Autoimmune Hepatitis, Cirrhosis, and Hepatocellular Carcinoma (HCC)

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer death. The success of treatment for HCC largely depends on the stage at which it is diagnosed, with 5-year survival rates of 70–75% in patients with compensated cirrhosis and early HCC [1–4]. As HCC usually arises in individuals with the clearly defined underlying risk factor of chronic liver disease, a focus on early detection through screening and surveillance programs in individuals with proven cirrhosis had been adopted by most clinicians [5, 6] despite an initial lack of supportive evidence. A randomised controlled trial of surveillance versus no surveillance performed in China in 2004 recruited nearly 19,000 patients having markers of current or past hepatitis B infection. Despite poor compliance, the HCC-related mortality in the surveillance arm was reduced by 37% [7]. It is not clear, however, whether screening is appropriate and cost effective for all aetiologies of cirrhosis. The decision to enter a patient into a surveillance program is dependant on the risk of HCC development. There are a number of models which calculate cost-effectiveness dependant upon the incidence of HCC in a particular population, and the modality of screening used. A study published in 1996, which did not include orthotopic liver transplantation (OLT) as a treatment option, found that if the incidence of HCC was 1.5% per year, surveillance resulted in an increased longevity of approximately 3 months. If the incidence was 6% per year, the survival was increased to 9 months [8]. Using a similar analysis, Arguedas et al. [9] found that surveillance with computed tomography (CT) scanning (either alone or in combination with ultrasound) became cost effective when the incidence of HCC was greater than 1.4%. A more recent study published in 2004 by Lin et al. [10] demonstrated that surveillance with ultrasound (US) and alpha-fetoprotein (AFP) is cost effective regardless of HCC incidence. The cost-effectiveness largely depends on the outcomes of treatment, and so studies like the Chinese program, which lacked access to OLT, are not necessarily relevant to other centers where transplantation is the first-line treatment for patients with cirrhosis and a small tumour. The incidence of HCC in cirrhosis caused by non-viral aetiologies is still not accurately established due to many preliminary studies being performed prior to the discovery of the hepatitis C virus. Current guidelines of the American Association for the Study of Liver Diseases (AASLD) suggest that surveillance should be offered when the risk of HCC exceeds 1.5%/year [5, 6]. The optimal interval for US surveillance is still controversial. The Clinical Practice Guidelines for Hepatocellular Carcinoma 2005 (Japan) recommends US surveillance with an interval of 6 months for patients at a risk of HCC and surveillance every 3–4 months in those at extremely high risk [11]. In contrast, the guidelines proposed by the American Association for study of Liver Diseases (AASLD) proposes that US be performed at 6-month intervals for all patients at risk of HCC regardless of the magnitude of risk but based on expected tumour doubling times. Although the retrospective study by Zhang et al. used a surveillance interval of 6 months, [7] several other studies report that the likelihood of finding HCC at the single nodule stage is no different between 6and 12-month surveillance intervals [12, 13]. One nonrandomised prospective study in patients with hepatitis B P. J. Trivedi (&) S. Cullen Department of Gastroenterology, Wycombe General Hospital, Queen Alexandra Road, High Wycombe, Buckinghamshire HP11 2TT, UK e-mail: palak.trivedi@buckshosp.nhs.uk