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1.
BMC Gastroenterol ; 23(1): 103, 2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37013522

RESUMEN

BACKGROUND: Endoscopic retrograde cholangiography (ERC) possesses a translocation risk of microbes to the biliary system. We studied bile contamination during ERC and its impact on patients' outcome in a real-life-situation. METHODS: Ninety-nine ERCs were analyzed and microbial samples were taken from the throat before and from bile during ERC and from irrigation fluid of the duodenoscope before and after ERC. RESULTS: 91.2% of cholangitis patients had detectable microbes in the bile (sensitivity 91%), but the same was true for 86.2% in the non-cholangitis group. Bacteroides fragilis (p=0.015) was significantly associated with cholangitis. In 41.7% of ERCs with contaminated endoscopes these microbes were found in the bile after the procedure. Analysis of duodenoscopes' irrigation liquid after ERC matched the microbial bile analysis of these patients in 78.8%. Identical microbial species were in throat and in bile samples of the same ERC in 33% of all cases and in 45% in the non-cholangitis group. Transmission of microbes to the biliary tract did not result in more frequent cholangitis, longer hospital stays, or worse outcome. CONCLUSIONS: During ERC bile samples are regularly contaminated with microbes of the oral cavity but it did not affect clinical outcome.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Biliar , Sistema Biliar , Colangitis , Microbiota , Humanos , Colangiopancreatografia Retrógrada Endoscópica , Sistema Biliar/diagnóstico por imagen , Colangiografía
2.
Eur Radiol ; 30(1): 663-671, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31428825

RESUMEN

OBJECTIVES: The comparability of left ventricular ejection fraction (LVEF) measurements by cardiac magnetic resonance (CMR) and 2D echocardiography (2DE) early after ST-elevation myocardial infarction (STEMI) remains unclear. METHODS: In this study, LVEF measured by CMR and 2DE (Simpson's method) were compared in 221 patients after STEMI treated by primary percutaneous coronary intervention. 2DE image quality was systematically assessed and studies reported by an accredited examiner. Intermodality agreement was assessed by the Bland-Altman method. Major adverse cardiac events (MACE) were defined as the composite of death, myocardial infarction or hospitalisation for heart failure. Patients were followed up for a median of 40.9 months (IQR 28.1-56). RESULTS: After non-anterior STEMI, LVEF measurements by 2DE (single and biplane) were consistently underestimated in comparison to CMR (CMR 55.7 ± 9.5% vs. 2DE-4CV 49 ± 8.2% (p = 0.06), 2DE-2CV 52 ± 8% (p < 0.001), 2DE-biplane 53.5 ± 7.1% (p = 0.01)). After anterior STEMI, there was no significant difference in LVEF measurements by 2DE and CMR with acceptable limits of agreement (CMR 49 ± 11% vs. 2DE-4CV 49 ± 8.2% (p = 0.8), 2DE-2CV 49 ± 9.2% (p = 0.9), 2DE-biplane 49.6 ± 8% (p = 0.5)). In total, 15% of patients experienced a MACE during follow-up. In multivariate Cox regression analysis, reduced LVEF (< 52%) as assessed by either 2DE or CMR was predictive of MACE (2DE HR = 2.57 (95% CI 1.1-6.2), p = 0.036; CMR HR = 2.51 (95% CI 1.1-5.7), p = 0.028). CONCLUSIONS: At baseline after non-anterior STEMI, 2D echocardiography significantly underestimated LVEF in comparison to CMR, whereas after anterior infarction, measurements were within acceptable limits of agreement. Both imaging modalities offered similar prognostic values when a reduced LVEF < 52% was applied. KEY POINTS: • After non-anterior STEMI, 2D-echocardiography significantly underestimated LVEF compared with cardiac MRI • An ejection fraction of < 52% in the acute post-infarct period by both 2D echocardiography and CMR offered similar prognostic values.


