Effect of Long-Term Use of Tenofovir (TDF) on Bone Density in Patients With Chronic Hepatitis B

Hepatitis B is a viral infection that affects approximately 257 million people worldwide, with an estimated 820,000 deaths annually due to HBV-related complications. It is a leading cause of liver cirrhosis and hepato-cellular carcinoma (HCC), making it a major global public health concern .

The diagnosis of Chronic Hepatitis B (CHB) is established by the persistence of Hepatitis B surface antigen (HBsAg) for more than six months . Some patients with chronic HBV infection may experience acute exacerbation, potentially progressing to acute-on-chronic liver failure (ACLF), a condition with a high mortality rate despite intensive supportive care and resource utilization. While liver transplantation is considered a potential life-saving treatment for ACLF, its widespread clinical application is limited due to donor shortages and high financial costs. Therefore, early intervention and treatment are crucial in managing patients with ACLF .

The primary goals of antiviral therapy in CHB are to suppress viral replication and promote the loss of HBV-related antigens . Currently, there are two major classes of antiviral agents approved for treating CHB: Interferon-Alpha and Nucleos(t)ide Analogues (NUCs). Among the NUCs, Entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF), and Tenofovir Alafenamide (TAF) are the most widely used first-line treatments. These agents are effective, orally administered, and generally well-tolerated. However, long-term treatment is often required, as premature discontinuation may lead to virological relapse and liver failure.

TDF is considered one of the most potent antiviral agents against both HBV and HIV. However, it has been associated with bone toxicity, primarily through the development of osteoporosis via multiple mechanisms. Intracellular accumulation of TDF can lead to proximal tubular dysfunction and Fanconi syndrome, resulting in hypophosphatemic osteomalacia . Additionally, TDF has been shown to reduce osteoblast gene expression, impairing osteoblast function and decreasing bone formation .

Moreover, TDF-induced reduction in phosphate reabsorption in the proximal renal tubules can lead to bone disease, including hypouricemia and hypophosphatemia, ultimately contributing to osteomalacia and an increased risk of fractures. In contrast, TAF exhibits greater plasma stability, and therefore, its impact on renal and bone toxicity may be significantly lower

Inclusion criteria

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Inclusion criteria

Adult male or female patients aged 18 to 60 years.

Diagnosed as HBV-positive.

Long-term use of Tenofovir Disoproxil Fumarate (TDF) for more than five years.

Exclusion criteria

Presence of other chronic liver diseases.

Diagnosed with Chronic Kidney Disease (CKD), regardless of etiology.

Patients who refuse to participate in the study.

Patients on combination therapy, including:

Interferon and Nucleoside analogue combination therapy.

Multiple nucleoside analogue combination therapy.

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