Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B
ABSTRACT Chronic hepatitis B virus infection is a risk factor for development of hepatocellular carcinoma. Alpha-foetoprotein and liver ultrasonography are used to screen patients with chronic hepatitis B for hepatocellular carcinoma. It is uncertain whether screening is worthwhile.
To determine the beneficial and harmful effects of alpha-foetoprotein or ultrasound, or both, for screening of hepatocellular carcinoma in patients with chronic hepatitis B virus infection.
Electronic searches were performed until December 2011 in the Cochrane Hepato-Biliary Group Controlled Trials Register (December 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4) in The Cochrane Library, MEDLINE (1948 to 2011), EMBASE (1980 to 2011), Science Citation Index Expanded (1900 to 2011), Chinese Medical Literature Electronic Database (WanFang Data 1998 to 2011), and Chinese Knowledge Resource Integrated Database (1994 to 2011).
All published reports of randomised trials on screening for liver cancer were eligible for inclusion, irrespective of language of publication. Studies were excluded when the hepatitis B status was uncertain, the screening tests were not sensitive or widely-used, or when the test was used for diagnosis of hepatocellular carcinoma rather than screening.
We independently analysed all the trials considered for inclusion. We wrote to the authors of one of the trials to obtain further information.
Three randomised clinical trials were included in this review. All of them had a high risk of bias. One trial was conducted in Shanghai, China. There are several published reports on this trial, in which data were presented differently. According to the 2004 trial report, participants were randomised to screening every six months with alpha-foetoprotein and ultrasonography (n = 9373) versus no screening (n = 9443). We could not draw any definite conclusions from it. A second trial was conducted in Toronto, Canada. In this trial, there were 1069 participants with chronic hepatitis B. The trial compared screening every six months with alpha-foetoprotein alone (n = 532) versus alpha-foetoprotein and ultrasound (n = 538) over a period of five years. This trial was designed as a pilot trial; the small number of participants and the rare events did not allow an effective comparison between the two modes of screening that were studied. The remaining trial, conducted in Taiwan and published as an abstract, was designed as a cluster randomised trial to determine the optimal interval for screening using alpha foetoprotein and ultrasound. Screening intervals of four months and 12 months were compared in the two groups. Further details about the screening strategy were not available. The trial reported on cumulative four-year survival, cumulative three-year incidence of hepatocellular carcinoma, and mean tumour size. The cumulative four-year survival was not significantly different between the two screening intervals. The incidence of hepatocellular cancer was higher in the four-monthly screening group. The included trials did not report on adverse events. It appears that the sensitivity and specificity of the screening modes were poor, accounting for a substantial number of false-positive and false-negative screening results.
There is not enough evidence to support or refute the value of alpha-foetoprotein or ultrasound screening, or both, of hepatitis B surface antigen (HBsAg) positive patients for hepatocellular carcinoma. More and better designed randomised trials are required to compare screening against no screening.
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ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium "washout" in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and loco-regional therapies (alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion's stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib.03/2015; 7(3):362-76. DOI:10.4254/wjh.v7.i3.362
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