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1.
Chirurgia (Bucur) ; 115(2): 138-139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33119487

RESUMO

In chronic liver disease, the incidence of cirrhosis is increasing. About 1 million deaths from cirrhosis are reported annually by WHO, occupying the 11th position in the hierarchy of pathologies that cause death (1). The prevalence of cirrhosis is often underestimated based on the fact that one third of the patients are asymptomatic (2). Regardless of whether it is elective or urgent extra-hepatic surgery, operative interventions in this range of patients are burdened by an increased risk of perioperative morbidity and mortality (3,4). This reality requires the evaluation of the benefit-risk balance for each patient with the surgical firm indication. A journal of the medical literature, presented over the period 1995-2018 (PubMed), noted that the most frequent extrahepatic interventions in the cirrhotic patient were addressed to the cholecyst and CBD (23%), parietal defects (hernias, events) in 17 %, gastric pathology (19%) and rectum-colon (19%).v Liver cirrhosis is frequently associated with abnormalities of coagulation mechanisms: thrombopenia and platelet dysfunctions, decreased coagulation factors but also proteins involved in fibrinolysis. Cardio-circulatory changes are all the more important as the cirrhotic pathology is more evolved, being expressed by hyperkinetic syndrome and systemic vasodilation with hyper-flow, tachycardia and low peripheral resistance (5). The "trigger" element of these anomalies is the portal hypertension and the porto-systemic shunts that involve vasodilating mediators but also the compensatory activation of the renin-angiotensin system (6). The perioperative anaesthetic strategy in the patients is integrated in a multidisciplinary effort of specific management.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Cirrose Hepática/fisiopatologia , Doenças do Sistema Digestório/fisiopatologia , Doenças do Sistema Digestório/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Cirrose Hepática/complicações
3.
Int J Cardiovasc Imaging ; 36(11): 2121-2127, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32613383

RESUMO

Left atrial enlargement is a known marker of chronic diastolic dysfunction and was recently shown to be an independent predictor of mortality in cirrhosis. Real time 3-dimensional echocardiography (3DE) is an emerging modality that enables accurate measurements of the left atrial (LA) volume and function. Assessment of LA volumes with 3DE has never been applied in cases of cirrhosis. We therefore aimed to investigate LA volumes using the novel 3DE technique in relation to liver dysfunction and outcome in patients with cirrhosis. A prospective study of 47 cirrhotic patients without cardiovascular disease and ten healthy controls. The patients underwent clinical evaluation, blood sampling, liver vein catheterization, ECG and tissue Doppler echocardiography, including 3DE. Patients were followed up for a median of 25 months with registration of death and liver transplantation (LT). 3DE-derived maximal left atrial volume index (LAVImax) and minimal left atrial volume index (LAVImin) were higher in patients with a Child Pugh score of 8 or higher than in patients with a score lower than 8 (30.0 vs. 22.3 mL/m2, P=0.008 and 14.6 vs. 9.5 mL/m2, P=0.04, respectively). LA volumes correlated with model for end-stage liver disease (MELD) score (r=0.40, P=0.005), hepatic venous pressure gradient (r=0.34, P=0.04), and biochemical markers of advanced liver disease. Twelve patients experienced the composite end-point of death or LT during follow-up and these patients had increased LA volumes with a higher LAVImax (34.3±14.8 vs. 25.9±7.3 mL/m2, P=0.01) and a higher LAVImin (16.3±7.3 vs. 10.8±5.1 mL/m2, P=0.007). Patients with advanced cirrhosis have increased minimal and maximal left atrial volumes, which correlate with the degree of the liver dysfunction and poor prognosis.


