Gender, fatty liver and GGT

Abstract

We would like to comment on the paper by Cammà et al., 1 who report on gender differences in hepatitis C virus (HCV)-related steatosis and on elevated gamma-glutamyl transferase (GGT) values as a predictor of poor response to antiviral treatment. 1 In our opinion, these data could be better understood taking into account that HCV genotype 1-related steatosis closely resembles non-alcoholic fatty liver disease (NAFLD). 2 Interestingly, in unselected consecutive subjects referred by General Practitioners for the evaluation of a "bright" liver at ultrasound scanning and enrolled in the POLISTENA study, NAFLD also displays a gender-dimorphic pattern. Indeed, in the majority of studies published in the 2000-2005 literature, 3 it occurs more frequently in the male gender. 4 It is amazing that our results, which were collected in a series recruited in the GPs offices in Modena, 4 closely mirror those by Marchesini et al. in Bologna and Turin,5 in the context of metabolic and liver Units (Table 1). These data indicate that male patients with NAFLD are approximately 10 years younger than women with this condition. Women, though, tend to have a higher prevalence of metabolic derangements evaluated according to Adult Treatment Panel III.It is tempting to speculate that the circulating levels of estrogens within a physiological range might be responsible for a "protective" effect on the development of steatosis (due to both NAFLD and, presumably, HCV genotype 1). This would imply that women in the fertile age are relatively spared from the development of steatosis and that this protection vanes after menopause similar to what happens for cardiovascular disease. These findings are also supported by the association of NAFLD with the use of the anti-estrogen tamoxifen, 6 by the better profile of liver function enzymes in post-menopausal women taking hormone replacement therapy, 7 and finally by the finding that estradiol improves insulin sensitivity, 8 possibly preventing or reducing fat accumulation. In our opinion, gender differences in steatosis might also mirror derangements of other endocrine hormones, notably insulin, growth and thyroid hormones and cytokines, particularly adiponectin and leptin in NAFLD patients. 3 As far as GGT is concerned, this enzyme might be a simple and reliable marker of insulin resistance both in obesity 9 and in patients with NAFLD or HCV-related steatosis. 10 It is well known that both alanine aminotransferase and, more closely, GGT predict the onset of type 2 diabetes in the general population. 10 These observations fit with the finding that insulin resistance impairs the response to antiviral treatment, 1 and lead us to conclude that elevated GGT, insulin resistance, and impaired response to antiviral treatment form an ominous triangle in the context of chronic HCV infection.In conclusion, advances in the pathogenesis of NAFLD made over the past few years might give new clues to the understanding and, possibly, the treatment of HCV-associated steatosis. 2

Gender medicine: a task for the third millennium

“…A cross-sectional multicenter study from Spain found a prevalence of fatty liver in 25.8% of men and in 20.3% in females [ 80 ]. Interestingly, in the POLISTENA Italian study which enrolled unselected consecutive subjects referred by GPs for evaluation of a ' bright liver ' at ultrasound [ 81 ] the mean age of males with fatty liver was 43.3 ± 1.2 years versus 56.5 ± 1.1 in women. Carulli et al [ 81 ] speculated that the circulating levels of estrogens might be responsible for a protective effect on the development of hepatic steatosis.…”

“…Interestingly, in the POLISTENA Italian study which enrolled unselected consecutive subjects referred by GPs for evaluation of a ' bright liver ' at ultrasound [ 81 ] the mean age of males with fatty liver was 43.3 ± 1.2 years versus 56.5 ± 1.1 in women. Carulli et al [ 81 ] speculated that the circulating levels of estrogens might be responsible for a protective effect on the development of hepatic steatosis. These figures contrast with a recent paper in which the prevalence of NAFLD was explored in 1170 community-based adolescents in the Western Australian Pregnancy cohort [ 82 ].…”

Clinical epidemiology of prevalence and cardiovascular risk factors of nonalcoholic fatty liver disease among the elderly agricultural and fishing population in Taiwan

“…The gender disparity in liver cancer and inflammation may thus be because of oestrogen-dependent differences in IL-6 production [17]. Previous study also has demonstrated that NAFLD has a more even distribution between male and female and the possible reason was female hormones protect against NAFLD has been postulated and supported by evidence that NAFLD is twice as common in postmenopausal women as in premenopausal women [19,20]. However, it was interesting that that elderly female gender represented significant risk factors related to the likelihood of a NAFLD.…”

Association between Serum γ-Glutamyltransferase and Chronic Kidney Disease among US Adults

“…Trends in the OR of CKD across increasing serum GGT category were determined modeling GGT categories as an ordinal variable. As GGT levels are related to gender [15] , alcohol intake [16] and BMI, [17] , subgroup analyses taking these factors into consideration were performed. Also, we performed additional analyses after excluding subjects with self-reported cardiovascular disease and GGT levels indicative of cholestasis ( 1 80 U/l) to know whether the observed findings remained unchanged.…”