Allocation of patients with liver cirrhosis and organ failure to intensive care: Systematic review and a proposal for clinical practice

AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit(ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in Pub Med, MEDLINE and EMBASE databases. The search includes studies on hospitalized patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature on this topic is scarce and no studies specifically address allocation of patients with liver cirrhosis to ICU. Throughout the literature, there is consensus that selection criteria for ICU admission should be developed and validated for this group of patients and multidisciplinary approach is mandatory. Based on current available data we developed an algorithm, to determine if a patient is candidate to intensive care if needed, based on three scoring systems: premorbid Child-Pugh Score, Model of End stage Liver Disease score and the liver specific Sequential Organ Failure Assessment score.CONCLUSION: There are no established systems for allocation of patients with liver cirrhosis to the ICU and no evidence-based recommendations can be made.     

Acute-on-chronic liver failure: Controversies and consensus

Acute-on-chronic liver failure (ACLF) is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease. Consequences include high short-term morbidity, mortality, and healthcare resource utilisation. ACLF encompasses a dysregulated, systemic inflammatory response, which can precipitate extra hepatic organ failures. Common precipitants include infection, alcoholic hepatitis, and reactivation of viral hepatitis although frequently no cause is identified. Heterogenous definitions, diagnostic criteria, and treatment guidelines, have been proposed by international hepatology societies. This can result in delayed or missed diagnoses of ACLF, significant variability in clinical management, and under-estimation of disease burden. Liver transplantation may be considered but the mainstay of treatment is organ support, often in the intensive care unit. This review will provide clarity around where are the controversies and consensus in ACLF including: Epidemiology and resource utilisation, key clinical and diagnostic features, strategies for management, and research gaps.     

Organ system failure scoring system can predict hospital mortality in critically ill cirrhotic patients

GOALS: This study was conducted to assess and compare the accuracy of Child-Pugh classification and organ system failure (OSF) scores, obtained on the first day of ICU admission, in predicting the hospital mortality in critically ill cirrhotic patients. BACKGROUND: Cirrhotic patients admitted to the medical intensive care unit (ICU) are associated with high mortality rates. The prognosis of critically ill cirrhotic patients is determined by the extent of hepatic and extrahepatic organ dysfunction. STUDY: A total of 111 patients diagnosed with liver cirrhosis were admitted to medical ICU from July 2001 to June 2002. Information considered necessary to compute the Child-Pugh and OSF scores on the first day of ICU admission was prospectively collected. RESULTS: The overall hospital mortality rate was 64.9%. Liver disease was most commonly attributed to hepatitis B viral infection. The OSF scores demonstrate a good fit using the Hosmer and Lemeshow goodness-of-fit test. Meanwhile, by using the areas under receiver operating characteristic (AUROC) curve, the OSF scores demonstrated an excellent discriminative power (AUROC 0.901), whereas the performance of Child-Pugh scores is clearly poorer (AUROC 0.748). CONCLUSION: This investigation confirms that the prognosis for cirrhotic patients admitted to ICU is grave. The OSF score is a simple, reproducible, and easily applied tool with excellent prognostic abilities that can provide objective information for patients' families and physicians and supplement the clinical judgment of prognosis.     

Acute respiratory failure complicating advanced liver disease

Advanced liver disease is associated with hypoxemia and respiratory failure by various mechanisms. Patients with cirrhosis are especially prone to episodes of decompensation requiring intensive care unit admission and management. Such patients may already be in acute liver failure or have decompensated due to a concurrent illness such as spontaneous bacterial peritonitis, sepsis, encephalopathy, varices, or hepatorenal syndrome. Acute respiratory distress syndrome is one of the main reasons for intensive care unit admission and mortality. Overall, critically ill cirrhotic patients frequently progress to multiorgan failure requiring mechanical ventilation. Caring for such patients is therefore understandably complex and extremely challenging. Patients with end-stage liver disease are especially at risk for developing acute respiratory failure and hypoxemia secondary to hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. They should therefore be screened for these conditions because failure to recognize and adequately treat these serious complications of cirrhosis may have devastating consequences. This article is based on a review of the current literature on how to approach and manage acute respiratory failure in advanced liver disease, which is important to intensivists, anesthesiologists, and physicians as a whole.     

