167 research outputs found
A new prognostic algorithm based on stage of cirrhosis and HVPG to improve risk-stratification after variceal bleeding
Background & Aims: HVPG decrease â„20% or â€12mmHg (ârespondersâ) indicates good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed at simplifying riskâstratification after variceal bleeding using clinical data and HVPG. Methods: 193 cirrhotic patients (62% with ascites and/or hepatic encephalopathy, HE) included within 7âdays of bleeding had HVPG measured before and at 1â3 months of treatment with propranolol/nadolol plus endoscopic band ligation. Endâpoints: Rebleeding and rebleeding/transplantationâfree survival for 4âyears. Another cohort (n=231) served as validation set. Results: During followâup 45 patients had variceal bleeding and 61 died. HVPGâresponders (n=71) had lower rebleedingârisk (10% vs 34%, p=0.001) and better survival than 122 nonâresponders (61% vs 39%, p=0.001). Patients with/HE (n=120) had lower survival than patients without (40% vs 63%, p=0.005). Among patients with ascites/HE, those with baseline HVPGâ€16mmHg (n=16) had low rebleedingârisk (13%). By contrast, among patients with ascites/HE and baseline HVPG>16mmHg, only HVPGâresponders (n=32) had good prognosis, with lower rebleedingârisk and better survival than nonâresponders (n=72) (respective proportions: 7% vs 39%,p=0.018; 56% vs 30% p=0.010). These findings allowed developing a new algorithm for riskâstratification in which HVPGâresponse was only measured in patients with ascites and/or HE and baseline HVPG>16mmHg. This algorithm reduced the greyâzone (highârisk patients not dying on followâup) from 46% to 35% and decreased by 42% the HVPG measurements required. The validation cohort confirmed these results. Conclusion: Restricting HVPG measurements to patients with ascites/HE and measuring HVPGâresponse only if baseline HVPG>16mmHg improves detection of highârisk patients while markedly reducing the number of HVPG measurements required
Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis
BACKGROUND & AIMS: Noninvasive methods are needed to identify clinically significant portal hypertension (CSPH) and esophageal varices (EVs) in patients with compensated cirrhosis. We looked for markers of the presence of CSPH and EVs in patients with cirrhosis. METHODS: We performed a cross-sectional study that included a training set of 117 patients with compensated cirrhosis, confirmed by histology, from a tertiary referral center. Spleen diameter was measured by ultrasound, and liver stiffness (LS) was measured by transient elastography; endoscopy was used as the standard for detection of EVs, and measurements of hepatic venous pressure gradient were used as the standard for identifying CSPH. We assessed the ability of platelet count, spleen diameter, LS, and combinations of these factors (ie, ratio of platelet count to spleen size, and LS Ă spleen size/platelet count [LSPS]) to identify patients with CSPH and EV. The analysis included 2 new statistical models: the PH risk score and the varices risk score. Results were validated using an independent series of 56 patients with compensated patients from another center. RESULTS: LS was the best single noninvasive variable for identifying patients with CSPH (area under the receiver operating characteristic, 0.883; 95% confidence interval [CI], 0.824-0.943; P < .0001). The area under the receiver operating characteristic value increased when LS was combined with platelet count and spleen size, either as LSPS (0.918; 95% CI, 0.872-0.965; P < .0001) or PH risk score (0.935; 95% CI, 0.893-0.977; P < .0001). More than 80% of patients were accurately classified using LSPS and PH risk score. Analyses of the varices risk score and LSPS were superior to all other noninvasive tests for identifying patients with EVs (area under the receiver operating characteristic, 0.909; 95% CI, 0.841-0.954 and 0.882; 95% CI, 0.810-0.935, respectively); they correctly classified 85% of patients in the training set and 75% in the validation set. CONCLUSIONS: Combined data on LS, spleen diameter, and platelet count can be used to identify patients with compensated cirrhosis most likely to have CSPH and EV
a cohort study
Funding: This work was supported by grants from the National Institutes of Health (U19AI135964, P30AG059988), with institutional support from UL1TR001422. The funding agency played no role in the study design, collection of data, analysis, or interpretation of data.The impact of multidrug-resistant (MDR) colonization and MDR infection in critically ill cirrhosis patients remains unclear. We assessed the association of MDR colonization and MDR infection with these patients' survival. Observational cohort study including adult cirrhosis patients admitted to 5 intensive care units at Northwestern Memorial Hospital (Chicago, Illinois, USA) on January 1, 2010, to December 31, 2017. Patients admitted for elective liver transplant or with previous liver transplant were excluded. Patients were screened for MDR colonization on intensive care unit admission. Infection diagnoses during the intensive care unit stay were considered. The primary endpoint was hospital transplant-free survival. Among 600 patients included, 362 (60%) were men and median (interquartile range) age was 58.0 (49.0, 64.0) years. Median (interquartile range) Model for End-stage Liver Disease, Sequential Organ Failure Assessment, and Chronic Liver Failure-Acute-on-Chronic Liver Failure scores on intensive care unit day 1 were 28.0 (20.0, 36.0), 9.0 (6.0, 13.0), and 55.0 (48.0, 64.0), respectively. Overall, 76 (13%) patients were transplanted and 443 (74%) survived the hospital stay. Infections were diagnosed in 347 (58%) patients: pneumonia in 197 (33%), urinary tract infection in 119 (20%), peritonitis in 93 (16%), bloodstream infection in 99 (16%), Clostridium difficile colitis in 9 (2%), and catheter tip infection in 7 (1%). MDR colonization and MDR infection were identified in 200 (33%) and 69 (12%) patients, respectively. MDR colonization was associated with MDR infection (p < 0.001). MDR colonization or MDR infection was associated with higher number and duration of antibiotics (p < 0.001). Following adjustment for covariables (age, sex, etiology, portal hypertension, and Sequential Organ Failure Assessment score), MDR colonization [OR (95% CI), 0.64 (0.43, 0.95)] or MDR infection [adjusted OR (95% CI), 0.22 (0.12, 0.40)] were independently associated with lower transplant-free survival. Among critically ill cirrhosis patients, MDR colonization or MDR infection portended a worse prognosis.publishersversionpublishe
