Non-Alcoholic Fatty Liver Disease (NAFLD) is a condition that causes excess fat deposition in the liver, in individuals who do not consume alcohol as a causative factor.

Although NAFLD is considered a benign condition, it may progress to non-alcoholic steatohepatitis (NASH), cirrhosis and eventually liver failure. However, the associated complications of NAFLD go beyond just liver involvement and may affect other organs such as the cardiovascular system, endocrine system and the gastrointestinal system.

Cardiovascular Complications

Individuals with NAFLD have increased risk for developing cardiovascular disease (CVD) due to various mechanisms including dyslipidemia, insulin resistance, oxidative stress, inflammation among others.

A study by Targher et al (2010) found that there was a significant association between NAFLD and increased risk of atherosclerosis, which is a key process in the development of CVD. Additionally, NAFLD is also associated with increased risk of hypertension, which is another risk factor for CVD.

Endocrine Complications

NAFLD is associated with various endocrine disorders which include type 2 diabetes mellitus (T2DM), metabolic syndrome as well as hypothyroidism. Patients with NAFLD have an increased risk of developing insulin resistance, which contributes to T2DM.

In turn, patients with T2DM have an increased risk of developing NAFLD, in a vicious cycle. Hypothyroidism, on the other hand, contributes to increased adiposity and dyslipidemia- both of which may lead to development of NAFLD.

Gastrointestinal Complications

NAFLD is associated with various gastrointestinal complications, such as gastrointestinal reflux disease (GERD), esophageal varices and cholecystitis.

GERD may develop due to the increased intra-abdominal pressure from hepatic inflammation and ascites in patients with advanced liver disease. On the other hand, esophageal varices may develop due to portal hypertension, which is a complication of advanced liver disease in patients with NAFLD.

Psychological Complications

Patients with NAFLD may experience psychological complications such as depression and anxiety. Moscatiello et al (2010) found that there was a significant association between NAFLD and depression.

The study found that patients with NAFLD who had depression had more severe liver histology, increased visceral adiposity and higher body mass index (BMI), compared to those without depression. Anxiety may also develop as a result of the perceived stigma of having a liver disease, especially when the etiology is related to lifestyle.

Renal Complications

Patients with NAFLD may develop renal complications such as chronic kidney disease (CKD) and glomerular hyperfiltration.

A study by Zhou et al (2017) found that patients with NAFLD had a significantly higher prevalence of CKD compared to those without NAFLD. The study also found that patients with NAFLD had a higher prevalence of albuminuria, which is a marker of kidney damage.

Neurological Complications

NAFLD is associated with various neurological complications, such as peripheral neuropathy, headache and stroke. Peripheral neuropathy may develop as a result of oxidative stress, which leads to axonal damage and demyelination of nerves.

Headache may also develop due to the associated dyslipidemia and vascular changes that increase the risk of stroke in patients with NAFLD.

Pulmonary Complications

Patients with NAFLD may develop pulmonary complications such as obstructive sleep apnea (OSA) and non-alcoholic fatty lung disease (NAFLD). OSA may develop due to the associated obesity and dyslipidemia which leads to narrowing of the airways.

NAFLD, on the other hand, may lead to interstitial lung disease, a condition characterized by structural changes in the lungs that affect gas exchange.

Dermatological Complications

Patients with NAFLD may develop dermatological complications such as acanthosis nigricans, which is characterized as skin with a thick, velvety texture and hyperpigmentation.

Acanthosis nigricans may develop due to insulin resistance, a common complication in patients with NAFLD. Additionally, patients with NAFLD may also develop pruritus, which is an uncomfortable sensation that causes an individual to itch the skin.

Bone Complications

Patients with NAFLD have an increased risk of developing bone complications such as osteoporosis and osteopenia. A study by Sumida et al (2020) found that patients with NAFLD had lower bone mineral density (BMD) compared to those without NAFLD.

The study also found that patients with NASH had an even lower BMD compared to those with simple steatosis.

Hematological Complications

NAFLD is associated with various hematological complications such as anemia, thrombocytosis and coagulopathy. A study by Kotronen et al (2009) found that patients with NAFLD had lower hemoglobin levels compared to those without NAFLD.

Additionally, patients with NAFLD had increased platelet count which is a risk factor for thrombosis. Coagulopathy may develop as a result of liver inflammation and dysfunction, which affects the synthesis of clotting factors.