RESUMO
BACKGROUND: Acoustic radiation force impulse imaging (ARFI) is a new method of liver stiffness measurement (LSM). The aim was to compare ARFI, transient elastography (TE) and AST to platelet ratio index (APRI) for the noninvasive diagnosis of clinically significant portal hypertension (CSPH, hepatic venous pressure gradient; HVPG ≥â10 mmHg) and esophageal varices (EV). MATERIALS AND METHODS: LSM via ARFI and TE was performed in 88 consecutive patients with cirrhosis prior to HVPG measurement. The mean liver stiffness for ARFI was calculated out of 5 measurements for each lobe. RESULTS: LSM by TE and ARFI was not successful in 22 (25%) patients and 1 (1â%) patient, respectively, due to ascites or obesity. Both TE (râ=â0.765; pâ<â0.001) and ARFI (râ=â0.646; pâ<â0.001) correlated significantly with HVPG. At the optimal cut-off (16.8 kPa), TE (area under the curve, AUC 0.870) yielded a sensitivity and specificity of 89.7% and 75%, respectively, for predicting CSPH. At the optimal cut-off (2.58 m/s), the sensitivity and specificity for ARFI (AUC 0.855) were 71.4% and 87.5%, respectively. Using an APRI (AUC 0.838), the sensitivity and specificity were 69% and 87.5%, respectively. The AUC for the diagnosis of EV was 0.802 for TE (cut-off: 27.9 kPa), 0.743 for ARFI (cut-off: 2.74 m/s), and 0.805 for APRI (cut-off: 1.90). CONCLUSION: ARFI shows a higher applicability particularly in obese and ascitic patients. All three investigated methods show a high diagnostic accuracy for CSPH. Notably, APRI performed not significantly different compared to ARFI for the diagnosis of CSPH.
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Aspartato Aminotransferases/sangue , Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Hipertensão Portal/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Contagem de Plaquetas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND STUDY AIMS: Flat lesions pose new challenges for endoscopists, but the importance of detecting them is still controversial. Most screening studies do not survey macroscopic polyp morphology. The aims were to evaluate the percentage of flat polyp findings in a large asymptomatic adult screening population (n = 52 521), to assess the impact of shape and size on malignant transformation, and to assess the role of flat lesions regarding quality assurance in colorectal cancer prevention. MATERIAL AND METHODS: Retrospective analysis of screening colonoscopies performed between 2007 and 2011 according to the Austrian "Quality management for colon cancer prevention" program. RESULTS: 17 771 patients with polyps were included in the study. Patients with flat polyps represented 24.2 % (n = 4293), 62.4 % (n = 11 097) were classified as having sessile and 13.4 % (n = 2381) as pedunculated polyps. Among those with flat polyps 51.4 % had adenomas (n = 2207). High grade dysplasia (HGD) was found in 2.1 % (n = 47) of flat adenomas, in 1.5 % (n = 89) of sessile adenomas and 4.7 % (n = 92) of pedunculated adenomas (P < 0.0001. The risk for containing HGD was 1.0 % for flat lesions ≤ 10 mm in size compared with 10.3 % for lesions > 10 mm, and 1.0 % for polypoid lesions ≤ 10 mm compared with 9.3 % for lesions > 10 mm (P < 0.0001). Multivariable logistic regression showed that polyp size (P < 0.0001) but not polyp shape (P = 0.438) is an independent predictor for HGD. Adenoma detection rate (ADR) correlated weakly with the flat polyp detection rate (Pearson r = 0.24). CONCLUSION: Malignant potential of polyps is mostly affected by size but not by shape. Since flat polyp detection rate only correlates poorly with ADR we do not recommend its incorporation in quality assured screening colonoscopy.
