Journal of Visceral Surgery (2011) 148, 311

REVIEW

Hepatocellular cancer in the non-cirrhotic liver

B. Alkofer a,, V. Lepennec b, L. Chiche a

a
Unit de chirurgie hpato-biliaire et transplantation, service de chirurgie digestive, CHU de
Caen, Cte-de-Nacre, 14000 Caen, France
b
Service de radiologie, CHU de Caen, 14000 Caen, France

KEYWORDS Summary Less than 20% of hepatocellular carcinoma (HCC) develops in the non-cirrhotic liver
Hepatocellular (NCL). The diagnosis of HCC in NCL is suggested by a large hypervascular tumor in a 6075 year
carcinoma; old patient (usually male), particularly if the alpha-fetoprotein (AFP) level is high. But AFP is
Non-cirrhotic liver; normal more often than not. Surgical resection is the only curative therapy of HCC; resection
Surgical resection; is more commonly feasible in HCC in NCL due to the healthy parenchyma of the underlying
Intrahepatic liver. The prognosis of HCC in NCL is better than that for HCC on cirrhosis with a 5-year survival
recurrence approaching 50%. Prognosis is best in the patient with a small HCC with no vascular invasion or
satellite nodules for whom an R0 resection can be achieved without the need for intra-operative
transfusion. While intra-hepatic recurrence occurs frequently, it should be aggressively sought
and treated; there is a major role for repeat hepatic resection and a lesser role for hepatic
transplantation where results are poorer than those obtained for HCC on cirrhosis.
2011 Published by Elsevier Masson SAS.

Introduction
Hepatocellular carcinoma (HCC) is by far the most common primary tumor of the liver,
and it typically develops in the cirrhotic liver (80% of cases). It is a hepatocellular
tumor, typically hypervascular, and tends to have a long phase of intrahepatic growth;
it has the capacity to invade the hepatic vessels but only rarely exhibits the classical
presentation of tumor rupture. Worldwide, it is the fth most common human malig-
nancy (8th in women) but the third most common cause of mortality (5th in women)
[1,2].
HCC develops in the non-cirrhotic liver in less than 20% of cases. The normal quality
of the non-tumoral liver parenchyma makes this type of HCC a very different entity epi-
demiologically, clinically and in its management and prognosis. It is classically stated that
HCC is rare in the non-cirrhotic liver and it is usually diagnosed at a more advanced stage,
but is also more readily treated by surgery with a better prognosis than HCC on cirrhosis.
The purpose of this review is to dene the characteristics of HCC occurring in non-cirrhotic
healthy liver.

Corresponding author.
E-mail address: barbaraalkofer@yahoo.fr (B. Alkofer).

1878-7886/$ see front matter 2011 Published by Elsevier Masson SAS.