Coronavirus Disease 2019 and Liver Injury: A Retrospective Analysis of Hospitalized Patients in New York City

Background and AimsCoronavirus disease 2019 (COVID-19) is a global threat, affecting more than 100 million people and causing over 2 million deaths. Liver laboratory test abnormalities are an extrapulmonary manifestation of COVID-19, yet characterization of hepatic injury is incomplete. Our objective was to further characterize and identify causes of liver injury in patients with COVID-19.MethodsWe conducted a retrospective cohort study of 551 patients hospitalized with COVID-19 at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center between March 1, 2020 and May 31, 2020. We analyzed patient demographics, liver laboratory test results, vital signs, other relevant test results, and clinical outcomes (mortality and intensive care unit admission).ResultsAbnormal liver laboratory tests were common on hospital admission for COVID-19 and the incidence increased during hospitalization. Of those with elevated serum alanine aminotransferase and/or alkaline phosphatase activities on admission, 58.2% had a cholestatic injury pattern, 35.2% mixed, and 6.6% hepatocellular. Comorbid liver disease was not associated with outcome; however, abnormal direct bilirubin or albumin on admission were associated with intensive care unit stay and mortality. On average, patients who died had greater magnitudes of abnormalities in all liver laboratory tests than those who survived. Ischemic hepatitis was a mechanism of severe hepatocellular injury in some patients.ConclusionsLiver laboratory test abnormalities are common in hospitalized patients with COVID-19, and some are associated with increased odds of intensive care unit stay or death. Severe hepatocellular injury is likely attributable to secondary effects such as systemic inflammatory response syndrome, sepsis, and ischemic hepatitis.     

Viral hepatitis C in patients with renal disease

Hepatitis C in patients with chronic renal failure. Infection with hepatitis C virus (HCV) is a common complication in those patients under chronic dialysis. Prevalence varies from 8% to 65 percent. Immunization against hepatitis A and B for renal patients is always recommended, especially in countries with high prevalence of this type of hepatitis. Interferon as the only antiviral treatment is recommended for patients with chronic renal failure and chronic hepatitis who depend on dialysis. Viral hepatitis is the first cause of morbidity and mortality among renal recipients. Prevalence varies between 4 and 38%, depending on the geographic area. Infection with HCV usually begins before the transplant, although the patient is sometimes infected during the transplant because the donor organs carry the virus. The chronic HCV infection dosen't seem to affect the survival rate of the patient or the organ, compared to the survival rate in patients without the infection. Chronic hepatitis C without cirrhosis is not a contraindication for renal transplant, but cirrhosis is. Liver failure is the cause of death in 8-28% of renal transplant recipients infected with hepatitis C virus.     

Outcome predictors of cirrhosis patients admitted to the intensive care unit

OBJECTIVE: To evaluate outcome predictors of patients with cirrhosis admitted to an intensive care unit (ICU). METHODS: One hundred and twenty-nine consecutive patients with cirrhosis admitted to the ICU at a tertiary care transplant centre in Saudi Arabia between March 1999 and December 2000 were entered prospectively in an ICU database. Liver transplantation patients and readmissions to the ICU were excluded. The following data were documented: demographic features, severity of illness measures, parameters of organ failure, presence of gastrointestinal bleeding, and sepsis. The need for mechanical ventilation, renal replacement therapy and pulmonary artery catheter placement was recorded. The primary endpoint was hospital outcome. RESULTS: Cirrhotic patients admitted to the ICU had high hospital mortality (73.6%). However, the actual mortality was not significantly different from the predicted mortality using prediction systems. There was an association between the number of organs failing and mortality. Coma and acute renal failure emerged as independent predictors of mortality. All patients who were monitored with pulmonary artery catheterisation in this study died. Patients requiring mechanical ventilation and renal replacement therapy had very high mortalities (84% and 89%, respectively). All 13 cirrhotic patients admitted to ICU immediately post-cardiac arrest in this study died. CONCLUSIONS: Cirrhotic patients admitted to ICU have a poor prognosis, especially when admitted with coma, acute renal failure or post-cardiac arrest. The consistently poor prognosis associated with certain ICU interventions should raise new awareness regarding limitations of medical therapy. These mortality statistics compel a critical re-examination of uniformly aggressive life support for the critically ill cirrhotic patient, a percentage of whom will not benefit from invasive measures.     