Assuntos
Função do Átrio Esquerdo , Remodelamento Atrial , Ecocardiografia Tridimensional , Cardiopatias/diagnóstico por imagem , Cirrose Hepática/diagnóstico , Testes de Função Hepática , Progressão da Doença , Feminino , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Cirrose Hepática/cirurgia , Transplante de Fígado , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo
4.
Expert Rev Med Devices ; 17(8): 845-853, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32686517

RESUMO

PURPOSE: To evaluate the diagnostic performance of sound touch elastography (STE) for staging liver fibrosis in chronic hepatitis B (CHB) patients using pathological stage of surgical specimens as the reference standard. METHOD: 239 CHB patients were included. Liver stiffness measurements (LSMs) on STE and Supersonic shear imaging (SSI), gamma glutamyl transferase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI) and four-factor Fibrosis-4 (FIB-4) index were obtained. Areas under the receiver operating characteristic (ROC) curves (AUCs) for the diagnosis of fibrosis stage were calculated and compared. RESULTS: The LSMs obtained by STE and SSI significantly correlated with the fibrosis stages (r = 0.757; r = 0.758, respectively, both p < 0.001). No significant differences in AUCs were observed between STE and SSI in identifying fibrosis ≥stage 1 (0.92 vs. 0.94), ≥stage 2 (0.89 vs. 0.91), ≥stage 3 (0.90 vs. 0.91) or stage 4 (0.92 vs. 0.91). Both STE and SSI had significantly higher AUCs in identifying each fibrosis stage than the GPR (0.68, 0.77, 0.76 and 0.79), APRI (0.53, 0.66, 0.74 and 0.69) and FIB-4 (0.61, 0.77, 0.79 and 0.74). CONCLUSIONS: STE is an efficient tool for assessing liver fibrosis in CHB patients, with performance comparable to that of SSI and superior to that of biomarkers.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatite B Crônica/diagnóstico por imagem , Hepatite B Crônica/cirurgia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/cirurgia , Tato , Área Sob a Curva , Biomarcadores/sangue , Fenômenos Biomecânicos , Biópsia , Feminino , Hepatite B Crônica/patologia , Hepatite B Crônica/fisiopatologia , Humanos , Fígado/patologia , Fígado/fisiopatologia , Fígado/cirurgia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Curva ROC , gama-Glutamiltransferase/sangue
5.
Rev Gastroenterol Mex ; 85(3): 303-311, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32553772

RESUMO

The novel SARS-CoV-2 coronavirus is responsible for the infectious disease caused by coronavirus 19 (COVID-19). The current pandemic is growing worldwide and could affect 50-60% of the world population in the months to come. The most severe disease manifestations are atypical pneumonia and sepsis, but the gastrointestinal tract, particularly the liver, has recently been reported to be affected by SARS-CoV-2. Therefore, the aim of the present work was to review the literature available on the topic and provide information about COVID-19, in both healthy and diseased livers, and issue recommendations. The incidence of liver injury specifically associated with COVID-19 varies from 14.8-53%. The majority of case series have reported altered ALT and AST, elevated total bilirubin, and low serum albumin and liver compromise has been associated with the most severe cases of COVID-19. Cirrhosis of the liver has a recognized immune dysfunction status that includes immunodeficiency and systemic inflammation, making it reasonable for those patients to be more susceptible to SARS-CoV-2 infection. The recommendations for those patients, in addition to the general measures of physical distancing and handwashing for all persons, include social, medical, and psychologic support during the period of home quarantine to prevent lapses in treatment. Patients should be made aware that they need to keep abreast of changes in recommendations and social policies.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Cirrose Hepática/terapia , Hepatopatias/etiologia , Hepatopatias/fisiopatologia , Fígado/fisiopatologia , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Humanos , Incidência , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Cirrose Hepática/fisiopatologia , Hepatopatias/terapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia
6.
Med Clin North Am ; 104(4): 647-662, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32505258

RESUMO

Hospitalists often care for patients with liver disease, including those with acute liver injury and failure and patients with complications of decompensated cirrhosis. Acute liver failure is a true emergency, requiring intensive care and oftentimes transfer of the patient to a liver transplant center. Patients with decompensated cirrhosis have complications of portal hypertension, including variceal hemorrhage, ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy. These complications increase the risk of mortality among patients with decompensated cirrhosis. Comanagement by the hospitalist with gastroenterology/hepatology can optimize care, especially for patients being considered for liver transplant evaluation.


