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A. Djibre and N. Assy Recurrent post partum autoimmune hepatitis
A. Djibre and N. Assy, 11 June 2013


We report here the case of a female patient aged 30 with recurrent post partum acute autoimmune hepatitis and auto immune thyroiditis.

To our knowledge this is the first case reported of subsequent de novo recurrent post partum autoimmune hepatitis (AIH) and thyroiditis.

Post partum is known for its recrudescence in autoimmune manifestations, whether flares of previous disease or de novo autoimmune disease [1].

Autoimmune thyroiditis is frequently encountered in the first 3 months post partum (up to 5% of cases) [3], and rheumatoid arthritis aggravation at post partum period is well known [4].

Post partum liver function test elevation has been studied and shown to be related to anti cytochrome 2D6 antibody positivity, raising suspicion of an autoimmune process specifically directed against the liver [5].

A series of AIH female patients were observed during pregnancy with a high risk of flare post partum (31-52%) [1], [6, [7], and a few cases were reported of de novo AIH, 1- to 5 months post-partum.

Case history

Our patient, a young woman aged 30, was healthy until her first pregnancy and delivery at age 23 (12/2005) that was normal, but followed by typical autoimmune thyroiditis with a phase of thyrotoxicosis then hypothyroidism with eltyroxin supplementation.

The next pregnancy and delivery at age 25 (07/2007) were also normal , but at 1 month post partum the patient presented with nausea and dark urine. Blood tests revealed acute cytolytic hepatitis with AST 2139 U/l ALT 2560 U/l Alkaline phosphatases (Alk PH) 232 U/l, GGT 135 U/l, total bilirubin (tot bil) 7.97 mg/dl, direct bilirubin (dir bil) 5.8 mg/dl, INR 1.5, ferritin 1350 ng/ml, TSH 0.04 mUI/l , FT4 24.9 pmol/ml, albumin (alb) 3.7 g/dl, serum creatinin and electrolytes.

She was hospitalized. In hospital the patient was icteric, blood tests showed normal serum glucose and negative viral serologies for HAV, HBV, HCV, EBV, CMV.  An abdominal US was performed and showed a mild splenomegaly 13 cm with a normal liver.

The patient improved spontaneously and was discharged home after a few days, liver enzymes improve gradually. This survey is interrupted for about a year.

In 12/2008 at age 27, the patient is again pregnant, and being closely monitored for liver manifestations. At this point there is a mild elevation of ALT (81) and AST (43), with normal GGT and Alk P, alb, tot bil, INR, CBC. There was no evidence of hypergammaglobulinemia. Ceruloplasmin and alpha 1 antitrypsin levels are normal. The patient still has hyperthyroidism (TSH<0.01). Serology is negative for anti-SSA/ SSB /RNP/Smooth-muscle/, ANCA/mitochondrial/ASLO antibodies. A new abdominal US was performed that was normal.

The pregnancy is otherwise normal and the patient has a normal delivery in 08/2009.

One month after delivery blood tests revealed an elevation of liver enzyme up to AST 389, ALT 685 Alk P 112, GGT 74, alb 3.6, tot bil 2.2, dir bil 1.2. CBC and INR are normal. The liver enzyme elevation resolves after a month. The patient had not been symptomatic. The eltyroxin treatment was stopped at that time. The survey of this patient was then interrupted for 2 years.

In 03/2010 her general practitioner performed control liver tests that were normal.

In 01/2012 the patient is pregnant again. Liver function tests are strictly normal. The pregnancy is normal with normal liver tests at 6 months, and the patient has a caesarian section due to umbilical cord prolapse, in 09/2012.

One month after delivery the patient presents with general weakness, icterus, and dark urine. Blood tests reveal a severe hepatitis with AST 2861, ALT 1511, Alk PH 275, GGT 18, tot bil 9.7, dir bil 5.3, alb 3.7, INR 1.56, low vitamin D 8.1 ng/ml, normal CBC, blood glucose, creatinin and electrolytes, antinuclear antibodies negative.

Again the improvement was spontaneous and rapid, with blood tests after 10 days showing AST 345, ALT 493, Alk P 140, GGT 119, although bilirubin increased to tot bil 21 and dir bil 16. Fibroscan was performed and showed a high score of 16.3 kPa that can reflect the active acute hepatitis.  CAP was normal 165 dB/m without evidence of fatty liver. There was no evidence of encephalopathy at any point.

After again taking a precise anamnesis it was established that the patient did not drink alcohol or receive medication, but occasionally took what is called Chios mastic gum extract, which according to the scientific literature could have properties against Helicobacter pylori [8].

