Surveillance for hepatocellular carcinoma in chronic liver disease: Evidence and controversies

Abstract

Primary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and generally occurs in patients with underlying chronic liver disease such as viral hepatitis, hemochromatosis, primary biliary cirrhosis and non-alcoholic steatohepatitis. Especially cirrhotic patients are at risk of HCC and regular surveillance could enable early detection and therapy, with potentially improved outcome. We here summarize existing evidence for surveillance including ultrasound, other radiological modalities and various serum biomarkers, and current international guideline recommendations for surveillance. Ultrasound and α-fetoprotein (alone or in combination) are most frequently used for surveillance, but their sensitivities and specificities are still far from perfect, and evidence for surveillance remains weak and controversial. Various other potential surveillance tools have been tested, including serum markers as des-carboxyprothrombin, lectin-bound α-fetoprotein, and (most recently) circulating TIE2-expressing monocytes, and radiological investigations such as computed tomography-scan or magnetic resonance imaging-scan. Although early results appear promising, these tools have generally been tested in diagnostic rather than surveillance setting, and in most cases, no detailed information is available on their cost-effectiveness. For the near future, it remains important to define those patients with highest risk of HCC and most benefit from surveillance, and to restrict surveillance to these categories.

Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

“…Because mainly small tumors are accessible to curative treatments and such tumors are asymptomatic, identification of high risk individuals that would benefit from surveillance and novel biomarkers for early detection of this highly lethal disease are urgently needed. For the last 40 years, α-fetoprotein (AFP) has been the only serum marker routinely used by clinicians together with ultrasound for the detection and surveillance of HCC, despite its low sensitivity (ranging from 41 to 65%) for the detection of early-stage HCC (6, 7). …”

Proposal of a predictive model for advanced fibrosis containing Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein in chronic hepatitis C

“…The risk for development of HCC in patients with CHC is associated with liver fibrosis stage. In cirrhotic subjects, the annual incidence of HCC in Japan is extremely high (approximately 7% per year) . Although the introduction of highly effective direct‐acting antiviral agents for CHC patients is expected to reduce the incidence of CHC‐related HCC, the achievement of a sustained virological response does not mean that it eliminates the risk of HCC, especially when the subjects have already developed advanced liver fibrosis .…”

No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long‐term follow‐up

“…There is substantial evidence favoring surveillance in case of hepatitis B or C, and to a lesser extent, in case of cirrhosis due to alcohol, primary biliary cirrhosis, or hemochromatosis . However, strong evidence is lacking for many other cirrhotic conditions.…”