Risk Model for Hepatocellular Carcinoma Among Chronic HCV Patients

A newly developed hepatocellular carcinoma risk score enables risk stratification for hepatocellular carcinoma development among patients with chronic hepatitis C infections at sustained virologic response.

A newly developed hepatocellular carcinoma (HCC) risk score enables risk stratification for HCC development among patients with chronic hepatitis C (HCV) infections at sustained virologic response, according to data published in the European Journal of Gastroenterology & Hepatology.

HCV infection commonly progresses to a chronic infection for many patients; some patients with chronic HCV eventually develop HCC. The primary goal for anti-HCV treatment is the prevention of progression of the infection, and subsequent fibrosis, which may lead to hepatic decompensation and HCC. Sustained virologic response is regarded as the gold standard for successful prevention of disease progression and is commonly used to establish cured status in patients. However, there is still a substantial risk of developing HCC despite sustained virologic response.

Researchers, therefore, decided to build a model using independent predictors for chronic HCV infection after sustained virologic response. They used data obtained from 1193 patients with chronic HCV infection who demonstrated sustained virologic response using antiviral therapy. Of these patients, data from 669 were used as a training cohort and 524 patients’ data were used for the validation cohort. Multivariate Cox proportional hazards regression modeling was then used to develop the HCC risk score.

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HCC occurred in 19 patients, more frequently in older men. It was associated with liver cirrhosis, hypertension, diabetes, lower platelet count, lower total cholesterol, higher fibrosis-4 index (FIB-4), and higher α-fetoprotein, aspartate, and alanine aminotransferase levels (all associations, P < .05).

Factors that independently predicted HCC were FIB-4 (hazard ratio [HR], 1.080), male sex (HR, 8.189), and higher α-fetoprotein level (HR, 1.060) (all P < .05). Carcinoma development risk was successfully predicted by the HCC risk score (area under the curve [AUC]= 0.771, 0.857, and 0.911 at 2, 4, and 6 years, respectively) and the cumulative incidence rate of HCC differed significantly among groups stratified by the score.

A score of 0 to 2 points was low, 3 to 7 points was intermediate and 8 or 9 points was categorized as high risk (all P < .05 by log-rank test). The HCC risk score was maintained in the validation cohort (AUC = 0.728 at 2 years, 0.737 at 4 years, and 0.809 at 6 years).

Investigators listed several unresolved issues in the current study, including that the absolute number of patients with HCC development after sustained virologic response was small at 19, which may have biased the results. Several baseline characteristics were also significantly different between the training and validation cohorts. However, they do not believe this influenced the results, considering the acceptable accuracy of the HCC risk score in the validation cohort. In fact, for investigators, “it supports the rationale for the wide use of the [HCC risk score] in various cohorts with different characteristics.” It was also noted that despite relatively high AUC values, the predictive accuracy of the HCC risk score appeared rather weak in the validation cohort, meaning further validation studies with different cohorts are needed. Finally, histologic information was not available at sustained virologic response, so no detailed comparison between the histologic fibrotic burden and FIB-4 index was done.

The results revealed that the FIB-4 value at the time of sustained virologic response was an independent predictor of HCC development along with male sex and α-fetoprotein level in patients with chronic HCV infection. Based on this finding the new prediction model was established and validated in the cohorts and showed acceptable accuracy in the assessment of risk. According to the investigators, the easy-to-use score might enable risk stratification for carcinoma development in this patient population.


Chun HS, Kim BK, Park JY, et al. Design and validation of risk prediction model for hepatocellular carcinoma development after sustained virological response in patients with chronic hepatitis C. Eur J Gastroenterol Hepatol. 2020;32:378-385.