Short-chain fatty acids mitigate Methamphetamine-induced hepatic injuries in a Sigma-1 receptor-dependent manner.

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R-/-) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy.

Polystyrene nanoplastics exacerbate aflatoxin B1-induced hepatic injuries by modulating the gut-liver axis.

Dietary pollution of Aflatoxin B1 (AFB1) poses a great threat to global food safety, which can result in serious hepatic injuries. Following the widespread use of plastic tableware, co-exposure to microplastics and AFB1 has dramatically increased. However, whether microplastics could exert synergistic effects with AFB1 and amplify its hepatotoxicity, and the underlying mechanisms are still unelucidated. Here, mice were orally exposed to 100 nm polystyrene nanoplastics (NPs) and AFB1 to investigate the influences of NPs on AFB1-induced hepatic injuries. We found that exposure to only NPs or AFB1 resulted in colonic inflammation and the impairment of the intestinal barrier, which was exacerbated by combined exposure to NPs and AFB1. Meanwhile, co-exposure to NPs exacerbated AFB1-induced dysbiosis of gut microbiota and remodeling of the fecal metabolome. Moreover, NPs and AFB1 co-exposure exhibited higher levels of systemic inflammatory factors compared to AFB1 exposure. Additionally, NPs co-exposure further exacerbated AFB1-induced hepatic fibrosis and inflammation, which could be associated with the overactivation of the TLR4/MyD88/NF-κB pathway. Notably, Spearman's correlation analysis revealed that the exacerbation of NPs co-exposure was closely associated with microbial dysbiosis. Furthermore, microbiota from NPs-exposed mice (NPsFMT) partly reproduced the exacerbation of NPs on AFB1-induced systemic and hepatic inflammation, but not fibrosis. In summary, our findings indicate that gut microbiota could be involved in the exacerbation of NPs on AFB1-induced hepatic injuries, highlighting the health risks of NPs.

Gut Microbiota Participates in Polystyrene Microplastics-Induced Hepatic Injuries by Modulating the Gut-Liver Axis.

Dietary pollution by polystyrene microplastics (MPs) can cause hepatic injuries and microbial dysbiosis. Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, exerts beneficial effects on the liver by modulating the gut microbiota. However, the role of microbiota in MPs-induced hepatic injuries and the protective effect of EGCG have not been clarified. Here, 5 µm MPs were orally administered to mice to induce hepatic injuries. Subsequently, antibiotic cocktail (ABX) and fecal microbial transplant (FMT) experiments were performed to investigate the underlying microbial mechanisms. Additionally, EGCG was orally administered to mice to explore its protection against MPs-induced hepatic injuries. Our results showed that MPs activated systemic and hepatic inflammation, promoted fibrosis, and altered the liver metabolome; meanwhile, MPs damaged the gut homeostasis by disturbing the gut microbiome, promoting colonic inflammation, and impairing the intestinal barrier. Notably, MPs reduced the abundance of the probiotics Akkermansia, Mucispirillum, and Faecalibaculum while increasing the pathogenic Tuzzerella. Interestingly, the elimination of gut microbiota mitigated MPs-induced colonic inflammation and intestinal barrier impairment. Moreover, ABX ameliorated MPs-induced systemic and hepatic inflammation but not fibrosis. Correspondingly, microbiota from MPs-administered mice induced colonic, systemic, and hepatic inflammation, while their profibrosis effect on the liver was not observed. Finally, EGCG elevated the abundance of probiotics and effectively repressed MPs-induced colonic inflammation. MPs-induced systemic and hepatic inflammation, fibrosis, and remodeling of the liver metabolome were also attenuated by EGCG. These findings illustrated that gut microbiota contributed to MPs-induced colonic and hepatic injuries, while EGCG could serve as a potential prevention strategy for these adverse consequences.

Prognostic value of the albumin-bilirubin score in patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare life-threatening systemic disease. This study aimed to assess the prognostic value of pretreatment albumin-bilirubin (ALBI). We retrospectively analyzed 168 non-Hodgkin lymphoma-associated secondary hemophagocytic lymphohistiocytosis (NHL-sHLH) patients with hepatic injuries. Multivariable logistic/Cox models and restricted cubic spline models were conducted to evaluate the relationships between the ALBI score and short- and long-term survival. Among 168 adult NHL-sHLH patients, 82 (48.8%) patients died within 30 days after admission, and 144 (85.7%) patients died during the follow-up period. Multivariable logistic/Cox regression model indicated that ALBI grade could be an independent risk factor for predicting the prognosis of patients with 30-day mortality and overall survival (odds ratios [OR]30 days 5.37, 95% confidence interval 2.41-12.64, P < 0.001; hazard ratios [HR]OS 1.52, 95% confidence interval 1.06-2.18, P = 0.023), respectively. The restricted cubic spline curve displayed a linear and positive relationship between the ALBI score and risk of mortality (P for nonlinearity =0.503). Furthermore, receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for predicting mortality by integrative analysis of the ALBI score and ferritin was significantly improved compared to the ALBI score (AUC 30 days: 0.820 vs 0.693, P = 0.001; AUC1 year: 0.754 vs 0.681, P = 0.043) or ferritin (AUC30 days: 0.820 vs 0.724, P = 0.005; AUC1 year: 0.754 vs 0.658, P = 0.031) alone. The ALBI score could be a useful indicator of short and long-term survival for NHL-sHLH patients with hepatic injuries.

