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BACKGROUND & AIMS: Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied. METHODS: Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight. RESULTS: Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (p < .009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); p = .004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (R2 of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (p = .024) or lower (p < .001) urea was independently associated with lower explanted liver weight. CONCLUSIONS: Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.
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Intensive care unit (ICU) admission is frequently required in patients with decompensated cirrhosis for organ support. This entity, known as acute-on-chronic liver failure (ACLF), is associated with high short-term mortality. ICU management of ACLF is complex, as these patients are prone to develop new organ failures and infectious or bleeding complications. Poor nutritional status, lack of effective liver support systems, and shortage of liver donors are also factors that contribute to increase their mortality. ICU therapy parallels that applied in the general ICU population in some complications but has differential characteristics in others. This review describes the current knowledge on critical care management of patients with ACLF including organ support, prognostic assessment, early liver transplantation, and futility rules. Certainties and knowledge gaps in this area are also discussed.
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Insuficiência Hepática Crônica Agudizada , Transplante de Fígado , Humanos , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/terapia , Cuidados Críticos , Prognóstico , Unidades de Terapia Intensiva , Transplante de Fígado/efeitos adversos , Cirrose Hepática/complicações , Cirrose Hepática/terapiaRESUMO
BACKGROUND: This risk analysis aimed to explore all modifiable factors associated with prolonged mechanical ventilation (lasting > 24 h) after liver transplantation, based on prospectively collected data from a clinical trial. METHODS: We evaluated 306 candidates. Ninety-three patients were excluded for low risk for transfusion (preoperative haemoglobin > 130 g.l-1), and 31 patients were excluded for anticoagulation therapy, bleeding disorders, familial polyneuropathy, or emergency status. Risk factors were initially identified with a log-binomial regression model. Relative risk was then calculated and adjusted for age, sex, and disease severity (Model for End-Stage Liver Disease [MELD] score). RESULTS: Early tracheal extubation was performed in 149 patients (84.7%), and 27 patients (15.3%) required prolonged mechanical ventilation. Reoperations were required for 6.04% of the early extubated patients and 44% of patients who underwent prolonged ventilation (p = 0.001). A MELD score > 23 was the main risk factor for prolonged ventilation. Once modifiable risk factors were adjusted for MELD score, sex, and age, three factors were significantly associated with prolonged ventilation: tranexamic acid (p = 0.007) and red blood cell (p = 0.001) infusion and the occurrence of postreperfusion syndrome (p = 0.004). The median (IQR) ICU stay was 3 (2-4) days in the early extubation group vs. 5 (3-10) days in the prolonged ventilation group (p = 0.001). The median hospital stay was also significantly shorter after early extubation, at 14 (10-24) days, vs. 25 (14-55) days in the prolonged ventilation group (p = 0.001). Eight patients in the early-extubation group (5.52%) were readmitted to the ICU, nearly all for reoperations, with no between-group differences in ICU readmissions (prolonged ventilation group, 3.7%). CONCLUSION: We conclude that bleeding and postreperfusion syndrome are the main modifiable factors associated with prolonged mechanical ventilation and length of ICU stay, suggesting that trials should explore vasopressor support strategies and other interventions prior to graft reperfusion that might prevent potential fibrinolysis. TRIAL REGISTRATION: European Clinical Trials Database (EudraCT 2018-002510-13,) and on ClinicalTrials.gov (NCT01539057).
