RESUMO
BACKGROUND: Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS: This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS: The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION: No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.
Assuntos
Aterosclerose/etiologia , Doenças Cardiovasculares/etiologia , Transplante de Fígado/efeitos adversos , Síndrome Metabólica/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cálcio/análise , Doenças Cardiovasculares/epidemiologia , Feminino , Seguimentos , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Peroxidase/sangue , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Prevalência , Estudos Prospectivos , Fatores de Risco , Proteína Amiloide A Sérica/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
The role of hepatitis C virus (HCV) in the pathogenesis of atherosclerosis and cardiovascular events is unclear. The aim of this study was to evaluate the direct effect of HCV on cardiovascular risk and correlate it with pro and anti-inflammatory cytokines in patients with HCV. HCV monoinfected patients, genotype 1, naive, non-obese (BMI<30) and non-diabetics were included and compared to controls (blood donors). Patients with prior diagnosis of cardiovascular diseases, hypertension, chronic renal failure, cancer and chronic use of lipid-lowering drugs or immunosuppressants were excluded. Age, BMI, systolic blood pressure (SBP) and diastolic (DBP), fasting glucose and lipid levels were determined. Serum cytokines (IL-6, IL-10 and TNF-α) and Framingham score were also evaluated. 62 HCV patients, 34 (54.8%) were males and none of them was smoking. The Framingham scores (median and 25th and 75th percentiles) were 12% (6.5-14%), showing an intermediate cardiovascular risk in patients with HCV. There was significant direct correlation between Framingham and total cholesterol (p=0.043) and DBP (p=0.007). HDL-C (p=0.002) was inversely correlated with the Framingham score. HCV patients had higher levels of proinflammatory cytokines (IL-6 and TNF-α) compared to controls (p<0.0001) and the relation of proinflammatory/anti-inflammatory TNF-α/IL10 and IL-6/IL10 were higher in HCV patients (p<0.01). The Framingham score was directly correlated to IL-6 and TNF-α, but differences were not statistically significant. Patients with HCV monoinfected, nonobese, naïve and non diabetic have an intermediate cardiovascular risk, as measured by the Framingham score and high levels of proinflammatory cytokines (IL-6 and TNF).
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/virologia , Hepacivirus/patogenicidade , Hepatite C/epidemiologia , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/patologia , Feminino , Hepatite C/patologia , Hepatite C/virologia , Humanos , Inflamação/epidemiologia , Inflamação/patologia , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same transmission routes. About 30% of HIV-positive patients are co-infected with HCV. Of the various HCV-related extrahepatic events, those involving the skin may be the first sign of infection. AIM: To specify the skin presentations in patients co-infected with HIV and HCV (co-infected patients; CP) and compare them with those found in patients with HCV mono-infection (mono-infected patients; MP). METHODS: This was a cross-sectional study, in which the studied population consisted of MP and CP from a tertiary hospital in the South of Brazil, who underwent complete skin examination and laboratory tests. RESULTS: In total, 201 patients were assessed, of whom 108 were CP, and 93 were MP. Pruritus tended to be more common in MP. MP also had significantly more dermatological conditions (mean of 5.2) than CP (mean of 4.5). In total, 104 different skin diseases were identified. There was a higher prevalence of infectious diseases and pigmentation disorders, such as verruca vulgaris and facial melasma, in CP, whereas trunk and facial telangiectasias, palmar erythema, and varicose veins were more common in MP. CONCLUSION: We found a high prevalence of skin conditions both in MP and in CP; however, the patterns of the dermatological conditions were different. CP were found to have significantly fewer skin lesions than MP, but had a higher prevalence of infectious and pigmentation disorders. By contrast, vascular conditions were more common in MP.
