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Farmacia Hospitalaria

versión On-line ISSN 2171-8695versión impresa ISSN 1130-6343

Farm Hosp. vol.40 no.4 Toledo jul./ago. 2016

https://dx.doi.org/10.7399/fh.2016.40.4.10492 

ORIGINALES

 

Comparison of the effectiveness and renal safety of tenofovir versus entecavir in patients with chronic hepatitis B

Comparación entre la efectividad y la seguridad renal del tenofovir y el entecavir en pacientes con hepatitis B crónica

 

 

Beatriz López Centeno1, Roberto Collado Borrell1, Montserrat Pérez Encinas1, María Luisa Gutiérrez García2 and Patricia Sanmartín Fenollera1

1Servicio de Farmacia, Hospital Universitario Fundación Alcorcón, Madrid.
2Servicio de Aparato Digestivo, Hospital Universitario Fundación Alcorcón, Madrid. España.

Correspondence

 

 


ABSTRACT

Objective: To compare the effectiveness and renal safety of treatment with tenofovir versus entecavir in patients with chronic hepatitis-B.
Methods: Retrospective study in hepatitis-B patients who initiated treatment with tenofovir or entecavir since January 1998 until 2013. The primary effectiveness variable was defined as viral DNA < 20 Ul/ml (HBV-DNA) and the variable for renal safety was variations in glomerular filtration rate (eGFR) after 48 weeks of treatment.
Results: The analysis was conducted in 64 patients (1:1), with similar characteristics except for the prevalence of naive patients (p=0.036), comorbidities (p=0.077) and nephrotoxic drugs (p=0.088) in the entecavi arm, while the tenofovir arm presented a prevalence of patients with HBV-DNA < 20 Ul/ml (p=0.032) and HBeAg-positive (p=0.050). Statistical univariate analysis and adjustment for confounding variables was conducted through the Propensity Score (PS). The outcomes for the primary effectiveness variable showed tenofovir superiority after PS adjustment, with an ORadj=6.7 (95% CI:1.2-35.3; p=0.028). Three patients on tenofovir experienced seroconversion (p=0.148). The outcomes for the primary safety variable (eGFR < 60 ml/min/1.73m2) showed no difference between both arms after adjustment, achieving an ORadj=0.6 (95% CI:0.1-2.8; p=0.521). The tenofovir arm registered two cases of treatment interruption due to renal toxicity, with subsequent recovery, including one Fanconi Syndrome.
Conclusions: In our study, there are significant differences between both treatments regarding effectiveness, with tenofovir demonstrating superiority. In terms of renal safety, we have not found any significant differences, but two cases of treatment interruption due to renal toxicity with tenofovir lead us to the conclusion that treatment decision in patients with renal function alteration should include an individualized assessment of each case.

Key words: Tenofovir; Entecavir; Chronic hepatitis B; Renal safety; Effectiveness.


RESUMEN

Objetivo: Comparar la efectividad y seguridad renal del tratamiento con tenofovir frente al entecavir en pacientes con hepatitis B crónica.
Métodos: Estudio retrospectivo en pacientes con hepatitis B que iniciaron tratamiento con tenofovir o entecavir entre enero 1998-2013. La variable principal de la efectividad fue definida como DNA viral < 20 Ul/ml (HBV-DNA) y la de la seguridad renal como variaciones en el filtrado glomerular (eGFR) tras 48 semanas de tratamiento.
Resultados: Se analizaron un total de 64 pacientes (1:1), con características semejantes excepto por el predominio de pacientes sin tratamiento previo p=0,036), comorbilidades (p=0,077) y fármacos nefrotóxicos (p=0,088) en el grupo-entecavir, y de pacientes con HBV-DNA < 20 Ul/ml (p=0,032) y HBeAg-positivo (p=0,050) en el grupo-tenofovir. Se realizaron análisis estadísticos univariantes y se ajustaron las variables confusoras mediante Propensity score (PS). Los resultados para la variable principal de efectividad (HBV-DNA < 20 Ul/ml) denotan una superioridad del tenofovir tras el ajuste por PS con una ORadj= 6,7 (IC95%: 1,2-35,3; p=0,028). Tres pacientes con tenofovir sufrieron seroconversión (p=0,148). Los resultados para la variable principal de seguridad (eGFR < 60ml/min/1.73m2) no mostraron diferencias entre ambas ramas tras el ajuste, obteniendo una ORad = 0,6 (IC95%: 0,1-2,8; p=0,521). El grupo-tenofovir registró dos casos de suspensión por toxicidad renal, con posterior recuperación, entre ellos un síndrome de Fanconi.
Conclusiones: En nuestro estudio existen diferencias significativas entre ambos tratamientos respecto a su efectividad, mostrándose el tenofovir superior. En cuanto a la seguridad renal, no hemos encontrado diferencias significativas, pero dos casos de suspensión de tratamiento por toxicidad renal con tenofovir nos llevan a concluir que la decisión de tratamiento en los pacientes con alteraciones en la función renal debería incluir un análisis individualizado de cada caso.

