Lactate and number of organ failures predict intensive care unit mortality in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Patients with acute-on-chronic liver failure (ACLF) have high mortality rates. Most prognostic scores were not developed for the intensive care unit (ICU) setting. We aimed to improve risk stratification for patients with ACLF in the ICU. METHODS: A training set with 240 patients with cirrhosis and organ failures (Chronic Liver Failure Sequential Organ Failure Assessment score [CLIF-SOFA]) from Curry Cabral Hospital (Portugal) and University of Alberta Hospital (Canada) in 2010-2016 was used to derive a prognostic model for ICU mortality. A validation set with 237 patients with cirrhosis and organ failures from Vancouver General Hospital (Canada) in 2000-2011 was used to evaluate its performance. RESULTS: Amongst patients in the training set, ICU and hospital mortality rates were 39.2% and 54.6% respectively. Median lactate (4.4 vs 2.5 mmol/L) and number of organ failures (3 vs 2) on admission to ICU were associated with higher likelihood of ICU mortality (P < 0.001 for both). The lactate and organ failures predictive model (LacOF) was derived to predict ICU mortality: -2.420 + 0.072 × lactate + 0.569 × number of organ failures (area under-the-curve [AUC], 0.76). In the validation set, the LacOF model discriminative ability (AUC, 0.85) outperformed the CLIF-SOFA (AUC, 0.79), Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure (AUC, 0.73), Model for End-stage Liver Disease score (AUC, 0.78) and Acute Physiology and Chronic Health Evaluation II scores (AUC, 0.74; P < 0.05 for all). The LacOF model calibration was good up to the 25% likelihood of ICU mortality. CONCLUSIONS: In patients with ACLF, lactate and number of organ failures on admission to ICU are useful to predict ICU mortality. This early prognostic evaluation may help to better stratify the risk of ICU mortality and thus optimize organ support strategies.

The Impact of Donor Risk Index, Recipients' and Operative Characteristics on Post Liver Transplant One-Year Graft Failure: A Cohort Analysis.

Background and Aims: The donor risk index (DRI) quantifies donor-related characteristics potentially associated with increased risk of early graft failure. We aimed to assess the impact of the DRI, recipient and perioperative factors on post liver transplant (LT) outcomes. Methods: This was a single-center retrospective cohort study including all adult (≥18 years) patients who underwent LT from 01/2019 to 12/2019 at Curry Cabral Hospital, Lisbon, Portugal. Primary endpoint was 1-year graft failure post LT. Associations were studied with logistic regression. Results: A total of 131 cadaveric donor LT procedures were performed in 116 recipients. Recipients' median (IQR) age was 57 (47-64) years and 101/131 (77.1%) were males. Cirrhosis was the underlying etiology in 95/131 (81.2%) transplants. Based on 8 predefined donors' characteristics, median (IQR) DRI was 1.96 (1.67-2.16). Following adjustment for MELDNa score pre LT and SOFA score (adjusted odds ratio [aOR], 95% confidence interval [CI] = 0.91 [0.56-1.47]) or lactate (aOR [95% CI] = 2.76 [0.71-10.7]) upon intensive care unit (ICU) admission post LT, DRI was not associated with 1-year graft failure. However, higher SOFA score (aOR [95% CI] = 1.20 [1.05-1.37]) or lactate (aOR [95% CI] = 1.27 [1.10-1.46]) upon ICU admission post LT were independently associated with higher odds of 1-year graft failure. Conclusions: In a recent cohort of patients who underwent LT, DRI, despite being high, was not associated with 1-year graft failure, but SOFA score or lactate upon ICU admission post LT were.

