Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Lamivudine Therapy Exacerbates Bilirubinemia in Patients Underlying Severely Advanced Hepatitis

  • Choi, Young Hee (College of Pharmacy, Dongguk University_Seoul) ;
  • Lee, Chang Ho (Department of Pharmacology, College of Medicine, Hanyang University) ;
  • Ko, Myong Suk (Korea Intellectual Property Strategy Agency, Business Cooperation Team) ;
  • Han, Hyun Joo (Department of Pharmacy, Seoul National University Hospital) ;
  • Kim, Sang Geon (Department of Pharmacy, Seoul National University Hospital)
  • Received : 2017.09.12
  • Accepted : 2017.09.25
  • Published : 2017.10.15
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Abstract

Lamivudine belongs to the set of antiviral agents effective against hepatitis B virus infection. Given case reports on liver injuries after certain antiviral agent treatments, this study examined the effects of lamivudine on alanine aminotransferase (ALT) and total bilirubin (TB) using a medical system database. A total of 1,321 patients taking lamivudine alone or with others were evaluated using laboratory hits in an electronic medical system at Seoul National University Hospital from 2005 through 2011. The patients were grouped according to prior ALT results: G#1, ALT < 40 IU/L; G#2, 40 IU/L ${\leq}$ ALT < 120 IU/L; G#3, 120 IU/L ${\leq}$ ALT < 240 IU/L; and G#4, ALT ${\geq}$ 240 IU/L. In G#1 and G#2 patients, lamivudine or adefovir treatment decreased ALT and TB compared to prior values. In G#3 and G#4 patients with three times the upper limit of normal (ULN) ${\leq}$ ALT < 15 times the ULN, both ALT and TB were decreased after treatment with lamivudine alone, or adefovir following lamivudine therapy, indicating that lamivudine therapy ameliorated liver functions. However, in G#4 patients who experienced severely advanced hepatitis (ALT ${\geq}$ 15 times the ULN, or ${\geq}$ 600 IU/L), lamivudine augmented TBmax ($6.3{\rightarrow}13.3mg/dL$) despite a slight improvement in ALT ($839{\rightarrow}783IU/L$), indicative of exacerbation of bilirubinemia. Patients who used adefovir after lamivudine also showed a high incidence of hyperbilirubinemia when they experienced severely advanced hepatitis. Treatment with adefovir alone did not show the effect. In conclusion, lamivudine may increase the risk of hyperbilirubinemia in patients with severely advanced hepatitis, implying that caution should be exercised when using lamivudine therapy in certain patient populations.

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References

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