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Adenoma/patologia , Pólipos do Colo/patologia , Colonoscopia/normas , Neoplasias Colorretais/patologia , Idoso , Colonoscopia/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Melhoria de Qualidade , Estudos RetrospectivosRESUMO
BACKGROUND: Portal hypertension associated with liver cirrhosis increases the risk of postoperative complications after liver resection for hepatocellular carcinoma (HCC). This study assessed the role of preoperative hepatic venous pressure gradient (HVPG) assessment in identifying portal hypertension. METHODS: All patients who underwent liver resection for HCC between January 2000 and December 2009 at the Department of General Surgery, Medical University Vienna, were analysed retrospectively. HVPG was assessed prospectively in a subset of patients before liver resection. The influence of this assessment on postoperative complications was investigated. RESULTS: A total of 132 patients were enrolled, of whom 39 underwent HVPG measurement. Mean(s.d.) HVPG was 6·4(3·0) and 4·3(1·4) mmHg in patients with and without postoperative complications respectively (P = 0·028). Complication rates differed significantly at a cut-off HVPG value of 5 mmHg: 11 of 21 patients with a gradient of 1-5 mmHg developed complications versus 12 of 14 patients with a higher value (P = 0·045). HVPG exceeding 5 mmHg was associated with worse liver fibrosis (P = 0·004), higher rates of postoperative liver dysfunction (5 of 13 versus 1 of 18; P = 0·022) and ascites (7 of 14 versus 3 of 21; P = 0·022), and a longer hospital stay (median (range) 11 (7-26) versus 8 (4-20) days; P = 0·034). Overall postoperative morbidity did not differ between patients who had preoperative HVPG assessment and those who did not (P = 0·142). CONCLUSION: Preoperative HVPG assessment predicted liver fibrosis and postoperative complications.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hipertensão Portal/diagnóstico , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Idoso , Determinação da Pressão Arterial/métodos , Carcinoma Hepatocelular/fisiopatologia , Feminino , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Reoperação , Estudos Retrospectivos , Fatores de Risco , Pressão Venosa/fisiologiaRESUMO
Patients co-infected with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) are fraught with a rapid fibrosis progression rate and with complications of portal hypertension (PHT) We aimed to assess the influence of immune function [Centers of Disease Control and Prevention (CDC) stage] on development of PHT and disease progression in HIV-HCV co-infection. Data of 74 interferon-naïve HIV-HCV co-infected patients undergoing liver biopsy, measurement of portal pressure and of liver stiffness and routine laboratory tests (including CD4+ cell count, HIV and HCV viral load) were analysed. Time of initial exposure (risk behaviour) was used to assess fibrosis progression. Fibrosis progression, time to cirrhosis and portal pressure were correlated with HIV status (CDC stage). HIV-HCV patients had rapid progression of fibrosis [0.201 +/- 0.088 METAVIR fibrosis units/year (FU/y)] and accelerated time to cirrhosis (24 +/- 13 years), high HCV viral loads (4.83 x 10(6) IU/mL) and a mean HVPG at the upper limit of normal (5 mmHg). With moderate or severe immunodeficiency, fibrosis progression was even higher (CDC-2 = 0.177 FU/y; CDC-3 = 0.248 FU/y) compared with patients with higher CD4+ nadirs (CDC-1 = 0.120 FU/y; P = 0.0001). An indirect correlation between CD4+ cell count and rate of fibrosis progression (R = -0.6654; P < 0.001) could be demonstrated. Hepatic venous pressure gradient (HVPG) showed early elevation of portal pressure with median values of 4, 8 and 12 mmHg after 10, 15 and 20 years of HCV infection for CDC-3 patients. Patients treated with highly active anti-retroviral therapy (HAART) had similar rates of progression and portal pressure values than patients without HAART. Progression of HCV disease is accelerated in HIV-HCV co-infection, being more pronounced in patients with low CD4+ cell count. A history of a CD4+ cell nadir <200/microL is a risk factor for rapid development of cirrhosis and PHT. Thus, HCV treatment should be considered early in patients with HIV-HCV co-infection and largely preserved CD4+ cell counts.
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Infecções por HIV/complicações , Infecções por HIV/imunologia , Hepatite C Crônica/complicações , Hepatite C Crônica/imunologia , Hipertensão Portal/complicações , Cirrose Hepática/patologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Progressão da Doença , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Hipertensão Portal/patologia , Fígado/patologia , Cirrose Hepática/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Skills in gastrointestinal endoscopy mainly depend on experience and practice. Patients upon whom trainees perform their first endoscopic examinations are likely to suffer more discomfort and prolonged procedures. Training on endoscopy simulators may reduce the time required to reach competency in patient endoscopy. PATIENTS AND METHODS: Residents in internal medicine without experience of endoscopy were randomized to a group who trained on a simulator before conventional training (group S) or one that received conventional training only (group C) before starting upper gastrointestinal endoscopy in patients. After endoscopy, discomfort and pain were evaluated by patients, who were blind to the beginners' training status. Results in terms of time, technique (intubation, pyloric passage, J-maneuver), and diagnosis of pathological entities were evaluated by experts. RESULTS: From 2003 to 2007, 28 residents were enrolled. Comparing group S with group C in their first ten endoscopic examinations in patients, time taken to reach the duodenum (239 seconds (range 50â-â620) vs. 310 seconds (110â-â720; P < 0.0001) and technical accuracy ( P < 0.02) were significantly better in group S. Diagnostic accuracy did not differ between the groups. Fourteen residents (7 simulator-trained, 7 not simulator-trained) continued endoscopy training. After 60 endoscopic examinations, investigation time was still shorter in group S. Technical and diagnostic accuracy improved during on-patient training in both groups; here differences between groups were no longer observable. There were no significant differences in discomfort and pain scores between the groups after 10 and after 60 endoscopies. Discomfort and pain were higher than for endoscopy performed by experts. CONCLUSION: This randomized controlled trial shows that virtual simulator training significantly affects technical accuracy in the early and mid-term stages of endoscopic training. It helps reduce the time needed to reach technical competency, but clinically the effect is limited. Simulator training could be useful in an endoscopy training curriculum but cannot replace on-patient training.