Angioembolization May Improve Survival in Patients With Severe Hepatic Injuries.

INTRODUCTION: Although reports on angioembolization (AE) show favorable results for severe hepatic trauma, information is lacking on its benefit in the management and mechanisms of injury (MOI). This study examined patient outcomes with severe hepatic injuries to determine the association of in-hospital mortality with AE. The hypothesis is that AE is associated with increased survival in severe hepatic injuries. METHODS: Demographics, age, sex, MOI, shock index (SI), ≥6 units packed red blood cells (PRBCs) per hospital length of stay (LOS), intensive care unit LOS, injury severity score (ISS), and AE were collected. The primary outcome was in-hospital mortality. Patients were stratified into groups according to MOI, AE, and operative vs non-operative management. Multivariable logistic regression determined the independent association of mortality with AE vs no AE and operative vs nonoperative management and modeled the odds of mortality controlling for MOI, AE vs no AE, age and ISS groups, SI >.9, and ≥6 units PRBCs/LOS. RESULTS: From 2013 to 2018, 2462 patients (1744 blunt; 718 penetrating) were treated for severe hepatic injuries. AE was used in only 21% of patients. Mortality rates increased with higher ISS and age. AE was associated with mortality when compared to patients who did not undergo AE. The strongest associations with mortality were ISS ≥25, transfusion ≥ 6 units PRBCs/LOS, and age ≥65 years. CONCLUSIONS: AE is underutilized in severe hepatic trauma. AE may be a valuable adjunct in the treatment of severe hepatic injuries especially in older patients and those needing exploratory laparotomy.

A modern, multicenter evaluation of hepatic angioembolization - Complications and readmissions persist.

BACKGROUND: Indications for angioembolization (AE) following liver injury are not clearly defined. This study evaluated the outcomes and complications of hepatic AE. We hypothesize hepatic angioembolization is a useful adjunct to non-operative management of liver injury but with significant morbidity. METHODS: Subjects were identified utilizing trauma registries from centers in a regional trauma network from 2010 to 2017 with an Abbreviated Injury Scale (AIS) coded hepatic injury and an ICD9/10 for hepatic angiography (HA). RESULTS: 1319 patients with liver injuries were identified, with 30 (2.3%) patients undergoing HA: median ISS was 26, and median liver AIS was 4. Twenty-three subjects required AE. 81% had extravasation on CT from a liver injury. 63% underwent HA as initial intervention. 43% of AE subjects had liver-related complications with 35% 30-day readmission but with zero 30-day mortality. CONCLUSIONS: While there were zero reported deaths, a high rate of morbidity and readmission was found. This may be due to the angioembolization or the liver injury itself.

Is the Grading of Liver Injuries a Useful Clinical Tool in the Initial Management of Blunt Trauma Patients?

BACKGROUND: Computed tomography (CT) has become the preferred method for evaluation of the abdomen for victims of blunt trauma. Grading of liver injuries, primarily by CT, has been advocated as a measure of severity and, by implication, the likelihood for intervention or complications. We have sought to determine if grading of liver injuries, as a clinical tool, affects immediate or extended management of patients. METHODS: We have retrospectively reviewed all patients sustaining blunt liver injuries as diagnosed by CT over a five-year period at a Level I trauma center to determine if grading of injury influenced management. The AAST organ scaling system was utilized (major grade 4-5, minor grade 1-3), as well as the ISS, AIS, mortality, morbidity, and treatment. There were 133 patients available for review. The patients were grouped into major (n = 20) and minor (n = 113) liver injuries and operative (n = 12) and nonoperative (n = 121) management. RESULTS: Major liver injuries had a higher ISS (39 + 13 vs. 27 + 15, p = 0.001) and were more likely to require operative intervention (5/20 vs. 7/113, p = 0.02). Mortality in this group was not different (major vs. minor), and there were no differences in the incidence of complications. Twelve patients (9%) required operation, all for hemodynamic instability, all within 24 h, and 11/12 within 6 h. At operation 8/12 patients had other sources of bleeding beside the liver injury, and 7/12 had minor hepatic injuries. The operative patients had higher ISS and AIS scores (head/neck, chest, abdomen, extremities) than those managed nonoperatively. More patients died in the operative group (6/12 vs. 8/121, p = 0.0003). There were more pulmonary (6/12 vs. 16/121, p = 0.005), cardiovascular (6/12 vs. 19/121, p = 0.01), and infectious (5/12 vs. 20/121, p = 0.049) complications in the operative group. There were 14 deaths overall; 13/14 were due to traumatic brain injury, and 8/14 required urgent operation for hemorrhage. CONCLUSIONS: In conclusion, grading of liver injuries does not seem to influence immediate management. Physiologic behavior dictated management and need for operative intervention, as well as prognosis. However, both major hepatic injuries and need for early operation reflected overall severity and the possibility of associated injuries.

