RESUMO
OBJECTIVE: To investigate the relationship between tissue inhibitor of metalloproteinase-1 (TIMP-1) expression and the severity of liver fibrosis in chronic hepatitis B (CHB) patients, and to explore the diagnostic value of serum TIMP-1. METHODS: A total of 159 CHB patients underwent liver biopsy for the analysis of liver fibrosis stages and inflammation. Serum TIMP-1 was determined by ELISA. Hyaluronic acid (HA), procollagen type III (PCIII), collagen type IV (CIV), laminin (LN), and FIB-4 index were determined and calculated, and diagnostic accuracy was analyzed using receiver operating characteristic (ROC) curve. RESULTS: Serum levels of TIMP-1 were associated with the grade of liver inflammation in CHB patients (r = 0.695, P < 0.01), especially in those without fibrosis or with stage 1 fibrosis, and were also positively correlated with liver fibrosis in CHB patients (r = 0.854, P < 0.01), particularly in those with inflammation at grade 1, 2 and 3. The area under the ROC curve (AUROC) of serum TIMP-1 was 0.918 for significant liver fibrosis (≥stage 2), and a sensitivity of 89.4% and specificity of 83.6% were obtained with a cut-off value of ≥174.5 ng/mL of serum TIMP-1, which were higher than that of HA, CIV and FIB-4 index. CONCLUSION: TIMP-1 is a valuable single biomarker for the evaluation of significant fibrosis in CHB patients.
Assuntos
Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Inibidor Tecidual de Metaloproteinase-1/sangue , Adolescente , Adulto , Biomarcadores/sangue , Biópsia , Colágeno Tipo III/sangue , Colágeno Tipo IV/sangue , Progressão da Doença , Feminino , Humanos , Ácido Hialurônico/sangue , Laminina/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Adulto JovemRESUMO
OBJECTIVE: To examine serum tissue inhibitors of metalloproteinases (TIMP) -1 and -2 levels in children with nonalcoholic fatty liver disease and to investigate possible roles of the two markers. METHODS: One hundred and five obese children were classified into 4 groups: simple obesity (n=44), simple nonalcoholic fatty liver (SNAFL, n=25), and nonalcoholic steatohepatitis (NASH, n=36). Serum TIMP-1 and -2 levels were measured using ELISA. Serum ALT and gamma-GT levels were measured with totally automatic enzymatic method. RESULTS: Serum levels of TIMP-1 and gamma-GT increased with the disease development from simple obesity to SNAFL and NASH (P<0.05). Both serum TIMP-1 and -2 levels were positively correlated with gamma-GT levels (r=0.534, P<0.01; r=0.351, P<0.05, respectively). Ninety-seven percent of children in the NASH group had serum TIMP-1 levels over 2 standard deviations of healthy controls (83.35 microg/ L) compared with 76% in the SNAFL group (P<0.05). There were no significant differences in the case proportion with TIMP-2 levels over 2 standard deviations of healthy controls between the NASH and the SNAFL groups. CONCLUSIONS: Both TIMP-1 and -2 may reflect the state of liver fibrosis in children with nonalcoholic fatty liver disease, and serum TIMP-1 appears to be more reliable.
Assuntos
Fígado Gorduroso/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Adolescente , Alanina Transaminase/sangue , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , gama-Glutamiltransferase/sangueRESUMO
Acute liver failure (ALF) is a life-threatening medical emergency and occurs when the liver rapidly loses its function within a short period. ALF can develop secondary to a variety of causes. Currently, the orthotopic liver transplantation is the "Gold Standard" therapy for the disease. However, due to the limited availability of donor organs and rapid progression of the disease, the mortality of ALF remains high. Therefore, it is imperative to develop novel therapeutic reagents for ALF. Gene therapy by delivering a target gene to the patients appears to be a promising approach for the treatment of ALF. Here, we review the recent advance of gene therapy for ALF, focusing on the three technical elements, animal models, vehicles for gene delivery and technique for gene delivery, which are important for the success of gene therapy as well as the potential targets used for the treatment of ALF.
Assuntos
Terapia Genética/métodos , Falência Hepática Aguda/terapia , Animais , DNA/administração & dosagem , Modelos Animais de Doenças , Técnicas de Transferência de Genes , Genes , Vetores Genéticos , Humanos , Lipossomos , Falência Hepática Aguda/genética , NanopartículasRESUMO
INTRODUCTION: We previously reported that both experimental and human studies have shown the importance of TIMP-1 and TIMP-2 in the development of liver fibrosis, a disease mostly caused by HBV and HCV infection in China. Inhibiting the expression of TIMP-1 by an antisense oligonucleotide (ASON) can prevent liver fibrosis through decreasing the deposition of collagen I and III. Whether blocking the expression of TIMP-2 has the same effect on liver fibrosis is not clear. MATERIALS AND METHODS: To interfere with this potentially effective target, we designed and synthesized two different ASON targeting TIMP-2, then mixed and transfected them by hydrodynamic injection into the rat livers with immune-induced liver fibrosis. We isolated HSCs from the HSA-induced rat model with liver fibrosis, and transfected them with ASON or sense oligonucleotide in vitro. RESULTS: We observed that TIMP-2 ASON markedly reduced the expression of TIMP-2 by real-time PCR, Western blot, and enzyme linked immunosorbent assay. However, TIMP-2 ASON had little effect on alpha-SMA expression in vitro by Western blot. Inhibition of the expression of TIMP-2 by TIMP-2 ASON clearly decreased deposition of collagen I and IV, ameliorated liver pathology, and improved the liver function among the rats with immune-induced liver fibrosis. CONCLUSION: The results suggested that TIMP-2 ASON could prevent the progression of liver fibrosis in this rat model. It is possible that this could form the basis for exploration of new liver anti-fibrosis drugs at a genetic level.