Autoimmune Hepatitis in Pregnancy

Author Information

Mehta V*, Prasad M**, Gupta AS***
(* Third Year Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)

Abstract

The common causes of derangement in liver enzymes during pregnancy include HELLP syndrome, acute fatty liver of pregnancy, cholestasis of pregnancy and viral hepatitis. Rarely, other causes may be present. A case of autoimmune hepatitis in pregnancy is presented here.

Introduction

Autoimmune hepatitis (AIH) is a condition characterised by destruction of liver parenchyma which eventually leads to cirrhosis. Abnormal presentation of HLA class 2 on surface of liver either due to genetic cause or due to infection leads to cell mediated immune response and subsequent autoimmune hepatitis. The disease is more common in women in the age group of 15-40 years of age. This disease is also called as lupoid hepatitis, when associated with ANA positivity. Common early symptoms are fatigue, muscle ache and sign of acute inflammation of liver leading to fever, abdominal pain and jaundice. Many a times incidental abnormality in liver function test is the only manifestation.

Case Report

A 26 year old primigravida with 35 weeks of gestation was referred to our tertiary care centre in view of breech presentation with IUGR and oligohydramnios. On admission, patient was well oriented, with normal pulse and blood pressure. Cardiovascular and respiratory systems were unremarkable. Abdominal examination showed live fetus of 32 weeks size in breech presentation. Cervical os was closed. There was no show or leak. BP monitoring was done and remained within normal limits. There was no proteinuria. Ultrasonography showed gestational age of 33 weeks with abdominal circumference (AC) lag of 2 weeks and amniotic fluid index of 6 cm. Investigations were sent. Bedside bleeding time, clotting time tests were within normal limits. Hemoglobin was 11.2 gm/ dl and white blood count was 9000 /cu mm. Platelet count was 1.8 lakh /cu mm. Bilirubin was not elevated. Prothrombin time was in normal range and INR was 1.1. Only abnormal reports were SGOT (234 IU/ml) and SGPT (290 IU/ml). Specialist gastroenterology opinion was taken. Viral markers for hepatitis, γ glutaryltransferase, complete coagulation profile, hepato-renal Doppler ultrasonography were advised along with blood glucose monitoring to prevent hypoglycemia. Viral markers for hepatitis A, B, C and E were negative. γ glutaryltransferase was within normal limits and all coagulation parameters were in the normal range. Ultrasonography showed normal liver echotexture and no focal lesions or ascites. Patient did not develop episodes of hypoglycemia. SGOT /SGPT serial values are shown in the table 1.
Provisional diagnosis of autoimmune hepatitis was considered. However, patient went in to spontaneous labour and emergency LSCS was done for breech with IUGR under spinal anesthesia. A male child of 1.36 kg was delivered with an Apgar score of 9/10. LSCS was uneventful.  Baby was transferred to NICU and was discharged on day 10 of life.  Patient had unremarkable post-operative course. Hepatotoxic drugs were avoided in the postoperative period.  Liver function tests continued to be monitored and showed stable SGOT/ SGPT levels (as shown in the table). Autoimmune profile was sent, and serum IgG, IgA and IgM levels were sent; IgG was found to be raised: (normal range 736-1195 mg/dl) patient’s value being 1400 mg/dl. However, ANA and anti-smooth muscle antibody (ASMA) were negative. In view of the raised IgG levels, the diagnosis of autoimmune hepatitis was confirmed, and the gastroenterologist decided to start her on oral prednisolone in the dose of 10 mg per day and she was advised follow up.

