SUMMARYWhat is known and Objective: Adefovir dipivoxil (ADV) is an oral bioavailable prodrug of adefovir that possesses potent in vitro activity against hepadnaviruses, retroviruses and herpes viruses. ADV is excreted unchanged in the urine through glomerular filtration and tubular secretion and is known to be nephrotoxic at doses of 60 mg daily and above. Thus, the long-term safety of ADV, particularly nephrotoxicity, is a major concern. Our objective is to comment on the nephrotoxcicity of low-dose (10 mg daily) ADV through a case report. Comment: The clinical features of nephrotoxicity because of ADV are described. A case report of acquired Fanconi's syndrome in a chronic hepatitis B patient treated with ADV 10 mg daily is used to illustrate several key aspects. What is new and Conclusion: Adefovir dipivoxil can be nephrotoxic at conventional dosage and therefore, patients treated with long-term ADV should have regular monitoring of renal function, and calcium and phosphate levels. WHAT IS KNOWN AND OBJECTIVESWorldwide, an estimated 400 million individuals are chronically infected with hepatitis B virus (HBV).1 Carriers of HBV are at increased risk of developing cirrhosis, hepatic decompensation and hepatocellular carcinoma.2 Approximately 15% to 40% will develop serious sequelae during their lifetime and approximately one million die each year from complications of infection.3 Thus, the aims of treatment are to achieve suppression of HBV replication and remission of liver disease. Currently, the main therapeutic agents are pegylated interferon and oral nucleos(t)ide analogues. Adefovir dipivoxil (ADV) is an oral bioavailable prodrug of adefovir [9-(2-phosphonylmethoxyethyl) adenine (PMEA)], an analogue of adenosine monophosphate that possesses potent in vitro activity against hepadnaviruses, retroviruses and herpes viruses. The active intracellular metabolite adefovir diphosphate of longer intracellular half-life, produced by the addition of two phosphate groups by ubiquitous cellular nucleotide kinases, cause inhibition of both reverse transcriptase and HBV DNA polymerase and is incorporated into DNA, causing chain termination. Clinical studies have shown that adefovir is effective in suppressing wild-type as well as lamivudine (LAM)-resistant HBV. ADV is excreted unchanged in the urine through glomerular filtration and tubular secretion and administration of 60 mg daily and above have been associated with nephrotoxicity. Thus, the long-term renal safety of ADV is a major concern. Here, we comment on the potential nephrotoxicity of low-dose ADV through a case report of acquired Fanconi's syndrome associated with prolonged low-dose (10 mg daily) ADV therapy in a chronic hepatitis B e-antigen-negative patient. COMMENTA 74-year-old woman was admitted with progressive muscle weakness and generalized bone pain. She was a known case of chronic hepatitis B e-antigen-negative-related cirrhosis of ChildPugh-Turcotte (CPT) class B and had been on LAM since February 2004. She developed LAM resistance because of HBV mu...
Patients with first presentation UC are more commonly seen in colorectal surgery clinics where rigid sigmoidoscopy is more frequently undertaken, allowing earlier commencement of UC treatment.
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