J Hepatobiliary Pancreat Surg (2003) 10:26–30
DOI 10.1007/s10534-002-0808-6
IHPBA report
IHPBA concordant classification of primary liver cancer:
working group report
Masatoshi Makuuchi, Jacques Belghiti, Giulio Belli, Sheung-Tat Fan, Joseph Wan Yee Lau,
Burckhardt Ringe, Steven Martin Strasberg, Jean-Nicolas Vauthey, Yoshio Yamaoka,
and Susumu Yamasaki
The Working Group of the International Scientific Committee of the International Hepato-Pancreato-Biliary Association
Abstract
The working group of the International Scientific Committee
of the International Hepato-Pancreato-Biliary Association
(IHPBA) examined conventional staging systems and decided
to establish a new staging system that depended on macro-
scopic findings after liver resection. The TNM/International
Union Against Cancer (UICC) classification has been widely
used but is too complicated. Vauthey and colleagues, and the
Liver Cancer Study Group of Japan (LCSGJ) have proposed
new simplified classifications. These are compared and dis-
cussed. The IHPBA working group proposed a new classifica-
tion, as follows. T factor:
1. Solitary
2. No more than 2 cm
3. No vascular invasion to portal vein, hepatic vein, and bile
duct
T1 meets all of the above three requirements.
T2 meets two of the three requirements.
T3 meets one of the three requirements.
T4 does not meet any requirements.
Stage:
I T1N0M0
II T2N0M0
III T3N0M0
IV A T4N0M0
Any TN1M0
IV B Any T/N, M1
The survival curves of each stage were separated clearly
(P ⬍ 0.0001). The staging system is easy to remember and easy
to use. We hope this staging system will be generally used in
future.
Offprint requests to: M. Makuuchi
Hepato-Biliary-Pancreatic Surgery Division, Depart-
ment of Surgery, Graduate School of Medicine, The
University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo
113-8655, Japan
Received: September 17, 2002 / Accepted: October 20,
2002
Key words Hepatocellular carcinoma · Prognostic factors ·
Staging · Survival
Introduction
The International Scientific Committee of the Interna-
tional Hepato-Pancreato-Biliary Association (IHPBA)
decided to form a working group on concordant clas-
sification of primary liver cancer during the Fourth
IHPBA World Congress in Brisbane, in May 2000. The
first author (M.M.) was nominated as the chairman of
the working group and then members were selected.
Our task was to propose a new classification before the
Fifth IHPBA World Congress was held in Tokyo in
April 2002.
We collected extensive materials on published classi-
fications of hepatocellular carcinoma world wide, inves-
tigated these, and selected a suitable staging system for
the IHPBA; we also determined the need for modifica-
tions, if any.
As for the fundamental policy of the new IHPBA
classification: (1) it should be based on the TNM Inter-
national Union against Cancer (UICC) the former
American Joint Committee on Cancer (AJCC) classifi-
cation, and that of the Liver Cancer Study Group of
Japan (LCSGJ) 3rd edition. (2) It was to categorize
each stage as in the TNM system for the macroscopic
findings. (3) Its validation was based on the survival of
resected patients. (4) A more simplified classification
system was regarded as optimal.
A staging system depending on macroscopic findings
has advantages because staging can be estimated by
preoperative imagings and intraoperative findings, so
that surgeons can utilize it in gaining informed consent
before and just after a hepatectomy. Microscopic
findings may be more precise and accurate but are ret-
rospective in clinical practice. Therefore microscopic
M. Makuuchi et al.: IHPBA report on HCC staging
findings were not employed in our staging system. Stag-
ing systems for other treatment modalities such as
transplantation, ablation, and transcatheter arterial
embolization will be required in future.
Various classifications including liver function
It is well known that most patients with hepatocellular
carcinoma (HCC) present with an underlying liver
disease, usually well-established cirrhosis. As a conse-
quence, some staging systems for HCC combine liver
function and appropriate tumor stage, while some
others do not do so, and this results in a heterogeneous
panel of classifications. Furthermore, concerning tumor
