Extracorporeal Liver Assist Device for
Alcoholic Hepatitis: A Potential Silver
SEE ARTICLE ON PAGE 380
Alcoholic hepatitis (AH) describes a spectrum of liver
injury caused by chronic, heavy alcohol use, marked
clinically by jaundice and histologically by hepatocellu-
lar necrosis and apoptosis, inﬂammation, and ﬁbrosis.
Although several formulas are used to assess the
prognosis of AH (ie, Maddrey’s discriminant
function [mDF], Model for End-Stage Liver Disease
[MELD], Glasgow scale, and albumin/bilirubin/inter-
national normalized ratio [INR]/creatinine score), the
absence of an unequivocally effective medical therapy
limits their utility. Current American Association for
the Study of Liver Diseases (AASLD) and European
Association for the Study of the Liver (EASL) guide-
lines endorse prednisolone as the ﬁrst-line treatment
for patients with mDF 32, with pentoxifylline being
considered for patients with exclusions to prednisolone
treatment (eg, uncontrolled infection, renal failure,
hepatitis B, uncontrolled diabetes).
Unfortunately, prednisolone is not very effective.
Several studies, as well as meta-analyses,
modest improvement in 1-month survival among
patients receiving prednisolone. However, no study has
shown an improvement in 3-month or 6-month survival
with prednisolone treatment.
The ineffectiveness of
prednisolone in improving 3-6–month survival is partic-
ularly noteworthy among clinical trials performed in the
past 15 years, in which the mortality among the
placebo/control groups is lower than it was in earlier
clinical trials. The proposed explanation for improve-
ment in 1-month survival among control subjects in
recent clinical trials is an improvement in medical care
for liver failure (eg, intensive care unit care, antibiotics
for infection, variceal banding, treatment of hepatorenal
syndrome, and encephalopathy).
Extracorporeal cellular therapy (ELAD) removes
venous blood from which the cellular components
are separated and returned to the systemic circula-
tion, and the serum is circulated through the ELAD
device. Within the device is a cylinder with C3A
cells, a metabolically active human hepatocyte cell
line. Semipermeable capillary tubes carry the patient’s
serum through the living C3A cells, which secrete
anti-inﬂammatory, proregeneration, antioxidant, and
antiapoptotic proteins that pass through the semiper-
meable membranes and into the patient’s serum.
Among the beneﬁcial proteins secreted by the C3A
cells is interleukin (IL) 1 receptor antagonist (RA), a
protein that binds and inhibits IL1a and IL1b, 2
cytokines hypothesized to play a major role in
inﬂammation and hepatocyte death.
Thompson et al. conducted a prospective, random-
ized, unblinded, clinical trial comparing standard of
care (SOC) versus SOC 1 ELAD among patients
18 years old who had a clinical diagnosis of AH.
The study was performed at 40 clinical sites in the
United States, United Kingdom, and Australia.
ELAD was performed continuously for 3-5 days. The
primary outcome was survival at 91 days (Kaplan-
Meier analysis). Secondary outcomes included survival
at 28 days (a historical outcome variable) and survival
at 6 months. Other protocol-speciﬁed analyses
included survival according to baseline MELD score
and age (each analysis dichotomized according to
above/below the median).
A total of 203 patients were randomized (96 to
ELAD and 107 to SOC). The patients had severe
Abbreviations: AASLD, American Association for the Study of Liver
Diseases; AH, alcoholic hepatitis; EASL, European Association for
the Study of the Liver; ELAD, extracorporeal cellular therapy;
GCSF, granulocyte colony stimulating factor; IL, interleukin; INR,
international normalized ratio; mDF, Maddrey’s discriminant func-
tion; MELD, Model for End-Stage Liver Disease; NAC, N-acetyl-
cysteine; RA, receptor antagonist; SOC, standard of care.
Address reprint requests to Timothy Morgan, M.D., Medical Service,
VA Long Beach Healthcare System, 5901 E. 7th Street, Long Beach,
CA 90822. Telephone: 562-826-5756; FAX: 562-826-5436;
Received January 22, 2018; accepted January 22, 2018.
2018 by the American Association for the Study of Liver
View this article online at wileyonlinelibrary.com.
Potential conflict of interest: Nothing to report.