Patients with acute decompensated cirrhosis or chronic acute liver failure (ACLF) often require ICU admission for organ support. It is estimated that 2% to 3% of patients admitted to the ICU have a history of cirrhosis. Mortality rates in patients with ACLF admitted to the ICU are as high as 36% to 89%, depending on the severity of the ACLF grade and organ failure score.
Recent studies have shown that short-term in-hospital survival has improved in patients with cirrhosis over the past decade. One small retrospective study found that patients with ACLF admitted to the ICU had similar short-term outcomes compared to those without liver disease when disease severity was matched.
However, current data on outcomes in critically ill patients with cirrhosis or ACLF are mainly focused on short-term outcomes such as 30-day and 90-day mortality, with few data on long-term outcomes. In addition, the data currently available are mainly from specialized liver transplant centers, which limits the generalizability of the findings, as most patients with critically ill cirrhosis are likely to be treated outside of these centers.
Currently, there are no Europe-wide information on the characteristics and survival outcomes of patients admitted to different ICUs with cirrhosis. Although ACLF is considered to be an important predictor of mortality, there may be other factors that influence the outcome of these patients, such as patient characteristics, complications, predisposing factors, organ failure, etc.
近期， 荷兰伊拉斯姆斯医学中心的Jubi de Haan教授团队于Journal of Hepatology发表了研究One-year transplant-free survival following hospital discharge after ICU Admission for ACLF in the Netherlands，评估了在荷兰所有ICU收治的危重病肝硬化患者出院后1年的无移植死亡率，并评估了ICU入院时的ACLF严重程度是否是患者预后不佳的独立风险因素。
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Research Methods:
We conducted a nationwide observational cohort study of patients admitted to the ICU in the Netherlands between 2012 and 2020 with a history of cirrhosis or complications of cirrhosis of portal hypertension. The effect of ACLF severity on 1-year transplant-free survival at discharge in patients admitted to the ICU was assessed using an unadjusted Kaplan-Meier (KM) survival curve and an adjusted Cox proportional hazards model.
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Findings:
1) Baseline characteristics of the patient
A total of 3035 patients were included in the study cohort. Thirty-one patients (11.9%) did not have ACLF, 227 patients (7.5%) had ACLF grade 1 at ICU admission, 628 patients (20.7%) had ACLF grade 2, and 1819 patients (59.9%) had ACLF grade 3.
The majority of patients were male (66.6%), with a median age of 61 years (IQR 52-67), and a BMI above 30 kg/m2 in 22.8%. A total of 49.7% of patients had one or more comorbidities, with diabetes mellitus (24.7%) being the most prevalent.
The majority (54.3%) were hospitalized in non-academic hospitals. Confirmed infection (67.1%) or sepsis (76.4%) were the most common at ICU admission, followed by acute kidney injury (43.6%), gastrointestinal bleeding (29.7%), and hepatic encephalopathy (13.1%). The proportion of patients requiring mechanical ventilation or vasoactive drugs increases with the severity of ACLF. Higher ACLF grades are associated with higher serum creatinine and bilirubin levels. In addition, higher MELD scores were associated with higher ACLF grades.
2) Outcomes of 3035 ICU patients
The overall mortality rate in the ICU was 42.1% and the in-hospital mortality rate was 53.2%. Both ICU and in-hospital mortality increased with the severity of ACLF (P < 0.001). The estimated overall transplant-free survival probability after ICU admission was 0.43 (0.42-0.45) at day 28, 0.37 (0.35-0.38) at day 90, and 0.29 (0.28-0.31) at 1 year.
and 3) factors associated with in-hospital mortality
As the severity of ACLF increases, so does the risk of in-hospital mortality. The adjusted in-hospital mortality odds ratios were 2.52 (95% CI 1.55-4.11), 4.89 (95% CI 3.23-7.40), and 11.29 (95% CI 7.34-17.35), respectively, for patients with ACLF-1, ACLF-2, and ACLF-3 compared with patients without ACLF. Infection, sepsis, and a higher MELD score at ICU admission are associated with higher in-hospital mortality. Male sex, chronic renal failure, or dialysis are associated with lower in-hospital mortality.
4) Transplant-free survival at 1 year after discharge
A total of 1420 patients (46.8%) survived ICU admission. Within one year of ICU admission, 35 patients (1.2%) underwent liver transplantation (LT), of which 12 (0.4%) received transplantation during initial hospitalization and 7 (1.9%) received liver transplantation without ACLF after discharge. As the severity of ACLF increased, the proportion of patients receiving transplantation decreased (P = 0.0074).
The overall probability of transplant-free survival at one year after discharge was 0.61 (95% CI 0.59-0.64). The one-year transplant-free survival rate for patients without ACLF was 0.71 (95% CI 0.66-0.76), 0.60 (95% CI 0.52-0.68) for grade 1, 0.65 (95% CI 0.61-0.70) for grade 2, and 0.53 (95% CI 0.49-0.58) for grade 3.
5) Factors associated with liver transplantation or death
In ICU survivors, multivariate Cox regression analyses were performed to identify factors associated with an increased risk of liver transplantation or death after ICU admission and within one year of discharge.
The adjusted hazard ratios for liver transplantation or death within one year of ICU admission were 1.49 (95% CI 1.15-1.93), 1.84 (95% CI 1.49-2.28), and 3.11 (95% CI 2.50-3.87), respectively, for patients with ACLF-1, ACLF-2, and ACLF-3 compared with patients without ACLF.
Increasing age, presence of malignancy, and higher MELD scores at ICU admission are associated with increased hazard ratios, whereas men and chronic renal failure or dialysis are associated with a reduced risk of liver transplantation or death within one year of ICU admission.
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Conclusions of the study
In this national observational cohort study of outcomes in all ICU admissions in the Netherlands, we have four main findings.
First, the majority of ICU admissions include patients with ACLF grade 3 who exhibit end-stage organ failure.
Second, higher ACLF and MELD scores were independently associated with in-hospital mortality.
Third, in the subgroup of hospitalized surviving patients, there was no independent correlation between ACLF grade and 1-year transplant-free survival at discharge at ICU admission. Age, malignancy, and MELD score were closely related to transplant-free survival at 1 year after discharge.
Finally, our findings suggest that only a small percentage of patients admitted to the ICU for ACLF undergo liver transplantation within one year.
Ponder
This study found that the severity of ACLF assessed at ICU admission did not have a significant effect on one-year transplant-free survival after discharge in those patients who survived hospitalization. We found that age, presence of malignancy, and severity of liver disease played a more prominent role in influencing transplant-free survival at one year after discharge. These findings highlight the need to focus on other complications and severity of liver disease when assessing the long-term prognosis of critically ill patients with cirrhosis. In addition, only a small percentage of patients admitted to the ICU for ACLF receive liver transplantation within one year. Future studies should explore whether improving the referral, screening, and evaluation process for liver transplantation can improve long-term outcomes for people with ACLF.
文献索引：Haan D J ,Termorshuizen F ,Keizer D N , et al. One-year transplant-free survival following hospital discharge after ICU Admission for ACLF in the Netherlands. [J]. Journal of hepatology,2024.
Source: Yimaitong Hepatology