Metabolic associated fatty liver disease is highly prevalent in the post-acute COVID syndrome

Background Recently a proposal has been advanced to change the traditional definition of Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic Associated Fatty Liver Disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long COVID is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with post-acute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods We included 235 patients followed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first post-discharge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (p<0.001). Insulin resistance (OR=1.5, 95%CI: 1.14-1.96), body mass index (OR=1.14, 95%CI: 1.04-1.24), and the metabolic syndrome (OR=2.54, 95%CI: 1.13-5.68), were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR=0.86, 95%CI: 0.76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions MAFLD was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

Association of Hepatic Steatosis Index with Nonalcoholic Fatty Liver Disease Diagnosed by Non-Enhanced CT in a Screening Population

The noninvasive diagnosis of hepatic steatosis is of increasing concern. This study investigated the association of hepatic steatosis determined by non-enhanced CT criteria with clinical parameters in a screening population. Asymptomatic patients who underwent abdominal CT at our healthcare center were retrospectively analyzed (n = 339). Two radiologists measured the attenuation values of the liver parenchyma and spleen using non-enhanced CT images. CT criteria for hepatic steatosis were (a) absolute liver attenuation value <48 Hounsfield units (HU), (b) liver-to-spleen attenuation ratio <0.8, and (c) attenuation difference between the liver and spleen <−10. Body mass index (BMI) and hepatic steatosis index (HSI) were calculated, and laboratory findings were recorded. The association of hepatic steatosis with clinical parameters was assessed using univariate and logistic regression analyses. The presence of hepatic steatosis was significantly associated with the levels of serum fasting glucose and triglycerides, the alanine aminotransferase to aspartate aminotransferase (ALT/AST) ratio, BMI, and HSI values using any of the CT criteria. Logistic regression analysis revealed that the serum fasting glucose level and HSI were significantly associated with hepatic steatosis using criterion (a), while the ALT/AST ratio and HSI were associated with hepatic steatosis using criteria (b) and (c). The presence of hepatic steatosis on non-enhanced CT should be considered to indicate possible clinical profile abnormalities regarding metabolic syndrome.

Diagnostic accuracy and limitations of non-invasive tests in patients with metabolic-associated fatty liver disease

Resumen La incidencia de la enfermedad del hígado graso asociada al metabolismo (MAFLD) ha aumentado en los últimos años debido al estilo de vida actual. La biopsia de hígado sigue siendo la herramienta estándar de oro para detectar y estadificar MAFLD. Por otro lado, se están desarrollando múltiples biomarcadores y pruebas no invasivas para superar las limitaciones de la biopsia hepática, incluidos el costo y la invasividad. Las pruebas no invasivas se centran principalmente en la esteatosis y, en particular, en la fibrosis hepática y se pueden clasificar en pruebas patentadas y no patentadas. Si bien hepatic steatosis index y fatty liver index son las pruebas más comunes utilizadas para la detección de esteatosis, Hepamet Fibrosis Score, NAFLD fibrosis score, FIB-4, OWLiver®, y ELF® son las más utilizadas para la fibrosis hepática. Sin embargo, las pruebas no invasivas también tienen limitaciones que conviene resaltar ya que sus resultados podrían verse afectados por la presencia de diabetes, obesidad o por edades extremas que podrían dar lugar a falsos positivos o negativos. Para maximizar la precisión de los tests no invasivos, se han propuesto diferentes combinaciones integradas en algoritmos escalonados. Esta revisión tiene como objetivo destacar las fortalezas y limitaciones de dichos tests para detectar y estadificar MAFLD.

Xanthine Oxidoreductase Activity Is Correlated With Hepatic Steatosis

The enzyme xanthine oxidoreductase (XOR) catalyzes the formation of uric acid (UA) from hypoxanthine and xanthine, which in turn are products of purine metabolism starting from ribose-5-phosphate. Several studies suggested a relationship between hyperuricemia and hepatic steatosis; however, few previous studies have directly examined the relationship between XOR and hepatic steatosis. A total of 223 subjects with one or more cardiovascular risk factors were enrolled. Hepatic steatosis was calculated according to the liver-to-spleen (L/S) ratio on computed tomography and the hepatic steatosis index (HSI). We measured a plasma XOR activity assay using a newly established highly sensitive assay based on [13C2, 15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. XOR activity and the UA level were increased in subjects with L/S ratio <1.1 and HSI <36. Multivariate logistic regression analysis indicated that plasma XOR activity was associated with the risk of hepatic steatosis as assessed by the L/S ratio and HSI independently of insulin resistance, whereas UA levels were not associated with risk of hepatic steatosis. The results of this study indicated that plasma XOR activity is associated with hepatic steatosis independently of insulin resistance and serum UA levels.