However, no significant blood cell changes were observed when tested in the rabbit [9] and no hepatotoxicity has so far been reported in man.

The underlying mechanism seems to be the relationship between sex hormones and autoimmune system. Estrogen production and concentration influences the immune cell proliferation and activity: during pregnancy there is a transient increase in Th1 and the Th1/Th2 balance shifts back to Th1 after delivery, monocytes activity decreases after delivery, likewise there is a modulation of cytokine production as for Il-1, Il-12 and TNF alpha [10], [11].

Furthermore it  has been observed that patients with RA do not show the regular post partum immunomodulation pattern [4] and it is possible that specific individual immune dysfunction increases the risk of autoimmune manifestations especially in the already higher risk period of post partum.


The case we reported here showed three flares of post partum hepatitis, without evidence of viral, toxic, genetic, obstructive or metabolic cause. According to the international AIH group score the patient had a score of 12 = probable AIH.

Although we did not observe any positive serology for auto antibodies, and no biopsy was performed due to the quick amelioration of the patient, the diagnosis of autoimmune hepatitis seems the most probable due to the exclusive post partum pattern of the flares and the absence of other cause of hepatitis.

In term of therapy, there are two main questions:

1) How hazardous will be next pregnancy for this patient? How can we appreciate the risk of fulminant hepatitis, considering that no de novo AIH with fulminant hepatitis was reported until now, and that our patient always improved rapidly and spontaneously?

2) As a consequence should she be treated with corticosteroids in the post partum to try and decrease the risk or the intensity of the flare that will be expected?

We plan to redo a fibroscan after 6 months to check for inflammation resolution and presence of fibrosis, and a liver tests survey every 6 months after return to normal for the next two years, and once a year after that for as long as the patient is asymptomatic.




  1.  Schramm C, Herkel J, Beuers U, Kanzler S, Galle PR, Lohse AW. Pregnancy in autoimmune hepatitis: outcome and risk factors. Am J Gastroenterol. 2006 ;101:556-60. 
  2.  Samuel D, Riordan S, Strasser S, Kurtovic J, Singh-Grewel I, Koorey D. Severe autoimmune hepatitis first presenting in the early post partum period. Clin Gastroenterol Hepatol. 2004 ; 2:622-4.
  3.  Tomas-Desrousseaux P. Dysthyroidism in the post-partum period. Rev Fr Gynecol Obstet. 1989 ;84:928-31.
  4.  Häupl T, Řstensen M, Grützkau A, Radbruch A, Burmester GR, Villiger PM. Reactivation of rheumatoid arthritis after pregnancy: increased phagocyte and recurring lymphocyte gene activity. Arthritis Rheum. 2008;58:2981-92.
  5.  Izumi Y, Tanaka S, Hidaka Y, Shimaoka Y, Tatsumi KI, Takano T, Kaneko A, Oku K, Amino N. Relation between post-partum liver dysfunction and anti-cytochrome 2D6 antibodies. . Am J Reprod Immunol. 2003 ;50:355-62.
  6.  Terrabuio DR, Abrantes-Lemos CP, Carrilho FJ, Cançado EL. Follow-up of pregnant women with autoimmune hepatitis: the disease behavior along with maternal and fetal outcomes. J Clin Gastroenterol. 2009 ;43:350-6.
  7.  Buchel E, Van Steenbergen W, Nevens F, Fevery J. Improvement of autoimmune hepatitis during pregnancy followed by flare-up after delivery. Am J Gastroenterol. 2002 ;97:3160-5.
  8.  Sotirios Paraschos, Prokopios Magiatis, Sofia Mitakou, Kalliopi Petraki, Antonios Kalliaropoulos, Petros Maragkoudakis, Andreas Mentis, Dionyssios Sgouras, and Alexios-Leandros Skaltsounis. In vitro and in vivo activities of chios mastic gum extracts and constituents against Helicobacter pylori. Antimicrob Agents Chemother. 2007; 51: 551–559.
  9.  J. S. Al- Helali. Effect of mastic tree ( Pistacia lenticus) resins on some blood parameters in rabbits. Coll. of Vet. Med. / Unive.of Al-Qadisiya AL-Qadisiya Journal of Vet. Med.Sci. Vol./11 No./1 2012M.
  10.  González DA, Díaz BB, Rodríguez Pérez Mdel C, Hernández AG, Chico BN, de León AC. Sex hormones and autoimmunity. Immunol Lett. 2010 ;133:6-13.
  11.  Cutolo M, Capellino S, Sulli A, Serioli B, Secchi ME, Villaggio B, Straub RH Estrogens and autoimmune diseases.  Ann N Y Acad Sci. 2006;1089:538-47.

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