Extra-hepatic Effects of Nucleoside and Nucleotide Analogues in Chronic Hepatitis B Treatment.

Journal of Gastroenterology and Hepatology (Impact Factor: 3.5). 12/2013; 29(3). DOI: 10.1111/jgh.12499
Source: PubMed


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 extra-hepatic 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 has been described with the use of nucleotide analogues, although the overwhelming studies have been with HIV-infected patients. However, not all extra-hepatic 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 extra-hepatic effects associated with NA use.

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    • "Tenofovir treatment has been reported to cause some loss in bone mineral density in patients infected with Human Immunodeficiency Virus (HIV) [2]. In two other recent reports [3] [4], Tenofovir in combination with or without emtricitabine was shown to reveal a small decrease (mean <2%) in both spine and hip bone mineral density, although clinically not relevant without increased fracture risk. Other studies have shown excellent long-term safety with very low numbers of side-effects [5] [6] in mono-infected HBV patients. "

    Journal of Hepatology 12/2014; 62(3). DOI:10.1016/j.jhep.2014.12.003 · 11.34 Impact Factor
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    • "The introduction of more potent NUCs with a better resistance profile than LAM and an excellent safety record such as Entecavir (ETV), Tenofovir, and Telbivudine lead to further improvement in the care of patients with imminent hepatic decompensation [3] [4]. Yet, with the cumulative clinical experience using such NUCs, it became clear that use of anti-viral agents may be associated with a number of hepatic and extra hepatic undesirable adverse effects [5]. In 2006, Lange and co-workers reported the development of lactic acidosis believed to be the consequence of mitochondrial toxicity, observed in 5 out of 16 patients with cirrhosis and advanced liver disease and a MELD score >20 treated with ETV [6]. "

    Journal of Hepatology 03/2014; 60(6). DOI:10.1016/j.jhep.2014.03.004 · 11.34 Impact Factor
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    ABSTRACT: Over the last decade, treatment options for chronic Hepatitis B and Hepatitis C infection have markedly evolved. Several FDA---approved drugs are now available for the treatment of chronic hepatitis B, including immunomodulators (standard and pegylated interferon alpha), nucleoside analogues (lamivudine, entecavir and telbivudine) and nucleotide analogues (adefovir dipivoxil and tenofovir). For hepatitis C, the FDA---approved therapies include peginterferon---α. ribavirin, boceprevir, telaprevir, simeprevir and sofosbuvir with expected approval of more agents in the foreseeable future. Some of these antiviral medications have been reported to have nephrotoxic effects, particularly with long---standing therapy, although the exact mechanism has not been fully elucidated. Secondary forms of glomerulonephritis that can be associated with Hepatitis B and Hepatitis C viral infection can further complicate the evaluation of renal failure in this population. Knowledge of the different antiviral medications and their potential nephrotoxic effects is crucial, since early identification and substitution to a different agent with withdrawal of the offending medication, may result in recovery or stabilization of renal function. Close monitoring of renal function while taking new antiviral medications is recommended, as some of the nephrotoxic effects may only appear after long---term use.
    Minerva gastroenterologica e dietologica 07/2014; 60(3).
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