Palabras clave: Tenofovir; Entecavir; Hepatitis B crónica; Seguridad renal; Efectividad.


 

Contribution to scientific literature

This study provides a direct comparison between two drugs in patients with chronic Hepatitis B (CHB) under actual clinical practice, a comparison that has been made in several studies against other analogues used in the CHB treatment but with limited data in as for the comparison between these two agents; and it also provides a direct comparison between the renal safety of entecavir and tenofovir and analysis of additional risk factors for developing kidney disease in CHB patients.

The results of the study confirm the effectiveness and safety in clinical practice of both drugs and help improve the selection and individualization of treatment based on patient baseline characteristics; the role of hospital pharmacists is key to controlling and monitoring both the effectiveness and safety of pharmacological treatment of chronic ambulatory dispensation mainly due to its high impact on hospital costs and quality of care.

 

Introduction

The therapy objective in chronic Hepatitis B (CHB) is an increase in survival by preventing the progression of the hepatic lesion. This objective is achieved by a sustained suppression of viral replication. Treatment indication is based on the combination of three criteria: virus DNA and alanine aminotransferase in serum levels, and liver biopsy1,2.

Treatment options can be divided into two classes of drugs: pegylated interferon alpha and nucleoside/nucleotide analogues (NUCs). For treatment selection, the following must be taken into account: antiviral efficacy, resistances, safety profile, way of administration, and costs. Entecavir (ETV) and tenofovir (TDF) are two potent inhibitors with a high resistance barrier, which positions them as first choice for monotherapy treatment. ETV presents high potency, a good safety profile, and a minimum rate of resistance development in naive patients (1.2% after 5 years); however, it has a lower response rate in patients with resistance to lamivudine (LAM), as well as an increase in resistance (up to 51% at 5 years), which prevents it from being a drug of choice for these patients. TDF is a potent and selective nucleotide analogue, active both in naive patients and in previously treated patients with resistance to LAM. It also has an indication for naive patients with HIV infection, and its resistance profile is still to be defined (no resistances described at 5 years)1,3-5.

All NUCs are renally excreted unchanged; therefore, it is recommended to watch and conduct a dose adjustment when required in patients with kidney failure4,6. ADV and TDF have been associated to nephrotoxicity, and it has been primarily described in HIV-infected patients7-10. Some cases in CHB patients have been described in literature; however, this association has not been conclusively established in long-term clinical trials. Renal toxicity presents as a proximal tubule dysfunction, even with cases of Fanconi Syndrome (eGFR reduction, hypophosphatemia, hypouricemia, renal loss of ions)10,11.

Even though the efficacy of ETV and TDF has been demonstrated and compared vs. other analogues, there are limited data regarding the comparison between these two potent agents. Data are also limited regarding renal safety; however a potential nephrotoxicity has been more widely studied in TDF, basically in the HIV co-infected population7. The objective of the present study was to compare the effectiveness and renal safety of treatment with tenofovir vs. entecavir in CHB patients after 48 weeks of treatment.

 

Methods

Study Design and Setting

We performed a comparative retrospective cohort study of adult CHB patients (over 18-year-old, of both genders) who initiated treatment with TDF or ETV between January 1998 and 2013 and were followed-up during 48 weeks in a public university hospital. Patients were excluded if they had evidence of co-infected with HIV or Hepatitis-C. The patient list was obtained through the drug dispensing module for Hospital Pharmacy outpatients (Farmatools®). Clinical data were obtained from electronic clinical records (Selene®/GPC®).

