Acute Disease ; Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Hepatitis, Viral, Human ; classification ; pathology ; therapy ; Humans ; Liver Failure, Acute ; etiology ; pathology ; therapy ; Liver Transplantation ; Liver, Artificial ; Prognosis ; Receptors, Cell Surface ; blood ; Troponin I ; blood

Acute-On-Chronic Liver Failure ; blood ; pathology ; Case-Control Studies ; Cytochrome Reductases ; metabolism ; Humans ; Prospective Studies ; alpha-Fetoproteins ; metabolism

Alanine Transaminase ; blood ; Animals ; Bilirubin ; blood ; Disease Models, Animal ; Endotoxemia ; etiology ; Endotoxins ; blood ; Gastrointestinal Hormones ; blood ; Gastrointestinal Motility ; physiology ; Intestine, Small ; physiopathology ; Liver ; pathology ; Liver Failure, Acute ; blood ; etiology ; physiopathology ; Liver Function Tests ; Rats ; Thioacetamide ; administration & dosage

OBJECTIVETo study the role of tumor necrosis factor-alpha (TNFalpha) on enterocyte apoptosis in the experimental model of fulminant hepatic failure (FHF).

METHODSLiver damage was induced by lipopolysaccharide (LPS)/TNFalpha in D-galactosamine (GalN) sensitized BALB/c mice. Serum TNFalpha levels were determined by enzyme-linked immunosorbent assays (ELISA). The intestinal tissues were studied micro- and ultra-microscopically at 2 h, 6 h, 9 h, 12 h and 24 h time points in mice with fulminant hepatic failure. Enterocyte apoptosis was determined by TUNEL method. The TNFR I expression in the intestinal tissue was tested by immunohistochemistry.

RESULTS(1) Gut mucosa was morphologically normal at every time point in all groups, but typical apoptotic cells could be seen in the experimental groups under the electron microscope. Apoptosis rate of gut mucosal epithelial cells was significantly increased at 6 h (large intestine: 6.47e(-3)+/-2.91e(-4); small intestine: 6.64e(-3)+/-3.78e(-4)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 h (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)), and peaked at 12 h in mice with FHF. (2) TNFalpha induced apoptosis of enterocytes in mice with FHF. Anti-TNFalpha inhibited this effect. (3) The integrated OD (IOD) levels of TNFalpha receptor I protein expressed differently in the intestine of mice with GalN/LPS and GalN/ TNFalpha-induced FHF at 9 h after GalN/LPS and GalN/ TNFalpha administration, in comparison with those of the control groups. IOD level of TNFRI changed significantly at 6 h (large intestine: 2.82e(+4)+/-4.60e(+3); small intestine: 1.14e(+4)+/-2.13e(+3)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)) hours after GalN/LPS and GalN/ TNFa administration. The expression of TNFR1 protein was significantly higher at 9 and 12 h after GalN/LPS and GalN/TNFa administration than other time points. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis.

CONCLUSIONTNFa can induce enterocyte apoptosis in mice with FHF. Anti- TNFalpha IgG can inhibit this role. Excessive TNFRI expression of enterocyte in fulminant hepatic failure can be induced by TNFa, which suggests that TNFalpha can induce apoptosis of enterocyte by up-regulation of TNFRI protein expression.

Animals ; Apoptosis ; physiology ; Enterocytes ; pathology ; Galactosamine ; Lipopolysaccharides ; Liver Failure, Acute ; chemically induced ; pathology ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; blood

Animals ; Biotransformation ; Cell Line, Tumor ; Cell Proliferation ; Culture Media ; Diazepam ; pharmacokinetics ; Fibroblasts ; metabolism ; pathology ; Hepatitis, Chronic ; blood ; complications ; Humans ; Liver Failure, Acute ; blood ; etiology ; Liver Neoplasms ; metabolism ; pathology ; Plasma

OBJECTIVE: To study the effect of alprostadil lipid microballoons (lipo PGE1) on the function and morphous of livers from brain-dead rats. METHODS: Twenty-four SD rats were randomly assigned into 4 groups: a control group(Group C),a brain-dead group (Group B) and 2 lipo PGE1 protection groups (Group L1 and Group L2). Brain-dead models were established in Group B,L1 and L2.There was no inflation of Fogarty balloon in Group C, while other operations were the same as Group B. Lipo PGE1 [20 ng/(kg.min) and 40 ng/(kg.min)] was injected via the femoral vein in Group L1 and Group L2 immediately after the establishment of the brain-dead model. The serum levels of alanine aminotransferase (ALT), aspartate amino transferase (AST), endothelin (ET)-1, and tumor necrosis factor (TNF)-α were detected by radioimmunological analyzer. Liver tissues were observed by HE staining 6 h after the brain death. RESULTS: At the time of brain death, the level of ALT, AST, ET-1, and TNF-α in Group B, L1 and L2 was significantly different compared with that in Group C. That in Group L1 and L2 was significantly lower than in Group B(P<0.05). There was no significant difference between Group L1 and L2(P>0.05). CONCLUSION Brain death can cause damage to the liver of rats. Lipo PGE1 can relieve the injury of brain death donors.The protective mechanism of Lipo PGE1 is to decrease the release of serum inflammatory mediators.
Alprostadil ; pharmacology ; Animals ; Brain Death ; blood ; pathology ; physiopathology ; Endothelin-1 ; blood ; Female ; Liver Failure, Acute ; blood ; etiology ; prevention & control ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

