17 July 2023: Meta-Analysis
Unraveling the Interplay between Nonalcoholic Fatty Liver Disease and Polycystic Ovary Syndrome in Adolescents: Pathogenesis, Prevalence, and Management Strategies
Kinga Półkośnik 1ABCDEFG* , Agnieszka Łebkowska 2ACDEF , Irina Kowalska 2ACDEF , Dariusz M. Lebensztejn 1ABCDEFGDOI: 10.12659/MSM.940398
Med Sci Monit 2023; 29:e940398
Table 2 Characteristics of the studied groups and main outcomes of the included studies.
| No. | First author (year) [refernce] | Comparison groups | Factors associated with higher prevalence of NAFLD/MAFLD/HS in PCOS | Conclusion |
|---|---|---|---|---|
| 1. | Tollefson et al (2018) []37 | Children divided into 4 groups: (1) non-obese, without psoriasis; (2) nonobese, with psoriasis; (3) obese, without psoriasis; and (4) obese, with psoriasis | – | Children with psoriasis are at a greater risk of developing NAFLD and PCOS, although obesity is a stronger contributor in development of comorbidities in this group |
| 2. | Cree-Green et al (2016) []29 | Obese adolescents with PCOS vs obese non-PCOS controls | De novo lipogenesis, visceral adiposity | 49% of obese adolescents with PCOS had hepatic steatosis. It was related to visceral fat and de novo lipogenesis |
| 3. | Ware (2022) []32 | Obese adolescents with PCOS vs without PCOS | Higher PFF | PFF is not related to PCOS status, hepatic fat fraction, or serum androgen concentration, although HS is more common in individuals with greater PFF |
| 4. | Leon et al (2018) []43 | Obese adolescents | – | NAFLD was diagnosed in 15.6% of obese children, and PCOS in 12% of girls over 10 years of age |
| 5. | de Zegher et al (2021) []22 | Non-obese adolescents with PCOS vs BMI-matched healthy controls; Adolescents with PCOS: treated with OC vs SPIOMET | OC (vs SPIOMET) treatment | SPIOMET treatment, by mimicking weight loss in normal-weight adolescents with PCOS, normalizes liver fat and decreases the risk of further metabolic dysfunction |
| 6. | Garcia-Beltran et al (2021) []23 | Non-obese adolescents with PCOS vs BMI-matched healthy controls; Adolescents with PCOS: treated with OC vs SPIOMET | Alteration of gut microbiota; ie, higher abundance of Family XI; OC (vs SPIOMET) treatment | SPIOMET treatment normalizes dysbiosis of gut microbiota in normal-weight adolescents with PCOS |
| 7. | Cree-Green et al (2017) []31 | Normal-weight adolescents: with PCOS vs healthy controls | – | Normal-weight girls with PCOS had increased hepatic fat compared with controls. Metabolic risk was higher in the PCOS group, despite normal BMI |
| 8. | Díaz et al (2018) []24 | Non-obese adolescents with PCOS vs BMI-matched healthy controls; Adolescents with PCOS: treated with OC vs SPIOMET | OC (vs SPIOMET) treatment; lower fetuin-A | Concentration of fetuin-A was decreased in adolescents with PCOS. SPIOMET treatment resulted in its increase to normal level |
| 9. | de Zegher et al (2021) []26 | Non-obese adolescents with PCOS vs BMI-matched healthy controls; Adolescents with PCOS: treated with OC vs SPIOMET | OC (vs SPIOMET) treatment | Relative deficit of growth differentiation factor-15 seems to contribute to difficulties with maintaining an adequate body weight in adolescents with PCOS. SPIOMET treatment is followed by its normalization |
| 10. | Ibáñez et al (2020) []27 | Non-obese adolescents with PCOS vs BMI-matched healthy controls; Adolescents with PCOS: treated with OC vs SPIOMET | OC (vs SPIOMET) treatment | SPIOMET treatment, compared with OC, results in better normalizing effect, including hepatovisceral adiposity, insulin sensitivity and ovulation rate |
| 11. | Malpique et al (2019) []28 | Non-obese adolescents with PCOS vs BMI-matched healthy controls; Adolescents with PCOS: treated with OC vs SPIOMET | Higher S100A4 concentration; OC (vs SPIOMET) treatment | S100A4 concentration was 71% higher among adolescents with PCOS compared with healthy controls, and was associated with greater hepatovisceral adiposity. It may become a circulating marker of excess fat in this group.Reduction of S100A4 level was higher with SPIOMET than OC treatment. |
| 12. | Ayonrinde et al (2016) []36 | Adolescent girls with NAFLD and PCOS vs girls with NAFLD without PCOS vs boys with NAFLD | Higher adiposity, CRP, HOMA-IR, lower SHBG | Pre-existing PCOS predicts NAFLD in adolescent girls. Girls with NAFLD and PCOS have adverse metabolic phenotype |
| Studies based on patients diagnosed with PCOS, general population: | ||||
