Novel Liver Stiffness-Based Nomogram for Predicting Hepatocellular Carcinoma Risk in Patients with Chronic Hepatitis B Virus Infection Initiating Antiviral Therapy

Abstract

Hepatocellular carcinoma (HCC) risk prediction is important to developing individualized surveillance approaches. We designed a novel HCC prediction model using liver stiffness on transient elastography for patients receiving antiviral therapy against hepatitis B virus (HBV) infection. We recruited 2037 patients receiving entecavir or tenofovir as first-line antivirals and used the Cox regression analysis to determine key variables for model construction. Within 58.1 months (median), HCC developed in 182 (8.9%) patients. Patients with HCC showed a higher prevalence of cirrhosis (90.7% vs. 45.9%) and higher liver stiffness values (median 13.9 vs. 7.2 kPa) than those without. A novel nomogram (score 0–304) was established using age, platelet count, cirrhosis development, and liver stiffness values, which were independently associated with increased HCC risk, along with hepatitis B e antigen positivity and serum albumin and total bilirubin levels. Cumulative HCC probabilities were 0.7%, 5.0%, and 22.7% in the low- (score ≤87), intermediate- (88–222), and high-risk (≥223) groups, respectively. The c-index value was 0.799 (internal validity: 0.805), higher than that of the PAGE-B (0.726), modified PAGE-B (0.756), and modified REACH-B (0.761) models (all p < 0.05). Our nomogram showed acceptable performance in predicting HCC in Asian HBV-infected patients receiving potent antiviral therapy.

Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis

“…Notably, multivariate Cox regression analyses revealed that the known risk factors for HCC development in patients with CHB on AVT, such as old age, low platelet count, low serum albumin level, and high LS value by TE [22], were still independently associated with HCC development in patients with HBV cirrhosis. Moreover, patients who showed a very high cumulative incidence of HCC development were classified as a highrisk group by the models containing all or some of these risk factors, such as modified PAGE-B, modified REACH-B, CAGE-B, and SAGE-B (5-year: 15.5-24.0%, and 8-year: 42.4-52.8%).…”

“…Many models have been suggested to assess the risk stratification of HCC development in CHB patients [13][14][15]. Since the prognostic role of serum HBV DNA has weakened in the current era of potent NUCs, models established within one decade have adopted the presence of baseline cirrhosis and/or fibrosis parameters, rather than virological factors such as hepatitis B e-antigen (HBeAg) and/or serum HBV-DNA level [16][17][18][19][20][21][22][23]. This provides an overall superior prognostic performance to old models (i.e., REVEAL [24], CU-HCC [25], GAG-HCC [26], LSM-HCC [27], and REACH-B [28]), which primarily depend on virological factors.…”

A new model predicts hepatocellular carcinoma in patients with HBV-related decompensated liver cirrhosis and long-term antiviral therapy: a prospective study

“…Based on a logistic regression analysis, Model (Age_DC_PLT_TBil) consisting of age, DC stage, platelets and TBil, was developed and it showed superiority in stratifying patients at high risk. Compared with aMAP ( Gui et al, 2021 ) or transient elastography ( Lee et al, 2021 ), this new model with potential clinical utility, is more easily to calculate, and it does not increase the economic burden to the patients. For patients at high-risk group, surveillance strategy including alpha-fetoprotein and imaging examinations are recommended to be performed routinely every 3 to 6 months ( Sohn et al, 2022 ).…”

Cost–Utility Analysis of Tenofovir Alafenamide and Entecavir in Chronic Hepatitis B Patients: A Markov Decision Model

“…Oral antiviral drugs, such as tenofovir disoproxil (TDF), tenofovir alafenamide (TAF), and entecavir (ETV), offer more sustained options. However, the long-term use of TDF is associated with potential renal and skeletal issues, with TAF emerging as an alternative with a more favorable side effect profile [6][7][8][9][10].…”

“…Additionally, CHB is characterized by a substantial relapse rate upon the discontinuation of antiviral medications, requiring repeated treatment cycles. The cessation of TAF therapy has demonstrated significantly earlier and higher clinical relapse rates compared to ETV therapy [9,10]. This may necessitate lifelong medication for some patients, resulting in substantial medical expenditures [11].…”