Clinical features of patients with drug-induced liver injury in Shaanxi Province from 2009 to 2019 / 临床肝胆病杂志

Objective To investigate the clinical features of patients with drug-induced liver injury (DILI). Methods A retrospective analysis was performed for the clinical data of 1 376 patients with DILI who were admitted to 20 hospitals in Shaanxi Province, China, from 2009 to 2019 and were diagnosed with RUCAM scale as the diagnostic criteria, and these patients were analyzed in terms of sex, age, underlying diseases, suspected drugs causing DILI, clinical manifestations, laboratory examination, treatment process, and prognosis. The t -test and Wilcoxon test were used for comparison of continuous data between two groups, the chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H rank sum test was used for comparison of ordered polytomous data between groups. Results Among the 1 376 patients, there were 577(41.93%) male patients and 799 (58.07%) female patients, with a male/female ratio of 0.72:1. As for different age groups, the 40-60 years group had a higher incidence rate and accounted for 44.77%, and there was a significant difference in sex distribution between different age groups ( χ 2 =20.784, P =0.008). As for the three clinical types, there was no significant difference in incidence rate between men and women ( χ 2 =1.409, P =0.494), and there was a significant difference in the distribution of clinical types between different age groups ( χ 2 =47.025, P 0.05). Conclusion There is a high incidence rate of DILI in women and middle-aged and elderly people, and traditional Chinese medicine is the leading cause of DILI. Patients with different clinical types tend to have different prognoses, with a good overall prognosis.

The relationship between NLRP3 inflammsomes expression and liver damage after allogeneic hematopoietic stem cell transplantation in mice model / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the function of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammsomes in liver damage after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The study presented a murine (BALB/c-based) model of allo-HSCT. Chimera rate was measured by flow cytometry. The hematoxylin-eosin, Masson's trichrome, immunohistochemistry staining were used to observe the pathology changes in liver, then measured the degree of liver damage. Inflammation cells and NLRP3 were measured by Western blot, cytokines IL-1β, IL-18 and NLRP3 related genes were tested with real-time quantitative polymerase chain reaction (q-PCR).</p><p><b>RESULTS</b>Hematopoietic stem cells had been successfully transplanted, the chimera rate was geater than 97% on the 10th day. Liver damage occurred after allo-HSCT and suffered infiltration of inflammation cells, which reached the peak on day 15, then moved to moderate; the cytokines IL-1β, IL-18 had the similar trend with liver injury, and reached the highest level on day 15, their mRNA expressions increased by (1.19 ± 0.40) fold and (1.64 ± 0.76) fold, respectively; Meanwhile, caspase-1 had the similar trend, its mRNA expression increased by (3.51 ± 0.46) fold on day 15; the inflammasomes NLRP1, NLRP3, NLRC4 and NLRP5 expressed in liver on day 15 of post-allo-HSCT, and NLRP3 inflammasome expressed highest among them. The mRNA and protein level of NLRP3 inflammasomes were kept with the serious degree of the liver damage, its mRNA expression increased by (2.91 ± 0.41) fold on day 15.</p><p><b>CONCLUSION</b>NLRP3 inflammsome expressed in liver injury during allo-HSCT in mice, and may be one of the important factors contributed to liver injury.</p>

Characterization of a reproducible mouse model of hepatic veno-occlusive disease / 中华器官移植杂志

Objective To establish a reproducible mouse model of hepatic veno-occlusive disease (HVOD) after allogeneic bone marrow transplantation (aallo-ABMT) and explore its pathogenesis.Methods Balb/c mice were randomly divided into three groups:(1) normal saline (NS) control group; (2) total body irradiation (TBI) group; (3) allogeneic bone marrow transplantation (allo-BMT) group.Liver weight,total bilirubin (TBil),tumor necrosis factor α (TNF-a),interleukin 6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) were detected on the day 0,5,10,15 and 20 after transplantation.Hepatic vein and sinusoid congestion,infiltration of inflanmatory cells,and damage to hepatic cells and vascular endothelial cells were observed under the light microscopy after HE staining.Fibrosis of hepatic sinusoids and venule was observed under the light microscopy after Masson staining.Results Liver weight and TBil levels were elevated at 5th day and reached the peak at 15th day after all-ABMT.The changes of hepatic congestion and edema were obviously observed and there was infiltration of inflammatory cells at 5th and 10th day after alloABMT.At 15th and 20th day,hepatic congestion,edema and necrosis were reduced and liver damage was mainly presented with liver fibrosis and inflammatory infiltration.All mice died within 10 days after TBI,and hepatic congestion and edema were aggravated.As compared with NS control group,TNF-α,IL-6 and MCP-1 concentrations were significantly increased after all-ABMT.Conclusion A reproducible mouse model of hepatic veno-occlusive disease after all-ABMT was successfully established,and the pathogenesis was closely related to endothelial damage caused by total body irradiation,inflammatory cell infiltration and increased concentrations of cytokines.