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1.
Medicine (Baltimore) ; 99(3): e18806, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011485

RESUMO

RATIONALE: Esophagopleural fistula (EPF) is a rare critical life-threatening condition that features high misdiagnosis rate. Although various surgical and conservative techniques have been developed for the treatment of EPF, the mortality rate of EPF remains high. PATIENT CONCERNS: An 81-year-old man with hepatic cirrhosis caused by schistosomiasis was admitted with upper gastrointestinal bleeding. DIAGNOSES: Upper endoscopy revealed bleeding large esophageal varices, and endoscopic injection sclerotherapy (EIS) was performed. Two weeks after the EIS was performed, the patient developed pyrexia, left-sided pleuritic chest pain. Air and pleural effusion were showed in the left pleural cavity by high-resolution computed tomography (HRCT), and a linear fistulous communication was noticed from the distal esophagus. These findings were consistent with hepatic cirrhosis, esophageal varices, upper gastrointestinal bleeding, and esophagopleural fistula. INTERVENTIONS: The patient was intensively treated with endoscopic self-expandable metallic stent (covered-SEMS) implantation and comprehensive treatments (including thoracic closed drainage, antibiotics, nasojejunal nutrition, and antacids). OUTCOMES: The patient was completely cured without recurrence during a 6 months of follow-up by comprehensive conservative treatments. LESSONS: This case indicates that pleural effusion with food residue is a specific finding in EPF. Thorax CT exhibited high sensitivity for the diagnosis of EPF. Endoscopic self-expandable metallic stent implantation and comprehensive conservative treatments may be preferable for the severe liver disease with EPF.


Assuntos
Endoscopia Gastrointestinal , Fístula Esofágica/etiologia , Varizes Esofágicas e Gástricas/terapia , Escleroterapia , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal/efeitos adversos , Endoscopia Gastrointestinal/métodos , Fístula Esofágica/diagnóstico por imagem , Fístula Esofágica/terapia , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/etiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Masculino , Esquistossomose mansoni/complicações , Esquistossomose mansoni/terapia , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Stents Metálicos Autoexpansíveis
2.
Z Gastroenterol ; 58(1): 49-56, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931540

RESUMO

BACKGROUND: Hepatic encephalopathy (HE) is a severe complication of liver cirrhosis with impairment of quality of life and prognosis. Management patterns among physicians have not been investigated yet. METHODS: A questionnaire containing 17 questions was sent out to 1468 gastroenterologists and 120 general practitioners (GPs). It included questions regarding diagnostic, therapeutic, and management strategies used in patients with overt HE (OHE) and covert HE (CHE). RESULTS: The response rate was 12 % (n = 172) for gastroenterologists and 45 % (n = 54) for GPs. Of gastroenterologists, 26.7 % examine patients with an initial diagnosis of liver cirrhosis regarding HE. Gastroenterologists favored a combination of different testing strategies (27.9 %) and clinical examination (23.0 %), while the biggest part of the GPs use clinical examination (55.3 %); 63.7 % of gastroenterologists and 28.3 % of GPs give correct nutritional advices to patients with HE. Treatment strategies for acute bouts of OHE and secondary prophylaxis varied widely in both groups. Preferred medication was lactulose followed by rifaximin or a combination therapy. More than half of the GPs (53.7 %) were not familiar with minimal HE (MHE). About one-third of both groups never tried to diagnose MHE. CONCLUSION: Our data strongly indicate that management of HE is very heterogeneous among gastroenterologists as well as selected GPs working in Germany and not driven by evidence-based international guidelines. Thus, the national guideline is more than welcome.


