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1.
Aliment Pharmacol Ther ; 60(2): 246-256, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38778481

RESUMEN

BACKGROUND: The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min. AIMS: Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests. METHODS: This study combined the data from two prospectively conducted US studies: HALT-C and SHUNT-V. A total of 455 subjects underwent both the SHUNT test and esophagogastroduodenoscopy (EGD). RESULTS: DSI scores correlated with the probability of LEVs (p < 0.001) and demonstrated a stepwise increase from healthy lean controls without liver disease to subjects with chronic liver disease and no, small or large varices. Furthermore, a cutoff of DSI ≤ 18.3 from DuO had a sensitivity of 0.98 (missing only one case) and, if applied to the endoscopy (EGD) decision, would have prevented 188 EGDs (41.3%). The AUROC for DSI from DuO did not differ from that of the reference SHUNT test method (0.82 versus 0.81, p = 0.3500). CONCLUSIONS: DSI from HepQuant DuO links liver function and physiology to the risk of LEVs across a wide spectrum of patient characteristics, disease aetiologies and liver disease severity. DuO is minimally invasive, easy to administer, quantitative and may aid the decision to avoid or perform EGD for LEVs.


Asunto(s)
Várices Esofágicas y Gástricas , Pruebas de Función Hepática , Índice de Severidad de la Enfermedad , Humanos , Várices Esofágicas y Gástricas/fisiopatología , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Pruebas de Función Hepática/métodos , Adulto , Estudios Prospectivos , Anciano , Endoscopía del Sistema Digestivo/métodos , Factores de Riesgo , Hígado/fisiopatología , Hígado/irrigación sanguínea
2.
Lancet Gastroenterol Hepatol ; 9(7): 646-663, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38642564

RESUMEN

Portal hypertension represents the primary non-neoplastic complication of liver cirrhosis and has life-threatening consequences, such as oesophageal variceal bleeding, ascites, and hepatic encephalopathy. Portal hypertension occurs due to increased resistance of the cirrhotic liver vasculature to portal blood flow and is further aggravated by the hyperdynamic circulatory syndrome. Existing knowledge indicates that the profibrogenic phenotype acquired by sinusoidal cells is the initial factor leading to increased hepatic vascular tone and fibrosis, which cause increased vascular resistance and portal hypertension. Data also suggest that the phenotype of hepatic cells could be further impaired due to the altered mechanical properties of the cirrhotic liver itself, creating a deleterious cycle that worsens portal hypertension in the advanced stages of liver disease. In this Review, we discuss recent discoveries in the pathophysiology and treatment of cirrhotic portal hypertension, a condition with few pharmacological treatment options.


Asunto(s)
Hipertensión Portal , Cirrosis Hepática , Hipertensión Portal/fisiopatología , Hipertensión Portal/etiología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/fisiopatología , Várices Esofágicas y Gástricas/terapia , Resistencia Vascular/fisiología , Hígado/fisiopatología , Hígado/irrigación sanguínea
3.
Dig Dis Sci ; 67(1): 159-169, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33590404

RESUMEN

BACKGROUND: There are few reports about reflux esophagitis (RE) as a cause of severe upper gastrointestinal bleeding (UGIB). AIMS: This study aims to evaluate (1) changes in its prevalence over the last three decades and (2) clinical and endoscopic characteristics and 30-day outcomes among RE patients with and without focal esophageal ulcers (EUs) and stigmata of recent hemorrhage (SRH). METHODS: A retrospective study of prospectively collected data of esophagitis patients hospitalized with severe UGIB between 1992 and 2020. Descriptive analysis and statistical comparisons were performed. RESULTS: Of 114 RE patients, the mean age was 61.1 years and 76.3% were males. 38.6% had prior gastroesophageal reflux disease (GERD) symptoms; overall 36% were on acid suppressants. Over three consecutive decades, the prevalence of RE as a cause of severe UGIB increased significantly from 3.8 to 16.7%. 30-day rebleeding and all-cause mortality rates were 11.4% and 6.1%. RE patients with focal EUs and SRH (n = 23) had worse esophagitis than those with diffuse RE (n = 91) (p = 0.012). There were no differences in 30-day outcomes between RE patients with and without EUs and SRH. CONCLUSIONS: For patients with severe UGIB caused by RE, (1) the prevalence has increased significantly over the past three decades, (2) the reasons for this increase and preventive strategies warrant further study, (3) most patients lacked GERD symptoms and did not take acid suppressants, and (4) those with focal ulcers and SRH had more severe esophagitis and were treated endoscopically.


