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Recently, Park et al., reported renal safety of tenofovir (TDF) in decompensated cirrhosis patients. Currently, most guidelines recommend the use of nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) infection as a treatment of choice. Among the treatments, TDF and entecavir (ETV) are the two proven effective drugs for CHB patients. However, all NAs have potential risk for mitochondrial dysfunction, and TDF is particularly associated with proximal renal tubule damage. There are several reports regarding risk of TDF associated renal toxicity and osteoporosis. Although several studies emphasized the possibility that TDF might impair renal function and bone density; it is not clear whether this decline in renal function and bone density has clinical meaning. Therefore, we reviewed several studies on the renal safety of TDF and ETV. In the current issue, Park et al. conducted a single center retrospective cohort study of CHB patients with compensated and decompensated cirrhosis. At 96 weeks of observation, changes in estimated glomerular fraction rate (eGFR) and serum creatinine in TDF users were not statistically different with that of ETV users. There was no significant difference in number of patients showing more than 0.2 mg/dL increase in serum creatinine or 20% decrease in eGFR at the end points of the study. Multivariate analysis showed that baseline eGFR, diabetes, and diuretics use was associated with eGFR reduction of more than 20%, and the use of antiviral agents was not an independent risk factor for renal insufficiency incidence. It is still debatable whether TDF compared to ETV could decrease eGFR, which is both clinically and statistically significant. Lok et al., 11 studies meta-analysis showed no significant difference in renal safety profiles of TDF and ETV. However, Han et al., recently reviewed 12 studies, and showed that the incidence of creatinine increase and eGFR decrease was higher in TDF group compare to ETV group (relative risk, 1.601; 95% confidence interval, 1.035 to 2.478; p=0.0034; I=0.0%). Recent European Association for Study of the Liver (EASL) guidelines recommend the use of ETV rather than TDF in patients who are over 60 years, with bone disease or with decreased renal function (eGFR <60 mL/min, albuminuria, on hemodialysis). Park et al.’s paper is very interesting in several respects. First, all the study participants were cirrhotic. The studies focusing only on cirrhotic patients are rare. Although, about 12 studies comparing NAs safety have been published; however, most studies focused on hepatitis naïve patients, and the study sample did not had cirrhotic patients. Moreover, most studies did not even mention the exact proportion of cirrhosis patients, and sometimes decompensated cirrhosis patients were also excluded. Second, Park et al. provided detail information on changes of creatinine/eGFR over 2 years. Most studies simply suggested the prevalence of acute kidney injury (AKI) using various AKI criteria during different observation periods. However, the precise serum creatinine and eGFR changes were not mentioned. According to Han et al., systematic review, only two of 12 articles (including randomized controlled trial, cohort) mentioned quantitative numerical values regarding renal safety. In this paper, multivariate analysis showed that diuretics use, diabetes, and low eGFR are the risk factors for renal dysfunction which is not different from previous studies. Shin et al. analyzed 4,178 CHB patients and found that age, hypertension, diabetes, liver or kidney transplantation, underlying chronic kidney disease (CKD), and diuretics were the risk factors for renal insufficiency during NAs use. Importantly, the prevalence of diabetes and diuretics prescription also increases in decompensated cirrhosis. Al-

Can We Trust Safety of Tenofovir Disoproxil in Patients with Decompensated Cirrhosis?