Hepatic Steatosis Index and Chronic Kidney Disease among Middle-Aged Individuals: A Large-Scale Study in Japan

Background. Though nonalcoholic fatty liver disease (NAFLD) is related to chronic kidney disease (CKD), it is unclear whether the hepatic steatosis index (HSI), a screening tool for NAFLD, is related to CKD. The present study investigated the relationship between HSI and CKD among middle-aged individuals in Japan. Methods. Subjects were adults (aged 40–64 years) who received an annual health checkup in Japan between April 2013 and March 2014. Height and weight were measured, and venous blood samples were obtained to determine alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine levels. HSI was calculated by the following formula: HSI = 8 × ALT / AST ratio + body mass index (+2, if diabetes; +2, if female). CKD was defined as an estimated glomerular filtration rate < 60 mL / min / 1.73 m 2 and/or urinary protein of ≥ (+). Logistic regression analysis was performed to estimate the odds ratio (OR) and its 95% confidence interval (CI) for CKD. Results. Data of 94,893 adults were analyzed. Compared with men with an HSI < 30 , men with 30 ≤ HSI ≤ 36 (OR: 1.50, 95% CI: 1.40–1.61) and HSI > 36 (OR: 2.14, 95% CI: 1.99–2.31) had significantly higher ORs for CKD. Moreover, there was a significant dose-response relationship between HSI and CKD ( P for trend < 0.001 ). Even after adjusting for confounders, the significant results persisted. These findings in men were similar to those in women. Conclusions. This study showed that the HSI was associated with CKD among middle-aged adults in Japan. Additionally, a dose-response relationship of HSI to CKD was observed. The present study suggested that it might be useful to monitor the HSI among middle-aged individuals to detect CKD at an early stage.

Validity of routine biochemical and ultrasound scores for prediction of hepatic fibrosis and steatosis in NAFLD

Background We evaluated the validity of some non-invasive scores and ultrasound findings to predict fibrosis and steatosis in a cohort of NAFLD patients who underwent liver biopsy. Ninety-seven NAFLD patients were enrolled and classified into NASH (66) and simple steatosis groups (31) based on liver biopsy. ROC curves were constructed for Fibrosis-4 index (FIB4), aspartate aminotransferase to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) in fibrosis prediction, also for (hepatic steatosis index; HSI, fatty liver index; FLI) and ultrasonographic subcutaneous and visceral adipose tissue measurements (SAT and VAT) for steatosis prediction. Results FIB4 had AUC of 0.6, APRI and NFS at cutoffs of 0.3 and -.2.4 had AUC of 0.64 and 0.63 in detecting the presence of any grade of fibrosis, and of (0.52, 0.55, and 0.58) for significant fibrosis. FIB4 at a cut-off of (0.76) had the highest AUC in detecting any grade of fibrosis in the simple steatosis group (0.81). SAT (at cutoff of 2.1 and 2.5) was superior to VAT. HSI (at cutoff 45.35 and 45.7) was superior to FLI in detecting moderate or marked steatosis. Conclusion FIB4 and NFS can be used in screening for silent liver disease with ongoing fibrosis in simple steatosis. They are unsatisfactory predictors for significant fibrosis in NAFLD. SAT is better than VAT in predicting moderate steatosis and is slightly better than biochemical HSI.

External Validation of Surrogate Indices of Fatty Liver in the General Population: The Bagnacavallo Study

We externally validated the fatty liver index (FLI), the lipid accumulation product (LAP), the hepatic steatosis index (HSI), and the Zhejiang University index (ZJU) for the diagnosis of fatty liver (FL) and non-alcoholic fatty liver disease (NAFLD) in the general population. The validation was performed on 2159 citizens of the town of Bagnacavallo (Ravenna, Italy). Calibration was evaluated by calculating the calibration slope and intercept and by inspecting calibration plots; discrimination was evaluated using the c-statistic. The average calibration slope was 1 and the average intercept was 0 for all combinations of outcomes and indices. For the diagnosis of FL, the c-statistic was 0.85 for FLI, 0.83 for ZJU, 0.82 for HSI, and 0.80 for LAP; for the diagnosis of NAFLD, the c-statistic was 0.77 for FLI, 0.76 for ZJU, 0.75 for HSI, and 0.74 for LAP. All indices were strongly correlated with each other. In conclusion, FLI, LAP, HSI, and ZJU perform similarly well to diagnose FL and NAFLD in the Bagnacavallo population, even if FLI has a small advantage as discrimination is concerned.