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A MERICAN A SSOCIATION FOR
T HE STUDY OF LIVER D I S E ASES
AASLD PRACTICE GUIDELINE

Management of Hepatocellular Carcinoma: An Update
Jordi Bruix,1 and Morris Sherman2
Since the publication of the American Association for
the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma
(HCC) in 2005, new information has emerged that
requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD
Web site at http://www.aasld.org/practiceguidelines/
Documents/Bookmarked%20Practice%20Guidelines/
HCCUpdate2010.pdf. Here, we briey describe only
new or changed recommendations.
Surveillance and Diagnosis

In the previous guideline, groups were specied for
which surveillance was likely to be cost-effective
because the hepatocellular carcinoma (HCC) incidence
was high enough. New data on dening HCC risk
have emerged for hepatitis B virus,1,2 hepatitis C virus,3 and autoimmune hepatitis.4 Surveillance is
deemed cost-effective if the expected HCC risk exceeds
1.5% per year in patients with hepatitis C and 0.2%
per year in patients with hepatitis B. Analysis of recent
studies show that alpha-fetoprotein determination lacks
adequate sensitivity and specicity for effective surveillance (and for diagnosis).5,6 Thus, surveillance has to
be based on ultrasound examination. The recommended screening interval is 6 months. Diagnosis of
HCC should be based on imaging techniques and/or
biopsy.The 2005 diagnostic algorithm has been validated and the diagnostic accuracy of a single dynamic
Abbreviations: AASLD, American Association for the Study of Liver
Diseases; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular
carcinoma.
From the 1Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital
Clnic, University of Barcelona, Institut dInvestigacions Biome`diques August Pi i
Sunyer, Barcelona, Spain; and 2University of Toronto and University Health
Network, Toronto, Canada.
Received January 3, 2011; accepted January 8, 2011.
Address reprint requests to: Jordi Bruix, M.D., Hospital Clinic, University of
Barcelona, IDIPAPS, CIBERehd, c/Villarroel 170, Barcelona 08036,
Catalonia, Spain. E-mail: [email protected]; fax: (34) 93-227-9803.
C 2011 by the American Association for the Study of Liver Diseases.
Copyright V
View this article online at wileyonlinelibrary.com.
DOI 10.1002/hep.24199
Potential conict of interest: Dr. Bruix advises, consults for, serves on the
speakers bureau of, and received grants from Bayer. Dr. Bruix consults for
Biocompatibles, GlaxoSmithKline, Kowa, Novartis, and Arqule. Dr. Bruix also
advises and consults for Bristol-Myers Squibb. Dr. Sherman serves on the
speakers bureau of Bayer
1020
technique showing intense arterial uptake followed by

washout of contrast in the venous-delayed phases has
been demonstrated.7-9 Contrast-enhanced US may
offer false positive HCC diagnosis in patients with
cholangiocarcinoma and thus, has been dropped from
the diagnostic techniques. The diagnostic algorithm is
shown in Fig. 1. The application of dynamic imaging
criteria should be applied only to patients with cirrhosis of any etiology and to patients with chronic hepatitis B who may not have fully developed cirrhosis or
have regressed cirrhosis. Interpretation of biopsies and
distinction between high-grade dysplatic nodules and
HCC is challenging. Expert pathology diagnosis is reinforced by staining for glypican 3, heat shock protein
70, and glutamine synthetase, because positivity for
two of these three stains conrms HCC.10
Staging and Treatment of HCC