Discussion

When elevated liver enzymes are encountered in pregnancy, the main issue would be to rule   out the common causes. Our patient remained normotensive throughout, hence hypertensive disorders of pregnancy and related syndrome such as HELLP syndrome was ruled out. Viral markers were sent but all were negative. There were no other features of cholestasis or of acute fatty liver of pregnancy. In such a setting, a more detailed approach was followed in investigating the cause of the isolated elevation of liver enzymes in our patient, which ultimately lead to the recognition of AIH. 
Autoimmune hepatitis is a disorder with continuing hepatocellular necrosis, inflammation and fibrosis with propensity to progress to cirrhosis and liver failure. Though there is a 40% chance of mortality in severe untreated cases, the reported 10-year survival is 90% in treated cases.  
Clinical features are similar to chronic viral hepatitis. Patient may present with features of arthalgia, jaundice, upper quadrant pain, fever, thrombocytopenia and myalgia. Traditionally, a term called “lupoid hepatitis” was used for patients with positive ANA titres. These patients are predominantly middle-aged women having marked hyperglobulinemia and circulating ANAs in high-titre. There may be overlap with other autoimmune disorders.[1]
Diagnostic criteria based on elevation of IgG, autoantibody demonstration, histological characterisation of hepatic inflammation in the absence of viral disease are helpful. The cornerstone of management in AIH is glucocorticoid therapy. The treatment objectives include restoration of the normality of liver function tests, which need to be weighed closely against the possible adverse effects of immunosuppressive therapy. Prednisolone is the preferred drug. Our patient responded to prednisolone and there was a prompt reduction in the SGOT and SGPT values (Table 1).

Table 1: Serial values of SGOT and SGPT
SGOT (IU/ml)
SGPT ( IU/ml)
At admission (35 wk1day)
234
290
35wk 2 days
250
300
35wk 4 days
663
934
Pre- LSCS 35 wk 6 day
343
718
Post LSCS
428
209
On day 2 of steroids
88
265
On day 3 of steroids
58
204

Approximately 60-70% respond to therapy. In these, immunosuppressive requirement may reduce. However, a large number suffer from relapses. Aminotransferase levels can be taken as indicators of relative disease activity but should be interpreted cautiously. Though histologic improvement may be delayed by many months, serial liver biopsies are not recommended to guide continuation of therapy. In medically refractory cases, intensive treatment with high-dose glucocorticoid monotherapy is needed; failure of which may necessitate combination of glucocorticoids with high-dose azathioprine (150 mg daily) therapy.[1,2] Newer modalities of treatment such as calcineurin inhibitors, mycophenolatemofetil may be required if failure occurs with conventional therapy. Sometimes, lifelong glucocorticoid therapy is needed. In decompensated patients, liver transplantation may be necessary.  It is well recognised that elderly patients and pregnant patients need treatment modifications.[3] Saini et al have described a patient whose condition was recognized in the postpartum period, which is quite similar to our patient.[4] While the fetal affection has not been extensively documented, fetal intestinal perforation and meconium peritonitis have been described.[5] Thrombocytopenia worsens the outcomes in patients with autoimmune hepatitis.[6] Very few studies have followed the course of patients of AIH with pregnancy.  In a cohort of 81 patients with AIH studied by Westbrook et al, the live birth rate was 73%. A flare in the disease activity occurred in 1/3rd of the patients. 11% of the patients had a serious maternal adverse event in the year following delivery.  Poor control during the year prior to conception was a significant determinant of poor maternal and neonatal outcome.[7] Our patient had a preterm birth and delivered a SGA neonate.  A 5 year cohort study of all pregnancies with 171 births in women with diagnosed autoimmune hepatitis concluded that women with AIH had an increased risk of gestational diabetes, preterm birth and of low-birth-weight child. There was no significant association between autoimmune hepatitis and pre-eclampsia, cesarean section, low 5 minute Apgar score, congenital malformation and neonatal mortality.[8]
One particular concern is the effect of glucocorticoids and other immunosuppressants during pregnancy on the offspring.  While cyclophosphamide and methotrexate are contraindicated during pregnancy, drugs such as glucocorticoids, cyclosporine and hydroxychloroquine are not associated with any major risk of congenital malformations.  The risk of preterm delivery, low birth weight and IUGR is probably related to a combination of both the maternal disorder and immunosuppressive therapy. However long term follow-up of such babies show normal neuro-cognitive maturity. [9, 10]
As concluded by Czaja et al, with the advent of modern drugs, patients should be counselled regarding the nature of the disease and good control should be attempted peri-conceptionally.  Pregnancy is usually well-tolerated by mother and fetus. However, protection against postpartum exacerbation needs to kept in mind. Our patient has been advised to monitor LFTs and follow up regularly with the gastroenterologist.[11]

References 
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Citation

Mehta V, Prasad M, Gupta AS. Autoimmune Hepatitis in Pregnancy. JPGO 2016. Volume 3 No. 8. Available from: http://www.jpgo.org/2016/08/autoimmune-hepatitis-in-pregnancy.html