Asunto(s)
Esofagitis Péptica , Hemorragia Gastrointestinal , Antiácidos/uso terapéutico , Endoscopía del Sistema Digestivo/métodos , Endoscopía del Sistema Digestivo/estadística & datos numéricos , Várices Esofágicas y Gástricas/fisiopatología , Várices Esofágicas y Gástricas/terapia , Esofagitis Péptica/complicaciones , Esofagitis Péptica/diagnóstico , Esofagitis Péptica/epidemiología , Esofagitis Péptica/fisiopatología , Femenino , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/fisiopatología , Úlcera Péptica/terapia , Prevalencia , Recurrencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
4.
J Chin Med Assoc ; 84(10): 917-922, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34613941

RESUMEN

BACKGROUND: The prevalence of esophagogastric varices (EGV) in patients with advanced pancreatic cancer is not rare. However, its clinical significance has never been investigated. This study was aimed to explore the clinical implication and outcomes of these patients. METHODS: A retrospective analysis comprising 224 patients with advanced pancreatic cancer managed from October 2012 to December 2019 at a tertiary medical center identified 35 patients who had presented with EGV. Clinical characteristics and outcomes were analyzed with special emphasis on comparison between patients with early-onset and late-onset EGV. RESULTS: Patients with EGV had lower platelet count and a higher proportion of splenomegaly but no difference in overall survival in comparison to those without EGV. Patients with early-onset EGV had a poorer bleeding survival (hazard ratio, 8.347; CI, 2.509-27.772; p = 0.001) in comparison to those with late-onset EGV. On multivariate analysis, initial serum bilirubin, γ-Glutamyltransferase, lactate dehydrogenase, cancer stage, and the response to cancer treatment determine the patient's survival. Patients with tumor invasion to superior mesenteric and portal vein are more likely to have esophageal varices (EV) (EV: 13/15 vs gastric varices [GV]: 4/20; p < 0.001); those with splenic vein invasion are more likely to have GV (EV: 4/15 vs GV: 20/20; p < 0.001). CONCLUSION: Patients with advanced pancreatic cancer and early-onset EGV had poorer bleeding-free survival than those with late-onset EGV. Further studies are needed to clarify the benefits of the prophylactic intervention.


Asunto(s)
Várices Esofágicas y Gástricas/fisiopatología , Neoplasias Pancreáticas/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Análisis de Supervivencia
6.
Biomed Res Int ; 2021: 5587566, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33997022

RESUMEN

BACKGROUND AND AIMS: Nonselective beta-blockers (NSBBs) are the main drug to prevent portal hypertension. It could alter free hepatic venous pressure (FHVP); however, the significance is unknown. This prospective study was to explore the change of FHVP after use of NSBBs and its predictive value for gastroesophageal varices (GOV) bleeding in cirrhotic patients. Patients and Methods. Cirrhotic patients with medium-large GOV between September 2014 and January 2019 were enrolled. After initial hepatic venous pressure gradient (HVPG) measurement, patients received oral NSBBs. Seven days later, the secondary HVPG was examined to evaluate the FHVP alteration and hemodynamic response. The variceal bleeding between patients with FHVP increased and decreased/unchanged was compared. RESULTS: A total of 74 patients were enrolled, and 62 patients completed the secondary HVPG measurement and was followed up. The cumulative bleeding rate was significantly higher in patients with FHVP increased ≥ 1.75 mmHg than those with FHVP decreased/unchanged (54.5% vs. 22.5%, p = 0.021), while there was no significant difference in bleeding between HVPG responders and nonresponders (32.6% vs. 37.5%, p = 0.520). For HVPG responders, variceal bleeding in patients with FHVP increased ≥ 1.75 mmHg was significantly more than that in patients with FHVP decreased/unchanged (57.9% vs. 28.6%, p = 0.041). Cox regression analysis showed that change of FHVP was an independent predictor of variceal bleeding. CONCLUSION: Increase ≥ 1.75 mmHg in FHVP responding to beta-blockers in cirrhotic patients with GOV indicates high risk of variceal bleeding. Besides HVPG response, change of FHVP should also be valued in hemodynamic evaluation to beta-blockers. This trial is registered with Chinese Clinical Trial Registry ChiCTR-IPR-17012836.


