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

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.
Adult ; Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blotting, Western ; End Stage Liver Disease ; genetics ; pathology ; virology ; Female ; Gene Expression ; Hepatitis, Viral, Animal ; genetics ; pathology ; virology ; Host-Pathogen Interactions ; Humans ; Interleukin-1beta ; genetics ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Leukocytes, Mononuclear ; metabolism ; virology ; Liver Failure, Acute ; genetics ; pathology ; virology ; Male ; Mice, Inbred BALB C ; Middle Aged ; Murine hepatitis virus ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Severity of Illness Index ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; blood ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Young Adult

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

OBJECTIVETo investigate the dynamics and clinical significance of serum hepatitis B virus (HBV) DNA levels during the terminal phase of acute-on-chronic liver failure (ACLF) with different hepatitis B e antigen (HBeAg) status.

METHODSOne-hundred-and-seven patients with terminal ACLF were tested for HBeAg status by electrochemiluminescence immunoassay and serum HBV DNA levels by real-time PCR at three chronological time ranges, representing increasing severity of disease phases prior to death (day 0): 29-56 d, 15-28 d, and 0-14 d.

RESULTSIn the 37 HBeAg(+) patients, HBV DNA levels at above-mentioned phases were 6.10+/-1.63, 5.61+/-1.50, and 5.29+/-1.96 log10 copies/mL. In the 70 anti-HBe(+) patients, HBV DNA levels were 4.63+/-1.82, 5.81+/-1.78, and 4.93+/-1.73 log10 copies/mL. Phase to phase comparisons revealed that the HBV DNA level in the HBeAg(+) group was significantly higher than that in the anti-HBe(+) group at 29-56 d (P less than 0.05), and that 15-28 d and 0-14 d were not significantly different (P more than 0.05). Intragroup comparisons of phases revealed no significant differences in the HBeAg(+) group (P more than 0.05), but a significant difference between 15-28 d and 0-14 d (P less than 0.05) for the anti-HBe(+) group.

CONCLUSIONSerum levels of HBV DNA in patients with HBeAg positivity are higher than those in patients with anti-HBe positivity as the disease phase of ACLF nears fatality. Following the deterioration to liver failure, the HBV DNA load in HBeAg(+) patients remains stable while that in anti-HBe(+) patients decreases.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; DNA, Viral ; blood ; End Stage Liver Disease ; blood ; virology ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; pathology ; Humans ; Liver Failure, Acute ; blood ; virology ; Male ; Middle Aged ; Viral Load ; Young Adult

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

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

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

Acute Disease ; Animals ; Apoptosis ; drug effects ; Aspartate Aminotransferases ; blood ; Caspase 3 ; genetics ; metabolism ; Disease Models, Animal ; Lipopolysaccharides ; administration & dosage ; Liver ; drug effects ; metabolism ; pathology ; Liver Failure, Acute ; chemically induced ; metabolism ; prevention & control ; Male ; Mice ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Thiazolidinediones ; administration & dosage ; therapeutic use ; Tumor Necrosis Factor-alpha ; genetics ; 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 analyze the prognostic factors for patients with acute-on-chronic liver failure, and to build a scoring system for assessment of the prognosis of liver failure.

METHODS480 patients with acute-on-chronic liver failure in our hospital from January 2006 to June 2008 were enrolled in this study. The patients were divided into improved group and deteriorated group. The clinical data were analyzed by using chi square test, independent-Samples T Test and Binary logistic regression.

RESULTSThe factors that significantly affected the prognosis of Acute-on-chronic Liver Failure included age, hepatitis or liver cirrhosis, Staging, Hyponatremias, alpha-fetoprotein (AFP), the prothrombin time activity (PTA), total bilirubin (TBil), creatinine (Cr), albumin (ALB) and Hepatic encephalopathy, ascites, alimentary tract hemorrhage (P less than 0.05, P less than 0.01). PTA, Hyponatremias, hepatitis or liver cirrhosis, Hepatic encephalopathy and alimentary tract hemorrhage were independent risk factors of prognosis.

CONCLUSIONPTA, Hyponatremias, hepatitis or liver cirrhosis, Hepatic encephalopathy and alimentary tract hemorrhage are important to build a scoring system to assess the prognosis of Acute-on-chronic Liver Failure and may be useful to guide clinical treatment.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers ; blood ; Child ; Child, Preschool ; Chronic Disease ; Female ; Hepatic Encephalopathy ; complications ; Hepatitis, Viral, Human ; complications ; epidemiology ; Humans ; Hyponatremia ; complications ; Infant ; Liver Failure, Acute ; blood ; etiology ; pathology ; Logistic Models ; Male ; Middle Aged ; Prognosis ; Prothrombin Time ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; Young Adult