Development of a simple dynamic algorithm for individualized hepatocellular carcinoma risk-based surveillance using pre- and post-treatment general evaluation score.

BACKGROUND AND AIMS: With the growing number of treated hepatitis C patients, the current 'one-size-fits-all' hepatocellular carcinoma (HCC) surveillance strategies for patients with advanced fibrosis represents a great burden on healthcare systems. An individualized HCC risk strategy incorporates the dynamic changes of HCC risk are lacking. METHODS: This single-centre observational study included 3075 patients, with advanced fibrosis (≥F3) who achieved SVR following DAAs at Egyptian Liver research institute and hospital (ELRIAH) with follow-up period (range 6-72 months). The performance of a recently developed General Evaluation Score (GES) HCC risk stratification score was calculated pre- and post-treatment using Harrell's c statistic. Times to HCC and cumulative incidences were calculated with Kaplan-Meier method and compared using log-rank (Mantel-Cox) test. RESULTS: Pre-treatment GES score stratified patients into low (60.4%), intermediate (23.4%), and (16.2%) high-risk score where 5-year cumulative incidences of HCC were 1.66%, 4.45% and 7.64%, respectively. Harrell's c statistic was 0.801. Post-treatment GES score stratified patients into low (57.4%), intermediate (30.7%) and (11.9%) high-risk score where 5-year cumulative incidences of HCC were 1.35%, 3.49% and 11.09% respectively. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.818. Using pre- and post-treatment GES score, GES algorithm was developed with higher predictive value. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.832. CONCLUSION: A dynamic algorithm incorporating both pre- and post-GES scores have better performance and predictive value compared with only pre-treatment assessments. The proposed algorithm would help to stratify those who need intensive or being excluded from screening.

[Application of aMAP score to assess the risk of hepatocarciongenesis in population of chronic liver disease in primary hospitals].

Objective: The aMAP score is a hepatocellular carcinoma (HCC) risk prediction model based on an international cooperative cohort, which can be applied to various liver diseases. The aim of this study is to use the aMAP score to stratify the risk of HCC in patients with chronic liver disease (combined or non-combined metabolic diseases) admitted to People's Hospital of Yudu County, Ganzhou City, Jiangxi Province, in order to guide personalized HCC screening. Methods: The demographic information, laboratory test results (platelets, albumin, and total bilirubin) and combined disease information of patients with chronic liver disease who were admitted to People's Hospital of Yudu from January 2016 to December 2020 were collected, and the aMAP score was calculated to stratify HCC risk in this population. Results: A total of 3629 cases with chronic liver disease were included in the analysis, including 3 452 (95.1%) cases with hepatitis B virus (HBV) infection, 177 (4.9%) cases with fatty liver, and 22 (0.6%) cases with HBV infection and fatty liver. There were 2 679 (73.8%) male and the median age was 44 (35, 54). In the overall population, low, medium and high risk of HCC accounted for 52.6%, 29.0%, and 18.4% respectively. In the HBV-infected population, the proportion of high risk of HCC was significantly higher than that of fatty liver (18.9% vs. 9.6%, P = 0.001). The proportion of chronic liver disease patients with combined hypertension or diabetes was significantly higher than that of those with non-combined metabolic diseases (combined hypertension: 32.3% vs. 17.9%, P < 0.001; combined diabetes: 36.5% vs. 18.1%, P < 0.001). Moreover, the proportion of high-risk population with two metabolic diseases was significantly higher than that with one and no metabolic diseases (40.9% vs. 31.8% vs. 17.7%, P < 0.001). Conclusion: The aMAP score can be used as a simple tool for HCC screening and management of chronic liver disease in primary hospitals, and it is helpful to improve the personalized follow-up management system of chronic liver disease population. Chronic liver disease patients with metabolic diseases have a higher risk of HCC, and people with high risk of HCC should be given special priority in follow-up visits, so as to improve the rate of HCC early diagnosis and reduce the mortality rate.