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Competência Clínica , Simulação por Computador , Instrução por Computador , Educação de Pós-Graduação em Medicina/métodos , Endoscopia Gastrointestinal/educação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Gastroenteropatias/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Método Simples-Cego , Estatísticas não Paramétricas , Estudos de Tempo e Movimento , Adulto JovemRESUMO
OBJECTIVE: Patients with chronic pancreatitis usually have a long and debilitating history of disease with frequent hospital admissions, episodes of intractable pain and multiple interventions. The sequences of treatment at initial presentation, endoscopy, surgery, or conservative treatment may affect the time course and admissions needed for disease control, thereby determining quality of life and overall outcome. METHODS: A total of 292 patients with initial endoscopic, surgical, or conservative pharmacological treatment were retrospectively analyzed regarding frequency of interventions, days in hospital, symptom-free intervals, morbidity, and mortality. Quality of life (QoL) at the latest follow-up was measured by two standardized quality of life questionnaires (EORTC C30 and PAN26). RESULTS: Endoscopic treatment was initially performed in 150 (51.4%) patients, whereas 99 (33.9%) underwent surgery and 43 (14.7%) patients were treated conservatively at their initial presentation. Patients who underwent surgery had a significantly shorter time in the hospital (25.3 ± 24.6, 34.4 ± 35.1, 61.1 ± 37.9; P < 0.001), fewer subsequent therapies (0.43 ± 1.0, 2.1 ± 2.4, 3.1 ± 3.0; P ≤ 0.001), and a longer relapse-free interval (P = 0.004) compared with endoscopically treated patients. The overall complication rate was 32% both after surgery and endoscopy. Infectious-related complications occurred more often after surgical treatment (P ≤ 0.001), whereas patients after endoscopic intervention developed acute or chronic pancreatitis or pseudocyst formation (P = 0.023). CONCLUSIONS: Patients who undergo surgery as their initial treatment for chronic pancreatitis require less consecutive interventions, a shorter hospital stay, and have a better quality of life compared with any other treatment. Surgery should therefore be considered early for the treatment of chronic pancreatitis, when endoscopic or conservative treatment fails and patients require further intervention.
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Endoscopia do Sistema Digestório/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Pancreatite Crônica/terapia , Qualidade de Vida , Adulto , Feminino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background: Although optimal bowel preparation is essential for high-quality screening colonoscopy, documentation of preparation quality, patient satisfaction and adherence is scarce. Aim: The aim of this article is to compare low-volume (LV, 300 ml sodium picosulfate), intermediate-volume (IV, 2 l polyethylene glycol, PEG + ascorbic acid and sodium ascorbate), and high-volume (HV, 4 l PEG) purgatives. Results: A total of 5000 individuals (50.5% women) were enrolled between March 2015 and July 2017 (LV:IV:HV = 3.61:1.54:1). Overall sex- and age-adjusted adenoma detection rate was 25.4% (LV 23.8%, IV 25.4%, HV 29.8%), median age was 59.6 years, and cleansing was successful in 96.8%. Success rates of bowel cleansing were highest with HV (97.6%), followed by LV (97.2%) and IV (95.3%) with OR 2.04 (CI 95% 1.20-3.45, p = 0.008) and OR 1.79 (CI 95% 1.27-2.50, p = 0.001), respectively, compared to IV. A total of 93.5% of the LV group would use the same purgative in the future, 73.2% of IV and 69.4% of HV. A total of 84.4% would prefer overnight preparation, 12.1% same-day preparation. Conclusion: All purgatives investigated showed good bowel cleansing quality results, patient satisfaction and compliance. Improvement in patient information might lead to even higher participation rates in screening colonoscopy since one in five patients stated that bowel preparation worried him or her most prior to colonoscopy.
