Infectious Mononucleosis Increases the Risk of NAFLD

Sven H. Loosen, MD

A diagnosis of infectious mononucleosis may increase the risk of developing non-alcoholic fatty liver disease (NAFLD), according to new research.

A team, led by Sven H. Loosen, MD, Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, compared the prevalence of NAFLD in a cohort of patients with infectious mononucleosis with the prevalence of NAFLD in a healthy control group.

A Growing Problem

NAFLD is currently the leading cause of liver cirrhosis and hepatocellular carcinoma globally.

While research in the past has identified various genetic and lifestyle-related risk factors, the pathophysiology has not yet been identified.

“While acute EBV infection in the setting of infectious mononucleosis can lead to acute hepatitis, the long-term hepatic sequelae of infectious mononucleosis are still poorly understood,” the authors wrote.

The Cohort

In the retrospective cohort, the investigators examined 13,859 patients with NAFLD and 13,859 matched participants without infectious mononucleosis from the Disease Analyzer database (IQVIA).

The investigators used multivariable Cox-regression analyses to evaluate the association between infectious mononucleosis and NAFLD.

The results show 2.64% of patients with infectious mononucleosis had been diagnosed with NAFLD within 10 years of the index date (P <0.001), compared to 1.78% of individuals without infectious mononucleosis.

The incidence of NAFLD was 263.9 cases per 100,000 person-years in the infectious mononucleosis group, compared to 164.5 cases per 100,000 person-years in individuals without it.

The multivariable regression analyses showed that infectious mononucleosis was significantly associated with the incidence of NAFLD (HR, 1.73) in both women (HR, 1.73) and men (HR, 1.70).

After conducting an age-stratified analyses, the investigators found the link between infectious mononucleosis and NAFLD was most pronounced in the 41-50 age group (HR, 2.94), as well as for those older than 50 years (HR, 2.68).

“Infectious mononucleosis is significantly associated with the incidence of NAFLD in a large cohort from Germany. These findings suggest a pathophysiological involvement of EBV in the development of NAFLD and could stimulate research efforts to better understand the pathophysiology of this emerging global medical burden,” the authors wrote.

NAFLD Cases Rising Globally

Earlier this year, investigators found the prevalence of NAFLD is increasing worldwide and remains especially high among men.

A team, led by Kiarash Riazi, MD, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, examined the burden of NAFLD by estimating the temporal trends of worldwide prevalence and incidence.

In the systematic review and meta-analysis, the investigators searched various databases between inception and May 25, 2021 for observational cross-sectional or longitudinal studies in patient populations representative of the general adult population for which NAFLD was diagnosed using an imaging method in absence of excessive alcohol consumption and viral hepatitis.

Overall, they identified 28,557 total records, 13,577 of which were screened, with 299 records also identified through other methods. There was a total of 72 publications with a sample population of 1.03 million participants from 17 countries in the prevalence analysis.

The prevalence of NAFLD worldwide was 32.4% (95% CI, 29.9-34.9%). However, the prevalence of the disease has significantly increased over time, from 25.5% (95% CI, 20.1-31.0%) in or before 2005 to 37.8% (95% CI, 32.4-43.3%) in 2016 or later (P = 0.013).

The prevalence of disease was also higher in men (39.7%; 95% CI, 36.6-42.8%) than it was in women (25.6%; 95% CI, 22.3-28.8) (P <0.0001).

The investigators also estimated an overall incidence of NAFLD of 46.9 cases per 1000 person-years. However, the incidence rate was higher in men (70.8 cases per 1000 person-years; 95% CI, 48.7-92.8) than it was in women (46.9 cases per 1000 person-years; 95% CI, 20.2-38.9) (P <0.0001).

There was also considerable heterogeneity between studies focused on NAFLD prevalence (I2 = 99·9%) and NAFLD incidence (I² = 99·9%).

The study, “Infectious mononucleosis is associated with an increased incidence of NAFLD,” was published online in the European Journal of Clinical Investigation.