Effect of Tenofovir (TDF) on Renal Function in Patients With Chronic Hepatitis B

Overview

Effect of Long-Term Use of Tenofovir (TDF) on Renal Function in Patients with Chronic Hepatitis B Over a Five-Year Period

Hepatitis B is a viral infection that affects 257 million people worldwide and approximately 820,000 die annually of HBV-related causes and is a leading cause of liver cirrhosis and hepato-cellular carcinoma . Thus, it is a global public health problem. The diagnosis of chronic hepatitis B (CHB) infection is based on the persistence of hepatitis B surface antigens (HBsAg) for more than six months . Some patients may experience acute exacerbation of the HBV infection and progression to acute-on chronic liver failure (ACLF), which has a high mortality rate in spite of substantial supporting and the use of a great quantity resources. Liver transplantation is a latent treatment election for most ACLF patients; hence, factors such as donor shortage and high cost restrict its clinical application. Hence, Early intervention and treatment are very important in patients with ACLF. The goals of antiviral therapy are to suppress viral replication and to ensure the loss of related antigens . Currently, there are two classes of antiviral drugs that are approved for the treatment of chronic Hepatitis B infection: Interferon alpha and Nucleoside analogues. Among the Nucleoside analogues, Entecavir (ETV), Tenofovir disoproxil fumarate (TDF), and Tenofovir alafenamide fumarate (TAF), are the most widely used as first-line treatments. The effectiveness of Nucleos(t)ide analogues (NUCs) is evident, and their usage is easier as they are administered orally and have fewer side effects. But most patients require long-term treatment as premature discontinuation of NUCs treatment may result in virological relapse and liver failure. TDF is one of the most potent antiviral agents against HBV and HIV. However, its potential effects on renal insufficiency are still being questioned . Tenofovir, Entecavir, and Telbivudine are more widely used due to their superior virological, biochemical, and clinical efficacy. They also have a higher barrier to resistance and more tolerable side effect profiles .The kidney is the primary route for the excretion of NUCs so that nephrotoxicity can be encountered during usage of these agents. Although the exact mechanism of nephrotoxicity is not well known, it can be attributed to alterations in renal tubular transporters especially in the proximal renal tubules, as well as apoptosis and mitochondrial toxicity. The tubular damage leads to defective proximal tubular secretion and reabsorption of several substances including phosphate, resulting in reduced serum phosphate levels, elevated phosphate levels in the urine and elevated serum levels of creatinine. Tenofovir disoproxil fumarate (TDF), the prodrug of the Nucleotide analogue reverse transcriptase inhibitor (NRTI) Tenofovir, is active against both HIV and HBV. TDF use as part of antiretroviral therapy (ART) carries a risk of proximal tubular dysfunction and declining glomerular filtration rate (GFR), and monitoring of renal function is recommended during treatment . The risk is related to both level and length of TDF exposure and is enhanced by co-administration of pharmacological boosters (e.g., Ritonavir), low body weight, and pre-existing chronic kidney disease (CKD). Whilst TDF discontinuation is generally associated with improved renal function, longer exposure and lower GFR at TDF interruption predict a reduced likelihood of GFR recovery.

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