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Doença Hepática Terminal , Transplante de Fígado , Humanos , Hemorragia , Unidades de Terapia Intensiva , Tempo de Internação , Transplante de Fígado/efeitos adversos , Respiração Artificial , Fatores de Risco , Índice de Gravidade de Doença , Ensaios Clínicos como Assunto , Masculino , FemininoRESUMO
BACKGROUND: More than a half of patients undergoing liver transplantation (LT) receive intraoperative transfusion. Portal hypertension (PHT) may contribute to perioperative blood loss. We study the relationship between preoperative hepatic venous pressure gradient (HVPG) values and intraoperative transfusion requirements in adult patients undergoing LT. METHODS: 160 cirrhotic patients undergoing first elective LT (2009-2019) with an HVPG measurement within the previous 6 months were included. Surgical technique was piggyback with portocaval shunt (PCS). The association of HVPG and other variables with transfusion requirements and blood loss were studied. RESULTS: Blood loss (ml/kg) was positively correlated with HVPG, among other variables, but at multivariable analysis it only remained associated with MELD-Na and HCC indication. Regarding RBC transfusion, MELD-Na and hemoglobin were independently associated with the need and magnitude of RBC transfusion. Subanalysis by surgical stage (hepatectomy, anhepatic, neohepatic) and by serial HVPG cut-offs found no clear associations with either bleeding or transfusion. DISCUSSION: The severity of PHT plays a minor role on bleeding and transfusion during LT in a contemporary cohort with systematic PCS. Main determinants of transfusion are liver function and baseline hemoglobin, which would seem the suitable goal to optimize transfusion in LT.
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Carcinoma Hepatocelular , Hipertensão Portal , Neoplasias Hepáticas , Transplante de Fígado , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Carcinoma Hepatocelular/cirurgia , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Hipertensão Portal/diagnóstico , Hipertensão Portal/etiologia , Hipertensão Portal/cirurgia , Hemorragia , Pressão na Veia PortaRESUMO
BACKGROUND & AIMS: It remains unclear whether rectal colonization with multidrug-resistant organisms (MDROs) is prevalent and predisposes to infections by the same pathogens in patients with cirrhosis. METHODS: Two series of critically ill patients were evaluated. In the Barcelona cohort, 486 consecutive patients were prospectively evaluated, 129 with and 357 without cirrhosis (2015-2016). Rectal swabs were performed at admission and weekly thereafter (until intensive care unit [ICU] discharge) to detect MDRO colonization. Risk factors for colonization and infection by MDROs were evaluated. A retrospective cohort from Frankfurt (421 patients with cirrhosis; 2010-2018) was investigated to evaluate MDRO rectal colonization in another epidemiological scenario. RESULTS: In the Barcelona cohort, 159 patients were colonized by MDROs (32.7%), 102 (64.2%) at admission and 57 (35.8%) during follow-up. Patients with cirrhosis showed higher rates of rectal colonization at admission than those without cirrhosis (28.7% vs. 18.2%, p = 0.01) but similar colonization rates during ICU stay. Extended-spectrum beta-lactamase-Enterobacterales were the most frequent MDROs isolated in both groups. Colonization by MDROs independently increased the risk of infection by MDROs at admission and during follow-up. Risk of new infection by the colonizing strain was also significantly increased in patients with (hazard ratio [HR] 7.41) and without (HR 5.65) cirrhosis. Rectal colonization by MDROs was also highly prevalent in Frankfurt (n = 198; 47%; 131 at admission [66.2%] and 67 [33.8%] during follow-up), with vancomycin-resistant enterococci being the most frequent colonizing organism. Rectal colonization by MDROs was also associated with an increased risk of infection by MDROs in this cohort. Infections occurring in MDR carriers were mainly caused by the colonizing strain. CONCLUSION: Rectal colonization by MDROs is extremely frequent in critically ill patients with cirrhosis. Colonization increases the risk of infection by the colonizing resistant strain. LAY SUMMARY: Rectal colonization by multidrug-resistant organisms (MDROs) is a prevalent problem in patients with cirrhosis requiring critical care. The pattern of colonizing bacteria is heterogeneous with relevant differences between centers. Colonization by MDROs is associated with increased risk of infection by the colonizing bacteria in the short term. This finding suggests that colonization data could be used to guide empirical antibiotic therapy and de-escalation policies in patients with cirrhosis.
