Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV

A. Karampatou, X. Han, L.A. Kondili, G. Taliani, A. Ciancio, F. Morisco, R.M. Critelli, E. Baraldi, V. Bernabucci, G. Troshina, M. Guarino, S. Tagliavini, F. D'Ambrosio, L. Bristot, L. Turco, S. Rosato, S. Vella, T. Trenti, I. Neri, A. La MarcaS. Manthena, A.S. Goldstein, S. Bruno, Y. Bao, Y.S. Gonzalez, E. Villa, A. Craxì, S. Petta, V. Calvaruso, M. Brunetto, B. Coco, L. Chessa, M.C. Pasetto, E. Bigliotti, F. Tamburrini, G. Montalto, M. Monti, E. Finati, M. Milella, F.P. Russo, M. Gemma, A. Gori, R. Bruno, S. Cima, C. Coppola, G. Simonetti, G. Brancaccio, M. Mondelli, S. Ludovisi, M. Persico

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130–2.794), premature birth (OR 1.34; 95% CI 1.060–1.690), gestational diabetes (OR 1.24; 95% CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks. © 2017 European Association for the Study of the Liver
Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalJournal of Hepatology
Volume68
Issue number1
DOIs
Publication statusPublished - 2018

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Birth Rate
Spontaneous Abortion
Odds Ratio
Infertility
Gestational Diabetes
Live Birth
Liver Diseases
Chronic Disease
Pregnancy Outcome
Pre-Eclampsia
Hormones
Reproductive History
Hospital Units
Stillbirth

Keywords

  • Anti-Müllerian hormone
  • Antiviral therapy
  • HBV
  • HCV
  • Sustained viral response
  • antivirus agent
  • boceprevir
  • estradiol
  • estrogen
  • Muellerian inhibiting factor
  • peginterferon
  • ribavirin
  • somatomedin C
  • telaprevir
  • adult
  • antiviral therapy
  • Article
  • cell aging
  • chronic liver disease
  • clinical trial
  • controlled study
  • estradiol blood level
  • estrogen blood level
  • female
  • female fertility
  • follow up
  • hepatitis C
  • human
  • live birth
  • major clinical study
  • ovary
  • preeclampsia
  • pregnancy diabetes mellitus
  • pregnancy outcome
  • prematurity
  • priority journal
  • prospective study
  • protein blood level
  • risk reduction
  • spontaneous abortion
  • stillbirth
  • sustained virologic response

Cite this

Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV. / Karampatou, A.; Han, X.; Kondili, L.A.; Taliani, G.; Ciancio, A.; Morisco, F.; Critelli, R.M.; Baraldi, E.; Bernabucci, V.; Troshina, G.; Guarino, M.; Tagliavini, S.; D'Ambrosio, F.; Bristot, L.; Turco, L.; Rosato, S.; Vella, S.; Trenti, T.; Neri, I.; La Marca, A.; Manthena, S.; Goldstein, A.S.; Bruno, S.; Bao, Y.; Gonzalez, Y.S.; Villa, E.; Craxì, A.; Petta, S.; Calvaruso, V.; Brunetto, M.; Coco, B.; Chessa, L.; Pasetto, M.C.; Bigliotti, E.; Tamburrini, F.; Montalto, G.; Monti, M.; Finati, E.; Milella, M.; Russo, F.P.; Gemma, M.; Gori, A.; Bruno, R.; Cima, S.; Coppola, C.; Simonetti, G.; Brancaccio, G.; Mondelli, M.; Ludovisi, S.; Persico, M.

In: Journal of Hepatology, Vol. 68, No. 1, 2018, p. 33-41.

