RESUMO
In Chronic hepatitis B (CHB) infection, virus and immune response interplay is thought to be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (T-bet+)] and viral antigen expression (HBsAg and HBcAg). Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system. All studied populations were identified in the portal-periportal (P-P) areas with a CD4+ lymphocyte predominance, while only CD8+ and FoxP3+ cells were observed in the intralobular area. Both P-P CD4+ and intralobular CD8+ cell frequencies were increased among severe hepatitis cases. Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was observed. HBcAg was mainly detected among HBeAg-positive patients and was associated with hepatitis severity and higher frequency of P-P FoxP3+, intralobular CD8+ and FoxP3+ cells. HBsAg was identified among HBeAg-negative cases with less severe hepatitis grade and lower frequency of P-P CD4+ and intralobular FoxP3+ lymphocytes. In conclusion, the HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication which impacts the host immune response and liver damage process. While HBcAg might be an inducer of a regulatory microenvironment, the intralobular CTL population seemed to have a key role in hepatitis severity.
Assuntos
Antígenos Virais/imunologia , Hepatite B Crônica/imunologia , Fígado/imunologia , Fígado/patologia , Subpopulações de Linfócitos/imunologia , Adulto , Idoso , Antígenos Virais/genética , Biópsia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos E da Hepatite B/genética , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B , Humanos , Imuno-Histoquímica , Inflamação , Fígado/citologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T Reguladores/imunologia , Adulto JovemRESUMO
A double-blind randomized controlled trial was performed to compare the safety and efficacy of α-lipoic acid (ALA) in liver transplantation (LT). The grafts were randomized to receive ALA or placebo before the cold ischemia time. Furthermore, patients transplanted with the ALA-perfused graft received 600 mg of intravenous ALA, while patients with the nonperfused graft received the placebo just before graft reperfusion. Hepatic biopsy was performed 2 h postreperfusion. Blood samples were collected before, during and 1 and 2 days after reperfusion. Quantitative polymerase chain reaction (qPCR) analysis was performed on biopsies to assess genes involved in the response to hypoxia, apoptosis, cell growth, survival and proliferation, cytokine production and tissue damage protection. Nine of 40 patients developed postreperfusion syndrome (PRS), but seven of them belonged to the control group. There was a decrease in PHD2 and an increase in alpha subunit of hypoxia-inducible factor-1 (HIF-1α) and baculoviral IAP repeat containing 2 (Birc2) transcript levels in the biopsies from the ALA-treated versus the control group of patients. Additionally, plasma levels of alarmins were lower in ALA-treated patients than control patients, which suggests that ALA-treated grafts are less inflammatory than untreated grafts. These results showed that ALA is safe for use in LT, induces gene changes that protect against hypoxia and oxidative stress and reduces the appearance of PRS.
Assuntos
Transplante de Fígado , Traumatismo por Reperfusão/prevenção & controle , Ácido Tióctico/farmacologia , Idoso , Alarminas/metabolismo , Apoptose , Biópsia , Isquemia Fria , Citocinas/metabolismo , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Segurança do Paciente , Projetos Piloto , Reperfusão/métodos , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Chronic Hepatitis C Virus (HCV) infection is a major risk for hepatocellular carcinoma (HCC) development. HCV Core protein has been associated with the modulation of potentially oncogenic cellular processes and E2 protein has been useful in evolutive studies to analyze the diversity of HCV. Thus, the aim of this study was to evaluate HCV compartmentalization in tumoral, non-tumoral liver tissue and serum and to identify viral mutations potentially involved in carcinogenesis. Samples were obtained from four patients with HCC who underwent liver transplantation. Core and E2 were amplified, cloned and sequenced. Phylogenies and BaTS Test were performed to analyze viral compartmentalization and a signature sequence analysis was conducted by VESPA. The likelihood and Bayesian phylogenies showed a wide degree of compartmentalization in the different patients, ranging from total clustering to a more scattered pattern with small groups. Nevertheless, the association test showed compartmentalization for the three compartments and both viral regions tested in all the patients. Signature amino acid pattern supported the compartmentalization in three of the cases for E2 protein and in two of them for Core. Changes observed in Core included polymorphism R70Q/H previously associated with HCC. In conclusion, evidence of HCV compartmentalization in the liver of HCC patients was provided and further biological characterization of these variants may contribute to the understanding of carcinogenesis mediated by HCV infection. © 2016 Wiley Periodicals, Inc.