Asunto(s)
Ecocardiografía/métodos , Imagen por Resonancia Magnética/métodos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Infarto del Miocardio con Elevación del ST/complicaciones , Volumen Sistólico , Disfunción Ventricular Izquierda/complicaciones
3.
Hepatology ; 65(1): 202-216, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27775822

RESUMEN

Acute-on-chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrome characterized by acute decompensation, organ failure(s) and high short-term mortality. Recent findings suggest that an overexuberant systemic inflammation plays a primary role in ACLF progression. In this study, we examined whether genetic factors shape systemic immune responses in patients with decompensated cirrhosis. Six single-nucleotide polymorphisms (SNPs) in inflammation-related genes (interleukin [IL]-1 beta [IL-1ß], rs1143623; IL-1 receptor antagonist [IL-1ra], rs4251961; IL-10, rs1800871; suppressor of cytokine signaling-3, rs4969170; nucleotide-binding oligomerization domain-containing protein 2, rs3135500; and chemerin chemokine-like receptor 1, rs1878022) were genotyped in 279 patients with cirrhosis with (n = 178) and without (n = 101) ACLF from the CANONIC study of the CLIF consortium. Among these SNPs, we identified two polymorphisms belonging to the IL-1 gene cluster (IL-1ß and IL-1ra) in strong association with ACLF. Both SNPs were protective against ACLF; IL-1ß (odds ratio [OR], 0.34, 95% confidence interval [CI], 0.13-0.89; P < 0.05) and IL-1ra (OR, 0.58; 95% CI, 0.35-0.95; P < 0.05) under the recessive and overdominant inheritance models, respectively. These protective SNPs translated into reduced circulating levels of IL-1ß, IL-1α, IL-6, granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor, and C-reactive protein at enrollment as well as after 7-14 days of admission. These findings were confirmed in vitro in leukocytes incubated with plasma from patients with decompensated cirrhosis carrying the protective SNP genotypes. Notably, a higher frequency of the protective genotypes was observed in patients without (80%) than in those with (20%) ACLF. Consistently, patients carrying the combined protective genotypes showed a lower 28-day mortality rate. CONCLUSION: These data identify two common functional polymorphisms in the IL-1 gene cluster, which are associated with the inflammatory process related to development of ACLF. (Hepatology 2017;65:202-216).


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/genética , Inflamación/genética , Interleucina-1/genética , Familia de Multigenes , Polimorfismo de Nucleótido Simple , Insuficiencia Hepática Crónica Agudizada/epidemiología , Femenino , Humanos , Inflamación/complicaciones , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Factores de Riesgo
4.
Hepatology ; 66(6): 1910-1919, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28653750

RESUMEN

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate between "high-" and "low-benefit" patients. To do so, the concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2,103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (Model for End-Stage Liver Disease, alpha-fetoprotein, Milan-Criteria status, and radiological response) displayed a high effect in terms of delta benefit. According to these risk factors, four benefit groups were identified. Patients with three to four factors ("no-benefit group"; n = 405 of 2,103; 19.2%) had no benefit of LT compared to alternative treatments. Conversely, patients without any risk factor ("large-benefit group"; n = 108; 5.1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The ITT transplant survival benefit presented here allows physicians to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equitable method of organ allocation. Patients without benefit should be de-listed, whereas patients with large benefit ratio should be prioritized for LT. (Hepatology 2017;66:1910-1919).


Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Carcinoma Hepatocelular/mortalidad , Europa (Continente) , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
5.
Liver Int ; 38(7): 1188-1197, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29197145

RESUMEN

BACKGROUND & AIMS: Excellent efficacy and safety profile of second-generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT. PATIENTS & METHODS: A total of 62 OLT recipients (male: 50%/81%; age: 60.7 ± 8.5 years [mean ± SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%. RESULTS: Data of at least 96 weeks of FUP after treatment cessation (mean: 120; up to 167 weeks) were analysed. All patients showed on-treatment response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment-free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1 respectively). Reasons for death were: multi-organ failure (N = 4), impaired graft function (N = 1) and unknown (N = 1). CONCLUSION: RBV-free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long-term data show that viral eradication is durable but not necessarily translated into beneficial long-term clinical outcome.


Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Trasplante de Hígado , Anciano , Austria , Bencimidazoles/uso terapéutico , Carbamatos , Carcinoma Hepatocelular/virología , Quimioterapia Combinada , Femenino , Fluorenos/uso terapéutico , Estudios de Seguimiento , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/mortalidad , Humanos , Imidazoles/uso terapéutico , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Pirrolidinas , Recurrencia , Ribavirina , Simeprevir/uso terapéutico , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , Valina/análogos & derivados
6.
Liver Int ; 38(6): 1028-1035, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29136329

RESUMEN

BACKGROUND: The introduction of direct-acting antivirals (DAA) has increased sustained virological response (SVR) rates in patients with advanced liver disease and chronic hepatitis C(CHC)infection. At present, data on clinical outcome and long-term durability of viral eradication after successful DAA therapy are scarce. AIM: To evaluate the long-term success of viral eradication in patients with advanced fibrosis or cirrhosis treated with DAAs. METHODS: Five hundred and fifty-one patients with advanced fibrosis (n = 158) or cirrhosis (CPS-A:317,CPS-B/C:76) and SVR after interferon and ribavirin-free DAA therapy treated between October 2013 and April 2016 were studied with a median follow-up of 65.6 (13.0-155.3) weeks. Only patients without hepatocellular carcinoma (HCC) at baseline and without liver transplantation were included. RESULTS: Twelve patients (2.2%) died during follow-up: the mortality rate was 0.6% in F3, 2.2% in CPS-A and 5.3% in CPS-B/C patients (P = .08). During follow-up 36 patients with cirrhosis (9.1%) developed a liver related event, including 16 with de-novo HCC (4.1%). Seven patients were transplanted at a median of 9.7 (range 3.8-21.7) months after EOT. History of decompensation was significantly associated with liver related events during follow-up (HR 7.9; 95% CI 2.7-22.6; P < .001), and with mortality (HR 5.5; 95% CI 1.5-20.2, P = .01). CONCLUSIONS: Eradication of HCV by DAA therapy was durable irrespective of the DAA combination used. Most of the cured patients had an excellent long-term clinical prognosis. Nevertheless, the risk of new occurrence of HCC remains worrisome and thus regular surveillance is obligatory even after clinical stabilization and improvement of the patient.


Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/complicaciones , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicaciones , Anciano , Austria , Carcinoma Hepatocelular/virología , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/mortalidad , Humanos , Interferones , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Ribavirina , Respuesta Virológica Sostenida
7.
Liver Int ; 36(5): 688-95, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26386273

RESUMEN

BACKGROUND & AIMS: Current treatment guidelines preclude liver transplantation for patients with BCLC B (intermediate stage) HCC, and expanding transplantation criteria for selected patients beyond early stage HCC remains controversial. The aim of this study was to determine stage-dependent HCC recurrence and overall survival rates in transplant recipients and the impact of response to neoadjuvant treatment on outcome. METHODS: The CT/MRI scans of patients who underwent liver transplantation for HCC at our transplant centre during a time period of 12 years were reviewed by two radiologists to assess tumour stage and response to neoadjuvant treatment according to mRECIST. RESULTS: Of 174 HCC patients, 48 (28%) were BCLC intermediate stage. Neoadjuvant treatment was performed in 94% of patients. When patients were stratified according to tumour stage, no significant difference in overall survival was observed between very early or early and intermediate stage. When stratified according to treatment response, patients with complete response had a 5-year overall survival of 87%, which was significantly higher than in patients with progressive disease (62%, P = 0.02). HCC recurrence in intermediate stage patients without disease progression after neoadjuvant treatment was equal to that in patients with very early or early stage HCC. Tumour grading, histological and radiological evidence of vascular invasion, but not tumour stage were identified as independent risk factors for HCC recurrence. CONCLUSIONS: Liver transplantation may be an option for selected patients with BCLC intermediate stage HCC and complete response after neoadjuvant treatment because of excellent long-term survival and low recurrence rates.


