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This article is linked to Wong et al paper. To view this article, visit
https://doi.org/10.1111/apt.14497.
Chen‐Hua Liu1,2
Jia‐Horng Kao1,2,3
1Department of Internal Medicine, National Taiwan University Hospital,
Taipei, Taiwan
2Hepatitis Research Center, National Taiwan University Hospital, Taipei,
Taiwan
3Graduate Institute of Clinical Medicine, National Taiwan University
College of Medicine, Taipei, Taiwan
Email: [email protected]
INVITED EDITORIALS
Editorial: nephrotoxicity and oral anti‐viral therapy for HBV—facts or fiction?
Chronic hepatitis B virus (HBV) infection remains a major global health problem that leads to cirrhosis, hepatic decompensation,
and hepatocellular carcinoma (HCC).1
Currently, PEG‐interferon and oral nucleot(s)ide analogues have been approved to treat
HBV infection. Among the oral nucleot(s)ide analogues, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF),
and entecavir (ETV) are recommended first line by Western and Eastern guidelines because of potent viral suppression, limited adverse events, and easy use, although most patients need a prolonged course of therapy.2–4
Although TDF and adefovir dipivoxil(ADV) have exhibited potentially dose‐dependent nephrotoxicity in animal and clinical studies, other factors such as HBV‐associated
glomerulonephritis (GN), age, hypertension, and diabetes may also compromise renal function, making the role of long‐term oral
nucleot(s)ide analogues on the renal evolution in HBV patients elusive.5–7
Udompap et al serially assessed the estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration CKD‐EPI) equation in Stanford cohort including 815 patients
with HBV infection who received ETV, TDF, ADV, or no therapy.
Furthermore, the authors evaluated the expected age‐dependent
decline in eGFR in 23 051 participants in the National Health and
Nutrition Examination Survey (NHANES) and compared the trend to the patients in the Stanford cohort.8
By using the generalised
estimating equation method, there was no significant difference in
the expected and observed rates of eGFR decline in untreated patients during a median follow‐up of 4 years, implying that HBV
per se does not increase age‐related eGFR loss decline. In contrast, patients receiving anti‐viral therapy showed a significant eGFR
decline than expected. In a linear mixed‐effect regression model,
ETV was associated with eGFR decline of 1.81 units per year(P=0.06, compared to untreated patients). TDF and ADV treated
patients experienced significantly higher rates of eGFR decline at 2.21 and 2.63 units per year, respectively (both P<0.01). The sensitivity analyses to assess eGFR by Modification of Diet in Renal Disease (MDRD) equation, findings were similar in the healthy population with compensated liver disease and baseline eGFR>60 mL/min/1.73 m2 and treatment naïve subjects. Based on the strict study design, the authors concluded that patients with HBV infection receiving anti‐viral therapy, particularly TDF and ADV, experienced a more rapid decline in eGFR.
This conclusion is in line with a recent large
scale report showing
that patients with HBV infection receiving TDF had higher risks of
renal impairment compared to those receiving ETV or no therapy by propensity score matching.9
Furthermore, another study showed that
decline in renal function was more pronounced in patients receiving TDF than ETV in the presence of baseline poor renal reserve.10
Therefore, treating physicians should judiciously weigh the risk and benefit of using TDF or ADV in patients with HBV infection. TAF or ETV are alternative options to minimise the risk of rapid renal decline in patients with HBV infection and advanced age, hypertension, or baseline poor renal reserve, and those receiving prolonged anti‐viral therapy.
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发表于 2019-1-13 17:36
