Contrast-enhanced ultrasound is useful for the evaluation of focal liver lesions in children.

INTRODUCTION: Contrast-enhanced ultrasound (CEUS) is a widely used diagnostic method. In adults, it has been proven to be a useful alternative to CT and MRI for the characterisation of focal liver lesions (FLLs). However, since there is no official paediatric licensing for any ultrasound contrast agents in Europe, its use has been restricted. PURPOSE: To retrospectively outline our experience with CEUS as a tool for the characterisation of FLLs in paediatric patients. METHODS: An eleven-year retrospective single-centre study. During this period, we identified 287 CEUS examinations performed on children, of these 36 were relevant first-time examinations with the aim of characterising a focal liver lesion. Clinical and radiological data were collected from the hospital chart. RESULTS: The overall agreement between the CEUS diagnosis and the reference diagnosis for benign versus malignant differentiation was 75%. When analysing conclusive CEUS examinations only, the overall agreement was 96%. The specificity for correctly characterising a lesion as benign was 96%, and the negative predictive value was 100%. No side effects from CEUS were detected. CONCLUSIONS: Our study reinforces that CEUS can be useful in the medical workup for the identification and classification of focal liver lesions in children.

Contrast-Enhanced Ultrasound for identifying circulatory complications after liver transplants in children.

Our main goal with this study was to share our off-label experience with CEUS for identifying circulatory complications after liver transplantation in children. A total of 74 CEUS examinations performed on 34 pediatric patients who underwent a liver transplant were retrospectively included. About 53% of the examinations were performed on children 2 years old or younger. About 82% of the examinations were performed within 30 days from the transplant. About 62% of patients were transplanted due to a cholestatic disease, 11% due to a metabolic disease, 8% were re-transplanted due to graft failure, and 19% was due to other conditions. BA was the most common reason for transplantation and represented 38% of patients. About 38% of the transplantations were performed with whole grafts from DD, 40% with split liver grafts, and 22% with left lateral segments from LD. For diagnosing arterial circulatory complications, the PPV was 80%. For diagnosing portal vein circulatory complications, the PPV was 66.7%. NPV was 100%. In 28% of the examinations, the examiner could not visualize the normal arterial blood flow without CEUS. CEUS is a non-invasive and safe imaging technique that seems valuable in these patients and further efforts are needed to license its use in the post-transplant setting.

Contrast-enhanced ultrasound using sulfur hexafluoride is safe in the pediatric setting.

Background Contrast-enhanced ultrasound (CEUS) by using sulfur hexafluoride microbubbles is not licensed for use in children, but its off-label use is widespread. Purpose To outline our experience with the off-label use of CEUS in children, specifically with regards to safety. Material and Methods We retrieved all records of 10681 patients aged under 18 years who underwent abdominal ultrasound (US) January 2004 to December 2014. We then identified those who underwent an abdominal CEUS using sulfur hexafluoride microbubbles. Electronic patient charts were used to verify the indication for contrast agent, dose, possible adverse effects as well as information on patient height, weight, and age. Results We identified 173 patients (mean age, 11 years; range, 0.1-18 years) who underwent a total of 287 CEUS exams. Of all exams, 46% were performed on the native liver, 31% on a transplanted liver, and 23% on other organs. The indications were "circulatory status?" (40%), "characterization of lesion?" (40%), and miscellaneous (20%). Mean contrast dose was 2.3 mL (range, 0.1-8.1 mL). No immediate adverse effects were recorded. One patient experienced itching the day after, but this was considered to be a reaction to concomitantly administered fentanyl. Conclusion The use of intravenous ultrasound contrast seems safe in patients aged under 18 years and our results do not support the current practice to restrict the use of CEUS in children.

Liver transplantation in the Nordic countries - An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982-2013.

AIM AND BACKGROUND: The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013. MATERIALS AND METHODS: The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report. RESULTS: Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004-2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively. CONCLUSION: The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).

Peg-IFN and ribavirin treatment for recurrence of genotype 2 and 3 hepatitis C after liver transplantation.