Assuntos
Gastroenterologistas , Fármacos Gastrointestinais/uso terapêutico , Clínicos Gerais , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/terapia , Cirrose Hepática/complicações , Padrões de Prática Médica/estatística & dados numéricos , Gerenciamento Clínico , Alemanha , Encefalopatia Hepática/psicologia , Humanos , Lactulose/uso terapêutico , Cirrose Hepática/terapia , Qualidade de Vida , Rifaximina/uso terapêutico , Prevenção Secundária/métodos , Inquéritos e Questionários
4.
Life Sci ; 241: 117121, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31794772

RESUMO

AIMS: This study addressed whether endogenous hepatic stem/progenitor (HSP) cells survival were related to the injured signals during liver cirrhosis. MATERIAL AND METHODS: Liver cirrhosis was induced in C57BL/6 mice by administering diethylnitrosamine (DEN) in drinking water. Hematoxylin-eosin staining and Masson's trichrome staining were used to identify infiltrative cells and connective tissues, respectively. The inflammatory activity grade and fibrotic stage, represented as G and S respectively, and evaluated by the International Simplified Grading and Staging System (ISGSS). Endogenous HSP cells (Ng2+HSP) were identified by immunofluorescence staining with an anti-neuro/glial antigen 2 (Ng2) antibody. All data were analyzed using SPSS 22.0 and GraphPad Prism 6 and Student's t-test was performed to determine statistical significance. p-values < 0.05 were considered statistically significant. KEY FINDINGS: All mice administered oral DEN developed liver fibrosis, liver cirrhosis and hepatocellular carcinoma (HCC). During the fibrosis period, observed a positive correlation of survival of endogenous HSP (Ng2+HSP) cells with inflammatory activity. As the disease developed into the cirrhotic stage, when lost correlation of endogenous HSP cells with inflammatory activity, revealed a dramatically reduced survival rate of endogenous HSP (Ng2+HSP) cells. SIGNIFICANCE: The DEN-induced liver cirrhosis could develop into three time zone of fibrosis, cirrhosis and cancer, and the histological patterns in the model are similar to those described in humans. Dramatic survival and less apoptosis of endogenous HSP (Ng2+HSP) cells was within fibrotic state, where inflammation signals is strong, indicating such time zone (1-6 weeks) during liver cirrhosis is important for mobilizing endogenous HSP-based regeneration.


Assuntos
Carcinoma Hepatocelular/terapia , Inflamação/terapia , Cirrose Hepática/terapia , Neoplasias Hepáticas Experimentais/terapia , Fígado/citologia , Células-Tronco/citologia , Animais , Carcinoma Hepatocelular/etiologia , Dietilnitrosamina/toxicidade , Modelos Animais de Doenças , Inflamação/etiologia , Fígado/imunologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Neoplasias Hepáticas Experimentais/etiologia , Regeneração Hepática , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco/fisiologia
5.
Am Fam Physician ; 100(12): 759-770, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31845776

RESUMO

Cirrhosis is the 12th leading cause of death in the United States. Newer research has established that liver fibrosis is a dynamic process and that early cirrhosis may be reversible. Only one in three people with cirrhosis knows they have it. Most patients with cirrhosis remain asymptomatic until the onset of decompensation. When clinical signs, symptoms, or abnormal liver function tests are discovered, further evaluation should be pursued promptly. The most common causes of cirrhosis are viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis. Initial workup includes viral hepatitis serologies, ferritin, transferrin saturation, and abdominal ultrasonography as well as complete blood count, liver function tests, and prothrombin time/international normalized ratio, if not already ordered. Additional testing is based on demographics and risk factors. Common serum and ultrasound-based screening tests to assess fibrosis include the aspartate transaminase to platelet ratio index score, Fibrosis 4 score, FibroTest/FibroSure, nonalcoholic fatty liver fibrosis score, standard ultrasonography, and transient elastography. Generally, noninvasive tests are most useful in identifying patients with no to minimal fibrosis or advanced fibrosis. Chronic liver disease management includes directed counseling, laboratory testing, and ultrasound monitoring. Treatment goals are preventing cirrhosis, decompensation, and death. Varices are monitored with endoscopy and often require prophylaxis with nonselective beta blockers. Ascites treatment includes diuresis, salt restriction, and antibiotic prophylaxis for spontaneous bacterial peritonitis, when indicated. Hepatic encephalopathy is managed with lifestyle and nutritional modifications and, as needed, with lactulose and rifaximin. Hepatocellular carcinoma screening includes ultrasound screening every six months for patients with cirrhosis.


