Glucocorticoids ; therapeutic use ; Humans ; Liver Failure ; drug therapy

Objective To investigate the effects of YAP on the occurrence and progression of acute liver failure by regulating the ferroptosis pathway and its underlying mechanism. Methods A total of 20 8-week-old C57BL/6 mice were randomly divided into four groups: a control group, an acute liver failure model group, a YAP agonist XMU-MP-1 treatment group and a YAP inhibitor verteporfin treatment group, five mice for each group. HE staining was used to observe the pathological changes of hepatic inflammation and necrosis. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by liver biochemistry. Iron (Fe), malondialdehyde (MDA), glutathione (GSH) determination kits were used to measure their levels in liver tissues of each group. The changes of hepatocyte mitochondrial in each group were observed by electron microscopy. Real time PCR and Western blot analysis were used to detect the mRNA and protein expressions of YAP, glutathione peroxidase 4 (GPX4) and 5-lipoxygenase (5-LOX). Results Compared with the control group, mice in the acute liver failure model group and the YAP inhibitor verteporfin treatment group showed severe liver tissue congestion with inflammatory cell infiltration and structural damage to hepatic lobules. Liver injury was alleviated in the XMU-MP-1 treatment group. With the occurrence of liver failure, plasma ALT and AST levels significantly increased, and liver function was improved in XMU-MP-1 treatment group. Electron microscopy showed that mitochondria in hepatocytes of mice with liver failure became smaller and bilayer membrane density increased, while mitochondria changes in the XMU-MP-1 group were alleviated. In addition, the acute liver failure model group showed an increase in Fe and MDA contents, decreased protein expressions of GPX4, and enhanced expression of 5-LOX, suggesting that ferroptosis was involved in acute liver failure in C57BL/6 mice. Ferroptosis was inhibited by activation of YAP. Conclusion Activation of YAP may ameliorate liver injury by inhibiting ferroptosis.
Animals ; Mice ; Ferroptosis ; Glutathione ; Liver Failure ; Liver Failure, Acute/drug therapy* ; Mice, Inbred C57BL ; Verteporfin ; YAP-Signaling Proteins/metabolism*

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.
Humans ; Antiviral Agents/therapeutic use* ; Ribavirin/therapeutic use* ; Hepatitis, Chronic/drug therapy* ; Hepatitis E virus ; Liver Diseases/drug therapy* ; Liver Failure/drug therapy*

Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Bacterial Infections ; drug therapy ; Humans ; Liver Failure ; drug therapy ; microbiology

Antiviral Agents ; therapeutic use ; Hepatitis B ; drug therapy ; Hepatitis B virus ; Humans ; Liver Failure ; drug therapy ; virology ; Nucleotides ; therapeutic use

OBJECTIVESTo study the clinical characteristics of hepatic failure with aspergillosis.

METHODSThe data of hepatic failure patients with fungal infection hospitalized in our hospital form January 1985 to June 2006 were collected. This research mainly focused on the clinical characteristics of the patients co-infected with aspergillosis.

RESULTSThe occurrence of aspergillosis was 20.5% (104 cases) among 507 hepatic failure patients with fungal infection. Compared with other fungal infection in hepatic failure patients, the effective rate of antifungal therapy and the improvement rate of underlying disease were worse in patients with aspergillus infection (36.5% vs 57.8%, P = 0.000; 26.0% vs 36.7%, P = 0.049). Aspergillus fumigatus was the most common species among 108 fungal species. The species next to Aspergillus fumigatus were Aspergillus niger and Aspergillus flavus. The mainly infected organ was lung and its clinical manifestation was atypical. Liver function could be improved with effective anti-fungus therapy.

CONCLUSIONSDiagnosis and treatment of aspergillosis is difficult in hepatic failure patients co-infected with aspergillosis. Early and effective antifungal therapy is helpful to the recovery of liver function in the hepatic failure patients suspected with aspergillosis co-infection.

Antifungal Agents ; therapeutic use ; Aspergillosis ; diagnosis ; drug therapy ; Aspergillus ; isolation & purification ; Humans ; Liver Failure ; diagnosis ; drug therapy ; microbiology