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

Relative adrenal insufficiency is frequent in patients with severe sepsis and is associated with hemodynamic instability, renal failure, and increased mortality. This study prospectively evaluated the effects of steroids on shock resolution and hospital survival in a series of 25 consecutive patients with cirrhosis and septic shock (group 1). Adrenal function was evaluated by the short corticotropin test within the first 24 hours of admission. Patients with adrenal insufficiency were treated with stress doses of intravenous hydrocortisone (50 mg/6 h). Data were compared to those obtained from the last 50 consecutive patients with cirrhosis and septic shock admitted to the same intensive care unit in whom adrenal function was not investigated and who did not receive treatment with steroids (group 2). Incidence of adrenal insufficiency in group 1 was 68% (17 patients). Adrenal dysfunction was frequent in patients with advanced cirrhosis (Child C: 76% vs. Child B: 25%, P = .08). Resolution of septic shock (96% vs. 58%, P = .001), survival in the intensive care unit (68% vs. 38%, P = .03), and hospital survival (64% vs. 32%, P = .003) were significantly higher in group 1. The main causes of death in group 1 were hepatorenal syndrome or liver failure (7 of 9 patients). In contrast, refractory shock caused most of the deaths in group 2 (20 of 34 patients). In conclusion, relative adrenal insufficiency is very frequent in patients with advanced cirrhosis and septic shock. Hydrocortisone administration in these patients is associated with a high frequency of shock resolution and high survival rate.     

Acute-on-chronic Liver Failure

Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame. ACLF is characterized by a state of deregulated inflammation. Initial cytokine burst presenting as SIRS, progression to CARS and associated immunoparalysis leads to sepsis and multi-organ failure. Early identification of the acute insult and mitigation of the same, use of nucleoside analogue in HBV-ACLF, steroid in severe alcoholic hepatitis, steroid in severe autoimmune hepatitis and/or bridging therapy lead to recovery, with a 90-day transplant-free survival rate of up to 50 %. First-week presentation is crucial concerning SIRS/sepsis, development, multiorgan failure and consideration of transplant. A protocol-based multi-disciplinary approach including critical care hepatology, early liver transplant before multi-organ involvement, or priority for organ allocation may improve the outcome. Presentation with extrahepatic organ involvement or inclusion of sepsis as an acute insult in definition restricts the therapy, i.e., liver transplant or bridging therapy, and needs serious consideration. Augmentation of regeneration, cell-based therapy, immunotherapy, and gut microbiota modulation are the emerging areas and need further research.     

慢加急性肝衰竭的国际标准与临床管理优化

慢加急性肝衰竭(ACLF)是明显区别于急性肝衰竭和单纯肝硬化急性失代偿的一类临床群体。起病于慢性肝病基础上,急性进展可出现肝脏以及肝外多器官衰竭,短期死亡率高,已成为全球的经济卫生负担。近年来,几大国际性肝病学会提出了不同的ACLF诊断标准并相继发布了各自定义下的ACLF诊疗共识或综述,在慢性肝病、急性损伤、器官衰竭等方面的理解存在较大分歧。目前我国在ACLF管理各个关键环节,如肝移植、ICU和姑息治疗方面数据仍较为有限,在全球ACLF诊断尚未达成共识的背景下,需进一步加强国际已有标准和证据的借鉴运用以及国内循证医学证据的积累。     

