Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

Endocrine

Volumn 51, Issue 2, 2016, Pages 211-221

  Targher, Giovanni ^a   Rossini, Maurizio ^a   Lonardo, Amedeo ^b  

^a UNIVERSITY HOSPITAL OF VERONA   (Italy)

^b UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

Author keywords

Metabolic syndrome; Non alcoholic fatty liver disease; PCOS; Polycystic ovary syndrome; Review

Indexed keywords

ADIPONECTIN; AMINOTRANSFERASE; PIOGLITAZONE; VASCULAR ADHESION PROTEIN 1;

ABDOMINAL OBESITY; AMINOTRANSFERASE BLOOD LEVEL; CASE CONTROL STUDY; CLINICAL FEATURE; CROSS-SECTIONAL STUDY; DIET THERAPY; DISEASE ASSOCIATION; DISEASE EXACERBATION; ECHOGRAPHY; EXERCISE; GENETIC VARIABILITY; HIGH RISK POPULATION; HUMAN; HYPERANDROGENISM; INSULIN RESISTANCE; LIVER BIOPSY; LIVER CIRRHOSIS; LIVER FIBROSIS; METABOLIC SYNDROME X; MOLECULAR PATHOLOGY; NONALCOHOLIC FATTY LIVER; NUCLEAR MAGNETIC RESONANCE IMAGING; OVARY POLYCYSTIC DISEASE; PREVALENCE; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; REVIEW; COMPLICATION; FEMALE; LIVER; OVARY; PATHOLOGY; RISK FACTOR;

FEMALE; HUMANS; INSULIN RESISTANCE; LIVER; NON-ALCOHOLIC FATTY LIVER DISEASE; OVARY; POLYCYSTIC OVARY SYNDROME; RISK FACTORS;

EID: 84956891878     PISSN: 1355008X     EISSN: 15590100     Source Type: Journal    
DOI: 10.1007/s12020-015-0640-8     Document Type: Review

References (84)