Asunto(s)
Antagonistas Adrenérgicos beta/efectos adversos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/fisiopatología , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/fisiopatología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Presión Venosa/fisiología , Femenino , Hemodinámica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Curva ROC
7.
Biomed Res Int ; 2021: 6635963, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33928154

RESUMEN

BACKGROUND: Baveno VI criteria, based on liver stiffness (LS) measured by transient elastography and platelet counts (PLT), have been proposed to avoid unnecessary endoscopy screening for high-risk varices (HRVs). However, the cut-off value of LS measured by 2D-SWE and PLT to predict HRVs in compensated hepatitis B-related cirrhotic patients remains unknown. AIMS: To prospectively analyze the cut-off of the combination of LS measured by 2D-SWE and PLT in predicting HRVs and the influence of antiviral therapies in its efficacy. METHODS: Serum parameters, LS, and endoscopy results were obtained from 160 compensated hepatitis B-related cirrhotic patients. The accuracy of the combined algorithm was assessed in the whole cohort and subgroups with or without consecutive antiviral therapies in the past 6 months. RESULTS: In the whole cohort, the optimal cut-off value of LS for HRVs was 14.5 kPa. Patients with a LS value < 14.5 kPa with a PLT value > 110 × 109/L can be excluded from HRVs (NPV = 0.99, endoscopy saved rates = 0.68). Conversely, a LS value of ≥14.5 kPa and a PLT value of ≤110 × 109/L indicated HRVs, with accurate rates of 82.35%, and 10.63% of patients can avoid additional endoscopy screening. Moreover, antiviral therapy had no significant effect on the accuracy and rates saved from further endoscopy screening, when comparing patients with or without antiviral therapies (all p values > 0.05). CONCLUSIONS: The combination of LS (14.5 kPa) measured by 2D-SWE and PLT (110 × 109/L) can predict HRVs accurately in compensated hepatitis B-related cirrhotic patients without significant interference of antiviral therapy histories.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas/sangre , Várices Esofágicas y Gástricas/diagnóstico por imagen , Hepatitis B/sangre , Hepatitis B/complicaciones , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Resistencia al Corte , Algoritmos , Antivirales/farmacología , Antivirales/uso terapéutico , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Hepatitis B/diagnóstico por imagen , Hepatitis B/fisiopatología , Humanos , Hígado/fisiopatología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Factores de Riesgo
8.
Hepatology ; 74(3): 1660-1673, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33421158

RESUMEN

Rifaximin is an oral nonsystemic antibiotic with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both gram-positive and gram-negative organisms. Rifaximin is currently used worldwide in patients with cirrhosis for preventing recurrent HE because its efficacy and safety have been proven by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which in turn can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted because evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas in the second part, its clinical effects are critically discussed. It clearly emerges that, because of its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than HE deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure, and mortality, are therefore eagerly awaited.


Asunto(s)
Antibacterianos/uso terapéutico , Encefalopatía Hepática/prevención & control , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Rifaximina/uso terapéutico , Infecciones Bacterianas/prevención & control , Ensayos Clínicos como Asunto , Várices Esofágicas y Gástricas/fisiopatología , Várices Esofágicas y Gástricas/prevención & control , Hemorragia Gastrointestinal/fisiopatología , Hemorragia Gastrointestinal/prevención & control , Microbioma Gastrointestinal/fisiología , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/metabolismo , Encefalopatía Hepática/fisiopatología , Síndrome Hepatorrenal/metabolismo , Síndrome Hepatorrenal/fisiopatología , Síndrome Hepatorrenal/prevención & control , Humanos , Hipertensión Portal/metabolismo , Hipertensión Portal/fisiopatología , Inflamación , Cirrosis Hepática/metabolismo , Cirrosis Hepática/fisiopatología , Peritonitis/prevención & control
9.
Surg Endosc ; 35(4): 1786-1795, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32323014

RESUMEN

BACKGROUND: Digestive system complications are among the most important causes of postoperative poor quality of life after open and conventional laparoscopic splenectomy and azygoportal disconnection (CLSD). We firstly developed a modified vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection (MVLSD). In this study, we aimed to evaluate whether MVLSD is feasible and safe and to determine whether MVLSD can effectively eliminate postoperative digestive system complications, in comparison with CLSD. METHOD: In this randomized controlled single-center study, 60 patients with cirrhosis were randomly assigned to undergo either CLSD (n = 30) or MVLSD (n = 30) between April and December 2018. The primary outcome was delayed gastric emptying (DGE). Endoscopic physicians were blinded to group assignments. RESULTS: One patient who received MVLSD withdrew from the study. There were no significant differences in intraoperative blood loss, incidence of blood transfusion, time to off-bed activity, time to first flatus, and postoperative hospital stay between the two groups. Compared with CLSD, operation time and incidences of DGE, diarrhea, epigastric fullness, and overall postoperative complications were all significantly reduced in the MVLSD group (all P < 0.05). Compared with CLSD, MVLSD was associated with significantly increased weight and albumin levels at 1, 6, and 12 months postoperatively versus preoperative values (all P < 0.05). The curative effect of resolving gastroesophageal variceal bleeding was similar between the groups. CONCLUSION: MVLSD is not only a technically feasible and safe procedure, it is also succinct and convenient. Furthermore, MVLSD effectively reduces postoperative digestive system complications, contributing to improved quality of life.


