Prevalence of Increased Hepatic Stiffness and Fat Fraction in STAT3 Dominant Negative Disease

Abstract

Liver disease in inborn errors of immunity (IEI) is increasingly recognized. Nodular regenerative hyperplasia (NRH) has been seen in STAT3 GOF but not in STAT3 DN disease. Fatty liver disease has been on imaging and on a biopsy in our STAT3 DN cohort. With improving long-term prognosis in STAT3 DN, the impact of liver disease deserves attention. MRI at 3T was used to measure Liver Fat Fraction (FF) using Quantitative Dixon and liver stiffness was assessed by MR Elastography (MRE). Fatty liver was defined as a FF percent > 5%, and abnormal stiffness was considered > 2.5kPa. Records were reviewed for body mass index (BMI), liver transaminases, platelets, lipid panels, and signs of insulin resistance. Thirty-seven patients (21 females) ranging in age from 18–70 years (median 29) had liver fat assessed; 27 were assessed for liver stiffness. One patient with high liver FF and stiffness was excluded for degree of alcohol consumption. Ten of 36 patients (27.8%) had liver FF above 5% (mean 7.8%). Fifteen of 27 (55.6%) patient had elevated liver stiffness (>2.5 kPa). Two had both elevated liver FF and stiffness. Sixteen of 36 (44%) had BMI of 30 or above, similar to the US population. Higher BMI was seen with fatty liver (35.5 vs 27.0). Although females had significantly higher BMI than males (31.1 vs 26.8), gender differences were not seen in fatty liver. BMI was lower in those with liver stiffness (21.6 vs. 32.2); a higher percentage of males had liver stiffness than females. HgbA1C above 6.0% was seen in five of 24 assessed (20.8%), two of whom had higher serum insulin levels. Four others had high insulin despite normal HgbA1C. Only three of 36 (8.3%) patients had high serum ALT. Nine of 36 (25%) had mild thrombocytopenia (123 000–170 000); 6 of the nine had abnormal liver stiffness.Liver disease in STAT3 DN disease is likely under-estimated with fatty liver corresponding with high BMI despite chronic illness. Increased liver stiffness was seen, and of concern was associated with thrombocytopenia for several patients, potentially indicating portal hypertension. Further study is needed to understand the pathogenesis and clinical implications.