An observational study on long‐term renal outcome in patients with chronic hepatitis B treated with tenofovir disoproxil fumarate

Abstract

In patients with chronic hepatitis B (CHB), long‐term effects of tenofovir disoproxil fumarate (TDF) on renal function have been controversial. This study aimed to analyse the real‐world long‐term effects of TDF on renal function in Korean patients with CHB. We analysed a cohort of 640 treatment‐naïve patients with CHB who were treated with TDF between May 2012 and December 2015 at Severance Hospital, Seoul, Republic of Korea. The mean age was 48.3 years old, and 59.5% were male. The proportions of hypertension and diabetes mellitus (DM) were 11.6% and 14.2%, respectively, and that of liver cirrhosis was 20.8%. During the 5‐year follow‐up, using a linear mixed model, serum creatinine increased from 0.77 ± 0.01 mg/dL to 0.85 ± 0.02 mg/dL (P < .001), and eGFR decreased from 102.6 ± 0.6 mL/min/1.73 m2 to 93.4 ± 1.4 mL/min/1.73 m2 (P < .001). In subgroup analysis, eGFR was statistically more decreased in patients with age > 60 than ≦60 years old (P = .027), and in patients with diuretic use than without diuretic use (P = .008). In multivariate analysis, the independent risk factors for eGFR decrease > 20% were baseline eGFR < 60mL/min/1.73 m2 (P = .034) and the use of diuretics (P < .001). CHB patients on TDF experienced greater reduction in renal function with age > 60 and with diuretic use compared to those without these characteristics. Baseline eGFR < 60 mL/min/1.73 m2 and use of diuretics were independent risk factors of eGFR decline of more than 20% on TDF therapy.

Comparison of viral control between two tenofovir dose reduction regimens (300 mg every 48 hours versus 300 mg every 72 hours) in chronic hepatitis B patients with moderate renal impairment from tenofovir‐induced renal dysfunction

“…In an observatory study of 640 CHB patients who received TDF treatment, the proportion of patients who had decreased renal function greater than 20% and greater than 50% from baseline during the 5-year follow-up was 15.2% and 0.7%, respectively. 21 Another prospective study of 400 CHB patients who received entecavir or TDF for 3 years showed a decrease in the mean eGFR in both groups (P > .05). The proportion of patients with decreased renal function greater than 20% in the TDF group after 3 years of treatment was 16.8%, and that rate was not significantly different than the rate in the entecavir group.…”

“…TmP/GFR was lower in the aggressive dose reduction group than in the standard dose reduction group at every time point, as shown in Figure 3. Percentages of patients with TmP/GFR below 2.4 mg/dL for standard dose reduction group were 17.4%, 30.4%, 21.7%, 21.7% and 26.1% at baseline, month 3, month 6, month 9 and month 12, respectively, whereas percentages of patients with TmP/ GFR below 2.4 mg/dL for aggressive dose reduction group were 39.1%, 47.8%, 43.5%, 47.8% and 43.5% at baseline, month 3, month 6, month 9 and month 12, respectively. However, these differences were not statistically significant.…”

The Risk of Acute Kidney Injury in Hepatitis B Virus-Related Acute on Chronic Liver Failure with Tenofovir Treatment

“…As reported previously, renal injury associated with TDF use usually develops after at least one year of treatment. A recent real-world study from Korea showed that TDF therapy did decrease overall renal function in CHB patients during the first two years of TDF use [13]. Therefore, long-term follow-up might be helpful to access the renal impairment in ACLF patients with different antiviral therapies.…”

“…Currently, tenofovir (TDF) and entecavir (ETV) are both recommended as the first-line antiviral agents for their potent antiviral activity and high genetic barrier for drug resistance [9,10]. However, TDF has also been demonstrated to have potential kidney toxicity by several observational studies and case reports [11][12][13][14]. It is unclear whether or not the use of TDF may increase the risk of AKI in ACLF.…”

Efficacy and safety of tenofovir disoproxil fumarate (TDF) in hepatitis B virus (HBV) monoinfection: longitudinal analysis of a UK cohort

“…Secondly, concerns about renal toxicity should not limit access to treatment; we found that CHB without treatment also had a risk of CKD progression (consistent with a preceding cohort study (27)), which is not significantly different from the risk in treated patients. Previous studies found that risk factors associated with renal function decline in CHB patients include old age, hypertension, diabetes, baseline eGFR, and use of diuretics (44)(45)(46)(47). Therefore, concerns about nephrotoxicity may be more pertinent in these subgroups, and risks should be assessed on a case-by-case basis.…”