Assuntos
Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Doença Crônica , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/complicações
6.
Nat Med ; 25(10): 1560-1565, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31591593

RESUMO

Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 107, 108 or up to 109 cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Doença Hepática Terminal/terapia , Cirrose Hepática/terapia , Macrófagos/transplante , Idoso , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Relação Dose-Resposta Imunológica , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/patologia , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Regeneração Hepática , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade
7.
Nihon Yakurigaku Zasshi ; 154(4): 203-209, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597900

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a rising cause of chronic liver disease worldwide. Although majority of patients with NAFLD are benign and non-progressive, having only steatosis, some fraction of patients develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis, hepatocellular carcinoma, and eventually increased liver-related mortality. Among histological features of NAFLD, it has been reported that liver fibrosis is the most important predictor of long-term outcomes. Liver fibrosis is a dynamic process characterized by the over-accumulation of extracellular matrix due to chronic liver injury resulting from any etiology including not only NASH, but also viral infection and alcoholic liver disease. Activation of hepatic stellate cells (HSCs) has been well established as a central driver of fibrosis in experimental animal models and human liver injury. It is a transdifferentiation of quiescent, vitamin-A­storing cells into proliferative and fibrogenic myofibroblasts. However, the discovery of novel pathways and mediators reveals the complexity of HSC activation. These emerging pathways include hedgehog, autophagy, free cholesterol, YAP1, hepcidin, and nuclear/G-protein coupled receptor-mediated signals. In addition, pathways of HSC clearance have been uncovered such as apoptosis, senescence, and reversion to an inactivated state. Thus, clarifying the underlying mechanisms of HSC activation could lead to the identification of novel therapeutic targets for NASH, and several drug candidates are currently being developed in clinical trials.


Assuntos
Células Estreladas do Fígado/citologia , Cirrose Hepática/terapia , Hepatopatia Gordurosa não Alcoólica/terapia , Animais , Transdiferenciação Celular , Humanos
8.
World J Gastroenterol ; 25(36): 5403-5422, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576089

RESUMO

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists' consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.


Assuntos
Doença Hepática Terminal/complicações , Gastroenterologia/normas , Encefalopatia Hepática/terapia , Cirrose Hepática/complicações , Sociedades Médicas/normas , China , Consenso , Doença Hepática Terminal/terapia , Gastroenterologia/métodos , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Cirrose Hepática/terapia , Prognóstico , Prevenção Secundária/métodos , Prevenção Secundária/normas , Fatores de Tempo
9.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 582-593, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594075

RESUMO

Portal hypertension(PH) is one of the main complications of cirrhosis.Transjugular intrahepatic portosystemic shunt(TIPS) is the percutaneous creation of a conduit from the hepatic vein to the portal vein that is used to manage consequences of PH (i.e., variceal bleeding and refractory ascites) and used as a bridging therapy to liver transplant for decompensated cirrhosis. The following Clinical Practice Guidelines (CPGs) presents profession associational recommendations of the Chinese College of Interventionalists(CCI) on TIPS for PH. The CPGs was written by more than 30 experts in the field of TIPS in China (including interventional radiologists, liver surgeons, hepatologists and gastroenterologist, et al.). The panel of experts, produced these CPGs using evidence from PubMed and Cochrane database searches and combined with relevant expert consensuses and high quality clinical researches in China providing up to date guidance on TIPS for PH with the only purpose of improving clinical practice.


Assuntos
Hipertensão Portal/terapia , Derivação Portossistêmica Transjugular Intra-Hepática , China , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Humanos , Cirrose Hepática/terapia , Resultado do Tratamento
10.
Zhonghua Gan Zang Bing Za Zhi ; 27(9): 657-667, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594088

RESUMO

Hepatic fibrosis is a reparative response of diffuse over deposition and abnormal distribution of extracellular matrix (collagen, glycoprotein and proteoglycans) after exposure to various kinds of liver injuries, and is a key step in the developmental process of various chronic liver diseases to cirrhosis. Recently, many advances in our understanding of hepatic fibrosis have been recognized through the basic and clinical research. Therefore, we have organized the relevant domestic experts of this field to form consensus on the diagnosis and evaluation, treatment, and clinical development and application of therapy in order to better guide the diagnosis and treatment, and drug research and development.


