Sedentary liver: How this hepatic condition connects to other diseases and lifestyle

A new term has emerged in the medical lexicon: sedentary liver. The phrase, coined by German researchers, describes the effects of sedentary living on the hepatic organ. Clinically, sedentary liver presents with a lower V02max, decreased hand grip strength, and a smaller, stiffer heart. 

We can add sedentary liver to the dark triad of metabolic disease, obesity, and non-alcoholic fatty liver disease (NAFLD). Patient education is critical for stemming the effects of all of these conditions.

Sedentary liver explained

Researchers published findings on sedentary liver in Liver International and cited previous research on the subject. Prolonged sitting and lower rates of physical activity were related to the presence of hepatic steatosis on ultrasound. Furthermore, lower rates of cardiorespiratory fitness were also linked to hepatic steatosis on ultrasound. 

In their study, the investigators assessed the association between VO2max, liver enzymes, and liver fat content via MRI in a cohort of adults. They also assessed the effect of obesity on these measures.

They found that lower VO2peak was correlated with increased liver fat content and higher serum GGT levels. They suggested that low VO2peak could predict hepatic steatosis. 

In other findings, participants who were obese and overweight with low VO2peak had more liver fat content than did participants with high VO2peak. Similarly, low VO2peak was independently correlated with a higher risk of hepatic steatosis in obese and overweight participants.

As for a possible mechanism, the researchers hypothesized the following: 

“Low muscle activity may have a direct effect on the normal body physiology, contributing to obesity and coexisting insulin resistance, dysglycaemia and atherogenic dyslipidemia, all of which will have a deleterious influence on LFC (liver fat content). On the other hand, our statistical regression models considered the influences of fat-free mass, fat mass and plasma glucose levels suggesting a possible direct effect of low levels of physical activity on HS (hepatic steatosis).”

Intriguingly, the rise in liver enzymes (ie, GGT levels) could be due to higher levels of oxidative stress as hepatic steatosis progresses.

Metabolic disease and NAFLD

Those with type 2 diabetes (T2DM) have a prevalence of NAFLD of between 60% and 70%. Disconcertingly, T2DM is linked with higher risk of progressive forms of NAFLD such as nonalcoholic steatohepatitis and advanced liver disease. In those with T2DM the prevalence of advanced fibrosis can be as high as between 10% and 15%.

T2DM also results in a twofold increase in hepatocellular carcinoma and liver-related death, which are NAFLD complications. Furthermore, impaired glycemic control may be tied to worsened liver fibrosis in NAFLD in addition to the presence of T2DM. In other words, those with poor glycemic control may be at extra risk of NAFLD and poor liver outcomes. 

“Despite an increasing clinical burden of NAFLD, and calls to action across the medical community to prepare for this rising public health threat, NAFLD remains under-recognized in primary care settings,” the authors of a 2021 Journal of the Endocrine Society study wrote. “It is likely that this underrecognition extends to T2DM populations—even in those with poor glycemic control—though data specific to poorly controlled T2DM are lacking.”

In the study, the researchers assessed NAFLD testing and care patterns in a cohort of 228 patients with poorly controlled T2DM. They found that one-third of participants without known NAFLD had abnormal liver enzymes, yet only 7% had a liver ultrasound. Of note, liver ultrasounds are first-line imaging tests used to support a diagnosis of NAFLD. Moreover, fewer than 5% were referred to a hepatologist or for a transient elastography, and of those referred, half had advanced fibrosis.

“To put these findings into context, current guidelines suggest a high index of suspicion for progressive forms of NAFLD in T2DM, and they recommend use of noninvasive risk assessment tools, such as FIB-4 or transient elastography, to assess for risk of advanced fibrosis,” the authors wrote. “At minimum, abnormal liver enzymes and/or fatty liver noted on imaging should be followed by some form of liver fibrosis assessment.”

Interventions

The two types of NAFLD are nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Patients usually develop one or the other, but one form can follow another in some patients. NAFL refers to fat around the liver but little/no inflammation or liver damage. It typically does not lead to liver damages or complications but can result in pain.

On the other hand, NASH is marked by fat in the liver, as well as inflammation and liver damage. This form can lead to fibrosis, cirrhosis, and liver cancer.

There is no cure for NASH, however comorbidities can be treated including obesity, diabetes, and hyperlipidemia. Specific interventions include weight loss, and treatment of insulin resistance. Vitamin E might also be helpful to decrease liver damage, as well as liver biopsy to determine prognosis.

Sources

1. Zinterl I. Low Cardiopulmonary Fitness is Associated with Higher Liver Fat Content and Higher Gamma‐Glutamyltransferase Concentrations in the General Population – “The Sedentary’s Liver” (wiley.com). Liver International. 

2. Alexopoulos A. Underrecognition of Nonalcoholic Fatty Liver Disease in Poorly Controlled Diabetes: A Call to Action in Diabetes Care. Journal of the Endocrine Society.

3. Definition & Facts of NAFLD & NASH. NIH.