Assuntos
Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/etiologia , Cirrose Hepática/terapia , Falência Hepática Aguda/etiologia , Ascite/epidemiologia , Ascite/etiologia , Varizes Esofágicas e Gástricas/epidemiologia , Hemorragia Gastrointestinal/epidemiologia , Encefalopatia Hepática/epidemiologia , Encefalopatia Hepática/etiologia , Humanos , Hipertensão Portal/epidemiologia , Hipertensão Portal/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Falência Hepática Aguda/epidemiologia , Transplante de Fígado , Peritonite/epidemiologia , Peritonite/etiologia
7.
Am J Physiol Endocrinol Metab ; 319(2): E305-E314, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32516028

RESUMO

Obesity promotes nonalcoholic fatty liver disease (NAFLD). The intestinal microbiota contributes to NAFLD progression through a gut-to-liver pathway that promotes inflammation and fibrosis. Gut microbiota-derived factors can travel to the liver and activate immune responses in liver resident cells to promote inflammation and NAFLD. Little is known about bacterial sensors or immune responses that can protect against NAFLD. We tested whether the bacterial cell wall sensor nucleotide-binding oligomerization domain-containing (NOD)2 protects against diet-induced NAFLD in mice. Whole body deletion of NOD2 exacerbated liver steatosis and fibrosis in mice fed a NAFLD-promoting diet. Mice with a hepatocyte-specific deletion of NOD2 (Nod2-/-HKO) also had higher liver steatosis and fibrosis compared with littermate wild-type mice (WT) fed a NAFLD-promoting diet. Hepatocyte-specific NOD2 deletion altered the composition of the gut microbiome. Nod2-/-HKO mice had increased relative abundance of Clostridiales and lower Erysipelotrichaceae among other changes in cecal bacteria compared with littermate WT mice. Hepatocyte-specific NOD2 deletion altered a transcriptional program of liver inflammation, metabolism, and fibrosis. Nod2-/-HKO mice had higher levels of transcripts involved in lipid and cholesterol metabolism. Nod2-/-HKO mice had higher transcript levels of transforming growth factor-ß and collagen isoforms, which coincided with higher levels of liver collagen compared with WT mice. These data show that bacterial cell wall sensing within hepatocytes can engage retrograde cross-talk from the liver to the gut, where liver immunity communicates with the gut to influence the intestinal host-microbe relationship during diet-induced NAFLD, and NOD2 within the hepatocyte confers protection from liver steatosis and fibrosis.


Assuntos
Disbiose/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Cirrose Hepática/fisiopatologia , Fígado/fisiopatologia , Proteína Adaptadora de Sinalização NOD2/fisiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Dieta , Disbiose/prevenção & controle , Hepatócitos/química , Hepatócitos/fisiologia , Cirrose Hepática/etiologia , Cirrose Hepática/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Adaptadora de Sinalização NOD2/deficiência , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Receptor Cross-Talk
8.
J Hepatol ; 73(5): 1063-1071, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32526252

RESUMO

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities, but its impact on patients with cirrhosis is currently unknown. Herein, we aimed to evaluate the impact of COVID-19 on the clinical outcome of patients with cirrhosis. METHODS: In this multicentre retrospective study, patients with cirrhosis and a confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were enrolled between 1st and 31th March 2020. Clinical and biochemical data at diagnosis of COVID-19 and at the last outpatient visit were obtained through review of medical records. RESULTS: Fifty patients with cirrhosis and confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or a prolonged stay if already in hospital. Respiratory support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with a model for end-stage liver disease (MELD) score ≥15 increased from 13% to 26% (p = 0.037), acute-on-chronic liver failure and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4-13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. The severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. In patients with cirrhosis, mortality was significantly higher in those with COVID-19 than in those hospitalized for bacterial infections. CONCLUSION: COVID-19 is associated with liver function deterioration and elevated mortality in patients with cirrhosis. LAY SUMMARY: Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities. Herein, we assessed its impact on patients with cirrhosis. Infection with COVID-19 was associated with liver function deterioration and elevated mortality in patients with cirrhosis.