Assuntos
Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Consenso , Matriz Extracelular/patologia , Humanos , Fígado/patologia
11.
Med Sci Monit ; 25: 7182-7190, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31550244

RESUMO

BACKGROUND The role of bone marrow-derived mesenchymal stem cells (BM-MSCs) in liver fibrosis remains poorly understood. This study aimed to use a mouse model of carbon tetrachloride (CCL4)-induced liver fibrosis to investigate the effects of BM-MSCs during liver hypoxia and the involvement of the transforming growth factor beta 1 (TGF-ß1) and SMADs pathway. MATERIAL AND METHODS Thirty C57BL/6 mice were randomly divided into the control group (n=10), the model group (n=10), and the BM-MSC-treated model group (n=10). In the model group, liver fibrosis was induced by intraperitoneal injection of CCl4. BM-MSCs were transplanted after 12 weeks of CCl4 treatment. The serum biochemical parameters and histological changes in the liver, using histochemical stains, were investigated. The expression of collagen type I (collagen I), alpha-smooth muscle actin (alpha-SMA), TGF-ß1, SMAD3, SMAD7, hypoxia-inducible factor 1 alpha (HIF-1alpha), and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and quantitative real-time polymerase chain (RT-qPCR) reaction. RESULTS Treatment with BM-MSCs reduced the expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with the model group, and reduced liver fibrosis determined histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining compared with the model group. The area of liver fibrosis decreased after BM-MSCs treatment (p<0.05). Protein expression of HIF-1alpha and VEGF were decreased after BM-MSCs treatment (p<0.05). Transplantation of BM-MSCs reduced the mRNA expression of TGF-ß1, collagen I, alpha-SMA, and SMAD3 (p<0.05). CONCLUSIONS BM-MSC transplantation reduced CCl4-induced murine liver fibrosis, indicating that in a hypoxic microenvironment, BM-MSCs may inhibit the TGFß-1/SMADs pathway.


Assuntos
Fibrose/metabolismo , Cirrose Hepática/terapia , Células-Tronco Mesenquimais/fisiologia , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Medula Óssea/metabolismo , Tetracloreto de Carbono/farmacologia , Hipóxia Celular/fisiologia , China , Modelos Animais de Doenças , Fibrose/fisiopatologia , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Smad/metabolismo , Proteínas Smad/fisiologia , Fator de Crescimento Transformador beta/metabolismo
12.
Pediatr Surg Int ; 35(12): 1379-1388, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31552493

RESUMO

PURPOSE: Mesenchymal stem cell (MSC)-based cell therapies have emerged as a promising treatment option for various diseases. Due to the superior survival and higher differentiation efficiency, three-dimensional spheroid culture systems have been an important topic of MSC research. Stem cells from human exfoliated deciduous teeth (SHED) have been considered an ideal source of MSCs for regenerative medicine. Thus, in the present study, we introduce our newly developed method for fabricating SHED-based micro-hepatic tissues, and demonstrate the therapeutic effects of SHED-based micro-hepatic tissues in mouse disease models. METHODS: SHED-converted hepatocyte-like cells (SHED-HLCs) were used for fabricating spherical micro-hepatic tissues. The SHED-HLC-based spheroids were then transplanted both into the liver of mice with CCl4-induced chronic liver fibrosis and the kidney of factor VIII (F8)-knock-out mice. At 4 weeks after transplantation, the therapeutic efficacy was investigated. RESULTS: Intrahepatic transplantation of SHED-HLC-spheroids improved the liver dysfunction in association with anti-fibrosis effects in CCl4-treated mice. Transplanted SHED-converted cells were successfully engrafted in the recipient liver. Meanwhile, renal capsular transplantation of the SHED-HLC-spheroids significantly extended the bleeding time in F8-knock-out mice. CONCLUSIONS: These findings suggest that SHED-HLC-based micro-hepatic tissues might be a promising source for treating pediatric refractory diseases, including chronic liver fibrosis and hemophilia A.


