BACKGROUND: This study aimed to assess whether long-term entecavir monotherapy induces mitochondrial toxicity in patients with chronic hepatitis B (CHB).

MATERIAL AND METHODS: This was a prospective study in 34 antiviral treatment-naïve patients with CHB who received entecavir monotherapy and were followed up for 4 years. Blood samples were collected after 0, 2, 3, and 4 years of entecavir (ETC) monotherapy (ETC0, ETC2, ETC3, and ETC4, respectively). Mitochondrial DNA (mtDNA) contents were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and mtDNA4977 depletions were detected using nested PCR. Levels of hepatitis B virus (HBV) DNA, alanine aminotransferase, alanine aminotransferase, hepatitis B e antigen (HBeAg), creatine kinase, urea nitrogen, and serum creatinine were recorded.

RESULTS: mtDNA contents at ETC0 (9.6±6.3) and ETC4 (10.3±6.2) were markedly higher than at ETC2 (0.8±0.5, P<0.01) and ETC3 (1.3±0.9, P<0.01), but there were no differences between ETC2 and ETC3 or between ETC0 and ETC4. MtDNA4977 depletion appeared in 79.4% cases at ETC2 and in 70.6% at ETC3, which were much higher than at ETC0 (32.4%, P<0.01) and ETC4 (8.8%, P<0.01), but there were no differences in mtDNA4977 depletion ratio between ETC2 and ETC3, or between ETC0 and ETC4. mtDNA content was negatively correlated to mtDNA4977 depletion (partial regression coefficient of –4.555, P<0.001, R2=0.315). mtDNA content was positively correlated with age (partial regression coefficient of 0.131, P=0.045).

CONCLUSIONS: Results suggest that during 4-year entecavir monotherapy for CHB, the mtDNA contents initially decreased and then increased, while the mtDNA4977 depletion rates first increased and then decreased.

Keywords: Antiviral Agents - blood, DNA, Mitochondrial - metabolism, Follow-Up Studies, Guanine - blood, Hepatitis B, Chronic - genetics, Leukocytes, Mononuclear - metabolism, Mitochondria - metabolism, Prospective Studies, Real-Time Polymerase Chain Reaction