doi:10.1016/j.jviscsurg.2010.12.012
4 B. Alkofer et al.
Epidemiology
It would be an oversimplication to compare HCC on cir-
rhosis with HCC in the healthy liver because, between
these two extremes, there is a wide range of parenchy-
mal pathology without cirrhosis including F2 and F3 brosis;
steatosis greater than 30% and steatohepatitis (NASH), and
early-stage hemochromatosis.
Frequency
The incidence of HCC in non-cirrhotic liver (NCL) is esti-
mated at about 1520% of all HCC [13]. If we restrict the
entity to HCC in perfectly healthy livers, the percentage
is closer to 1012% [13]. In the most recent French pop-
ulation survey [3], 15% of a cohort of 1007 patients with
HCC had no underlying cirrhosis. These tumors are more
likely to be amenable to surgical excision leading to an over-
representation of HCC on NCL in surgical series reaching
almost 25% [4]. Recognizing that the estimated incidence
of new cases of HCC worldwide is 600,000 cases per year,
we can extrapolate an incidence of 90,000 to 120,000 new
cases of HCC on NCL per year [1].
Age and sex ratio
Epidemiological studies show that men are affected by HCC
two to four times more frequently than women, but this
distribution mirrors the incidence of cirrhosis [3,4]. Male
predominance is less marked for HCC on NCL (75% men for
HCC on NCL versus 85% for HCC on cirrhosis); more strikingly,
the sex ratio is equal in patients younger than 50 years [4,5].
The average age of onset in published series is lower for
HCC on NCL (60 years) than for HCC on cirrhosis. This is due
to a subset of HCC on NCL that arises in the second and
third decades [5]. It is within this age group that we see the
unusual entity of brolamellar HCC (mean age of 27 years)
[6].
Risk factors
Certain toxic risk factors, while classical, are rarely seen
in practice: aatoxin B, androgens, vinyl chloride. . .. Other
risk factors mirror risk factors for cirrhosis:
hepatitis B and C: we know that the integration of frag-
ments of viral DNA into the genome of hepatocytes has an
intrinsic carcinogenic role. Thus, the presence of anti-HBs
antibodies, even in the absence of viral DNA, is a risk fac-
tor for development of HCC [3]. However, the presence of
anti-HCV antibodies does not seem to be a risk factor in
the absence of cirrhosis;
obesity and diabetes, which are oftentimes associated
with nonalcoholic steatohepatitis (NASH), seem to be
related to the development of HCC [7,8]. While these fac-
tors are clearly associated with an increased incidence of
HCC in cirrhosis, their risk in the non-cirrhotic liver is more
controversial. At any rate, the metabolic syndrome
is increasingly recognized as a hepatic carcinogenic fac-
tor. In the series published by the French Association of
Surgery (AFC), the metabolic syndrome was present in
29% of cases of HCC on NCL [4]. In addition, disorders of
glucose metabolism are probably implicated in carcino-
genesis, as suggested by the high prevalence of HCC in
glycogen storage diseases [9];
iron overload, particularly hemochromatosis, is an impor-
tant risk factor, iron being both directly and indirectly
involved in carcinogenesis [10]. Again, while this data is
clearly established in patients with cirrhosis, it remains
more controversial in HCC on NCL;
neither alcohol nor alcoholism is recognized as an intrinsic
carcinogen.
Natural history and tumor characteristics
The natural history of HCC on NCL is poorly understood,
particularly the tumor doubling time. Some cases of mis-
diagnosis have resulted in prolonged observation of these
tumors; this and the discovery of asymptomatic tumors at
advanced stages also suggest that the doubling time is quite
long, with tumors evolving over several years.
Clinical presentations
There are several distinct clinical presentations [35]:
the classic form: the patient typically presents with symp-
toms of pain associated with a large tumor (average of
810 cm), often necrotic, and unifocal (in more than 50%
of cases). The AFP is elevated in only 40% of these cases
(Fig. 1A, B);
tumor rupture with hemorrhage: these tumors are usu-
ally large and hypervascular, and sometimes present with
portal vein thrombosis: hemoperitoneum is a rare but
classical presentation, occurring in about 5% of cases
(which is more common than in HCC on cirrhosis) (Fig. 2);
the massive late-stage form: this is often the initial
presentation in young subjects: there is major tumoral
invasion within the liver with concurrent nodal, pul-
monary, or osseous metastases. This clinical presentation
occurs frequently in HCC on NCL related to neonatal
hepatitis B infection, especially among young Africans
(Fig. 3);
the asymptomatic form: this is diagnosed with increasing
frequency. HCC is either discovered incidentally by imag-
ing studies (the tumor often, but not always, being small)
or because of abnormal laboratory ndingsliver function
tests, or paraneoplastic syndromes such as polycythemia.
Typical histology and unusual variants
The histological features of the tumor are similar to HCC on
cirrhosis. Stages of differentiation vary from well- to poorly-
differentiated, there may be satellite nodules, the tumor
may or may not have penetrated its capsule, Vascular inva-
sion may include tumor embolization or budding into the
portal or hepatic veins.
Three special variants, while rare, must be recognized
because they may pose diagnostic problems:
degeneration of an adenoma: malignant transformation
of a hepatic adenoma is rare (less than 8%) and seems
to be related to a mutation of beta-catenin [11]. In the
subset of HCC on NCL, this entity represents only a tiny
proportion, given the low incidence of adenoma;
brolamellar HCC: this form has a unique histology with a
brous component that can be misleading. This explains
some diagnostic confusion with focal nodular hyperplasia,
especially since it also tends to occur in young patients
with a slight female predominance and with a normal AFP.
The overall prognosis of brolamellar HCC is somewhat
better despite frequent recurrence; this justies post-
Hepatocellular cancer in the non-cirrhotic liver
Figure 1. Typical presentation of hepatocellular carcinoma in healthy liver: intra-operative view prior to hepatectomy. The arrows point
to the primary tumor and a satellite nodule (A); specimen from a left lobectomy extended to include a portion of segment IVthe tumor
deforms the contours of the left lobe (B).
operative surveillance and an aggressive re-intervention
policy [12,13];
the cystic form of HCC: Here again the diagnosis can be
difcult. This rare presentation includes cases of tumor
necrosis with liquefaction leading to degenerative cysts,
but there is also a truly cystic form HCC, which can be very
misleading for both imaging and histological diagnosis [14]
(Fig. 4).
Management
Management is based on these currently accepted princi-
pals:
surgical excision is the only curative treatment;
prognostic factors, as described in the literature, are
tumor size and vascular invasion, the ability to achieve R0
resection, and intraoperative blood transfusion (Table 1)
[1519];
recurrences must be aggressively treated because they
are sometimes amenable to a second curative resection,
which may result in prolonged survival.
Figure 2. View of a ruptured HCC on healthy liver: clotted blood
adjacent to the capsular rupture.
5
For all HCC on NCL, the primary objective is an oncologi-
cally complete surgical resection with minimal hemorrhage.
Diagnosis
In most cases, diagnosis is straightforward. CT with con-
trast injection shows a large heterogeneous tumor with
necrotic and hemorrhagic components, hypervascular in the
arterial phase (Fig. 5), and with no evidence of underlying
liver disease (Fig. 6). Fibrolamellar HCC has a characteristic
appearance; it is usually located on the left, and often has
a central brous component and calcications.
Magnetic resonance imaging (MRI) provides additional
information: T1 images show an isointense lesion with a
hypointense capsule, while T2 images show an isointense
lesion with a slightly hyperintense capsule. After injection of
gadolinium in the arterial phase, the lesion becomes hyper-
intense; in the portal phase, the lesion is isointense relative
to adjacent parenchyma, and, in the late phase, it becomes
hypointense. A well-delineated capsule during the portal
phase supports the diagnosis of HCC (Fig. 7).
Figure 3. CT image of a massive HCC on NCL in the portal phase.
There are numerous bilobar hypodense nodules and a thrombus in
the right portal vein (*).
6 B. Alkofer et al.