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Carcinoma Hepatocelular/virologia , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Neoplasias Hepáticas/virologia , Fígado/virologia , Mutação , Idoso , Sequência de Aminoácidos , Carcinoma Hepatocelular/sangue , Feminino , Hepatite C/sangue , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/sangue , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Filogenia , Proteínas do Core Viral/química , Proteínas do Core Viral/genéticaRESUMO
Type I interferons are potent cytokines that possess antiviral, immunomodulating and antiproliferative actions. The development of autoimmune hepatitis is a well recognized complication of treatment with alpha IFN in patients with chronic viral hepatitis. Yet, the occurrence in patients under treatment with beta IFN for other indications is controversial and its occurrence often underestimated. We report two cases of severe acute autoimmune hepatitis in two patients undergoing therapy with IFN beta 1a for multiple sclerosis who recovered under early immunosuppressive therapy.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite Autoimune/etiologia , Fatores Imunológicos/efeitos adversos , Interferon beta/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Feminino , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Interferon beta-1a , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/imunologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Incidental hepatocellular carcinoma (iHCC) generates uncertainty over risk of recurrence after liver transplantation (LT). AIM: To compare recurrence between iHCC and confirmed HCC diagnosed prior to transplant based on imaging criteria (cHCC). MATERIAL AND METHODS: Fifty-four HCC patients were analyzed from a series of 309 consecutive adult transplanted patients. We developed a recurrence predicting score (RPS) applying ORs based on pathologic risk variables. RESULTS: Incidence of iHCC was 4.8% (n = 15) and overall recurrence 12.9% (cHCC 15.4% and iHCC 7%; P = 0.39). Variables included in the RPS were: microvascular invasion OR 17.8 (1.78-178.97; P = 0.014: 2 points), neural invasion OR 15.5 (1.13-212.17; P = 0.04: 1.5 points), nuclear grade > II OR 9.3 (1.17-74.84; P = 0.035: 1 point), and beyond Up-to 7 criteria OR 13.1 (1.66-103.67; P = 0.015: 1.5 points). Two risk groups were identified: low risk for recurrence (0-1 point) and intermediate-high risk groups (2-6 points). Low risk category remained an independent predictor of recurrence: OR 0.11 (0.01-0.67; P = 0.017); AUROC of 0.75 (0.54-0.96). A tendency towards more patients categorized as low risk group among iHCC patients was observed (69.2%; P = 0.13). CONCLUSIONS: In this series iHCC was not associated to lower risk of recurrence when compared to cHCC. We propose application of an RPS as a clinical tool for recurrence risk estimation.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Achados Incidentais , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Modelos Estatísticos , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Biópsia , Carcinoma Hepatocelular/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who underwent a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.