Critical Illness ; DNA, Viral ; blood ; genetics ; Genotype ; Hepatitis B Surface Antigens ; blood ; genetics ; Hepatitis B virus ; classification ; genetics ; physiology ; Hepatitis B, Chronic ; pathology ; virology ; Humans ; Liver Failure, Acute ; pathology ; virology ; Mutation ; Promoter Regions, Genetic ; genetics ; Virus Replication

AIMTo study the therapeutic effects of N,N'-diacetyl-L-cystine (DiNAC) on immunological liver failure.

METHODSSerum ALT, AST and T cell subsets in peripheral blood of the experimental animals during the trial period were analyzed by an automatic serum analyzer and a flow cytometer, respectively. The sectioned liver specimens were examined under a light microscope. And 24 h after the injection of Gal/LPS, the survival rate of rats was calculated.

RESULTSDiNAC (50, 200, 800 mg x kg(-1), i.p.) suppressed the elevation of serum levels of ALT and AST, markedly enhanced proliferation and differentiation of T cell subsets (CD4+, CD8+ and Th1, Th2), and improved all the histopathological features. In mice of fulminant hepatic failure (FHF), the survival time significantly prolonged and the survival rate increased 24 h after i.p. DiNAC. These effects were obviously dose-dependent.

CONCLUSIONDiNAC on mice with FHF has an inhibitory action which is related to immune mechanism.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; CD4 Antigens ; metabolism ; CD8 Antigens ; metabolism ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cystine ; analogs & derivatives ; pharmacology ; Liver ; pathology ; Liver Failure, Acute ; blood ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes ; pathology

OBJECTIVETo investigate the expression and role of augmenter of liver regeneration (ALR) in hepatic failure.

METHODSALR polyclonal antibody was prepared and purified. Serum ALR in patients with hepatic failure, chronic hepatitis B and healthy persons were quantified by ELISA, ALR mRNA in hepatic tissues were quantified by real-time PCR.

RESULTSDifferent serum ALR levels foreshowed different outcomes for hepatic failure patients: The liver function was restored in 6 patients with higher ALR level [(1613.5+/-369.6) pmol/ml], and the liver function was deteriorated in 12 patients with lower ALR level [(462.3+/-235.8) pmol/ml]. ALR level in patients with chronic hepatitis B [(969.2+/-332.5) pmol/ml] was similar to that in healthy persons [(806.9+/-240.8) pmol/ml]. ALR mRNA level in hepatic failure patients receiving OLT (103.45 copies/microl) was lower than that in chronic hepatitis B patients (104.37 copies/microl) and healthy persons (104.31 copies/microl), ALR mRNA level in chronic hepatitis B and healthy persons was similar.

CONCLUSIONThese findings suggest serum ALR level reflected ALR mRNA level in liver and is helpful in estimating the survival time of patients with hepatic failure.

Animals ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Expression ; Hepatitis B, Chronic ; blood ; metabolism ; pathology ; Hepatocytes ; metabolism ; Humans ; Liver ; metabolism ; pathology ; Liver Failure, Acute ; blood ; metabolism ; pathology ; Liver Regeneration ; Mice ; Mice, Inbred BALB C ; Polymerase Chain Reaction ; methods ; Prognosis ; Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Recombinant Proteins ; genetics ; metabolism

PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.
Acute Disease ; Adult ; Alanine Transaminase/blood ; Biomarkers/blood ; Cytokines/*blood ; Enzyme-Linked Immunosorbent Assay ; Fas Ligand Protein/blood ; Female ; Hepatitis A/blood/virology ; Hepatitis A virus/*genetics/immunology ; Hepatitis B/blood/virology ; Hepatitis B virus/*genetics/immunology ; Humans ; Interleukin-6/blood ; Interleukin-8/blood ; Interleukins/blood ; Liver Failure/immunology/metabolism/*pathology ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic/immunology/*metabolism