Case Reports

Indian Pediatrics 2002; 39:189-192  

Liver Transplantation for Fulminant Hepatitis A Infection

From the Apollo Center for Advanced Pediatrics, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi 110 044, India.

Correspondence to: Dr. Anupal Sibal, Senior Consultant Pediatric Gastroenterologist and Hepatologist, Apollo Center for Advanced Pediatrics, Indra- prastha Apollo Hospital, Sarita Vihar, New Delhi 110 044, India.

E-mail: [email protected]

Manuscript received: May 25, 2001;
Initial review completed: June 27, 2001;
Revision accepted: August 8, 2001.

Hepatitis A infection is the commonest cause of acute hepatitis and fulminant hepatic failure (FHF) in Indian children(1,2). Although FHF develops in only 0.1% of cases with hepatitis A infection, it carries a mortality of 30%(3,4). We report the clinical course of a child with hepatitis A who developed FHF necessitating liver transplantation. Liver transplantation for FHF has not been previously reported in India.

A 7-year-old male child was referred to our center with a three-day history of jaundice and high-grade fever, and a two-day history of abdominal distension. There was history of altered sleep rhythm and irritability since one day but no history of bleeding prior to transfer.

On examination, the child was tachypneic, deeply icteric, pale, with a tender hepato-megaly of 7 cm below costal margin, and a just palpable spleen. Minimal free fluid was present in the abdominal cavity. Neuro-logically the child was irritable but well oriented. Motor system, sensory system and cranial nerve examination was normal.

Investigations revealed high serum bilirubin (total 18.2 mg/dl, direct fraction 14.8 mg/dl), increased transaminases (AST 2740 U/L, ALT 1470 U/L) and deranged hepatic synthetic functions [serum albumin 2.3 g/dl, PT 49 sec (control 12 sec), PTT 69 sec (control 30 sec)]. There were leukocytosis and thrombocytopenia (leukocyte count 27.9 × 109/L, platelet count 78 × 109/L). The hematocrit (0.21) and hemoglobin (7.2g/dl) were deranged. Renal function tests and electrolytes were normal and ascitic tap revealed a transudate. G6PD levels were 96 mu/109 red blood cells (normal range 118-114 mu/109 RBC, Boehringer Mannheim, USA). Peripheral smear showed evidence of intravascular hemolysis.

IgM antibody against hepatitis A virus was positive and markers for hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus and cytomegalovirus were negative. Cultures of various clinical specimens revealed no growth. There was a worsening of encephalopathy on day 2 of admission, which rapidly progressed to grade III during the next 24 hours despite all supportive measures. The liver size was noted to regress, bilirubin levels continued to rise (peak level 24.7 mg/dl on day 4 of admission), upper gastrointestinal hemorrhage started, transaminase levels fell (AST 2250 U/L, ALT 1190 U/L) and prothrombin time worsened (test>60 sec, control 12 sec) despite fresh frozen plasma transfusion. In view of worsening encephalopathy, the child was electively ventilated.

The patient was considered for an urgent living related liver transplant as he met the criteria for liver transplantation (prothrombin time >50 sec, bilirubin >17.5 mg/dL, age <10 years)(5). Within 12 hours, he underwent a cava preserving hepatectomy followed by transplantation of segment II, III and IV from the left lobe of his father. The child was hemodynamically stable during the procedure and the transplanted left lobe of liver perfused well with early signs of graft function.

Postoperatively his general condition was stable and the liver function tests started to normalize from the third postoperative day. He was extubated, oral feeds started and broad-spectrum antibiotics stopped on the fourth, sixth and seventh postoperative day, respectively. On the seventh post-operative day, he developed acute cellular rejection, which did not respond to high dose methylprednisolone therapy, and satisfactory cyclosporin levels could also not be main-tained despite high doses. Immuno-suppression was therefore modified with FK 506 replacing cyclosporin, which controlled the acute rejection. The donor had an uneventful hospital stay and was discharged on day 7.

The child was discharged at 4 weeks with a total bilirubin of 4.7 mg/dL, direct fraction 2.5 mg/dL, AST 38 U/L, ALT 27 U/L, alkaline phosphatase 253 U/L, albumin 3.9 g/dL and PT 14 sec (control 12 sec). The child was readmitted with varicella infection after 2 weeks and despite varicella-zoster immuno-globulin and acyclovir, he developed varicella pneumonia and myocarditis and passed away 10 days later.

Hepatitis A is the commonest cause of acute hepatitis and FHF in Indian children. The incidence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency has been reported to vary between 2.2% to 14% in north Indian children(6). Hepatitis A infection is known to trigger hemolytic anemia in G-6-PD deficient individuals(7). This clinical syn-drome manifests as hemolytic anemia, high peak serum bilirubin levels and acute renal failure. The prognosis is reported to be good with convalescence generally complete(8). Although a rapid rise in serum bilirubin has been reported, it was not found in this case (6.5 mg/dL in 72 hours). Also, our case did not develop acute renal failure. The G-6-PD levels in our case were not greatly reduced which may be because the test was carried out during a hemolytic episode. Tests for G-6-PD deficiency may be negative during and immediately after a hemolytic episode as the old red blood cells deficient in G-6-PD get hemolytic and the newly formed red blood cells (reticulocytes) have a higher content of G-6-PD enzyme; hence a repeat test 8 weeks later is recommended(8).

As rapid deterioration can take place in a child with FHF, the need for liver transplantation (which is the only definite treatment for FHF) should be constantly assessed. The decision to perform liver transplantation (LT) should take into account three questions: Is spontaneous recovery possible? If not, is transplant feasible? Or, have irretrievable complications occurred? While a number of prognostic factors for determining the likelihood of spontaneous recovery have been studied, the criteria proposed by the King’s College group for LT in FHF have found wide acceptance(5). We had applied the King’s College criteria to 17 cases of FHF seen previously in our center and found that 5 children (3 with hepatitis A) needed liver transplantation(9). Unfortu-nately, none of the five could receive liver transplantation as all of them had contra-indication and all of them died. As our patient satisfied the King’s College criteria, he was, therefore, listed for an emergency living related liver transplantation. While the overall one year acturial survival rates for pediatric liver transplantation are 85-90%, the survival rates for FHF are 56-66%(10,11). Varicella - zoster virus is known to produce serious complica-tions post liver transplantation(12). Our patient was highly immunosuppressed with FK 506 and high dose corticosteroids and despite varicella - zoster immunoglobulin and acyclovir, the infection could not be controlled. While potential pediatric liver transplant recipients received the varicella vaccine before being placed on the waiting list, this is not possible in the case of emergency liver transplantation, as once vaccinated the subject cannot be transplanted for 4 weeks (due to risk of disseminated varicella secondary to immunosuppression). It was unfortunate that despite a successful liver transplant we lost our patient.

This case demonstrates the need for a proactive approach regarding need for liver transplantation in children with FHF. In the absence of cadaver donors, the only option is an emergency living related liver transplant.

Contributors: DM and RS drafted the paper under the supervision of AS. AS was the pediatric hepato-logist incharge and will serve as guarantor for the paper.

Funding: None.

Competing interests: None stated.

 

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