age at initiation (OR=5.0, 95%CI: 1.1-23.4; P=0.040) and longer treatment duration (OR=3.2, 95%CI: 1.2-8.6; P=0.020) as significant factors associated with PKTD.Our results suggest that the tubular function of the kidney of older patients undergoing long-term ADV treatment should be carefully evaluated.

SUBMITTER: Shimizu M

PROVIDER: S-EPMC4326148 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B.

Shimizu Motohiro M Furusyo Norihiro N Ikezaki Hiroaki H Ogawa Eiichi E Hayashi Takeo T Ihara Takeshi T Harada Yuji Y Toyoda Kazuhiro K Murata Masayuki M Hayashi Jun J

World journal of gastroenterology 20150201 7

<h4>Aim</h4>To investigate the predictors of proximal kidney tubular dysfunction (PKTD) induced by adefovir dipivoxil (ADV) treatment for chronic hepatitis B.<h4>Methods</h4>Seventy-nine patients (age at the evaluation of PKTD: 56.9±10.7 years) with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited. PKTD was defined by the presence of at least two of the following five abnormalities: phosphate diabetes, nondiabetic glucosuria, m ...[more]

PMID: 25717246

Similar Datasets

Project description:PURPOSE: This study aimed to clarify the long-term efficacy of the lamivudine treatment in Japanese patients with chronic hepatitis B either with or without lamivudine resistance or with or without adefovir add-on treatment. METHODS: We followed 110 patients who received lamivudine for more than 12 months, including 67 hepatitis B e antigen (HBeAg)-positive and 43 HBeAg-negative patients. RESULTS: The median follow-up after the onset of lamivudine was 48 (range = 12-86) months. In all the patients with or without lamivudine resistance, the level of alanine aminotransferase (ALT) normalization decreased from 70.0% at 1 year to 36.4% at 5 years and the loss of serum HBV DNA level decreased from 72.7% at 1 year to 31.8% at 5 years. Sixty patients (54.6%) developed a lamivudine-resistant mutation, and this occurrence was more frequently observed in those who were HBeAg-positive (P < 0.01), those with a low level of ALT (P < 0.05), and those with a high level of serum HBV DNA (P < 0.01). Thirty-six of 60 patients received adefovir in addition to lamivudine to treat breakthrough hepatitis. A Cox proportional hazards model analysis revealed the level of baseline HBV DNA to be the best predictive factor for the virus recrudescence (risk ratio = 0.466, 95% confidence interval [CI]: 0.246-0.842, P = 0.011) and the breakthrough hepatitis (risk ratio = 0.444, 95% CI: 0.218-0.879, P = 0.019). We carefully monitored the efficacy of this treatment both in patients who received adefovir and in those who did not since the beginning of the lamivudine treatment. The normalization level of ALT was 61.4% at 5 years and the loss of serum HBV DNA was 61.4% at 5 years since lamivudine was started. A histologic improvement was observed in patients with ALT levels less than two times the upper limit of normal at the time of a second liver biopsy. CONCLUSIONS: Although the efficacy of lamivudine is limited because of breakthrough hepatitis, adefovir was used as a salvage treatment of patients with lamivudine-resistant chronic hepatitis B. In addition, lamivudine was used for the treatment of Japanese patients with chronic hepatitis B with or without lamivudine resistance, and was found to be useful regarding the long-term virologic and biochemical responses.

Dataset Information

Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B.

Publications

Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets