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Williams LT in ACLF

1.0 Early transplanted d3-7 ACLF-2 or 3 patients (n = 21)
89.6%
1.0 95.2% (95%CI: 86.1-100)
90.5% (95%CI: 77.9-100) (95%CI: 64.2-97.7)
Probability of transplant-free survival 0.6 42.9% 58.4% d3-7 ACLF (n = 61) 62% Probability of survival 0.6 Non-transplanted d3-7 ACLF-2 or 3 patients (n = 120)
0.8
78.7%
76%
No d3-7 ACLF (n = 135)
80.9%
0.8
53%
P < 0.0001
0.4
0.4
26.2% d3-7 ACLF-2 (n = 42)
21.4%
23.3% (95%CI: 15.8-30.8)
0.2
0.2
12.8%
12.5% (95%CI: 6.3-18.7)
10%
5.1% d3-7 ACLF-3 (n = 78) 3.8% (95%CI: 4.6-15.4)
0.0 0.0
0 28 60 90 120 150 180 0 28 60 90 120 150 180
Time (days) Time (days)
Figure 1: (A) Kaplan-Meier’s 180-day transplant-free survival curves of patients based on their acute-on-chronic liver failure (ACLF) Grade
at days 3-7 (d3-7 ACLF); (B) probability (180-day) of survival in patients with d3-7 ACLF-2 or -3 not transplanted and in patients undergoing
early (28-day) liver transplantation. Kaplan-Meier’s curves were compared using log-rank test. (Copyright Permission: Copyright © 2015
by the American Association for the Study of Liver Diseases. Gustot et al. Clinical Course of Acute-on-Chronic Liver Failure Syndrome and
Effects on Prognosis. Hepatology. Publisher: Wiley)
on-Chronic Liver Failure in Cirrhosis (CANONIC) is the observation that the final clinical grade is usually
multicentre study of more than 1,300 patients with reached by day 7 and at that time the prognosis in the
liver failure from cirrhosis admitted to 29 European individual case can be reliably predicted.
hospitals. The subject of an excellent symposium
published in the May 2016 issue of Seminars in Liver The development of scoring systems for the
[1]
Disease with Rajiv Jalan as Guest Editor. ACLF quantitation of prognosis in ACLF and for acute
is marked by rapid deterioration in liver function decompensation without MOF represent a major step
in a previously compensated or decompensated forward. The CLIF-ACLF prognostic score is based
cirrhotic patient is accompanied by 1 or more other on the CLIF organ failure score for 3 categories of
organ failures - kidney, brain, circulation, lungs and severity for the 6 potential organ failures, namely, liver,
coagulation. Short-term mortality is high, more than kidney, brain, coagulation, circulation and respiration
15% at 28 days. There is often a precipitating factor is combined with age and the white cell count as
most frequently an exacerbation of liver damage from independent predictors of outcome. The scoring
[5]
alcohol excess or HBV reactivation or the effects ranges from 0 to 100 points. ACLF scores have
indirectly on the liver of a variceal bleed or infection. been shown to have superior prognostic accuracy
Interestingly, in 40% of cases no clear precipitating compared to MELD and other commonly used scores
factor is identified. ACLF is to be distinguished as a result of capturing the markers of inflammation
clinically from acute decompensation in cirrhosis, so important in the pathophysiology of the syndrome
with similar precipitating factors but which does not in addition to the quantitative assessment of organ
lead to failure of other organs apart from that of the failure severity. The probability of death for an
liver and some form of non-kidney organ failure, and individual patient at any one time can be determined
which has very much better overall prognosis with a by calculation of the equation, using an app or through
< 5% mortality figure. Inflammation and the systemic the CLIF Consortium website.
inflammatory reaction is the driving force in the
underlying pathophysiology as further indicated by The major influence of the ACLF grade at days
high white cell and C-reactive protein levels. 3-7 in determining prognosis by the transplant
free survival curve [Figure 1]. The top 2 curves
It is important to take note of the dynamic nature of comprising patients with single organ failures and
ACLF as evidenced by the findings of the CANONIC normal or raised serum creatinine values; 62% and
Study. With ACLF Grade 1 defined by 1 organ failure 53% are alive at 180 days. Whereas for grade 2 and
and mild renal impairment, over 50% of the cases 3 ACLF survival figures at 180 days are considerably
resolve or improve. But with higher grades particularly reduced at 21.4% and 3.8% respectively. The other
Grade 3 when there are 3 or more organ failures, half of the figure shows how well patients with grade
the percentage showing improvement is much lower 2 or 3 ACLF can do when transplanted; 80.9% of the
(16%). These figures give some indication of the cohort of 35 patients transplanted within 28 days of
[4]
scope for LT in ACLF. Changes in clinical status occur diagnosis alive at 180 days and with little fall off in
rapidly in ACLF and relevant to the consideration of LT survival at 1 year (77%). [4]
Hepatoma Research ¦ Volume 3 ¦ May 17, 2017 91