Assuntos
Coinfecção/complicações , Infecções por HIV/complicações , Hepatite C/complicações , Dermatopatias/etiologia , Adulto , Idoso , Brasil/epidemiologia , Coinfecção/virologia , Estudos Transversais , Feminino , Infecções por HIV/virologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Dermatopatias/epidemiologia , Dermatopatias/patologiaRESUMO
Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation. S-Nitroso-N-acetylcysteine (SNAC), a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100µM) or vehicle (control group) for 72h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGFß-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion of myofibroblast-like phenotype into quiescent cells. SNAC decreased gene and protein expression of TGFß-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis.
Assuntos
Acetilcisteína/análogos & derivados , Desdiferenciação Celular/efeitos dos fármacos , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Acetilcisteína/síntese química , Acetilcisteína/química , Acetilcisteína/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , CamundongosRESUMO
BACKGROUND: Fructose 1,6-biphosphate (FBP) has been shown to exert therapeutic effects in models of ischemia-reperfusion in organs other than the liver. This study compared FBP and University of Wisconsin (UW) solution during cold storage and reperfusion, among mitochondria of adult male Wistar rat livers. METHODS: Adult male Wistar rats were assigned to two groups according to the preservation solution used; UW or FBP Aspartate transaminase (AST), alanine transferase (ALT); and lactic dehydrogenase (LDH) were measured in samples of the storage solution obtained at 2, 4 and 6 hours of preservation. After 6 hours of cold storage, we reperfused the liver, taking blood samples to measure AST, ALT, LDH, and throbarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis; for determinations of TBARS, catalase, and nitric oxide as well as for mitochondrial evaluation by infrared spectroscopy. RESULTS: During cold preservation, levels of AST and LDH in the storage solution were lower among the FBP group, but after reperfusion, serum levels of AST, ALT, and LDH were higher in this group, as was catalase activity. TBARS and nitric oxide were comparable between the groups. In the UW group there was a higher amide I/amide II ratio than in the FBP group, suggesting an abnormal protein structure of the mitochondrial membrane. No signs of preservation injury were observed in any liver biopsy, but sinusoidal congestion was present in livers preserved with FBP. CONCLUSION: FBP showed a protective effect for preservation during cold storage seeming to protect the mitochondrial membrane although it did not prevent reperfusion injury.
Assuntos
Frutosedifosfatos/administração & dosagem , Fígado , Mitocôndrias Hepáticas/efeitos dos fármacos , Preservação Biológica , Animais , Frutosedifosfatos/farmacologia , Masculino , Mitocôndrias Hepáticas/patologia , Ratos , Ratos Wistar , SoluçõesRESUMO
BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is among the major causes of poor graft function early after liver transplantation that adversely influences patient survival. A variety of mediators have been implicated in the pathogenesis of I/R vascular injury, including nitric oxide (NO). Because of the beneficial effects of NO during preconditioning and reperfusion, strategies to prevent or ameliorate I/R injury through the stimulation of hepatic NO production are an area of significant clinical interest. We evaluated the role of S-nitroso-N-acetylcysteine (SNAC) as an NO donor in the prevention of liver I/R injury in an animal model. METHODS: Adult male Wistar rats were randomly assigned to 3 experimental groups containing 5 animals each: the University of Wisconsin (UW) solution group; SNAC solution group; and SNAC-containing UW solution (SNAC+UW) group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were determined in samples of the cold storage solution at 2, 4, and 6 hours of preservation. After 6 hours of cold storage, We applied a 15-minute reperfusion period. Thereafter, the reperfusion was interrupted with blood samples obtained to measure AST, ALT, LDH, and thiobarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis, and to determine of TBARS, catalase, and glutathione levels. RESULTS: During cold preservation, AST and LDH were significantly lower among the SNAC than the UW group or the SNAC+UW group (P = .004 and P = .03, respectively). ALT was comparable among the groups (P = .3). After reperfusion, serum levels of AST, ALT, and LDH, as well as of hepatic TBARS and catalase showed no differences among the groups. Glutathione concentration was lower in the SNAC and SNAC+UW group (P < .001) compared with the UW group. We did not observe histologic signs of preservation injury. CONCLUSION: The SNAC solution showed a greater protective effect to preserve rat livers during cold storage, but it was comparable with UW.