stage, although there is general agreement on some
of the factors which should be considered for classifica-
tion (tumor size; tumor number; presence or not of
vascular invasion, lymph node metastasis, and distant
metastases), combinations of the factors themselves are
generally too complex and heterogeneous among the
proposed staging systems. All these aspects make it dif-
ficult to analyze clinical and pathological findings and,
therefore, there is a need for a consensus on the staging
system which should be employed.
The degree of functional liver impairment is usually
assessed by the Child-Pugh classification,1 which was
devised to predict tolerance to portosystemic shunting,
but it does not include any information about the tumor,
and offers a vague estimate in patients with HCC. The
Okuda classification combines both tumor area occupy-
ing the liver (more or less than 50%) and liver function
(bilirubin and albumin levels, presence of ascites) and
divides HCC patients into three strata;2 however, it does
not take into account very important tumor characteris-
tics, such as vascular invasion. The Cancer of the Liver
Italian Program (CLIP) score has added to Okuda’s
classification the alphafetoprotein serum level and the
presence or not of portal vein invasion;3 however, in
spite of a clear separation of survivals among the differ-
ent groups, only 50% of patients with the most favor-
able outcome (CLIP score, 0) survived at 3 years and 6
months, which may indicate the inadequacy of this scor-
ing system. The Barcelona Clinic Liver Cancer (BCLC)
Staging Classification4 is derived from the aforemen-
tioned Okuda classification and the data reported in
studies describing the outcomes in patients treated by
potentially curative options and in untreated HCC
patients. Each stage contains the relevant prognostic
variables of the tumor, the patient’s performance
status, and the liver functional status independently
related to survival. This staging system attempts to pro-
vide not only a classification with prognostic relevance
but to give indications that are useful for treatment
selection.
27
Table 1. TNM/UICC classification
T factor
T1 Solitary, ⱕ2 cm, no vascular invasion
T2 Solitary, ⱕ2 cm, vascular invasion
Multiple/unilobar, ⱕ2 cm, no vascular invasion
Solitary, ⬎2 cm, no vascular invasion
T3 Solitary, ⬎2 cm, vascular invasion
Multiple/unilobar, ⱕ2 cm, vascular invasion
Multiple/unilobar, ⬎2 cm, irrespective of vascular
invasion
T4 Multiple/bilobar
Invasion of major portal or hepatic vein branch
(Invasion of adjacent organs)
(Perforation of visceral peritoneum)
Stage
I T1N0M0
II T2N0M0
III A T3N0M0
III B T1-3N1M0
IV A T4N0/1M0
IV B Any T/NM1
UICC, International Union Against Cancer
TNM/UICC classification
Most of the aforementioned staging systems consider
both the liver function and the tumor stage for the
classification, and certainly, background liver status and
hepatitis B virus (HBV) or HCV infections influence
survival. However, this makes staging classification too
complex. Furthermore, a cancer staging system which
does not include factors not strictly linked to the tumor
itself is probably to be preferred.
The TNM/UICC classification is wedely used by
oncologists, but it is too complicated and is not really
representative of the patients’ outcomes (Table 1): in
fact, for the T parameter, TNM classification considers,
other than factors such as tumor size, number, and
vascular invasion, variables such as tumor location
(uni- and bilateral) on which there are no unequivocal
reports.6,7 Furthermore, the lymph node involvement
cannot be established on the basis of the macroscopic
evidence, because swollen nodes can be consequences
of the chronic liver disease: therefore, for estimation of
the N factor, pathological diagnosis is needed.
History and database of the Liver Cancer Study
Group of Japan
The LCSGJ database started in 1964 and, since 1969,
periodical National Surveys have been performed. The
first LCSGJ report was about 452 patients with HCC.
Since then, every 2–3 years, LCSGJ reports have been
published. The 15th report has been released, and it
includes 18 843 new patients and, since the past decade,
28 M. Makuuchi et al.: IHPBA report on HCC staging