Assuntos
Hemofilia A/terapia , Cirrose Hepática/terapia , Transplante de Células-Tronco Mesenquimais , Esferoides Celulares/transplante , Dente Decíduo , Transplante Heterólogo , Animais , Diferenciação Celular , Criança , Pré-Escolar , Doença Crônica , Modelos Animais de Doenças , Hepatócitos , Humanos , Masculino , Células-Tronco Mesenquimais , Camundongos , Camundongos Endogâmicos C57BL , Medicina Regenerativa/métodos
13.
World J Gastroenterol ; 25(31): 4437-4451, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31496623

RESUMO

Portal vein thrombosis (PVT) represents a well-known complication during the natural course of liver cirrhosis (LC), ranging from asymptomatic cases to life-threating conditions related to portal hypertension and hepatic decompensation. Portal flow stasis, complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development. However, PVT occurrence remains unpredictable and many issues regarding its natural history, prognostic significance and treatment are still elusive. In particular although spontaneous resolution or disease stability occur in most cases of PVT, factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet. Moreover, PVT impact on LC outcome is still debated, as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression. Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases, even if the safer therapeutic option and the optimal therapy duration are still unknown. Nevertheless, their impact on mortality rates should be addressed more extensively. In this review we present the most debated questions regarding PVT, whose answers should come from prospective cohort studies and large sample-size randomized trials.


Assuntos
Anticoagulantes/administração & dosagem , Hipertensão Portal/terapia , Cirrose Hepática/complicações , Derivação Portossistêmica Transjugular Intra-Hepática , Trombose Venosa/terapia , Administração Oral , Anticoagulantes/efeitos adversos , Progressão da Doença , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/mortalidade , Cirrose Hepática/mortalidade , Cirrose Hepática/terapia , Seleção de Pacientes , Veia Porta/patologia , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa/etiologia , Trombose Venosa/mortalidade
14.
Immunol Med ; 42(2): 71-78, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31498713

RESUMO

Results of recent studies have shown that disease models using human induced pluripotent stem (iPS) cells have recapitulated the pathophysiology of genetic liver diseases, viral hepatitis and hepatic fibrosis. The utilization of human iPS cells as a model of liver diseases has several substantial advantages compared with primary hepatocytes and cancer cell lines, such as the potential for unlimited expansion and similarity of biological characteristics to normal liver cells. In this review, we have focused on modeling liver diseases using human iPS cells and discussed the experimental evidence that supports the utility of such disease models, including that in our recent studies. Genetically modified or patient-derived human iPS cells can mimic congenital liver disease phenotypes. Human iPS-derived hepatic cells can be infected with the hepatitis viruses. The co-culture of human iPS-derived hepatocytes and mesenchyme partially mimics the process of liver fibrosis. Human iPS cell-derived hepatic cells and the co-culture system of such cells will contribute to the progress of studies on the pathophysiology of genetic and non-genetic liver diseases and development of novel therapeutic strategies for treating liver diseases.


Assuntos
Células-Tronco Pluripotentes Induzidas , Hepatopatias , Hepatite Viral Humana/genética , Hepatite Viral Humana/terapia , Humanos , Cirrose Hepática/genética , Cirrose Hepática/terapia , Hepatopatias/genética , Hepatopatias/terapia
15.
Cochrane Database Syst Rev ; 9: CD013120, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31524949