The following data were collected: demographic data (age and gender), pharmacological (previous treatment and concomitant nephrotoxic drugs), comorbidities (hypertension and diabetes) and clinical (serum levels of: virus DNA (HBV-DNA)(UI/ml), alanine aminotransferase (ALT)(UI/L), creatinine (Cr)(mg/dl) and phosphate (P)(mg/dl), CHB serotype (HBeAg-positive or negative) and estimated glomerular filtration rate (eGFR)(ml/min/1,73m2) according to the CDK-EPI formula12), at baseline and at 48 weeks.

Outcome Measurements

The effectiveness variable was studied in terms of response: virological (HBV-DNA<20UI/ml), biochemical (ALT normalization), and serological (seroconversion) at 48 weeks of treatment initiation. A high HBV-DNA level was defined as values above 6log10. Seroconversion is understood as HBeAg loss and anti-HBe development, confirmed in two different tests. Elevated ALT levels were those 3 times over the normal upper limit (0-41UI/L).

Regarding safety, renal toxicity was assessed. Glomerular safety variables were defined as: changes in eGFR (proportion of patients with: eGFR<60ml/min/1.73m2 and eGFR reduction >25%) and increase in Cr (Cr>1.4mg/dl; normal range: 0.6-1.4mg/dl) at 48 weeks after initiating treatment. Preexisting kidney failure is understood as <60ml/min/1.73m2. The magnitude of Cr increases and eGFR reductions >25% are tested in order to detect kidney failure. P level was used as tubular toxicity variable, considering: mild (2-2.5mg/dl), moderate (1-1.99mg/dl) and severe hypophosphatemia (<1mg/dl)13. To assess the evolution, data were collected at baseline, 24 and 48 weeks.

Comorbidities, previous treatment and age were also analyzed; and regarding concomitant treatment, only those drugs which are nephrotoxic according to their product specifications were taken into account.

Statistical Analysis

All statistical analyses were performed using the Statistical Program for Social Sciences (SPSS v.18.0). Data were described as mean ± standard deviation (SD) or absolute and relative frequencies.

In order to compare effectiveness and safety measures between treatments, Chi-Square Test was used for hypothesis contrast, and Odds Ratio (OR) was estimated, with a 95% Confidence Interval (95%CI). The homogeneity of both treatment arms was studied through univariate analysis, applying the Chi-Square Test for qualitative variables, and Student's t test or Mann Whitney's U to compare quantitative variables. A 95%CI was determined, with p<0.05 as statistically significant differences.

The Propensity Score (PS) is used in order to reduce and control any selection and confusion bias14,15. Rosenbaum and Rubin14 put PS forward as the conditioned propensity of being assigned to a treatment, given a set of observed co-variables (potential confounding factors) before receiving the treatment. Comparison through PS is a way to correct the estimation of a treatment effect in non-experimental designs, based on the idea that there is a reduction in bias when the comparison of outcomes is conducted using subjects as similar as possible in both treatments.

Mixed models were used for the assessment of renal function evolution over time, which allow to model unbalanced longitudinal data16. These models included time as repeated measure, and the time*treatment interaction. Different structures of co-variance were modeled, and the best model was selected according to a likelihood test. A statistically significant interaction effect indicated that time evolution differs between treatments. Bonferroni Correction was used for multiple comparisons.

 

Results

The study included 64 CHB patients (1:1). A 62.5% of patients treated with TDF received the drug as mo-notherapy, and 37.5% received it in combination with LAM. All patients in the ETV arm were treated with mo-notherapy.

Baseline patient characteristics included in the study appear in table 1. Both treatment arms appeared de-mographically comparable, with significant differences in basal HBV-DNA, HBeAg-positive and prior treatment. Patients were classified into the following treatment subgroups: without any previous treatment (naive), previously treated with ADV, and treated with other drugs for CHB.

The concomitant nephrotoxic drugs collected were: trimethoprim-sulfamethoxazole, metformin, enalapril/ ramipril, spirinolactone, cyclosporin-A, methotrexate, and cyclophosphamide.

In view of these data, we have identified the following as potential confounding variables in terms of effectiveness: basal HBV-DNA, HBeAg-positive and prior treatment; and in terms of safety: age, basal eGFR, prior treatment, nephrotoxic drugs, and comorbidities, which we have compared through univariate analysis in order to study treatment homogeneity. For PS development, those variables with p<0.1 were selected (basal HBV-DNA, HBeAg-positive, prior treatment, nephrotoxic drugs, and comorbidities). We assessed the discriminant validity of the model through the Under the Curve Area (ROC). With our model, we have a 0.8 area (95%CI: 0.70.9), which indicates a good discriminant validity. We used PS as quantitative variable for adjustment in a multivariate logistic regression model (dependent variable is the treatment group), in order to assess treatment effect on the primary variables of effectiveness and safety, as defined in our study (Fig. 1a-b).

