Introduction: Hepatocellular carcinoma (HCC) represents the main cause of death in patients with nonalcoholic steatohepatitis (NASH) cirrhosis and is a leading indication for liver transplantation. Identification of high-risk patients for HCC is essential for long term monitoring of disease progression, early detection, and effective intervention. Fibrosis-4 (FIB-4) is a noninvasive index of readily available laboratory measurements and is widely validated for predicting cirrhosis and HCC. We sought to determine if FIB-4 score is associated with high risk of HCC among patients with NASH cirrhosis.
Methods: We conducted a retrospective cohort study of adult patients with NASH cirrhosis (n=1,441) who were evaluated at our medical center between 2005 and 2015. Those who developed HCC were identified via ICD codes until the end of September 2021. At day of index NASH cirrhosis diagnosis, clinical and biochemical measurements were recorded on each patient. Descriptive statistics were calculated for all factors. Kaplan-Meier analysis was performed to evaluate time to HCC event. Cox regression models were used to evaluate associations between HCC and factors of interest. Models were adjusted for age, sex, number of comorbidities, and laboratory values.
Results: During a median follow-up time of 8.3 years, 218 (15%) patients with NASH cirrhosis developed HCC. At index visit, the study population had a median age 57 years, 44% males, 78.6% White, median BMI 31.5 kg/m2, 26.7% had diabetes mellitus, 10.4% current smokers, mean FIB-4 score 4.2, and mean MELD score 8.1. Multivariable Cox regression models revealed that age, sex, race/ethnicity, BMI and FIB-4 were independent factors associated with development of HCC in patients with NASH cirrhosis (table 1). Compared to patients with FIB-4 < 1.45, patients with FIB-4 between 1.45-3.25 had a similar risk of HCC (95% CI: 0.61-1.86, p=0.82). Patients with FIB-4 > 3.25 had a 2.51 (95% CI: 1.53-4.12, p< 0.001) increased hazard of HCC (figure 1).
Discussion: Age, sex, race/ethnicity, BMI and FIB-4 were independently associated with HCC in NASH cirrhosis. We found that FIB-4 > 3.25 was an independent predictor of HCC risk. Providers should pay attention to FIB-4 for long term monitoring of disease progression. An inexpensive, available, validated marker like FIB-4 is a promising tool for identification of high-risk patients and may be used in routine clinical practice as a simple screening strategy for HCC risk in patients with NASH cirrhosis.