Assuntos
Infecções por Coronavirus , Cirrose Hepática , Testes de Função Hepática , Pandemias , Pneumonia Viral , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Itália/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/fisiopatologia , Testes de Função Hepática/métodos , Testes de Função Hepática/estatística & dados numéricos , Masculino , Mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Fatores de Risco
9.
Medicine (Baltimore) ; 99(22): e20003, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481371

RESUMO

BACKGROUND: Blood flow factors, such as congestion or ischemia after hepatectomy, have a significant impact on liver regeneration, but with the popularization of precise hepatectomy technology, segmental hepatectomy without congestion or ischemia has become the preferred treatment. Our aim is to investigate the factors affecting liver regeneration after hepatectomy without blood flow changes, and to provide clinical evidence for surgeons on the timing of second hepatectomy for cirrhosis patients with hepatocellular carcinoma (HCC). METHODS: This study retrospectively analyzed data from patients who underwent right hepatectomy without middle hepatic vein (MHV) in West China Hospital between January 2016 and January 2018. Eighteen living-donors without MHV as normal group and 45 HCC patients, further classified into 3 subgroups based on the severity of fibrosis using the Scheure system. Demographic data, pre- and postoperative liver function indexes, and remnant liver volume (RLV) were retrospectively compared. We also analyzed the remnant liver regeneration rate (RLRR) post-operatively in each group. The significant indexes in univariate analysis were further analyzed using both receiver operating characteristic (ROC) analysis and multivariate regression analysis. RESULTS: Liver regeneration occurred in both living-donor and HCC groups after hepatectomy; the RLRRs at 1 month were 59.46 ±â€Š10.39% and 57.27 ±â€Š4.77% (P = .509), respectively. Regeneration in the cirrhosis group occurred more slowly and less completely compared with that in other groups. The regeneration rate in the first 6 months showed rapid increase and the RLRR reached above 70% in cirrhosis group. Multivariate and ROC analyses revealed that Alb and the hepatic fibrosis grade in the early postoperative period were significant predictors of remnant liver regeneration. CONCLUSION: The liver regenerated in all HCC patients; however, regeneration was significantly slower and less complete compared with the normal liver, especially in the patients with cirrhosis. Therefore, it can be concluded that the degree of liver fibrosis is a major predictor of liver regeneration. Furthermore, the optimal time for second resection in recurrent HCC patients with cirrhosis was 6 months after the first operation.


Assuntos
Hepatectomia , Cirrose Hepática/fisiopatologia , Regeneração Hepática , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Transl Res ; 222: 28-40, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32434697

RESUMO

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease characterized by fat accumulation and inflammation in liver. Yet, the mechanistic insight and diagnostic and therapeutic options of NASH remain incompletely understood. This study tested the roles of cysteine protease cathepsin B (CatB) in mouse NASH development. Immunoblot revealed increased liver CatB expression in NASH mice. Fructose-palmitate-cholesterol diet increased body weight gain, liver to body weight ratio, blood fasting glucose, plasma total cholesterol and alanine transaminase levels, and liver triglyceride, but decreased plasma high-density lipoprotein in wild-type mice. All these changes were blunted in CatB-deficient (Ctsb-/-) mice. In parallel to reduced expression of genes involved in liver lipid transport and lipogenesis, liver CD36, FABP4, and PPARγ protein levels were also significantly decreased in Ctsb-/- mice, although CatB deficiency did not affect liver gluconeogenesis and fatty acid beta-oxidation-associated gene expression. Mechanistic studies showed that CatB deficiency decreased liver expression of adhesion molecules, inflammatory cytokine, and chemokine, along with reduced liver inflammatory cell infiltration. CatB deficiency also promoted M2 macrophage polarization and reduced liver TGF-ß1 signaling and fibrosis. Together, CatB deficiency improves liver function in NASH mice by suppressing de novo lipogenesis and liver inflammation and fibrosis.