1. F. Nascimbeni, R. Pais, S. Bellentani, C.P. Day, V. Ratziu, P. Loria, A. Lonardo, From NAFLD in clinical practice to answers from guidelines. J. Hepatol. 59, 859–871 (2013)
2. N. Chalasani, Z. Younossi, J.E. Lavine, A.M. Diehl, E.M. Brunt, K. Cusi, M. Charlton, A.J. Sanyal, American Association for the Study of Liver Diseases; American College of Gastroenterology; American Gastroenterological Association. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am. J. Gastroenterol. 107, 811–826 (2012)
3. Q.M. Anstee, G. Targher, C.P. Day, Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat. Rev. Gastroenterol. Hepatol. 10, 330–344 (2013)
4. G. Targher, C.P. Day, E. Bonora, Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N. Engl. J. Med. 363, 1341–1350 (2010)
5. G. Targher, C.D. Byrne, Diagnosis and management of nonalcoholic fatty liver disease and its hemostatic/thrombotic and vascular complications. Semin. Thromb. Hemost. 39, 214–228 (2013)
6. A. Lonardo, S. Ballestri, G. Targher, P. Loria, Diagnosis and management of cardiovascular risk in nonalcoholic fatty liver disease. Expert Rev. Gastroenterol. Hepatol. 9, 629–650 (2015)
7. A. Lonardo, S. Ballestri, G. Marchesini, P. Angulo, P. Loria, NAFLD a precursor of the metabolic syndrome. Dig. Liver Dis. 47, 181–190 (2015)
8. A. Lonardo, C. Carani, N. Carulli, P. Loria, ‘Endocrine NAFLD’a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis. J. Hepatol. 44, 1196–1207 (2006)
9. Y. Yilmaz, Z.M. Younossi, Obesity-associated nonalcoholic fatty liver disease. Clin. Liver Dis. 18, 19–31 (2014)
10. M. Machado, P. Marques-Vidal, H. Cortez-Pinto, Hepatic histology in obese patients undergoing bariatric surgery. J. Hepatol. 45, 600–606 (2006)
11. P. Loria, L. Carulli, M. Bertolotti, A. Lonardo, Endocrine and liver interaction: the role of endocrine pathways in NASH. Nat. Rev. Gastroenterol. Hepatol. 6, 236–247 (2009)
12. G. Targher, G. Zoppini, E. Bonora, P. Moghetti, Hemostatic and fibrinolytic abnormalities in polycystic ovary syndrome. Semin. Thromb. Hemost. 40, 600–618 (2014)
13. C.E. Kelley, A.J. Brown, A.M. Diehl, T.L. Setji, Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J. Gastroenterol. 20, 14172–14184 (2014)
14. G. Daskalopoulos, A. Karkanaki, A. Piouka, N. Prapas, D. Panidis, P. Gkeleris, V.G. Athyros, Excess metabolic and cardiovascular risk is not manifested in all phenotypes of polycystic ovary syndrome: implications for diagnosis and treatment. Curr. Vasc. Pharmacol 14(1), 109–119 (2015)
15. F. Nascimbeni, S. Ballestri, L. Di Tommaso, M. Piccoli, A. Lonardo, Inflammatory hepatocellular adenomatosis, metabolic syndrome, polycystic ovary syndrome and non-alcoholic steatohepatitis: chance tetrad or association by necessity? Dig. Liver Dis. 46, 288–289 (2014)
16. J.D. Yang, M.F. Abdelmalek, H. Pang, C.D. Guy, A.D. Smith, A.M. Diehl, A. Suzuki, Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis. Hepatology 59, 1406–1414 (2014)
17. H. Tomiyama, A. Yamashina, T. Arai, K. Hirose, Y. Koji, T. Chikamori, S. Hori, Y. Yamamoto, N. Doba, S. Hinohara, Influences of age and gender on results of noninvasive brachial-ankle pulse wave velocity measurement: a survey of 12517 subjects. Atherosclerosis 166, 303–309 (2003)
18. D. Roulot, J.L. Costes, J.F. Buyck, U. Warzocha, N. Gambier, S. Czernichow, H. Le Clesiau, M. Beaugrand, Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years. Gut 60, 977–984 (2011)
19. C. Bunchorntavakul, R. Bahirwani, D. Drazek, M.C. Soulen, E.S. Siegelman, E.E. Furth, K. Olthoff, A. Shaked, K.R. Reddy, Clinical features and natural history of hepatocellular adenomas: the impact of obesity. Aliment Pharmacol. Ther. 34, 664–674 (2011)
20. P. Loria, L.E. Adinolfi, S. Bellentani, E. Bugianesi, A. Grieco, S. Fargion, A. Gasbarrini, C. Loguercio, A. Lonardo, G. Marchesini, F. Marra, M. Persico, D. Prati, Baroni GS; NAFLD Expert Committee of the Associazione Italiana per lo Studio del Fegato. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee. Dig. Liver Dis. 42, 272–282 (2010)
21. R.S. Legro, S.A. Arslanian, D.A. Ehrmann, K.M. Hoeger, M.H. Murad, R. Pasquali, C.K. Welt, Endocrine Society, Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 98, 4565–4592 (2013)
22. T.L. Setji, N.D. Holland, L.L. Sanders, K.C. Pereira, A.M. Diehl, A.J. Brown, Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 91, 1741–1747 (2006)
23. M. Gambarin-Gelwan, S.V. Kinkhabwala, T.D. Schiano, C. Bodian, H.C. Yeh, W. Futterweit, Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Clin. Gastroenterol. Hepatol. 5, 496–501 (2007)
24. C. Cerda, R.M. Pérez-Ayuso, A. Riquelme, A. Soza, P. Villaseca, T. Sir-Petermann, M. Espinoza, M. Pizarro, N. Solis, J.F. Miquel, M. Arrese, Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. J. Hepatol. 47, 412–417 (2007)
25. A.J. Cussons, G.F. Watts, T.A. Mori, B.G. Stuckey, Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy. J. Clin. Endocrinol. Metab. 94, 3842–3848 (2009)
26. E. Vassilatou, S. Lafoyianni, A. Vryonidou, D. Ioannidis, L. Kosma, K. Katsoulis, E. Papavassiliou, I. Tzavara, Increased androgen bioavailability is associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome. Hum. Reprod. 25, 212–220 (2010)
27. M.M. Brzozowska, G. Ostapowicz, M.D. Weltman, An association between non-alcoholic fatty liver disease and polycystic ovarian syndrome. J. Gastroenterol. Hepatol. 24, 243–247 (2009)
28. Y. Gutierrez-Grobe, G. Ponciano-Rodríguez, M.H. Ramos, M. Uribe, N. Méndez-Sánchez, Prevalence of nonalcoholic fatty liver disease in premenopausal, postmenopausal and polycystic ovary syndrome women: the role of estrogens. Ann. Hepatol. 9, 402–409 (2010)
29. A. Markou, I.I. Androulakis, C. Mourmouris, A. Tsikkini, C. Samara, S. Sougioultzis, G. Piaditis, G. Kaltsas, Hepatic steatosis in young lean insulin resistant women with polycystic ovary syndrome. Fertil. Steril. 93, 1220–1226 (2010)
30. N. Hossain, M. Stepanova, A. Afendy, F. Nader, Y. Younossi, N. Rafiq, Z. Goodman, Z.M. Younossi, Non-alcoholic steatohepatitis (NASH) in patients with polycystic ovarian syndrome (PCOS). Scand. J. Gastroenterol. 46, 479–484 (2011)
31. R.C. Ma, K.H. Liu, P.M. Lam, L.P. Cheung, W.H. Tam, G.T. Ko, M.H. Chan, C.S. Ho, C.W. Lam, W.C. Chu, P.C. Tong, W.Y. So, J.C. Chan, C.C. Chow, Sonographic measurement of mesenteric fat predicts presence of fatty liver among subjects with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 96, 799–807 (2011)
32. M.F. Gangale, L. Miele, A. Lanzone, F. Sagnella, D. Martinez, A. Tropea, F. Moro, A. Morciano, A. Ciardulli, C. Palla, M. Pompili, C. Cefalo, A. Grieco, R. Apa, Long-term metformin treatment is able to reduce the prevalence of metabolic syndrome and its hepatic involvement in young hyper insulinaemic overweight patients with polycystic ovarian syndrome. Clin. Endocrinol. (Oxf). 75, 520–527 (2011)
33. H. Jones, V.S. Sprung, C.J. Pugh, C. Daousi, A. Irwin, N. Aziz, V.L. Adams, E.L. Thomas, J.D. Bell, G.J. Kemp, D.J. Cuthbertson, Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. J. Clin. Endocrinol. Metab. 97, 3709–3716 (2012)