Effectiveness

At 48 weeks, 90.3% of patients in the TDF arm achieved virological response vs. 67.7% in the ETV arm (Fig.2); after the univariate analysis, the OR was 4.4 (95%CI:1.1-18.2; p=0.059), and after adjustment by PS, the value was ORadj=6.7 (95%CI:1.2-35.3; <p=0.028).

The percentage of patients who achieved ALT normalization, was 97% in the TDF arm and 87.5% in the ETV arm, without significant differences (p=0.355). In the TDF arm, three patients (9.4%) presented seroconversion; there were no cases in the ETV arm (p=0.148).

Safety

Out of 63 patients (TDF n=31 and ETV n=32), and after 48 weeks, 19.4% of patients in the TDF arm showed eGFR<60ml/min/1.73m2 vs. 15.6% in the ETV arm. After univariate analysis, we obtained an OR=0.8 (95%CI:0.2-2.8; p=0.750), and the PS-adjusted outcome was an ORadj value of 0.6 (95%CI:0.1-2.8; p=0.521). Regarding the reduction in eGFR, only one patient in the ETV arm vs. none in the TDF arm suffered a reduction over 25%.

The percentage of patients with Cr outside the normal range was 12.9% in the TDF arm vs. 6.3% in the ETV arm, without statistical significance (p=0.672).

Phosphate determination was conducted, after 24 weeks of treatment, in 53.1% of patients (62.5% TDF and 43.8% ETV); 2 cases of moderate hypophosphatemia were observed in the TDF arm only. Both cases were >60-year-old male patients, with comorbidities, nephrotoxic drugs, and one of them, who would develop Fanconi Syndrome, had preexisting kidney failure. As a result, one of the patients interrupted treatment at 24 weeks, after achieving seroconversion, and the other one at 48 weeks, when he developed Fanconi Syndrome, and recovered his renal parameters 12 weeks after TDF interruption, and subsequently was switched to ETV treatment (Table 2).

After 48 weeks, 71% of patients had phosphate determination (84.4% TDF and 53.1% ETV) with normal levels or mild hypophosphatemia. In the analysis with mixed models we did not find any statistically significant interaction effect (p=0.882); P levels were reduced by 0.256 (p=0.051) and 0.226 (p=0.154) in the TDF and ETV arm respectively. We did not find statistically significant differences either in the evolution of Cr (p=0.110) or eGFR (p=0.659) (Table 3).

 

Discussion

The present study, conducted under real practice conditions, the effectiveness and safety of both therapeutic options is compared after 48 weeks of treatment, in a cohort of naïve and pre-treated patients, and naïve regarding NUC treatment. Our finding is that TDF is significantly more effective than ETV to achieve HBV-DNA<20UI/ml; and regarding safety, we did not find any significant differences between both drugs. We have not found any significant differences in biochemical response and seroconversion; however three seroconversion cases occurred in the TDF arm.

A retrospective study conducted by Gao et al.17 in naïve patients with high HBV-DNA, finds that in HBeAg-positive patients, TDF is significantly more effective than ETV to achieve complete viral suppression (<60UI/ml=-300copies/ml). However, no significant difference was found among HBeAg-negative patients. When comparing our TDF superiority outcomes with this study, we must take into account that in our cohort the patients with high HBV-DNA was below 50%, and are based on HBeAg-negative patients mainly, although we must consider that these variables has been identified as confounding, and included in PS.

Our outcomes are consistent with the meta-analysis by Woo et al.18 where 20 clinical trials to determine the most effective therapies during the first year of treatment in naïve patients were included. In HBeAg-positive patients, TDF was more effective at achieving viral suppression (<1000copies/ml) with an 88% probability, 66% ALT normalization and 20% seroconversion. ETV appeared second, with a 61% viral suppression, 70% ALT normalization and 19% seroconversion. Regarding HBeAg-negative, TDF was also the most effective, with 94% viral suppression and 73% ALT normalization vs. ETV with 88% and 76% respectively. The authors concluded that TDF and ETV were the most potent drugs in HBeAg-positive, while TDF was the most potent in HBeAg-negative patients, as happens in the meta-analysis by Govan et al.19

Zuo et al.20 conducted a meta-analysis with the conclusion that virological response (<400copies/ml) with TDF was superior to ETV in naïve patients during their first year of treatment, and no differences were found in ALT normalization, seroconversion, or safety. Our outcomes coincide to a great extent with this study, with the exception that our cohort included both naïve and pre-treated patients.