Assuntos
Catepsina B/deficiência , Dieta Hiperlipídica , Inflamação/patologia , Metabolismo dos Lipídeos , Cirrose Hepática/complicações , Cirrose Hepática/enzimologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Animais , Caderinas , Catepsina B/metabolismo , Polaridade Celular , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática/fisiopatologia , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ganho de Peso
11.
PLoS One ; 15(4): e0231701, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302330

RESUMO

Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.


Assuntos
Hipertensão Portal/diagnóstico , Sialoproteína de Ligação à Integrina/sangue , Cirrose Hepática/complicações , Pressão na Veia Porta/fisiologia , Adulto , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Hipertensão Portal/sangue , Hipertensão Portal/fisiopatologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Veia Porta/fisiopatologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
12.
PLoS One ; 15(4): e0231836, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32310974

RESUMO

BACKGROUND: Serum albumin level improves in patients with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) with antiviral therapy. However, it remains controversial whether liver volume increases along with SVR. METHODS: Patients with chronic HCV infection with a history of hepatocellular carcinoma (HCC) who achieved SVR with anti-HCV treatment from March 2003 to November 2017 were enrolled. Patients were followed up with periodic computed tomography (CT) scans to detect HCC recurrence. Patients who underwent treatment for HCC recurrence within 1 year after initiation of anti-HCV treatment were excluded. Laboratory data, including alanine aminotransferase (ALT) level, serum albumin level, and platelet count, were collected at baseline and timepoints after treatment initiation. Liver volume was evaluated at baseline and 24 and 48 weeks after treatment initiation using a CT volume analyzer. A linear mixed-effects model was applied to analyze the chronologic change in liver volume. The correlations between changes in ALT level, albumin level, and liver volume were also evaluated. RESULTS: Of 108 enrolled patients, 78 had cirrhosis. Serum albumin level continued to increase through 48 weeks after treatment initiation. A significant increase in liver volume was observed only in patients without cirrhosis (P = 0.005). There was a significant correlation between ALT level decrease and albumin level increase (P = 0.018). CONCLUSIONS: Improved liver albumin production with SVR was contributed by improved liver cell function rather than increased liver volume in patients with cirrhosis.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/fisiopatologia , Feminino , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/fisiopatologia , Humanos , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Fígado/virologia , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/efeitos dos fármacos , Estudos Retrospectivos , Resposta Viral Sustentada
13.
Arq Gastroenterol ; 57(1): 64-68, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294737

RESUMO

BACKGROUND: Liver cirrhosis is a highly prevalent disease that, at an advanced stage, usually causes ascites and associated respiratory changes. However, there are few studies evaluating and quantifying the impact of ascites and its relief through paracentesis on lung function and symptoms such as fatigue and dyspnea in cirrhotic patients. OBJECTIVE: To assess and quantify the impact of acute reduction of ascitic volume on respiratory parameters, fatigue and dyspnea symptoms in patients with hepatic cirrhosis, as well as to investigate possible correlations between these parameters. METHODS: Thirty patients with hepatic cirrhosis and ascites who underwent the following pre and post paracentesis evaluations: vital signs, respiratory pattern, thoracoabdominal mobility (cirtometry), pulmonary function (ventilometry), degree of dyspnea (numerical scale) and fatigue level (visual analog scale). RESULTS: There was a higher prevalence of patients classified as CHILD B and the mean MELD score was 14.73±5.75. The comparison of pre and post paracentesis parameters evidenced after paracentesis: increase of predominantly abdominal breathing pattern, improvement of ventilatory variables, increase of the differences obtained in axillary and abdominal cirtometry, reduction of dyspnea and fatigue level, blood pressure reduction and increased peripheral oxygen saturation. Positive correlations found: xiphoid with axillary cirtometry, degree of dyspnea with fatigue level, tidal volume with minute volume, Child "C" with higher MELD score, volume drained in paracentesis with higher MELD score and with Child "C". We also observed a negative correlation between tidal volume and respiratory rate. CONCLUSION: Since ascites drainage in patients with liver cirrhosis improves pulmonary volumes and thoracic expansion as well as reduces symptoms such as fatigue and dyspnea, we can conclude that ascites have a negative respiratory and symptomatological impact in these patients.