Figure 4. Cystic form of HCC: CT with IV contrast injection during the arterial phase: there is a frankly hypodense lesion which occupies
the entire right liver and part of segment IV; it contains loculations with contrast uptake (A); macroscopic view of the lesion in the same
patient: the lesion appears hemorrhagic and necrotic and several loculations are visible (B).

For any hypervascular tumor, HCC is statistically the
likely diagnosis. An increase in AFP is then sufcient to con-
rm the diagnosis. If the AFP is not elevated, a biopsy may be
necessary (biopsy was performed in 50% of cases in the AFC
series). Subclinical cirrhosis should be ruled out; depend-
ing on the context, this sometimes requires biopsy of the
uninvolved liver.
In some cases the diagnosis is more difcult: this is espe-
cially true for smaller tumors discovered incidentally or
having less characteristic imaging morphology; here the dif-
ferential diagnosis includes multiple entities: focal nodular
hyperplasia, adenoma, endocrine metastases, and others.
Circumstances vary but a biopsy is most often required for
diagnosis.
Evaluation of resectability
The assessment of resectability differs from HCC on cirrho-
sis. Since the liver parenchyma is healthy or only minimally
diseased, much more extensive resections are feasible; the
rate of resectability is therefore higher. The positive point
is that the liver is healthy or minimally diseased which
allows extensive resections and hence a fairly high rate of
resectability. On the negative side, these tumors are often
very large at presentation and are situated in close proximity
to vascular structures.
This emphasizes the need for an accurate assessment:
of the tumor characteristics including its vascular rela-
tionships (the intersection of the hepatic veins with
the vena cava), evidence of satellite nodules, the pres-
ence of tumor thrombus in a portal vein branch (vein
enlargement with an arterial signal on Doppler scan and
contrast enhancement during the arterial phase of the CT
scan);
of the quality of the underlying liver parenchyma
with estimation of the volume of residual liver
after resectionthis determination is usually quite
simple;

Table 1 prognostic factors for hepatocellular cancer in non-cirrhotic liver.