Assuntos
Acetilcisteína/análogos & derivados , Fígado/irrigação sanguínea , Doadores de Óxido Nítrico/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Acetilcisteína/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Masculino , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Isolated liver perfusion has been used to evaluate the beneficial effects of several agents. In the present study, we developed a model using a recipient rat to reperfuse harvested livers in an ex situ, in vivo recirculating system. A total of 25 reperfusion procedures using adult male Wistar rats as donors and recipients were done. The preservation of the livers was performed with University of Wisconsin solution for 6 hours. Thereafter, the liver was reperfused with blood from another rat. We believe that the model presented herein offers an alternative method to evaluate early hepatocellular damage or hepatic microcirculation.
Assuntos
Circulação Hepática , Sistema Porta/fisiologia , Traumatismo por Reperfusão/fisiopatologia , Reperfusão/métodos , Animais , Modelos Animais de Doenças , Masculino , Modelos Biológicos , Sistema Porta/patologia , Sistema Porta/fisiopatologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologiaRESUMO
BACKGROUND: Occult hepatitis B (HB) is characterized by the presence of HBV-DNA in patients who do not have HB surface antigen (HBsAg) detectable in sera, and is frequently described in patients with hepatitis C virus (HCV) infection. These viral liver diseases are common and may have a negative impact on the survival of renal transplant patients, especially if they are both present. In this study we aimed to evaluate the prevalence of occult HB in renal transplant patients either with or without HCV infection. PATIENTS AND METHODS: In a cross-sectional survey 101 HbsAg-negative renal transplant patients were evaluated; 51 were anti-HCV positive. Sera were analyzed for the presence of the S and core genes of the HBV-DNA by a nested polymerase chain reaction technique. Markers of HBV infection and liver function tests were also analyzed. RESULTS: The core gene was identified in 1 HCV-infected patient and 1 anti-HCV-negative patient who also presented the S gene (prevalence: 2% and 1% for each gene, respectively). HCV-infected patients had longer pre-transplant dialysis time (50.8 +/- 34.6 vs. 32.0 +/- 20.9; P < 0.001). Liver function tests were also increased in the HCV-infected group: alanine aminotransferase (P < 0.001), aspartate aminotransferase (P < 0.05), gamma-glutamyl transpeptidase (P<0.02), and alkaline phosphatase (P < 0.04). Multivariate analysis revealed that HCV infection was the only determinant of the altered results of the liver function tests. CONCLUSION: We found that occult HB is a condition present in our population of renal transplant patients and that HCV infection does not seem to be associated with occult HB infection in this setting.
Assuntos
DNA Viral/sangue , Antígenos de Superfície da Hepatite B/análise , Hepatite B/diagnóstico , Transplante de Rim/efeitos adversos , Adulto , Estudos Transversais , Feminino , Hepacivirus , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite B/virologia , Vírus da Hepatite B , Hepatite C/complicações , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , PrevalênciaAssuntos
Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Adenoide Cístico/secundário , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Carcinoma Adenoide Cístico/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico por imagemRESUMO
Caroli's disease, characterized by segmental or diffuse dilation of the intrahepatic biliary ducts, is a rare disease which is difficult to treat. The course of the disorder is characterized by recurrent episodes of cholangitis and hospital stays, with a consequent loss of quality-of-life and productive capacity, often ending in death due to uncontrolled infection. Endoscopic drainage of the bile duct, percutaneously or surgically, is palliative, and presents bad results in the follow-up of these patients. Orthotopic liver transplantation appears to be an effective curative option for the treatment of patients with Caroli's disease associated to complications. The authors present the course of two cases of this disease, associated with congenital fibrosis of the liver worsened by repeated episodes of cholangitis, submitted to orthotopic liver transplantation.