Prevalence and Factors Associated With Liver Fibrosis Among First-degree Relatives of Mexican Americans With Hepatocellular Carcinoma

Suzanne Sharpton; Kuangda Shan; Ricki Bettencourt; Miryoung Lee; Joseph B. McCormick; Susan P. Fisher-Hoch; Rohit Loomba


Aliment Pharmacol Ther. 2023;57(4):378-386. 

In This Article

Abstract and Introduction


Background and Aims: Whether hepatocellular carcinoma (HCC) increases the familial risk for hepatic fibrosis has not been thoroughly explored, particularly in Mexican Americans who are disproportionately affected by obesity and metabolic syndrome. We evaluated the risk of significant hepatic fibrosis in first-degree relatives of Mexican American adults with HCC.

Methods: We performed a cross-sectional analysis of a prospective cohort of Mexican American probands with HCC and first-degree relatives enrolled in the Hispanic Liver Cancer Cohort study. We evaluated the prevalence of hepatic fibrosis in first-degree relatives, defined by liver stiffness measurement (LSM) ≥ 7.0 kPa with transient elastography (TE). Secondary outcomes included the prevalence of definite hepatic steatosis, defined by controlled attenuation parameter ≥288 dB/m.

Results: We identified 70 probands diagnosed with HCC; 47% were female and the mean age was 62 years (±13 years). Among 112 first-degree relatives with a mean age of 43 years (±14 years), 19 (17%) had significant fibrosis and 47 (42%) had definite hepatic steatosis, respectively. The prevalence of significant fibrosis was 20% in first-degree relatives 40 years of age or older. Regression analysis revealed that diabetes (OR 3.2, 95% CI: 1.1–9.2, p = 0.03) and aspartate aminotransferase ≥30 units/L (OR 4.0, 95% CI: 1.4–11.7, p = 0.01) were predictors of significant fibrosis in first-degree relatives.

Conclusions: Using a well-phenotyped familial cohort, we found that the prevalence of significant fibrosis and definite hepatic steatosis are high in first-degree relatives of Mexican Americans with HCC, particularly those with diabetes, suggesting that this population may benefit from screening for liver disease.


The Hispanic population is the largest ethnic group within the United States with a growing population estimated to be around 110 million by the year 2060,[1] necessitating the need to accurately evaluate health disparities that affect this population. Hispanic Americans have a higher incidence rate of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC).[2–7] More specifically, Mexican Americans living in the southern region of Texas have one of the highest prevalence rates of NAFLD as well as the highest age-adjusted HCC incidence rate of any ethnic group in the United States,[8] representing a public health concern.[1]

Hepatic fibrosis is a primary risk factor for liver-related events and HCC. Previous studies have shown that both hepatic steatosis and hepatic fibrosis are heritable.[9] A recent study revealed increased incidences of fibrosis in first-degree relatives of patients with NAFLD cirrhosis, suggesting advanced fibrosis screening could be considered in first-degree relatives of patients with NAFLD cirrhosis.[10] However, to our knowledge there are no prospective data examining the prevalence of advanced fibrosis and hepatic steatosis in first-degree relatives of Mexican Americans with HCC. As such, there is currently insufficient insight into whether family members should be screened for NAFLD and hepatic fibrosis. As screening for fibrosis becomes more accessible with non-invasive imaging modalities, this discussion becomes more relevant and essential in this understudied patient population.[11–13]

To address this knowledge gap, we evaluated the prevalence of hepatic fibrosis and definite hepatic steatosis in first-degree relatives of Mexican Americans with HCC in a population-based cohort in South Texas and examined clinical factors associated with hepatic fibrosis and steatosis.