| 13. | Garoufi et al (2021) []12 | Adolescents with PCOS: overweight vs normal-weight | Obesity | Overweight adolescents with PCOS have features predisposing them to the development of atherosclerotic cardiovascular disease. NAFLD was diagnosed in 22% of girls with PCOS, with higher prevalence in overweight patients |
| 14. | Won et al (2021) []41 | Patients (13–35 years old) with PCOS: with NAFLD vs without NAFLD- among this group: adults (20–35 years old) vs adolescents (13–19 years old) | Higher BMI, AST, ALT, IR, FAI; MetS, hyperandrogenism, dyslipidemia; lower SHBG, LH, AMH | Diagnosis of MetS in adolescents with PCOS is associated with increased risk of NAFLD development, thus systematized screening can be useful |
| 15. | Urbano et al (2022) []44 | Adolescents with PCOS: with NAFLD vs without NAFLD | Higher body weight, BMI, WC, systolic and diastolic BP, insulinemia, HOMA-IR, lower SHBG | SHBG level was significantly lower in adolescents with PCOS and NAFLD than in a non-NAFLD group. It was also negatively correlated with body weight, BMI, WC, systolic and diastolic BP, insulinemia, HOMA-IR, suggesting a possible use of SHBG as a biomarker of metabolic impairment |
| 16. | Ibáñez et al (2017) []25 | Non-obese adolescents with PCOS: treated with OC vs SPIOMET | OC (vs SPIOMET) treatment; loss of liver fat correlated with higher ovulation rates | SPIOMET treatment, by reducing hepatovisceral fat, normalizes ovulation rate more effectively than OC, which can reduce the risk of later subfertility |
| 17. | Carreau et al (2019) []38 | Obese adolescents with PCOS: with NAFLD vs without NAFLD | Higher ALT, free testosterone, TG, fasting insulin, HOMA-IR, HbA1c; lower SHBG | A clinical index to identify patients with probable NAFLD from a group of obese adolescents with PCOS was proposed |
| 18. | Kim et al (2016) []39 | Obese adolescents with PCOS: metabolically healthy vs metabolically unhealthy | – | Higher IR is associated with greater visceral adiposity among girls with PCOS.IR stronger than obesity indicates increased metabolic risk. |
| 19. | Jobira et al (2021) []30 | Obese adolescents with PCOS with HS vs without HS | Higher ALT, fasting insulin and C-peptide, HbA1c, HOMA-IR; alteration of gut microbiota | Alteration in gut microbiota was observed in obese adolescents with PCOS and HS. It was correlated with increased markers of metabolic dysfunction, suggesting a modifying role of gut microbiota in HS development |
| 20. | Michaliszyn et al (2013) []42 | Obese adolescents with PCOS: with NAFLD vs without NAFLD | Age, abdominal obesity, IR, dyslipoproteinemia | In obese adolescents with PCOS, liver fat is associated with IR, dyslipoproteinemia and increasing abdominal adiposity. Therapeutic approach focused on these disorders can reduce the risk of liver dysfunction in the future |
| 21. | Simon et al (2020) []33 | Obese adolescents with PCOS with MetS vs without MetS | Poorer sleep efficiency | During sleep, disordered breathing correlates with greater liver steatosis and higher prevalence of MetS in obese adolescents with PCOS |
| 22. | Andrisse et al (2021) []34 | Overweight adolescents with PCOS divided into groups according to their race or ethnicity | – | Adolescents with PCOS show similar racial and ethnic variation of metabolic outcomes to the general population |
| 23. | Castro-Correia et al (2018) []40 | Adolescents with T1DM: normal-weight vs overweight | – | NAFLD and PCOS occurs in both normal-weight and overweight adolescents with T1DM, justifying the need for screening regardless of BMI |
| ALT – alanine aminotransferase activity; AMH – anti-Mullerian hormone; AST – aspartate aminotransferase activity; BMI – body mass index; BP – blood pressure; CRP – C-reactive protein; FAI – free androgen index; HbA1c – hemoglobin A1c; HOMA-IR – the homeostatic model assessment for insulin resistance; HS – hepatic steatosis; IR – insulin resistance; LH – luteinizing hormone; MAFLD – metabolic-dysfunction-associated fatty liver disease; MetS – metabolic syndrome; NAFLD – non-alcoholic fatty liver disease; OC – oral estroprogestogen contraception; PCOS – polycystic ovary syndrome; PFF – pancreatic fat fraction; S100A4 – a member of the S100 calcium-binding protein family; SHBG – sex-hormone binding globulin; SPIOMET – multi-drug therapy composed of low-dose spironolactone, pioglitazone, and metformin; T1DM – type 1 diabetes mellitus; TG – triglycerides; WC – waist circumference. | ||||