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Estado Terminal , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/uso terapêutico , Bactérias , Farmacorresistência Bacteriana Múltipla , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Thromboelastometry is considered the best method to assesses hemostasis in liver disease. Diagnostic performance could be improved by adding protein C activators such as thrombomodulin or Protac®. We assessed changes in ROTEM parameters after the addition of Protac® in patients with acute-on-chronic liver failure (ACLF), acute decompensation (AD), and healthy individuals (HI) to define different hemostasis patterns, considering standard and velocity ROTEM parameters, and assess whether Protac® can improve the definition of the pattern. METHODS: Pre-test, we investigated whether diluted EXTEM reagent improved the effect of Protac® on the clotting time (CT)-ratio with and without Protac®. Ten ACLF and 20 AD patients and 21 HI were included in the main study. RESULTS: Standard EXTEM was used in the main study. INTEM CFT, INTEM A5 (inverse), and INTEM TPI (inverse) were the parameters that best differentiated liver disease from HI (ROC AUC, 0.921, 0.906, and 0.928, respectively; all P-values < 0.001). Combining INTEM CFT with EXTEM LI60-ratio only slightly improved the diagnostic performance (ROC AUC, 0.948; P < 0.001). EXTEM LI60 and INTEM maxV-t were the parameters that best differentiated between ACLF and AD patients (ROC AUC, 0.743, P = 0.033; and 0.723, P = 0.050; respectively). Combining EXTEM LI60 + INTEM maxV-t moderately improved the diagnostic performance (ROC AUC, 0.81, P < 0.001). CONCLUSIONS: ROTEM velocity, fibrinolysis parameters and the indices calculated improve the diagnosis in combination with standard parameters (e.g., CFT and A5). Ratios calculated with and without Protac® (e.g., EXTEM LI60-ratio) only slightly increased the diagnostic performance in discriminating hemostasis patterns.
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BACKGROUND & AIMS: To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). METHODS: We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. RESULTS: One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. CONCLUSIONS: A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. LAY SUMMARY: Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.
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Cirrose Hepática Alcoólica/terapia , Transplante de Fígado/classificação , Listas de Espera , Adulto , Antivirais/uso terapêutico , Feminino , Humanos , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , EspanhaRESUMO
BACKGROUND & AIMS: Wedge hepatic vein pressure (WHVP) accurately estimates portal pressure (PP) in alcohol- or viral hepatitis-related cirrhosis. Whether this also holds true in cirrhosis caused by non-alcoholic steatohepatitis (NASH) is unknown. We aimed to evaluate the agreement between WHVP and PP in patients with NASH cirrhosis in comparison to patients with alcohol- or HCV-related cirrhosis. METHODS: All consecutive patients with NASH cirrhosis treated with a transjugular intrahepatic portosystemic shunt (TIPS) in 3 European centres were included (NASH group; n = 40) and matched with 2 controls (1 with alcohol-related and 1 with HCV-related cirrhosis) treated with TIPS contemporaneously (control group; n = 80). Agreement was assessed by Pearson's correlation (R), intra-class correlation coefficient (ICC), and Bland-Altman method. Disagreement between WHVP and PP occurred when both pressures differed by >10% of PP value. A binary logistic regression analysis was performed to identify factors associated with this disagreement. RESULTS: Correlation between WHVP and PP was excellent in the control group (R 0.92; p <0.001; ICC 0.96; p <0.001) and moderate in the NASH group (R 0.61; p <0.001; ICC 0.74; p <0.001). Disagreement between WHVP and PP was more frequent in the NASH group (37.5% vs. 14%; p = 0.003) and was mainly because of PP underestimation. In uni- and multivariate analyses, only NASH aetiology was associated with disagreement between WHVP and PP (odds ratio 4.03; 95% CI 1.60-10.15; p = 0.003). CONCLUSIONS: In patients with decompensated NASH cirrhosis, WHVP does not estimate PP as accurately as in patients with alcohol- or HCV-related cirrhosis, mainly because of PP underestimation. Further studies aimed to assess this agreement in patients with compensated NASH cirrhosis are needed. LAY SUMMARY: Portal pressure is usually assessed by measuring wedge hepatic vein pressure because of solid evidence demonstrating their excellent agreement in alcohol- and viral hepatitis-related cirrhosis. Our results show that in patients with decompensated cirrhosis caused by non-alcoholic steatohepatitis, wedge hepatic vein pressure estimates portal pressure with less accuracy than in patients with other aetiologies of cirrhosis, mainly because of portal pressure underestimation.