34. L.F. Zueff, W.P. Martins, C.S. Vieira, R.A. Ferriani, Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome. Ultrasound Obstet. Gynecol. 39, 341–347 (2012)
35. S. Borruel, E. Fernández-Durán, M. Alpañés, D. Martí, F. Alvarez-Blasco, M. Luque-Ramírez, H.F. Escobar-Morreale, Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS). J. Clin. Endocrinol. Metab. 98, 1254–1263 (2013)
36. R. Karoli, J. Fatima, A. Chandra, U. Gupta, F.U. Islam, G. Singh, Prevalence of hepatic steatosis in women with polycystic ovary syndrome. J. Hum. Reprod. Sci. 6, 9–14 (2013)
37. Z. Qu, Y. Zhu, J. Jiang, Y. Shi, Z. Chen, The clinical characteristics and etiological study of nonalcoholic fatty liver disease in Chinese women with PCOS. Iran J. Reprod. Med. 11, 725–732 (2013)
38. A.J. Dawson, T. Sathyapalan, J.A. Smithson, R.V. Vince, A.M. Coady, R. Ajjan, E.S. Kilpatrick, S.L. Atkin, A comparison of cardiovascular risk indices in patients with polycystic ovary syndrome with and without coexisting nonalcoholic fatty liver disease. Clin. Endocrinol. (Oxf). 80, 843–849 (2014)
39. C. Toso, L. Rubbia-Brandt, F. Negro, P. Morel, G. Mentha, Hepatocellular adenoma and polycystic ovary syndrome. Liver Int. 23, 35–37 (2003)
40. T.C. Liu, N. Vachharajani, W.C. Chapman, E.M. Brunt, Noncirrhotic hepatocellular carcinoma: derivation from hepatocellular adenoma? Clinico-pathologic analysis. Mod. Pathol. 27, 420–432 (2014)
41. H.F. Escobar-Morreale, M. Luque-Ramírez, F. González, Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and meta-analysis. Fertil. Steril. 95, 1048–1058 (2011)
42. F. González, Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 77, 300–305 (2012)
43. S. Palomba, A. Falbo, G. Chiossi, F. Orio, A. Tolino, A. Colao, G.B. La Sala, F. Zullo, Low-grade chronic inflammation in pregnant women with polycystic ovary syndrome: a prospective controlled clinical study. J. Clin. Endocrinol. Metab. 99, 2942–2951 (2014)
44. M. Ramezani-Binabaj, M. Motalebi, H. Karimi-sari, M.S. Rezaee-Zavareh, S.M. Alavian, Are women with polycystic ovarian syndrome at a high risk of nonalcoholic fatty liver disease? A meta-analysis. Hepat. Mon. 14, e23235 (2014)
45. R. Azziz, D.A. Dumesic, M.O. Goodarzi, Polycystic ovary syndrome: an ancient disorder? Fertil. Steril. 95, 1544–1548 (2011)
46. M.A. Brower, M.R. Jones, J.I. Rotter, R.M. Krauss, R.S. Legro, R. Azziz, M.O. Goodarzi, Further investigation in Europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals. J. Clin. Endocrinol. Metab. 100, E182–E186 (2015)
47. G. Targher, C.D. Byrne, Clinical review: nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J. Clin. Endocrinol. Metab. 98, 483–495 (2013)
48. A. Lonardo, S. Lombardini, F. Scaglioni, L. Carulli, M. Ricchi, D. Ganazzi, L.E. Adinolfi, G. Ruggiero, N. Carulli, P. Loria, Hepatic steatosis and insulin resistance: does etiology make a difference? J. Hepatol. 44, 190–196 (2006)
49. A.L. Birkenfeld, G.I. Shulman, Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology 59, 713–723 (2014)
50. K. Kobaly, P. Vellanki, R.K. Sisk, L. Armstrong, J.Y. Lee, J. Lee, M.G. Hayes, M. Urbanek, R.S. Legro, A. Dunaif, Parent-of-origin effects on glucose homeostasis in polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 99, 2961–2966 (2014)
51. E. Deligeoroglou, N. Vrachnis, N. Athanasopoulos, Z. Iliodromiti, S. Sifakis, S. Iliodromiti, C. Siristatidis, G. Creatsas, Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol. Endocrinol. 28, 974–978 (2012)