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Colonoscopia , Satisfação do Paciente , Cuidados Pré-Operatórios , Garantia da Qualidade dos Cuidados de Saúde , Adulto , Idoso , Colonoscopia/métodos , Colonoscopia/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/normas , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Sequential measurements of hepatic venous pressure gradient (HVPG) are used to assess the haemodynamic response to nonselective betablockers (NSBBs) in patients with portal hypertension. AIMS: To assess the rates of HVPG response to different doses of carvedilol. METHODS: Consecutive patients with cirrhosis undergoing HVPG-guided carvedilol therapy for primary prophylaxis of variceal bleeding between 08/2010 and 05/2015 were retrospectively included. After baseline HVPG measurement, carvedilol 6.25 mg/d was administered and HVPG response (HVPG-decrease ≥20% or to ≤12 mm Hg) was assessed after 3-4 weeks. In case of nonresponse, carvedilol dose was increased to 12.5 mg/d and a third HVPG-measurement was performed after 3-4 weeks. We also assessed HVPG-response rates according to the Baveno VI consensus (HVPG decrease ≥10% or to ≤12 mm Hg) and changes in systolic arterial pressure (SAP). RESULTS: Seventy-two patients (Child A, 37%; B, 35%; C, 28%) were included. 28 (39%) patients achieved a HVPG-decrease ≥ 20% with carvedilol 6.25 mg/d and another 10 (14%) with carvedilol 12.5 mg/d. Forty (56%) patients had a HVPG decrease ≥10% with carvedilol 6.25 mg/d and 24 (33%) with carvedilol 12.5 mg/d. Thus, in total, a HVPG-response of ≥20% and ≥10% and was achieved in 38 (53%) and 55 (76%) and of patients respectively. Notably, 6 patients (n = 4 with ascites) did not tolerate an increase to 12.5 mg/d due to hypotension/bradycardia. However, none of the other patients had a SAP < 90 mm Hg at the final HVPG measurement. CONCLUSION: Carvedilol 12.5 mg/d was more effective than 6.25 mg/d in decreasing HVPG in primary prophylaxis. A total of 76% of patients achieved a HVPG-response of ≥ 10% to carvedilol 12.5 mg/d, however, arterial hypotension might occur, especially in patients with ascites.
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Anti-Hipertensivos/uso terapêutico , Carvedilol/uso terapêutico , Varizes Esofágicas e Gástricas/tratamento farmacológico , Hemorragia Gastrointestinal/prevenção & controle , Hipertensão Portal/tratamento farmacológico , Pressão na Veia Porta/efeitos dos fármacos , Relação Dose-Resposta a Droga , Varizes Esofágicas e Gástricas/fisiopatologia , Feminino , Humanos , Hipertensão Portal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Estudos RetrospectivosRESUMO
BACKGROUND: The amino sulphonic acid taurine reduces oxidative endoplasmatic reticulum stress and inhibits hepatic stellate cell activation, which might lead to reduction of portal pressure in cirrhosis. AIM: To assess the haemodynamic effects of taurine supplementation in patients with cirrhosis and varices. METHODS: Patients with hepatic venous pressure gradient (HVPG) ≥12 mm Hg were included in this prospective proof of concept study. Concomitant nonselective beta-blockers therapy was not allowed. Patients received either 4 weeks of oral taurine (6 g/day), or placebo, prior to evaluation of HVPG response. RESULTS: Thirty patients were screened and 22 included in the efficacy analysis (12 taurine/10 placebo; 64% male, mean age: 52 ± 11 years, Child A: 9%, B:64%, C:27%, ascites:68%). In the taurine group, mean HVPG dropped from 20 mm Hg (±4) at baseline to 18 mm Hg (±4) on day 28 (mean relative change: -12%, P = .0093). In the placebo group, mean HVPG increased from 20 mm Hg (±5) at baseline to 21 mm Hg (±5) on day 28 (mean relative change:+2%, P = .4945). Taurine had no significant effects on systemic haemodynamics. Seven of 12 patients (58%) on taurine achieved a HVPG response >10%, compared to none in the placebo group (P = .0053). In a multivariate linear model, HVPG reduction was significantly larger in the taurine group compared to placebo group (P = .0091 and P = .0109 for absolute and relative change respectively). Treatment-related adverse events included gastrointestinal discomfort and fatigue, and were usually mild and comparable between treatment groups. CONCLUSION: Taurine is safe and may reduce portal pressure in cirrhotic patients. More studies on the underlying mechanisms of action and long-term effects of taurine supplementation are warranted.
