Characteristics of cirrhosis and ACLF hospitalization
The number of cirrhosis hospitalizations had increased every year from 2009 (n = 45,015) to 2013 (n = 58,113). Nearly a half of those hospitalizations were for alcoholic cirrhosis (48.6%) and the proportion for spontaneous bacterial peritonitis involvement was 29.2% of total hospitalizations. Among every discharge, the proportion who met the ACLF criteria increased almost double between 7.1% (n = 3,185) in 2009 and 13.2% (n = 7,666) in 2013. During the timeline of ACLF, there were no significant changes concerning patient characteristics comprising age, sex, hospital level as well as geographic distribution on hospitalized cirrhosis and ACLF patients.
Table 1 shows the patient demographic and disease characteristics of discharges which met the study inclusion criteria between 2009 and 2013.
Table 1
Demographic and Disease Characteristics of Hospitalized Patients with Cirrhosis and ACLF Between 2009 and 2013
Characteristic
|
|
|
All cirrhosis patients (including ACLF)
|
|
186,051
|
Age (mean ± sd)
|
|
52.1 ± 15.8
|
Male (%)
|
|
67
|
Cirrhosis etiology (%)
|
|
|
|
Viral
|
7
|
|
Alcohol
|
44
|
|
Nonalcohol/nonviral
|
49
|
Cirrhosis complications (%)
|
|
|
|
Hepatic encephalopathy
|
22
|
|
Esophageal varices
|
9
|
|
Hepatorenal syndrome
|
1
|
|
Spontaneous bacterial peritonitis
|
33
|
Sepsis (%)
|
|
8
|
Length of hospital stay (days) (mean ± sd)
|
|
6.4 ± 10.2
|
ACLF subgroup
|
|
22,950
|
Age (mean ± sd)
|
|
54.4 ± 14.2
|
Cirrhosis etiology (%)
|
|
|
|
Viral
|
19
|
|
Alcohol
|
41
|
|
Nonalcohol/nonviral
|
40
|
Rate of ACLF in cirrhosis (%)
|
|
12.3 (22950/186051)
|
Rate of ACLF in organ failure (%)
|
|
|
|
Respiratory
|
70
|
|
Cardiovascular
|
64
|
|
Renal
|
62
|
|
Cerebral
|
18
|
Sepsis (%)
|
|
27.9
|
Length of hospital stay (days) (mean ± sd)
|
|
8.7 ± 13.4
|
We identified 22,950 ACLF patients who satisfied study inclusion criteria. Overall, most ACLF patients were admitted in Northeastern and Central regions of Thailand, 10.8% were community hospital admissions (less than 120 beds), 37.8% were intermediate-level hospital admissions (121–500 beds) and 51.4% were referral hospital admissions (more than 500 beds). The mean age was 54 years, 67% were male, and 100% were Asian (Thai descent). The most common cirrhosis complication leading to hospitalization documented was spontaneous bacterial peritonitis, and this was followed by hepatic encephalopathy. The period of hospital stay remained fairly constant from 2009 to 2013, which was higher for ACLF (9 days) in comparison with cirrhosis without ACLF (4 days). Table 2illustrates the characteristics of ACLF patients hospitalized compared with those with cirrhosis.
Table 2
Characteristics of Patients Hospitalized with ACLF Versus Cirrhosis Without ACLF
Characteristic
|
|
Non-ACLF (Cirrhosis)
(n = 163,101)
|
ACLF
(n = 22,950)
|
Age (mean ± sd)
|
|
51.9 ± 15.9
|
53.7 ± 14.8
|
Male (%)
|
|
67
|
67
|
Hospital level (%)
|
|
|
|
|
Community hospital and Intermediate-level hospital
|
71
|
48
|
|
Referral hospital
|
29
|
52
|
Cirrhosis etiology (%)
|
|
|
|
|
Viral
|
5
|
19
|
|
Alcohol
|
44
|
41
|
|
Nonalcohol/nonviral
|
51
|
40
|
There were no differences found in age and sex between ACLF and cirrhosis.
Sepsis and septic shock were substantial trends within factors related to ACLF, which remarkably increased the proportion of septic shock from 2012 to 2013 (28.2% in 2009, 27% in 2010, 26.2% in 2011 to 39.2% in 2012 and 58.3% in 2013).