Asunto(s)
Vena Ácigos/cirugía , Laparoscopía , Tratamientos Conservadores del Órgano , Esplenectomía , Nervio Vago/patología , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/fisiopatología , Várices Esofágicas y Gástricas/cirugía , Femenino , Vaciamiento Gástrico , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Periodo Posoperatorio , Calidad de Vida
10.
J Hepatol ; 74(2): 274-282, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33038432

RESUMEN

BACKGROUND & AIMS: Non-alcoholic steatohepatitis is a leading cause of end-stage liver disease. Hepatic steatosis and lipotoxicity cause chronic necroinflammation and direct hepatocellular injury resulting in cirrhosis, end-stage liver disease and hepatocellular carcinoma. Emricasan is a pan-caspase inhibitor that inhibits excessive apoptosis and inflammation; it has also been shown to decrease portal pressure and improve synthetic function in mice with carbon tetrachloride-induced cirrhosis. METHODS: This double-blind, placebo-controlled study randomized 217 individuals with decompensated NASH cirrhosis 1:1:1 to emricasan (5 mg or 25 mg) or placebo. Patients were stratified by decompensation status and baseline model for end-stage liver disease-sodium (MELD-Na) score. The primary endpoint comprised all-cause mortality, a new decompensation event (new or recurrent variceal hemorrhage, new ascites requiring diuretics, new unprecipitated hepatic encephalopathy ≥grade 2, hepatorenal syndrome, spontaneous bacterial peritonitis), or an increase in MELD-Na score ≥4 points. RESULTS: There was no difference in event rates between either of the emricasan treatment groups and placebo, with hazard ratios of 1.02 (95% CI 0.59-1.77; p = 0.94) and 1.28 (95% CI 0.75-2.21; p = 0.37) for 5 mg and 25 mg of emricasan, respectively. MELD-Na score progression was the most common outcome. There was no significant effect of emricasan treatment on MELD-Na score, international normalized ratio, total serum bilirubin, albumin level or Child-Pugh score. Emricasan was generally safe and well-tolerated. CONCLUSIONS: Emricasan was safe but ineffective for the treatment of decompensated NASH cirrhosis. However, this study may guide the design and conduct of future clinical trials in decompensated NASH cirrhosis. LAY SUMMARY: Patients with decompensated cirrhosis related to non-alcoholic steatohepatitis are at high risk of additional decompensation events and death. Post hoc analyses in previous pilot studies suggested that emricasan might improve portal hypertension and liver function. In this larger randomized study, emricasan did not decrease the number of decompensation events or improve liver function in patients with a history of decompensated cirrhosis related to non-alcoholic steatohepatitis. CLINICALTRIALS. GOV IDENTIFIER: NCT03205345.


Asunto(s)
Ascitis , Hemorragia Gastrointestinal , Encefalopatía Hepática , Cirrosis Hepática , Pruebas de Función Hepática/métodos , Enfermedad del Hígado Graso no Alcohólico , Ácidos Pentanoicos , Peritonitis , Ascitis/etiología , Ascitis/prevención & control , Inhibidores de Caspasas/administración & dosificación , Inhibidores de Caspasas/efectos adversos , Progresión de la Enfermedad , Monitoreo de Drogas/métodos , Enfermedad Hepática en Estado Terminal/etiología , Enfermedad Hepática en Estado Terminal/prevención & control , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Encefalopatía Hepática/etiología , Encefalopatía Hepática/prevención & control , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Ácidos Pentanoicos/administración & dosificación , Ácidos Pentanoicos/efectos adversos , Peritonitis/etiología , Peritonitis/prevención & control , Resultado del Tratamiento
11.
Dig Dis Sci ; 66(6): 2084-2091, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32648078

RESUMEN

BACKGROUND AND AIMS: Several criteria have been described to noninvasively predict the presence of high-risk esophageal varices in patients with compensated advanced chronic liver disease (cACLD). However, a recent study showed that treatment with ß blockers could increase decompensation-free survival in patients with clinically significant portal hypertension, thereby making it important to predict the presence of any esophageal varices. We aimed to develop a simple scoring system to predict any esophageal varices. METHODS: We retrospectively reviewed patients who had vibration-controlled transient elastography (VCTE) at Cook County Hospital, Chicago, USA. Patients with cACLD and liver stiffness measurement (LSM) ≥ 10 kPa with esophagogastroduodenoscopy performed within one year of VCTE were analyzed. We generated a novel score to predict esophageal varices, using the beta coefficient of predictive variables. The score was validated in an external cohort at the University of Iowa Hospital, USA. RESULTS: There were 372 patients in the development cohort and 200 patients in the validation cohort. LSM, platelet count, and albumin were identified as predictors of esophageal varices and were included for generating the Cook County score as "platelet count * - 0.0155872 + VCTE score * 0.0387052 + albumin * - 0.8549209." The area under receiver operating curve for our score was 0.86 for any varices and 0.85 for high risk varices and avoided more endoscopies than the expanded Baveno VI criteria while maintaining a very low miss rate (negative predictive value > 99%). CONCLUSION: We propose a new, highly accurate, and easy-to-use scoring system to predict the presence of not only high-risk but any esophageal varices in patients with cACLD.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Enfermedad Hepática en Estado Terminal/diagnóstico por imagen , Várices Esofágicas y Gástricas/diagnóstico por imagen , Anciano , Diagnóstico por Imagen de Elasticidad/normas , Enfermedad Hepática en Estado Terminal/fisiopatología , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos
12.
J Vasc Interv Radiol ; 31(12): 2081-2088, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33261743