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Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Pressão na Veia Porta/efeitos dos fármacos , Taurina/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Ascite/complicações , Método Duplo-Cego , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: The rs738409 C>G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene promotes triglyceride accumulation in hepatocytes and hepatic stellate cell activation and has previously been linked to hepatic steatosis/liver fibrosis. AIM: To investigate its impact on hepatic decompensation and (liver-related) mortality in patients who had already developed portal hypertension. Moreover, we assessed its link with hepatic steatosis as evaluated by controlled attenuation parameter. METHODS: We performed a retrospective analysis in prospectively characterised patients with viral hepatitis/fatty liver disease-induced portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) diagnosed at the Medical University of Vienna who underwent HVPG measurement (until 2013; n = 372; longitudinal study) or simultaneous HVPG and controlled attenuation parameter measurement (2014-2017; n = 153; cross-sectional study). RESULTS: While survival was similar between PNPLA3-C/C and -C/G patients, we observed substantially increased mortality in PNPLA3-G/G patients. PNPLA3-G/G had no impact on mortality in the subgroup of patients with viral hepatitis; however, we observed a strong independent association between PNPLA3-G/G and hepatic decompensation (adjusted subdistribution hazard ratio [aSHR]: 2.1, 95% confidence interval [95% CI]: 1.1-4; P = 0.024) as well as mortality (overall: aSHR: 2.2, 95% CI: 1.22-3.98; P = 0.009; liver-related: aSHR: 2.2, 95% CI: 1.08-4.46; P = 0.029) in patients with fatty liver disease. Interestingly, even in the subgroup of patients who had already progressed to clinically significant portal hypertension (HVPG ≥ 10 mm Hg), PNPLA3-G/G substantially increased mortality (aSHR: 2.33, 95% CI: 1.27-4.29; P = 0.006). PNPLA3-genotype had no influence on controlled attenuation parameter or the prevalence of values ≥248 dB/m. CONCLUSION: PNPLA3-G/G-genotype seems to double the risks of hepatic decompensation and (liver-related) mortality in patients with portal hypertension due to fatty liver disease. Further studies are warranted to investigate potential underlying pathophysiological mechanisms unrelated to hepatic steatosis.
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Hipertensão Portal/genética , Hipertensão Portal/mortalidade , Lipase/genética , Falência Hepática/genética , Falência Hepática/mortalidade , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Estudos Transversais , Fígado Gorduroso/complicações , Fígado Gorduroso/genética , Fígado Gorduroso/mortalidade , Feminino , Predisposição Genética para Doença , Genótipo , Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Hepatite C Crônica/mortalidade , Hepatite C Crônica/patologia , Humanos , Hipertensão Portal/complicações , Falência Hepática/complicações , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Elevated plasma von Willebrand factor antigen (vWF) has been shown to indicate the presence of clinically significant portal hypertension, and thus, predicts the development of clinical events in patients with cirrhosis. AIM: To investigate the impact of bacterial translocation and inflammation on vWF, as well as the association between vWF and procoagulant imbalance. Moreover, we assessed whether vWF predicts complications of cirrhosis, independent of the severity of portal hypertension. METHODS: Our study population comprised 225 patients with hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg without active bacterial infections or hepatocellular carcinoma. RESULTS: vWF correlated with markers of bacterial translocation (lipopolysaccharide-binding protein [LBP; ρ = 0.201; P = 0.021]), inflammation (interleukin 6 [IL-6; ρ = 0.426; P < 0.001] and C-reactive protein [CRP; ρ = 0.249; P < 0.001]), and procoagulant imbalance (factor VIII/protein C ratio; ρ = 0.507; P < 0.001). Importantly, the associations between vWF and these parameters were independent of HVPG. Moreover, vWF (per 10%) independently predicted variceal bleeding (hazard ratio [HR]: 1.08 [95% confidence interval (95% CI): 1.01-1.16]; P = 0.023), requirement of paracentesis (HR: 1.05 [95% CI: 1.01-1.1]; P = 0.023) and bacterial infections (HR: 1.04 [95% CI: 1-1.09]; P = 0.04) including spontaneous bacterial peritonitis (HR: 1.09 [95% CI: 0.999-1.18]; P = 0.053) on a trend-wise level. After backward elimination, vWF (HR: 1.05 [95% CI: 1.02-1.08]; P = 0.003) and CRP (per 10 mg/L; HR: 1.53 [95% CI: 1.14-2.05]; P = 0.005) remained in the final model for transplant-free mortality. Finally, the independent prognostic value of vWF/CRP groups for mortality was confirmed by competing risk analysis. CONCLUSION: Our results demonstrate that vWF is not only a marker of portal hypertension but also independently linked to bacterial translocation, inflammation and procoagulant imbalance, which might explain its HVPG-independent association with most clinical events. Prognostic groups based on vWF/CRP efficiently discriminate between patients with a poor 5-year survival and patients with a favourable prognosis.
