Long-term Renal Safety Between Patients With Chronic Hepatitis B Receiving Tenofovir vs. Entecavir Therapy

A Multicenter Study

Young Eun Chon; Soo Young Park; Seung Up Kim; Han Pyo Hong; Jae Seung Lee; Hye Won Lee; Mi Na Kim; Jun Yong Park; Do Young Kim; Sang Hoon Ahn; Beom Kyung Kim

Disclosures

J Viral Hepat. 2022;29(4):289-296. 

In This Article

Methods

Patients

Treatment-naive CHB patients who received AVT with either daily 0.5 mg ETV (ETV group) or 300 mg TDF (TDF group) as the first-line regimen between 2007 and 2018 in the Division of Gastroenterology and Hepatology at three academic teaching hospitals in the Republic of Korea (Yonsei University Severance Hospital, Kyungpook National University Hospital, and Cha Bundang Medical Center), were screened for eligibility. The exclusion criteria were as follows: (1) age <19 years, (2) history of HCC at enrollment, (3) decompensated cirrhosis at enrollment, (4) AVT for less than 12 months, (5) co-infection with human immunodeficiency virus (HIV) or other hepatitis viruses, (6) history of organ transplantation, and (7) HCC occurrence within 6 months of enrollment (Figure S1).

The reimbursement criteria for ETV and TDF in the Republic of Korea are identical (Table S1). If histologic information was not available, cirrhosis was clinically defined according to the following criteria: (1) platelet count <150,000/μl and ultrasonographic findings suggestive of compensated cirrhosis, including a blunted, nodular liver surface accompanied by splenomegaly (>12 cm); or (2) clinical signs of portal hypertension, such as gastroesophageal varices.

The study protocol complied with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the institutional review board of each institute. Informed consent was waived because of the retrospective nature of the study.

Clinical Evaluation and Follow-up

During follow-up, patients underwent routine laboratory tests, including serum creatinine and HBV-DNA levels as well as other viral markers that were monitored at 3–6-month intervals. Patients were screened for HCC and cirrhotic complications every 6 months using ultrasonography and serum alpha-fetoprotein levels.[19–22]

Each patient's renal function was monitored every 3–6 months. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): eGFR = 141 × min(SCr/κ, 1)α × max(SCr/κ, 1)−1.209 × 0.993Age ×1.018 (if female) ×1.159 (if black).[23] Renal insufficiency was defined as an eGFR <60 ml/min, as calculated by the CKD-EPI equation.

Statistical Analysis

Data are presented as mean ± standard deviation, or number (%) as appropriate. Differences among continuous and categorical variables were compared using Student's t-test and chi-squared test, respectively. To evaluate the change in eGFR during the 6 years of observation, we used the Joinpoint regression method to calculate the average annual percent change (AAPC) in eGFR, odds ratio (ORs), and 95% confidence interval (CI). Logistic regression analysis was performed to investigate the predictors of ongoing renal dysfunction; ORs and 95% CIs were also calculated. Subsequently, a multivariate regression analysis was performed to assess the independent association between the univariate predictors and ongoing renal dysfunction.

All statistical analyses were conducted using SAS software (v9.4; SAS Institute, Cary, NC, USA) and R (v3.6.0, https://cran.r-project.org/). Two-sided p-values <0.05 were considered to indicate statistical significance.

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