The proportion and type of organ failure in ACLF remained notably constant throughout the study period, while respiratory failure averaged 70% and renal failure averaged 58.4%. Among renal failure patients, approximately 7.2% received hemodialysis and 3% received peritoneal dialysis. Overall, 77.4% had two organ failures, 19.3% had three organ failures, and 3.1% had four organ failures.
Outcomes of cirrhosis and ACLF hospitalization
The in-hospital mortality rate was 51.7%. The 30-day mortality rate was nearly equal between 67.9% in 2009 and 68.3% in 2013 for ACLF and between 32.1% in 2009 and 31.7% in 2013 for cirrhosis. The 90-day mortality rate also was almost equal between 74.1% in 2009 and 75.1% in 2013 for ACLF and between 25.9% in 2009 and 24.9% in 2013. Throughout the study period, we found the mortality rate was 85.6% for ACLF. Sepsis and bacterial infection were the most common causes of mortality, followed by liver-related death and hepatocellular carcinoma in ACLF. Readmission rate among ACLF was only 3.4% and 30-day readmission rate was just 1%.
Table 3 represents predictors of 30-day mortality in ACLF, including age (hazard ratio [HR], 1.014; 95% confidence interval [CI]: 1.013–1.015), and male sex (HR, 1.075; 95% CI 1.056–1.095).
Table 3
Determinants of 30-day Mortality in ACLF by Multivariate Analysis
|
|
Adjusted HR (95% CI)
|
P
|
Age
|
|
1.014 (1.013–1.015)
|
< 0.0001
|
Male
|
|
1.075 (1.056–1.095)
|
< 0.0001
|
Hospital level
|
|
|
|
|
Community hospital
|
Reference
|
|
|
Intermediate-level hospital
|
1.325(1.297–1.354)
|
< 0.0001
|
|
Referral hospital
|
1.255(1.227–1.283)
|
< 0.0001
|
Number and type of organ failure
|
|
|
|
Cirrhosis or one organ failure
|
|
Reference
|
|
Two organ failures
|
|
|
|
|
Respiratory + cardiovascular
|
4.686(4.534–4.843)
|
< 0.0001
|
|
Respiratory + renal
|
5.436(5.271–5.605)
|
|
|
Respiratory + cerebral
|
4.187(3.867–4.535)
|
< 0.0001
|
|
Cardiovascular + renal
|
2.184(2.081–2.293)
|
< 0.0001
|
|
Cardiovascular + cerebral
|
1.141(1.030–1.264)
|
0.012
|
|
Renal + cerebral
|
2.333(2.129–2.556)
|
< 0.0001
|
Three organ failures
|
|
5.416(5.215–5.624)
|
< 0.0001
|
Four organ failures
|
|
6.277(5.331–7.391)
|
< 0.0001
|
Compared with patients, who were admitted to a community hospital, risk of death in patients admitted to an intermediate-level hospital (HR, 1.325; 95% CI 1.297–1.354) and a referral hospital (HR, 1.255; 95% CI 1.227–1.283) were significantly higher. As anticipated, the risk of death in patients with three organ failures (HR, 5.416; 95% CI 5.215–5.624) and four organ failures (HR, 6.277; 95% CI 5.331–7.391) were significantly higher compared with patients with no, one, or two organ failures. Among patients with two organ failures, respiratory together with renal failure showed the highest risk of death (HR, 5.436; 95% CI 5.271–5.605).
Costs of cirrhosis and ACLF hospitalization
From 2009 to 2013, the yearly hospitalization costs for ACLF and cirrhosis increased from ฿ 964 million to ฿ 1,215 million. The mean cost per hospitalization for cirrhosis minimally increased from ฿ 21,562 to ฿ 21,655, while the mean hospitalization cost for ACLF decreased from ฿ 63,719 to ฿ 61,915. The mean cost per hospitalization for ACLF was 3.5-fold more than that for cirrhosis (฿ 61,928 versus ฿ 16,995). The hospital gets payment from the Universal Coverage Scheme by using a diagnosis-related group (DRG) payment system which is only 15% of the average treatment costs (฿ 9,371 from ฿ 61,928). Details of costs of ACLF and cirrhosis are summarized in Supporting Table S2.