Living Donor Liver Transplantation for Acute Liver Failure Due to Hepatitis E in a Pregnant Patient - Challenges in Management

Hepatitis E virus belonging to the family Hepeviridae, is an important cause of enterically transmitted hepatitis in developing countries.

Hepatitis E virus belonging to the family Hepeviridae, is an important cause of enterically transmitted hepatitis in the developing countries. Hepatitis E can lead to acute liver failure in pregnant patients and in patients with pre existing liver diseases. The mortality rates increase especially in the third trimester of pregnancy1. We describe a case of a 28-year-old female at 28 weeks of gestation who presented with acute liver failure due to hepatitis E virus.

Case report

A 28-year-old female at 28 weeks of gestation was referred from a peripheral centre with history of tiredness, jaundice of 6 days duration and altered sensorium for a day. She was investigated and found to be hepatitis E card test positive. Patient was admitted in the intensive care unit. Blood investigations revealed coagulopathy (INR- 6.76). Fetal ultrasound was done which showed appropriate results for gestational age fetus with good cardiac activity.

Patient was started on supportive management.Liver protective strategy in the form of NAC infusion started.Inotropes were started for hypotension. Coagulopathy worsened on the subsequent day, patient developed pervaginal bleeding,and encephalopathy worsened (grade 2). She met the King's College Criteria for transplantation and was reviewed by the transplant team. The spouse was identified as a suitable donor and all donor work up were initiated. She was simultaneously listed for cadaveric transplantation with the state registry (KNOS).

A multidisciplinary team decided to proceed for Liver Transplantation, with lower segment Caesarean section prior to transplant. Patient was shifted to the operating room; IV access was done with wide bore cannula and multiparameter monitoring started. Right radial artery was cannulated for invasive pressure monitoring.

Rapid sequence induction was done and Intubated. LSCS was done and a live female baby was delivered. Baby was handed over to the neonatal intensive unit ,where the baby was intubated and ventilated. Coagulopathy during surgery was corrected by use of fresh frozen plasma and platelet concentrate. Inotropes were increased in view of hypotension post cesarean section.

Once the LSCS completed, fresh drapings were made for Liver Transplantation surgery. Advanced venous access 9 F was done in the right IJV under ultrasound guidance. Triple lumen central venous catheter, 7 F was also secured to the Right internal jugular vein, one inch below the AVA insertion site. All lines were secured using sutures. Left sided radial artery was cannulated for sample collection and intraoperative coagulation monitoring.

ROTEM was used for coagulation assessment. Flotrac- EV 1000 (Edwards) was used for intraoperative hemodynamic monitoring. CVP monitoring was initiated during the entire surgery and to the post operative period. The dissection phase was accompanied by severe coagulopathy, the correction of which was done guided by the ROTEM values. Noradrenaline infusion, Phenylephrine infusion and Vasopressin infusion were started off early during the dissection phase due to hemodynamic instability.

Anhepatic phase blood gases showed acidosis which was corrected by Sodium Bicarbonate infusions. Correction of hypocalcemia was done during the anhepatic phase.

The implantation of the graft liver was done using IVC cross clamp. The total cold ischemia was 2 hour 11 minutes. The reperfusion phase was marked by severe post reperfusion syndrome which was tackled by increased dose of inotropes, infusion of soda bicarbonate, Calcium Chloride 10% and a single bolus dose of Adrenaline (1:100000).

The immediate reperfusion phase showed a rise in cvp and worsening acidosis which settled within half hour post reperfusion. Clearing of acidosis in the ABG was noted one hour post reperfusion. The warm ischemia time was 56 minutes.

All the anastomosis were done and meticulous hemostasis was done. Closure done after checking instrument and mop counts. The total duration of surgery noted was 11 hours. The patient was shifted to the transplant ICU for elective postoperative ventilation. She was put on pressure support ventilation and sedation done by propofol and fentanyl infusions. Tapering of inotropes were done gradually.