On the contrary, other retrospective comparative studies conducted showed that both antivirals are similar in terms of efficacy. Dogan et al.5 conducted a study in naïve and pre-treated patients with efficacy outcomes (<400copies/ml) of 72.3% for TDF and 69% for ETV. The authors concluded that there were no significant differences regarding the efficacy of both drugs. We must highlight that only one case of seroconversion with ETV was observed in this study, unlike what happened in our cohort. Guzelbulut et al.21 did not find any differences in efficacy either (<400copies/ml); all patients included were naïve and had high HBV-DNA, unlike our series. The outcomes of these retrospective studies coincided with a meta-analysis by Dakin et al.22 where 13 clinical trials with naive HBeAg-positive patients were analyzed; it was observed that, at one year of treatment, 94% of patients on TDF reached viral suppression (<300copies/ ml) vs. 73% on ETV; all treatments increased the probability of seroconversion, though no significant differences were found. A meta-analysis performed by Ke et al.23 considered ETV and TDF as similarly effective and safe after 24 and 48 weeks of treatment. Finally, Maratea et al.24 did not find any significant differences in effectiveness, after an indirect comparison between both drugs.

Regarding renal safety, no significant differences were found in our study between both treatment arms, for any of the renal parameters analyzed. When we compared our outcomes with the comparative study conducted by Gish et al.25 who evaluated the risk of renal toxicity (Cr, eGFR<60ml/min and renal events) with TDF (monotherapy or combination) vs. ETV (monotherapy) in naïve patients, we observed there was an agreement, because they did not find any significant differences in renal parameters. In the same line, another retrospective comparative study conducted by Nguyen et al.26 in patients on monotherapy studied the renal function (Cr, eGFR and P) at baseline, 6 and 12 months of treatment. The study did not find any significant deterioration in renal function after 12 months with TDF, but this was detected in the ETV cohort; however, the authors concluded that this deterioration was due to the worse basal renal function in this arm.

At the time of studying the renal toxicity of ETV and TDF separately, our findings coincided with the information available so far27-30, because we did not observe any worsening in renal function over the follow-up period. In our series, a slightly higher deterioration in renal function was observed in the TDF arm, even though there was a lower risk factors associated than in the ETV arm; and there was one case of treatment interruption due to renal toxicity, vs. none in the ETV arm. However, these differences did not achieve statistical significance.

If we analyze the patient who developed Fanconi Syndrome, we will find a 66-year-old male patient, with diabetes on treatment with metformin, previously treated with ADV, who presented preexisting kidney failure at baseline. Therefore, he presented various risk factors, according to the multivariate analysis conducted with postmarketing clinical data, which show that advanced age (>60 years), preexisting kidney failure, comorbidities, concomitant nephrotoxic drugs, advanced HIV co-infection, and even male gender, are all risk factors to induce eGFR reductions by TDF11,31. There are limited published data about TDF-induced Fanconi Syndrome in CHB monoinfection patients, which suggests this is a rare adverse effect; by contrast, there are numerous cases published in HIV co-infected patients8,9. Several studies publish cases of Fanconi Syndrome in CHB monoinfection patients treated with TDF; in all of them the patients has associated risk factors (hypertension, preexisting kidney failure, and three of them prior treatment with ADV)32,33. Those cases described are similar to ours in terms of the coincidence of additional risk factors for renal disease, and the reversibility of the disorder; but they differ regarding the time of development, because in their case Fanconi Syndrome appeared after 3-4 years of exposure to TDF, while our patient developed it after one year of treatment.