Assuntos
Ascite/complicações , Dispneia/etiologia , Fadiga/etiologia , Cirrose Hepática/complicações , Pulmão/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/fisiopatologia , Ascite/terapia , Estudos Transversais , Dispneia/fisiopatologia , Fadiga/fisiopatologia , Feminino , Humanos , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Paracentese , Testes de Função Respiratória , Índice de Gravidade de Doença , Adulto Jovem
14.
Life Sci ; 251: 117595, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32240681

RESUMO

AIMS: The activation of hepatic stellate cells (HSCs) plays a central role in liver fibrosis progression. Phospholipase D (PLD) enzymes participate in multiple cellular activities. However, whether and how PLD regulates HSCs activation remain elusive. MAIN METHODS: The expression of intrahepatic PLD1 and PLD2 was determined in CCl4-induced mouse liver fibrosis models by western blot and immunohistochemistry. Cell model of liver fibrogenesis was constructed using rat HSCs line (HSC-T6) treated with recombinant transforming growth factor ß1 (TGFß1). Fibrogenesis was evaluated on the aspects of proliferation, expression of pro-fibrogenic markers and migration. The effects mediated by PLD1-mTOR axis on TGFß1-induced fibrogenesis were evaluated using HSC-T6 treated with small-molecular PLD1 inhibitors, PLD1-SiRNA, rapamycin (mTOR inhibitor) and MHY1485 (mTOR activator). KEY FINDINGS: Significant increase of PLD1, not PLD2 was documented in CCl4-induced cirrhotic compared to normal liver tissues. Suppression of PLD1 activities by PLD inhibitors or down-regulation of PLD1 expression in HSC-T6 could significantly restrain TGFß1-induced fibrogenesis, as reflected by decreased cell proliferation and reduced expression of pro-fibrogenic markers. Besides, either PLD1 inhibitor or PLD1-SiRNA significantly inhibited mTOR activity of HSC-T6. Moreover, PLD1 inhibitors not only exhibited similar effects with rapamycin in TGFß1-induced fibrogenesis, but also blunted MHY1485 enhanced cell proliferation of HSC-T6. SIGNIFICANCE: The PLD1-mTOR axis of HSCs could be therapeutically targeted in advanced liver fibrosis.


Assuntos
Células Estreladas do Fígado/metabolismo , Cirrose Hepática/fisiopatologia , Fosfolipase D/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Progressão da Doença , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos
15.
Z Gastroenterol ; 58(3): 254-266, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-32198739

RESUMO

The hepatorenal syndrome (HRS) is only a part of the wide spectrum of renal injury in patients with end-stage liver cirrhosis. Besides that, the advanced liver disease itself, or its underlying causes, as well as comorbidities, like diabetes mellitus, adiposity and arterial hypertension, can directly cause parenchymal renal insults (bile acid nephropathy, ischemic tubular injury, diabetic/hypertensive nephropathy, hepatitis B- and C-associated glomerulonephritis etc.). This kind of kidney injury is collectively described as non-hepatorenal syndrome AKI (non-HRS AKI. Beyond that, accumulating evidence highlights the role of systemic inflammation as an important common factor in the pathogenesis of decompensated liver cirrhosis, acute in chronic liver failure (ACLF) and renal dysfunction.In this review, we discuss recent data about definition, classification and pathophysiology of HRS, HRS-AKI and Non-HRS-AKI and exploit in this regard the diagnostic and prognostic potential of respective newer serum and urine markers.