52. M.J. Armstrong, L.A. Adams, A. Canbay, W.K. Syn, Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 59, 1174–1197 (2014)
53. K. Kantartzis, A. Peter, F. Machicao, J. Machann, S. Wagner, I. Königsrainer, A. Königsrainer, F. Schick, A. Fritsche, H.U. Häring, N. Stefan, Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 58, 2616–2623 (2009)
54. A. Amaro, E. Fabbrini, M. Kars, P. Yue, K. Schechtman, G. Schonfeld, S. Klein, Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia. Gastroenterology 139, 149–153 (2010)
55. R.J. Perry, V.T. Samuel, K.F. Petersen, G.I. Shulman, The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 510, 84–91 (2014)
56. F. Tosi, R. Dorizzi, R. Castello, C. Maffeis, G. Spiazzi, G. Zoppini, M. Muggeo, P. Moghetti, Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome. Eur. J. Endocrinol. 161, 737–745 (2009)
57. F. Tosi, D. Di Sarra, J.M. Kaufman, C. Bonin, R. Moretta, E. Bonora, E. Zanolin, P. Moghetti, Total body fat and central fat mass independently predict insulin resistance but not hyperandrogenemia in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 100, 661–669 (2015)
58. J.J. Kim, Y.M. Choi, Dyslipidemia in women with polycystic ovary syndrome. Obstet. Gynecol. Sci. 56, 137–142 (2013)
59. R.L. Rosenfield, Clinical review: adolescent anovulation: maturational mechanisms and implications. J. Clin. Endocrinol. Metab. 98, 3572–3583 (2013)
60. F. González, C.L. Sia, D.M. Bearson, H.E. Blair, Hyperandrogenism induces a proinflammatory TNFα response to glucose ingestion in a receptor-dependent fashion. J. Clin. Endocrinol. Metab. 99, E848–E854 (2014)
61. M.W. O’Reilly, A.E. Taylor, N.J. Crabtree, B.A. Hughes, F. Capper, R.K. Crowley, P.M. Stewart, J.W. Tomlinson, W. Arlt, Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione. J. Clin. Endocrinol. Metab. 99, 1027–1036 (2014)
62. M. Lazo, I. Zeb, K. Nasir, R.P. Tracy, M.J. Budoff, P. Ouyang, D. Vaidya, Association between endogenous sex hormones and liver fat in a multi-ethnic study of atherosclerosis. Clin. Gastroenterol. Hepatol. (2015). doi:10.1016/j.cgh.2014.12.033
63. G. Targher, L. Bertolini, L. Zenari, Hypoadiponectinemia is closely associated with nonalcoholic hepatic steatosis in obese subjects. Diabetes Care 27, 2085–2086 (2004)
64. G. Targher, L. Bertolini, L. Scala, F. Poli, L. Zenari, G. Falezza, Decreased plasma adiponectin concentrations are closely associated with nonalcoholic hepatic steatosis in obese individuals. Clin. Endocrinol. (Oxf). 61, 700–703 (2004)
65. G. Targher, L. Bertolini, S. Rodella, G. Zoppini, L. Scala, L. Zenari, G. Falezza, Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease. Clin. Endocrinol. (Oxf). 64, 679–683 (2006)
66. S. Francque, A. Verrijken, S. Caron, J. Prawitt, R. Paumelle, B. Derudas, P. Lefebvre, M.R. Taskinen, W. Van Hul, I. Mertens, G. Hubens, E. Van Marck, P. Michielsen, L. Van Gaal, B. Staels, PPARα gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis. J. Hepatol. (2015). doi:10.1016/j.jhep.2015.02.019
67. S. Cankaya, B. Demir, S.E. Aksakal, B. Dilbaz, C. Demirtas, U. Goktolga, Insulin resistance and its relationship with high molecular weight adiponectin in adolescents with polycystic ovary syndrome and a maternal history of polycystic ovary syndrome. Fertil. Steril. 102, 826–830 (2014)