Asunto(s)
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Terapia Neoadyuvante , Adulto , Anciano , Austria , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Femenino , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia
8.
Transpl Int ; 29(4): 471-82, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26716608

RESUMEN

Nonoptimal liver grafts, and among them organs from anti-HBc+ donors, are increasingly used for liver transplantation. In this retrospective study including 1065 adult liver transplantations performed between 1977 and 2012, we analyzed long-term patient and graft survival and occurrence of HBV infection. A total of 52 (5.1%) patients received an anti-HBc+ graft. The 10-year graft and patient survival of these recipients were 50.9% and 59.0% compared to 72.0% and 76.5% (P = 0.001; P = 0.004) of patients receiving anti-HBc- grafts, respectively. Cox regression model showed that high urgency allocation (P = 0.003), recipient age (P = 0.027), anti-HCV+ recipients (P = 0.005), and anti-HBc+ organs (P = 0.048) are associated with decreased graft survival. Thirteen of 52 (25.0%) patients receiving anti-HBc+ grafts developed post-transplant HBV infection within a mean of 2.8 years. In this study, antiviral prophylaxis did not have significant impact on HBV infection, but long-term survival (P = 0.008). Development of post-transplant HBV infection did not affect adjusted 10-year graft survival (100% vs. 100%; P = 1). Anti-HBc+ liver grafts can be transplanted with reasonable but inferior long-term patient and graft survival. The inferior graft survival is not, however, related with post-transplant HBV infection as long as early diagnosis and treatment take place.


Asunto(s)
Supervivencia de Injerto , Hepatitis B/patología , Trasplante de Hígado , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Donantes de Tejidos , Obtención de Tejidos y Órganos , Resultado del Tratamiento , Carga Viral
9.
J Hepatol ; 60(1): 118-26, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24012941

RESUMEN

BACKGROUND & AIMS: Recently, we developed the ART score (assessment for re-treatment with TACE) to guide the decision for a second transarterial chemoembolization (TACE-2) in patients with hepatocellular carcinoma (HCC). Patients with an ART score of 0-1.5 points gained benefit from a second TACE session, while patients with an ART score ≥2.5 points did not. Here, we investigated (1) the prognostic significance of the ART score prior to the third (TACE-3) and fourth TACE (TACE-4), and (2) the feasibility of an ART score guided re-treatment strategy by sequential assessment of the ART score in HCC patients treated with multiple TACE sessions. METHODS: 109 patients, diagnosed with intermediate stage HCC and treated with ≥3 TACE sessions between January 1999 and December 2009 at the Medical Universities of Vienna and Innsbruck, were included. The ART score prior to each TACE session was assessed in comparison to the TACE naïve liver. The prognostic performance of the ART score before TACE-3 and 4 was evaluated with and without stratification based on the ART score prior to the respective last intervention. RESULTS: The pre-TACE-3 ART score discriminated two groups with different prognosis and remained a valid predictor of OS independent of Child-Pugh score (5-7 points), CRP-levels and tumor characteristics. Even in patients with an initially beneficial ART score (0-1.5 points) before TACE-2, repeated ART score assessment before TACE-3 identified a subgroup of patients with dismal prognosis (median OS: 27.8 vs. 10.8 months, p<0.001). Similar results were observed when the ART score was applied before TACE-4. CONCLUSIONS: The sequential assessment of the ART score identifies patients with dismal prognosis prior to each TACE session.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del Tratamiento
10.
J Hepatol ; 61(6): 1287-96, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25016222

RESUMEN

BACKGROUND & AIMS: We aimed to establish an objective point score to guide the decision for the first treatment with transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). METHODS: 277 patients diagnosed with HCC and treated with transarterial treatments between 1/2002 and 12/2011 at the Medical Universities of Vienna (training cohort) and Innsbruck (validation cohort) were included. We investigated the impact of baseline liver function and tumour load on overall survival (OS, log-rank test) and developed a point score (STATE-score: Selection for TrAnsarterial chemoembolisation TrEatment) in the training-cohort (n=131, Vienna) by using a stepwise Cox regression model. The STATE-score was externally validated in an independent validation cohort (n=146, Innsbruck) and thereafter combined with the Assessment for Retreatment with TACE (ART)-score to identify patients who are (un)suitable for TACE. RESULTS: The STATE-score starts with the serum-albumin level (g/L), which is reduced by 12 points each, if the tumour load exceeds the up-to-7 criteria and/or C-reactive protein (CRP) levels are ⩾1 mg/dl (maximum reduction: 24 points). The STATE-score differentiated 2 groups (<18, ⩾18 points) with distinct prognosis (median OS: 5.3 vs. 19.5 months; p<0.001) and a lower STATE-score was associated with short-term harm and increased mortality after TACE-1 (39% vs. 14% p<0.001). Sequential use of the STATE and the ART-score (START-strategy) identified the most (un)suitable patients for TACE. Results were confirmed in the external validation-cohort and were independent from recently proposed baseline selection tools. CONCLUSION: The STATE-score identifies patients who are (un)suitable for the first TACE. The START-strategy identified the best candidates for multiple TACE sessions.


Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Selección de Paciente , Anciano , Proteína C-Reactiva/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Estudios de Cohortes , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Albúmina Sérica/metabolismo , Tasa de Supervivencia , Resultado del Tratamiento
11.
Clin Gastroenterol Hepatol ; 12(4): 683-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24076416

RESUMEN

BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in a well-characterized Austrian cohort of patients with Wilson disease. METHODS: We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes. For 53 patients lost during the follow-up period, those that died and reasons for their death were identified from the Austrian death registry. RESULTS: The mean observation period was 14.8 ± 11.4 years (range, 0.5-52.0 years), resulting in 3116 patient-years. Of the patients, 61% presented with hepatic disease, 27% with neurologic symptoms, and 10% were diagnosed by family screening at presymptomatic stages. Patients with a hepatic presentation were diagnosed younger (21.2 ± 12.0 years) than patients with neurologic disease (28.8 ± 12.0; P < .001). In 2% of patients, neither symptoms nor onset of symptoms could be determined with certainty. Most patients stabilized (35%) or improved on chelation therapy (26% fully recovered, 24% improved), but 15% deteriorated; 8% required a liver transplant, and 7.4% died within the observation period (71% of deaths were related to Wilson disease). A lower proportion of patients with Wilson disease survived for 20 years (92%) than healthy Austrians (97%), adjusted for age and sex (P = .03). Cirrhosis at diagnosis was the best predictor of death (odds ratio, 6.8; 95% confidence interval, 1.5-31.03; P = .013) and need for a liver transplant (odds ratio, 07; 95% confidence interval, 0.016-0.307; P < .001). Only 84% of patients with cirrhosis survived 20 years after diagnosis (compared with healthy Austrians, P =.008). CONCLUSION: Overall, patients who receive adequate care for Wilson disease have a good long-term prognosis. However, cirrhosis increases the risk of death and liver disease. Early diagnosis, at a precirrhotic stage, might increase survival times and reduce the need for a liver transplant.


Asunto(s)
Degeneración Hepatolenticular/epidemiología , Degeneración Hepatolenticular/mortalidad , Adolescente , Adulto , Austria/epidemiología , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
12.
Hepatology ; 57(6): 2224-34, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22961713

RESUMEN

UNLABELLED: We investigated the prognostic value of C-reactive protein (CRP) in patients with hepatocellular carcinoma (HCC) not amenable to surgery. A total of 615 patients diagnosed with HCC not amenable to surgery between April 1999 and December 2009 at the Department of Gastroenterology of the Medical Universities of Vienna and Innsbruck were included. We assessed the optimal CRP cutoff by regression spline analysis and tested its impact on median overall survival (OS) by the Kaplan-Meier method, univariate analysis (log-rank test), and multivariate analysis (Cox proportional hazard regression model) in a training cohort (n = 466, Vienna) and an independent validation cohort (n = 149, Innsbruck). We found a sigmoid-shaped association of CRP and the hazard ratio of death upon regression spline analysis and defined a CRP level <1/≥1 mg/dL as optimal cutoff for further survival assessments. Elevated CRP (≥1 mg/dL) at diagnosis was associated with poor OS (CRP-elevated versus CRP-normal; 4 versus 20 months; P < 0.001) and remained a significant negative predictor for OS upon multivariate analysis (hazard ratio, 1.7; P < 0.001), which was independent of age, Child-Pugh class, tumor characteristics, and treatment allocation. Analyses with respect to Barcelona Clinic Liver Cancer (BCLC) stage and Child-Pugh class supported the relevance of CRP (BCLC-stage C and Child-Pugh A: OS for CRP-elevated versus CRP-normal, 6 versus 14; P < 0.001; BCLC-stage C and Child-Pugh B: OS for CRP-elevated versus CRP-normal, 4 versus 15 months; P < 0.001). The prognostic significance of elevated CRP was reproducible at a second CRP determination timepoint and confirmed in the independent validation cohort. CONCLUSION: Elevated CRP is associated with a dismal prognosis in HCC patients and may become a useful marker for patient selection in HCC management. (HEPATOLOGY 2012).


