Description of the condition
Hepatocellular carcinoma is the most common type of primary liver cancer (Lau 2000; Di Bisceglie 2010). It is also the fifth most commonly occurring cancer worldwide and the third leading cause of cancer death. In 2008, 1.2% (700,000) of all deaths were due to hepatocellular carcinoma (WHO 2012). Hepatocellular carcinoma incidence varies worldwide. Traditionally, some countries with high endemicity of hepatitis B (eg, China, Southeast Asia, and sub-Saharan Africa) have had higher incidence of hepatocellular carcinoma. People in these countries become infected with hepatitis B virus at an earlier age compared to people living in high-income countries. However, since the early 2000s, high-income countries have also seen an increased incidence of hepatocellular carcinoma. This seems to be related to a rise in other risk factors such as alcoholism, hepatitis C, and type 2 diabetes mellitus (Davila 2004; Hassan 2010; McGlynn 2011). Additional risk factors can include aflatoxin B1, obesity, and rare metabolic disorders (Sanyal 2010). Early detection of hepatocellular carcinoma has always been difficult, and there are no satisfactory markers for surveillance or early screening of asymptomatic people (Bruix 2005). People at risk, such as hepatitis B carriers and those suffering from non-hepatitis B cirrhosis, are recommended for hepatocellular carcinoma screening every six to 12 months using abdominal ultrasound and an alpha-foetoprotein test (Bruix 2005). People may present with abdominal pain, hepatomegaly, jaundice, ascites, and liver dysfunction (Di Bisceglie 2010). Diagnostic tests commonly include blood tests which may reveal raised levels of alpha-fetoprotein or the more specific L3 subfraction of alpha-fetoprotein (AFP-L3) and des-γ-carboxyprothrombin (DCP) (Lui 2011). Other medical imaging methods include computed tomography and magnetic resonance imaging (Bruix 2005). Liver biopsy can usually confirm the diagnosis of hepatocellular carcinoma, but it is not always required (Bruix 2005). Despite the use of high-quality imaging and fluoroscopy-guided biopsy, most people are diagnosed either when the tumour has developed further locally or has metastasised.
The overall prognostic outlook remains poor once hepatocellular carcinoma has been diagnosed. Traditional prognostic variables, such as tumour size, lymph node involvement, and liver functions, have not been useful in predicting outcomes. The median survival of untreated people is about one to nine months from diagnosis, depending on the stage and geographical region (Okuda 1985; Calvet 1990; Kakizaki 1997; Yeung 2005). High-income countries have not had optimistic results either; in the US, one-year survival was less than 50% and five-year survival was 16% in last decade (Altekruse 2009; Siegel 2013). People who undergo resection could have better prognosis, with a median survival of around 40 months and five-year survival of 40% to 60% (Katz 2009; Nathan 2009; Zhou 2012). Although resection is considered a curative treatment for hepatocellular carcinoma, five-year recurrence remains at 70% to 100% (Poon 2000), and it is rare to have a long-term disease-free survival after resection (Yeh 2003). Adjuvant treatments may reduce recurrence of hepatocellular carcinoma and lead to better prognosis (Okada 2001).
Description of the intervention
Transarterial embolisation was first used in Japan to treat hepatocellular carcinoma (Doyon 1974). Hepatocellular carcinoma tumours are supplied by branches of the hepatic artery, while normal hepatic tissue receives the majority (two-thirds) of its blood supply from the portal vein (Breedis 1954; Nakashima 1986). It is this idiosyncrasy in vascularisation that is exploited by transarterial embolisation techniques when branches of the hepatic artery are embolised. Transarterial embolisation is usually performed by catheterising the femoral artery under a local anaesthetic, and a catheter is guided into the hepatic artery under direct fluoroscopic visualisation, followed by injection of iodised oil, gelatin, or polyvinyl alcohol particles (Lin 2003; Pua 2008). As its use has become more widespread, transarterial embolisation was augmented using antineoplastic drugs. This is also known as transarterial chemoembolization (Sakamoto 1998; Lee 2002; Liapi 2011).
How the intervention might work
Embolisation of the hepatic artery may lead to ischaemia of the hepatocellular carcinoma and consequent necrosis. Intra-arterial perfusion of antineoplastic drugs (eg, cisplatin, doxorubicin, adriamycin, mitomycin C) may intensify the antineoplastic effect, with higher local drug concentration and fewer systemic adverse effects. The key to the success of transarterial (chemo)embolization is the exact identification of the arteries supplying the hepatocellular carcinoma and selectively (chemo)embolising them. Important complications of transarterial embolisation/transarterial chemoembolization include vascular perforation, portal vein thrombosis, deterioration of hepatic function, liver abscess and subsequent sepsis, tumour rupture, gastrointestinal bleeding, and postembolization syndrome (Kurokawa 2006).
Transarterial embolisation/transarterial chemoembolization has been used as adjunctive treatment during hepatectomy and as a bridge for liver transplantation, among other indications. It has been used for both resectable and unresectable hepatocellular carcinomas, although evidence for its effectiveness is lacking (Chua 2010; Oliveri 2011). Survival following curative resections is also unsatisfactory. Intrahepatic recurrence following hepatectomy at three years was more than 50% and at five years it was 70% (Otto 1998; Imamura 2003). Most of these recurrences occurred early, within six months (Lu 2008), and are likely to be related to intrahepatic metastases (Poon 2011). The early use of transarterial embolisation/transarterial chemoembolization following hepatectomy may reduce the likelihood of intrahepatic metastases and thereby help reduce recurrence and improve survival.
Why it is important to do this review
Various interventions for hepatocellular carcinoma have been used, either singly or in combination. These have included surgical interventions (eg, tumour resection, cryosurgery, liver transplantation), percutaneous interventions (eg, ethanol, radiofrequency ablation), transarterial interventions (eg, embolisation, chemoembolization), immunotherapy, or hormonal therapy. Curative treatments such as tumour resection and liver transplantation seem ideal. However, only 30% of people are eligible (Rampone 2009). For advanced stages of the tumour, treatments such as tamoxifen, octreotide, and interferon have proved unsuccessful, and more recently, sorafenib has shown promise, but it needs further evaluation (Zhang 2010).
Postoperative transarterial embolisation/transarterial chemoembolization may enhance the curative effects of hepatectomy by erasing the tumour cells that were not removed by surgery, but several studies have reported mixed results (Izumi 1994; Li 1995; Li 2006; Peng 2009; Zhong 2009). Some meta-analyses have reviewed this and suggested that postoperative adjuvant transarterial embolisation/transarterial chemoembolization is a promising method (Mathurin 2003; Marelli 2006; Lau 2009; Zhong 2010). However, there have been concerns about their methodological quality of these studies. It is important to evaluate the available evidence systematically in order to provide objective information to policy-makers and patients who may be able to make better-informed choices of the treatment options available for this condition. We have been unable to identify any systematic reviews on the topic.