Selection of patients for liver transplantation

Liver transplantation is now available world-wide. It plays an important role in the treatment of irreversible acute and chronic liver disease (CLD). Selection of patients for liver transplantation is subject to many factors including economic, cultural, availability of donor organs and degree of illness. This article looks at seven general considerations for receipients of liver transplantation. As well, disease-specific criteria are investigated and include such areas as cirrhosis due to chronic hepatitis B virus (HBV), hepatitis C virus (HCV) positive cirrhosis, fulminant hepatic failure (FHF), malignancy, alcoholic liver disease (ALD), metabolic conditions and Budd–Chiari syndrome. If hepatic transplantation surivival rates were to approach 95%, the relative risk ratio between transplantation and conservative therapy would increase. At present an 80% 1–5 year survival rate following transplantation should be expected.     

Akut-auf-chronisches Leberversagen

Acute-on-chronic liver failure (ACLF) represents a relatively new entity for which the diagnostic criteria have only recently been defined. It describes an acute hepatic decompensation of a preexisting chronic liver disease with subsequent organ failure and very poor stage-dependent short-term survival. Acute decompensated cirrhosis and acute liver failure are conditions that must be clearly differentiated from ACLF. Bacterial infections are common precipitating events and trigger a frequently devastating state of immune dysregulation leading to systemic inflammation. The sequential succession of hyperinflammation and immune paralysis often results in death due to severe organ failure and secondary infections. Renal dysfunction is a critical factor for the limited prognosis because renal failure alone already results in a significantly worse 30-day mortality. Failure of two or more organs is associated with a fatal outcome in more than 50?% of cases. Apart from treating the underlying event and intensive care measures, liver transplantation is an effective therapeutic tool but its use is restricted by limited organ availability. Experimental therapeutic methods including albumin dialysis and the administration of recombinant granulocyte colony stimulating factor (G-CSF) warrant further investigation.     

Characteristics and outcomes of chronic liver disease patients with acute deteriorated liver function by severity of underlying liver disease

AIM: To analyze characteristics and outcome of patients with acute-on-chronic liver failure(ACLF) according to the severity of underlying liver disease. METHODS: One hundred and sixty-seven adult patients with chronic liver disease and acute deteriorated liver function, defined by jaundice and coagulopathy, were analyzed. Predisposition, type of injury, response, organ failure, and survival were analyzed and compared between patients with non-cirrhosis(type A), cirrhosis(type B) and cirrhosis with previous decompensation(type C).RESULTS: The predisposition was mostly hepatitis B in type A, while it was alcoholic liver disease in typesB and C. Injury was mostly hepatic in type A, but was non-hepatic in type C. Liver failure, defined by CLIF-SOFA, was more frequent in types A and B, and circulatory failure was more frequent in type C. The 30-d overall survival rate(85.3%, 81.1% and 83.7% for types A, B and C, respectively, P = 0.31) and the 30-d transplant-free survival rate(55.9%, 65.5% and 62.5% for types A, B and C, respectively P = 0.33) were not different by ACLF subtype, but 1-year overall survival rate were different(85.3%, 71.7% and 58.7% for types A, B and C, respectively, P = 0.02).CONCLUSION: There were clear differences in predisposition, type of injury, accompanying organ failure and long-term mortality according to spectrum of chronic liver disease, implying classifying subtype according to the severity of underlying liver disease is useful for defining, clarifying and comparing ACLF.     

Cross‐sectional and dynamic change of serum metabolite profiling for Hepatitis B‐related acute‐on‐chronic liver failure by UPLC/MS

Summary Acute‐on‐chronic liver failure(ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function and results in the failure of one or more organs with high short‐term mortality. The focus of this study was to discover noninvasive and reliable biomarkers for the diagnosis and prognosis of hepatitis B‐related ACLF. Ultra‐performance liquid chromatography–mass spectrometry (UPLC/MS) was used to analyse serum metabolites of 28 patients with hepatitis B‐related ACLF, 35 patients with Child‐Pugh A cirrhosis, 30 patients with chronic hepatitis B and 35 healthy volunteers (HS). Characteristic metabolites were screened, identified and dynamically tracked to investigate their value for diagnosis and prognosis. After comparing serum metabolic profile of hepatitis B‐related ACLF and Child‐Pugh A cirrhosis, 99 characteristic metabolites were selected, and 38 of them were identified. Dynamic tracking model demonstrated that 17 metabolites were related to prognosis of hepatitis B‐related ACLF, and there were also 11 metabolites which improved with treatment in the survival group. The correlations between these characteristic metabolites and the model for end‐stage liver disease score were strong. These observations contributed to the investigation of the mechanisms of hepatitis B‐related ACLF manifestation and progression on the metabolic level, and they provided information for the identification of biomarkers for the diagnosis and prognosis of hepatitis B‐related ACLF.     