Asunto(s)
Proteína C-Reactiva/metabolismo , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Austria/epidemiología , Biomarcadores/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Causas de Muerte , Femenino , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico
13.
Hepatology ; 57(6): 2261-73, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23316013

RESUMEN

UNLABELLED: We aimed to establish an objective point score to guide the decision for retreatment with transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). In all, 222 patients diagnosed with HCC and treated with multiple TACE cycles between January 1999 and December 2009 at the Departments of Gastroenterology/Hepatology of the Medical Universities of Vienna (training cohort) and Innsbruck (validation cohort) were included. We investigated the effect of the first TACE on parameters of liver function and tumor response and their impact on overall survival (OS, log rank test) and developed a point score (ART score: Assessment for Retreatment with TACE) in the training cohort (n = 107, Vienna) by using a stepwise Cox regression model. The ART score was externally validated in an independent validation cohort (n = 115, Innsbruck). The increase of aspartate aminotransferase (AST) by >25% (hazard ratio [HR] 8.4; P < 0.001), an increase of Child-Pugh score of 1 (HR 2.0) or ≥2 points (HR 4.4) (P < 0.001) from baseline, and the absence of radiologic tumor response (HR 1.7; P = 0.026) remained independent negative prognostic factors for OS and were used to create the ART score. The ART score differentiated two groups (0-1.5 points; ≥2.5 points) with distinct prognosis (median OS: 23.7 versus 6.6 months; P < 0.001) and a higher ART score was associated with major adverse events after the second TACE (P = 0.011). These results were confirmed in the external validation cohort and remained significant irrespective of Child-Pugh stage and the presence of ascites prior the second TACE. CONCLUSION: An ART score of ≥2.5 prior the second TACE identifies patients with a dismal prognosis who may not profit from further TACE sessions. (HEPATOLOGY 2013;57:2261-2273).


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Austria/epidemiología , Carcinoma Hepatocelular/mortalidad , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Modelos de Riesgos Proporcionales , Adulto Joven
14.
J Hepatol ; 59(5): 978-83, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23811308

RESUMEN

BACKGROUND & AIMS: Impaired binding function of albumin has been demonstrated in end-stage liver disease. This and other functional disturbances of albumin may be related to oxidative stress which is believed to play an important role in the pathogenesis of liver failure as well as sepsis. The aim of the present study was to relate oxidative modification of albumin to loss of albumin binding function in advanced chronic liver failure and in sepsis. METHODS: Patients with decompensated cirrhosis or sepsis and healthy controls were investigated. Three fractions of albumin were separated by chromatography according to the redox state of cysteine-34: non-oxidized human mercaptalbumin, reversibly oxidized human non-mercaptalbumin-1, and irreversibly oxidized human non-mercaptalbumin-2 (HNA2). Binding properties of albumin site II were measured using dansylsarcosine as a ligand. RESULTS: Both in cirrhotic and septic patients, fractions of oxidized albumin were increased and binding capacity for dansylsarcosine was decreased. Mass spectroscopy confirmed specific oxidation of cysteine-34. In cirrhotic patients, dansylsarcosine binding correlated strongly with liver function parameters and moderately with HNA2. Baseline levels of HNA2 accurately predicted 30-day and 90-day survival in cirrhotic patients and this was confirmed in an external validation cohort. CONCLUSIONS: Our results suggest that oxidative damage impairs binding properties of albumin. In advanced liver disease, reduced binding capacity of albumin site II is mainly related to impaired liver function. The plasma level of HNA2 is closely related to survival and may represent a novel biomarker for liver failure.


