Abstract: Objective To investigate the expression of anti-fumarate hydratase autoantibodies (anti-FH antibodies) in the serum of patients with chronic hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), and assess their potential as a biomarker for predicting the prognosis of HBV-ACLF. Methods Between January 2019 and December 2021, 43 patients with chronic hepatitis B (CHB), 40 patients with hepatitis B-related liver cirrhosis (HBV-LC), and 46 patients with HBV-ACLF were enrolled. Anti-FH antibody levels in CHB, HBV-LC and HBV-ACLF patients were compared, and general clinical data were collected for followed-up. Patients with HBV-ACLF were further categorized into an improvement group and a death group, and comparisons were made between the two groups. Results In the HBV-ACLF group, the levels of ALT, AST, TBil and DBil were 72 (36.5, 103.7) U/L, 88 (43.1, 145.6) U/L, 145.8 (100.2, 223.8) μmol/L and 101.9 (88.2, 163.9) μmol/L, respectively. These values were significantly higher than those in the HBV-LC group [32 (27.2, 58.4) U/L, 33 (25.3, 44.3) U/L, 35.4 (20.3, 51.6) μmol/L and 17.1 (14.9, 30.7) μmol/L] and the CHB group [17 (19.3, 31.6) U/L, 15 (18.8, 32.4) U/L, 20.1 (9.4, 32.1) μmol/L and 12.9 (10.5, 26.3) μmol/L], with the differences being statistically significant (P<0.05). The Alb and PLT levels in the HBV-ACLF group were 26.1 (14.2, 38.7) g/L and (90.3±4.6) ×10⁹/L, which were significantly lower than those in the HBV-LC group [38.2 (19.8, 60.2) g/L and (104.4±1.4) ×10⁹/L and the CHB group [40.1 (21.4, 56.8) g/L, (146.6±0.3) ×10⁹/L]. The Anti-FH antibody levels in the CHB group, HBV-LC group and HBV-ACLF groups were (3.5±1.2) mg/L, (25.3±12.5) mg/L and (53.7±11.4) mg/L, respectively. With statistically significant differences(P<0.05). Patients in HBV-ACLF group were categorized into an improvement group (n=31) and a death group (n=15) based on follow-up outcomes. The anti-FH antibody levels, ALT, AST, Alb, TBil, DBil, PT, AFP and MELD scores in the improved group were (13.6±6.8) mg/L, 69.4 (30.6, 80.3) U/L, 79.1 (38.5, 97.8) U/L, 29.3 (23.7, 33.4) g/L, 146.6 (124.7, 200.9) μmol/L, 63.5 (52.2, 93.2) μmol/L, 14.3 (12.0, 26.8), 29 (21.2, 30.4) ng/mL and 1.0 (0.0, 2.4) points, respetively. These values were significantly different from those in the death group, where the values were [ (50.8±25.5) mg/L, 109.9 (68.9, 163.1) U/L, 143.8 (70.3, 193.9) U/L, 16.7 (9.8, 30.4) g/L, 297.4 (208.7, 374.2) μmol/L, 86.7 (53.7, 99.4) μmol/L, 26.8 (20.6, 45.5) seconds, 3.5 (2.1, 7.3) ng/mL and 14.2 (6.0, 20.4) points, with all differences being statistically significant (P<0.05). The area under the ROC curve (AUC) for anti-FH antibodies in predicting mortality in HBV-ACLF patients was 0.751, with an optimal cutoff value of 29.8 mg/L (P<0.05). The sensitivity and specificity at this cutoff were 73.3% and 67.7% respectively. Conclusion The serum expression level of anti-FH antibodies is elevated in patients with HBV-ACLF making it a valuable marker for assessing disease severity and serving as an important prognostic indicator.

Key words: Chronic hepatitis B-acute-on-chronic liver failure, Anti-fumarate hydratase autoantibody, Prognosis