Predictive factors for 28-day mortality in acute-on-chronic liver failure patients admitted to the intensive care unit

BackgroundAcute-on-chronic liver failure (ACLF) is an entity comprising an acute deterioration of liver function in cirrhotic patients, associated with organ failure(s) and high short-term mortality. We aimed to identify predictive factors for short-term mortality in patients admitted with ACLF that may benefit most from liver transplantation.MethodsRetrospective analysis of patients admitted in ACLF to a tertiary intensive care unit between 2013 and 2017 was performed. The EASL-CLIF acute-on-chronic liver failure in cirrhosis (CANONIC) criteria were used to define ACLF grade. Multivariable analysis using 28-day mortality as an end-point was performed, including severity-of-disease scores and clinical parameters.ResultsSeventy-seven patients were admitted in ACLF over the study period. The commonest aetiology of liver disease was alcohol related 52/77(68%) and the commonest precipitant of ACLF was variceal haemorrhage 38/77(49%). Overall 28-day mortality was 42/77(55%) [ACLF-(grade)1:3/42(7%); ACLF-2:10/42(24%); and, ACLF-3:29/42(69%);p = 0.002]. On multivariable analysis MELD ≥ 26 [odds ratio(OR) = 11.559; 95% confidence interval(CI):2.820–47.382;p = 0.001], ACLF-3 (OR = 3.287; 95%CI:1.047–10.325;p = 0.042) at admission and requirement for renal replacement therapy (OR = 5.348; 95%CI:1.385–20.645;p = 0.015) were independently associated with 28-day mortality.ConclusionPatients admitted with ACLF to intensive care have a high mortality rate. Defined early thresholds at admission can identify patients at the highest risk that may benefit most from liver transplantation.     

Acute hepatic failure: a Western perspective

Acute hepatic failure (AHF) is an uncommon, devastating syndrome, which results in death or the need for liver transplantation in more than 50% of cases. While AHF has numerous causes, most cases are due to viral hepatitis and drug toxicity or idiosyncratic reactions. A significant group with indeterminate causation remains, despite careful investigation. In many of these cases a viral aetiology is suspected, although yet not proven. Major differences exist in the aetiology of AHF between the West and Eastern countries. A wider range of aetiologies exists in the West. Common causes include acetaminophen toxicity and idiosyncratic drug reactions, while viral hepatitis is less frequent. Hepatitis E infection is rarely seen in Western countries in contrast to its high prevalence in the East. The mainstay of AHF management is supportive care in an intensive care unit. Liver transplantation is now the standard of care in many Western liver units for individuals who have a less than 20% probability of survival. Lack of availability of donor livers at short notice remains a significant problem. Methods of liver support used while waiting for a donor liver or for the native liver to regenerate include bioartificial livers, extracorporeal liver-assist devices, extracorporeal whole organ perfusion (human and transgenic pig) and hepatocyte transplantation. The effectiveness of these methods remains unproven and awaits controlled clinical trials. Both transplantation and liver-support methods require specialized units and expensive and complicated equipment. Further research is necessary to identify modalities of therapy that would be effective as well as widely accessible.     