Research output: Contribution to journalArticle

Karampatou, A, Han, X, Kondili, LA, Taliani, G, Ciancio, A, Morisco, F, Critelli, RM, Baraldi, E, Bernabucci, V, Troshina, G, Guarino, M, Tagliavini, S, D'Ambrosio, F, Bristot, L, Turco, L, Rosato, S, Vella, S, Trenti, T, Neri, I, La Marca, A, Manthena, S, Goldstein, AS, Bruno, S, Bao, Y, Gonzalez, YS, Villa, E, Craxì, A, Petta, S, Calvaruso, V, Brunetto, M, Coco, B, Chessa, L, Pasetto, MC, Bigliotti, E, Tamburrini, F, Montalto, G, Monti, M, Finati, E, Milella, M, Russo, FP, Gemma, M, Gori, A, Bruno, R, Cima, S, Coppola, C, Simonetti, G, Brancaccio, G, Mondelli, M, Ludovisi, S & Persico, M 2018, 'Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV', Journal of Hepatology, vol. 68, no. 1, pp. 33-41. https://doi.org/10.1016/j.jhep.2017.08.019
Karampatou, A. ; Han, X. ; Kondili, L.A. ; Taliani, G. ; Ciancio, A. ; Morisco, F. ; Critelli, R.M. ; Baraldi, E. ; Bernabucci, V. ; Troshina, G. ; Guarino, M. ; Tagliavini, S. ; D'Ambrosio, F. ; Bristot, L. ; Turco, L. ; Rosato, S. ; Vella, S. ; Trenti, T. ; Neri, I. ; La Marca, A. ; Manthena, S. ; Goldstein, A.S. ; Bruno, S. ; Bao, Y. ; Gonzalez, Y.S. ; Villa, E. ; Craxì, A. ; Petta, S. ; Calvaruso, V. ; Brunetto, M. ; Coco, B. ; Chessa, L. ; Pasetto, M.C. ; Bigliotti, E. ; Tamburrini, F. ; Montalto, G. ; Monti, M. ; Finati, E. ; Milella, M. ; Russo, F.P. ; Gemma, M. ; Gori, A. ; Bruno, R. ; Cima, S. ; Coppola, C. ; Simonetti, G. ; Brancaccio, G. ; Mondelli, M. ; Ludovisi, S. ; Persico, M. / Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV. In: Journal of Hepatology. 2018 ; Vol. 68, No. 1. pp. 33-41.
@article{2e90c9dfe22d4120aa4c07d1b130395c,
title = "Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV",
abstract = "Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-M{\"u}llerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95{\%} CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95{\%} CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0{\%} of women (44.6{\%} had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95{\%} CI 2.130–2.794), premature birth (OR 1.34; 95{\%} CI 1.060–1.690), gestational diabetes (OR 1.24; 95{\%} CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95{\%} CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95{\%} CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks. {\circledC} 2017 European Association for the Study of the Liver",
keywords = "Anti-M{\"u}llerian hormone, Antiviral therapy, HBV, HCV, Sustained viral response, antivirus agent, boceprevir, estradiol, estrogen, Muellerian inhibiting factor, peginterferon, ribavirin, somatomedin C, telaprevir, adult, antiviral therapy, Article, cell aging, chronic liver disease, clinical trial, controlled study, estradiol blood level, estrogen blood level, female, female fertility, follow up, hepatitis C, human, live birth, major clinical study, ovary, preeclampsia, pregnancy diabetes mellitus, pregnancy outcome, prematurity, priority journal, prospective study, protein blood level, risk reduction, spontaneous abortion, stillbirth, sustained virologic response",
author = "A. Karampatou and X. Han and L.A. Kondili and G. Taliani and A. Ciancio and F. Morisco and R.M. Critelli and E. Baraldi and V. Bernabucci and G. Troshina and M. Guarino and S. Tagliavini and F. D'Ambrosio and L. Bristot and L. Turco and S. Rosato and S. Vella and T. Trenti and I. Neri and {La Marca}, A. and S. Manthena and A.S. Goldstein and S. Bruno and Y. Bao and Y.S. Gonzalez and E. Villa and A. Crax{\`i} and S. Petta and V. Calvaruso and M. Brunetto and B. Coco and L. Chessa and M.C. Pasetto and E. Bigliotti and F. Tamburrini and G. Montalto and M. Monti and E. Finati and M. Milella and F.P. Russo and M. Gemma and A. Gori and R. Bruno and S. Cima and C. Coppola and G. Simonetti and G. Brancaccio and M. Mondelli and S. Ludovisi and M. Persico",
note = "Export Date: 2 March 2018 CODEN: JOHEE Correspondence Address: Villa, E.; Department of Internal Medicine, Gastroenterology Unit, Universit{\`a} degli Studi di Modena & Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Via del Pozzo 71, Italy; email: erica.villa@unimore.it Chemicals/CAS: boceprevir, 394730-60-0; estradiol, 50-28-2; Muellerian inhibiting factor, 80497-65-0; ribavirin, 36791-04-5; somatomedin C, 67763-96-6; telaprevir, 402957-28-2 Funding details: PRUa2-2013-00002033 Funding text: This work was supported by Programma di Ricerca Regione-Universit{\`a} 2013 – Area 2 ‘Ricerca per il Governo Clinico’ (Regione Emilia Romagna), code PRUa2-2013-00002033 to EV and TT. The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. 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Okuda, M., Li, K., Beard, M.R., Showalter, L.A., Scholle, F., Lemon, S.M., Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein (2002) Gastroenterology, 122, pp. 366-375; Huang, Q.T., Huang, Q., Zhong, M., Wei, S.S., Luo, W., Li, F., Chronic hepatitis C virus infection is associated with increased risk of preterm birth: a meta-analysis of observational studies (2015) J Viral Hepatol, 22, pp. 1033-1042; Cacoub, P., Comarmond, C., Domont, F., Savey, L., Desbois, A.C., Saadoun, D., Extrahepatic manifestations of chronic hepatitis C virus infection (2016) Ther Adv Infect Dis, 3, pp. 3-14; Hofny, E.R., Ali, M.E., Taha, E.A., Nafeh, H.M., Sayed, D.S., Abdel-Azeem, H.G., Semen and hormonal parameters in men with chronic hepatitis C infection (2011) Fertil Steril, 95, pp. 2557-2559; Durazzo, M., Premoli, A., Di Bisceglie, C., Bertagna, A., Faga, E., Biroli, G., Alterations of seminal and hormonal parameters: an extrahepatic manifestation of HCV infection? (2006) World J Gastroenterol, 12, pp. 3073-3076",
year = "2018",
doi = "10.1016/j.jhep.2017.08.019",
language = "English",
volume = "68",
pages = "33--41",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier B.V.",
number = "1",