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Hipertensão Portal , Cirrose Hepática , Fígado , Hepatopatia Gordurosa não Alcoólica , Pressão na Veia Porta , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Estudos Transversais , Precisão da Medição Dimensional , Progressão da Doença , Feminino , Veias Hepáticas/fisiopatologia , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/etiologia , Hipertensão Portal/cirurgia , Itália/epidemiologia , Fígado/irrigação sanguínea , Fígado/patologia , Circulação Hepática , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/fisiopatologia , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Derivação Portossistêmica Transjugular Intra-Hepática/estatística & dados numéricos , Espanha/epidemiologiaRESUMO
BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a relatively frequent event in patients with cirrhosis. While different risk factors for PVT have been reported, such as decreased portal blood flow velocity (PBFV) and parameters related with severity of portal hypertension, these are based on retrospective studies assessing only a discrete number of parameters. The aim of the current study was to evaluate the incidence and risks factors for non-tumoral PVT development in a large prospective cohort of patients with cirrhosis. METHODS: We performed an exhaustive evaluation of clinical, biochemical, inflammatory and acquired/hereditary hemostatic profiles in 369 patients with cirrhosis without PVT who were prospectively followed-up. Doppler ultrasound was performed at baseline and every 6 months or whenever clinically indicated. PVT development was always confirmed by computed tomography. RESULTS: Twenty-nine patients developed non-tumoral PVT, with an incidence of 1.6%, 6% and 8.4% at 1, 3 and 5 years, respectively. Low platelet count, PBFV <15 cm/sec and history of variceal bleeding were factors independently associated with a high PVT risk. No relationship between PVT development and any other clinical biochemical, inflammatory and acquired or hereditary hemostatic parameter was found. CONCLUSIONS: In patients with cirrhosis, the factors predictive of PVT development were mainly those related to the severity of portal hypertension. Our results do not support the role of hemostatic alterations (inherited or acquired) and inflammatory markers in the prediction of PVT in patients with cirrhosis. LAY SUMMARY: Patients with cirrhosis and more severe portal hypertension are at higher risk of non-tumoral portal vein thrombosis development. Acquired or inherited hemostatic disorders, as well as inflammatory status, do not seem to predict the development of portal vein thrombosis in patients with cirrhosis.
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Fibrose/complicações , Hemostáticos/uso terapêutico , Veia Porta/diagnóstico por imagem , Ultrassonografia/métodos , Trombose Venosa/líquido cefalorraquidiano , Idoso , Feminino , Fibrose/sangue , Fibrose/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Veia Porta/fisiopatologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Ultrassonografia/estatística & dados numéricos , Trombose Venosa/diagnóstico por imagemRESUMO
BACKGROUND: To determine the predictive capacity of baseline haemoglobin and maxim clot firmness (MCF) EXTEM thromboelastometry for intraoperative red blood cell (RBC) requirements and its influence on mortality. METHODS: 591 adult liver transplant (LT) recipients from ten Spanish centres were reviewed. The main outcomes were the percentage of patients who received RBC and massive transfusion (≥ 6 RBC units), RBC units transfused, and mortality. RESULTS: 76 % received a donor after brain death graft and 24 % a controlled donor after circulatory death graft. Median (interquartile ranges) RBC transfusion was 2 (0-4) units, and 63 % of patients were transfused. Comparing transfused and non-transfused patients, mean (standard deviation) for baseline haemoglobin was 10.4 (2.1) vs. 13.0 (1.9) g/dl (p = 0.001), EXTEM MCF was 51(11) vs. 55(9) mm (p = 0.001). Haemoglobin and EXTEM MCF were inversely associated with the need of transfusion odds ratio (OR) of 0.558 (95 % CI 0.497-0.627, p < 0.001) and OR 0.966 (95 % CI0.945-0.987, p = 0.002), respectively. Pre-operative baseline haemoglobin ≤ 10 g/dL predicted RBC transfusion, sensitivity of 93 % and specificity of 47 %. Massive transfusion (MT) was received by 19 % of patients. Haemoglobin ≤10 g/dL predicted MT with sensitivity 73 % and specificity of 52 %. One-year patient and graft survival were significantly lower in patients who required MT (78 % and 76 %, respectively) vs. those who did not (94 % and 93 %, respectively). DISCUSSION: whereas EXTEM MCF is less dreterminant predicting RBC requirements, efforts are required to improve preoperative haemoglobin up to 10 g/dl in patients awaiting LT.
