A risk prediction model for hepatocellular carcinoma after hepatitis B surface antigen seroclearance: Need a closer look!

A risk prediction model for hepatocellular carcinoma after hepatitis B surface antigen seroclearanceJournal of HepatologyVol. 77Issue 3PreviewAfter hepatitis B surface antigen (HBsAg) seroclearance, the risk of hepatocellular carcinoma (HCC) remains, and the optimal surveillance strategy has yet to be determined. Herein, we aimed to evaluate incidence and risk factors for HCC and establish a novel prediction model for HCC development after HBsAg seroclearance. Full-Text PDF The authors received no financial support to produce this manuscript. Wentian Lu (Conceptualization; Writing – original draft; Writing – review & editing). With great interest I read the article by Yang H et al.[1]Yang H. Bae S.H. Nam H. Lee H.L. Lee S.W. Yoo S.H. et al.A risk prediction model for hepatocellular carcinoma after hepatitis B surface antigen seroclearance.J Hepatol. 2022; 77: 632-641Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar The retrospective study predominantly developed a risk prediction model for hepatocellular carcinoma (HCC) after hepatitis B surface antigen (HBsAg) seroclearance. Of 831 patients finally included in the study, 40 developed HCC after HBsAg was cleared. By multivariate Cox proportional modeling, four independent risk factors, i.e., age at HBsAg seroclearance, presence of cirrhosis, family history of HCC, and more-than-moderate alcohol consumption, were included in the novel model. Notably, the model showed an excellent performance, with Harrell's C-index of 0.804 as well as the time-dependent AUROC curves for 5-year, 10-year, and 15-year prediction for HCC of 0.799, 0.835, and 0.817, respectively. However, I would like to raise the following comments: Firstly, the study aimed to investigate risk factors for HCC development after HBsAg seroclearance, and presence of cirrhosis at baseline was identified as one. However, some patients with diabetes, dyslipidemia, or heavy alcohol drinking were enrolled in this study. In other words, some cases of cirrhosis may mainly originate from the progression of nonalcoholic fatty liver disease (NAFLD) and/or alcoholic liver disease (ALD), which can also progress to HCC.[2]Polyzos S.A. Chrysavgis L. Vachliotis I.D. Chartampilas E. Cholongitas E. Nonalcoholic fatty liver disease and hepatocellular carcinoma:Insights in epidemiology, pathogenesis, imaging, prevention and therapy.Semin Cancer Biol. 2023; 93: 20-35Crossref Scopus (6) Google Scholar,[3]Gao B. Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets.Gastroenterology. 2011; 141: 1572-1585Abstract Full Text Full Text PDF PubMed Scopus (1446) Google Scholar To some extent, the risk of HCC in patients with HBsAg seroclearance might be overestimated. Secondly, 16 cirrhotic patients were diagnosed by aspartate aminotransferase to platelet ratio (APRI) score or fibrosis-4 index (FIB-4) score, as described in Results Section. Both APRI and FIB-4 are calculated on the basis of some simple parameters, including platelet count.[4]Wai C.T. Greenson J.K. Fontana R.J. Kalbfleisch J.D. Marrero J.A. Conjeevaram H.S. et al.A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.Hepatology. 2003; 38: 518-526Crossref PubMed Scopus (3363) Google Scholar,[5]Sterling R.K. Lissen E. Clumeck N. Sola R. Correa M.C. Montaner J. et al.Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection.Hepatology. 2006; 43: 1317-1325Crossref PubMed Scopus (3039) Google Scholar According to univariate analysis, cirrhosis, low platelet count, and other parameters were associated with development of HCC, and they were included in multivariate analysis. That is to say, collinearity may occur in cirrhosis and platelet count. Thirdly, some patients diagnosed with hepatitis B virus infection may continue to receive antiviral treatment after HBsAg seroclearance.[6]Tang L.S.Y. Covert E. Wilson E. Kottilil S. Chronic Hepatitis B Infection: A Review.JAMA. 2018; 319: 1802-1813Crossref PubMed Scopus (447) Google Scholar And current evidence indicates that long-term nucleos(t)ide analogue therapy can significantly lower the chance of developing HCC in patients with chronic hepatitis B. Thus history of long-term antiviral therapy may be another factor associated with development of HCC.[7]Manne V. Gochanour E. Kowdley K.V. Current perspectives into the evaluation and management of hepatitis B: a review.Hepatobiliary Surg Nutr. 2019; 8: 361-369Crossref PubMed Google Scholar Despite the limitations of the study, additional analyses by including more meaningful parameters (e.g., history of long-term antiviral therapy after HBsAg seroclearance) in the future, even the further validation in large-scale prospective studies, will strengthen validity and credibility of the conclusions and improve this model. This novel predictive model, based on four easily accessible clinical variables, allows for reliable risk assessment of HCC, easy to implement and available to doctors from community hospitals to tertiary hospitals. In order to apply this model to clinical practice as soon as possible, it is proposed to develop a user-friendly software and/or website. The clinical promotion and wide application of the model will facilitate the improvement of scheme for HCC surveillance in patients with HBsAg seroclearance to optimize current guidelines. The authors declare no conflicts of interest that pertain to this work.