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Translocação Bacteriana , Transtornos da Coagulação Sanguínea/diagnóstico , Hipertensão Portal/diagnóstico , Inflamação/diagnóstico , Fator de von Willebrand/metabolismo , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/fisiopatologia , Fatores de Coagulação Sanguínea/metabolismo , Varizes Esofágicas e Gástricas/sangue , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/diagnóstico , Feminino , Hemorragia Gastrointestinal/sangue , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/diagnóstico , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/microbiologia , Hipertensão Portal/patologia , Inflamação/sangue , Inflamação/etiologia , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/microbiologia , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. AIM: To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. METHODS: (Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. RESULTS: Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P = 0.353) nor mortality (log-rank: P = 0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL + NSBB vs EBL alone (log-rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log-rank: P<0.001). A decreased risk of death with EBL + NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6-months mortality (HR: 0.53, P = 0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P = 0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P = 0.567). CONCLUSIONS: EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6 months after EBL.
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Antagonistas Adrenérgicos beta/uso terapêutico , Endoscopia Gastrointestinal/métodos , Varizes Esofágicas e Gástricas/mortalidade , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/mortalidade , Hemorragia Gastrointestinal/terapia , Adulto , Idoso , Quimioprevenção/métodos , Terapia Combinada , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/tratamento farmacológico , Feminino , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Humanos , Ligadura , Cirrose Hepática/tratamento farmacológico , Pessoa de Meia-Idade , Prevenção Primária/métodos , Estudos Retrospectivos , Prevenção Secundária/métodos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: HIV/HCV co-infected patients show accelerated fibrosis progression and higher risk for complications of portal hypertension (PHT). AIM: To assess the effects of interferon-free therapy on portal pressure, liver histology and plasma biomarkers in HIV/HCV-coinfected patients with PHT. METHODS: Twenty-two patients with paired hepatic venous pressure gradient (HVPG) measurements prior and after successful treatment (SVR) with interferon-free regimens were included. Liver stiffness was assessed by transient elastography and biopsies were scored according to METAVIR. Plasma biomarkers were determined by ELISA. RESULTS: Overall, HVPG decreased from 10.7 ± 4.1 mmHg at baseline to 7.4 ± 4.2 mmHg after HCV treatment (Δ:-3.3 ± 2.7 mmHg; p < 0.001). In patients with clinically significant PHT (HVPG≥10 mmHg, n = 11), HVPG decreased from 14.1 ± 2.9 to 10.4 ± 3.9 mmHg (Δ:-3.7 ± 3.3 mmHg; p = 0.004) and a haemodynamic response (HVPG decrease ≥10%) was observed in 73%. In 64% of patients with subclinical PHT (HVPG 6-9 mmHg, n = 11), portal pressure normalised at SVR. Mean liver stiffness decreased from 20.8 kPa to 11.5 kPa (Δ:-8.8 ± 7.4 kPa; p < 0.001). Fifty percent (7/14) of patients with cirrhosis were re-classified as METAVIR ≤F3 and all patients with decompensated cirrhosis improved their Child-Pugh stage. After successful HCV treatment, 39% still had persistent histological necroinflammatory activity (METAVIR A1), which correlated with less HVPG response and more steatosis. While most biomarkers improved with SVR, METAVIR A1 patients had significantly higher plasma levels of fibrogenic (PDGF, TGF-ß) and angiogenic (VEGF, Angiopoietin1) biomarkers. CONCLUSIONS: Interferon-free therapy reduces PHT and halts histological necroinflammatory activity in the majority of HIV/HCV-coinfected patients after SVR, which may lead to re-compensation of liver function in cirrhosis. Biomarkers could identify patients with persisting hepatic necroinflammation.