Some of the limitations of the present study are its retrospective nature and the reduced sample size, that doesn't allow subgroup analysis based on the presence or lack of prior treatment, the HBeAg sign, the magnitude of basal HBV-DNA, and combination treatment with LAM, which can make it difficult to extrapolate our outcomes. Regarding the follow-up period, even though sufficient to assess effectiveness, it is not enough in order to assess long-term safety. On the other hand, in order to evaluate effectiveness, we have only assessed viral suppression, ALT normalization and seroconversion, without considering other parameters such as histological improvement and loss of surface antigen. Regarding the safety study, we have used only eGFR, Cr and P, because the retrospective nature of the study did not allow an analysis of other parameters, due to the lack of records in most cases. Furthermore, we have not been able to estimate the effect of prior treatment with ADV as a risk factor, due to the small proportion of pre-treated patients in our series. We consider of interest the analysis of its potential influence in the development of nephrotoxicity in subsequent treatments with TDF and ETV; however, we have not found any published evidence on this respect.

As our study was non-randomized, we have adjusted outcomes by using PS, in order to reduce the influence of confounding factors. This index shows the probability that a patient will fall into one arm of the study or the other, when there has been no randomization. When outcomes are adjusted using PS, even though with certain limitations, it can be assumed that the characteristics of the study patients which could have any influence in outcomes will be distributed in an "almost-random" manner. This adjustment offers some robustness to our outcomes; therefore, our study is relevant, because there are only a few studies to this date with a direct comparison between ETV and TDF in CHB patients under real practice conditions.

In summary, we have found that TDF performs as the more potent option vs. ETV during the first year of treatment in CHB patients, both naïve and pre-treated. On the contrary, both drugs are equivalent in term of renal safety in patients with preserved renal function. Given that it is still to be determined if ETV and TDF are equivalent therapeutic options or not, we believe it is necessary to conduct direct comparisons of a prospective nature with a larger population, allowing analysis by subgroups, and to determine in terms of effectiveness which is the NUC to choose based on the basal characteristics of patients. On the other hand, studies on safety are required, both in naïve and pre-treated patients, with long follow-up periods, focused on the renal profile, in order to obtain more conclusive outcomes. Meanwhile, while waiting for new evidence, the decision of treatment in patients with renal function alteration should include an individualized assessment, and it would be advisable to monitor glomerular and tubular function during TDF treatments.

 

Acknowledgements

Elia Pérez Fernández (Research Unit at the Hospital Universitario Fundación Alcorcón) for her assistance with statistical analysis.

 

Conflict of interest

The authors declare that they have no conflict of interest.

 

References

1. European Association For The Study Of The Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227-42.         [ Links ]

2. Lok ASF, McMahon BJ. Chronic hepatitis B: update 2009 (AASLD Practice Guidelines). Hepatology. 2009;50:661-2.         [ Links ]

3. Morillo Verdugo R, Madrazo Berenguer A, Gil Navarro MV, Suárez García E. Drugs treatment of hepatitis B. Farm Hosp. 2008;32:234-48.         [ Links ]

4. Petersen J, Buti M. Considerations for the long-term treatment of chronic hepatitis B with nucleos(t)ide analogs. Expert Rev Gastroenterol Hepatol. 2012;6:683-94.         [ Links ]

5. Do˘gan ÜB, Kara B, Gümürdülü Y, Soylu A, Akin MS. Comparison of the efficacy of tenofovir and entecavir for the treatment of nucleos(t)ide-naive patients with chronic hepatitis B. Turk J Gastroenterol. 2012;23:247-52.         [ Links ]

6. Pipili C, Cholongitas E, Papatheodoridis G. Review article: nucleos(t) ide analogues in patients with chronic hepatitis B virus infection and chronic kidney disease. Aliment Pharmacol Ther. 2014;39:35-46.         [ Links ]

7. Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. 2010;51:496-505.         [ Links ]

8. Karras A, Lafaurie M, Furco A, Bourgarit A, Droz D, Sereni D, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis. 2003;36:1070-3.         [ Links ]

9. Krummel T, Parvez-Braun L, Frantzen L, Lalanne H, Marcellin L, Hannedouche T, et al. Tenofovir-induced acute renal failure in an HIV patient with normal renal function. Nephrol Dial Transplant. 2005;20:473-4.         [ Links ]

10. Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559-85.         [ Links ]

11. Fernandez-Fernandez B, Montoya-Ferrer A, Sanz AB, Sanchez-Niño MD, Izquierdo MC, Poveda J, et al. Tenofovir nephrotoxicity: 2011 update. AIDS Res Treat. 2011;2011:354908.         [ Links ]

12. Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, et al. Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA. 2012;307:1941-51.         [ Links ]

13. Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and treatment. Am J Med. 2005;118:1094-1101.         [ Links ]

14. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41-55.         [ Links ]

