Development of a nomogram for screening of hepatitis B virus-associated hepatocellular carcinoma

Abstract

Current strategy of hepatocellular carcinoma (HCC) surveillance evaluates individual risks of HCC for defining candidates for surveillance, but estimated risks are not utilized for clinical decision-making during actual screening. We sought to determine whether consideration of individual risks improve the performance of ultrasound (US)-based HCC screening in a real-world chronic hepatitis B (CHB) cohort. This single center retrospective cohort study analyzed 27,722 screening US tests from 4,175 consecutive CHB patients. Logistic regression analysis was performed to identify independent parameters predicting presence of HCC. A nomogram was built based on the independent predictors of HCC and compared with US-only screening by receiver operating characteristics analysis. The cost-effectiveness of the nomogram was assessed by decision curve analysis. HCC developed in 222 patients with the incidence of 0.769 per 1000 person-year during the median follow-up of 63 months. Age, sex, presence of cirrhosis, serum alpha-fetoprotein (AFP) levels and positive US test results were independent predictors of HCC presence. A nomogram based on these predictors showed higher C-statistics compared to US-only screening (0.960 vs. 0.731 and 0.935 vs. 0.691 for derivation and validation cohort, respectively; p < 0.001). Decision curve analysis showed higher net benefit of the HCC nomogram-guided screening model compared to US-only screening in the risk threshold range between 0 and 0.3. A nomogram composed of age, sex, presence of cirrhosis, serum AFP levels and US findings better predicted the presence of HCC compared to US-only screening in CHB on surveillance.

Risk Prediction Models for Liver Cancer in Adults: A Systematic Review and Meta-Analysis

“…But the completeness and authenticity of this design were limited. In this study, retrospective cohort studies with logistic regression model were applied in two studies [27,31]. Case-control design was used in only one study [22], which needed relatively fewer subjects and thus the accuracy was less reliable.…”

“…There are sophisticated methods to handle missing data, and the most common way is multiple imputations [41][42][43]. Only one study used multiple imputations methods to impute data with missing values [31], whereas many studies did not provide this information. Enough external and internal validation is of signi cance to increase the credibility of the model, which could increase on the applicability of the model in real-world practice and reduce the possibility of over tting.…”

“…However, all models were classi ed as overall high risk of bias, due to a low number of events per variable, lack of internal validation, less reporting information on missing data and performance measures. Only ve studies were assessed at high risk of bias for the participants [22,23,27,30,31], suggesting that the target population of models has good representatives. Only two of these studies were rated at high risk in terms of predictors [11,22].…”

“…All reports were conducted between 2009 and 2020. Most of studies were conducted in China (N=10, 50%) [8,11,20,[21][22][23][24][25][26][27], USA (N=3, 15%) [28][29][30], Korea (N=2, 10%) [31,32], and Japan (N=2, 10%) [33,34]. Among all the observational studies, 16 were prospective cohort study and four were retrospective cohort study.…”

An incidentally Diagnosed Hepatocellular Carcinoma That Exhibited Unusual Metastasis

“…[1] HCC develops after chronic hepatitis B and C infections in approximately 80% of patients. [2] In addition to viral infections, alcohol consumption, aflatoxin exposure, metabolic disorders, such as hereditary hemochromatosis, alpha-1 antitrypsin deficiency, primary biliary cirrhosis, obesity, diabetes mellitus, and nonalcoholic fatty liver are important in HCC etiology. [3,4] Most cases of HCC are diagnosed late because of the absence of early and pathognomonic symptoms.…”