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Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment
Author(s) -
Fung James,
Seto WaiKay,
Lai ChingLung,
Yuen ManFung
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12499
Subject(s) - telbivudine , medicine , lactic acidosis , entecavir , mitochondrial toxicity , nephropathy , myopathy , adefovir , gastroenterology , immunology , hepatitis b virus , toxicity , endocrinology , lamivudine , virus , diabetes mellitus
Oral nucleoside/nucleotide analogues ( NAs ) are the mainstay of therapy for patients with chronic hepatitis B and are generally well tolerated. Despite this, the safety profile of NAs is of paramount importance since the majority of patients will require long‐term treatment. All NAs can potentially affect human DNA polymerase with decrease in mitochondrial DNA , leading to manifestations of mitochondrial toxicity. As a class effect, therefore, NAs can potentially cause extrahepatic conditions, such as myopathy, nephropathy, neuropathy, and lactic acidosis. Indeed, effects on muscles, including myopathy and creatine kinase elevations, have been described with clevudine and telbivudine use. Both adefovir and tenofovir are associated with dose‐dependent nephropathy, predominantly affecting the proximal renal tubules. Neuropathy appears to be rare, and most commonly reported in patients receiving combination therapy with telbivudine and interferon. Increased risk of lactic acidosis has also been described for those with impaired liver and renal function taking entecavir. Loss of bone mineral density and hypophosphatemia have been described with the use of NAs , although the overwhelming studies have been with human immunodeficiency virus‐infected patients. However, not all extrahepatic effects are detrimental. Recent evidence has suggested a potential renal beneficial effect with the use of telbivudine. The effect of NAs on pregnancy appears to be minimal for all NAs , with telbivudine and tenofovir having a more favorable category B rating. Ongoing pharmacovigilance is essential to identify new and monitor existing extrahepatic effects associated with NA use.