(13C)-Methacetin breath test provides evidence of subclinical liver dysfunction linked to fat storage but not lifestyle

Abstract

Background & Aims Non-alcoholic fatty liver disease (NAFLD) is characterised by the presence of hepatic steatosis in the absence of other causes of secondary hepatic fat accumulation, and is usually associated with visceral, metabolically active obesity. However, the subclinical effects of body and liver fat accumulation on liver function are still unclear. Methods We used orally administered ( 13 C)-methacetin and breath test to quantify the efficiency of hepatic extraction from portal blood flow and liver microsomal function in 81 participants, in relation to presence/absence of ultrasonographic NAFLD, extent of body fat accumulation, insulin resistance, dietary models, and lifestyle. Results NAFLD was present in 23% of participants with normal weight, and prevalence increased with body fat and insulin resistance. Fat accumulation, NAFLD, and insulin resistance were associated with decreased hepatic extraction efficiency, and liver microsomal function was impaired in moderate-to-severe NAFLD. Caloric intake, dietary models, and lifestyles had a minor role in promoting functional changes. Conclusions The interplay between body fat accumulation, insulin resistance, and NAFLD is linked with altered hepatic extraction efficiency from blood flow and deranged microsomal function. Non-invasive diagnosis of subclinical alterations of liver function is relevant for primary and secondary prevention measures. Furthermore, the occurrence of NAFLD in lean individuals and the evidence that caloric intake, dietary models, and lifestyle played a minor role require further studies exploring the role of environmental factors in the natural history of these diseases. Lay summary Obesity is progressively increasing worldwide and is paralleled by fat accumulation in the liver (non-alcoholic fatty liver disease [NAFLD]), the most common chronic liver disease worldwide. NAFLD can alter liver structure and function, with a variety of consequences ranging from asymptomatic and subclinical alterations to cirrhosis and cancer. ( 13 C)-Methacetin breath test, a non-invasive diagnostic tool, can reveal early subclinical alterations of liver dynamic function in individuals with obesity and in patients with NAFLD.

Multiplying effects of COVID‐19 lockdown on metabolic risk and fatty liver

“…Subjects in this subgroup also underwent, 1 year (basal) and 3 months before the lockdown (T1), anthropometric evaluation and measurement of liver steatosis. Liver steatosis was assessed with the Noblus‐E ultrasonographic equipment (Hitachi Medical) using a convex multifrequency (3.5‐12.0 MHz) probe according to a well‐standardized protocol, previously described by our group 19,20 . In brief, in the fasting subject, the echogenicity of liver parenchyma was compared against the kidney cortex echogenicity as the control parenchyma and defined as either isoechoic (normal liver) or hyperechoic = ‘bright’ parenchyma (steatotic liver).…”

“…A bright liver is a sensitive marker of liver steatosis, although its accuracy is poor for mild steatosis (<30%) and for the detection of underlying inflammation 21 . Liver steatosis was graded as grade 0: absence of fatty liver; grade 1: minor increase in liver echogenicity; and grade 2: marked increase in liver echogenicity with poor penetration of posterior segment from the right lobe, poor or any visual images from the hepatic vessels and diaphragm 20 …”

Nonalcoholic Fatty Liver Disease (NAFLD). Mitochondria as Players and Targets of Therapies?

“…With at least 10% weight reduction, liver fibrosis can improve in NASH. This goal, however, is difficult to maintain for a long time and to achieve in the majority of patients [149,152]. A healthy diet should be based on long-term caloric restriction rather than intermittent fasting to improve insulin sensitivity [153] and to prevent oxidative damage [154,155].…”

Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests

“…Liver BT can provide information about the complex metabolic function of the liver by marking a given substrate with the stable isotope 13 C, measured in breath as 13 CO 2 . Our group has provided studies dealing with evaluation of both mitochondrial and microsomal activity in the liver [ 36 , 96 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 ]. The rationale of BT depends on a given substrate that is metabolized at different levels in the body.…”

“…This approach can improve liver biochemical tests, liver histology, serum insulin levels, and quality of life [ 204 , 205 , 206 , 207 , 208 , 209 ]. We have learnt that in NASH, liver fibrosis can improve after at least 10% weight reduction, although this goal is difficult to achieve in the majority of patients and to maintain for a long time [ 142 , 207 ]. To improve insulin sensitivity and reduce body weight, the diet must be based on long-term caloric restriction rather than intermittent fasting [ 210 ].…”