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Transfusão de Eritrócitos/métodos , Hemoglobinas/análise , Hemoglobinas/metabolismo , Transplante de Fígado/mortalidade , Tromboelastografia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Adulto JovemRESUMO
This editorial comments on the findings from the study by Jindal et al. recently published in The American Journal of Gastroenterology. Weaknesses and strengths of the study are presented, and potential therapeutic strategies for compensated cirrhotic patients with an HVPG ≥20 mm Hg are proposed.
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Hipertensão Portal , Humanos , Cirrose Hepática/complicações , Pressão na Veia PortaRESUMO
OBJECTIVES: Infection by severe acute respiratory syndrome coronavirus-2 can induce uncontrolled systemic inflammation and multiple organ failure. The aim of this study was to evaluate if plasma exchange, through the removal of circulating mediators, can be used as rescue therapy in these patients. DESIGN: Single center case series. SETTING: Local study. SUBJECTS: Four critically ill adults with coronavirus disease 19 pneumonia that failed conventional interventions. INTERVENTIONS: Plasma exchange. Two to six sessions (1.2 plasma volumes). Human albumin (5%) was used as the main replacement fluid. Fresh frozen plasma and immunoglobulins were administered after each session to avoid coagulopathy and hypogammaglobulinemia. MEASUREMENTS AND MAIN RESULTS: Serum markers of inflammation and macrophage activation. All patients showed a dramatic reduction in inflammatory markers, including the main cytokines, and improved severity scores after plasma exchange. All survived to ICU admission. CONCLUSIONS: Plasma exchange mitigates cytokine storm, reverses organ failure, and could improve survival in critically ill patients with coronavirus disease 2019 infection.
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COVID-19/complicações , COVID-19/terapia , Insuficiência de Múltiplos Órgãos/etiologia , Troca Plasmática/métodos , Estado Terminal , Citocinas/biossíntese , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND AIMS: Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti-HEV IgM and IgG, and HEV-RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology. METHODS: One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non-AIH). RESULTS: Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non-AIH). Patients with acute AIH and positive anti-HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti-HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021). CONCLUSION: Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross-reactivity between HEV and liver antigens.
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Vírus da Hepatite E , Hepatite E , Hepatite Autoimune , Anticorpos Anti-Hepatite , Hepatite E/epidemiologia , Hepatite Autoimune/epidemiologia , Humanos , Imunoglobulina M , Estudos SoroepidemiológicosRESUMO
BACKGROUND & AIMS: Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pressure gradient (HVPG) and other variables in elective extrahepatic surgery in patients with cirrhosis. METHODS: A total of 140 patients with cirrhosis (Child-Pugh A/B/C: 59/37/4%), who were due to have elective extrahepatic surgery (121 abdominal; 9 cardiovascular/thoracic; 10 orthopedic and others), were prospectively included in 4 centers (2002-2011). Hepatic and systemic hemodynamics (HVPG, indocyanine green clearance, pulmonary artery catheterization) were assessed prior to surgery, and clinical and laboratory data were collected. Patients were followed-up for 1â¯year and mortality, transplantation, morbidity and post-surgical decompensation were studied. RESULTS: Ninety-day and 1-year mortality rates were 8% and 17%, respectively. Variables independently associated with 1-year mortality were ASA class (American Society of Anesthesiologists), high-risk surgery (defined as open abdominal and cardiovascular/thoracic) and HVPG. These variables closely predicted 90-, 180- and 365-day mortality (C-statistic >0.8). HVPG values >16â¯mmHg were independently associated with mortality and values ≥20â¯mmHg identified a subgroup at very high risk of death (44%). Twenty-four patients presented persistent or de novo decompensation at 3â¯months. Low body mass index, Child-Pugh class and high-risk surgery were associated with death or decompensation. No patient with HVPG <10â¯mmHg or indocyanine green clearance >0.63 developed decompensation. CONCLUSIONS: ASA class, HVPG and high-risk surgery were prognostic factors of 1-year mortality in cirrhotic patients undergoing elective extrahepatic surgery. HVPG values >16â¯mmHg, especially ≥20â¯mmHg, were associated with a high risk of post-surgical mortality. LAY SUMMARY: The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.
