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.
[Show abstract] [Hide abstract]
ABSTRACT: Aiming to find novel non-invasive biomarkers with high accuracy for the detention of early-stage hepatocellular carcinoma (HCC), we examined the predictive power of two microRNAs (miR; miR-375 and miR-199a-3p) as potential biomarkers in early-stage HCC. A total of 234 serum samples (78 samples from HCC patients, 156 samples from healthy controls) were collected. We measured the levels of the two mature microRNAs (miRNAs) (miR-375 and miR-199a-3p) with probe-based stem-loop quantitative reverse-transcriptase PCR (RT-qPCR) in all subjects. In addition, the correlation between the expression levels of two miRs and clinicopathological factors was explored. Receiver operating characteristic curve (ROC) analyses revealed that the two serum miRs could be promising biomarkers for HCC, with relatively high area under the curve (AUC) values as follows: miR-375, 0. 637 with 95 % confidence interval (CI) of 0.560-0.741; miR-199a-3p, 0. 883 with 95 % CI of 0.827-0.938. Stratified analyses indicated that circulating miR-199a-3p showed better predictive value in patients with long-term drinking. Our data suggested that circulating miR-375 and miR-199a-3p could be a novel serum biomarker for HCC. Nevertheless, further validating and improving study with larger sample should be conducted to confirm our results.Tumor Biology 01/2015; DOI:10.1007/s13277-015-3092-0 · 2.84 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Several popular screening tests, such as mammography and prostate-specific antigen, have met with wide controversy and/or have lost their endorsement recently. We systematically evaluated evidence from randomized controlled trials (RCTs) as to whether screening decreases mortality from diseases where death is a common outcome. We searched three sources: United States Preventive Services Task Force (USPSTF), Cochrane Database of Systematic Reviews, and PubMed. We extracted recommendation status, category of evidence and RCT availability on mortality for screening tests for diseases on asymptomatic adults (excluding pregnant women and children) from USPSTF. We identified meta-analyses and individual RCTs on screening and mortality from Cochrane and PubMed. We selected 19 diseases (39 tests) out of 50 diseases/disorders for which USPSTF provides screening evaluation. Screening is recommended for 6 diseases (12 tests) out of the 19. We assessed 9 non-overlapping meta-analyses and 48 individual trials for these 19 diseases. Among the results of the meta-analyses, reductions where the 95% confidence intervals (CIs) excluded the null occurred for four disease-specific mortality estimates (ultrasound for abdominal aortic aneurysm in men; mammography for breast cancer; fecal occult blood test and flexible sigmoidoscopy for colorectal cancer) and for none of the all-cause mortality estimates. Among individual RCTs, reductions in disease-specific and all-cause mortality where the 95% CIs excluded the null occurred in 30% and 11% of the estimates, respectively. Among currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon and reductions in all-cause mortality are very rare or non-existent. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.International Journal of Epidemiology 01/2015; DOI:10.1093/ije/dyu140 · 9.20 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Screening for hepatocellular carcinoma (HCC) is clinically important as its early detection has remarkable survival benefits. We investigated the possible role of FIB-4, a recently developed noninvasive marker for liver fibrosis based on routine laboratory tests, as a clinical indicator for predicting future HCC among hepatitis B surface antigen (HBsAg) carriers. Our retrospective cohort study involved 986 Korean HBsAg carriers aged 40 or older who visited Seoul National University Hospital for health check-up. National medical service claims data was used to determine HCC incidence. Median follow-up time was 5.4 years (interquartile range 4.4 years). Adjusted for age, sex, body mass index, smoking, alcohol, and anti-viral medication for hepatitis B, compared to subjects with FIB-4 <1.25, subjects with 1.7≤ FIB-4 <2.4 showed aHR 4.57 (95% CI 1.50-13.92) and subjects with FIB-4 ≥2.4 showed aHR 21.34 (95% CI 7.73-58.92) for HCC incidence. FIB-4 was shown to have incremental predictive value to ultrasonographic liver cirrhosis for HCC incidence (C-index 0.701 vs. 0.831; P=0.001). FIB-4 was also better predictive of HCC incidence compared to that of ultrasonographic liver cirrhosis (C-index 0.775 vs. 0.701; P=0.040). Conclusion: High FIB-4 is a highly predictive risk factor for HCC incidence among Korean HBsAg carriers. FIB-4 is a promising, easily applicable, and cost-effective clinical tool in identifying a subpopulation of HBsAg carriers who are at heightened risk. Our study needs to be replicated in larger future studies on various ethnic groups; nonetheless, our study suggests FIB-4 may play a valuable role in HCC screening among HBsAg carriers. This article is protected by copyright. All rights reserved.Hepatology 12/2014; DOI:10.1002/hep.27654 · 11.19 Impact Factor