Objective To evaluate the association between N-acetyltransferase 2 (NAT2) gene polymorphisms and the risk of antituberculosis drug-induced liver injury (ATDILI). Methods We searched the PubMed, Embase, Wanfang, China National Knowledge Internet and VIP databases to find case-control studies, with the last updated search being performed on June 2017. Odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the strength of association. Results A total of 29 studies, involving 1 382 cases and 5 967 controls were included. The results of the Meta-analysis indicated that NAT2 slow acetylators were associated with increased risk of ATDILI compared with fast and intermediate acetylators [OR=3.08, 95%CI (2.44, 3.88), P<0.000 01]. Similar results were also found in subgroup analysis when stratified by ethnicity, isoniazid dosage and diagnostic criteria of ATDILI. Conclusion Individuals with NAT2 slow acetylators may have increased risk of ATDILI.
ObjectiveTo investigate the protective effect of hesperdin (HDN) on acetaminophen (APAP)-induced acute liver injury in mice. MethodsForty-eight male BALB/c mice were randomly divided into six groups:normal group, model group, HDN (the doses respectively were 500, 250 and 125 mg/kg) group and bifendate group. The HDN group was separately intragastrically given different doses of hesperidin for ten days. The bifendate group was given bifendate. Acute liver injury was induced by injecting APAP (150 mg/kg) in all mice except those in the normal group. After 16 hours, all mice were sacrificed. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. The contents of glutathione (GSH) and malondialdehyde (MDA) in liver homogenates were determined. Pathological changes in hepatic tissue were observed under an optical microscope. The expression of high mobility group protein B1 (HMGB1) in hepatic tissue was measured by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. ResultsHDN could significantly reduce serum ALT, AST, liver homogenate MDA levels, improve liver tissue GSH activity and the liver injury was lightened. By RT-PCR and immunohistochemistry, it showed that HDN could inhibit the releasing and expression of HMGB1. ConclusionHDN protects mice from acetaminophen-induced liver injury possibly via mechanisms related to inhibition of the expression and releasing of HMGB1.
Objective To investigate the protective effect of aprotinin on liver injury in septic rats and its mechanism. Methods Thirty male SPF rats were randomly divided into sham operation group, cecum ligation and puncture (CLP) group and aprotinin intervention group (10 rats in each group). The sham operation group was treated with cecal exploration, CLP group and aprotinin group were treated with CLP method to establish sepsis rat model. The rats in each group were sacrificed 24 hours after operation, and the morphological changes of liver tissue in rats were observed, the serum liver function indicators and inflammatory cytokines levels were detected, and the protein expression of Toll-like receptor (TLR4)/nuclear factor κB (NF-κB) signaling pathway in liver tissue was detected. ResultsIn the CLP group, septic rats exhibited significant inflammatory cell infiltration in hepatic tissue and disordered hepatocyte morphology. Compared with the CLP group, the aprotinin group exhibited nearly normal hepatocyte morphology with significant improvement in vacuolar degeneration. Compared with the sham operation group, the serum aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor-α, interleukin-6 were increased, and the expression of TLR4 and p-NF-κB protein in liver tissue was up-regulated in the CLP group (P<0.05). Compared with the CLP group, serum aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor-α, interleukin-6 were decreased, and the expression of TLR4 and p-NF-κB protein in liver tissue was decreased in the aprotinin group (P<0.05). ConclusionAprotinin may play a protective role against sepsis related liver injury by inhibiting TLR4 / NF-κB signaling axis, reducing the production of inflammatory factors and alleviating inflammatory reactions.
ObjectiveTo summarize the mechanism and research progress of ferroptosis in acute liver injury. MethodThe domestic and foreign literatures related of ferroptosis and acute liver injury were searched and reviewed. ResultsFerroptosis was a newly identified form of iron-dependent cell death. The loss of lipid peroxidation repair activity of glutathione peroxidase 4, the presence of redox active iron and the oxidation of phospholipids containing polyunsaturated fatty acids were considered to be distinctive features of ferroptosis. At present, the research on the regulation of ferroptosis genes involved common liver diseases, including drug-induced liver injury, hepatocellular carcinoma, liver fibrosis, liver ischemia-reperfusion injury, liver failure, nonalcoholic fatty liver and so on. Based on the high correlation between ferroptosis and acute liver injury, chemical therapy targeting ferroptosis could provide individualized treatment for patients with acute liver injury in the future. ConclusionsThe ferroptosis plays a critical role in governing various cellular processes and downstream effects. Its aberrant expression contributes to the development and advancement of acute liver injury through diverse mechanisms. Thoroughly exploring the involvement of the ferroptosis in acute liver injury is of utmost significance, as it holds the potential to unveil novel therapeutic targets for effective management of acute liver injury.
