EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Liver transplant is the preferred therapy for children with end-stage liver disease, resulting in excellent long-term outcomes. The need for transplant in small children implies that the liver disease is progressing rapidly. As a result, children who are candidates for transplant are usually in a poor clinical state due to malnutrition and complications related to end-stage liver disease. Young age and very low weight make transplant a challenging intervention with high morbidity in children.¹

Diaphragmatic hernia is an unusual complication after pediatric liver transplant. Nearly one-half of bowel obstruction cases requiring surgical inter-vention in patients with liver transplant are caused by diaphragmatic hernia.² It has been suggested that the use of a left lobe liver graft, surgical trauma, malnourishment, elevated intra-abdominal pressure, and mammalian target of rapamycin inhibitors are predisposing factors for development of diaphrag-matic hernia. The use of a segmental graft may increase the risk of diaphragmatic hernia because the surgically damaged right hemidiaphragm often remains exposed to underlying viscera, instead of being covered by the right hepatic lobe.³

Smaller patients are therefore at risk for higher rates of diaphragmatic complications after pediatric liver transplant,¹ but diaphragmatic hernia has not been reported as a unique occurrence. Here, we report 3 cases of diaphragmatic hernia after liver transplant and discuss the possible contributing factors.

A 2-year-old boy with end-stage liver failure secondary to progressive familial intrahepatic cholestasis type 2 underwent liver transplant and received a left lateral segment liver graft from his uncle in June 2004 at our center. He was discharged from the hospital 97 days after transplant. Nearly 1 year later, he was admitted to the hospital with a 4-day history of fever, cough without respiratory distress, and abdominal pain with vomiting. A physical examination revealed diminished breath sounds at the right base and an axillary temperature of 38°C. Laboratory investigation revealed a normal total blood count and blood biochemistry. Initial chest radiographs revealed marked elevation of the right hemidiaphragm, prompting a diagnosis of right-sided diaphragmatic eventration. Chest and abdominal computed tomography scans were conducted to exclude other diseases, revealing the right-sided diaphragmatic eventration. A chest radiograph was performed due to a differential diagnosis of pneumonia, which resulted in a diagnosis of diaphragmatic hernia with enterothorax on the right side (Figure 1A). Computed tomography scans also showed diaphragmatic hernia and acute appendicitis (Figure 1B).

The patient’s surgical procedure was through the previous right subcostal incision. On exploration, a posterolateral 4x2-cm defect was found in the right side of the diaphragm, through which the colon moved into the right thorax (Figures 1A and 1B). An inflamed and edematous appendix was also found in the hernia sac (Figures 2A and 2B). The patient had perforated appendicitis; therefore, the appendix was removed. In February 2008, the patient developed an asymptomatic diaphragmatic hernia and underwent elective diaphragmatic hernia repair through a right posterolateral thoracotomy incision with Teflon mesh. The patient had an uneventful recovery and was discharged 1 week after the surgical procedure.

Patient 2
A 7-month-old girl (8 kg) with mild intellectual disability underwent left lateral segment liver transplant from her mother due to biliary atresia. Liver graft was 315 g. Hepaticojejunostomy for the right diaphragm was performed with no complications. After the surgical procedure, an immunosuppressive therapy regimen of tacrolimus, mycophenolate mofetil, and steroids was started. The patient had no bleeding during or after the procedure. The mean level of albumin was 3.1 g/dL. The patient was discharged 16 days after the surgical procedure without any complications. Clinical follow-up, liver enzyme levels and radiologic evaluation were normal. After 2 months, the patient was admitted to the emergency department of another hospital with sudden onset of severe respiratory distress. The patient’s condition was diagnosed as diaphragmatic hernia. Unfortunately, she died during the transfer to our center by air ambulance.

