Table 2.
Studies investigating the risk factors for the development of NAFLD in GHD patients.
| Studies | Study design | Study population | Diagnostic criteria | Findings |
|---|---|---|---|---|
| Ichikawa et al (2003) (119) |
Cross-sectional | 18 adult patients with hypopituitarism (n=18) GHD patients (n=13) (BMI <25 Kg/m2) |
NAFLD: computer tomography (liver/spleen CT value <0.9) |
Higher prevalence of hepatic steatosis in GHD patients vs hypopituitaric subjects without GHD |
| Adams et al (2004) (120) |
Longitudinal cohort | Patients with pituitary/ hypothalamic dysfunction (n=879) (Mean age: 30 yr., BMI> 25 Kg/m2) |
NAFLD: Imaging + liver enzyme Alteration, liver biopsy on (n=10) NAFLD patients |
GHD patients with NAFLD (n=21) with a 2.3% prevalence |
| Ichikawa et al (2007) (121) |
Cross-sectional | Country: Japan NAFLD patients (n=55) (Mean age: 49.7 yr., Mean BMI: 29 Kg/m2) |
NAFLD: ALT, ultrasound, CT and liver biopsy |
Probable association between low IGF-1 levels and liver fibrosis as well as low GH levels and steatosis |
| Arturi et al (2011) (122) |
Ambulatory-care cross-sectional |
Country: Italy
Non- diabetic subjects (n=503) (Mean age: 52 yr., BMI> 25 Kg/m2) |
NAFLD: ultrasound | Reduced IGF-1 levels in NAFLD patients |
| Hong et al (2011) (123) |
Cross-sectional observational | Country: Korea Patients with hypopituitarism (n=34) Matched lean healthy controls (n=40) (Mean age: 55 yr., Mean BMI: 25.2 Kg/m2) |
NAFLD: ultrasound GHD: peak GH level of <3 ng/mL |
Significantly higher prevalence of NAFLD in men with hypopituitarism vs controls, lower GH levels in NAFLD patients, negative correlation between GH levels and the severity of steatosis |
| Koehler et al (2012) (124) |
Cross-sectional | Country: USA Patients with complicated Class III obesity (n=160) (Mean age:47.7 yr., Mean BMI: 46.8 Kg/m2) |
NAFLD and NASH: Liver biopsy | Lower serum levels of GH in obese patients with NASH and advanced fibrosis |
| Gardner et al (2012) (125) |
Cross-sectional | Country: UK GHD patients (n=28) Matched controls (n=24) GHRT group (n=12) (Mean age: 52.6 yr., Mean BMI: 27.8 Kg/m2) |
NAFLD: MRI-assessed IHLC (IHLC) > 5.6% GHD: GH response <3 mg/L after glucagon stimulation |
No differences in liver enzyme and intra-hepatic fat content in GHD group vs controls, reduced adiposity and IHLC with GHRT in patients with baseline high liver fat |
| Nishizawa et al (2012) (126) |
Cross-sectional retrospective | Country: Japan Adults with hypopituitarism and GHD (n=66) Matched healthy controls (n= 83) GHRT group (n=19) (Mean age: 48 yr., Mean BMI: 25 Kg/m2) |
NAFLD: ultrasound Liver biopsy on (n=16) patients GHD: insulin tolerance test or GH releasing peptide-2 test |
Significant higher prevalence (6.4-fold) of NAFLD in GHD group vs controls independently of obesity, higher risk of IR and overweight in GHD+ NAFLD group |
| Xu et al (2012) (127) |
Cross-sectional | Country: China NAFLD patients (n=1667) Healthy controls (n=5479) (Mean age: 49 yr., BMI> 22 Kg/m2) |
NAFLD: ultrasound | Significant association between GH and NAFLD, GH levels as a risk factor for NAFLD (OR = 0.651) |
| Sumida et al (2015) (128) |
Cross- sectional | Country: Japan Biopsy- proven NAFLD patients (n=199) Matched healthy controls (n=2911) (Age >50 yr., BMI >26 Kg/m2) |
NAFLD: liver biopsy | Significant lower circulating IGF-1 levels in NAFLD patients vs controls, decreased IGF-1 SDS values by elevated lobular inflammation |
| Meienberg et al (2016) (129) |
Cross-sectional | Multi-ethnic Adult GHD patients (n=22) Matched healthy controls (n=44) GHRT group (n=9) (Mean age: 21.6 yr., Mean BMI: 27.9 Kg/m2) |
NAFLD: proton magnetic resonance spectroscopy (IHLC >5.56%) GHD: GH levels <7.8 mU/L after glucagon stimulation test |
No differences in the prevalence of steatosis and IHLC between two groups, no observed changes in IHLC in GHRT group |
| Chishima et al (2017) (130) |
Cross- sectional | Biopsy-proven NAFLD patients (n=222) Patients with HCV-related- CLD (n=55) (Mean age: 53 yr., Mean BMI: 26.9 Kg/m2) |
NAFLD: liver biopsy | The role of increased GH levels and lowered IGF-1 levels in NAFLD progression |
| Dichtel et al (2017) (131) |
Retrospective cross- sectional | Multi- racial NAFLD patients (n=142) (Mean age: 50 yr., BMI> 35 Kg/m2) |
NAFLD: liver biopsy | Significant association between lower serum IGF-1 levels and the severity of NAFLD |
| Liang et al (2018) (132) |
Cross- sectional | Obese children (n=84) Normal weigh children (n=43) (Mean age: 10.5 yr.) |
NAFLD: ALT, ultrasound GH: standard provocative testing |
Significant inverse relation between NAFLD and IGF-1 as well as GH response test in children |
| Nguyen et al (2018) (133) |
Cross- sectional | Country: France Patients with PD (n=89) Healthy controls (n=74) (Mean age; 53.1 yr., Mean BMI: 29.2 Kg/m2) |
Steatosis: MRI (LFC>5.5%) | Significant higher prevalence of steatosis and higher LFC in patients with PD due to the lower IGF-1 levels |
| Yuan et al (2019) (134) |
Cross-sectional retrospective | Country: China Adults with hypopituitarism/pan- hypopituitarism (n=50) GHD patients (n=43) (Mean age: 22.8 yr., Mean BMI: 22.2 Kg/m2) |
NAFLD: ultrasound and liver biopsy GHD: serum GH level<3 μg/L | GHD in 87% of NAFLD patients, no significant differences in serum GH and IGF-1 among studied groups |
ALT, Alanine transaminase; GH, growth hormone; GHD, growth hormone deficiency; GHRT, growth hormone replacement therapy; HCV-related- CLD, Hepatitis C virus (HCV)- related chronic liver disease (CLD); IGF-1, Insulin- like growth factor-1; IHLC, intra-hepatic lipid content; IR, Insulin resistance; LFC, Liver fat content; MRI, Magnetic resonance imaging; NAFLD, Non-alcoholic fatty liver disease; NASH, Non-alcoholic steatohepatitis; OR, Odds ratio; PD, Pituitary disease; SDS, Standard deviation score.