Heterologous adenovirus-vector/messenger RNA regimen is associated with improved severe acute respiratory syndrome coronavirus 2 humoral response in liver transplant recipients
Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)-based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing anti-spike immunoglobulin G (IgG). In this prospective cohort study, SARS-CoV-2 anti-spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21â90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26-rAd5 (Sputnik V), inactivated BBIBP-CorV (Sinopharm), or the heterologous combination rAd26/mRNA-1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti-spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA-1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03â0.3; p < 0.001) and with increased BMI (OR, 0.4; 95% CI, 0.2â0.7; p = 0.005); and it was significantly higher in those immunized with rAd26/mRNA-1273 (OR, 13.1; 95% CI, 2.3â72.9; p = 0.003). In LTRs anti-spike IgG concentrations showed a very good correlation with NA titers (R2 = 0.949; 95% CI, 0.919â0.967; p < 0.001). No serious adverse events were reported in either group. Conclusion: In LTRs, rAd26/mRNA-1273 was independently associated with higher antibody response. Future studies are necessary to evaluate whether combining different vaccine platforms and MMF reduction may lead to a better booster response.Fil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Ducasa, NicolĂĄs. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; ArgentinaFil: Benencio, Paula. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; ArgentinaFil: Anders, Margarita. Hospital AlemĂĄn; ArgentinaFil: Cairo, Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. NĂ©stor Carlos Kirchner Samic; ArgentinaFil: Barbero, Manuel. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. NĂ©stor Carlos Kirchner Samic; ArgentinaFil: Etcheves, Patricia. No especifĂca;Fil: Alter, Adriana. Hospital Italiano; ArgentinaFil: Scarton, Giampaolo. No especifĂca;Fil: Abraldes, Juan G.. University of Alberta; CanadĂĄFil: Biglione, Mirna Marcela. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; ArgentinaFil: Mauro, Ezequiel. Hospital Italiano; Argentin
Sinusoidal Endothelial Dysfunction Precedes Inflammation and Fibrosis in a Model of NAFLD
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Most morbidity associated with the metabolic syndrome is related to vascular complications, in which endothelial dysfunction is a major pathogenic factor. However, whether NAFLD is associated with endothelial dysfunction within the hepatic vasculature is unknown. The aims of this study were to explore, in a model of diet-induced overweight that expresses most features of the metabolic syndrome, whether early NAFLD is associated with liver endothelial dysfunction. Wistar Kyoto rats were fed a cafeteria diet (CafD; 65% of fat, mostly saturated) or a control diet (CD) for 1 month. CafD rats developed features of the metabolic syndrome (overweight, arterial hypertension, hypertryglyceridemia, hyperglucemia and insulin resistance) and liver steatosis without inflammation or fibrosis. CafD rats had a significantly higher in vivo hepatic vascular resistance than CD. In liver perfusion livers from CafD rats had an increased portal perfusion pressure and decreased endothelium-dependent vasodilation. This was associated with a decreased Akt-dependent eNOS phosphorylation and NOS activity. In summary, we demonstrate in a rat model of the metabolic syndrome that shows features of NAFLD, that liver endothelial dysfunction occurs before the development of fibrosis or inflammation
Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis
Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P <0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P=0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone
Proceedings from the 2018 Canadian Association for the Study of the Liver Single Topic ConferenceâDecompensated Cirrhosis : from clinic to transplant
Actes publiés dans le Canadian Liver Journal; vol. 2, no. 4, Fall 2019, p. 137-170
Human and experimental evidence supporting a role for osteopontin in alcoholic hepatitis: Hepatology
We identified in the transcriptome analysis of patients with alcoholic hepatitis (AH) osteopontin (OPN) as one of the most up-regulated genes. Here, we used a translational approach to investigate its pathogenic role. OPN hepatic gene expression was quantified in patients with AH and other liver diseases. OPN protein expression and processing were assessed by immmunohistochemistry, Western blotting and ELISA. OPN gene polymorphisms were evaluated in patients with alcoholic liver disease. The role of OPN was evaluated in OPNâ/â mice with alcohol-induced liver injury. OPN biological actions were studied in human hepatic stellate cells and in precision-cut liver slices. Hepatic expression and serum levels of OPN were markedly increased in AH compared to normal livers and other types of chronic liver diseases and correlated with short-term survival. Serum levels of OPN also correlated with hepatic expression and disease severity. OPN was mainly expressed in areas with inflammation and fibrosis. Two proteases that process OPN (thrombin and MMP-7) and cleaved-OPN were increased in livers with AH. Patients with AH had a tendency of a lower frequency of the CC genotype of the +1239C SNP of the OPN gene compared to patients with alcohol abuse without liver disease. Importantly, OPNâ/â mice were protected against alcohol-induced liver injury and showed decreased expression of inflammatory cytokines. Finally, OPN was induced by LPS and stimulated inflammatory actions in hepatic stellate cells
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