Tumor chemotherapy is a treatment method that employs chemotherapeutic drugs to eradicate cancer cells. These drugs are cytotoxic, meaning they can affect both tumor cells and normal cells. In recent years, there has been a gradual increase in chemotherapy-induced liver injury. Chemotherapy-induced parenchymal liver injury often manifests as diffuse lesions, although focal lesions can occasionally be observed. There is a diversity in the pathogenesis and pathological changes of chemotherapy-induced focal liver disease. Radiologically, there is often challenging in differentiating chemotherapy-induced focal liver disease from hepatic metastases. Therefore, early and accurate diagnosis of this condition poses a certain challenge in clinical practice. This article presents the radiological findings of a case of chemotherapy-induced focal liver disease induced by chemotherapy for gastric cancer, and summarizes the radiological features and differential diagnostic points of chemotherapy-induced focal liver disease, aiming to enhance the understanding of this type of lesion among radiologists and clinicians and reduce related missed diagnoses and misdiagnoses.
Objective To assess the effect of pregnant rat adipose-derived stem cells (ADSCs) on repair of acute liver injury. Methods ADSCs were isolated from 18-week pregnant Sprague Dawley rats and were identified by flow cytometry. Twenty Sprague Dawley rats were randomly divided into groups A, B, C, and D (n=5); rats in group A were not treated as normal controls; rats in groups B, C, and D were injected intraperitoneally with CCl4 to establish the acute liver injury model. At 2 hours after modeling, DPBS, 0.1 mL normal rat ADSCs (2×106cells/mL), and pregnant rat ADSCs (2×106cells/mL) were injected into the spleen in groups A, C, and D respectively; rats in group B was not treated. After 7 days, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartic acid transaminase (AST), albumin (ALB), and total protein (TP) in serum were measured. The liver tissue sections were stained with HE. The expressions of Ki67, alpha-fetoprotein (AFP), and ALB were measured by immunohistochemistry. Results The serum levels of TBIL, ALT, and AST in group B were significantly higher than those in groups A, C, and D (P<0.05), but ALB and TP were significantly lower than those in groups A, C, and D (P<0.05). The levels of TBIL, ALT, and AST were significantly higher in groups C and D than group A, and in group C than group D (P<0.05). There was no significant difference in serum levels of ALB among groups A, C, and D (P>0.05). The serum level of TP in groups C and D was significantly lower than that in group A (P<0.05), but no significant difference was found between group C and group D (P>0.05). HE staining showed that the liver tissue of group A had clear structure; the cells arranged neatly with uniform size. The hepatocytes in group B showed obvious edema, disorderly arrangement, dot necrosis in liver lobules, and diffuse infiltration of inflammatory cells. In groups C and D, the inflammation and hepatocellular necrosis were obviously reduced when compared with group B, and the number of vacuoles caused by dilation of mitochondria and rough endoplasmic reticulum was decreased; especially in group D, improvement of liver injury was more effective. The Ki67 positive cell rate was significantly higher in groups C and D than groups A and B (P<0.05), in group B than group A (P<0.05), and in group D than group C (P<0.05). There was no expression of AFP in groups A and B, but positive expression was observed in groups C and D, and AFP positive cell rate of group D was significantly higher than that of group C (t=3.006,P=0.017). ALB expression was significantly higher in groups C and D than groups A and B (P<0.05), and in group D than group C (P<0.05). Conclusion Pregnant rat ADSCs could promote repair of liver injury induced by CCl4.
ObjectiveTo understand the latest development in lineage tracing techniques and their applications in the study of liver regeneration mechanisms. MethodA review of domestic and international literature on the application of lineage tracing techniques in liver regeneration was conducted. ResultsA variety of more reliable and advanced lineage tracing techniques had been developed, such as single-cell RNA sequencing, DNA barcode technology, etc., providing powerful tools for a deeper understanding of the mechanisms of liver regeneration. The marked progress had been made in identifying the origins of liver regeneration cells, identifying liver regeneration areas, and studying the mechanisms of liver regeneration after injury. The lineage tracing techniques help to understand the position and function of different types of liver cells within the liver structure, revealing the regenerative potential and contribution of different subpopulations of liver cells. Moreover, these techniques had supported the phenomenon of transdifferentiation between the hepatocytes and the bile duct cells under chronic liver injury conditions, aiding in understanding the specific roles of key signaling pathways in liver regeneration, such as Wnt/β-catenin, Hippo/YAP, and Notch signaling pathways.ConclusionsAlthough lineage tracing techniques have made marked progress in liver regeneration research, liver regeneration is a complex and important physiological process, and the technique still has limitations, such as challenges in marker specificity, longer research cycles and higher costs, potential limitations in translating from animal models to human clinical applications, inability to solve all questions about liver regeneration mechanisms, and ethical and legal issues. Therefore, more in-depth and comprehensive research is still needed to reveal more details of liver regeneration mechanism.