El carcinoma hepatocelular (HCC) es el tumor primario más frecuente del hígado, con 905 677 casos diagnosticados en 2020, en todo el mundo, y 830 180 muertes. Es responsable de la novena causa de muerte por cáncer en los hombres y la décima en mujeres en Argentina. A diferencia de otros tumores de alta prevalencia, la evidencia científica acerca del HCC se limita principalmente a pequeñas cohortes y estudios retrospectivos. El objetivo de este estudio fue describir epidemiológicamente a aquellos pacientes con diagnóstico de HCC en el Hospital Italiano de Buenos Aires en un periodo de 12 años. La supervivencia global para nuestra cohorte fue de 58, 46 y 36% a 1, 3 y 5 años respectivamente. El promedio de supervivencia en pacientes con tratamiento paliativo fue de 5 meses, 23 para aquellos que recibieron tratamientos no curativos y 75 meses para los que recibieron tratamientos curativos. El porcentaje de pacientes libres de enfermedad a 1, 3 y 5 años fue de 89%, 76% y 61% respectivamente. Se realizó un estudio minucioso de la etiología, factores de riesgo, incidencia, mortalidad y tratamientos realizados. Su importancia yace en su tamaño muestral, calidad y cantidad de información disponible.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Feminino , Hospitais Universitários , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Masculino , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/patologia , Estudos RetrospectivosRESUMO
Nodular regenerative hyperplasia of the liver is a rare condition. We describe here the case of a patient with HIV who presented with a clinical syndrome of portal hypertension. After multiple evaluations the diagnosis was recognized by the histology. The findings were attributed to the prolonged use of didanosine.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Didanosina/efeitos adversos , Hiperplasia Nodular Focal do Fígado/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Hipertensão Portal/etiologia , Adulto , Feminino , Hiperplasia Nodular Focal do Fígado/complicações , HumanosRESUMO
Complications of celiac disease could present with intestinal perforation and rarely, gastrointestinal bleeding, which are usually secondary to nongranulomatous ulcerative jejunoileitis or T-cell lymphoma. We describe the case of a 66-year-old male patient with an 8-year history of celiac disease (CD) who presented with recurrent abdominal pain and gastrointestinal bleeding. Several tests were performed to find out possible complications associated to CD. Due to an overt gastrointestinal bleeding, an arteriography was performed and signs of polyarteritis nodosa were found. Vascular disease was aggressive, and despite multiple medical and surgical treatments the patient died. As arteriography is not usually performed for the study of the complications of CD, it is possible that the association between CD and PAN has been underdiagnosed.
Assuntos
Doença Celíaca/complicações , Hemorragia Gastrointestinal/etiologia , Perfuração Intestinal/etiologia , Poliarterite Nodosa/complicações , Idoso , Evolução Fatal , Humanos , MasculinoRESUMO
PURPOSE: The aim of this study was to determine the effect of hyperbilirubinemia in the sensitivity of percutaneous transluminal forceps biopsy (PTFB) in patients with suspected malignant biliary stricture. MATERIALS AND METHODS: Ninety-three patients with suspicion of malignant biliary stricture underwent percutaneous transhepatic cholangiography followed by PTFB. Sensitivity, specificity and predictive values were analysed based on the presence or absence of hyperbilirubinemia, defined as total bilirubin equal to, or higher than 5 mg/dL. Variables included demographic and clinical features, laboratory, tumour type and localization, stricture length, therapeutic approach and histopathology. Additionally, major morbidity and mortality were assessed. RESULTS: The overall sensitivity, specificity, positive predictive value and accuracy of PTFB were 61.1%, 100%, 100%, and 62.4%, respectively. Hyperbilirubinemia affected 57% of patients at the time of PTFB. There were 35 (37%) false negative results, none of them related to tumour type or localization, stricture length, or previous biliary intervention (i.e. PBBD (percutaneous biliary balloon dilatation), ERCP (endoscopic retrograde cholangiopancreatography)) (p > 0.05). However, when bilirubin was < 5 mg/dL, false negative results decreased globally (p = 0.024) and sensitivity increased significantly for intrahepatic and hilar localization, as well as for colorectal metastasis, gallbladder carcinoma, and pancreatic carcinoma. No major morbidity occurred. CONCLUSION: The sensitivity of percutaneous transluminal biopsy for diagnosis of malignant stricture may significantly increase if samples are obtained in the absence of hyperbilirubinemia, without adding morbidity to the procedure. LEVEL OF EVIDENCE: Level 3, Case- Control studies.