Introdução: O índice de risco do dador (DRI) quantifica as características relacionadas com o dador potencialmente associadas com risco acrescido de falência precoce do enxerto. Procurou-se avaliar o impacto do DRI e factores relacionados com os receptores e cirurgia nos resultados clínicos após transplante hepático (LT). Materiais e Métodos: Estudo coorte retrospectivo de centro único incluindo todos os doentes adultos (≥18 anos) que receberam LT entre 01/2019 e 12/2019 no Hospital Curry Cabral, Lisboa, Portugal. O endpoint primário foi a falência do enxerto após um ano do LT. As associações foram estudadas com regressão logística. Resultados: Um total de 131 transplantes de dadores cadavéricos foram realizados em 116 receptores. A idade mediana (IQR) destes foi 57 (47­64) anos e 101/131 (77.1%) eram homens. A cirrose foi a etiologia subjacente em 95/131 (81.2%) transplantes. Com base nas 8 características dos dadores predefinidas, o DRI mediano (IQR) foi 1.96 (1.67­2.16). Após ajuste para o score MELDNa pre LT e o score SOFA (odds ratio ajustado [aOR], intervalo de confiança 95% [CI] = 0.91 [0.56­1.47]) ou o lactato (aOR [95% CI] = 2.76 [0.71­10.7]) após admissão na unidade de cuidados intensivos (ICU) pós LT, o DRI não se associou com a falência do enxerto um ano depois do LT. Contudo, um maior score SOFA (aOR [95% CI] = 1.20 [1.05­1.37]) ou lactato (aOR [95% CI] = 1.27 [1.10­1.46]) após admissão na ICU depois do LT associaram-se independentemente com a falência do enxerto um ano depois do LT. Conclusões: Num coorte recente de doentes submetidos a LT, o DRI, apesar de alto, não se associou com a falência precoce do enxerto precoce. Contudo, o score SOFA ou lactato após admissão na ICU depois do LT associaram-se com a falência precoce do enxerto.

Early serum ammonia variation in critically ill patients with cirrhosis: A multicentre cohort study.

BACKGROUND: Serum ammonia variation in critically ill patients with cirrhosis has been poorly studied. AIM: To describe and assess the impact of serum ammonia variation in these patients' outcomes. METHODS: We studied patients ≥18 years old admitted to the intensive care units (ICUs) at University of Alberta Hospital (Edmonton, Canada) and Curry Cabral Hospital (Lisbon, Portugal; derivation cohort, n = 492) and Northwestern University Hospital (Chicago, USA; validation cohort, n = 600) between January 2010 and December 2021. Primary exposure was ICU days 1-3 serum ammonia. Primary endpoint was all-cause hospital mortality. RESULTS: In the derivation cohort, 330 (67.1%) patients were male and median (IQR) age was 57 (50-63) years. On ICU day 1, median ammonia was higher in patients with grade 3/4 hepatic encephalopathy (HE) than those with grade 2 HE or grade 0/1 HE (112 vs. 88 vs. 77 µmoL/L, respectively; p < 0.001). Furthermore, medium ammonia was higher in hospital non-survivors than survivors (99 vs. 86 µmol/L; p < 0.030). Following adjustment for significant confounders (age, HE, vasopressor use and renal replacement therapy delivery), higher ICU day 2 ammonia was independently associated with higher hospital mortality (adjusted OR per each 10 µmoL/L increment [95% CI] = 1.11 [1.01-1.21]; p = 0.024). In the validation cohort, this model with serial ammonia (ICU days 1 and 3) predicted hospital mortality with reasonably good discrimination (c-statistic = 0.73) and calibration (R2 = 0.19 and Brier score = 0.17). CONCLUSIONS: Among patients with cirrhosis in the ICU, early serum ammonia variation was independently associated with hospital mortality. In this context, serial serum ammonia may have prognostic value.

Alcohol Consumption Post-Liver Transplantation: A Cross-Sectional Study.

Background: Listing patients with alcohol-associated liver disease (ALD) for liver transplant (LT) remains challenging especially due to the risk of alcohol resumption post-LT. We aimed to evaluate post-LT alcohol consumption at a Portuguese transplant center. Methods: We conducted a cross-sectional study including LT recipients from 2019 at Curry Cabral Hospital, Lisbon, Portugal. A pretested survey and a validated Portuguese translation of the Alcohol Use Disorder Identification Test (AUDIT) were applied via a telephone call. Alcohol consumption was defined by patients' self-reports or a positive AUDIT. Results: In 2019, 122 patients underwent LT, and 99 patients answered the survey (June 2021). The mean (SD) age was 57 (10) years, 70 patients (70.7%) were males, and 49 (49.5%) underwent ALD-related LT. During a median (IQR) follow-up of 24 (20-26) months post-index LT, 22 (22.2%) recipients consumed any amount of alcohol: 14 had a drink monthly or less and 8 drank 2-4 times/month. On drinking days, 18 patients usually consumed 1-2 drinks and the remainder no more than 3-4 drinks. One patient reported having drunk ≥6 drinks on one occasion. All post-LT drinking recipients were considered low risk (score <8) as per the AUDIT score (median [IQR] of 1 [1-2]). No patient reported alcohol-related problems, whether self-inflicted or toward others. Drinking recipients were younger (53 vs. 59 years, p = 0.020), had more non-ALD-related LT (72.7 vs. 44.2%, p = 0.018) and active smoking (31.8 vs. 10.4%, p = 0.037) than abstinent ones. Conclusion: In our cohort, about a quarter of LT recipients consumed alcohol early posttransplant, all with a low-risk pattern according to the AUDIT score.