Objective To summarize the clinical and genetic characteristics of patients with erythropoietic protoporphyria (EPP) and explore treatment strategies for this disease. Methods We systematically searched Chinese and English databases (PubMed, China National Knowledge Infrastructure, Wanfang, VIP database, and China Biomedical Literature Service System) for case reports on Chinese (including overseas Chinese) EPP patients published up to November 2025. Data from 7 genetically confirmed patients diagnosed at the Second Hospital of Hebei Medical University were retrospectively analyzed. A descriptive comparison was conducted between the aggregated data of Chinese patients and published large-scale foreign studies with clear population representativeness. Results A total of 46 EPP patients were included, with 44 from China and 2 from Singapore, comprising 40 males (87.0%) and 6 females (13.0%). The median age at onset was 4 years, the median age at diagnosis was 26 years, and the median diagnostic delay was 18.5 years. Patients who initially presented with cutaneous manifestations (n=14) had a significantly shorter diagnostic delay than those presenting with hepatic or other manifestations (n=32) (7 vs. 24.5 years, Z=–2.160, P=0.031). Liver function impairment was present in 92.9% (39/42) of patients. Genetically, 50.0% (23/46) of patients exhibited compound heterozygous pathogenic variants in the FECH gene, and 78.3% (36/46) carried the c.315-48T>C variant. Strict photoprotection served as the cornerstone of management. Patients with concomitant liver disease received additional treatments such as ursodeoxycholic acid, glucocorticoids, plasma exchange, or liver transplantation. Notably, two patients from the Second Hospital of Hebei Medical University showed significant clinical improvement following therapeutic phlebotomy. There were differences in the clinical and genetic characteristics of EPP patients between Chinese and other ethnic groups. Conclusions Chinese (including Singaporean Chinese) EPP patients are characterized by male predominance, a high prevalence of the c.315-48T>C variant, frequent liver injury, and significant diagnostic delay. EPP should be suspected in cases of unexplained photosensitivity accompanied by hepatic dysfunction. Therapeutic phlebotomy may represent a valuable exploratory option for EPP patients.
ObjectiveTo summarize the protective effect of peroxisome proliferator-activated receptor-beta (PPAR-β) in sepsis-induced liver injury and the mechanism, and to provide new ideas for the prevention and treatment of sepsis-induced liver injury.MethodRelevant literatures about protective effect of PPAR-β in sepsis-induced liver injury were collected and reviewed.ResultsPPAR-β played an important role in cell survival, anti-inflammatory, and anti-oxidation. It acted on a variety of pathophysiological processes, could reduce the activation of inflammatory factors, reduce the production of oxygen free radicals, and inhibit the expression of apoptotic proteins, as well as played an important role in anti-inflammatory, anti-oxidative, and anti-apoptotic.ConclusionPPAR-β can inhibit the activation of NF-κB, reduce the release of inflammatory factors, reduce apoptosis, and reduce liver injury by antioxidation, thereby reducing the mortality of sepsis-induced liver injury.
ObjectiveTo explore the protective effects of abdominal paracentesis drainage (APD) on pancreatitis-associated liver injury in the early phase of severe acute pancreatitis (SAP). MethodsOne hundred and fourteen consecutive patients with SAP, admitted to the General Hospital of Western Theater Command from January 2015 to January 2021, were included in this retrospective study. The patients were divided into the APD group (n=61) and the non-APD group (n=53) based on whether they underwent APD treatment within 72 h of admission. The variables including baseline data, liverfunction tests, inflammation indexes, severity scores and other variables of the two groups were statistically analyzed. ResultsThe hospital mortality in the APD group was lower than that in the non-APD group (8.2% vs. 22.6%, P=0.031). These severity scores (including APACHE Ⅱ score, Ranson score and modified Marshall score) and inflammation indexes (including C-reactive protein, interleukin-6, interleukin-1 and tumor necrosis factor-α) in the APD group were all lower than those in the non-APD group (P＜0.05). In terms of liver function related indexes, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL), and direct bilirubin (DBIL) after treatment in both two groups were significantly lower than those before treatment (P＜0.05). The levels of ALT, AST, TBIL and DBIL after treatment in the APD group were lower than those in the non-APD group (P＜0.05), and the levels of prealbumin and albumin after treatment in the APD group were higher than those in the non-APD group (P＜0.05), but there were no significant differences in the levels of alkaline phosphatase, GGT and 5′ -nucleotidase after treatment in the two group (P＞0.05). ConclusionFor SAP patients with ascitic fluid, application of APD can attenuate liver injury and improve liver function in the early stage of SAP.