15. D'Agostino RB. Propensity Score Methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265-81.         [ Links ]

16. Cnaan A, Laird NM, Slasor P. Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Stat Med. 1997;16:2349-80.         [ Links ]

17. Gao L, Trinh HN, Li J, Nguyen MH. Tenofovir is superior to entecavir for achieving complete viral suppression in HBeAg-positive chronic hepatitis B patients with high HBV DNA. Aliment Pharmacol Ther. 2014;39:629-37.         [ Links ]

18. Woo G, Tomlinson G, Nishikawa Y, Kowgier M, Sherman M, Wong DKH, et al. Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and Bayesian meta-analyses. Gastroenterology. 2010;139:1218-29.         [ Links ]

19. Govan L, Wu O, Xin Y, Hutchinson SJ, Hawkins N. Comparative effectiveness of antiviral treatment for hepatitis B: a systematic review and Bayesian network meta-analysis. Eur J Gastroenterol Hepatol. 2015;27:882-94.         [ Links ]

20. Zuo SR, Zuo XC, Wang CJ, Ma YT, Zhang HY, Li ZJ, et al. A meta-analysis comparing the efficacy of entecavir and tenofovir for the treatment of chronic hepatitis B infection. J Clin Pharmacol. 2015;55:288-97.         [ Links ]

21. Güzelbulut F, Ovünç AOK, Oetinkaya ZA, Senates E, Gökden Y, Saltürk AGD, et al. Comparison of the efficacy of entecavir and tenofovir in chronic hepatitis B. Hepatogastroenterology. 2012;59:477-80.         [ Links ]

22. Dakin H, Fidler C, Harper C. Mixed treatment comparison meta-analysis evaluating the relative efficacy of nucleos(t)ides for treatment of nucleos(t)ide-naive patients with chronic hepatitis B. Value Health. 2010;13:934-45.         [ Links ]

23. Ke W, Liu L, Zhang C, Ye X, Gao Y, Zhou S, et al. Comparison of efficacy and safety of tenofovir and entecavir in chronic hepatitis B virus infection: a systematic review and meta-analysis. PloS One. 2014;6:9:e98865.         [ Links ]

24. Maratea D, Fadda V, Trippoli S, Messori A. Letter: First-line monotherapies for chronic hepatitis B-indirect comparison between entecavir and tenofovir. Aliment Pharmacol Ther. 2013;37:584-5.         [ Links ]

25. Gish RG, Clark MD, Kane SD, Shaw RE, Mangahas MF, Baqai S. Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B. Clin Gastroenterol Hepatol. 2012;10:941-6.         [ Links ]

26. Nguyen HL, Al-Freah MA, Joe D, Carey I, Boyer T, Suddle A, et al. A single centre, large 'real-life' cohort treated with tenofovir versus entecavir: no deterioration in renal function in tenofovir cohort over 12 months of therapy. Hepatology. 2011;54 Suppl 1:604A.         [ Links ]

27. Ridruejo E, Silva MO. Safety of long-term nucleos(t)ide treatment in chronic hepatitis B. Expert Opin Drug Saf. 2012;11:357-60.         [ Links ]

28. Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442-55.         [ Links ]

29. Heathcote EJ, Marcellin P, Buti M, Gane E, De Man RA, Krastev Z, et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology. 2011;140:132-43.         [ Links ]

30. Fung J, Seto W-K, Lai C-L, Yuen M-F. Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment. J Gastroenterol Hepatol. 2014;29:428-34.         [ Links ]

31. Nelson MR, Katlama C, Montaner JS, Cooper DA, Gazzard B, Clotet B, et al. The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years. AIDS Lond Engl. 2007;21:1273-81.         [ Links ]

32. Gracey DM, Snelling P, McKenzie P, Strasser SI. Tenofovir-associated Fanconi syndrome in patients with chronic hepatitis B monoinfection. Antivir Ther. 2013;18:945-48.         [ Links ]

33. Viganò M, Brocchieri A, Spinetti A, Zaltron S, Mangia G, Facchettl F, et al. Tenofovir-induced Fanconi syndrome in chronic hepatitis B monoinfected patients that reverted after tenofovir withdrawal. J Clin Virol. 2014;61:600-3.         [ Links ]

 

 

Correspondence:
Correo electrónico: blopezcenteno@gmail.com
(Beatriz López Centeno)

Recibido el 26 de febrero de 2016;
Aceptado el 16 de mayo de 2016.

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