68. T.P. Ciaraldi, V. Aroda, S.R. Mudaliar, R.R. Henry, Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary syndrome: effects of pioglitazone and metformin treatment. Metabolism 62, 1587–1596 (2013)
69. C.J. Weston, E.L. Shepherd, L.C. Claridge, P. Rantakari, S.M. Curbishley, J.W. Tomlinson, S.G. Hubscher, G.M. Reynolds, K. Aalto, Q.M. Anstee, S. Jalkanen, M. Salmi, D.J. Smith, C.P. Day, D.H. Adams, Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis. J. Clin. Invest. 125, 501–520 (2015)
70. K.M. Seow, C.C. Juan, P.H. Wang, L.T. Ho, J.L. Hwang, Expression levels of vascular cell adhesion molecule-1 in young and nonobese women with polycystic ovary syndrome. Gynecol. Obstet. Invest. 73, 236–241 (2012)
71. A. Rohatgi, A. Khera, J.D. Berry, E.G. Givens, C.R. Ayers, K.E. Wedin, I.J. Neeland, I.S. Yuhanna, D.R. Rader, J.A. de Lemos, P.W. Shaul, HDL cholesterol efflux capacity and incident cardiovascular events. N. Engl. J. Med. 371, 2383–2393 (2014)
72. A. Roe, J. Hillman, S. Butts, M. Smith, D. Rader, M. Playford, N.N. Mehta, A. Dokras, Decreased cholesterol efflux capacity and atherogenic lipid profile in young women with PCOS. J. Clin. Endocrinol. Metab. 99, E841–E847 (2014)
73. S. Ballestri, A. Lonardo, S. Bonapace, C.D. Byrne, P. Loria, G. Targher, Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J. Gastroenterol. 20, 1724–1745 (2014)
74. A. Lonardo, S. Lombardini, F. Scaglioni, S. Ballestri, A.M. Verrone, M. Bertolotti, L. Carulli, D. Ganazzi, N. Carulli, P. Loria, Fatty liver, carotid disease and gallstones: a study of age-related associations. World J. Gastroenterol. 12, 5826–5833 (2006)
75. A.L. Fracanzani, L. Valenti, M. Russello, L. Miele, C. Bertelli, A. Bellia, C. Masetti, C. Cefalo, A. Grieco, G. Marchesini, S. Fargion, Gallstone disease is associated with more severe liver damage in patients with non-alcoholic fatty liver disease. PLoS One 7, e41183 (2012)
76. A.R. Moschen, S. Kaser, H. Tilg, Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol. Metab. 24, 537–545 (2013)
77. C.E. Ruhl, J.E. Everhart, Relationship of non-alcoholic fatty liver disease with cholecystectomy in the US population. Am. J. Gastroenterol. 108, 952–958 (2013)
78. M.V. Machado, H. Cortez-Pinto, Gut microbiota and nonalcoholic fatty liver disease. Ann. Hepatol. 11, 440–449 (2012)
79. K. Tremellen, K. Pearce, Dysbiosis of Gut Microbiota (DOGMA): a novel theory for the development of polycystic ovarian syndrome. Med. Hypotheses 79, 104–112 (2012)
80. A.B. Sopher, G. Grigoriev, D. Laura, T. Cameo, J.P. Lerner, R.J. Chang, D.J. McMahon, S.E. Oberfield, Anti-Mullerian hormone may be a useful adjunct in the diagnosis of polycystic ovary syndrome in nonobese adolescents. J. Pediatr. Endocrinol. Metab. 27, 1175–1179 (2014)
81. A. Köninger, L. Koch, P. Edimiris, A. Enekwe, J. Nagarajah, S. Kasimir-Bauer, R. Kimmig, T. Strowitzki, B. Schmidt, Anti-Mullerian hormone: an indicator for the severity of polycystic ovarian syndrome. Arch. Gynecol. Obstet. 290, 1023–1030 (2014)
82. S. Ballestri, A. Lonardo, D. Romagnoli, L. Carulli, L. Losi, C.P. Day, P. Loria, Ultrasonographic fatty liver indicator, a novel score which rules out NASH and is correlated with metabolic parameters in NAFLD. Liver Int. 32, 1242–1252 (2012)
83. L. Castera, V. Vilgrain, P. Angulo, Noninvasive evaluation of NAFLD. Nat. Rev. Gastroenterol. Hepatol. 10, 666–675 (2013)
84. S. Ballestri, D. Romagnoli, F. Nascimbeni, G. Francica, A. Lonardo, Role of ultrasound in the diagnosis and treatment of NAFLD and its complications. Expert Rev. Gastroenterol. Hepatol. 19, 1–25 (2015)