Assuntos
Infecções por HIV/patologia , Hepatite C Crônica/patologia , Hipertensão Portal/patologia , Interferons , Cirrose Hepática/patologia , Adulto , Coinfecção , Progressão da Doença , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Hepatite C Crônica/sangue , Hepatite C Crônica/epidemiologia , Humanos , Hipertensão Portal/sangue , Hipertensão Portal/epidemiologia , Interferons/uso terapêutico , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta/fisiologiaRESUMO
BACKGROUND: A pegylated interferon-alpha-induced decrease in platelet counts may become a limiting factor for continuation of therapy. AIM: To evaluate the effect of pegylated interferon-alpha administration on platelet plug formation and von Willebrand factor antigen release in patients with chronic hepatitis C. METHODS: Thirty patients with chronic hepatitis C (genotype 1; fibrosis 1-3: n = 16, cirrhosis: n = 14) received a single dose of 9 MU interferon-alpha2a, followed by weekly administration of 180 mug of pegylated interferon-alpha2a/ribavirin for 48 weeks. Platelet counts, platelet function (collagen-epinephrine-induced closure time) and von Willebrand factor antigen were measured. RESULTS: Platelet counts and collagen-epinephrine-induced closure time decreased by 13% and 16%, respectively, 24 h after the first dose of interferon-alpha2a, and von Willebrand factor antigen levels increased by 31% (P < 0.01) compared with baseline. During a 48-week observation period, platelet counts decreased by a maximum of 33% (P < 0.001), von Willebrand factor antigen levels increased by 69% (P < 0.001) whereas collagen-epinephrine-induced closure time did not change. In noncirrhotic patients, the increase of von Willebrand factor antigen levels was maintained throughout therapy without a change in collagen-epinephrine-induced closure time. In contrast, in cirrhotics, von Willebrand factor antigen levels did not increase, while collagen-epinephrine-induced closure time was prolonged. CONCLUSION: Single-dose interferon-alpha decreases platelet counts but improves platelet function, possibly by the release of von Willebrand factor antigen. Accordingly, long-term antiviral treatment had no effect on collagen-epinephrine-induced closure time, despite the decrease in platelet count in noncirrhotic patients. Such a compensation of decreased platelet counts by increased von Willebrand factor antigen level did not occur in cirrhotics.
Assuntos
Plaquetas/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Fator de von Willebrand/metabolismo , Adulto , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Estudos Prospectivos , Proteínas RecombinantesRESUMO
BACKGROUND: Portal hypertension is the strongest predictor of virological response to pegylated interferon (IFN)/ribavirin in patients with chronic hepatitis C (CHC)-related cirrhosis. AIM: To investigate the effects of portal pressure assessed by hepatic venous pressure gradient (HVPG) measurement on virological responses in patients treated with IFN-free regimens outside of clinical trials. METHODS: Fifty-six patients with CHC and cirrhosis who underwent HVPG measurement before starting an IFN-free therapy were retrospectively studied. Patients were treated with sofosbuvir in combination with daclatasvir (n = 32), ribavirin (n = 12) or simeprevir (n = 11), or the combination of simeprevir/daclatasvir (n = 1), for 12-24 weeks. RESULTS: Hepatic venous pressure gradient values ≥10 mmHg and ≥16 mmHg were observed in 41 (73%) and 31 (55%) patients respectively. The distributions of treatment regimens and durations were comparable between patients with or without portal hypertension. Patients with portal hypertension had lower platelet counts and albumin levels, while bilirubin levels, INR, MELD and Child-Pugh scores were higher than in patients without portal hypertension. Importantly, rates of on-treatment virological response and viral kinetics, as well as the rates of sustained virological response 12 weeks after the end of therapy [96% (54/56)] were not affected by portal hypertension. Anti-viral therapy improved liver stiffness, platelet count, serum albumin and bilirubin levels, as well as prothrombin time. CONCLUSIONS: This is the first study to demonstrate that IFN-free regimens overcome the negative effect of portal hypertension on virological responses and viral kinetics. Improvements in liver stiffness and platelet count might reflect an anti-portal hypertensive effect of IFN-free treatments.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hipertensão Portal/etiologia , Cirrose Hepática/etiologia , Pressão na Veia Porta/efeitos dos fármacos , Adulto , Idoso , Antivirais/administração & dosagem , Carbamatos , Quimioterapia Combinada , Feminino , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Estudos Retrospectivos , Ribavirina/uso terapêutico , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
BACKGROUND: Patients with liver cirrhosis have a complex haemostasis disturbance including thrombocytopenia and abnormal bleeding time. Erythropoietin is the primary stimulator for erythrocyte production and also induces megakaryocyte formation. In healthy men erythropoietin increased platelet count and platelet reactivity. AIM: As patients with liver cirrhosis often undergo invasive procedures, we were interested to study whether erythropoietin could improve platelet function in addition to thrombocytopenia. METHODS: In total, 22 thrombocytopenic (platelet counts < 120 g/L) patients with alcoholic liver cirrhosis received either 100 IE/kg erythropoietin or placebo on days 1, 3 and 5 in a 2:1 randomized, placebo-controlled double-blind fashion. Platelet counts and platelet reactivity (activator-stimulated expression of P-selectin on platelets measured by flow cytometry) were determined on study days 1, 3, 5 and 9. RESULTS: Median platelet count was 80 g/L which is borderline for major elective surgical interventions. Baseline values were not different between groups (P > 0.05). Treatment with erythropoietin increased platelet count by 25% (P = 0.01) and platelet reactivity twofold (P < 0.01) vs. baseline. The increase in platelet count vs. baseline was more pronounced in patients with platelet counts <80 g/L. No significant effect was observed in the placebo group. CONCLUSIONS: Treatment with erythropoietin significantly increased platelet counts and platelet reactivity in patients with alcoholic liver cirrhosis. Preoperative treatment with erythropoietin is therefore expected to yield higher platelet levels and better platelet function.
