Therapeutic effect of nucleoside/nucleotide analogues on HBeAg-negative chronic hepatitis B patients with normal or slightly elevated alanine aminotransferase

Abstract

Abstract: Objective To investigate the therapeutic effect of nucleoside/nucleotide analogues (NAs) on hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT). Methods A total of 102 HBeAg-negative CHB patients from June 2018 to July 2021 in our hospital were included, including 68 males and 34 females, with an average of (41.7±9.2) years. According to the baseline level of serum ALT, the cases were divided into normal ALT group (n=59) and slightly elevated ALT group (n=43) [ALT lower than 2 times the upper limit of normal value (ULN)]. The changes of viral response (VR) rate, hepatitis B virus (HBV) DNA, ALT and liver hardness (LSM) were compared between the 2 groups after NAs treatment. Results The male ratio, ALT, aspartate aminotransferase (AST) and HBV DNA in normal group were 57.6%, (25.4±8.0) U/L, (24.2±8.3) U/L and (4.4±1.0) log₁₀ IU/mL, which were significantly lower than those in mildly elevated ALT group [79.1%, (70.3±17.5) U/L, (52.3±16.2) U/L and (5.2±1.3) log₁₀ IU/mL, P<0.05]. The VR rates of normal ALT group were 49.2% (29/59), 66.1% (39/59), 81.4% (48/59), 84.7% (50/59) and 93.2% (55/59) at the 12th, 24th, 36th, 48th, 72nd and 96th week respectively. The corresponding VR rates in the group with mild elevation of ALT were 41.9% (18/43), 58.1% (25/43), 69.8% (30/43), 76.7% (33/43), 86.0% (37/43) and 95.3% (41/43). Logarithmic rank test showed that there was no significant difference in VR rate between the 2 groups (P>0.05). HBV DNA load decreased significantly during NAs antiviral treatment. In the normal group, after 48 weeks and 96 weeks of treatment, the average level of HBV DNA decreased by (2.8±1.2) log₁₀ IU/mL and (3.7±1.1) log₁₀ IU/mL. The level of HBV DNA in the group with slight elevation of ALT decreased (3.6±1.5) log₁₀IU/mL and (4.3±1.5) log₁₀IU/mL on average. There was no significant difference in the average decline of HBV DNA between the 2 groups (P>0.05). At the 12th, 24th, 36th, 48th, 72nd and 96th week, the normal group's ALT normalization rates were 71.2% (42/59), 86.4% (51/59), 91.5% (54/59), 94.9% (56/59) and 96.6% (57/59), respectively. The ALT normalization rates of the corresponding mildly elevated ALT group were 53.5% (23/43), 76.7% (33/43), 83.7% (36/43), 88.4% (38/43), 95.3% (41/43) and 100% (43/43). There was no significant difference in the normalization rate of ALT between the 2 groups (P>0.05). Thirty-seven HBeAg-negative CHB patients with normal ALT and slightly elevated ALT were examined by FibroScan at 48 weeks after NAs treatment, and LSM was significantly improved [(7.9±3.2) kPa compared with (6.6±2.9) kPa, P<0.05]; FibroScan examination was performed in 25 patients after 96 weeks of NAs treatment, which showed that LSM value was significantly improved after treatment [(8.1±3.3) kPa vs (6.2±2.7) kPa, P<0.05]. Conclusion NAs effectively inhibited the HBV DNA level of HBeAg-negative CHB patients with normal or slightly elevated ALT, and improved the liver histology. Therefore, even HBeAg-negative CHB cases with normal ALT are recommended for antiviral treatment. In addition, significant liver fibrosis is not uncommon in HBeAg-negative CHB patients with normal or mildly elevated ALT, and they should be routinely evaluated for liver fibrosis such as FibroScan.

Key words: Chronic hepatitis B, Hepatits B e antigen, Nucleoside/nucleotide analogues, Alanine aminotransferase, Liver stiffness measurement

CAO Jing-jing, LI Rong, LI Jing, PAN Feng. Therapeutic effect of nucleoside/nucleotide analogues on HBeAg-negative chronic hepatitis B patients with normal or slightly elevated alanine aminotransferase[J]. Chinese Hepatolgy, 2023, 28(4): 432-435.

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