Assuntos
Lesão Renal Aguda , Síndrome Hepatorrenal , Cirrose Hepática , Lesão Renal Aguda/fisiopatologia , Síndrome Hepatorrenal/fisiopatologia , Humanos , Rim , Cirrose Hepática/fisiopatologia
16.
Medicina (Kaunas) ; 56(3)2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32151106

RESUMO

. Background and Objectives: Cirrhosis is a liver disease that causes about one million deaths annually worldwide. The estimated cirrhosis prevalence ranges from 4.5-9.5% in the general population. Up to 40% of cirrhotic patients are asymptomatic and may be diagnosed late. Studies have described the importance of the functions of the liver and autonomic nervous system (ANS) and their relationship. There is limited information available on non-alcoholic cirrhosis and heart rate variability (HRV), which is a measure of the ANS. This study aimed to evaluate cardiac autonomic modulation through HRV in non-alcoholic cirrhosis individuals reported in previous observational and clinical trial studies. Materials and Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement using the Medline, Scopus, and Web of Science electronic databases. Five studies were identified and reviewed. Results: HRV was decreased in patients with non-alcoholic cirrhosis, even in the first stage. Conclusions: HRV could be used as a complementary method to improve both the diagnosis and prognosis of non-alcoholic cirrhosis.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Frequência Cardíaca , Coração/inervação , Coração/fisiopatologia , Cirrose Hepática/fisiopatologia , Feminino , Humanos , Masculino
17.
Niger J Clin Pract ; 23(2): 226-231, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32031098

RESUMO

Background: Chronic liver disease may be reversed through treatment, and it is crucial to have a definitive diagnosis of liver fibrosis for this treatment. Aims: In this study, we aimed to determine whether regression of liver fibrosis in naive patients undergoing strong antiviral therapy is reflected in noninvasive tests. Materials and Methods: We systematically reviewed and monitored medical records of patients with chronic hepatitis B who underwent liver biopsy for patient qualification. We selected patients with a liver fibrosis score of two or more who had not previously received antiviral treatment. We used previously described formulas to compute the indirect indicators of fibrosis for the patients and noted the values of Aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), fibrosis index-based 4 factor (FIB-4), AST-platelet ratio index (APRI), mean platelet volume (MPV) and platelet count (PLT). Results: We found a significant difference between the three measurements for APRI, AAR and FIB-4 scores and MPV and PLT distributions in patients who were administered entecavir and tenofovir (Friedman P < 0.05). In the post-hoc binary comparison for both entecavir and tenofovir, we found significant differences between the baseline measurements and the 3rd- and 5th-year measurements in terms of APRI, AAR, FIB-4, MPV, and PLT. Conclusion: Liver biopsy is considered the gold standard for the treatment and follow-up of hepatitis B but may not be appropriate in all cases. Non-invasive tests may be effective in monitoring antiviral therapy. We demonstrated that non-invasive tests improved with antiviral therapy, which may be a reflection of treatment-regression in liver histopathology.


Assuntos
Alanina Transaminase/sangue , Antivirais/efeitos adversos , Aspartato Aminotransferases/sangue , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/fisiopatologia , Fígado/patologia , Tenofovir/efeitos adversos , Adulto , Antivirais/uso terapêutico , Biomarcadores/sangue , Biópsia , Plaquetas/patologia , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Contagem de Plaquetas , RNA Viral/sangue , Estudos Retrospectivos , Tenofovir/uso terapêutico , Resultado do Tratamento
18.
Medicina (Kaunas) ; 56(2)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050594

RESUMO

Background and Objectives: Cirrhotic cardiomyopathy is a chronic cardiac dysfunction associated with liver cirrhosis, in patients without previous heart disease, irrespective of the etiology of cirrhosis. Electrocardiography (ECG) is an important way to evaluate patients with cirrhosis and may reveal significant changes associated with liver disease. Our study aimed to evaluate ECG changes in patients with diagnosed liver cirrhosis and compare them to patients with chronic hepatitis. Materials and Methods: We evaluated laboratory findings and ECG tracings in 63 patients with cirrhosis and 54 patients with chronic hepatitis of viral etiology. The end points of the study were prolonged QT interval, QRS hypovoltage and T-peak-to-T-end decrease. We confirmed the diagnosis of cirrhotic cardiomyopathy using echocardiography data. Results: Advanced liver disease was associated with prolonged QT intervals. Also, QRS amplitude was lower in patients with decompensated cirrhosis than in patients with compensated liver disease. We found an accentuated deceleration of the T wave in patients with cirrhosis. These findings correlated to serum levels of albumin, cholesterol and ammonia. Conclusions: ECG changes in liver cirrhosis are frequently encountered and are important noninvasive markers for the presence of cirrhotic cardiomyopathy.


