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

Emilio Molina-Molina; Harshitha Shanmugam; Agostino Di Ciaula; Ignazio Grattagliano; Domenica Maria Di Palo; Vincenzo O Palmieri; Piero Portincasa

doi:10.1016/j.jhepr.2020.100203

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

JHEP Rep. 2020 Nov 4;3(1):100203. doi: 10.1016/j.jhepr.2020.100203. eCollection 2021 Feb.

Authors

Emilio Molina-Molina¹, Harshitha Shanmugam¹, Agostino Di Ciaula¹, Ignazio Grattagliano², Domenica Maria Di Palo¹, Vincenzo O Palmieri¹, Piero Portincasa¹

Affiliations

¹ Clinica Medica 'A. Murri', Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy.
² Italian College of Family Medicine, Bari, Italy.

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 (¹³C)-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. (¹³C)-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.

Keywords: (13C), carbon-13; ALT, alanine aminotransferase; ARFI, acoustic radiation force impulse; AST, aspartate aminotransferase; BT, breath test; Body mass index; DOB, delta over baseline; FLI, fatty liver index; GGT, gamma-glutamyl transferase; HOMA, Homeostatic Model Assessment for Insulin Resistance; HRQoL, health-related quality of life; IDF, International Diabetes Federation; KICA, ketoisocaproic acid; Liver function; MBT, methacetin breath test; MD, Mediterranean diet; MET, metabolic equivalent task; Microsomal function; NAFL, non-alcoholic fatty liver; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; Non-alcoholic fatty liver disease; OR, odds ratio; Portal blood flow; R-ATPIII, Revised National Cholesterol Education Programme-Adult Treatment Panel III; SF-36, 36-Item Short Form Health Survey Questionnaire; US, ultrasonography; cPDR, cumulative per cent dose recovery.