RESUMO

BACKGROUND: Approximately 2.5% of all hospitalisations in people with cirrhosis are for spontaneous bacterial peritonitis (SBP). Antibiotics, in addition to supportive treatment (fluid and electrolyte balance, treatment of shock), form the mainstay treatments of SBP. Various antibiotics are available for the treatment of SBP, but there is uncertainty regarding the best antibiotic for SBP. OBJECTIVES: To compare the benefits and harms of different antibiotic treatments for spontaneous bacterial peritonitis (SBP) in people with decompensated liver cirrhosis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until November 2018 to identify randomised clinical trials on people with cirrhosis and SBP. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and SBP. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of SBP, liver transplantation, and other decompensation events. We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio with 95% credible intervals (CrIs) based on an available-case analysis, according to the National Institute of Health and Care Excellence (NICE) Decision Support Unit guidance. MAIN RESULTS: We included a total of 12 trials (1278 participants; 13 antibiotics) in the review. Ten trials (893 participants) were included in one or more outcomes in the review. The trials that provided the information included patients having cirrhosis with or without other features of decompensation of varied aetiologies. The follow-up in the trials ranged from one week to three months. All the trials were at high risk of bias. Only one trial was included under each comparison for most of the outcomes. Because of these reasons, there is very low certainty in all the results. The majority of the randomised clinical trials used third-generation cephalosporins, such as intravenous ceftriaxone, cefotaxime, or ciprofloxacin as one of the interventions.Overall, approximately 75% of trial participants recovered from SBP and 25% of people died within three months. There was no evidence of difference in any of the outcomes for which network meta-analysis was possible: mortality (9 trials; 653 participants), proportion of people with any adverse events (5 trials; 297 participants), resolution of SBP (as per standard definition, 9 trials; 873 participants), or other features of decompensation (6 trials; 535 participants). The effect estimates in the direct comparisons (when available) were very similar to those of network meta-analysis. For the comparisons where network meta-analysis was not possible, there was no evidence of difference in any of the outcomes (proportion of participants with serious adverse events, number of adverse events, and proportion of participants requiring liver transplantation). Due to the wide CrIs and the very low-certainty evidence for all the outcomes, significant benefits or harms of antibiotics are possible.None of the trials reported health-related quality of life, number of serious adverse events, or symptomatic recovery from SBP. FUNDING: the source of funding for two trials were industrial organisations who would benefit from the results of the trial; the source of funding for the remaining 10 trials was unclear. AUTHORS' CONCLUSIONS: Short-term mortality after SBP is about 25%. There is significant uncertainty about which antibiotic therapy is better in people with SBP.We need adequately powered randomised clinical trials, with adequate blinding, avoiding post-randomisation dropouts (or performing intention-to-treat analysis), and using clinically important outcomes, such as mortality, health-related quality of life, and adverse events.


Assuntos
Antibacterianos/uso terapêutico , Cirrose Hepática/complicações , Peritonite/tratamento farmacológico , Qualidade de Vida , Teorema de Bayes , Humanos , Cirrose Hepática/terapia , Transplante de Fígado , Metanálise em Rede , Peritonite/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Dtsch Med Wochenschr ; 144(18): 1251-1258, 2019 09.
Artigo em Alemão | MEDLINE | ID: mdl-31514215

RESUMO

Liver cirrhosis is a major healthcare problem and is associated with an increased mortality due to the development of complications. Therefore, after diagnosis of liver cirrhosis, it is highly clinically relevant to evaluate the reason for liver cirrhosis and to assess the presence of complications in order to prevent progression of liver cirrhosis.


Assuntos
Cirrose Hepática , Progressão da Doença , Alemanha , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/terapia , Guias de Prática Clínica como Assunto
17.
Dtsch Med Wochenschr ; 144(18): 1259-1266, 2019 09.
Artigo em Alemão | MEDLINE | ID: mdl-31514216

RESUMO

The prognosis of patients with liver cirrhosis is impaired by complications such as variceal bleeding, ascites, hepatorenal syndrome, hepatic encephalopathy and hepatocellular carcinoma. A steadily increasing array of treatment options for these complications is available, including pharmaceutical treatment (e. g. beta blockers for varices or diuretics for ascites), endoscopic treatment (e. g. band ligation of varices), radiological interventions (e. g. transjugular shunt, transarterial chemoembolization) and liver transplantation. Most of the complications occur due to portal hypertension. Therefore, decompressive treatment by implantation of a transjugular intrahepatic portosystemic shunt (TIPS) an effective therapeutic option for many complications of liver cirrhosis. Its main indications are acute and recurrent variceal bleeding in patients with advanced disease as well as refractory ascites. The TIPS does not affect options of abdominal surgery and may therefore be used as a bridge to liver transplantation.