RESUMEN

PURPOSE: To quantitatively analyze the impact of intrahepatic venovenous shunt (IHVS) on hepatic venous pressure gradient (HVPG) measurement. MATERIALS AND METHODS: From 2015 to 2019, 222 HVPG measurements performed during transjugular intrahepatic portosystemic shunt creation were eligible for this study. Digital subtraction angiography (DSA) software color-coded each pixel of a two-dimensional DSA series by time-intensity curve to classify IHVS. Different degrees of IHVS were found in 36.5% of patients (81/222). Mild IHVS was found in 10.8% of patients (24/222), moderate IHVS was found in 10.8% of patients (24/222), and severe IVHS was found in 14.9% of patients (33/222). RESULTS: Mean wedged hepatic vein pressure (WHVP) and HVPG were significantly lower in patients with IHVS compared with patients without IHVS (WHVP: 17.78 mm Hg ± 7.00 vs 24.89 mm Hg ± 8.69, P = .001; HVPG: 11.93 mm Hg ± 5.76 vs 18.6 mm Hg ± 6.85, P < .001). Mild IHVS had little effect on WHVP and HVPG. Mean WHVP and HVPG were 11 mm Hg lower in patients with moderate IHVS (WHVP: 20.38 mm Hg ± 8.38 vs 31.5 mm Hg ± 9.39, P = .026; HVPG: 13.88 mm Hg ± 6.33 vs 25.00 mm Hg ± 9.81, P < .001) and 15 mm Hg lower in patients with severe IHVS (WHVP: 13.45 mm Hg ± 5.28 vs 28.64 mm Hg ± 6.38, P = .017; HVPG: 8.27 mm Hg ± 3.85 vs 23.45 mm Hg ± 6.95, P < .001) than mean portal vein pressure and portal vein gradient. CONCLUSIONS: For patients with moderate or severe IHVS, HVPG might greatly underestimate the actual value of portal vein pressure, and the portal vein should be catheterized to measure portal pressure.


Asunto(s)
Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/cirugía , Venas Hepáticas/cirugía , Hipertensión Portal/cirugía , Derivación Portosistémica Intrahepática Transyugular , Presión Venosa , Adulto , Anciano , Angiografía de Substracción Digital , Angiografía por Tomografía Computarizada , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/fisiopatología , Venas Hepáticas/diagnóstico por imagen , Venas Hepáticas/fisiopatología , Humanos , Hipertensión Portal/diagnóstico por imagen , Hipertensión Portal/fisiopatología , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Flebografía , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento
13.
Eur Radiol Exp ; 4(1): 65, 2020 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-33263169

RESUMEN

We evaluated sequential computed tomography (CT) arterioportography-arteriosplenography for the assessment of venous pathways in children with portal hypertension without cirrhosis. Institutional Review Board approval was obtained for this retrospective, single-centre study. CT was performed after contrast application via catheters placed in the superior mesenteric artery (CT arterioportography) and the splenic artery (CT arteriosplenography) consecutively. Venous pathways in 22 children were evaluated. In all patients, the detailed haemodynamic consequences of portal hypertension could be characterised. The supply of varices at different locations could be assigned to the superior mesenteric vein or splenic vein system. Retrograde blood flow through the splenic vein and inferior mesenteric vein, portosystemic shunting, and patency of splanchnic veins were determined. CT arterioportography-arteriosplenography allowed a complete evaluation of individual haemodynamic pathways in children with portal hypertension.


