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 briefly describe only new or changed recommendations.
Surveillance and Diagnosis
In the previous guideline, groups were specified for which surveillance was likely
to be cost-effective because the hepatocellular carcinoma (HCC) incidence was high
enough. New data on defining 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 specificity 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 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 confirms
HCC.10
Fig. 1
Diagnostic algorithm for suspected HCC. CT, computed tomography; MDCT, multidetector
CT; MRI, magnetic resonance imaging; US, ultrasound.
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.
Fig. 2
The BCLC staging system for HCC. M, metastasis classification; N, node classification;
PS, performance status; RFA, radiofrequency ablation; TACE, transarterial chemoembolization.
The recommendations for liver transplantation have not changed. No new data have emerged
that can be used to define a new limit for expanding the patient selection criteria.
The usefulness of portal pressure measurement to predict the outcome of patients and
define optimal candidates for resection has been validated in Japan.12 Thus, resection
should remain the first option for patients who have the optimal profile, as defined
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 confirmed
by other groups before positioning ablation as the first-line 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 there
are no data comparing its efficacy 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 efficacy of sorafenib (a multikinase inhibitor with activity against
Raf-1, B-Raf, vascular endothelial 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 associated toxicity is easily
managed without treatment-related mortality. The most frequent adverse events were
diarrhea (sorafenib versus placebo: 11% versus 2%) and hand–foot skin reaction (sorafenib
versus placebo: 8% versus <1%), fatigue, and weight loss. Sorafenib is now considered
first-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.