Abstract
Nonalcoholic fatty liver disease (NAFLD) is known to be associated with insulin resistance, atherosclerosis, and low serum IGF1 levels. We have described a large cohort of patients with isolated GH deficiency (IGHD) due to the c.57+1G→A mutation in the GHRH receptor gene. These subjects have increased insulin sensitivity (IS), delayed atherosclerosis, and normal longevity. We hypothesized that, despite visceral obesity, NAFLD would be absent or mild due to the increased IS. To assess the prevalence and severity of NAFLD in adult subjects with lifetime, congenital, untreated IGHD, we studied 22 IGHD adults and 25 controls (COs) matched for age and sex. NAFLD was assessed by a comprehensive liver function panel, and ultrasonographic pattern (hyperechogenic pattern, HP) coded as follows: 0, absent; 1, mild; 2, moderate; and 3, severe. Compared with COs, IGHD individual had lower serum IGF1 (P<0.0001), higher total cholesterol (P=0.027), lower prothrombin time (P=0.017), and similar activated partial thromboplastin time and fibrinogen values. Alanine transaminase (ALT) values were similar in the two groups, but aspartate transaminase was higher in IGHD (P=0.013). However, more IGHD subjects (7/22) than COs (3/23) had ALT above the upper limit of normal (P=0.044). The prevalence of NAFLD was higher in IGHD than COs (61 vs 29%, P=0.032), and the HP score was higher in IGHD than COs (P=0.041), but severe NAFLD was not observed in any IGHD (or CO) individual. Liver HP score is increased in lifetime, untreated, congenital IGHD, but the increase in transaminases is mild, suggesting a lack of advanced forms of NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome and is associated with very common conditions such as obesity, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis (1)
In Itabaianinha County, in the Brazil Northeast, we have identified a large cohort of patients with congenital isolated GH deficiency (IGHD) due to a homozygous mutation (c.57C1G/A) in the GHRH receptor gene (GHRHR) (15)
IGHD subjects had higher total and LDL-C, lower prothrombin time (PT), and similar HDL-C, triglycerides, g-GT, activated partial thromboplastin time (APTT), and fibrinogen values compared with COs
Summary
Nonalcoholic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome and is associated with very common conditions such as obesity, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis (1). NAFLD includes the mere accumulation of lipid within hepatocytes (hepatic steatosis, HS), or the inflammation of the liver (nonalcoholic steatohepatitis, NASH), liver fibrosis, or cirrhosis (2). 3 : 133 occurs through the development of insulin resistance, by accumulation of fat in visceral tissue, and increased oxidative stress, with the consequent development of hepatitis (3). The consequences of NAFLD on mortality are an issue of debate (5), as this can be influenced by variable definitions and associated conditions. Cardiovascular mortality is increased in NASH cirrhosis compared with other types of cirrhosis, and the incidence of associated hepatocellular carcinoma is higher than 10% in 5 years (6). It is important to define the causes of NAFLD
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