Asunto(s)
Hipertensión Portal/diagnóstico por imagen , Hipertensión Portal/fisiopatología , Portografía , Tomografía Computarizada por Rayos X , Adolescente , Niño , Preescolar , Medios de Contraste , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Hemodinámica , Humanos , Yohexol/análogos & derivados , Masculino , Venas Mesentéricas/fisiopatología , Estudios Retrospectivos , Bazo/irrigación sanguínea
14.
Sci Rep ; 10(1): 20068, 2020 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-33208832

RESUMEN

Upper gastrointestinal bleeding (UGIB) is common in liver cirrhosis. Although esophageal and gastric varices (EGV) is the main bleeding source, there were still a proportion of patients with peptic ulcer bleeding. Thus, this study aimed to analyze the characteristic of variceal bleeding and peptic ulcer bleeding in liver cirrhosis. Cirrhotic patients with confirmed UGIB by urgent endoscopy from July 2012 to June 2018 were enrolled, and classified into peptic ulcer bleeding group (n = 248) and variceal bleeding group (n = 402). Clinical and endoscopic characteristics, therapeutic efficacy and prognosis were evaluated, and independent risk factors for 42-day morality were determined. The mean age and gender ratio of peptic ulcer bleeding group were higher than those in variceal bleeding group (55.58 ± 11.37 vs. 52.87 ± 11.57, P < 0.01; 4.51:1 vs. 2.87:1, P = 0.023). Variceal bleeding group most commonly presented as red blood emesis and coffee grounds (67.16%), while peptic ulcer group primarily manifested as melena (62.10%). Hepatocellular carcinoma was more prevalent in peptic ulcer group (141 vs. 119, P < 0.01). Albumin level in variceal bleeding group was lower higher (P < 0.01), but serum bilirubin, creatinine and prothrombin time were significantly higher (all P < 0.01). Success rate of endoscopic hemostasis for variceal bleeding and peptic ulcer bleeding was 89.05% and 94.35% (P = 0.021). Univariate and multivariate analysis identified prothrombin time (P = 0.041, OR [95% CI] 0.884 [0.786-0.995]), MELD score (P = 0.000, OR [95% CI] 1.153 [1.073-1.240]), emergency intervention (P = 0.002, OR [95% CI] 8.656 [2.219-33.764]), hepatic encephalopathy before bleeding (P = 0.003, OR [95% CI] 8.119 [2.084-31.637]) and hepatic renal syndrome before bleeding (P = 0.029, OR [95% CI] 3.877 [1.152-13.045]) as the independent predictors for 42-day mortality. Peptic ulcer bleeding should be distinguished from variceal bleeding by clinical and endoscopic characteristics.


Asunto(s)
Várices Esofágicas y Gástricas/fisiopatología , Hemorragia Gastrointestinal/complicaciones , Cirrosis Hepática/complicaciones , Úlcera Péptica/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/etiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
15.
Dig Liver Dis ; 52(9): 1017-1025, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32653417

RESUMEN

BACKGROUND/AIMS: Despite secondary-prophylaxis with ß-blockers and endoscopic-variceal-ligation rebleeding is frequent, particularly within the first-6-weeks. Early-rebleeding may have greater impact on death-risk than late rebleeding, which may affect therapy. We assessed whether the influence of rebleeding on long-term survival of patients on secondary-prophylaxis is greater in patients with early-rebleeding. METHODS: 369 patients with cirrhosis were consecutively included once recovered from first variceal-bleeding. The impact of rebleeding on survival was investigated according to whether it occurred within 6-weeks (early-rebleeding) or later (late-rebleeding). RESULTS: During 46-months of follow-up (IQR: 14-61), 45 patients (12%) had early-rebleeding, 74(20%) had late-rebleeding and 250(68%) had not rebleeding. Mortality risk was higher in early-rebleeding group vs. late-rebleeding (HR = 0.476, 95%CI = 0.318-0.712, p < 0.001) and was similar in late-rebleeding group vs. no-rebleeding (HR = 0.902, 95%CI = 0.749-1.086, p = 0.271). Adjusting for baseline risk-factors, early-rebleeding was independently associated with mortality-risk (HR = 1.58, 95%CI = 1.02-2.45; p = 0.04). Child-Pugh&MELD scores improved at 3rd-4th-week only in patients without early-rebleeding (p < 0.05). Presence of ascites or encephalopathy, MELD-score>12 and HVPG>20 mmHg identified patients at risk of early-rebleeding. CONCLUSIONS: Patients with early-rebleeding have higher risk of death than patients without rebleeding and even than those rebleeding later. Our results suggest that patients at risk of early rebleeding might benefit from preemptive therapies such as early-TIPS.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Adulto , Anciano , Terapia Combinada , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/mortalidad , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/fisiopatología , Encefalopatía Hepática/etiología , Humanos , Ligadura/métodos , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Derivación Portosistémica Intrahepática Transyugular/mortalidad , Estudios Prospectivos , Recurrencia , Prevención Secundaria , Índice de Severidad de la Enfermedad , España/epidemiología , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
16.
J Hepatol ; 73(4): 829-841, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32298768

