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Page 2 of 9 Pasini et al. Hepatoma Res 2020;6:26 I http://dx.doi.org/10.20517/2394-5079.2019.47

INTRODUCTION
[1]
Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide
[2]
and its incidence in Western countries has increased by 75% in the last three decades . Liver resection
represents first-line treatment in patients with early tumors and preserved liver function, with a 5-year
overall survival ranging from 60% to 80%. Nonetheless, HCC frequently arises from chronic liver disease
[3]
and the recurrence rate in the remnant liver, even after R0 resection, has been reported to be up to 80% .
Although guidelines from European, American and Eastern societies recommend hepatic resection as
[3-5]
first-line treatment with curative intent for primary HCC , none exist for recurrent liver cancers. Liver
transplantation, in the case of recurrent HCC (rHCC), would offer the best chance at disease-free survival,
by treating both the cancer and the underlying cirrhosis at the same time, but the scarcity of deceased
organs limits its application. Furthermore, surgical treatment may not always be feasible and non-surgical
options should then be considered.

To date, many papers have been published on the treatment algorithm for rHCC but evidence and
consensus are still lacking. These studies are mainly from Eastern centers and almost all are retrospective
data.

In this paper, we reviewed the literature on treatment for rHCC and propose our personal strategy based
on the available evidence.

TREATMENT OPTIONS FOR RECURRENT HCC
Repeat hepatectomy
Liver resection is recognized as the mainstay of treatment in patients with HCC. In both Eastern and
[6]
Western countries , it is the first choice option in non-cirrhotic patients who can tolerate resections with
[7,8]
low morbidity and mortality . On the other hand, HCC resection in cirrhotic livers requires careful
patient selection and adequate surgical skills. Patient selection relies mainly on the preoperative assessment
of reserve liver function and portal hypertension. Traditionally, liver function is evaluated through
[9]
standard liver biochemical tests integrated into several scores such as the Child-Pugh or MELD score ,
but nowadays, more sophisticated quantitative liver function tests such as indocyanine green retention
(ICG) test [10,11] or hepatobiliary scintigraphy [12,13] , are used in predicting post-hepatectomy liver failure. The
presence of clinically relevant portal hypertension can be ruled out by measuring the hepatic vein pressure
gradient, or indirectly by liver stiffness, to decrease the risk of postoperative decompensation [14-16] .

According to the BCLC algorithm, patients with a single, very early- or early-stage HCC and preserved liver
function should be offered liver resection . While international guidelines tend to reserve resection for
[4]
patients harboring early stage HCC, expert institutions have shown good outcomes even in patients with
multinodular, large, and macrovascular, invasive HCC , thus justifying expansion of HCC resectability
[17]
criteria. However, even after potentially curative resections with negative margins, early recurrence
accounts for more than 70% of rHCC and occurs within 2 years in 30%-50% of patients. The recurrence
rate at 5 years has been reported to range from 50% to 70% [18-20] . The key parameters related to recurrence
include tumour size, multinodular tumours, serum alpha-fetoprotein and microvascular invasion .
[21]
Currently, there are no guidelines or clinical algorithms for the best treatment option in rHCC [22,23] except
for expert opinion and local policies. Many authors agree with re-resection as the best therapeutic option
for rHCC, when feasible. Improvement in surgical technique and implementation of the use of energy
devices have led to a lower incidence of complications. Liver resections are therefore safer in patients with
previous resection. Concern still exists however and is mainly related to poor remnant liver function and
adhesions caused by previous surgery that could lead to iatrogenic injuries. Many studies have addressed