Table 2. New Liver Cancer Study Group of Japan (LCSGJ) 100

and International Hepato-Pancreato-Biliary Association 90
(IHPBA) classification
80
T factor 70
1. Solitary
2. No more than 2 cm 60

3. No vascular invasion (to PV, HV, and BD) 50

T1 meets all of the above three requirements. 40
T2 meets two of the three requirements.
30
T3 meets one of the three requirements.
T4 does not meet any requirements. 20

Stage 10
I T1N0M0
0
II T2N0M0 0 12 24 36 48 60 72 84 96 108 120 132 144
III T3N0M0
IV A T4N0M0
Any TN1M0 Fig. 2. Survival curves of patients classified by number of
IV B Any T/NM1 nodules, according to the 15th report by the Liver Cancer
PV, portal vein; HV, hepatic vein; BD, bile duct Study Group of Japan (LCSGJ)

100
100
90
90
80
80
70
70
60
60
50
50
40
40
30
30
20
20
10
10
0
0
0 12 24 36 48 60 72 84 96 108 120 132 144
0 12 24 36 48 60 72 84 96 108 120 132 144

Fig. 3. Survival curves of patients classified by presence and

Fig. 1. Survival curves of patients classified by tumor size,
according to the 15th report by the Liver Cancer Study Group
of Japan (LCSGJ)
every year 7000 to 10 000 patients have been enrolled.8
The General rules for clinical and pathological study of
primary liver cancer have been periodically published
since 1983, and now the 4th edition, with a new cancer-
stage classification has been published9 (Table 2). Based
on this classification, prognosis after hepatectomies has
been clearly differentiated, grouping the patients for
tumor size (Fig. 1), number (Fig. 2), and vascular inva-
sion (Fig. 3). However, differentiation of patients’ sur-
vival including the N factor did not have completely
satisfactory results, probably because of the afore-
mentioned difficulty in macroscopically differentiating
metastatic nodes from inflammatory ones. As a conse-
quence, T1–3N1 patients (stage IVA) had a survival
similar to that of T3N0M0 (stage III) (Fig. 4), while
T4N1 patients had significantly worse survivals than
T4N0 patients (Fig. 5). Therefore N parameters are still
a problem, with the prognosis of those patients with N1
degree of portal vein branch tumor invasion, according to the
15th report by the Liver Cancer Study Group of Japan
(LCSGJ). Vp0, no invasion; Vp1, invasion of third branches;
Vp2, invasion of secondary branches; Vp3, invasion of right or
left portal branches; Vp4, invasion of main portal vein
lymph node metastases ranging from stage III to stage
IVB. In fact, even considering the biases inherent in
this retrospective inference, there were no survivors at
2-year follow-up among patients who received lym-
phadenectomy and had histologically proven metastatic
involvement. This finding substantiates the fact that (i)
clinical and surgical staging are not adequate to define
the degree of lymph node involvement and (ii) the re-
sulting classifications contain discrepancies which make
prognostic evaluation not accurate.
AJCC vs LCSGJ classifications
Vauthey et al.10 have recently proposed a simplified
staging for HCC (Table 3), based on the AJCC/UICC
M. Makuuchi et al.: IHPBA report on HCC staging 29

% 100
100

90

80

70

60

50
50
40

30

20

10

0
0
0 12 24 36 48 60 72 84 96 108 120 100
0 50 150

Fig. 4. Impact of lymph node metastases on patients’ survival, Fig. 6. Patients’ survival according to new American Joint
according to the classification in the 14th report by the Liver Committee on Cancer (AJCC) classification (Vauthey et al.10)
Cancer Study Group of Japan (LCSGJ). Stage IVA due to
lymph node metastasis has better survival than stage III
100
%
100 90