RESUMEN

BACKGROUND & AIMS: Whether the effect of ß-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of ß-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis. METHODS: Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting ß-blockers and again after 1 to 3 months of treatment (short-term). RESULTS: Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under ß-blockers, decompensated patients had lower portal pressure decrease (10 ± 18% vs. 15 ± 12%; p <0.05) and had greater reductions in heart rate (p <0.001) and CO (17 ± 15% vs. 10 ± 21%; p <0.01). Among patients with decompensated cirrhosis, those who died had a greater decrease in CO with ß-blockers than survivors (21 ± 14% vs. 15 ± 16%; p <0.05) and CO under ß-blockers independently predicted death by competing-risk regression analysis, with good diagnostic accuracy (C-index 0.74; 95% CI 0.66-0.83). Death risk was higher in decompensated patients with CO <5 L/min vs. CO ≥5 L/min (subdistribution hazard ratio 0.44; 95% CI 0.25-0.77; p = 0.004). CONCLUSIONS: In patients with high-risk varices treated to prevent first bleeding, the systemic hemodynamic response to ß-blockers is greater and the portal pressure decrease is smaller in those with decompensated cirrhosis. The short-term effect of ß-blockers on CO might adversely influence survival in decompensated cirrhosis. LAY SUMMARY: ß-blockers are often used to reduce the risk of variceal bleeding in patients with cirrhosis. However, it is not known whether the effect of ß-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure. Herein, we show that in patients with decompensated cirrhosis the potentially detrimental systemic effects of ß-blockers are greater than in compensated patients, while the beneficial pressure lowering effects are reduced. The short-term effect of ß-blockers on cardiac output may adversely influence survival in patients with decompensated cirrhosis.


Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Várices Esofágicas y Gástricas/etiología , Hemodinámica/efectos de los fármacos , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Hígado/fisiopatología , Progresión de la Enfermedad , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Cirrosis Hepática/mortalidad , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo
17.
J Hepatol ; 73(5): 1082-1091, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32339602

RESUMEN

BACKGROUND & AIMS: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. CONCLUSIONS: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. LAY SUMMARY: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Cirrosis Hepática , Derivación Portosistémica Intrahepática Transyugular , Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/cirugía , Intervención Médica Temprana/métodos , Intervención Médica Temprana/estadística & datos numéricos , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/fisiopatología , Europa (Continente)/epidemiología , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/prevención & control , Humanos , Hipertensión Portal/etiología , Hipertensión Portal/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Derivación Portosistémica Intrahepática Transyugular/métodos , Derivación Portosistémica Intrahepática Transyugular/estadística & datos numéricos , Prevalencia , Pronóstico , Recurrencia , Ajuste de Riesgo/métodos , Medición de Riesgo
18.
Am J Gastroenterol ; 115(5): 729-737, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32079861

RESUMEN

INTRODUCTION: Beta-blockers are the mainstay agents for portal pressure reduction and to modestly reduce hepatic venous pressure gradient (HVPG). We studied whether addition of simvastatin to carvedilol in cirrhotic patients for primary prophylaxis improves the hemodynamic response. METHODS: Cirrhotic patients with esophageal varices and with baseline HVPG > 12 mm Hg were prospectively randomized for primary prophylaxis to receive either carvedilol (group A, n = 110) or carvedilol plus simvastatin (group B, n = 110). Primary objective was to compare hemodynamic response (HVPG reduction of ≥20% or <12 mm Hg) at 3 months, and secondary objectives were to compare first bleed episodes, death, and adverse events. RESULTS: The groups were comparable at baseline. The proportion of patients achieving HVPG response at 3 months was comparable between groups (group A-36/62 [58.1%], group B-36/59 [61%], P = 0.85). The degree of mean HVPG reduction (17.3% and 17.8%, respectively, P = 0.98) and hemodynamic response (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.43-1.83, P = 0.74) was also not different between the groups. Patients who achieved target heart rate with no hypotensive episodes in either group showed better hemodynamic response (77.8% vs 59.2%, P = 0.04). Failure to achieve target heart rate (OR: 0.48; 95% CI: 0.22-1.06) and Child C cirrhosis (OR: 4.49; 95% CI: 1.20-16.8) predicted nonresponse. Three (3.7%) patients on simvastatin developed transient transaminitis and elevated creatine phosphokinase and improved with drug withdrawal. Two patients in each group bled (P = 0.99). Three patients and 1 patient, respectively, in group A and B died (P = 0.32), with sepsis being the cause of death. DISCUSSION: Addition of simvastatin to carvedilol for 3 months for primary prophylaxis of variceal bleeding does not improve hemodynamic response over carvedilol monotherapy. Simvastatin usage should be closely monitored for adverse effects in Child C cirrhotic patients.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Carvedilol/uso terapéutico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/prevención & control , Hemodinámica , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Simvastatina/uso terapéutico , Adulto , Quimioterapia Combinada , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/fisiopatología , Venas Hepáticas/fisiopatología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Presión Portal/fisiología , Prevención Primaria , Resultado del Tratamiento , Presión Venosa/fisiología
19.
Hepatology ; 72(4): 1353-1365, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-31960441