GES: A validated simple score to predict the risk of HCC in patients with HCV-GT4-associated advanced liver fibrosis after oral antivirals.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) risk persists after hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs), particularly in patients with cirrhosis. Identifying those who are likely to develop HCC is a critical unmet medical need. Our aim is to develop a score that offers individualized patient HCC risk prediction. METHODS: This two-centre prospective study included 4400 patients, with cirrhosis and advanced fibrosis who achieved a sustained virologic response (SVR), including 2372 patients (derivation cohort). HCC-associated factors were identified by multivariable Cox regression analysis to develop a scoring model for prediction of HCC risk; and subsequently internally and externally validated in two independent cohorts of 687 and 1341 patients. RESULTS: In the derivation cohort, the median follow-up was 23.51 ± 8.21 months, during which 109 patients (4.7%) developed HCC. Age, sex, serum albumin, α fetoprotein and pretreatment fibrosis stage were identified as risk factors for HCC. A simple predictive model (GES) score was constructed. The 2-year cumulative HCC incidence using Kaplan-Meier method was 1.2%, 3.3% and 7.1% in the low-risk, medium-risk and high-risk groups respectively. Internal and external validation showed highly significant difference among the three risk groups (P < .001) with regard to cumulative HCC risk. GES score has high predictive ability value (Harrell's C statistic 0.801), that remained robustly consistent across two independent validation cohorts (Harrell's C statistic 0.812 and 0.816). CONCLUSION: GES score is simple with validated good predictive ability for the development of HCC after eradication of HCV and may be useful for HCC risk stratification in those patients.

Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy.

In the treatment of chronic hepatitis B (CHB), the ultimate goal is preventing hepatitis B virus (HBV)-associated liver disease, including hepatocellular carcinoma (HCC). Recently published studies show that in CHB patients treated with the currently recommended first-line nucleos(t)ide analogs (NAs) entecavir or tenofovir, annual HCC incidences range from 0.01% to 1.4% in non-cirrhotic patients, and from 0.9% to 5.4% in those with cirrhosis. In Asian studies including matched untreated controls, current NA therapy consistently resulted in a significantly lower HCC incidence in patients with cirrhosis, amounting to an overall HCC risk reduction of ∼30%; in non-cirrhotic patients, HCC risk reduction was overall ∼80%, but this was only observed in some studies. For patients of Caucasian origin, no appropriate comparative studies are available to date to evaluate the impact of NA treatment on HCC. Achievement of a virologic response under current NA therapy was associated with a lower HCC risk in Asian, but not Caucasian studies. Studies comparing entecavir or tenofovir with older NAs generally found no difference in HCC risk reduction between agents, except for one study which used no rescue therapy in patients developing lamivudine resistance. Overall, these data indicate that with the current, potent NAs, HCC risk can be reduced but not eliminated, probably due to risk factors that are not amenable to change by antiviral therapy, or events that may have taken place before treatment initiation. Validated pre- and on-therapy HCC risk calculators that inform the best practice for HCC surveillance and facilitate patient counseling would be of great practical value.

Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection.

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and represents a global health challenge. Liver cancer ranks third in cancer-related mortality with 830,000 deaths and sixth in incidence with 906,000 new cases annually worldwide. HCC most commonly occurs in patients with underlying liver disease, especially chronic hepatitis B virus (HBV) infection in highly endemic areas. Predicting HCC risk based on scoring models for patients with chronic liver disease is a simple, effective strategy for identifying and stratifying patients to improve the early diagnosis rate and prognosis of HCC. We examined 23 HCC risk scores published worldwide in CHB patients with (n=10) or without (n=13) antiviral treatment. We also described the characteristics of the risk score's predictive performance and application status. In the future, higher predictive accuracy could be achieved by combining novel technologies and machine learning algorithms to develop and update HCC risk score models and integrated early warning and diagnosis systems for HCC in hospitals and communities.