Tenofovir-induced Fanconi syndrome in chronic hepatitis B monoinfected patients that reverted after tenofovir withdrawal

Viganò, Mauro; Brocchieri, Alessandra; Spinetti, Angiola; Zaltron, S.; Mangia, G.; Facchetti, F.; Fugazza, Alessandro; Castelli, Francesco; Colombo, M.; Lampertico, Pietro

doi:10.1016/j.jcv.2014.09.016

Cited by 62 publications

(67 citation statements)

References 9 publications

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“…Lampertico et al suggested making dose reduction also in patients with eGFR <60 ml/min [estimated using Modification of Diet in Renal Disease (MDRD) study equation] and/or low levels of serum phosphorus. In their study cohort, the estimated cumulative probability of dose reduction for renal adverse events was 11% for naïve patients and 24% in patients previously treated with ADV at month 48 (36,37).…”

Section: Dose Adjustment Of Tdf and Early Diagnosis Of Tdf-related Rementioning

confidence: 97%

Renal Concerns in the Treatment of Chronic Hepatitis B with Tenofovir

Coppolino

Cernaro

Rivoli

et al. 2017

jrenhep

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Tenofovir, a third generation oral nucleos(t)ide analogue, currently represents one of the first-line drugs recommended for treating chronic hepatitis B virus (HBV) infection. After oral administration, tenofovir is mostly excreted in the urine by glomerular filtration and proximal tubular secretion. Hence, an impaired kidney function may lead to an increased renal exposure to the drug in patients with coexistent renal damage. This could further worsen kidney disease through different mechanisms of nephrotoxicity such as mitochondrial DNA depletion and tubular cytotoxicity. Despite several studies performed so far to assess tenofovir-related renal toxicity, data in HBV patients are not yet conclusive. Screening of risk factors for kidney disease before starting therapy and a careful monitoring of serum creatinine, glomerular filtration rate, serum phosphate and urine analysis during treatment are advocated to adjust the dose or stop treatment if needed. New biomarkers of tubular injury, such as neutrophil gelatinase associated lipocalin, could become helpful in the future for the timely identification and risk stratification of renal damage induced by tenofovir.

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Section: Dose Adjustment Of Tdf and Early Diagnosis Of Tdf-related Rementioning

confidence: 97%

Renal Concerns in the Treatment of Chronic Hepatitis B with Tenofovir

Coppolino

Cernaro

Rivoli

et al. 2017

jrenhep

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“…Adefovir or tenofovir-related Fanconi syndrome is a severe adverse event that results from proximal renal tubular toxicity, which leads to impaired re-absorption of amino acids, uric acid, bicarbonate, glucose and phosphate associated with the increased urinary excretion of these solutes [103][104][105][106] . Some cases associated with Fanconi syndrome induced by NUCs-treatment were fully recovered following tenofovir withdrawal [106] .…”

Section: Stoppage Of Entecavir or Tenofovirmentioning

confidence: 99%

“…Some cases associated with Fanconi syndrome induced by NUCs-treatment were fully recovered following tenofovir withdrawal [106] . Mitochondrial DNA depletion results in mitochondrial dysfunction in the lamivudine/telbivudine-associated neuromyopathy [107] .…”

Section: Stoppage Of Entecavir or Tenofovirmentioning

confidence: 99%

Current and future directions for treating hepatitis B virus infection

Tawada

Yokosuka

2015

WJH

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Hepatitis B virus (HBV) persistently infects approximately 350 million people, and approximately 600000 liverrelated deaths are observed per year worldwide. HBV infection is also one of the major risk factors for hepatocellular carcinoma (HCC). The persistence of serum hepatitis B e antigen (HBeAg) and high level of serum HBV DNA are thought to reflect a high HBV replication status in hepatocytes, causing cirrhosis, HCC and liver-related deaths. It has been reported that antiviral therapy, such as peginterferon and nucleos(t)ide analogues (NUCs), could suppress liver-related death by inhibiting the HBV DNA levels and inducing seroconversion from HBeAg to antibody to HBe antigen. Currently, peginterferon is widely used, but there are also several disadvantages in the use of peginterferon, such as various adverse events, the administration route and duration. It is difficult to predict the effects of treatment and interferon is contraindicated for the patients with advanced fibrosis of the liver and cirrhosis. With respect to NUCs, entecavir and tenofovir disoproxil fumarate are current the first-choice drugs. NUCs can be administered orally, and their anti-viral effects are stronger than that of peginterferon. However, because cessation of NUC administration leads to high levels of viral replication and causes severe hepatitis, they must be administered for a long time. On the other hand, the use of both interferon and NUCs cannot eliminate covalently closed circular DNA of HBV. In this review, we evaluate the natural course of chronic HBV infection and then provide an outline of these representative drugs, such as peginterferon, entecavir and tenofovir disoproxil fumarate.

