Sex-specific changes in triglyceride profiles in liver cirrhosis and hepatitis C virus infection

Abstract

Background: Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. METHODS: The study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student's t test were used as appropriate. P values were adjusted for multiple comparisons.

Results: HCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females.

Conclusions: The decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV.

Keywords: Direct acting antivirals; Fibrosis-4 score; Genotype; Liver cirrhosis; Polyunsaturated triglycerides.

Fig. 1

Serum TG species in relation to sex in patients with chronic HCV. (a) Total TGs in female and male patients (median level and range); (b) TG species with an identical number of carbon atoms were grouped together and compared between female and male patients (mean concentration ± standard deviation); (c) TG species with an identical number of double bonds were grouped together and compared between female and male patients (mean concentration ± standard deviation). * P < 0.05, ** P < 0.01

Fig. 2

Serum TG species in relation to body mass index (BMI) in female and male patients with chronic HCV. (a) Total TGs in female patients stratified for BMI; (b) Total TGs in male patients stratified for BMI; (c) Total TGs in female patients with and without liver steatosis; (d) Total TGs in male patients with and without liver steatosis; (e) Total TGs in female patients with and without diabetes; (f) Total TGs in male patients with and without diabetes. * P < 0.05

Fig. 3

TGs in relation to the FIB-4 score. (a) TGs with an identical number of carbon atoms in females with no (33 patients), inconclusive (INC, 24 patients) and definite fibrosis (Yes, 17 patients); (b) TGs with identical double bonds in females with no, inconclusive and definite fibrosis; (c) TGs with an identical number of carbon atoms in males with no (42 patients), inconclusive (28 patients) and definite fibrosis (33 patients); (d) TGs with identical double bonds in males with no, inconclusive and definite fibrosis. * P < 0.05 for comparison of No and Yes

Fig. 4

TGs in relation to cirrhosis diagnosed by ultrasound. (a) TGs with an identical number of carbon atoms and (b) TGs with identical double bonds in females without (No) and with (Yes) liver cirrhosis diagnosed by ultrasound; (c) TGs with an identical number of carbon atoms and (d) TGs with identical double bonds in males without (No) and with (Yes) liver cirrhosis diagnosed by ultrasound; (e) TGs with an identical number of carbon atoms in males and females without liver cirrhosis; (f) TGs with an identical number of carbon atoms in males and females with liver cirrhosis. * P < 0.05, ** P < 0.01, *** P < 0.001

Fig. 5

TGs stratified for viral genotypes in patients without liver cirrhosis. (a) TGs with an identical number of carbon atoms and (b) TGs with identical double bonds in females with different viral genotypes; (c) TGs with an identical number of carbon atoms and (d) TGs with identical double bonds in males with different viral genotypes. * P < 0.05, ** P < 0.01, & P < 0.05

Fig. 6

TG levels during the study. (a) TG levels during the study in females; (b) TG levels during the study in males

Fig. 7

TGs in male patients at the end of therapy. (a) TGs with an identical number of carbon atoms in males without (No) and with (Yes) ultrasound diagnosed liver cirrhosis; (b) TGs with identical double bonds in males without and with ultrasound diagnosed liver cirrhosis. * P < 0.05, ** P < 0.01, ^*** P < 0.001