Introdução: Incluir doentes com doença hepática associada ao álcool (DHA) em lista ativa de transplante hepático (TH) é desafiante, especialmente pelo risco de recidiva de consumo de álcool pós-TH. O objetivo foi avaliar o consumo de álcool pós-TH num centro de transplantação português. Métodos: Realizamos um estudo transversal incluindo doentes submetidos a TH em 2019 no Hospital Curry Cabral, Lisboa, Portugal. Foi realizado um questionário previamente testado e uma tradução validada para o português do Alcohol Use Disorder Identification Test (AUDIT), através de uma chamada telefónica. O consumo de álcool foi definido pelo autorrelato do doente ou por um AUDIT positivo. Resultados: Durante 2019, 122 doentes foram submetidos a TH e 99 responderam ao questionário (junho de 2021). A idade média (SD) foi de 57 (10) anos, 70 doentes (70,7%) eram do sexo masculino e 49 (49,5%) foram submetidos a TH relacionado com DHA. Com uma mediana (IQR) de follow-up de 24 (20­26) meses após o TH-índex, 22 (22,2%) doentes admitiram algum consumo de álcool: 14 beberam mensalmente ou menos e oito beberam 2­4 vezes/mês. Nos dias em que bebiam, 18 consumiam normalmente 1­2 bebidas e os restantes não mais do que 3­4 bebidas. Um doente reportou o consumo de ≥6 bebidas em uma ocasião. Todos os doentes transplantados com consumo alcoólico pós-TH foram considerados de baixo risco (pontuação >8) de acordo com o AUDIT (mediana [IQR] de 1 [1­2]). Nenhum doente reportou problemas relacionados com o álcool, tanto autoinfligido como a terceiros. Os indivíduos transplantados com consumo alcoólico eram mais jovens (53 vs. 59 anos, p = 0,020), o motivo de TH era mais frequentemente não relacionado com DHA (72,7 vs. 44,2%, p = 0,018) e apresentavam mais tabagismo ativo (31,8 vs. 10,4%, p = 0,037) quando comparado com os abstinentes. Conclusão: Na nossa coorte, cerca de um quarto dos doentes transplantados hepáticos consumiram álcool no período pós-transplante precoce, todos com um padrão de baixo risco, de acordo com o AUDIT.

Positive fluid balance was associated with mortality in patients with acute-on-chronic liver failure: A cohort study.

PURPOSE: We aimed to study the effect of FB in the outcomes of critically-ill patients with cirrhosis. MATERIALS: Retrospective analysis of all adult consecutive admissions of patients with cirrhosis and organ failures to the Intensive Care Unit (ICU) at Curry Cabral Hospital (Lisbon, Portugal) and University of Alberta Hospital (Edmonton, Canada) on 08/2013-08/2017. Primary exposure was FB at 3 and 7 days post ICU admission. Primary endpoint was hospital mortality. RESULTS: Amongst 333 patients, median age was 56 years and 67.6% were men. Median MELD, APACHEII, CLIF-SOFA, and CLIF-C-ACLF scores on ICU admission were 27, 28, 14, and 54, respectively. ICU and hospital mortality rates were 33.0% and 49.2%, respectively. While median FB at 3 days post ICU admission (+5.46 l vs. +6.62 l; P = 0.74) was not associated with hospital mortality, higher median FB at 7 days post ICU admission (+13.50 l vs. +6.90 l; P = 0.036) was associated with higher hospital mortality. This association remained significant (OR 95%CI = 1.04 [1.01;1.07] per each l) after adjustment for confounders (age, ascites, infection, lactate, and number of organ failures). CONCLUSIONS: FB may be a therapeutic target that helps to improve the outcomes of patients with acute-on-chronic liver failure. This data may inform future clinical trials.

