Gastroenterology

Gastroenterology

Volume 150, Issue 4, April 2016, Pages 835-853
Gastroenterology

Reviews and Perspectives
Reviews in Basic and Clinical Gastroenterology and Hepatology
Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma

https://doi.org/10.1053/j.gastro.2015.12.041Get rights and content

Evidence-based management of patients with hepatocellular carcinoma (HCC) is key to their optimal care. For individuals at risk for HCC, surveillance usually involves ultrasonography (there is controversy over use of biomarkers). A diagnosis of HCC is made based on findings from biopsy or imaging analyses. Molecular markers are not used in diagnosis or determination of prognosis and treatment for patients. The Barcelona Clinic Liver Cancer algorithm is the most widely used staging system. Patients with single liver tumors or as many as 3 nodules ≤3 cm are classified as having very early or early-stage cancer and benefit from resection, transplantation, or ablation. Those with a greater tumor burden, confined to the liver, and who are free of symptoms are considered to have intermediate-stage cancer and can benefit from chemoembolization if they still have preserved liver function. Those with symptoms of HCC and/or vascular invasion and/or extrahepatic cancer are considered to have advanced-stage cancer and could benefit from treatment with the kinase inhibitor sorafenib. Patients with end-stage HCC have advanced liver disease that is not suitable for transplantation and/or have intense symptoms. Studies now aim to identify molecular markers and imaging techniques that can detect patients with HCC at earlier stages and better predict their survival time and response to treatment.

Section snippets

Identification of Patients at Risk

The most significant risk factor for HCC is cirrhosis. Not all patients with cirrhosis are at equal risk for HCC, and HCC is not always found in patients with cirrhosis. There are no reliable data on the incidence of HCC in patients without cirrhosis. In addition to cirrhosis, other factors associated with increased risk include male sex, older age, persistent increase in alanine aminotransferase level, increased α-fetoprotein (AFP) level, and progressive impairment of liver function.9 However,

Diagnosis

Patients can be diagnosed with HCC based on imaging or biopsy analyses. The specific imaging patterns observed by magnetic resonance imaging or computed tomography analyses in nodules >10 mm in cirrhotic livers or livers of patients at high risk for HCC are intense uptake of contrast during the arterial phase followed by contrast washout in the venous or delayed phases.9, 43, 64, 65, 66, 67, 68 HCCs contain mostly arterial blood and are therefore brighter during the arterial phase than the

Staging

The Barcelona Clinic Liver Cancer (BCLC) system has been widely validated and is the most commonly used staging system for HCC (Figure 2).79, 80, 81, 82 It determines cancer stage and patient prognosis based on tumor burden, severity of liver disease, and the patient’s performance status. Very early and early-stage HCC (BCLC 0 or BCLC A) include patients with a solitary lesion or up to 3 nodules ≤3 cm (without macrovascular invasion or extrahepatic spread) with preserved liver function.

Molecular Markers of Risk, Diagnosis, and Determination of Prognosis and Treatment

Recent insights into mechanisms of HCC pathogenesis as well as studies of large sets of tumors and patients have identified factors that might be used in determining patients’ risk of HCC, their prognosis, or the best treatment. However, translation of findings from studies of cells and experimental models requires clinical trials. Most analyses have been based on retrospective studies of tumor and patient samples from tissue banks. Clinical information has been limited and does not incorporate

Treatment

The end point of treatment is to increase survival. Treatments should not be offered because they are technically possible.102 Treatment indications have been refined, and if patients are not candidates for first-line therapy as per stage, they can be given the treatment for a more advanced-stage tumor (treatment stage migration; see Figure 3).82

Radioembolization

Radioembolization is the intra-arterial injection of microspheres loaded with yttrium-90, a pure β-emitter with a short half-life (2.67 days) and a limited capacity to penetrate tissues (mean depth of penetration of 2.5 mm; maximum of 11 mm). Two types of yttrium-90 microspheres are commercially available: glass (TheraSphere; BTG, London, United Kingdom) and resin microspheres (SIR-Spheres; Sirtex SIR-Spheres Pty Ltd, Sidney, Australia).188 The efficacy of radioembolization has been assessed in

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    Conflicts of interest The authors disclose the following: Morris Sherman has received consulting honoraria from Bayer, Daichii Sankyo, Merck, and Celsion. Jordi Bruix has consulted for for Gilead, Abbvie, Kowa, Bayer, BTG, Arqule, Terumo, BMS, Boehringer Ingelheim, Kowa, Novartis, OSI, Roche and Onxeo. Maria Reig has received consulting honorari from Bayer.

    Funding CIBEREHD is supported by the Instituto de Salud Carlos III. J.B. and M.R. are supported by a grant from the Instituto de Salud Carlos III (PI14/00962 and PI15/00145). J.B. from AECC PI044031.

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