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“…I dati estrapolati dagli studi clinici registrativi [15][16][17] e dagli studi di real life [24][25][26][27][28] sui singoli farmaci mostrano tassi di risposta virologica, resistenza e tollerabilità simili fra ETV e TDF. Anche il rischio di nefrotossicità associata a TDF, emerso durante la sorveglianza post-marketing dei pazienti HIV-positivi trattati con TDF [29], appare molto basso nei pazienti con CHB [23,30], sebbene recentemente siano stati riportati 3 casi di sindrome di Fanconi in pazienti con CHB trattati con TDF [31,32]; lo stesso vale per la riduzione della densità minerale ossea [30]. Tuttavia, pochi studi hanno messo direttamente a confronto ETV con TDF.…”

Section: Punti Chiave Y Entecavir E Tenofovir Sono Analoghi Nucleosidunclassified

A comparison between entecavir and tenofovir in chronic hepatitis B in the clinical practice: a single-center experience

Sollima

Torre

2015

CMI

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45fegato sono dovuti a una malattia (ESLD o HCC) HBV-correlata [2][3][4]. In assenza di terapia, la CHB progredisce in cirrosi nell'8-20% dei casi nell'arco di 5 anni. I pazienti evoluti in cirrosi sono a rischio, inoltre, di scompenso epatico e di HCC, con una incidenza cumulativa a 5 anni rispettivamente del 20% e 10-15%. Infine, lo scompenso epatico si associa a una prognosi infausta, con una probabilità di sopravvivenza a 5 anni del 14-35% [5][6][7]. È dimostrato che il rischio di progressione IntroduzIone L'epatite cronica B (CHB) costituisce un problema di sanità pubblica globale [1]. Si stima che 350-400 milioni di persone nel mondo siano cronicamente infette dal virus dell'epatite B (HBV) e che circa un milione di pazienti muoia ogni anno di cirrosi, insufficienza epatica terminale (ESLD) ed epatocarcinoma (HCC), quale risultato dell'infezione cronica da HBV. Inoltre, il 5-10% dei trapianti di TDF showed greater, though not statistically significant, effectiveness, in the three groups considered, i.e. naïve, pretreated with nucleoside/nucleotide analogs other than ETV or TDF, and pretreated with ETV or TDF patients. In particular, in naïve patients, those treated with TDF attained not detectable levels of viremia more rapidly (7 months versus 9 months) than ETV-treated patients, even starting from higher HBV DNA levels. In addition, virologic failure was observed in 0 versus 11% in TDF and ETV group, respectively. Also in patients pretreated with nucleoside/nucleotide analogs other than ETV or TDF, virologic failure was observed just in ETV patients. In patients who switched from ETV or TDF the mean time to attain undetectable HBV DNA levels was shorter in TDF group (3 months versus 6 months). Considering renal toxicity, there was no difference in creatinine and GFR levels between the two groups. Proteinuria and phosphaturia were greater in TDF patients, reaching statistical significance just in those pretreated with nucleoside/nucleotide analogs other than ETV or TDF. Therefore, ETV and TDF are similarly effective and safe, though TDF seems slightly more convenient in clinical practice. Keywords

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Tenofovir-induced Fanconi syndrome in chronic hepatitis B monoinfected patients that reverted after tenofovir withdrawal

Cited by 62 publications

References 9 publications

Renal Concerns in the Treatment of Chronic Hepatitis B with Tenofovir

Renal Concerns in the Treatment of Chronic Hepatitis B with Tenofovir

Current and future directions for treating hepatitis B virus infection

A comparison between entecavir and tenofovir in chronic hepatitis B in the clinical practice: a single-center experience

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