Acute-on-chronic liver failure syndrome - clinical results from an intensive care unit in a liver transplant center. / Síndrome da doença hepática crônica agudizada - resultados clínicos de uma unidade de terapia intensiva em centro de transplante hepático.

OBJECTIVE: To characterize a cohort of acute-on-chronic liver failure patients in Intensive Care and to analyze the all-cause 28-day mortality risk factors assessed at ICU admission and day 3. METHODS: This was a retrospective cohort study of consecutive patients admitted to the intensive care unit between March 2013 and December 2016. RESULTS: Seventy-one patients were included. The median age was 59 (51 - 64) years, and 81.7% of patients were male. Alcohol consumption alone (53.5%) was the most frequent etiology of cirrhosis and infection (53.5%) was the most common acute-on-chronic liver failure precipitating event. At intensive care unit admission, the clinical severity scores were APACHE II 21 (16 - 23), CLIF-SOFA 13 (11 - 15), Child-Pugh 12 (10 - 13) and MELD 27 (20 - 32). The acute-on-chronic liver failure scores were no-acute-on-chronic liver failure: 11.3%; one: 14.1%; two: 28.2% and three: 46.5%; and the number of organ failures was one: 4.2%; two: 42.3%; three: 32.4%; four: 16.9%; and five: 4.2%. Liver transplantation was performed in 15.5% of patients. The twenty-eight-day mortality rate was 56.3%, and the in-ICU mortality rate was 49.3%. Organ failure at intensive care unit admission (p = 0.02; OR 2.1; 95%CI 1.2 - 3.9), lactate concentration on day 3 (p = 0.02; OR 6.3; 95%CI 1.4 - 28.6) and the international normalized ratio on day 3 (p = 0.03; OR 10.2; 95%CI 1.3 - 82.8) were independent risk factors. CONCLUSION: Acute-on-chronic liver failure patients presented with high clinical severity and mortality rates. The number of organ failures at intensive care unit admission and the lactate and international normalized ratio on day 3 were independent risk factors for 28-day mortality. We consider intensive care essential for acute-on-chronic liver failure patients and timely liver transplant was vital for selected patients.

Massive organ embolization from primary aortic thrombosis.

A 49-year-old woman was hospitalized for acute left foot arterial ischemia. Arterial Doppler revealed occlusion of the dorsalis pedis and posterior tibial arteries. A computed tomography angiography performed to assess abdominal pain showed hepatic, splenic, renal and pancreatic infarctions. A splenic artery embolism and a small aortic wall thrombus at the celiac trunk were identified. No radiological signs of aortic atherosclerosis were found. No predisposing conditions for secondary aortic thrombosis or intracardiac embolic sources were detected. It was determined that primary aortic thrombosis, a rare though potentially serious condition, was to blame. Isolated aortic mural thrombosis therapy is not well established, although systemic anticoagulation, thrombolysis, thromboaspiration, endovascular stent grafting and surgical thrombectomy have been attempted with varying success. In our patient, systemic anticoagulation therapy was initiated and resulted in aortic thrombus resolution. Close clinical follow-up is crucial, as the aortic thrombus can recur despite anticoagulation and aggressive control of the atherosclerotic risk factors.