Assuntos
Neoplasias dos Ductos Biliares , Colestase , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/terapia , Biópsia , Colangiopancreatografia Retrógrada Endoscópica , Colestase/diagnóstico por imagem , Colestase/etiologia , Colestase/terapia , Constrição Patológica , Humanos , Sensibilidade e Especificidade , Instrumentos CirúrgicosRESUMO
The immune response is critical in NAFLD pathogenesis, but the liver infiltrate's composition and the role of each T cell population is still up for debate. To characterize liver pathogenesis in pediatric and adult cases, frequency and localization of immune cell populations [Cytotoxic T Lymphocytes (CD8+), T helper Lymphocytes (CD4+), Regulatory T lymphocytes (Foxp3+) and Th17 (IL-17A+)] were evaluated. In portal/periportal (P/P) tracts, both age groups displayed a similar proportion of CD8+ and CD4+ lymphocytes. However, comparable Foxp3+ and IL-17A+ cell frequencies were observed in pediatric cases, meanwhile, in adults Foxp3+ was higher than IL-17A+ cells. Interestingly, IL-17A+ lymphocytes seemed to be nearly exclusive of P/P area in both age groups. In intralobular areas, both pediatric and adult cases showed CD8+ lymphocytes predominance with lower frequencies of CD4+ lymphocytes followed by Foxp3+ . Severe inflammation was associated with higher intralobular Foxp3+ lymphocytes (p = 0.026) in children, and lower P/P Foxp3+ and higher IL-17A+ lymphocytes in adults. All cases with fibrosis ≥ 2 displayed P/P low Foxp3+ and high IL-17A+ lymphocyte counts. Pediatric cases with worse steatosis showed high P/P CD4+ (p = 0.023) and intralobular CD8+ (p = 0.027) and CD4+ cells (p = 0.012). In NAFLD cases, the lymphocyte liver infiltrate composition differs between histological areas. Treg and Th17 balance seems to condition damage progression, denoting their important role in pathogenesis.
Assuntos
Linhagem da Célula/imunologia , Fígado/imunologia , Hepatopatia Gordurosa não Alcoólica/genética , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Linhagem da Célula/genética , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Interleucina-17/genética , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Pediatria , Linfócitos T/patologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th1/imunologia , Células Th1/patologiaRESUMO
INTRODUCTION: The Budd-Chiari syndrome is a low-prevalence disease due to an hepatic outflow obstruction. It is associated with procoagulant status and liver transplantation is one of the therapeutic tools for the treatment. OBJECTIVE: To evaluate the etiology, presenting form, treatment and evolution of patients with Budd-Chiari syndrome. PATIENTS AND METHOD: Ten consecutive adult patients with Budd-Chiari syndrome evaluated from January 1998 to June 2009 were prospectively included. The median follow up was 32.4 months (4-108 months). RESULTS: The mean age of patients was 34 +/- 12 years old. Presentation was acute in 1 patient, chronic in 2 and subacute in 7. The mean time from consultation to diagnosis was 4 +/- 2 days. Clinical manifestations were splenomegaly in 8 patients, malnutrition in 7, ascites in 6 and encephalopathy in 4. Diagnosis was confirmed by angiography in all cases. Initial prothrombin concentration was < 30% in 3 patients, 31% to 50% in 5, and > 50% in 2; hematocrit was > 45% in 5 patients and platelet count was > 400.000/mm3 in 6. MELD distribution at diagnosis was < or = 13 points in 4 patients, between 14 and 16 points in 5 and > or = 17 points in 1. Policytemia vera was detected in 7 patients, essential thrombocythemia in 1 and positive lupus inhibitor in 4. Nine patients were anticoagulated after diagnosis. Angioplasthy was required in 1 patient and 6 were treated with a transjugular intrahepatic portosystemic shunt. Death occurred in 1 patient due to gastrointestinal bleeding. Two patients were transplanted. CONCLUSION: In our experience all patients with Budd-Chiari syndrome have a procoagulant status. The transjugular intrahepatic portosystemic shunt is effective in treating this syndrome and liver transplantation should be reserved for patients who are refractory to other therapeutics.
