Journal of the Formosan Medical Association (Jan 2021)

Role of hepatitis D virus in persistent alanine aminotransferase abnormality among chronic hepatitis B patients treated with nucleotide/nucleoside analogues

  • Tyng-Yuan Jang,
  • Yu-Ju Wei,
  • Ming-Lun Yeh,
  • Shu-Fen Liu,
  • Cheng-Ting Hsu,
  • Po-Yao Hsu,
  • Ta-Wei Liu,
  • Yi-Hung Lin,
  • Po-Cheng Liang,
  • Meng-Hsuan Hsieh,
  • Yu-Min Ko,
  • Yi-Shan Tsai,
  • Kuan-Yu Chen,
  • Ching-Chih Lin,
  • Pei-Chien Tsai,
  • Shu-Chi Wang,
  • Ching-I. Huang,
  • Zu-Yau Lin,
  • Shinn-Cherng Chen,
  • Wan-Long Chuang,
  • Jee-Fu Huang,
  • Chia-Yen Dai,
  • Chung-Feng Huang,
  • Ming-Lung Yu

Journal volume & issue
Vol. 120, no. 1
pp. 303 – 310

Abstract

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Background: The biochemical response is a crucial indicator of prognosis in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs). The impact of hepatitis D virus (HDV) infection on alanine aminotransferase normalization is elusive. Methods: The longitudinal study recruited 1185 CHB patients who received NAs. These patients were tested for anti-HDV antibody and HDV RNA at the initiation of anti-hepatitis B virus (HBV) therapy and annually for patients who were HDV-seropositive. ALT levels were examined at the first and second year of anti-HBV therapy. ALT abnormality was defined as ALT levels above 40 IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. Results: Rates of seropositivity for anti-HDV and HDV RNA were 2.0% and 0.8% among 1185 NA-treated CHB patients, respectively. The strongest factor associated with ALT abnormality (>40 IU/mL) after first year treatment with NAs was HDV RNA seropositivity at year 1 (odds ratio [OR]/95% confidence interval [CI]: 31.44/3.49–283.56, P = 0.002), followed by liver cirrhosis (2.18/1.51–3.15, P < 0.001), detectable HBV DNA at year 1 (OR/CI: 1.99/1.36–2.92, P < 0.001), diabetes (OR/CI: 1.75/1.10–2.78, P = 0.02), body mass index (BMI) (OR/CI: 1.13/1.09–1.18, P < 0.001) and age (OR/CI: 0.97/0.96–0.98, P < 0.001). Among patients who were seronegative for HBV DNA at year 1, the strongest factor associated with ALT abnormality was HDV RNA seropositivity at year 1 (OR/CI: 30.00/3.28–274.05, P = 0.003), followed by liver cirrhosis (OR/CI: 1.83/1.21–2.75, P = 0.004), BMI (OR/CI: 1.16/1.11–1.21, P < 0.001) and age (OR/CI: 0.97/0.96–0.99, P < 0.001). Similarly, the impact of HDV RNA seropositivity on ALT abnormality was noted in patients without detectable HBV DNA but not in those with hepatitis B viremia at treatment year 2 (OR/CI: 10.16/1.33–77.74, P = 0.03). Conclusion: HDV infection played an important role in ALT abnormality in CHB patients receiving 1-year and 2-year NAs. The impact was particularly noted in patients who had successfully suppressed HBV DNA.

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