Acute-on-Chronic Liver Failure: A Portuguese Single-Center Reference Review.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of a patient with cirrhosis, frequently associated with multi-organ failure and a high short-term mortality rate. We present a retrospective study that aims to characterize the presentation, evolution, and outcome of patients diagnosed with ACLF at our center over the last 3 years, with a comparative analysis between the group of patients that had ACLF precipitated by infectious insults of bacterial origin and the group of those with ACLF triggered by a nonbacterial infectious insult; the incidence of acute kidney injury and its impact on the prognosis of ACLF was also analyzed. Twenty-nine patients were enrolled, the majority of them being male (89.6%), and the mean age was 53 years. Fourteen patients (48.3%) developed ACLF due to a bacterial infectious event, and 9 of them died (64.2%, overall mortality rate 31%); however, no statistical significance was found (p < 0.7). Of the remaining 15 patients (51.7%) with noninfectious triggers, 11 died (73.3%, overall mortality rate 37.9%); again there was no statistical significance (p < 0.7). Twenty-four patients (83%) developed acute kidney injury (overall mortality rate 65.5%; p < 0.022) at the 28-day and 90-day follow-up. Twelve patients had acute kidney injury requiring renal replacement therapy (41.37%; overall mortality rate 37.9%; p < 0.043). Hepatic transplant was performed in 3 patients, with a 100% survival at the 28-day and 90-day follow-up (p < 0.023). Higher grades of ACLF were associated with increased mortality (p < 0.02; overall mortality 69%). CONCLUSIONS: ACLF is a heterogeneous syndrome with a variety of precipitant factors and different grades of extrahepatic involvement. Most cases will have some degree of renal dysfunction, with an increased risk of mortality. Hepatic transplant is an efficient form of therapy for this syndrome.

A Doença Hepática Crónica Agudizada/Falência é um síndrome caracterizado por uma deterioração aguda de um doente com cirrose, frequentemente associada com falência multiorgânica e elevada mortalidade a curto prazo. Apresentamos estudo retrospetivo que teve como objetivo caracterizar a apresentação, evolução e prognóstico de doentes diagnosticados com Doença Hepática Crónica Agudizada/Falência no nosso Centro nos últimos 3 anos, comparando o grupo de doentes que tiveram Doença Hepática Crónica provocada por infeções bacterianas e os doentes com Doença Hepática Crónica Agudizada/Falência desencadeada por precipitantes que não a infeção bacteriana; foi também analisada a incidência de lesão renal aguda e o seu impacto no prognóstico na Doença Hepática Crónica Agudizada/Falência. Vinte e nove doente foram incluídos no estudo, a maioria do género masculino (89.6%), idade media de 53 anos. Catorze doentes (48.3%) desenvolveram Doença Hepática Crónica Agudizada devido a infeção bacteriana, 9 dos quais faleceram (64.2%, mortalidade global 31%), contudo, sem significado estatístico (p < 0.7); dos restantes 15 (51.7%) sem infeção bacteriana, 11 faleceram (73.3%, mortalidade global 37.9%), também sem significado estatístico (p < 0.7%). Vinte e quatro doentes (83%) desenvolveram lesão renal, mortalidade global de 65.5% (p < 0.022) aos 28 e 90 dias de seguimento. Doze doentes desenvolveram lesão renal aguda com necessidade de terapêutica de substituição da função renal (41.37%), mortalidade global de 37.9% (p < 0.043). O transplante hepático foi realizado em 3 doentes, com uma sobrevida de 100% aos 28 e 90 dias de seguimento (p < 0.023); Graus elevados de Doença Hepática Crónica Agudizada estão associadas a mortalidade mais elevada (p < 0.02); mortalidade global de 69%. CONCLUSIONS: A Doença Hepática Crónica Agudizada é um síndrome heterogéneo, com uma variedade de fatores precipitantes e diferentes graus de envolvimento extra-hepático; a maioria das situações estará associada a disfunção renal, com aumento do risco de mortalidade; O transplante hepático será uma eficaz de tratamento deste síndrome.

Acute liver failure: An up-to-date approach.

Acute liver failure is a rare but potentially devastating disease. Throughout the last few decades, acute liver failure outcomes have been improving in the context of the optimized overall management. This positive trend has been associated with the earlier recognition of this condition, the improvement of the intensive care unit management, and the developments in emergent liver transplantation. Accordingly, we aimed to review the current diagnostic and therapeutic approach to this syndrome, especially in the intensive care unit setting.