Assuntos
Síndrome de Budd-Chiari , Adulto , Síndrome de Budd-Chiari/diagnóstico , Síndrome de Budd-Chiari/etiologia , Síndrome de Budd-Chiari/cirurgia , Feminino , Seguimentos , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: IgG4-related disease can manifest diversely, including autoimmune pancreatitis and IgG4-related cholangiopathy. We are reporting a very unusual cause of pancreatic cancer triggered in a previously unknown IgG4-related disease. CASE SUMMARY: A 75-year-old man was diagnosed with a 43 mm × 33 mm pancreatic head tumor after consulting for abdominal pain and jaundice. A pancreaticoduodenectomy was carried out uneventfully, and the histopathology report showed an early stage of acinar-cell pancreatic cancer. The patient reconsulted on the 30th postoperative day with fever, jaundice and asthenia. Magnetic resonance cholangiopancreatography evidenced an extense bile duct stricture. A percutaneous biliary drainage proved to be ineffective, even after exchanging it with larger bore drainage. Reviewing the surgical specimen, features compatible with IgG4-related disease were observed. Consequently, empiric treatment with steroids was initiated achieving excellent results. CONCLUSION: IgG4-related disease may cause chronic inflammation of the pancreas and can condition pancreatic malignancies.
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BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications. CASE SUMMARY: A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up. CONCLUSION: HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.
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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has been increasing constantly and linked to the global obesity epidemic. The NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Liver biopsy is the only reliable means to diagnose and stage NASH, but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition and cell-death markers, which correlate with liver injury in an NAFLD patient cohort. PATIENTS AND METHODS: Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. Matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloproteinase inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)] were measured in serum samples. RESULTS: HA showed an association with fibrosis severity (P=0.03) and M30 with steatosis (P=0.013), inflammation (P=0.004), and fibrosis severity (P=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The evaluation of diagnostic accuracy showed good performance as less invasive markers of significant fibrosis of both HA (area under the receiver operating characteristic curve: 0.928) and M30 (area under the receiver operating characteristic curve: 0.848). CONCLUSION: Biomarkers are essential tools that may provide a quick and accurate diagnosis for patients with life-threatening NAFLD and NASH. HA and M30, together or determined sequentially, have been found to be straightforward tests that may be sufficient to predict significant fibrosis even in a primary care center of an underdeveloped country.
Assuntos
Ácido Hialurônico/sangue , Queratina-18/sangue , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Área Sob a Curva , Argentina , Biomarcadores/sangue , Biópsia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
Mutation of the mismatch repair genes MLH1 and MSH2 account for the majority of the genetic abnormalities in Lynch syndrome. Immunohistochemical detection of their protein products is becoming an increasingly common method to detect these mutations. The aim of this study was to compare the expression of MLH1 and MSH2 by immunohistochemistry and its relationship with a group of clinical and histological variables in patients with known Lynch syndrome (n=16) and in cohort of young patients (less than 50 years) who did not meet Amsterdam criteria (n=25). The mean age was 40.7 and 64% were women. Conclusive results were obtained in 40 cases (97.6%). Eighteen cases (45%) showed abnormal expression of either MLH1 (11 cases) or MSH2 (6 cases) and both stains (1 case). Alteration of the normal staining pattern was seen more commonly in patients with Lynch syndrome than in the sporadic group (68.7% vs 28%, p=0.01). A significant correlation was obtained between abnormal protein expression and microsatellite instability (MSI): normal expression: 5.9%, lack of expression: 92.3%, p<0.0001. The sensitivity and specificity of the immunohistochemical to predict MSI were 92.3% and 94.1% respectively. Immunohistochemistry and MSI results did not correlate with any histopathological parameter. In conclusion, in our experience abnormal staining of MLH and MSH correlates strongly with the presence of MSI. In addition it appears that in our population a significant proportion of young patients (< 50 years old) demonstrate alterations in the mismatch repair gene products suggesting an important role of these molecules in tumorigenesis.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Instabilidade de Microssatélites , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/metabolismo , Proteínas Nucleares/metabolismo , Reação em Cadeia da PolimeraseRESUMO