RESUMEN

BACKGROUND AND AIMS: A hepatic venous pressure gradient (HVPG) decrease of 20% or more (or ≤12 mm Hg) indicates a good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed to simplify the risk stratification after variceal bleeding using clinical data and HVPG. METHODS: A total of 193 patients with cirrhosis (62% with ascites and/or hepatic encephalopathy [HE]) who were within 7 days of bleeding had their HVPG measured before and at 1-3 months of treatment with propranolol/nadolol plus endoscopic band ligation. The endpoints were rebleeding and rebleeding/transplantation-free survival for 4 years. Another cohort (n = 231) served as the validation set. RESULTS: During follow-up, 45 patients had variceal bleeding and 61 died. The HVPG responders (n = 71) had lower rebleeding risk (10% vs. 34%, P = 0.001) and better survival than the 122 nonresponders (61% vs. 39%, P = 0.001). Patients with HE (n = 120) had lower survival than patients without HE (40% vs. 63%, P = 0.005). Among the patients with ascites/HE, those with baseline HVPG ≤ 16 mm Hg (n = 16) had a low rebleeding risk (13%). In contrast, among patients with ascites/HE and baseline HVPG > 16 mm Hg, only the HVPG responders (n = 32) had a good prognosis, with lower rebleeding risk and better survival than the nonresponders (n = 72) (respective proportions: 7% vs. 39%, P = 0.018; 56% vs. 30% P = 0.010). These findings allowed us to develop a strategy for risk stratification in which HVPG response was measured only in patients with ascites and/or HE and baseline HVPG > 16 mm Hg. This method reduced the "gray zone" (i.e., high-risk patients who had not died on follow-up) from 46% to 35% and decreased the HVPG measurements required by 42%. The validation cohort confirmed these results. CONCLUSIONS: Restricting HVPG measurements to patients with ascites/HE and measuring HVPG response only if the patient's baseline HVPG is over 16 mm Hg improves detection of high-risk patients while markedly reducing the number of HVPG measurements required.


Asunto(s)
Várices Esofágicas y Gástricas/fisiopatología , Hemorragia Gastrointestinal/fisiopatología , Venas Hepáticas/fisiopatología , Cirrosis Hepática/fisiopatología , Presión Venosa/fisiología , Adulto , Anciano , Várices Esofágicas y Gástricas/mortalidad , Femenino , Hemorragia Gastrointestinal/mortalidad , Humanos , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Riesgo
20.
Infect Disord Drug Targets ; 20(4): 511-516, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31057113

RESUMEN

OBJECTIVES: To study the hemodynamic changes of hepatic & renal vessels in systemic bacterial infection with fever in HCV related cirrhosis with possible complications. METHODS: Three groups of patients with systemic bacterial infection with fever were included in the study; group І included 15 patients with decompensated cirrhosis, group ІІ included 15 patients with compensated cirrhosis and group ІІІ included 10 patients without liver affection. Laboratory parameters and Doppler US of hepatic and renal vessels were evaluated during and after subsidence of fever in all patients. RESULTS: Forty patients were enrolled in this prospective study. There were 22 male and 18 female patients. We found that the direction of blood flow in the portal and splenic veins was hepatopetal and the veins were non pulsatile in all cases with no change during and after subsidence of infection. There was no significant difference in portal or splenic vein diameters during and after subsidence of infection in the three studied groups. However, the mean values of portal and splenic veins peak velocities were significantly lower during infection in cirrhotic groups. The mean value of hepatic artery resistive index during fever was significantly higher than after fever in cirrhotic groups. Renal resistive and pulsatility indices were significantly higher during fever in cirrhotic groups. CONCLUSION: Systemic bacterial infection with fever can affect hepatic haemodynamics leading to aggravation of portal hypertension and increasing the risk of complications as variceal bleeding and hepatic encephalopathy and can also affect renal haemodynamics with increased risk of renal impairment.


Asunto(s)
Infecciones Bacterianas/complicaciones , Hepatitis C/complicaciones , Riñón/fisiopatología , Circulación Hepática , Cirrosis Hepática/fisiopatología , Egipto , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Hemorragia Gastrointestinal/etiología , Hemodinámica , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/fisiopatología , Riñón/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vena Esplénica/diagnóstico por imagen , Vena Esplénica/fisiopatología
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