The burden of hepatocellular carcinoma (HCC) is a major healthcare problem and remains the most common histological type of primary liver cancer. Additionally, HCC is the fastest growing cause of cancer-related death in the United States.
The increasing incidence of HCC in the United States is largely explained by increasing rates of hepatitis C virus (HCV)-related HCC, but more recently alcoholic liver disease (ALD) and liver disease. Non-alcoholic fatty liver disease (NAFLD) are among the most common chronic liver diseases associated with HCC. Annual incidence rates of HCC among high-risk patients are around 2% per year.
Direct acting antivirals ( DAAs) have been very effective in the treatment of hepatitis C virus (HCV). However, patients treated with DAAs remain at risk for HCC even after achieving a sustained viral response (SVR). Similarly, hepatitis B virus (HBV) patients with or without cirrhosis treated with oral nucleosides continue to have a significant, although reduced, risk of HCC. Therefore, those with chronic viral hepatitis remain under surveillance for HCC even after starting treatment for HBV, regardless of fibrosis/cirrhosis, or after HCV eradication has been achieved, while they have residual fibrosis/cirrhosis.
With the shift in epidemiology of cirrhosis etiology from viral hepatitis to non-infectious causes , there is a need to better determine the risk of HCC in a contemporary cohort of patients such as those with NAFLD, ALD, and treated viral hepatitis. Having a better understanding of the progression to HCC among these patients would allow for better risk stratification, which may improve and expedite prevention and early detection efforts.
Previous studies have mostly been retrospective in design . Among the prospective studies that have been conducted, only a few are based on study populations in the United States. Furthermore, these previous studies conducted in the US have limitations in the evaluation of risk factors for HCC incidence, recognition of high- and low-risk patient groups, and geographic diversity.
We followed a prospective cohort of patients with cirrhosis cared for at multiple centers in geographically diverse areas of the United States to examine the incidence and risk factors of HCC.
Background and objectives
Worldwide, hepatocellular carcinoma (HCC) is a common malignancy. Our objective was to prospectively determine the incidence and risk factors of HCC in a US cohort.
Methods
The multicenter National Institutes of Health Hepatocellular Carcinoma Early Detection Strategy study prospectively enrolled patients with cirrhosis who underwent standard surveillance for HCC. Demographic data, medical and family history, etiology of liver disease, and clinical characteristics were evaluated for associations with HCC.
Results
Between April 10, 2013 and December 31, 2021, 1,723 patients were enrolled and confirmed eligible .
During a median follow-up of 2.2 years (range, 0 to 8.7 years), there were 109 incident cases of HCC for an incidence rate of 2.4 per 100 person-years: 88 (81%) patients with disease very early/early liver disease from Barcelona Clinic . Cancer stage (0, A), 20 (18%) intermediate stage (B) and 1 (1%) unknown stage.
Risk factor analyzes were limited to 1325 patients, including 95 incident HCC, with at least 6 months of follow-up. The majority were men (53.2%), obese or very obese (mean body mass index, 30.2 kg/m 2), and white (86.3%); 42.0% had a history of hepatitis C virus infection, 20.7% had alcoholic liver disease, and 24.9% had nonalcoholic fatty liver disease.
Fourteen HCC risk factors were significant (P < 0.05) in univariate analyses, and a multivariate subset was selected by stepwise logistic regression.
The multivariate subset contained gender ( P < 0.001; male; odds ratio [OR], 2.47; 95% confidence interval [CI], 1.54–4.07), years with cirrhosis ( P = 0.004; OR , 1.06; 95% CI, 1.02–1.1), family history of liver cancer ( P = 0.02; yes; OR, 2.69; 95% CI, 1.11–5), 86), age (every 5 years; P = 0.02; OR, 1.17; 95% CI, 1.03–1.33), obesity ( P = 0.02; yes; OR, 1.7; 95% CI, 1.08–2.73), aspartate aminotransferase (log(1+AST); P = 0.06; OR, 1.54; 95% CI, 0.97–2.42), alpha-fetoprotein ( log(1+AFP); P = 0.07; OR, 1.32; 95% CI, 0.97–1.77) and albumin ( P = 0.10; OR, 0.7; 95% CI) 0.46–1.07).
Conclusions To date, this is the largest prospective, geographically diverse study of a US cohort of patients with cirrhosis validating known risk factors for HCC ( sex, age, obesity, years with cirrhosis, family history of liver cancer, AFP basal, albumin and AST ). The incidence of HCC was 2.4% per 100 person-years. |
Final synthesis
HCC remains an important malignancy worldwide, although the incidence has been variable. Several patient characteristics and the rigor of surveillance may influence HCC detection and, therefore, incidence. Chronic HBV and HCV are risk factors for the development of HCC, and the risk increases substantially in patients with cirrhosis.
According to a systematic review conducted in Asia, HCC incidence rates per 100 person-years were 0.2 in inactive HBV carriers, 0.6 in non-cirrhotic patients with chronic HBV, and 3.7 in cirrhotic patients with chronic HBV. . In HCV cohort studies, the annual incidence of HCC ranged from 1% to 3%, and the rate increased to 1% to 8% after HCV-related cirrhosis developed.
Background and context
Hepatocellular carcinoma (HCC) is an important malignancy worldwide, but its incidence and risk factors have not been investigated with respect to the geographic diversity of patients in the United States.
New findings
During a median follow-up of 2.2 years between 2013 and 2021, the incidence of HCC in the largest, multicenter, geographically diverse study conducted in the US was found to be 2.4% per 100 person-years.
Limitations
The conclusions of this study are limited by the small number of minority patients enrolled, and a clinical evaluation of our models is beyond the scope of this article.
Relevance of clinical research
Most studies on the incidence and risk factors of HCC have been retrospective in nature. To date, our study is the largest prospective, geographically diverse investigation of a US patient cohort validating several known risk factors for HCC, including male sex, older age, low albumin, and obesity. .
Relevance of basic research
Although our study focuses on the clinical detection and manifestations of HCC, it draws attention to the need to further investigate the physiological and biochemical mechanisms behind the unique roles of newer biomarkers in the early detection and development of HCC. . Understanding these mechanisms will bring healthcare providers closer to earlier diagnosis of HCC in those who are at high risk for this malignancy.
In conclusion , in a carefully conducted prospective cohort of US patients at risk for HCC, the incidence was 2.4 per 100 person-years over a follow-up of 4510 person-years. The complementary set of HCC predictors was sex, age, obesity, years with cirrhosis, family history of liver cancer, baseline AFP, albumin, and AST.