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Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos Eletivos/mortalidade , Procedimentos Cirúrgicos Eletivos/métodos , Hipertensão Portal , Cirrose Hepática/cirurgia , Pressão na Veia Porta , Idoso , Feminino , Seguimentos , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Risco , Resultado do TratamentoRESUMO
Balanced hemostasis with hypocoagulable and hypercoagulable features may occur in acute-on-chronic liver failure (ACLF). The characteristics and prognostic impact of the coagulation profile in ACLF are unknown. Consecutive patients with ACLF (n = 36) and acute decompensation (AD; n = 24) were included. Blood samples for thromboelastometry (TE) were obtained at admission and 72 hours thereafter. The coagulation profile was evaluated in patients with and without ACLF and in those with and without systemic inflammatory response syndrome. The impact of the coagulation profile on transfusion requirements, bleeding events, and short-term survival was assessed. At admission, patients with ACLF showed more hypocoagulable characteristics compared to AD subjects, with prolonged time to initial fibrin formation and clot formation time and decreased maximum clot firmness and alpha-angle values. TE parameters worsened at 72 hours in ACLF but improved in patients with AD. Prevalence of a hypocoagulable profile (three or more TE parameters outside range) was significantly higher in patients with ACLF either at admission (61% versus 29% in AD; P = 0.03) or during follow-up. Hypocoagulability correlated with systemic inflammation and was associated with higher 28-day (45% versus 16%; P = 0.02) and 90-day (52% versus 19%; P = 0.01) mortality rates but not with transfusion requirements or bleeding. Prolonged time to initial fibrin formation (extrinsic TE assay >80 seconds) and Model for End-Stage Liver Disease score at baseline were independent predictors of 28-day mortality. Conclusion: Patients with ACLF frequently show hypocoagulable features with prolonged time to initial fibrin formation and clot formation time and reduced clot firmness; these alterations worsen after admission, correlate with systemic inflammation, and translate into higher short-term mortality; hypofibrinolysis could contribute to organ failure in ACLF.
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Insuficiência Hepática Crônica Agudizada/sangue , Transtornos da Coagulação Sanguínea/etiologia , Coagulação Sanguínea , Cirrose Hepática/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Idoso , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia , TromboelastografiaRESUMO
BACKGORUND & AIMS: Mushroom poisoning with Amanita phalloides or similar species can lead to liver failure with 10-30% mortality rates. We aimed at defining the prognostic value of urinary amatoxin quantification in patients with hepatotoxic mushroom poisoning. METHODS: Data from 32 patients with hepatotoxic mushroom poisoning (Hospital Clínic Barcelona, 2002-16) in whom urinary amatoxins were determined (ELISA) were retrospectively reviewed. Correlations between urinary amatoxin and collected baseline variables with outcomes including hepatotoxicity (ALT>1000 U/L), severe acute liver injury (ALI, prothrombin <50%), acute liver failure (ALF, ALI and encephalopathy), transplantation/death and hospital length-of-stay, were evaluated. RESULTS: 12/32 patients developed increased aminotransferase activity. Among the 13/32 amatoxin negative patients, 1 developed ALI and 12/13 no hepatotoxicity. Among the 19/32 amatoxin positive patients, 8/19 (42%) developed hepatotoxicity, including 5 who progressed to severe ALI, of whom 3 developed ALF (2 deaths, 1 transplantation). Urinary amatoxin and prothrombin were independent predictors of hepatotoxicity, ALT peak values (along with age) and hospital length-of-stay. In positive amatoxins patients, urinary concentrations > 55 ng/ml (or a baseline prothrombin ≤ 83%), were associated to hepatotoxicity (presented by 8/9 patients with ALT>1000 U/L). Among 5 patients with urinary amatoxin ≥ 70 ng/ml, 4 developed severe ALI. CONCLUSIONS: In patients with hepatotoxic mushroom poisoning, a negative urinary amatoxin quantification within 72h of intake ruled out the risk of hepatotoxicity in 92% of patients, whereas positive urinary amatoxins were associated with hepatotoxicity and severe ALI. Concentrations >55 ng/ml and ≥ 70 ng/ml were predictive of hepatotoxicity and severe ALI, respectively.
