Elsevier

The Lancet

Volume 362, Issue 9399, 6 December 2003, Pages 1907-1917
The Lancet

Seminar
Hepatocellular carcinoma

https://doi.org/10.1016/S0140-6736(03)14964-1Get rights and content

Summary

Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer, and its incidence is increasing worldwide because of the dissemination of hepatitis B and C virus infection. Patients with cirrhosis are at the highest risk and should be monitored every 6 months. Surveillance can lead to diagnosis at early stages, when the tumour might be curable by resection, liver transplantation, or percutaneous treatment. In the West and Japan, these treatments can be applied to 30% of patients, and result in 5-year survival rates higher than 50%. Resection is indicated among patients who have one tumour and well-preserved liver function. Liver transplantation benefits patients who have decompensated cirrhosis and one tumour smaller than 5 cm or three nodules smaller than 3 cm, but donor shortage greatly limits its applicability. This difficulty might be overcome by living donation. Most HCC patients are diagnosed at advanced stages and receive palliative treatments, which have been assessed in the setting of 63 randomised controlled trials during the past 25 years. Meta-analysis shows that only chemoembolisation improves survival in well-selected patients with unresectable HCC.

Section snippets

Risk factors and prevention

HCC is one of the few cancers with well-defined major risk factors.6, 7 In 80% of cases HCC develops in cirrhotic livers, and cirrhosis is the strongest predisposing factor.7 Geographical differences in incidence reflect variations of the main causal factors (Table 2, Table 3).6 In Asia and Africa, hepatitis B virus infection is common,8 together with aflatoxin B1 intake from contaminated food.9 In the West and Japan, hepatitis C virus infection is the main risk factor,10, 11, 12, 13 as well as

Surveillance and diagnosis

In established cirrhosis, surveillance to detect early HCC is recommended to decrease tumour-related deaths.27 Despite the lack of randomised controlled trials, in cohort studies of surveillance, the early detection rate and applicability of curative treatments increases. Randomised controlled trials with non-screened groups are unlikely to be developed, at least in the West, and, thus, the survival benefit cannot be proven.28, 29 A panel of specialists set up by the European Association for

Natural history and prognosis

Two decades ago, the reported prognosis of HCC was dismal. Most patients died within 1 year, irrespective of treatment.39 In developed countries this outcome has completely changed, since 30–40% of patients are now being diagnosed at initial stages when curative treatments can be optimally applied.40 Therefore, estimates of outcome need to take into account the stage at diagnosis.

Staging systems

Staging systems should separate patients into groups with homogeneous prognosis, and serve to select appropriate treatment. In oncology, tumour stage is the main outcome predictor, but prognostic modelling in HCC is more complex. Survival is also determined by liver function, which in turn affects the applicability of treatments. This pattern is relevant, since survival at early stages is modified by treatment and thus prognostic prediction has to include treatment-related variables.27

Treatment of HCC

Treatments for HCC have been conventionally divided into curative and palliative. Curative treatments, such as resection, liver transplantation, and percutaneous ablation, induce complete responses in a high proportion of patients and are expected to improve survival. Palliative treatments are not aimed to cure, but in some cases can obtain good response rates and even improve survival. Table 4 summarises the sources of evidence of the benefits of all these treatments in HCC patients. Table 5,

Treatment strategy

Evidence-based treatment for HCC relies on fewer than 100 randomised controlled trials and many observational studies. Furthermore, geographical differences in the incidence, presentation, and treatments available, have promoted the debate of a treatment strategy for this disease. Several treatment guidelines have been published.54, 79, 128, 129 The Barcelona-Clínic Liver Cancer staging system links tumoural stage with a treatment strategy, and is aimed at incorporating prognosis estimation and

Search strategy

We searched PubMed, Cancerlit (National Cancer Institute), and the Cochrane Library database, using hepatocellular carcinoma, liver cancer, and primary liver carcinoma as free text words, and in combination with randomized, controlled clinical trials, clinical trials, phase III studies, double-blind, placebo, review, meta-analysis, therapy, and treatment. We also did a manual search and review of reference lists. We selected for inclusion randomised controlled trials published as full papers in

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