Asunto(s)
Albúminas/metabolismo , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/fisiopatología , Hígado/fisiopatología , Estrés Oxidativo/fisiología , Adulto , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Enfermedad Hepática en Estado Terminal/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/mortalidad , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Unión Proteica/fisiología , Sepsis/metabolismo , Sepsis/mortalidad , Sepsis/fisiopatología , Albúmina Sérica/metabolismo , Tasa de Supervivencia
15.
Clin Gastroenterol Hepatol ; 11(12): 1667-72, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23872669

RESUMEN

BACKGROUND & AIMS: The G-allele in position rs738409 of patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with an increased hepatic concentration of triglyceride and is a risk factor for advanced liver disease. We investigated the association of donor and recipient risk alleles with the development of graft steatosis after liver transplantation. METHODS: PNPLA3 genotypes were determined in 237 transplant recipients and in 255 organ donors. Macrovesicular steatosis was assessed by unenhanced computed tomography 5 years after liver transplantation in 95 patients and correlated with donor and recipient PNPLA3 genotype. RESULTS: The risk allele was significantly more frequent in transplant recipients than in donors (42% vs 28%; P < .001). A prevalence of graft steatosis of 30% or greater significantly increased from 11.6% at 1 year after liver transplantation to 32.6% at 5 years after transplantation. Five years after liver transplantation, steatosis was present in 63.2% of patients homozygous for the rs738409-G allele, in 31.4% of heterozygous recipients, and in 12.0% of rs738409-CC recipients (P = .002). Donor genotypes were not associated with the development of graft steatosis. In multivariate regression analysis, recipients who carried rs738409-GG had a 13.7-fold higher risk of graft steatosis than recipients who carried rs738409-CC (P = .022), independent of recipient age, weight gain after liver transplantation, or the underlying disease. CONCLUSIONS: Liver transplant recipients who carry rs738409-G in PNPLA3 are at increased risk for hepatic triglyceride accumulation, independent of the graft PNPLA3 genotype.


Asunto(s)
Hígado Graso/genética , Lipasa/genética , Trasplante de Hígado , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Hígado Graso/patología , Femenino , Genotipo , Técnicas de Genotipaje , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X , Trasplante
16.
Liver Transpl ; 19(8): 879-86, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23696006

RESUMEN

Acute-on-chronic liver failure (ACLF) is characterized by high short-term mortality. Liver transplantation (LT) is a potential therapy for patients who do not improve with supportive measures, but the efficacy of LT has not been shown. The aim of this study was to investigate the feasibility of LT and to determine the postoperative outcomes of patients with ACLF. All patients referred to our liver unit between 2002 and 2010 were registered in a database. The diagnosis of ACLF was made in accordance with the Asian Pacific Association for the Study of the Liver consensus. The post-LT outcomes were compared with the outcomes of a cohort of patients with chronic liver disease who underwent transplantation for other indications during the same period. One hundred forty four of 238 patients fulfilled the ACLF criteria. In an intention-to-treat analysis, the median transplant-free survival time was 48 days. Multiorgan failure was the most common cause of death. Ninety-four patients (65%) were evaluated for LT, 71 patients (49%) were listed, and 33 patients (23%) finally underwent deceased donor LT; this resulted in a wait-list mortality rate of 54%. Patients who developed infectious complications (particularly pneumonia and/or sepsis) and patients who received renal replacement therapy or mechanical ventilation were less likely to undergo LT. The 1- and 5-year survival rates of 87% and 82% were comparable to the rates for non-ACLF patients. In conclusion, this study shows that LT remains the only therapeutic option for the vast majority of patients with ACLF. However, LT was feasible in less than one fourth of the patients with a 5-year survival rate greater than 80%.


Asunto(s)
Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/terapia , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/terapia , Trasplante de Hígado/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica , Respiración Artificial , Estudios Retrospectivos , Resultado del Tratamiento , Listas de Espera
17.
Liver Transpl ; 19(10): 1108-18, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23873764

RESUMEN

Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010. A prospectively collected database originating from 6 collaborating European centers was used for the study. Sixty-one patients (14.5%) developed HCC recurrence. For both MC-IN and MC-OUT patients, an AFP slope > 15 ng/mL/month and mRECIST progression were unique independent risk factors for HCC recurrence and patient death. When the radiological Milan criteria (MC) status was combined with radiological and biological progression, MC-IN and MC-OUT patients without risk factors had similarly excellent 5-year tumor-free and patient survival rates. MC-IN patients with at least 1 risk factor had worse outcomes, and MC-OUT patients with at least 1 risk factor had the poorest survival (P < 0.001). In conclusion, both radiological and biological modifications permit documentation of the response to LRT in patients waiting for LT. According to these 2 parameters, tumor progression significantly increases the risk of recurrence and patient death not only for MC-OUT patients but also for MC-IN patients. The monitoring of both parameters in combination with the initial radiological MC status is an essential element for further refining the selection criteria for potential liver recipients with HCC.