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Amanitinas/urina , Falência Hepática Aguda/induzido quimicamente , Intoxicação Alimentar por Cogumelos/diagnóstico , Intoxicação Alimentar por Cogumelos/urina , Adolescente , Adulto , Idoso , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Falência Hepática Aguda/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Espanha , Adulto JovemRESUMO
BACKGROUND: In cirrhosis, a decrease in hepatic venous pressure gradient (HVPG) > 10% after acute iv propranolol (HVPG response) is associated with a lower risk of decompensation and death. Only a part of patients are HVPG responders and there are no accurate non-invasive markers to identify them. We aimed at discovering metabolomic biomarkers of HVPG responders to propranolol. METHODS: Sixty-six patients with cirrhosis and HVPG ≥ 10 mm Hg in whom the acute HVPG response to propranolol was assessed, were prospectively included. A targeted metabolomic serum analysis using ultrahigh-performance liquid chromatography coupled to mass spectrometry was performed. Different combinations of 2-3 metabolites identifying HVPG responders (HVPG reduction > 10%) were obtained by stepwise logistic regression. The best of these model (AUROC, Akaike criterion) underwent internal cross-validation and cut-offs to classify responders/non-responders was proposed. RESULTS: A total of 41/66 (62%) patients were HVPG responders. Three hundred and eighty-nine metabolites were detected and 177 were finally eligible. Eighteen metabolites were associated to the HVPG response at univariate analysis; at multivariable analysis, a model including a phosphatidylcholine (PC(P-16:0/22:6)) and a free fatty acid (20:2(n-6), eicosadienoic acid) performed well for HVPG response, with an AUROC of 0.801 (0.761 at internal validation). The cut-off 0.629 was the most efficient for overall classification (49/66 patients correctly classified). Two cut-off values allowed identifying responders (0.688, PPV 84%) and non-responders (0.384, NPV 82%) with undetermined values for 17/66 patients. Clinical variables did not add to the model. CONCLUSIONS: The combination of two metabolites helps at identifying HVPG responders to acute propranolol. It could be a useful non-invasive test to classify the HVPG response to propranolol.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Metabolômica , Propranolol/administração & dosagem , Idoso , Biomarcadores/sangue , Feminino , Humanos , Hipertensão Portal/sangue , Hipertensão Portal/complicações , Infusões Intravenosas , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Pressão Venosa/efeitos dos fármacosRESUMO
BACKGROUND & AIMS: Detailed hepatitis C virus (HCV) kinetics modelling is scarce in patients with advanced liver disease receiving direct-acting antivirals (DAAs). Due to budget restrictions, patients and health systems would benefit from the shortest possible treatment course. We investigated whether modelling very early HCV kinetics in cirrhotic patients under DAAs therapy could be used to individualize care and reduce treatment duration to achieve cure. METHODS: We included 74 patients with HCV-related cirrhosis who received interferon-free treatments for 12-24 weeks. HCV genotype, liver disease stage and treatment regimen were recorded. Viral load was determined prospectively at very frequent intervals until target not detected (TND, <15 IU/mL). A viral kinetic model was used to predict time to cure based on HCV clearance in extracellular body fluid (CL-EF). RESULTS: Sixty-eight patients (92%) achieved cure. Thirteen (18%) had MELD ≥15, 35 (47%) were Child-Pugh (CTP) ≥7. Median time to reach TND was 2 weeks (IQR: 1-4 weeks). Modelling indicated an average DAAs efficacy in blocking viral production of ε = 99.1%. HCV half-life (t1/2 ) was significantly shorter in patients with CTP <7, LSM <21 kPa or MELD <15 (1.5 vs 2.5 hours; P = 0.0057). The overall median CL-EF was 5.6 weeks (4.1-7.8). A CTP >7 and a LSM ≥21 kPa were significantly (P = 0.016) associated with longer CL-EF. CONCLUSIONS: The study provides insights into HCV dynamics during DAAs therapy in patients with compensated and decompensated cirrhosis. Viral kinetics modelling suggests that treatment duration may be optimized in patients with compensated cirrhosis.