Assuntos
Eritropoetina/uso terapêutico , Cirrose Hepática Alcoólica/terapia , Trombocitopenia/terapia , Adulto , Tempo de Sangramento , Plaquetas/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Cirrose Hepática Alcoólica/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Contagem de Reticulócitos , Reticulócitos/efeitos dos fármacos , Trombocitopenia/sangueRESUMO
Isoprostanes (IP) generated during free radical catalyzed oxidation injury have been claimed as a reliable indicator of oxidative stress in vivo. In particular, they are formed during LDL-oxidation. Vascular content, plasma levels and urinary excretion of IP were reported to be elevated in hypercholesterolemia. We therefore assessed the values of the IP 8-epi-PGF2alpha in plasma and urine in nine patients (7 males, 2 females) suffering from severe heterozygous hypercholesterolemia before and after LDL-apheresis as well as during the interval. LDL-apheresis caused a significant (P<0.01) drop in 8-epi-PGF2alpha in plasma and urine. The respective values in smokers (n = 4) were significantly (P<0.01) higher as compared to non-smokers. No sex difference was seen. Together with the findings of a parallel decrease in oxidized LDL, these data show a significant benefit of LDL-apheresis reducing in vivo oxidation injury. This benefit may at least partly contribute to the clinical improvement seen in the patients treated.
Assuntos
Remoção de Componentes Sanguíneos , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Hiperlipoproteinemia Tipo II/terapia , Lipoproteínas LDL/sangue , Adulto , Análise de Variância , Dinoprosta/sangue , Dinoprosta/urina , Feminino , Variação Genética , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/urina , Masculino , Pessoa de Meia-Idade , Oxirredução , Fumar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de TempoRESUMO
In order to improve the possibilities of genetic counselling in multifactorial inheritance, dermatoglyphic investigations were performed in a family with atrial septal defect (ostium secundum) - ASD II - affecting two out of six children of a married couple and a maternal aunt. The frequency of finger-print patterns differed widely between the husband and his father on the one hand and the wife and her relatives on the other hand. Assuming some partial effect of the ASD II genes on the total gene influence on dermatoglyphics, it seemed possible that the finger-prints of the two affected siblings and of those brothers who were fairly near the threshold of ASD manifestation might resemble more closely the finger-prints of their mother and their mother's relatives than the finger-prints of their father and their paternal grandfather. This assumption was, however, disproven.
Assuntos
Dermatoglifia , Aconselhamento Genético , Comunicação Interatrial/genética , Cromossomos , Feminino , Genética , Comunicação Interatrial/diagnóstico , Humanos , Masculino , Linhagem , FenótipoRESUMO
The syndrome of juvenile diabetes mellitus, primary optic atrophy and hydronephrosis, hydroureter and megacystis was observed in two brothers. One patient showed consistent elevation of the plasma creatine phosphokinase activity (isoenzymes MM 71%, MB 29%), without any sign of myocardial or skeletal muscle disease. This rare syndrome is inherited in an autosomal recessive manner. It has not yet been reported in Austria, to our knowledge.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Atrofia Óptica/etiologia , Criança , Creatina Quinase/metabolismo , Diabetes Mellitus Tipo 1/genética , Humanos , Hidronefrose/etiologia , Isoenzimas/metabolismo , Masculino , Linhagem , Síndrome , Doenças da Bexiga Urinária/etiologiaRESUMO
30 patients with systemic lupus erythematosus (SLE), 19 patients with rheumatoid arthritis (RA) and 34 controls were investigated with regard to measles antibodies (AB). The titres were compared with clinical and immunological parameters. As previously reported by several authors we found increased measles AB titres more frequently (kappa 2-test, p less than 0.05) in patients with SLE than in those with RA and controls. No significant correlation was found between immunoglobulins, antinuclear antibodies, CH50 or rheumatoid factor, and an elevation of the measles AB titre. A trend was noted, however, towards a positive correlation between measles antibodies and IgM. An elevated measles AB titre in SLE can be explained on the basis of several mechanisms. However, hyperimmunoglobulinaemia with non-specific, secondary AB elevation can be ruled out as a cause of elevated measles AB titre according to our results.