Asunto(s)
Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Bases de Datos Factuales , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunosupresores/uso terapéutico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Selección de Paciente , Pronóstico , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Resultado del Tratamiento , Listas de Espera
18.
Wien Med Wochenschr ; 163(5-6): 109-12, 2013 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-23361850

RESUMEN

Since the introduction of abdominal ultrasound liver lesions have been increasingly detected. Being usually diagnosed by chance these lesions create psychological stress among patients because a potential malignant disease has to be taken into consideration. The increasing use of oral contraceptives with high estrogen doses starting in the 1980s led to a rising incidence of adenomas, whose natural history differed from those described in surgical and autoptic studies. This fact brought about a change towards a modern pathophysiologic and prognostic differentiation. Current histologic and molecular biological techniques are able to distinguish benign adenomas from those with malignant potential.


Asunto(s)
Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/patología , Adenoma de Células Hepáticas/terapia , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Diagnóstico Diferencial , Diagnóstico por Imagen , Femenino , Hiperplasia Nodular Focal/diagnóstico , Hiperplasia Nodular Focal/patología , Hiperplasia Nodular Focal/terapia , Hemangioma/diagnóstico , Hemangioma/patología , Hemangioma/terapia , Humanos , Hallazgos Incidentales , Hígado/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos , Estadificación de Neoplasias , Pronóstico
19.
Wien Klin Wochenschr ; 135(Suppl 3): 493-523, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37358642

RESUMEN

The Billroth IV consensus was developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on the 26th of November 2022 in Vienna.Based on international recommendations and considering recent landmark studies, the Billroth IV consensus provides guidance regarding the diagnosis and management of portal hypertension in advanced chronic liver disease.


Asunto(s)
Várices Esofágicas y Gástricas , Hipertensión Portal , Humanos , Austria , Consenso , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Hipertensión Portal/terapia , Hemorragia Gastrointestinal , Cirrosis Hepática
20.
Radiology ; 263(2): 590-9, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22438359

RESUMEN

PURPOSE: To compare the efficacies of transarterial chemoembolization (TACE) and sorafenib in patients with advanced-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The retrospective analysis of the data was approved by the institutional review board; the requirement to obtain informed consent was waived. Three hundred seventy-two patients with HCC were treated between January 1999 and December 2009. Patients with advanced HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging classification (Child-Pugh class A or B, Eastern Cooperative Oncology Group performance status of 1-2, and/or macrovascular invasion or extrahepatic metastasis) were included in the study (n = 97). Thirty-four patients underwent conventional TACE with doxorubicin plus lipiodol or TACE with drug-eluting beads; 63 patients were treated with sorafenib. RESULTS: The median duration of sorafenib treatment was 4.6 months (95% confidence interval [CI]: 3.2, 6.0 months). The median number of TACE sessions per patient was 3 ± 2. Side effects of TACE and sorafenib were comparable to those reported in the literature. The median time to progression was similar between the two treatment groups (P = .737). The median overall survival was 9.2 months (95% CI: 6.1, 12.3 months) for patients treated with TACE and 7.4 months (95% CI: 5.6, 9.2 months) for those treated with sorafenib (P = .377). Only Child-Pugh class was associated with a better overall survival at uni- and multivariate analysis. CONCLUSION: TACE achieved a promising outcome in select patients with advanced HCC (BCLC stage C).


Asunto(s)
Antineoplásicos/administración & dosificación , Bencenosulfonatos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Piridinas/administración & dosificación , Adulto , Anciano , Antineoplásicos/efectos adversos , Bencenosulfonatos/efectos adversos , Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/patología , Distribución de Chi-Cuadrado , Medios de Contraste/administración & dosificación , Progresión de la Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Aceite Etiodizado/administración & dosificación , Aceite Etiodizado/efectos adversos , Femenino , Humanos , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Modelos de Riesgos Proporcionales , Piridinas/efectos adversos , Estudios Retrospectivos , Sorafenib , Análisis de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
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