Assuntos
Cirrose Hepática , Ascite , Humanos , Hipertensão Portal , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Cirrose Hepática/terapia , Transplante de Fígado , Derivação Portossistêmica Transjugular Intra-Hepática
18.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(12): 158526, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31520775

RESUMO

Although human adipose tissue-derived stromal vascular fraction (SVF) has been considered a promising source of stem cells, its characteristics relevant to treatment of a damaged liver have not been fully elucidated. In the present study, we sought to characterize the property of human SVF and determine the therapeutic utility of SVF in the liver cirrhosis model. We performed microarray, quantitative (q)-PCR experiments, and in vivo therapeutic assays using a liver cirrhotic mouse model. q-PCR results revealed that hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)-A, Interleukin (IL)-10 and microRNA (miR)-146 were more highly upregulated in SVF than in human adipose-derived mesenchymal stem cells (ASCs). The SVF culture medium (CM) inhibited the activation of hepatic stellate cells in vitro. Injection of SVF significantly suppressed TAA-induced liver fibrosis and repaired liver function by inhibition of infiltrating inflammatory cells and induction of capillary/hepatocyte regeneration in vivo. Injection of IL-10 siRNA treated SVF cells decreased anti-inflammation and anti-fibrotic effects in TAA-induced mice liver. Our data indicate that SVF show a high anti-inflammatory property for treating fibrotic liver diseases through IL-10 secretion. Therefore, SVF might be a novel therapeutic alternative for the treatment of liver cirrhosis in clinical settings.


Assuntos
Inflamação/terapia , Cirrose Hepática/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Animais , Linhagem Celular , Células Cultivadas , Modelos Animais de Doenças , Fator de Crescimento de Hepatócito/análise , Fator de Crescimento de Hepatócito/imunologia , Humanos , Inflamação/imunologia , Inflamação/fisiopatologia , Interleucina-10/análise , Interleucina-10/imunologia , Fígado/imunologia , Fígado/fisiopatologia , Cirrose Hepática/imunologia , Cirrose Hepática/fisiopatologia , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos NOD , Camundongos SCID , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/imunologia
19.
Med Sci Monit ; 25: 6615-6623, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479436

RESUMO

Primary hepatocellular carcinoma (HCC) is the fifth most frequently reported malignancy, and it is also the second most common cause of cancer-related deaths worldwide. Although most HCC cases have been reported to develop from cirrhosis, accumulating data suggest that HCC is also closely related to non-cirrhotic chronic liver disease. Traditionally, HCC was thought to develop mostly from cirrhosis; however, an increasing number of reports have found that HCC can develop directly from inflammation without cirrhosis. The incidence of HCC in non-cirrhotic liver (HCC-NCL) is high, especially in developed countries. Studies have found that the most common cause of HCC-NCL is neglected fatty liver disease. This type of HCC has unique clinical characteristics and is closely related to metabolic disorders. Unfortunately, the prevention of HCC-NCL has not received enough attention worldwide, and there is also a lack of specific screening methods and clinical guidelines. This article mainly reviews the etiology, incidence, clinical characteristics, and screening markers of HCC-NCL to improve the understanding and prevention of this disease.


Assuntos
Carcinoma Hepatocelular/complicações , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/terapia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/prevenção & controle , Cirrose Hepática/terapia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/terapia , Prognóstico
20.
World J Gastroenterol ; 25(28): 3738-3752, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31391769

RESUMO

This review describes current approaches to the management of patients with cirrhotic ascites in relation to the severity of its clinical manifestations. The PubMed database, the Google Scholar retrieval system, the Cochrane Database of Systematic Reviews, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 1991-2018 using the keywords: "liver cirrhosis," "portal hypertension," "ascites," "pathogenesis," "diagnostics," and "treatment." Uncomplicated and refractory ascites in patients with cirrhosis were the inclusion criteria. The literature analysis has shown that despite the achievements of modern hepatology, the presence of ascites is associated with poor prognosis and high mortality. The key to successful management of patients with ascites may be the stratification of the risk of an adverse outcome and personalized therapy. Pathogenetically based approach to the choice of pharmacotherapy and optimization of minimally invasive methods of treatment may improve the quality of life and increase the survival rate of this category of patients.


Assuntos
Ascite/terapia , Doença Hepática Terminal/terapia , Hipertensão Portal/terapia , Cirrose Hepática/terapia , Agonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Ascite/diagnóstico , Ascite/etiologia , Ascite/mortalidade , Ensaios Clínicos como Assunto , Diuréticos/uso terapêutico , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/etiologia , Hipertensão Portal/mortalidade , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Transplante de Fígado , Paracentese/instrumentação , Paracentese/métodos , Derivação Portossistêmica Transjugular Intra-Hepática , Prognóstico , Qualidade de Vida , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
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