Weaning from the ventilator was started 6 hours post surgery and was extubated after 12 hours post surgery. Her higher mental functions were intact and inotropes were tapered off 14 hours post transplant. The baby was put on elective ventilation for 48 hours, ECHO revealed PDA, which was managed medically. Liver function tests of the recipient started declining to normal level 24 hours post liver transplant. 72 hours post transplant immunosuppression was started and was titrated according to the enzyme values. Patient was discharged 20 days post surgery with no complication. The patient and baby is on regular follow up for the past one year with no post op surgical or medical issues.

Discussion

Hepatitis E is an important cause of enterically transmitted hepatitis in developing countries. It can lead to acute liver failure especially in pregnant patients and in patients with pre existing liver diseases 1. The mortality rates increased in the third trimester of pregnancy and with increasing grades of hepatic encephalopathy. The frequency of infection and mortality rate increase with the gestational age.

The severe course in pregnant women is related to a reduction in the expression of progesterone-receptor, which led to a predominance of T-helper type 1 lymphocytes. This immunologic shift results in an exuberant cytotoxic T-cell reaction resulting in foetal and maternal injury.2 Orthotopic Liver Transplantation (OLT) is a treatment option for patients with ALF.

To the best of our knowledge, doing a combined lower segment Cesarean section along with a Living Donor Liver Transplant for Hepatitis E induced ALF was a rare entity. Our case at the time of hospitalisation had worsening encephalopathy and a viable fetus.

The worsening encephalopathy, coagulopathy, viable fetus and availability of transplant facility in our centre favoured the decision for combined LSCS and a Living Donor Liver Transplant. The mortality rates were higher as found in other studies when the transplant was done at a later stage of encephalopathy. So, we decided upon terminating the pregnancy with the hope of saving a viable fetus and following up with a Living Donor Liver Transplantation to save the mother.

A case where LSCS was done to terminate the pregnancy and later proceeding with transplant option with a successful outcome was available in the literature 3. Our case had higher grades of encephalopathy and coagulopathy which made us to proceed for the transplant, without waiting for further worsening of the clinical condition of the patient.

Combined lower segment Caesarean section and liver transplantation is a rare entity. Timing of LSCS and liver transplantation is an always debatable topic. Various case reports are available in literature where LSCS was done and later transplantation was done. Centres have done induction of labour and then depending on the clinical condition, transplantation was done at a later stage 4. Delaying the delivery of fetus will interfere with the immunosuppressive regimen as many of the immunosuppressive agents are not pregnancy safe 5.

In our case we decided upon LSCS and liver transplant with the idea that a viable fetus could be saved and better hemodynamic control could be achieved in a controlled way and transplant offered in the same session could have a better prognosis for both the mother and the baby.

Summary

Hepatitis E can cause severe hepatic failure in pregnancy. Early intensive care management is the key to survival.Termination of pregnancy depends on the viability of the fetus.Liver transplantation can be a suitable option where facilities are available. Combined liver transplant and Caesarean section or liver transplant followed by delayed delivery of fetus can be considered depending on the clinical situation.

References

1. Patra S, Kumar A, Trivedi SS, Puri M, Sarin SK. Maternal and Fetal Outcomes in Pregnant Women with Acute Hepatitis E Virus Infection. Ann Intern Med. 2007;147:28-33. doi: 10.7326/0003-4819-147-1-200707030-00005

2.Shalimar, & Acharya, S. K. (2013). Hepatitis E and Acute Liver Failure in Pregnancy. Journal of Clinical and Experimental Hepatology, 3(3), 213–224. http://doi.org/10.1016/j.jceh.2013.08.009

3 Banait VS, Sandur V, Parikh F, et al. Outcome of acute liver failure due to acute hepatitis E in pregnant women. Indian J Gastroenterol 2007; 26: 6-10.

4 Bertuzzo, V. R., Ravaioli, M., Morelli, M. C., Calderaro, A., Viale, P. and Pinna, A. D. (2014), Pregnant woman saved with liver transplantation from acute liver failure due to hepatitis E virus. Transpl Int, 27: e87–e89. doi:10.1111/tri.12305

5. Mukherjee S, Mukherjee U. A comprehensive review of immunosuppression used for liver transplantation. Journal of transplantation. 2009 Jul 16;2009

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