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Williams LT in ACLF

Excellent survival results in those receiving a liver the three studies summarised [Table 1], [8-10] there
graft were also shown in the series reported by was a statistically significant improvement either in
[6]
Finkenstedt et al. from centres in Austria of 144 survival or in the obtaining of a reduced MELD score
patients fulfilling ACLF criteria of which 94 (65%) prior to LT. I would ask you also to take note of the
were evaluated and 71 (49%) listed for a transplant. very recently published study of high volume plasma
One- and five-year survival figures for the 32 (23%) exchange in acute liver failure (ALF) showing in those
patients transplanted were 87% and 82% respectively. not transplanted, significant survival improvement. [11]
Less than half of those who had got to the stage of In ALF, the underling dysfunctional immune
being listed underwent transplantation and deaths reaction responsible for the multi-organ failure and
on the waiting list were unacceptably high at 50% - susceptibility to sepsis is very similar to that which has
a measure of the very short period of time available been demonstrated in ACLF.
for these sick patients to obtain a donor organ. Only
10 (7%) of 144 patients in this series survived without It is relevant also in the context of LT for ACLF to
a transplant - a similar figure to that for the French mention a number of therapeutic measures which
series of patients requiring mechanical ventilation may enhance resolution and improve the survival of
shown earlier. At present ACLF is not considered an patients with hepatic decompensation. These include
indication for priority or high urgency organ allocation reduction in bacterial translocation with rifaximin or
despite the good outcomes that can be obtained. probiotics and oral carbon for absorption of toxic
bacterial products. Currently under clinical trial also is
An important question to ask is whether some of IV human serum albumin with its wide range of anti-
the deaths on the waiting list could have been oxidant and immunomodulatory effects. Enhancing
prevented by the use of extra corporeal liver support liver hepatic regeneration through administration
devices, thereby giving more time for an organ to of G-CsF is another approach and there is some
be obtained and allowing more patients in the grade experience of this use in ACLF. The mechanism is
2 to 3 categories to be considered for LT. Currently thought to be mobilisation of hematopoietic stem
the answer has to be “no”. With the extracorporeal cells to the liver leading to an increased number
liver assist device containing a module of cultured of CD34 positive progenitor cells stimulating the
hepatocytes (hepatoblastoma cell clone) providing regeneration process. This was demonstrated in the
synthetic and detoxifying functions in addition to toxin study of Garg et al. [12] leading to a significant survival
removal, survival as compared to the control group benefit. Duan et al. [13] also reported improved
was improved only in those with a MELD score less survival at 90 days, in ACLF from HBV reactivation
than 28 and an age of less than 40 years, indicative in association with a rise in peripheral neutrophil and
perhaps of the potential for regeneration in this group CD34 positive cell counts. Sarin and Choudhury
[2]
68.6 vs. 53.6 in controls (P = 0.077). In the major from New Delhi have pioneered this exciting new
molecular adsorbents recirculating system trial of therapeutic approach and more details of later
albumin dialysis, there was also no significant benefit studies are in the reference I gave at the beginning
overall with figures of 60.7% and 58.9% at 28 days for of this presentation.
the treated and control groups despite improvement
in some of the organ failures, namely, hepatic In addition to the CLIF scoring, a number of
[7]
encephalopathy and circulatory disturbances. biomarkers reflecting the severity of liver injury and
Possible reasons for this include the failure to correct of multi-organ failure have been identified which may
the systemic reaction which is such an important add to prognostic information of the ACLF score and
part of the underlying pathophysiology of ACLF. may be of particular value in early diagnosis and
Furthermore, in neither of the trials were the inclusion in assessing progression. Hyponatremia has been
criteria based on CLIF diagnostic criteria and scoring. shown to have an independent predictive effect on 90
Of the new devices currently under clinical trial, one is days survival and plasma copeptin reflecting changes
based on membrane absorption of endotoxin from the in vasopressin level have been shown to improve
circulation, the other has a more powerful microporous
charcoal as the absorbent.
Table 1: Value of plasma exchange widely used in Far
East for ACLF from HBV reactivation
Turning to plasma exchange which is widely used Studies Changes
in the Far East for the commonest form of ACLF, [8]
namely, hepatitis B reactivation. Replacement of Mao et al. (2010) 30 days survival 50% vs. 31.7%
[9]
Ling et al. (2012)
Reduced MELD prior to LT
the patients’ plasma with its wide range of toxins Wan et al. [10] (2015) 12 weeks survival 29% vs. 14%
and mediators by fresh frozen plasma is thought to ACLF: acute-on-chronic liver failure; HBV: hepatitis B virus; MELD:
facilitate liver regeneration and recovery. In each of Model for End-stage Liver Disease; LT: liver transplantation
92 Hepatoma Research ¦ Volume 3 ¦ May 17, 2017