The diagnosis and treatment of hepatocellular carcinoma

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Abstract

Hepatocellular carcinoma is a leading cancer worldwide. Its incidence is increasing, and is closely related to advanced liver disease. Cirrhosis represents the greatest risk factor for this malignancy, and is the main indication for screening and surveillance. The diagnosis of hepatocellular carcinoma can frequently, and uniquely, be made on characteristic multiphase contrast based cross-sectional imaging rather than strict need for tissue sampling. Despite advances in medical, locoregional and surgical therapies, hepatocellular carcinoma remains one of the most common causes of cancer-related death globally. In this review, current approaches to management of hepatocellular carcinoma are discussed, which incorporate both tumor and patient factors. The salient considerations in surgical (resection, liver transplantation), locoregional (ablation and embolic therapies) and medical therapies are highlighted.

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Background

As of 2008, hepatocellular carcinoma (HCC) was the 5th and 7th most common cancer in adult men and women, and the 2nd and 6th leading cause of cancer death worldwide, respectively.1 The number of deaths worldwide, 695,900 in 2008, was nearly equal to the annual incidence of 748,300 newly diagnosed HCCs in 2008, nearly 80% of which were attributed to chronic hepatitis B and C.2 In developing countries for instance, HBV and HCV are responsible for 60% and 33% of HCC respectively, versus 23% and

Risk factors

Cirrhosis of any etiology increases the risk of HCC, especially if due to hepatitis C (HCV), hepatitis B (HBV), Non-Alcoholic Fatty Liver disease (NAFLD) or Hereditary Hemochromatosis (HH). Chronic HCV is responsible for over one-third of HCC cases in United States, with over 90% either cirrhotic or advanced fibrosis at time of diagnosis.8, 9 Risk increases with age, male gender, HBV or HIV co-infection, heavy alcohol use and diabetes mellitus and decreases following successful HCV treatment.10

Screening guidelines

The American Association for the Study of the Liver Disease (AASLD) recommends screening all cirrhotics and high-risk chronic HBV patients with liver ultrasound every 6 months. The criteria for screening in patients with HBV include; cirrhosis, Asian men >40 years old, Asian women >50 years old, Africans/North American blacks, and a family history of HCC. Furthermore, HCC screening is recommended in Caucasian patients with long-term high viral load and/or active inflammation defined by elevated

Diagnosis

The diagnosis of HCC is unique in that histopathological tissue examination is not mandatory. In most cases, diagnosis can be established on imaging based on guidelines promulgated by AASLD and European Association for the Study of the Liver (EASL).21, 26 In brief, assuming tumor meets imaging criteria in patient at increased risk, biopsy is rarely needed. As such, any solid nodule in a cirrhotic patient not consistent with a hemangioma is HCC until proven otherwise. These diagnostic imaging

Staging

Accurate staging of HCC ultimately dictates therapeutic options and overall prognosis. There are multiple staging systems; the commonly used staging systems for HCC assess some or all of the following clinical features: tumor size, local tumor extent, extra-hepatic metastases, severity of liver disease and patient performance status. The two commonly used systems are American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) which only characterizes tumor features and metastases, and

Treatment

There are multiple therapeutic modalities for HCC, which include surgical options (resection or liver transplantation (LT)), ablative electrochemical therapies (e.g. radiofrequency ablation or ethanol injection). Non-ablative treatment includes catheter based embolic therapies (e.g. chemoembolization and radioembolization) and non-catheter based therapy such as stereotactic body radiotherapy (SBRT). Finally, systemic therapy in the current era comprises solely of sorafenib, a multikinase

Prognosis

Prognosis of HCC is extremely variable with multiple determinants. Though multiple staging and prognostic systems have been developed, none are universally applicable or agreed upon for predicting survival .51, 99, 100 Though BCLC is well accepted and recommended by EASL and AASLD for staging, prognostication and treatment allocation, TNM is better validated for resection and transplant compared to BCLC for non-surgical advanced HCC.45

Regarding TNM, 5-year survival rates for patients undergoing

Summary

In summary, HCC is an important worldwide cause of cancer related mortality. Risk of HCC is related almost entirely to liver disease with advanced fibrosis, particularly viral hepatitis. Early detection requires adherence to imaging surveillance guidelines. The treatment of HCC requires multidisciplinary teams due to the varied therapeutic options and risk of progression. The associated outcomes are dependent on both tumor and patient factors.

Conflict of interest

Dr. Justin Hartke and Dr. Marwan Ghabril have no conflicts of interest to disclose. Dr. Matthew Johnson receives research support from Novate Medical (Dublin, Ireland); BTG (London, United Kingdom); and, Cook, Inc. (Bloomington, IN). He is a Consultant for BTG plc (London, United Kingdom); Cook, Inc. (Bloomington, IN); Argon Medical Devices (Plano, TX); Avantec (San Francisco, CA); Bayer (Whippany, NJ); Boston Scientific (Natick, MA); Bristol Meyers Squibb (New York, NY); Guerbet (Paris,

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