The BCLC staging system (Fig. 2)11 has come to be
widely accepted in clinical practice and is also being used
for many clinical trials of new drugs to treat HCC. Therefore, it has become the de facto staging system that is used.
The recommendations for liver transplantation have
not changed. No new data have emerged that can be
used to dene a new limit for expanding the patient
selection criteria. The usefulness of portal pressure measurement to predict the outcome of patients and dene
optimal candidates for resection has been validated in
Japan.12 Thus, resection should remain the rst option
for patients who have the optimal prole, as dened by
the BCLC staging system. Although resection can be
performed in some of these patients with advanced liver
disease, the mortality is higher and they might be better
served by liver transplantation or ablation. A cohort
study of radiofrequency ablation demonstrated that
complete ablation of lesions smaller than 2 cm is possible in more than 90% of cases, with a local recurrence
rate of less than 1%.13 These data should be conrmed
by other groups before positioning ablation as the rstline approach for very early HCC.
The recommendations regarding patient selection
and method of administration of chemoembolization
are unchanged. Radioembolization, i.e., the intra-arterial injection of yttrium-90 bound to glass beads or to
resin, has been shown to induce tumor necrosis, but
HEPATOLOGY, Vol. 53, No. 3, 2011
BRUIX AND SHERMAN
1021
Fig. 1. Diagnostic algorithm for suspected HCC. CT, computed tomography;

MDCT, multidetector CT; MRI, magnetic
resonance imaging; US, ultrasound.
there are no data comparing its efcacy to transarterial

chemoembolization or to sorafenib treatment for those
with portal vein invasion. However, for patients who
have either failed transarterial chemoembolization or
who present with more advanced HCC, new data
indicates the efcacy of sorafenib (a multikinase inhibitor with activity against Raf-1, B-Raf, vascular endo-
thelial growth factor receptor 2, platelet-derived

growth factor receptor, c-Kit receptors, among other
kinases) in prolonging life.14,15 Sorafenib induces a
clinically relevant improvement in time to progression
and in survival The magnitude of the improvement in
survival compares with other established molecular targeted therapies for other advanced cancers, and the
Fig. 2. The BCLC staging system for HCC. M, metastasis classication; N, node classication; PS, performance status; RFA, radiofrequency
ablation; TACE, transarterial chemoembolization.
1022
BRUIX AND SHERMAN
associated toxicity is easily managed without treatment-related mortality. The most frequent adverse
events were diarrhea (sorafenib versus placebo: 11%
versus 2%) and handfoot skin reaction (sorafenib versus placebo: 8% versus <1%), fatigue, and weight
loss. Sorafenib is now considered rst-line treatment in
patients with HCC who can no longer be treated with
potentially more effective therapies.
In summary, in the past decade HCC has gone
from being an almost universal death sentence to a
cancer that can be prevented, detected at an early
stage, and effectively treated. Physicians caring for
patients at risk need to provide high-quality screening,
proper management of screen-detected lesions, and
provision of therapy that is most appropriate for the
stage of disease.
References
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Nomograms for risk of hepatocellular carcinoma in patients with
chronic hepatitis B virus infection. J Clin Oncol 2010;28:2437-2444.
3. Lok AS, Seeff LB, Morgan TR, di Bisceglie AM, Sterling RK, Curto
TM, et al. Incidence of hepatocellular carcinoma and associated risk
factors in hepatitis C-related advanced liver disease. Gastroenterology
2009;136:138-148.
4. Yeoman AD, Al-Chalabi T, Karani JB, Quaglia A, Devlin J, Mieli-Vergani G, et al. Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: Implications for follow-up
and screening. HEPATOLOGY 2008;48:863-870.
5. Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers MA, et al.
Meta-analysis: surveillance with ultrasound for early-stage hepatocellular
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A MERICAN A SSOCIATION FOR

T HE STUDY OF LIVER D I S E ASES

AASLD PRACTICE GUIDELINE

Surveillance and Diagnosis

technique showing intense arterial uptake followed by

Staging and Treatment of HCC

HEPATOLOGY, Vol. 53, No. 3, 2011

BRUIX AND SHERMAN

Fig. 1. Diagnostic algorithm for suspected HCC. CT, computed tomography;

there are no data comparing its efcacy to transarterial

thelial growth factor receptor 2, platelet-derived

BRUIX AND SHERMAN

HEPATOLOGY, March 2011

carcinoma in patients with cirrhosis. Aliment Pharmacol Ther 2009;30:

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