OBJECTIVE: The maintenance of the correction of kyphotic deformity is one of the difficult problem in tuberculous spondylitis after anterior debriment and fusion with tricortical bone graft. The goal of this study is to find out the efficacy of titanium mesh cage impacted with autogenous bone chip in tuberculous spondylitis treated with anterior intervertebral fusion. MATERIALS AND METHODS: Twelve patients were treated with anterior intervertebral fusion using titanium mesh cage for tuberculous spondylitis from January 1996 to June 1999. We analized the changes in the correction of kyphotic deformity, changes of ESR and CRP, fusion state and recurrence after anterior intervertebral fusion with titanium mesh cage. RESULTS: Clinical symptoms were improved in all twelve patients without any neurologic complications. The mean kyphotic angle corrected was 7.3 degrees immediately after operation, but the loss of correction of kyphotic angle was 2.2 degrees after 3 months and 2.6 degrees after 6 months. We found that the loss of correction of kyphotic deformity occurred mainly within the first 3 months after surgery. Only one patient, suffered from acute hepatic failure after first operation and had an insufficient anti-tuberculous medication therapy, showed recurrence of tuberculous spondylitis after 6 months. The patient underwent a second operation with posterior fixation procedure with good outcome. The changes of ESR and CRP were not specifically important factor to reveal recurrence of tuberculosis of the spine in our series. CONCLUSION: The surgical procedure of tuberculous spondylitis using titanium mesh cage with bone chip seems to be an effective procedure to minimize loss of the correction of kyphotic deformity without any aggravating inflammatory change and recurrence with titanium mesh cage, when sufficient debridement and anti-tuberculous chemotherapy are achieved.
Congenital Abnormalities ; Debridement ; Drug Therapy ; Humans ; Liver Failure, Acute ; Recurrence ; Spine ; Spondylitis* ; Titanium* ; Transplants ; Tuberculosis

BACKGROUND/AIMS: Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to investigate the prognosis predictors and the role of second-line cytotoxic systemic chemotherapy (CSC) in patients with advanced HCC after sorafenib discontinuation in the pre-regorafenib era. METHODS: From 2007 to 2015 in the pre-regorafenib era, the medical records of 166 HCC patients, who had permanently discontinued sorafenib, were retrospectively reviewed. For further analysis of survival factors after sorafenib treatment failure, we compared the survival of patients who had maintained liver function after second-line treatment with the best supportive care (BSC) group and selective BSC (SBSC) group. RESULTS: After discontinuation of sorafenib, median overall survival (OS) was 2.8 (1.9–3.7) months. The OS in patients who discontinued sorafenib due to adverse effect, progression, and poor clinical condition were 5.5 (2.4–8.6), 5.5 (2.2–8.9), and 0.9 (0.5–1.3) months, respectively (P<0.001). The independent predictive factors of survival after sorafenib failure were serum level of bilirubin and albumin, α-fetoprotein, discontinuation cause, and second-line CSC. In comparison with survival between second-line CSC and BSC group, the CSC group showed better survival outcome compared to the BSC group (10.6 vs. 1.6 months, P<0.001) and SBSC group (10.6 vs. 4.2 months, P=0.023). CONCLUSIONS: The survival after sorafenib failure in patients who discontinued sorafenib due to progression and adverse effects was significantly better than in those who discontinued treatment due to clinical deterioration. In the pre-regorafenib era, patients who received second-line CSC showed better survival than those who received only supportive care after sorafenib failure.
Bilirubin ; Carcinoma, Hepatocellular ; Drug Therapy ; Humans ; Liver ; Medical Records ; Prognosis ; Retrospective Studies ; Treatment Failure

It is proposed that gut-liver-lung axis plays an important role in the pathophysiologic development of the critical illness, and it induces excessive inflammatory response in vivo and multiple organ dysfunction syndrome. The mechanisms of therapeutic effects of rhubarb on critical patients are studied based on the theory of Chinese traditional medicine. Researches demonstrate that rhubarb can be used to protect gut barrier, maintain intestinal micro-ecological environment and prevent bacterial translocation. It also can be used to inhibit the release of inflammatory mediators by liver inflammatory-effector cells, reduce inflammatory reaction in the liver and protect hepatic cell functions. Furthermore, rhubarb can be used to reduce pulmonary vascular permeability and extenuate pulmonary edema, inhibit the release of neutrophil myeloperoxidase, and lower the level of inflammatory response and decrease inflammatory mediators in circulation. The above results indicate that rhubarb may interrupt or partly interrupt the gut-liver-lung axis after trauma and reduce the intensity of systemic inflammatory response syndrome. Therefore, rhubarb may obviously lower the incidence of multiple organ dysfunction syndrome and be used to prevent and treat systemic inflammatory response syndrome and multiple organ dysfunction syndrome after trauma.
Capillary Permeability ; drug effects ; Humans ; Intestines ; microbiology ; Liver ; immunology ; Multiple Organ Failure ; drug therapy ; Phytotherapy ; Rheum ; Sepsis ; drug therapy ; Systemic Inflammatory Response Syndrome ; drug therapy

Adult ; Aged ; Burns ; complications ; Female ; Glutathione ; therapeutic use ; Humans ; Liver ; physiopathology ; Liver Failure ; drug therapy ; physiopathology ; Male ; Middle Aged