Síndrome da doença hepática crônica agudizada - resultados clínicos de uma unidade de terapia intensiva em centro de transplante hepático / Acute-on-chronic liver failure syndrome - clinical results from an intensive care unit in a liver transplant center

RESUMO Objetivo: Caracterizar uma coorte de pacientes com insuficiência hepática crônica agudizada em unidade de terapia intensiva e analisar os fatores de risco da mortalidade global aos 28 dias presentes no dia da admissão e no dia 3. Métodos: Estudo de coorte retrospectiva de pacientes consecutivamente admitidos à unidade de terapia intensiva entre março de 2013 e dezembro de 2016. Resultados: Incluímos 71 pacientes com idade mediana de 59 (51 - 64) anos, sendo 81,7% do sexo masculino. Consumo de álcool isoladamente (53,5%) foi a etiologia mais frequente de cirrose, e infecção (53,5%) foi o evento que mais frequentemente precipitou a agudização da insuficiência hepática crônica. No momento da admissão à unidade de terapia intensiva, os escores de severidade foram: APACHE II 21 (16 - 23), CLIF-SOFA 13 (11 - 15), Child-Pugh 12 (10 - 13) e MELD 27 (20 - 32). Dentre os indivíduos, 14,1% tiveram escore 1 de insuficiência hepática crônica agudizada, 28,2% pontuaram 2, 64,5% pontuaram 3, e 11,3% se apresentaram sem insuficiência hepática crônica agudizada. Sobre o número de falências de órgãos, 4,2% tiveram um órgão; 42,3%, dois órgãos; 32,4%, três órgãos; 16,9%, quatro órgãos; e 4,2% cinco órgãos. Foi realizado transplante hepático em 15,5% dos pacientes. A taxa de mortalidade aos 28 dias foi de 56,3%, e a taxa de mortalidade na unidade de terapia intensiva foi de 49,3%. Foram fatores independentes de risco: falências do órgãos quando da admissão à unidade de terapia intensiva (p = 0,02; RC 2,1; IC95% 1,2 - 3,9), concentração de lactato em sangue arterial no dia 3 (p = 0,02; RC 6,3; IC95% 1,4 - 28,6) e RC internacional no dia 3 (p = 0,03; RC 10,2; IC95% 1,3 - 82,8). Conclusão: Pacientes com insuficiência hepática crônica agudizada apresentaram elevados níveis de severidade e taxa de mortalidade. O número de falências de órgãos no momento da admissão à unidade de terapia intensiva e o nível de lactato, assim como a razão normalizada internacional no dia 3 de permanência na unidade foram fatores independentes de risco para a mortalidade ao 28º dia. Consideramos que a terapia intensiva é essencial para pacientes com insuficiência hepática crônica agudizada, e a realização de um transplante hepático em tempo adequado foi vital para os pacientes selecionados.

ABSTRACT Objective: To characterize a cohort of acute-on-chronic liver failure patients in Intensive Care and to analyze the all-cause 28-day mortality risk factors assessed at ICU admission and day 3. Methods: This was a retrospective cohort study of consecutive patients admitted to the intensive care unit between March 2013 and December 2016. Results: Seventy-one patients were included. The median age was 59 (51 - 64) years, and 81.7% of patients were male. Alcohol consumption alone (53.5%) was the most frequent etiology of cirrhosis and infection (53.5%) was the most common acute-on-chronic liver failure precipitating event. At intensive care unit admission, the clinical severity scores were APACHE II 21 (16 - 23), CLIF-SOFA 13 (11 - 15), Child-Pugh 12 (10 - 13) and MELD 27 (20 - 32). The acute-on-chronic liver failure scores were no-acute-on-chronic liver failure: 11.3%; one: 14.1%; two: 28.2% and three: 46.5%; and the number of organ failures was one: 4.2%; two: 42.3%; three: 32.4%; four: 16.9%; and five: 4.2%. Liver transplantation was performed in 15.5% of patients. The twenty-eight-day mortality rate was 56.3%, and the in-ICU mortality rate was 49.3%. Organ failure at intensive care unit admission (p = 0.02; OR 2.1; 95%CI 1.2 - 3.9), lactate concentration on day 3 (p = 0.02; OR 6.3; 95%CI 1.4 - 28.6) and the international normalized ratio on day 3 (p = 0.03; OR 10.2; 95%CI 1.3 - 82.8) were independent risk factors. Conclusion: Acute-on-chronic liver failure patients presented with high clinical severity and mortality rates. The number of organ failures at intensive care unit admission and the lactate and international normalized ratio on day 3 were independent risk factors for 28-day mortality. We consider intensive care essential for acute-on-chronic liver failure patients and timely liver transplant was vital for selected patients.