Resumen La enfermedad de la vesícula biliar es una causa común de dolor abdominal. Si bien por lo general el dolor es secundario a la presencia de litiasis y colecistitis aguda, el espectro de la enfermedad es amplio e incluye anomalías congénitas, otros procesos inflamatorios y neoplasias. La tomografía computada (TC) y la resonancia magnética (RM) tienen un papel relevante en aquellos casos en los que la ecografía no es concluyente y en la planificación del tratamiento. Dentro de las anomalías congénitas, la forma en gorro frigio es la más frecuente. Los pólipos son en su mayoría lesiones benignas, siendo las características de malignidad un tamaño superior a 10 mm, solitario y sésil. La adenomiomatosis es reconocible por el engrosamiento de la pared vesicular y los componentes quísticos intramurales. Es importante reconocer el gas intramural e intraluminal en la colecistitis enfisematosa y los microabscesos y hemorragias intraluminales en la colecistitis gangrenosa debido a su alta morbilidad y mortalidad. La colecistitis xantogranulomatosa presenta nódulos intramurales que ocupan más del 60% del área de la pared engrosada y la conservación lineal del realce de la mucosa sin interrupción. El carcinoma vesicular se presenta como una lesión infiltrante que se extiende al hígado, un engrosamiento mural o una masa polipoide intraluminal.
Abstract Gallbladder disease is a common cause of abdominal pain. Although the pain is usually secondary to the presence of lithiasis and acute cholecystitis, the spectrum of the disease is broad and includes congenital anomalies, other inflammatory processes and neoplasms. Computed tomography (CT) and magnetic resonance (MRI) have a relevant role in those cases in which ultrasound is not conclusive and in treatment planning. Among the congenital anomalies, the phrygian cap shape is the most frequent. Polyps are mostly benign lesions, with the characteristics of malignancy being larger than 10 mm, solitary and sessile. Adenomyomatosis is recognizable by gallbladder wall thickening and intramural cystic components. It is important to recognize intramural and intraluminal gas in emphysematous cholecystitis and intraluminal microabscesses and hemorrhages in gangrenous cholecystitis because of its high morbidity and mortality. Xanthogranulomatous cholecystitis presents with intramural nodules occupying more than 60% of the thickened wall area and linear preservation of mucosal enhancement without interruption. Gallbladder carcinoma presents as an infiltrative lesion extending to the liver, a mural thickening or an intraluminal polypoid mass.
RESUMO
In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure episode, the family suffered gastrointestinal symptoms which were self-limited except in the child's case, who was admitted to hospital in Uruguay with diarrhea, vomiting, fatigue, and jaundice. The patient had increased serum levels of liver enzymes and bilirubin and five days later presented acute liver failure. She was referred to the Italian Hospital in Buenos Aires, being admitted with grade II-III encephalopathy and hepatomegaly and requiring mechanical respiratory assistance. Serology tests for hepatitis A, B, and C, Epstein-Barr virus, and cytomegalovirus were negative. Laboratory features showed anemia, coagulopathy, and increased serum levels of ammonium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Autoimmune Hepatitis Type-II (AH-II) was the initial diagnosis based on a liver kidney microsomal type 1 antibodies (LKM-1) positive result, and twenty days later a liver transplant was performed. The liver histopathology had indicated hemorrhagic necrosis in zone 3, and cholestasis and nodular regeneration, which were not characteristic of AH-II. LC/ESI-HRMS (liquid chromatography electrospray ionization high-resolution mass spectrometry) analysis of MCs in the explanted liver revealed the presence of Microsytin-LR (MC-LR) (2.4 ng·gr-1 tissue) and [D-Leu¹]MC-LR (75.4 ng·gr-1 tissue), which constitute a toxicological nexus and indicate a preponderant role of microcystins in the development of fulminant hepatitis.
