Inﬂexion of the Curve: Hepatitis C’s
Waning Role in Liver Transplantation
SEE ARTICLE ON PAGE 735
Five years after the introduction of sofosbuvir, the
management of hepatitis C virus (HCV) infection in
patients with advanced liver disease has rapidly
evolved. HCV has now been displaced from its role as
the single commonest indication for liver transplanta-
tion (LT) by nonalcoholic fatty liver disease.
Although this undoubtedly to a large extent reﬂects
the latter’s rising prevalence, other factors are clearly
involved namely effective and well-tolerated therapy
Sustained virological response rates in
well-compensated cirrhotics are now not appreciably
lower than for noncirrhotics. Extension of direct-act-
ing antiviral (DAA) therapy to patients with advanced
enough cirrhosis to prompt listing for transplant is
increasingly being reported with a subsequent modest
reduction in Model for End-Stage Liver Disease
(MELD) scores following viral clearance.
In the current issue, Kwong and colleagues address
the impact of DA therapy on wait-list mortality in
patients listed for LT for HCV-related liver disease as
well as its effect on the MELD score.
from Organ Procurement and Transplantation Net-
work (OPTN) from 2004 onward, they divided poten-
tial recipients listed for LT into 3 cohorts by date of
listing with the most recent cohort including transplant
candidates from January 2014 onward. The primary
outcome was death on the waiting list and the second-
ary rate of change in MELD score. In the most recent
cohort of liver transplant candidates with HCV, there
was a 21% lower risk of death compared with the
cohort before. This reduction in risk of death was not
observed in non-HCV–infected listed patients. Fur-
thermore, the rate of increase in MELD in listed
patients diminished only in the most recent HCV
group. Although the OPTN database does not capture
information about HCV therapy, it lends support to a
growing consensus that advanced HCV-related liver
disease is diminishing in the United States.
Flemming and colleagues had recently reported that
the number of LT candidates listed for HCV-related
liver disease had declined by 32% in the DA era through
the end of 2015.
Belli and colleagues in a multicenter
study described delisting for LT in HCV patients with-
out a complicating hepatocellular carcinoma (HCC) fol-
lowing successful DAA therapy.
Of 103 LT HCV-
infected LT candidates, delisting occurred in 34 due to
an improvement in hepatocellular function with a
decline in median MELD of 3.4. Delisting was more
likely with a lower MELD score (< 16) at time of listing
and improvement in serum albumin with antiviral ther-
apy. These trends mirror an earlier experience in LT fol-
lowing the introduction of effective oral therapies for
hepatitis B with a corresponding decrease in transplant
listing for decompensated cirrhosis and ability to salvage
listed patients with suppression of HBV replication.
These and similar data attest to the rapidly changing
management of HCV in patients especially as DAA
therapy has become feasible even in the face of advanced
cirrhosis. An unresolved issue is at what point is antiviral
therapy no longer appropriate in decompensated cirrho-
sis. Using a Markov model, Chhatwal and colleagues
incorporated data from trials of DAA in advanced cir-
rhosis as well as from UNOS to suggest HCV therapy
should be considered up to a MELD of between 23 and
Factors predicting likelihood of improvement with
antiviral therapy in cirrhosis appear to include factors not
captured by the MELD score such as serum albumin.
For HCV-infected patients an additional strategy to
reduce wait-list mortality is use of organs from donors,
which however is only feasible if HCV infection has
not been eradicated in the recipient. In Kwong’s analy-
sis, organs from HCV-positive donors increased to
Abbreviations: DAA, direct-acting antiviral; HCC, hepatocellular
carcinoma; HCV, hepatitis C virus; LT, liver transplantation;
MELD, Model for End-Stage Liver Disease; OPTN, Organ Pro-
curement and Transplantation Network.
Address reprint requests to Paul Martin, M.D., Paul Martin is an
investigator and consultant for Abbvie, Merck, and Gilead. 1400
N.W. 12th Avenue, Miami, FL 33136. Telephone: 305-243; E-
Received May 10, 2018; accepted May 10, 2018.
Paul Martin is an investigator and consultant for Abbvie, Merck, and
2018 by the American Association for the Study of Liver
View this article online at wileyonlinelibrary.com.