Assuntos
Antivirais/uso terapêutico , Duração da Terapia , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Idoso , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/complicações , Humanos , Cinética , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Resposta Viral Sustentada , Carga ViralRESUMO
Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk of infection. This investigation evaluated prevalence and characteristics of bacterial and fungal infections causing and complicating ACLF, predictors of follow-up bacterial infections and impact of bacterial infections on survival. PATIENTS: 407 patients with ACLF and 235 patients with acute decompensation (AD). RESULTS: 152 patients (37%) presented bacterial infections at ACLF diagnosis; 46%(n=117) of the remaining 255 patients with ACLF developed bacterial infections during follow-up (4 weeks). The corresponding figures in patients with AD were 25% and 18% (p<0.001). Severe infections (spontaneous bacterial peritonitis, pneumonia, severe sepsis/shock, nosocomial infections and infections caused by multiresistant organisms) were more prevalent in patients with ACLF. Patients with ACLF and bacterial infections (either at diagnosis or during follow-up) showed higher grade of systemic inflammation at diagnosis of the syndrome, worse clinical course (ACLF 2-3 at final assessment: 47% vs 26%; p<0.001) and lower 90-day probability of survival (49% vs 72.5%;p<0.001) than patients with ACLF without infection. Bacterial infections were independently associated with mortality in patients with ACLF-1 and ACLF-2. Fungal infections developed in 9 patients with ACLF (2%) and in none with AD, occurred mainly after ACLF diagnosis (78%) and had high 90-day mortality (71%). CONCLUSION: Bacterial infections are extremely frequent in ACLF. They are severe and associated with intense systemic inflammation, poor clinical course and high mortality. Patients with ACLF are highly predisposed to develop bacterial infections within a short follow-up period and could benefit from prophylactic strategies.
Assuntos
Insuficiência Hepática Crônica Agudizada , Infecções Bacterianas , Micoses , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/microbiologia , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/fisiopatologia , Idoso , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/complicações , Micoses/diagnóstico , Micoses/epidemiologia , Prevalência , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
Overt hepatic encephalopathy (OHE) negatively impacts the prognosis of liver transplant candidates. However, it is not taken into account in most prioritizing organ allocation systems. We aimed to assess the impact of OHE on waitlist mortality in 3 cohorts of cirrhotic patients awaiting liver transplantation, with differences in the composition of patient population, transplantation policy, and transplantation rates. These cohorts were derived from two centers in the Netherlands (reference and validation cohort, n = 246 and n = 205, respectively) and one in Spain (validation cohort, n = 253). Competing-risk regression analysis was applied to assess the association of OHE with 1-year waitlist mortality. OHE was found to be associated with mortality, independently of MELD score, other cirrhosis-related complications and hepatocellular carcinoma (HCC; sHR = 4.19, 95% CI = 1.9-9.5, P = 0.001). The addition of extra MELD points for OHE counteracted its negative impact on survival. These findings were confirmed in the Dutch validation cohort, whereas in the Spanish cohort, containing a significantly greater proportion of HCC and with higher transplantation rates, OHE was not associated with mortality. In conclusion, OHE is an independent risk factor for 1-year waitlist mortality and might be a prioritization rule for organ allocation. However, its impact seems to be attenuated in settings with significantly higher transplantation rates.