90 80

80 70

70 60

60 50

50 40

40 30

30 20

20 10

10 0
0 12 24 36 48 60 72 84 96 108 120
0
0 12 24 36 48 60 72 84 96 108 120

Fig. 7. Patient survivals according to the new Liver Cancer

Fig. 5. Impact of lymph node metastases on patients’ survival, Study Group of Japan (LCSGJ) classification
according to the classification in the 14th report by the Liver
Cancer Study Group of Japan (LCSGJ). In T4 patients, lymph
node involvement significantly modified patients’ prognosis classification. For patient prognosis, it considers tumor
size, number, vascular invasion, lymph node involve-
Table 3. New American Joint Committee on Cancer (AJCC)
ment, and distant metastasis; degree of liver fibrosis had
classification (Vauthey et al.10)
a negative impact on all categories and was added as a
T factor worsening factor. To validate their staging system they
sT1 Single tumor without microvascular invasion
sT2 Single tumor with microvascular invasion collected data for 557 patients from four institutions;
Multiple tumors no more than 5 cm in diameter survivals are shown in Fig. 6. The new LCSGJ classi-
sT3 Tumors involving major branches of portal or fication looks simpler than the Vauthey one, and has
hepatic veins been validated in a larger number of patients: in fact,
Multiple tumors and any ⬎5 cm 21 711 patients were included, and survivals were clearly
Background liver status differentiated on the basis of this classification (Fig. 7).
F0 Group 0–4 fibrosis (none to moderate fibrosis)
While 5 cm is the cutoff level for grouping patients ac-
F1 Group 5–6 (severe fibrosis/cirrhosis)
cording to tumor size in the new AJCC classification,
Stage
I sT1N0M0 the cutoff level is lowered to 2 cm in the new LCSGJ
II sT2N0M0 classification. Whether the tumor cutoff size is classified
III A sT3N0M0 as 2 cm or 5 cm depends on the general level of early
III B sT1–3N1M0 detection of HCC in each country. In fact, the LCSGJ
IV sT1–3N0/1M1 collected 4213 patients, while Vauthey’s data included
S, simplified 58 patients, representing 19.4% and 10.4% of the entire
30
100
90
80
70
60
50
40
30
20
10
0
0 12 24 36 48 60
Fig. 8. Survival curves of T2 patients according to new Liver
Cancer Study Group of Japan (LCSGJ) classification,
stratified on the basis of which factor (solitary; less than 2 cm;
without vascular invasion) is lacking. VI, vascular invasion.
Cited with permission, from reference 11
number of resected patients, respectively, although the
latter one containing a major Japanese institution.
When annual check-ups for HCV carriers are carried
out widely in the United States, the number of patients
with tumors less than 2 cm in size may increase, and a
cutoff level of 2 cm may then become the reality, as it is
in Japan. Vauthey et al. claimed that the new LCSGJ
classification may result in underestimating the survival
of patients with nodules larger than 2 cm but smaller
than 5 cm without vascular invasion, or that it may over-
estimate the prognosis of patients with nodules smaller
than 2 cm and vascular invasion. However, the 5-year
survival of T2 patients classified according to the
LCSGJ based on tumor size larger than 2 cm (62%)
(Fig. 8) was similar to that of the remaining T2 patients
(stage II, 59.6%) (Fig. 7), and as well as being similar to
that of patients with tumors with diameters ranging
from 2 to 5 cm (53.3%) (Fig. 1), which includes T3 and
T4 patients of the LCSGJ classification. Conversely, the
number of tumors smaller than 2 cm and with vascular
invasion was just 14 among 21 711 (Fig. 8); this last
subgroup is a so-called orphan group, as it is too small to
be included in a staging classification.11
Conclusion
Although both of the most recent classifications seem to
be simpler and more adequate than the previous ones,
the one proposed by the LCSGJ seems to allow a more
precise estimation of patients’ prognosis, and this has
M. Makuuchi et al.: IHPBA report on HCC staging
been selected by this working group as the new classifi-
cation of the IHPBA (Table 2). The N parameter re-
mains to be better classified, although in larger samples
of patients, survivals are well differentiated among the
stage classes.
Acknowledgments. We would like to express our sincere
thanks to the following colleagues: Iwao Ikai, M.D.
(University of Kyoto, Kyoto, Japan); Masakazu
Yamamoto (Tokyo Womens Medical College, Tokyo,
Japan); Junji Yamamoto, M.D. (Cancer Institute,
72
Tokyo, Japan); Masami Minagawa, M.D. (University of
Tokyo, Tokyo, Japan); and Keji Sano, M.D. (University
of Tokyo, Tokyo, Japan) for their cooperation in the
data collection. We address our thanks also to Guido
Torzilli, M.D. (Hospital of Lodi, Lodi, Italy) for
preparing the present manuscript.
References
1. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R
(1973) Transection of the esophagus for bleeding esophageal
varices. Br J Surg 60:646–649
2. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N,
Hasegawa H, Nakajima Y, Ohnishi K (1985) Natural history of
hepatocellular carcinoma and prognosis in relation to treatment.
Study of 850 patients. Cancer 56:918–928
3. The Cancer of the Liver Italian Program (Clip) Investigators
(1998) CLIP. A new prognostic system for hepatocellular carci-
noma: a retrospective study of 435 patients: the Cancer of the
Liver Italian Program (CLIP) investigators. Hepatology 28:751–
755
4. Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular
carcinoma: the BCLC staging classification. Semin Liver Dis
19:329–338
5. International Union Against Cancer (UICC) (1997) TNM
classification of malignant tumors, 5th Edn. Wiley-Liss, New York
6. Lau H, Fan ST, Ng IO, Wong J (1998) Long term prognosis after
hepatectomy for hepatocellular carcinoma: a survival analysis of
204 consecutive patients. Cancer 83:2302–2312
7. Wu CC, Ho WL, Lin MC, Yeh DC, Wu HS, Hwang CJ, Liu TJ,
P’eng FK (1998) Hepatic resection for bilobar multicentric hepa-
tocellular carcinoma: is it justified? Surgery 123:270–277
8. Liver Cancer Study Group of Japan (2002) The 15th report
on follow-up and survey of primary liver cancer in Japan (in
Japanese)
9. Liver Cancer Study Group of Japan (2000) The general rules for
the clinical and pathological study of primary liver cancer, 4th
edn. (in Japanese). Kanehara, Tokyo
10. Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza
N, Curley SA, Ellis LM, Regimbeau JM, Rashid A, Cleary KR,
Nagorney DM (2002) Simplified staging for hepatocellular carci-
noma. J Clin Oncol 20:1527–1536
11. Ikai I, Yamaoka Y (2000) Nationwide survey of hepatocellular
carcinoma in Japan based on macroscopic stage in Classification
of Primary Liver Cancer (3rd edn) (in Japanese). Kan Tan Sui
(Hepato Biliary Pancreas) 41:481–490