Liver transplantation

Liver transplantation represents the first choice treatment for patients with fulminant acute hepatitis and for patients with chronic liver disease and advanced functional failure. Patients in the waiting list for liver transplantation are classified according to the severity of their clinical conditions (evaluated using staging systems mostly based on hematochemical parameters related to liver function). This classification, together with the blood group and the body size compatibility, remains the main criterion for organ allocation. The main indications for liver transplantation are cirrhosis (mainly HCV-, HBV- and alcohol-related) and hepatocellular carcinoma emerging in cirrhosis in adult patients, biliary atresia and some inborn errors of metabolism in pediatric patients. In adults the overall 5-year survival ranges between 60 and 70%, in both American and European series. Even better results have been reported for pediatric patients: in fact, the 5-year survival rate for children ranges between 70 and 80% in the main published series. In this study we evaluated the main medical problems correlated with liver transplantation such as immunosuppressive treatment, acute and chronic rejection, infectious complications, the recurrence of the liver disease leading to transplantation, and cardiovascular and metabolic complications.     

Prognostic factors for intensive care unit admission, intensive care outcome, and post-intensive care survival in patients with de novo acute myeloid leukemia: a single center experience

Background

Acute myeloid leukemia is a life-threatening disease associated with high mortality rates. A substantial number of patients require intensive care. This investigation analyzes risk factors predicting admission to the intensive care unit in patients with acute myeloid leukemia eligible for induction chemotherapy, the outcome of these patients, and prognostic factors predicting their survival.

Design and Methods

A total of 406 consecutive patients with de novo acute myeloid leukemia (15–89 years) were analyzed retrospectively. Markers recorded at the time of diagnosis included karyotype, fibrinogen, C-reactive protein, and Charlson comorbidity index. In patients requiring critical care, the value of the Simplified Acute Physiology Score II, the need for mechanical ventilation, and vasopressor support were recorded at the time of intensive care unit admission. The independent prognostic relevance of the parameters was tested by multivariate analysis.

Results

Sixty-two patients (15.3%) required intensive care, primarily due to respiratory failure (50.0%) or life-threatening bleeding (22.6%). Independent risk factors predicting intensive care unit admission were lower fibrinogen concentration, the presence of an infection, and comorbidity. The survival rate was 45%, with the Simplified Acute Physiology Score II being the only independent prognostic parameter (P<0.05). Survival was inferior in intensive care patients compared to patients not admitted to an intensive care unit. However, no difference between intensive care and non-intensive care patients was found concerning continuous complete remission at 6 years or survival at 6 years in patients who survived the first 30 days after diagnosis (non-intensive care patients: 28%; intensive care patients: 20%, P>0.05).

Conclusions

Ongoing infections, low fibrinogen and comorbidity are predictive for intensive care unit admission in acute myeloid leukemia. Although admission was a risk factor for survival, continuous complete remission and survival of patients alive at day 30 were similar in patients who were admitted or not admitted to an intensive care unit.     

Liver transplantation: the Italian experience

BACKGROUND: Liver transplantation is the standard treatment for patients with end-stage liver disease no longer responsive to conventional medical treatment AIMS: To report the long-term experience of liver transplantation in Italy. PATIENTS AND METHODS: Data were obtained retrospectively by means of a multiple-item form collected from 15 Italian liver transplant centres. The filing centre was centralized. RESULTS: A total of 3323 liver transplants were performed on 3026 patients, with a cumulative proportional survival of 72.4%. Three, 5 and 10 years' patient survival rates were 72.3%, 68.8% and 61.3%, respectively. The most common indication for liver transplantation were hepatitis B virus (+/- hepatitis D virus)- and hepatitis C virus-related cirrhosis (59.4%). Excellent survival rates were observed particularly in controversial indications, such as alcoholic cirrhosis, hepatitis B virus-related cirrhosis and hepatocellular carcinoma. Retransplantation was required in 8.9% of the cases. The overall prevalence of acute cellular rejection episodes was 43.5%. In our study population, primary non-function and disease recurrence were the most common causes of graft failure (28.7% and 25.4%, respectively). Infections and/or sepsis were the most common causes of death after transplantation (42%). CONCLUSION: This study confirms that patients with controversial indications to liver transplantation such as alcoholic cirrhosis, HBV-related cirrhosis and hepatocellular carcinoma can achieve excellent survival when properly selected.