Oguz Canan

Neurological complications of liver transplantation in pediatric patients: A single center experience

Abstract:  Neurologic complications (NCs) are a significant cause of morbidity and mortality in patients who undergo liver transplantation (LT). The aim of this study was to evaluate the incidence and type of NCs and associated factors in pediatric LT patients. We retrospectively reviewed NCs in the medical records of 40 consecutive infants, children, and adolescents who underwent LT at our institution. The subjects consisted of 23 boys and 17 girls (median age, 8.5 ± 0.85 yr; range, 11 months to 17 yr). The indications for LT were Wilsons disease in 10 patients, fulminant hepatic failure (FHF) in nine, and other types of chronic liver disease in 21. NCs were found in 14 patients (35%). Those 14 individuals experienced a total of 16 episodes of NCs (two separate episodes in two of the patients). The most common NCs were seizure (seven episodes in six patients) and posterior leukoencephalopathy syndrome (PLES; five episodes in four patients). Seizure was the presenting symptom in three episodes of PLES. Two episodes of diffuse encephalopathy were observed in two patients, and two episodes of psychiatric symptoms occurred in two patients. We also noted one episode of tremor in one patient, one episode of acute dystonic reaction in one patient, and one episode of headache in one patient. Patients with Wilsons disease had a higher incidence of NCs (60%) than did patients without Wilsons disease (26.7%); however, this difference was not significant. The incidence of NCs was 44% in patients with FHF and 35% in those without FHF. That difference also was not significant. Immunosuppressive agents were the primary cause of 13 of the 16 episodes of NC. Uremia with hypertension, hypoxia, and hypomagnesemia caused one neurologic episode each. NCs, which are frequent in the first 30 days after pediatric LT, did not affect survival in this group. NCs were reversed by the discontinuation or reduction of immunosuppressive agents in 12 episodes, correction of hypomagnesemia and the reduction of immunosuppressive agents in one episode, and the correction of uremia and hypertension in one episode. Refractory epilepsy developed in one patient, and death unrelated to NCs occurred in one. The mortality rate was 7.1% (n = 1) in patients with NCs and 15.4% (n = 4) in those without NCs (p = 0.64). NCs are an important complication after LT. It is essential that each transplantation team collaborate with pediatric neurologists to ensure the rapid and accurate diagnosis of NCs in infants, children, and adolescents after LT and to prevent the delay of appropriate treatment.

Hepatocellular carcinoma in Wilson's disease: A rare association in childhood

Abstract:  Wilsons disease is a hereditary disorder of copper metabolism that results in the accumulation of copper in the body, primarily in the liver, brain, and cornea. Hepatocellular carcinoma, in contrast to other causes of cirrhosis, is seldom associated with Wilsons disease. We present a 12‐yr‐old boy with Wilsons disease in whom hepatocellular carcinoma was incidentally diagnosed in the pathologic specimen examined after liver transplantation.

Liver transplantation for hepatocellular carcinoma in children

Abstract:  We present our experience with living‐donor liver transplantation in the treatment of nine children with hepatocellular carcinoma. Between January 2001 and March 2007, we performed 81 liver transplantations in 79 children at our center. Nine of the 79 children (11.3%; mean age, 9.7 ± 5.5 yr; age range, 12 months–16 yr; male‐to‐female ratio, 2:1) underwent an living‐donor liver transplantation because of hepatocellular carcinoma. Two of nine children received right lobe grafts, three received left lateral segment grafts, and the remaining four children received a left lobe graft. According to the TNM staging system, two children had stage 1 carcinoma, three had stage 2, and four had stage 4A1. The mean follow‐up was 19.8 ± 10.6 months (range: 7–32 months). There has been only one tumor recurrence, which occurred in the omentum 26 months after liver transplantation. There was no evidence of recurrence or AFP elevation in the other eight children. Both graft and patient survival rates are 100%. In conclusion, liver transplantation is a life‐saving procedure for children with chronic liver disease with accompanying hepatocellular carcinoma. During follow‐up of patients with chronic liver disease, serial AFP screening and combined radiologic imaging studies should be mandatory.

Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma

Abstract:  We described six children with heritable liver disease and hepatocellular carcinoma treated with living‐related liver transplantation. Underlying liver diseases were type‐1 tyrosinemia (three patients), progressive familial intrahepatic cholestasis type II (two patients), and Wilsons disease (one patient). Two of the tumors were found incidentally during liver transplantation. Number of nodules was 12, 15, 3, 2, and 1 (in two patients). Three patients were treated with chemotherapy before the procedure. Chemotherapy was not given to any patient after liver transplantation. The mean follow‐up was 17.7 ± 6 months (range: 7–24). All patients are tumor recurrence free. Both graft and patient survival rates are 100% at a median of 18.5 months follow‐up. Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates.

INVASIVE ESOPHAGEAL ASPERGILLOSIS ASSOCIATED WITH ACUTE MYELOGENOUS LEUKEMIA: Successful Therapy with Combination Caspofungin and Liposomal Amphotericin B

Aspergillosis is one of the most common invasive fungal infections in patients with leukemia. In this patient group, this form of Aspergillus infection is a life-threatening condition with a mortality of 50–100%. The lungs are most often affected, but the esophagus can also be involved.The authors report the case of a child with leukemia who developed invasive esophageal aspergillosis. The condition was diagnosed by microscopic examination of endoscopic biopsy specimens. The patient was already receiving empirical liposomal amphotericin B when the diagnosis was made, so a second antifungal (caspofungin) was added to the regimen. This combination was successful. This case to demonstrates a case of successful treatment of invasive esophageal aspergillosis using combination therapy of liposomal amphotericin B and caspofungin.

Long term follow-up of glomerular and tubular functions in liver transplanted patients with Wilson’s disease

Abstract:  The aim of this study was to determine the long term outcome of renal glomerular and tubular functions in children receiving an LT for WD. Renal functions were examined in nine children with WD before and long after LT and compared with those of nine liver transplanted children with hepatic diseases other than WD. The duration of follow‐up was at least two yr for both groups. GFR, fractional TRP and tubular maximum rate of phosphate reabsorption in relation to GFR (TP/GFR) as well as daily protein and Ca excretion were studied in both groups before and after LT. Pretransplant mean GFR, TRP and TP/GFR were significantly lower in the study group than the controls. A significant increase in the post‐transplant TRP and TP/GFR was observed in the study group and the difference between the groups disappeared during the long term follow‐up. Urinary protein excretion decreased in both groups after LT. Tubular dysfunction is frequent in patients with WD. LT for hepatic failure secondary to WD is a lifesaving procedure correcting the underlying hepatic defect as well as renal defects.

Neurologic complications of liver transplantation in pediatric patients with the hepatic form of Wilson's disease.

The literature contains very little documentation on neurologic complications in liver transplant recipients for Wilsons disease. We retrospectively reviewed 17 consecutive cases of pediatric liver transplantation for the hepatic form of Wilsons disease to assess the types of neurologic complications that occurred, the incidence of those problems, and associated factors in this patient group. The patients were 12 boys and 5 girls; indications for liver transplantation were fulminant hepatic failure in 3 patients and chronic hepatic failure in 14 patients. Neurologic complications were observed in 10 of the 17 patients as 16 episodes. The most common neurologic complications were seizure (7 episodes in 6 patients) and sudden-onset headache (5 episodes in 4 patients). Tacrolimus was identified as the only possible cause of headache in 3 episodes. Encephalitis was the cause in 1 and intracranial hemorrhage was the cause in the other headache episode. We also noted 1 episode of tremor, 1 episode of acute dystonic reaction, 1 episode of diffuse encephalopathy, and 1 episode of common peroneal nerve palsy. Immunosuppressive agents were the primary cause of 12 of the 16 episodes of neurologic complications. Uremia with hypertension, compression of the right common peroneal nerve, encephalitis, and intracranial hemorrhages attributable to coagulopathy caused 1 neurologic episode each. Neurologic complications in patients with the hepatic form of Wilsons disease were frequent during the first 30 days after pediatric liver transplantation but did not affect survival. Transplantation teams should be aware of the high incidence of neurologic complications in pediatric patients with the hepatic form of Wilsons disease.

