Tri-typing of hepatitis B-related acute-on-chronic liver failure defined by the World Gastroenterology Organization.

BACKGROUND AND AIM: Tri-typing of acute-on-chronic liver failure (ACLF), as proposed by the World Gastroenterology Organization (WGO), has not been validated in patients infected with hepatitis B virus (HBV). We aim to compare the three types of ACLF patients in clinic characteristics. METHODS: Hospitalized ACLF patients with chronic hepatitis B from five hepatology centers were retrospectively selected and grouped according to the WGO classification. For each group, we investigated laboratory tests, precipitating events, organ failure, and clinical outcome. RESULTS: Compared with type-B (n = 262, compensated cirrhosis) and type-C (n = 129, decompensated cirrhosis) ACLF, type-A patients (n = 195, non-cirrhosis) were associated with a younger age, the highest platelet counts, the highest aminotransferase levels, and the most active HBV replications. HBV reactivation were more predominant in type-A, while bacterial infections in type-B and type-C ACLF cases. Liver failure (97.4%) and coagulation failure (86.7%) were most common in type-A compared with type-B or type-C ACLF patients. Kidney failure was predominantly identified in type-C subjects (41.9%) and was highest (23/38, 60.5%) in grade 1 ACLF patients. Furthermore, type-C ACLF showed the highest 28-day (65.2%) and 90-day (75.3%) mortalities, compared with type-A (48.7% and 54.4%, respectively) and type-B (48.4% and 62.8%, respectively) ACLF cases. Compared with type-A (11.7%) ACLF patients, the increased mortality from 28 to 90 days was higher in type-B (31.6%) and type-C (37.5%). CONCLUSION: Tri-typing of HBV-related ACLF in accordance with the WGO definition was able to distinguish clinical characteristics, including precipitating events, organ failure, and short-term prognosis in ACLF patients.

Establishment of a zebrafish hematological disease model induced by 1,4-benzoquinone.

Benzene exposure is associated with various hematological disorders, in particular leukemia. The reactive metabolite of benzene, 1,4-benzoquinone (BQ), generated in bone marrow, is suggested to be a key molecule in mediating benzene-induced hematotoxicity and carcinogenicity. However, its pathogenic role remains largely unknown due to a lack of suitable vertebrate whole-organism models. Here, we present an in vivo study to reveal the effect of BQ exposure on hematotoxicity in zebrafish. From embryonic stages to adulthood, BQ exposure suppressed erythroid and lymphoid hematopoiesis but led to abnormal accumulation of myeloid cells and precursors, which resembles benzene-induced cytopenia and myeloid dysplasia in humans. This myeloid expansion is caused by granulocyte, but not macrophage, lineage, emphasizing the significant role of lineage specificity in BQ-mediated hematopoietic toxicity. Analysis of the c-myb (also known as myb)-deficient mutant cmybhkz3 revealed that BQ induced neutrophilia in a c-myb-dependent manner, demonstrating that c-myb is a key intrinsic mediator of BQ hematotoxicity. Our study reveals that BQ causes lineage-specific hematotoxicity in zebrafish from embryonic stages to adulthood. Since c-myb is indispensable for BQ to induce neutrophilia, c-myb could serve as a potential drug target for reversing BQ hematotoxicity.