}

TY - JOUR

T1 - Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV

AU - Karampatou, A.

AU - Han, X.

AU - Kondili, L.A.

AU - Taliani, G.

AU - Ciancio, A.

AU - Morisco, F.

AU - Critelli, R.M.

AU - Baraldi, E.

AU - Bernabucci, V.

AU - Troshina, G.

AU - Guarino, M.

AU - Tagliavini, S.

AU - D'Ambrosio, F.

AU - Bristot, L.

AU - Turco, L.

AU - Rosato, S.

AU - Vella, S.

AU - Trenti, T.

AU - Neri, I.

AU - La Marca, A.

AU - Manthena, S.

AU - Goldstein, A.S.

AU - Bruno, S.

AU - Bao, Y.

AU - Gonzalez, Y.S.

AU - Villa, E.

AU - Craxì, A.

AU - Petta, S.

AU - Calvaruso, V.

AU - Brunetto, M.

AU - Coco, B.

AU - Chessa, L.

AU - Pasetto, M.C.

AU - Bigliotti, E.

AU - Tamburrini, F.

AU - Montalto, G.

AU - Monti, M.

AU - Finati, E.

AU - Milella, M.

AU - Russo, F.P.

AU - Gemma, M.

AU - Gori, A.

AU - Bruno, R.

AU - Cima, S.

AU - Coppola, C.

AU - Simonetti, G.

AU - Brancaccio, G.

AU - Mondelli, M.

AU - Ludovisi, S.

AU - Persico, M.

N1 - Export Date: 2 March 2018 CODEN: JOHEE Correspondence Address: Villa, E.; Department of Internal Medicine, Gastroenterology Unit, Università degli Studi di Modena & Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Via del Pozzo 71, Italy; email: erica.villa@unimore.it Chemicals/CAS: boceprevir, 394730-60-0; estradiol, 50-28-2; Muellerian inhibiting factor, 80497-65-0; ribavirin, 36791-04-5; somatomedin C, 67763-96-6; telaprevir, 402957-28-2 Funding details: PRUa2-2013-00002033 Funding text: This work was supported by Programma di Ricerca Regione-Università 2013 – Area 2 ‘Ricerca per il Governo Clinico’ (Regione Emilia Romagna), code PRUa2-2013-00002033 to EV and TT. The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. 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PY - 2018

Y1 - 2018

N2 - Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130–2.794), premature birth (OR 1.34; 95% CI 1.060–1.690), gestational diabetes (OR 1.24; 95% CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks. © 2017 European Association for the Study of the Liver

AB - Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130–2.794), premature birth (OR 1.34; 95% CI 1.060–1.690), gestational diabetes (OR 1.24; 95% CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks. © 2017 European Association for the Study of the Liver

KW - Anti-Müllerian hormone

KW - Antiviral therapy

KW - HBV

KW - HCV

KW - Sustained viral response

KW - antivirus agent

KW - boceprevir

KW - estradiol

KW - estrogen

KW - Muellerian inhibiting factor

KW - peginterferon

KW - ribavirin

KW - somatomedin C

KW - telaprevir

KW - adult

KW - antiviral therapy

KW - Article

KW - cell aging

KW - chronic liver disease

KW - clinical trial

KW - controlled study

KW - estradiol blood level

KW - estrogen blood level

KW - female

KW - female fertility

KW - follow up

KW - hepatitis C

KW - human

KW - live birth

KW - major clinical study

KW - ovary

KW - preeclampsia

KW - pregnancy diabetes mellitus

KW - pregnancy outcome

KW - prematurity

KW - priority journal

KW - prospective study

KW - protein blood level

KW - risk reduction

KW - spontaneous abortion

KW - stillbirth

KW - sustained virologic response

U2 - 10.1016/j.jhep.2017.08.019

DO - 10.1016/j.jhep.2017.08.019

M3 - Article

VL - 68

SP - 33

EP - 41

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 1

ER -