Lesiones Hepáticas en pacientes con síndrome de inmunodeficiencia adquirida (SIDA)

El hígado puede estar comprometido por el virus de inmunodeficiencia humana (VIH), tanto durante el período de la primoinfección como en la etapa avanzada de la enfermedad. Objetivo: el objetivo del presente trabajo fue determinar los hallazgos histológicos en biopsias hepáticas de pacientes con SIDA, hospitalizados en el Hospital Universitario de Caracas. Materiales y Métodos: se incluyeron 21 pacientes a quienes se les realizaron biopsias hepáticas entre marzo de 2001 y marzo de 2006, los datos clínicos fueron tomados de los registros de historias médicas. A todas las biopsias se les realizaron coloraciones especiales y fueron analizadas por patólogos con experiencia en patología hepática. Resultados: los pacientes estaban conformados por 16 del sexo masculino y 5 del sexo femenino con edades comprendidas entre 63-25 años. De las 21 biopsias se reportaron los hallazgos en 18. Entre éstos tenemos: 10 con hepatitis granulomatosa, 2 con esteatosis hepática, 1 hepatitis crónica por virus B, 1 esteatohepatitis, 1 linfoma no Hodgkin, 1 histoplasmosis, 1 hepatotoxicidad y 1 no concluyente. No hubo diferencias estadísticamente significativas al comparar el diagnóstico clínico con los hallazgos anatomopatológicos. conclusión: en nuestro estudio el hallazgo más frecuente fue la hepatitis granulomatosa. En algunos casos, la biopsia confirmó la sospecha clínica y en la mayoría de los estudios la indicación fue alteración del perfil hepático. Nosotros recomendamos la realización de la biopsia en aquellos pacientes en quienes los hallazgos clínicos y exámenes menos invasivos no hayan ayudado en el diagnóstico.

The liver can be frequently a target of the virus of acquired immunodeficiency syndrome (HIV), during the first infection period as in advanced stages of the disease. Aim: The objective of the present study was to determine the histological findings in hepatic biopsies of patient with AIDS hospitalized in our centre. Materials and Methods: 21 patients were included who had a hepatic biopsy taken between March 2001 and March 2006; the clinical data were taken from the registries of medical files. All specimens were treated with special colorations and were analyzed by pathologists with experience in hepathology. Results: There were 16 male patients and 5 female, with ages ranging between 63-25 years old. Of the 21 biopsies the findings were reported in 18, 10 had granulomatous hepatitis, 2 hepatic steatosis, 1 chronic hepatitis by virus B, 1 steatohepatitis, 1 non Hodgkin lymphoma, 1 histoplasmosis, 1 hepatotoxicity and 1 was not conclusive. Conclusion: In our study the most frequent finding was granulomatous hepatitis, the biopsy confirmed in some cases the clinical suspicion and in most of the cases the indication was an alteration in the laboratory hepatic profile. We recommend a liver biopsy to be performed in those patients where clinical findings and less invasive tests have not helped to come to a definite diagnosis.

Isolated Inferior Vena Cava Thrombosis after Traumatic Hepatic Injury

The incidence of acute deep vein thrombosis after multiple trauma has been reported to range from 1.7 to 10%. In general, a thrombus of the calf vein migrates to the proximal vein. An isolated inferior vena cava (IVC) thrombosis without a peripheral venous thrombosis is rare. A 35-year-old woman was admitted as a result of a large subcapsular hematoma in the right hepatic lobe after a blunt injury caused by an automobile accident. The thrombus in the IVC was detected incidentally during a follow up CT scan three weeks after the trauma. A compression of the IVC by the displaced hepatic parenchyme as a result of a large subcapsular hematoma is a possible mechanism for the IVC thrombosis because there was no distal venous thrombosis and no evidence of hypercoagulability. A retrievable caval filter (Gunther-Tulip(TM), Cook Inc. Bloominton, USA) was placed in the suprarenal vena cava via the right internal jugular venous approach. After placing the retrieval caval filter, aspiration thrombectomy was attempted through the right femoral vein. The luminal patency of the IVC was restored immediately after retrieving the thrombus. The subcapsular hematoma in the right hepatic lobe disappeared two months later and there was no evidence of a residual thrombus in the inferior vena cava.