1er author (references) Number of Dates of Overall 5 Year Factors of poor prognosis
patients study survival (%)
Bege et al. [15] 116 19872005 40.0 R1 resection
Vascular involvement
HBV infection
Dupont-Bierre et al. [16] 84 19982003 44.4 Multiple tumors
Gross vascular involvement
Lang et al. [17] 83 19982005 30.0 UICC stage
Vascular involvement
Tumor grade
Laurent et al. [18] 108 19872005 29.0 Blood transfusion
Absence of capsule
Satellite nodules
Resection margin < 1cm
Capussotti et al. [19] 47 19852002 30.9 Size > 10 cm
Satellite nodules
HBV: hepatitis B virus; UICC: Union Internationale Contre le Cancer
Hepatocellular cancer in the non-cirrhotic liver
Figure 5. CT of HCC on NCL: images without IV contrast shows an isodense lesion deforming the contours of the left liver (A); in the
arterial phase, the lesion takes up contrast but has a hypodense center. There is a subcapsular satellite nodule in segment IV (B); in the
portal phase, there is washout of the lesion (C).
of any evidence of extra hepatic extension;
metastasis to lymph nodes, lung, or bone is not
uncommon.
A good quality spiral CT of the chest and abdomen is
essential, possibly supplemented by MRI with vascular recon-
struction. This assessment is essential to the planning of the
operative procedure; vascular problems must be anticipated
in order to obtain an R0 resection. This is the basis for all
problematic decisions regarding surgical resection of large
malignant liver tumors. There is usually adequate hepatic
reserve in the non-cirrhotic residual liver, making the need
for portal vein embolization rare; but this procedure should
be performed without hesitation to obtain liver hypertro-
phy if the percentage of remaining liver is estimated at
less than 25%. When the size of the residual liver is the
limiting factor, it is essential to have biopsy evidence of
normal liver parenchyma since, in case of steatosis, early
brosis or other parenchyma abnormality, it is reasonable
to require at least a 3035% volume of residual liver, and
therefore to resort to pre-operative portal vein emboliza-
tion.
It is also unusual to have to resort to preoperative
chemotherapy-embolization, since its use in neoadjuvant
therapy has not been conrmed. It may nevertheless be
a useful technique to decrease tumor mass in exceptional
cases.
7
Operative management
The incision must be large and tailored to the tumoral loca-
tion and to patient morphology; a right subcostal incision
may be adequate for a centrally contained tumor or for a
superior location (segment VIII) or a left lobe tumor. It is
important to be able to enlarge this incision (bi-subcostal
with or without a xiphoid extension, or a J-shaped incision).
At times, a thoraco-abdominal incision with division of the
diaphragm may be necessary for large tumors near the junc-
tion of the hepatic veins and vena cava; this permits safe
supradiaphragmatic control of the vena cava.
Inow and outow cross clamping should be carefully
considered, prepared for, and used whenever there is need,
since morbidity and mortality and even long-term survival
are related to intraoperative blood loss. While selective
clamping of the hemi-liver to be resected is usually suf-
cient, one must still be prepared to resort to total vascular
exclusion of the liver.
The anterior approach now seems the technique of choice
for large tumors, especially since long-term prognosis is
improved by use of this technique [20].
The type of resection
The predilection of this lesion for endo-portal spread is an
argument in favor of anatomical resections. Whereas, in the
8 B. Alkofer et al.

Figure 6. CT of HCC on NCL with necrotic and hemorrhagic alterations: before contrast injection, the lesion in the right liver has a
hypodense center corresponding to the central necrosis (A); in the arterial phase, the hypodense center persists without contrast uptake
(necrosis). There is a satellite nodule in segment IV (B); in the portal phase, there is persistent central hypodensity (C).