Patient 3
A 3-year-old girl (14 kg) received a left lateral segment liver transplant from her father due to acute liver failure. The patient did not have malnutrition. Preoperative albumin level was 3.4 g/dL. After liver transplant, the patient had various neurologic deficits that improved over time. Postoperative tacrolimus, mycophenolate mofetil, and steroid therapy were given to the patient. During the early postoperative period, a chest tube was inserted into the patient because of massive pleural effusion in the right hemithorax. The chest tube was removed 10 days after surgery. During follow-up, the patient’s native liver pathology reported liver failure induced by hemophagocytic lymphohistiocytosis. The patient was discharged on postoperative day 20. The patient was admitted to our clinic with complaints of nausea approximately 4 months after discharge but had no respiratory distress. A physical examination that revealed sounds of the intestines in the lung prompted a chest radiograph, and bowel loops were observed in the right hemithorax. A thoracoabdominal computed tomography scan was taken (Figures 3A and B). Due to a diagnosis of diaphragmatic hernia, the patient underwent an emergency operation. The large intestine and jejunal segments of the small intestine were herniated into the chest through a defect of approximately 2.5 to 3 cm in the diaphragm on the right side. The intestines were pulled into the abdomen, and the diaphragm was repaired with continuous suture. The patient was discharged on postoperative day 5 (Figure 4).

Abdominal interventions for complications after pediatric liver transplant are not uncommon in children.⁵ However, most complications are infectious, with internal hernia of the small intestine with or without volvulus being a rare occurrence. According to the few available reports in the literature, such cases have most commonly been reported around the Roux-en-Y loop⁶ or through an inguinal or an incisional procedure and around a vascular conduit in a single case.⁷ Pulmonary problems are frequent in children who have undergone transplant, with around two-thirds developing pleural effusion and one-third having pneumonia or consolidation. In addition, 8% to 15% of patients develop diaphragm dysfunction or paralysis. These patients usually need prolonged ventilation and may require plication of the diaphragm.¹ However, right-sided diaphragmatic hernia occurring after a liver transplant is not a recognized complication. In our patients, we observed delayed symptoms (2 months after transplant). Furthermore, 1 patient had diaphragmatic hernia twice, but the cause remains unclear.

In an effort to explain the observations made in the presented patients, our first hypothesis is the existence of a congenital diaphragmatic hernia. Although this does not exclude the presence of a small right-sided congenital defect, it seems unrealistic that such a defect should be detected during the mobilization of the liver and hepatectomy during transplant. A second simple hypothesis is that direct trauma to the diaphragm may be caused during the transplant procedure. It is well accepted that total hepatectomy may be traumatic to the right side of the diaphragm, especially in the location overlying the bare area of the liver. The latter may be more important in critically ill patients (with portal hypertension and coagulopathy, especially those with a previous Kasai procedure), and they require a more extensive use of measures to control bleeding (suturing, conventional measures, or argon beam diathermy), which can directly damage the diaphragm. However, hepatectomy procedures are well standardized, and the various hemostatic devices are used routinely. Thus, with thousands of transplants performed each year, this complication would be well recognized if trauma was the simple, straightforward answer.

Ultimately, it is conceivable that minor trauma to the diaphragm may only lead to future problems in the presence of other predisposing factors. These may include the following, as detailed below.

First, small infants who are candidates for transplant are usually critically ill, with at least one-half already hospitalized or on mechanical support while waiting for a transplant.^3,8 They have low weight and typically have severe malnutrition (as was the case with 2 of our reported patients) and have generalized reduced muscle bulk.⁹ It is therefore likely that their diaphragm is quite thin and may be more sensitive to the effects of diathermy, resulting in an area of focal necrosis.

Second, infants with low body weight rapidly deteriorate and need urgent transplant. Thus, they often receive liver grafts from large donors. Despite the division or reduction of the liver, slightly oversized liver grafts are used, and it is not uncommon that prosthetic abdominal closure is required to deal with tight abdominal closure.³ The combination of ischemia caused by diathermy and that from abdominal overpressure might lead to focal diaphragmatic necrosis, progressing later to eventration or herniation.

It is likely that a combination of these factors, some related to techniques used and others related to the patient characteristics, might explain the pathophysiologic mechanism of these uncommon hernias. Although it is our belief that it will remain a rare occurrence, diaphragmatic hernia should nevertheless be added to the list of potential complications after liver transplant in the pediatric population. Pediatric transplant physicians and surgeons should be aware of this complication so that it is recognized promptly in both acute and nonacute settings and so that appropriate action is taken.

Volume: 13 Issue: 5 October 2015

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