Assuntos
Proliferação Nociva de Algas , Falência Hepática/etiologia , Microcistinas/toxicidade , Poluentes da Água/toxicidade , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Praias , Bilirrubina/sangue , Exposição Ambiental , Feminino , Humanos , Lactente , Fígado/metabolismo , Fígado/patologia , Falência Hepática/sangue , Falência Hepática/patologia , UruguaiRESUMO
The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg have opposite functions, their balance could affect disease progression. The aim was to explore liver microenvironment and its peripheral blood counterpart in adult CHC patients. CD4+ lymphocytes were predominant in the liver, with high Foxp3+ but low IL-17A+ frequency. IL-17A+ lymphocytes and IL-17A+/Foxp3+ ratio displayed association with advanced fibrosis (p = 0.0130; p = 0.0236, respectively), while Foxp3+ lymphocytes and IL-10 expression level inversely correlated with fibrosis severity (p = 0.0381, p = 0.0398, respectively). TGF-ß/IL-6 ratio correlated with IL-17A+/Foxp3+ ratio (p = 0.0036, r = 0.5944) and with IL-17A+ lymphocytes (p = 0.0093; r = 0.5203). TNF-α and TGF-ß were associated with hepatitis severity (p = 0.0409, p = 0.0321). Peripheral blood lymphocyte frequency was not associated with liver damage. There are functionally different immune cell populations actively involved in liver damage, but the liver cytokine milieu actually drives the pathogenesis. The intrahepatic Foxp3+ lymphocytes predominance beside the low IL-17A+ lymphocytes frequency, delineate a skewed IL-17A+/Foxp3+ balance towards Foxp3+ lymphocytes. However, the IL-17A+ lymphocytes association with advanced fibrosis denotes their role in the pathogenesis. Therefore, the interplay between Th17 and Treg conditions liver fibrogenesis.
Assuntos
Microambiente Celular , Hepatite C Crônica/patologia , Adulto , Idoso , Biomarcadores , Biópsia , Comunicação Celular , Microambiente Celular/imunologia , Feminino , Imunofluorescência , Hepatite C Crônica/imunologia , Hepatite C Crônica/metabolismo , Hepatite C Crônica/virologia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Carga ViralRESUMO
Resumen El carcinoma hepatocelular (HCC) es el tumor primario más frecuente del hígado, con 905 677 casos diagnosticados en 2020, en todo el mundo, y 830 180 muertes. Es responsable de la novena causa de muerte por cáncer en los hombres y la décima en mujeres en Argentina. A diferencia de otros tumo res de alta prevalencia, la evidencia científica acerca del HCC se limita principalmente a pequeñas cohortes y estudios retrospectivos. El objetivo de este estudio fue describir epidemiológicamente a aquellos pacientes con diagnóstico de HCC en el Hospital Italiano de Buenos Aires en un periodo de 12 años. La supervivencia global para nuestra cohorte fue de 58, 46 y 36% a 1, 3 y 5 años respectivamente. El promedio de supervivencia en pacientes con tratamiento paliativo fue de 5 meses, 23 para aquellos que recibieron tratamientos no curativos y 75 meses para los que recibieron tratamientos curativos. El porcentaje de pacientes libres de enfermedad a 1, 3 y 5 años fue de 89%, 76% y 61% respectivamente. Se realizó un estudio minucioso de la etiología, factores de riesgo, incidencia, mortalidad y tratamientos realizados. Su importancia yace en su tamaño muestral, calidad y cantidad de información disponible.
Abstract Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who under went a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.