setting of cirrhosis, the surgeon may be limited by the imper-
ative to preserve parenchyma, this is less often the case for
HCC on NCL. In the AFC series, 59% of HCC on NCL required
a major hepatectomy and 84%, an anatomical hepatectomy
[4].
Tumor extension or budding into the portal veins must
be identied because, even though such vascular invasion
is undoubtedly a factor of poor prognosis, many authors
have nonetheless shown a benet from surgical resection
despite this [21]: what is most important is to achieve an R0
resection with an optimal margin of at least 1 cm [18].
Similarly, it is critical to search for lymph node involve-
ment, which is more common than in HCC on cirrhosis.
Lymph node dissection in association with hepatectomy in
a young patient is justied, especially in the brolamellar
form of HCC [6].
Postoperative management
Long-term survival after surgical resection for HCC on NCL
is about 50% at 5 years; this is signicantly better than that
observed for HCC with cirrhosis [4,1519,22].
However:
the survival falls off at 10 years. Ten-year survival was
only 20% in the series of the AFC [4];
disease-free survival was lower (about 30%) [4,1519,22].
This means that recurrences are common and may be long
delayed [22]. This nding has led to consideration of adju-
vant therapy, and the need for a long-term surveillance
protocol with appropriate treatment of recurrences.
Adjuvant treatment
There is no generally recommended adjuvant therapy
after resection because none has been proven effective,
especially in this rare setting of HCC on NCL. Only the post-
operative intra-arterial infusion of lipiocis seems to have
demonstrated benet in the experience of the team of
Rennes (France) [16].
Management of recurrence
These patients must be monitored regularly over the long
term. The tendency to recurrence has been known for
years [20]. Intrahepatic recurrences can be amenable to
re-resection while extrahepatic recurrences (lung, adrenal)
may also be surgically treatable. These recurrences may
be delayed: while they are more frequent in the rst two
years, they may occur as late as 4 or 5 years after surgery.
Surveillance must therefore continue beyond 5 years.
An aggressive response to recurrence should always be
considered: the primary goal, as always, should be surgi-
cal removal, as long as an R0 resection can be achieved. In
the case of unresectable intrahepatic recurrence, treatment
options including the possibility of liver transplantation
(LT) with curative intent [23], or chemoembolization as
Hepatocellular cancer in the non-cirrhotic liver
Figure 7. Magnetic resonance image of an HCC on NCL (the same patient as in Fig. 6): the T1 sequence shows a heterogeneous lesion
with hypointensity of the capsule (A); T2 sequence (B); T2 sequence with gadolinium injection (C); late phase the capsule is visible with
a hyperintense signal (D).
a palliative procedure, should be discussed. In the case
of unresectable extrahepatic recurrence, chemotherapy
or systemic treatment with Sorafenib can be considered
(though it has not been validated for this indication). Pro-
longed survival is possible, even in case of recurrence [5].
What treatment for unresectable HCC on NCL?
Hepatic transplantation (HT) has a place in the treatment of
HCC on NCL, although it is less well-dened than for HCC on
cirrhosis. In many cases, HCC on NCL develops and remains
purely intra-hepatic for a long time, but recurrence after
resection is common. In some cases, HCC on NCL presents
in an unresectable multinodular form. HT is then a logical
consideration.
HT is not indicated for resectable HCC on NCL at present;
the results for HT are worse than those for resection.
However, the condition of the non-tumoral liver must be
carefully weighed in this equation: in effect, if there is
underlying liver disease (hemochromatosis, severe F3 bro-
sis), resection becomes more risky and TH should be included
in the discussion, in light of patient age and tumor charac-
teristics.
There is little published data on HT for HCC on NCL, and
the published series combine both HCC on NCL and bro-
lamellar HCC.
Indeed, two earlier series (1991 and 1995) analyzing their
results of HT for HCC on healthy liver, combined HCC and
brolamellar HCC on NCL. In both studies, the median over-
all survival was 26%, with survival at 1, 3 and 5 years of 70%,
9