Successful treatment of hepatitis B-associated leukocytoclastic vasculitis with lamivudine treatment in a child patient.

Chronic hepatitis B infection (HBI) has many extrahepatic manifestations such as vasculitis, glomerulonephritis, arthritis, dermatitis, pulmonary disease, and skin manifestations. The mechanism of these manifestations is thought to be immune mediated. Immune-suppressive treatment may enhance viral replication and worsen hepatic disease. Lamivudine is a nucleoside analogue used in chronic HBI treatment that works by suppressing replication of the hepatitis B virus (HBV). Recently, several reports have suggested that lamivudine treats vasculitis associated with HBV infection in adults. However, there are no data in the literature for children. Herein, we report a child with leukocytoclastic vasculitis due to chronic HBI who was successfully treated with lamivudine.

Frequency of urinary tract infection in pediatric liver transplantation candidates

Abstract:  An increased frequency of infections has been reported in patients with chronic liver disease. The tendency of patients in this population to acquire UTI is not completely understood. We aimed at investigating the incidence of UTI in children with cirrhosis, before liver transplantation. Twenty‐six children (9 girls, 17 boys; mean age, 7.66 ± 5.73 yr) with chronic liver disease who had undergone liver transplantation between 2002 and 2004 were included. On admission for liver transplantation, patients were examined for presence of UTI. Serum biochemistry, complete blood cell count, urinalysis and culture, glomerular filtration rate, and abdominal ultrasonography were performed prior to liver transplantation. Ten of 26 patients (38.5%) were found to have symptomatic UTI. Urine cultures revealed E. coli in five (50%), Klebsiella pneumoniae in three (30%), Enterococcus faecalis in one (10%), and Enterobacter aeruginosa in one (10%) patient(s), respectively, as etiologic factors. The etiologies of chronic liver disease in our patients with UTI were BA in five, PFIC in three, Wilsons disease in one, and alpha‐1 antitrypsin deficiency in one patient. We found a significantly greater number of UTIs in patients with biliary atresia than in those without biliary atresia (p < 0.05). The mean age of the patients with UTI was 2.75 ± 3.49 yr, which was significantly lower than in those without UTI (9.75 ± 4.86 yr, p < 0.05). Levels for white blood cells, thrombocytes, ALT, and alkaline phosphatase were significantly higher in patients with UTI than in those without UTI. There were no significant differences between the groups with regard to serum albumin, bilirubin, AST, GGT, BUN, or creatinine levels, glomerular filtration rate, duration of disease, and PELD scores. In patients with bacteriuria, renal USG revealed normal findings in all, but except one patient who had pelvicalyceal dilatation. Scintigraphic findings demonstrated acute pyelonephritis in six (60%) patients with UTI. VCUG demonstrated vesicoureteral reflux in two patients. In conclusion, symptomatic UTI is common in children with cirrhosis. It occurs more frequently in patients with biliary atresia than it does in patients with other types of chronic liver disease. In febrile children with chronic liver disease, UTI should be considered in the differential diagnosis.

Cows milk protein enteropathy and granulomatous duodenitis in a newborn

Abstract:  Cow’s milk protein enteropathy is a symptom complex that composed of severe diarrhoea and malnutrition. This disorder is caused by non‐immunoglobulin E‐mediated food allergy. Its clinical features and natural course have been explained in many reports, of different types of cow’s milk and soy reactions. In the present article, we describe a newborn patient who presented with chronic diarrhoea and failure to thrive diagnosed as cow’s milk protein enteropathy. The duodenal biopsy revealed granulamatous duodenitis which has not been described before. Her clinical and pathological findings responded well to cow’s milk elimination. We suggest that food allergies should be considered in differential diagnosis of patients with chronic diarrhoea and failure to thrive.