Assuntos
Cardiomiopatias/fisiopatologia , Eletrocardiografia , Hepatite Viral Humana/fisiopatologia , Cirrose Hepática/fisiopatologia , Amônia/sangue , Cardiomiopatias/sangue , Cardiomiopatias/diagnóstico , Colesterol/sangue , Doença Crônica , Feminino , Hepatite Viral Humana/sangue , Humanos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Albumina Sérica/análise
19.
Sci Rep ; 10(1): 2450, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051422

RESUMO

Although transplantation is the only definitive treatment for liver cirrhosis, there remains a shortage of donors, necessitating that novel treatments be developed. We aimed to establish a liver fibrosis model in Macaca fascicularis that can help accelerate preclinical research. Liver fibrosis was induced by administering thioacetamide (TAA) and carbon tetrachloride (CCl4). Analysis of residual liver function and fibrosis progression was based on clinical indices, such as the Child-Pugh score or fibrotic markers, besides histology. TAA-induced marked fibrosis, whereas CCl4 did not induce fibrosis. Concerning residual liver function, both of TAA and CCl4 worsened the indices of the Child-Pugh score, but only the TAA model increased the retention ratio of indocyanine green. The TAA-induced fibrosis model in Macaca fascicularis worsens fibrosis and residual liver function, mimicking Child-Pugh grade B. Given that our model was evaluated by clinical indices, it could be applicable to preclinical research.


Assuntos
Modelos Animais de Doenças , Cirrose Hepática/induzido quimicamente , Macaca fascicularis , Tioacetamida , Animais , Progressão da Doença , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Testes de Função Hepática , Macaca fascicularis/fisiologia
20.
Epilepsia ; 61(3): 400-407, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31981220

RESUMO

OBJECTIVE: To determine whether acute exacerbations of cirrhotic liver disease are associated with higher odds of readmission for epilepsy or status epilepticus. METHODS: The New York State Inpatient Database is a statewide dataset containing data on 97% of hospitalizations for New York State. In this retrospective, case-crossover design study, we used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify index status epilepticus and epilepsy admissions. The primary exposure was defined as admission due to an acute exacerbation of cirrhotic liver disease. The case-crossover analysis tested whether exposure to a hepatic exacerbation within progressively longer case periods (14, 30, 60, 90, 120, 150, and 180 days before index admission), compared to control periods 1 year before the case period, was associated with readmission for epilepsy or status epilepticus. RESULTS: The odds ratio for subsequent admission for epilepsy after exposure to an acute exacerbation of cirrhotic liver disease was significant in the 30-day window at 2.072 (95% confidence interval [CI] = 1.095-3.92, P = .0252) and peaked in the 150-day window at 2.742 (95% CI = 1.817-4.137, P < .0001). In the status epilepticus group, all case periods demonstrated significantly elevated odds of subsequent admission following hepatic exacerbation. SIGNIFICANCE: Hepatic exacerbations are associated with increased odds for hospital admissions for epilepsy and status epilepticus across several timeframes.


Assuntos
Epilepsia/epidemiologia , Hospitalização/estatística & dados numéricos , Cirrose Hepática/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Estado Epiléptico/epidemiologia , Adulto , Idoso , Ascite/epidemiologia , Ascite/etiologia , Bases de Dados Factuais , Progressão da Doença , Varizes Esofágicas e Gástricas/epidemiologia , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Encefalopatia Hepática/epidemiologia , Encefalopatia Hepática/etiologia , Síndrome Hepatorrenal/epidemiologia , Síndrome Hepatorrenal/etiologia , Humanos , Tempo de Internação/estatística & dados numéricos , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Peritonite/epidemiologia , Peritonite/etiologia
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