32.5% and 26%, respectively. Prognostic factors were nodal
status, bilobar disease, and TNM stage [23,24]. Unlike these
two studies, the team at Paul Brousse Hospital reported
their experience with 34 transplants for HCC on normal liver
excluding HCC and brolamellar HCC on NCL. Eight of these
patients had had a previous resection. Overall survival was
respectively 85%, 60% and 41% at 3, 5 and 10 years. Favorable
prognostic factors were surgical resection for recurrence
and a > 2 year interval between the rst resection and HT
[25].
The major axes of decision-making regarding HT include:
Patients with indications for HT for HCC on NCL are those
with unresectable tumor at the outset or unresectable
intrahepatic recurrence without evidence of associated
extrahepatic disease. For cases of recurrent HCC, the
indication of HT should principally reect the initial histo-
prognostic characteristics as well as those present at the
time of recurrence (histological differentiation, vascular
invasion, or lymph node spread) and the natural history of
the disease after resection.
Role of systemic therapy
HCC is relatively insensitive to chemotherapy. However,
chemotherapy is sometimes the only therapeutic option
for advanced stages of disease. Chemotherapy based on
5-uorouracil, epirubicin or adriamycin plus platinum,
using protocols similar to those used for hepatoblas-
toma, has been shown to provide objective responses
in 20 to 30% of cases [26]. The therapeutic role
10
of Sorafenib is worthy of evaluation for this indica-
tion.
Conclusion
HCC on NCL is a relatively rare condition for which surgery
plays the preponderant role. Indeed, only complete resec-
tion offers hope of a cure. After R0 resection, nearly one
out of two patients is alive at 5 years. However, recur-
rences are common, probably related not only to tumor
characteristics at the time of initial discovery but also to
the condition of the underlying non-tumoral parenchyma,
which may have subclinical liver disease. Routine long-term
surveillance is necessary to detect and treat recurrences,
thereby improving survival. The role of neoadjuvant and
adjuvant treatments is uncertain but should continue to be
evaluated, as data are too limited at this time to judge its
efcacy.
KEY POINTS
Hepatocellular carcinoma (HCC) develops in the
non-cirrhotic liver (NCL) in only 20% of cases. The
host liver parenchyma may be perfectly healthy or
may exhibit various degrees of brosis, steatosis or
other abnormalities such as hemochromatosis.
The diagnosis of HCC in the non-cirrhotic liver is
suggested by a large hypervascular tumor in a 60-
75 year old patient (usually male), particularly if
the alpha-fetoprotein (AFP) level is high. But the
frequent absence of AFP elevation and the large
number of entities in the differential diagnosis
often mandate protected biopsy to conrm the
diagnosis.
Fibrolamellar carcinoma is a variant form of HCC,
which characteristically arises, in young patients
(M:F ratio close to 1), with a normal AFP; despite
a high frequency of nodal spread, the prognosis is
generally favorable.
The only curative treatment for HCC is surgical
excision. The absence of cirrhosis makes resection
feasible more often. When the tumor is
unresectable, liver transplantation should be
considered if the clinical context is favorable,
as long as there is no vascular invasion or
extrahepatic metastasis. Chemotherapy based on
adriamycin and platinum salts, or antiangiogenic
agents results in response rates of 2040%.
The prognosis for 5-year survival after tumor
resection is 50%a much better prognosis than
for HCC on cirrhosis. However, recurrence after
surgery is common and may occur late. Such
recurrences may still be amenable to curative
resection, which justies ongoing surveillance
after resection.
The prognostic factors for HCC in the non-cirrhotic
liver are: R0 resection, those same histological
factors that have been observed in HCC on
cirrhosis (tumor size, satellite nodules, vascular
invasion), and intraoperative transfusion.
B. Alkofer et al.
Conict of interest statement
The authors have no conict of interests.
References
[1] Sherman M. Hepatocellular carcinoma: epidemiology, risk fac-
tors and screening. Semin Liver Dis 2005;25:14354.
[2] Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carci-
noma incidence, mortality, and survival trends in the United
