Multiple factors influence risks of cirrhosis, HCC in veterans with MAFLD

The incidence of cirrhosis and hepatocellular carcinoma (HCC) among veterans differs according to demographic and clinical characteristics, with the lowest rate seen among Asians, reports a study.

“Disparities in risk of cirrhosis and HCC were observed by demographic and clinical characteristics, emphasizing the importance of early identification of metabolic dysfunction-associated fatty liver disease (MAFLD) with modifiable high-risk features to implement earlier interventions to improve long-term outcomes,” the researchers said.

Adults with noncirrhotic MAFLD were identified using data from the 2010 to 2022 Veterans Affairs database. Researchers assessed and stratified the 5- and 10-year incidence of cirrhosis and HCC by demographics and relevant clinical variables. They also determined the predictors of cirrhosis and HCC using multivariate Cox proportional hazard models.

A total of 969,253 patients with noncirrhotic MAFLD (mean age 62.7 years, 94.5 percent males, 70.2 percent non-Hispanic White) were identified. The 10-year incidence of cirrhosis was 3.70 percent (95 percent confidence interval [CI], 3.66‒3.74), while that of HCC was 0.69 percent (95 percent CI, 0.67‒0.70). [J Clin Gastroenterol 2024;58:718-725]

Following stratification by race/ethnicity, Asians showed the lowest 10-year incidence of cirrhosis (2.63 percent, 95 percent CI, 2.37‒2.88) and Hispanics the highest (4.60, 95 percent CI, 4.45‒4.75). This pattern persisted with the incidence of HCC.

“Significant disparities in risk of cirrhosis or HCC were observed when stratified by sex, substance use, and comorbidities,” said the researchers, noting the highest risks of cirrhosis and HCC among patients with baseline fibrosis-4 (FIB-4) score >2.67.

Specifically, the 10-year risk of HCC among noncirrhotic MAFLD with FIB-4 score >2.67 was 2.87 percent. This translates into approximately 0.3 percent annual HCC risk, exceeding the “threshold that has been shown to be cost-effective to implement routine HCC screening in those with chronic hepatitis B without cirrhosis. [Hepatology 2018;68:723-750]

Diabetes and hypertension

An unforeseen trend was observed as regards the impact of diabetes and hypertension on the incidence of cirrhosis and HCC. At 5- and 10-year follow-ups, veterans without diabetes or hypertension had a relatively higher incidence of cirrhosis and HCC than those with these diseases.

“These findings may appear paradoxical to the expected effect of diabetes and hypertension on the progression of MAFLD to cirrhosis, HCC, or other complications of advanced liver disease,” the researchers said.

“One plausible explanation is that major cardiovascular disease events in those with diabetes and/or hypertension may lead to premature death and censoring from the analyses before the development of cirrhosis or HCC outcomes,” they added.

Previous studies comparing individuals with and without diabetes or hypertension at age 50 found that the presence of these diseases correlated with a shorter life expectancy by 6 years and 5 years, respectively. [N Engl J Med 2011;364:829-841; Hypertension 2005;46:280-286]

“A better understanding [of the] epidemiology of MAFLD and associated risk factors contributing to the risk of disease progression is important to improve our understanding of natural history, as well as to identify potential high-risk features that may be modifiable to improve long-term outcomes,” according to the researchers.