Longitudinal Changes in Liver Fat Content in Asymptomatic Adults: Hepatic Attenuation on Unenhanced CT as an Imaging Biomarker for Steatosis.

OBJECTIVE: The objective of this study was to evaluate changes in liver fat content over time in asymptomatic adults and to investigate the factors that may influence these changes. MATERIALS AND METHODS: Liver attenuation on unenhanced CT images of 1022 asymptomatic adults (556 women and 466 men; mean age at the time of the index CT examination, 56.7 years) was retrospectively measured on initial and surveillance CT colonography screening examinations (mean [± SD] interval, 5.5 ± 0.8 years). Changes in liver attenuation (expressed as Hounsfield units) were assessed according to various factors, including body mass index (BMI), age, and sex. RESULTS: Mean liver attenuation was 60.3 HU on the index CT scan and 58.4 HU on the 5-year follow-up CT scan (p < 0.0001). Changes in liver attenuation greater than 10 HU, 5-10 HU, and less than 5 HU were observed in 187 (18%), 212 (21%), and 623 (61%) individuals, respectively. Changes in attenuation greater than 10 HU were negative (i.e., fattier liver) in 130 of 187 individuals (70%) and were more likely to be associated with an increase in BMI (83 of 130 individuals [64%] vs 19 of 57 individuals [33%]; p < 0.0001). For changes in attenuation of 5 HU or more, negative (steatotic) changes outnumbered positive changes, occurring in 258 of 1022 individuals (25%) versus 141 of 1022 individuals (14%) (p < 0.0001). Changes in BMI were negatively correlated with changes in attenuation (p = 0.015). There was no statistically significant correlation between changes in attenuation and either age or sex. An improved lipid profile and the use of a lipid-lowering medication regimen correlated with an interval decrease in liver attenuation. CONCLUSION: Changes in liver attenuation over time, reflecting temporal changes in fat content, were quite variable in this asymptomatic adult population and were only partially explained by the factors examined. These observations may provide early insight into the natural history of incidental hepatic steatosis in asymptomatic adults.

Natural history of hepatic steatosis: observed outcomes for subsequent liver and cardiovascular complications.

OBJECTIVE: Hepatic steatosis is a common incidental finding at radiologic imaging. The natural history of nonalcoholic fatty liver disease (NAFLD) and its associated risks for cardiovascular complications are not well established in this context. Our purpose was to investigate the clinical outcome of moderate-to-severe hepatic steatosis detected incidentally at CT. MATERIALS AND METHODS: Liver attenuation was measured at unenhanced CT in 4412 consecutive adults scanned over a 12-month period. Moderate-to-severe steatosis was diagnosed by liver attenuation less than or equal to 45 HU, which is essentially 100% specific for histologic grading of 30% or more fat content. The control group was defined by a high-normal liver attenuation of 60-65 HU. The main exclusion criteria were preexisting liver disease (beyond asymptomatic NAFLD), alcoholism, or less than 1 year of clinical follow-up. A medical record review assessed for the development of symptomatic liver disease (including nonalcoholic steatohepatitis and cirrhosis) and seminal cardiovascular events (myocardial infarction, cerebrovascular accident, transient ischemic attacks, or coronary bypass or stent). Data for body mass index, diabetes, and liver enzyme levels were also recorded. RESULTS: Five hundred three adults (11.4%) had unenhanced CT liver attenuation of 45 HU or less, yielding a final steatosis cohort of 282 patients after exclusions; the control group consisted of 768 patients after exclusions. The mean (± SD) patient age (51.4 ± 14.7 vs 50.8 ± 17.4 years), sex (53.9% vs 54.7% female), and mean follow-up intervals (7.3 ± 3.2 vs 7.7 ± 3.2 years) were similar between groups. No patient in either group had progression of liver disease beyond incidental steatosis. Subsequent cardiovascular events were more common in the steatosis cohort (9.9% vs 5.9%; p = 0.028), but steatosis was not an independent risk factor after controlling for diabetes and body mass index in multiple logistic regression analysis. CONCLUSION: This longitudinal study failed to show progression of moderate-to-severe hepatic steatosis to symptomatic forms of fatty liver disease over a 5- to 10-year time horizon. Aggressive workup of hepatic steatosis found incidentally on imaging does not appear to be warranted. Steatosis was a biomarker for subsequent cardiovascular events but not an independent risk factor.

Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis.

OBJECTIVES: To determine a highly specific liver attenuation threshold at unenhanced CT for biopsy-proven moderate to severe hepatic steatosis (≥30% at histology). METHODS: 315 asymptomatic adults (mean age ± SD, 31.5 ± 10.1 years; 207 men, 108 women) underwent same-day unenhanced liver CT and ultrasound-guided liver biopsy. Blinded to biopsy results, CT liver attenuation was measured using standard region-of-interest methodology. Multiple linear regression analysis was used to assess the relationship of CT liver attenuation with patient age, gender, BMI, CT system, and hepatic fat and iron content. RESULTS: Thirty-nine subjects had moderate to severe steatosis and 276 had mild or no steatosis. A liver attenuation threshold of 48 HU was 100% specific (276/276) for moderate to severe steatosis, with no false-positives. Sensitivity, PPV and NPV at this HU threshold was 53.8%, 100% and 93.9%. Hepatic fat content was the overwhelming determinant of liver attenuation values, but CT system (P < 0.001), and hepatic iron (P = 0.035) also had a statistically significant independent association. CONCLUSIONS: Unenhanced CT liver attenuation alone is highly specific for moderate to severe hepatic steatosis, allowing for confident non-invasive identification of large retrospective/prospective cohorts for natural history evaluation of incidental non-alcoholic fatty liver disease. Low sensitivity, however, precludes effective population screening at this threshold. KEY POINTS: • Unenhanced CT liver attenuation is highly specific for diagnosing moderate/severe hepatic steatosis. • Unenhanced CT can identify large cohorts for epidemiological studies of incidental steatosis. • Unenhanced CT is not, however, effective for population screening for hepatic steatosis.