Presentation and Outcomes of Pregnancy in Patients With Autoimmune Hepatitis

Autoimmune hepatitis (AIH) frequently affects women of childbearing age in whom the desire to have a family raises the question regarding the potential risks for the fetus and the mother. The information on AIH in pregnant patients is scarce.1Czaja A.J. Autoimmune hepatitis in special patient populations.Best Pract Res Clin Gastroenterol. 2011; 36: 391-393Google Scholar The aims of this study were (1) to identify the risk factors associated with flares in pregnant patients diagnosed with AIH, (2) to determine the course of AIH in patients with pregnancy-related flares, and (3) to describe the outcome of AIH diagnosed in the postpartum period. This was a retrospective, multicenter, cohort study. All patients with a previous diagnosis of AIH presenting at least 1 pregnancy during follow-up and patients diagnosed with AIH in the postpartum period were included. A flare was defined as an increase in transaminase levels above the upper normal limit leading to a change in immunosuppressive treatment. Statistical analysis was performed by using Stata version (Stata Corp, College Station, TX). Forty-six pregnancies in 36 patients diagnosed with AIH were analyzed. Ten pregnancies (21.7%) resulted in an AIH flare (median, 2.6 months [1–3.4] after delivery). None of these flares were symptomatic or required hospitalization. The characteristics of the patients are shown in Table 1. Patients presenting a postpartum flare had been in remission for a shorter period of time, and the follow-up until pregnancy was shorter. In 17 patients (37%) immunosuppression was modified at the time of pregnancy awareness, but there were no differences between patients with and without flares. Seven patients (15.2%) developed complications during pregnancy (4 gestational diabetes, 2 miscarriages, and 1 gestational hypertension), with no differences between groups.Table 1Baseline Characteristics of Patients Previously Diagnosed With Autoimmune Hepatitis Becoming Pregnant During Follow-upVariablesOverall (n = 36)Flare after delivery (n = 10)No flare after delivery (n = 26)P valueAt diagnosis Age (y)26 (20–32)25 (18–33)26 (20–33).60 Autoimmune comorbidity (%)aOther autoimmune diseases included type 1 diabetes mellitus (n = 3), erythematosus systemic lupus (n = 2), multiple sclerosis (n = 1), Sjögren syndrome (n = 4), and antiphospholipid syndrome (n = 2).12 (33.3)2 (20)10 (38.5).87 AST at diagnosis (IU/L)167 (102–766)407 (144–1196)125 (88–440).15 ALT at diagnosis (IU/L)196 (109–1385)513 (196–1761)151 (94–589).09 Bilirubin (mg/dL)0.9 (0.7–5)1.7 (0.8–6.8)0.9 (0.5–2.6).18 International normalized ratio1.1 (1–1.2)1.1 (1–1.2)1.1 (1–1.3).84 Immunoglobulin G (g/dL)20.95 (16.5–29.8)24.9 (18.5–30)18.5 (16.2–29.4).20 ANA (titers)1:300 (1:0–1:640)1:300 (1:20–1:640)1:240 (1:0–1:320).51 ASMA (titers)1:40 (1:0-1:40)1:0 (1:0–1:40)1:40 (1:0–1:40).70 Simplified Score ≥6 (n, %)21 (58.3)9 (90)12 (46.2).09 Cirrhosis (n, %)7 (19.4)1 (10)6 (23.1).36 Initial treatment (n, %)Prednisone14 (38.9)5 (50)9 (34.6).40Azathioprine3 (8.3)0 (0)3 (11.5).55Prednisone + azathioprine19 (52.8)5 (50)14 (53.8).84At pregnancybAt pregnancy: 6 flares occurred in first pregnancy, 3 in second pregnancy, and 1 in third pregnancy.(n = 46)(n = 10)(n = 36) Age (y)33 (29–34)32 (29–34)33 (29–34).63 Follow-up until pregnancy (mo)81 (32–173)26 (11–144)69 (20–168).14 Remission until pregnancy (mo)20 (0–45)5 (0–20)25 (1–90).05 AST (U/L)27 (18–38)28 (23–35)24 (18–40).65 ALT (U/L)28 (19–43)28 (17–68)28 (19–43).73 Immunoglobulin G (g/L)12.5 (10.3–14.2)12.5 (11.3–17.4)12.1 (10.1–14.1).46 Complications during pregnancy (n, %)7 (15.2)2 (20)5 (13.8).78 Immunosuppression changes (n, %)cModifications in immunosuppressive treatment included withdrawal of all treatment (n = 11), azathioprine withdrawal or dose reduction (n = 4), and withdrawal of corticosteroids (n = 2).17 (37)3 (30)14 (39).52NOTE. Data expressed as median (interquartile range).ALT, alanine aminotransferase; ANA, antinuclear antibodies; ASMA, anti-smooth muscle antibodies; AST, aspartate aminotransferase; IgG, immunoglobulin G; INR, international normalized ratio.a Other autoimmune diseases included type 1 diabetes mellitus (n = 3), erythematosus systemic lupus (n = 2), multiple sclerosis (n = 1), Sjögren syndrome (n = 4), and antiphospholipid syndrome (n = 2).b At pregnancy: 6 flares occurred in first pregnancy, 3 in second pregnancy, and 1 in third pregnancy.c Modifications in immunosuppressive treatment included withdrawal of all treatment (n = 11), azathioprine withdrawal or dose reduction (n = 4), and withdrawal of corticosteroids (n = 2). Open table in a new tab NOTE. Data expressed as median (interquartile range). ALT, alanine aminotransferase; ANA, antinuclear antibodies; ASMA, anti-smooth muscle antibodies; AST, aspartate aminotransferase; IgG, immunoglobulin G; INR, international normalized ratio. Whereas at the time of diagnosis most patients received treatment with either a corticosteroid in monotherapy or combined with azathioprine, women who developed a flare more frequently required combined therapy to maintain remission (70% vs 23.1%, P = .01). Moreover, patients with flares were more prone to requiring second-line treatment because of lack of response to combined therapy (30% vs 0.04%, P = .04). Eight women diagnosed with AIH in the postpartum period (median of 1.54 months after delivery [1.05–2.69]) were included. The median aspartate aminotransferase values were 648 IU/L (48–1815), alanine aminotransferase 814 IU/L (146–2398), bilirubin 9.3 mg/dL (0.9–12.7), international normalized ratio 1.48 (1–1.7), and immunoglobulin G 18 g/L (14–20). All patients had a simplified AIH score of at least 6 points. Liver biopsy was compatible with the diagnosis of AIH in all patients. Three patients presented complications during pregnancy (1 gestational diabetes, 1 intrahepatic cholestasis, and 1 premature birth). At diagnosis, 5 patients received treatment with prednisone in monotherapy, and 3 received combined treatment. After a median follow-up of 50 months (21–79), immunosuppression was successfully withdrawn in 4 patients (50%). The remaining patients maintained in remission with prednisone in monotherapy. The rate of postpartum flares in patients previously diagnosed with AIH was slightly lower than that reported previously.2Terrabuio D.R.B. Abrantes-Lemos C.P. Carrilho F.J. et al.Follow-up of pregnant women with autoimmune hepatitis: the disease behavior along with maternal and fetal outcomes.J Clin Gastroenterol. 2009; 43: 350-356Crossref PubMed Scopus (76) Google Scholar, 3Westbrook R.H. Yeoman A.D. Kriese S. et al.Outcomes of pregnancy in women with autoimmune hepatitis.J Autoimmun. 2012; 38: J239-J244Crossref PubMed Scopus (115) Google Scholar In consonance with current literature, the presence of flares was not associated with an increase in the number of fetal and maternal complications.4Schramm C. Herkel J. Beuers U. et al.Pregnancy in autoimmune hepatitis: outcome and risk factors.Am J Gastroenterol. 2006; 101: 556Crossref PubMed Scopus (160) Google Scholar, 5Gronbaek L. Vilstrup H. Jepsen P. Pregnancy and birth outcomes in a Danish nationwide cohort of women with autoimmune hepatitis and matched population controls.Aliment Pharmacol Ther. 2018; 48: 655-663Crossref PubMed Scopus (22) Google Scholar However, patients with postpartum flares had a more aggressive form of the disease; they were more likely to need combined therapy or even second-line therapy to achieve remission, suggesting a more immunologically active disease. Similar to other series, AIH triggered by postpartum was found to be uncommon.6Efe C. Purnak T. Ozaslan E. Autoimmune hepatitis in the postpartum period.Clin Res Hepatol Gastroenterol. 2012; 36: 391-393Crossref PubMed Scopus (6) Google Scholar, 7Samuel D. Riordan S. Strasser S. et al.Severe autoimmune hepatitis first presenting in the early post partum period.Clin Gastroenterol Hepatol. 2004; 2: 622-624Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 8Izumi Y. Kaneko A. Oku K. et al.Development of liver dysfunction after delivery is possibly due to postpartum autoimmune hepatitis: a report of three cases.J Intern Med. 2002; 1: 361-367Crossref Scopus (22) Google Scholar Interestingly, most of these patients required none or minimal immunosuppression to control disease. Our study has several limitations. (1) The definition of flare lacked the need for immunoglobulin G elevation and relied on physician discretion for increasing immunosuppressive treatment, and (2) the rates of fetal or maternal complications could have been underestimated because gynecological information was not always available for review. In conclusion, postpartum AIH flares in patients diagnosed with AIH are frequent, particularly in patients with a shorter time of remission before conception. However, these patients do not present a significantly higher rate of fetal and maternal complications. The onset of AIH after delivery is uncommon and is associated with an excellent course. Our data indicate that pregnancy is safe in patients with AIH, but strict disease control is critical to prevent disease flares.