Abstract
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. 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 40IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. 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 (>40IU/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). 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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