States from 1975 to 2005. J Clin Oncol 2009;27:148591.
[3] Borie F, Bouvier AM, Herrero A, et al. Treatment and progno-
sis of hepatocellular carcinoma: a population based study in
France. J Surg Oncol 2008;98:5059.
[4] Boudjema K, Cherqui D. Le carcinome hpatocellulaire. Mono-
graphie de lAssociation Franc aise de Chirurgie. Arnette, 2006.
[5] Xu L, Huang L, Li BK, Zhang YQ, Li JQ, Yuan YF. Clinicopatho-
logic features and long- term outcomes of Chinese patients
with hepatocellular carcinoma in non-cirrhotic liver. Dig Surg
2008;25:37682.
[6] El-Gazzaz G, Wong W, El-Hadary MK, et al. Outcome of liver
resection and transplantation for brolamellar hepatocellular
carcinoma. Transpl Int 2000;13(Suppl. 1):S4069.
[7] Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AM. Obesity and
hepatocellular carcinoma. Gastroenterology 2004;127(5 Suppl.
1):S97103.
[8] El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of
chonic liver disease and hepatocellular carcinoma. Gastroen-
terology 2004;126:4608.
[9] Davis MK, Weinstein DA. Liver transplantation in children
with glycogen storage disease: controversies and evalua-
tion of the risk/benet of this procedure. Pediatr Transplant
2008;12:13745.
[10] Kowdley KV. Iron, hemochromatosis and hepatocellular carci-
noma. Gastroenterology 2004;127:S7986.
[11] Zucman-Rossi J, Jeannot E, Nhieu JT, et al. Genotype-
phenotype correlation in hepatocellular adenoma: new classi-
cation and relationship with HCC. Hepatology 2006;43:51524.
[12] El-Serag HB, Davila JA. Is brolamellar carcinoma different
from hepatocellular carcinoma? A US population-based study.
Hepatology 2004;39:798803.
[13] Stipa F, Yoon SS, Liau KH, et al. Outcome of patients with bro-
lamellar hepatocellular carcinoma. Cancer 2006;106:13318.
[14] Heywood G, Van Buren SF, Smyrk T, Nagorney DM. Mul-
tilocular cystic hepatocellular carcinoma (CHCC) mimick-
ing mucinous cystadenocarcinoma. Hepatogastroenterology
2003;50:36870.
[15] Bge T, Le Treut YP, Hardwigsen J, et al. Prognostic factors after
resection for hepatocellular carcinoma in nonbrotic or moder-
ately brotic liver. A 116-case European series. J Gastrointest
Surg 2007;11:61925.
[16] Dupont-Bierre E, Compagnon P, Raoul JL, Fayet G, de
Lajarte-Thirouard AS, Boudjema K. Resection of hepatocellu-
lar carcinoma in noncirrhotic liver: analysis of risk factors for
survival. J Am Coll Surg 2005;201:66370.
[17] Lang H, Sotiropoulos GC, Brokalaki EI, et al. Survival and recur-
rence rates after resection for hepatocellular carcinoma in
noncirrhotic livers. J Am Coll Surg 2007;205:2736.
[18] Laurent C, Blanc JF, Nobili S, et al. Prognostic factors and
longterm survival after hepatic resection for hepatocellular
carcinoma originating from noncirrhotic liver. J Am Coll Surg
2005;201:65662.
[19] Capussotti L, Muratore A, Amisano M, Massucco P, Polastri R,
Bouzari H. Liver resection for large-size hepatocellular carcino-
mas in 47 non-cirrhotic patients no mortality and long-term
survival. Hepatogastroenterology 2006;53:76872.
[20] Liu CL, Fan ST, Cheung ST, Lo CM, Ng IO, Wong J. Anterior
approach versus conventional approach right hepatic resection
for large hepatocellular carcinoma: a prospective randomized
controlled study. Ann Surg 2008;247:3901.
Hepatocellular cancer in the non-cirrhotic liver
[21] Pawlik TM, Poon RT, Abdalla EK, et al. Hepatectomy for hepato-
cellular carcinoma with major portal or hepatic vein invasion:
results of a multicenter study. Surgery 2005;137:40310.
[22] Bismuth H, Chiche L, Castaing D. Surgical treatment of hep-
atocellular carcinoma in non cirrhotic liver. World J Surg
1995;19:3541.
[23] Pilchmayr R, Weimann A, Oldhafer KJ, et al. Role of liver trans-
plantation in the treatment of unresectable liver cancer. World
J Surg 1995;19:80713.
[24] Iwatsuki S, Starzl TE, Sheahan DG, et al. Hepatic resection
versus transplantation for hepatocellular carcinoma. Ann Surg
1991;214:2218.
11
[25] Scatton O, Adam R, Plasse M, et al. Liver transplantation for
hepatocellular carcinoma in patients without cirrhosis: is it
worthwhile? Communication la 12e runion de lEuropean
Society for Organ Transplantation (ESOT), Genve, 1619 Octo-
bre 2005.
[26] Edeline J, Raoul JL, Vauleon E, Guillygomach A,
Boudjema K, Boucher E. Systemic chemotherapy for
hepatocellular carcinoma in non-cirrhotic liver: a
retrospective study. World J Gastroenterol 2009;15:
7136.