BACKGROUND: Relapse of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. Tolerance for treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV) is suboptimal and withdrawals due to adverse events frequent. We sought to improve tolerance for treatment to improve outcome. METHODS: We used concentration-guided RBV dosing to achieve an intended 10 µmol/L concentration with darbepoetin support in combination with peg-IFN alfa-2a, 180 µg for genotype 1 and 135 µg for genotype 2/3 to improve tolerance. RESULTS: A total of 51/54 patients (94%) completed a full treatment course. In the per-protocol analysis 43% of patients (22/51) achieved sustained virological response (SVR), 82% with HCV genotype 2/3 and 22% with genotype 1, p = 0.0001. Patients with IL28B CC achieved SVR in 73% (8/11) and patients with non-CC in 33% (14/43), p = 0.016. Patients with mild fibrosis (fibrosis stage 1-2) achieved SVR in 56% (15/27), and patients with advanced fibrosis (fibrosis stage 3-4) in only 26% (7/27), p = 0.0267. CONCLUSIONS: Concentration-guided RBV dosing with darbepoetin support substantially improves tolerance and offers high adherence to a full peg-IFN and RBV treatment course in patients with post-transplant HCV relapse. With this approach genotype 2 and 3 infections can be treated cost-effectively post-transplant. Genotype 1, IL28B non-CC genotype, and advanced fibrosis predicted a low SVR rate.

Introducing hand-assisted retroperitoneoscopic live donor nephrectomy: learning curves and development based on 413 consecutive cases in four centers.

BACKGROUND: Hand-assisted and retroperitoneoscopic techniques reduce the risk of bleeding and intraabdominal complications in living donor nephrectomy (LDN). This study reports on our four-center experience, development, and learning curves from the first 413 LDNs using a hand-assisted retroperitoneoscopic (HARS) technique. METHODS: The first 413 consecutive donors operated on using HARS were included in the study. Donor demographics, perioperative and postoperative data, complications, and recipient outcomes have been compiled. The data were analyzed as a whole and separately for each center, looking at center differences and learning curves over time. RESULTS: Significant differences were found in donor demographics between centers for the variables: age, body mass index, number of arteries, and side of operation. Mean operating time was 170.2 min, with significant differences between centers. Operating time was also significantly influenced by learning curves, sex/body mass index, and side of operation. Warm ischemia time differed significantly between centers and was influenced by center-wise learning and number of arteries. Overall conversion rate was 2.4% and differed significantly between centers. There was no mortality and no intraabdominal complications. Apart from the conversions and one pulmonary embolism, there were no major intraoperative or postoperative complications. Overall 3-month graft survival was 99%, with 96% immediate onset of function and 1% ureteral complications. CONCLUSIONS: The HARS technique reduces the risk of intraabdominal complications. It can be implemented with excellent donor and recipient outcomes despite different population demographics and center/surgeon-related tradition and experience. On the basis of our experience, we recommend the technique to increase the safety margin of LDN.

Living-related liver transplantation in children--a single center evaluation of the outcome of donor candidates and recipients.

The aim was to study the outcome of donor candidate investigations for living-related donor liver transplantation from adult to child. The charts of 25 donor candidates were reviewed. All 22 recipients, of whom 18 had BA, were already listed for DD organ transplantation. Eleven donor candidates were accepted. Seven of them successfully donated the left lateral liver segment. At follow-up, all donors and recipients were well from the surgery. However, one donor developed Crohn's disease. In the four remaining cases the recipient deteriorated before transplantation was possible or other surgical approaches were utilized. For three candidates the investigations were never finalized, due to either clinical deterioration of the recipient or the availability of a DD organ. Eleven donor candidates were rejected. Four of them (three being parents of BA patients) had liver abnormalities. Another three were rejected for cardiopulmonary disorders and the remaining four for other reasons. We conclude that only seven out of 25 (28%) candidates donated a liver segment. The fact that parents of BA patients have potential liver pathology may be of importance for the understanding of the etiology of the disease and have possible implications for the choice of donors.

High adherence with a low initial ribavirin dose in combination with pegylated-IFN alpha-2a for treatment of recurrent hepatitis C after liver transplantation.

Patients with recurrent hepatitis C after liver transplantation often cannot tolerate full dose of pegylated interferon (peg-IFN) and ribavirin (RBV) and are often withdrawn prematurely from treatment. We chose a low initial RBV dose, later increased due to tolerance to a mean dose of 600 mg daily (range 200-1000 mg daily) in combination with a peg-IFN alpha-2a 180 mcg weekly in an effort to improve tolerance and minimize withdrawals. 16 patients with hepatitis C recurrence and 1 with de novo HCV infection with a mean age of 54 y (range 43-66 y), 71% males, were treated. All patients completed the intended treatment schedule 24 weeks for genotype 2 and 3 and 48 weeks for genotype 1 and 4. Early viral response was achieved in 12 (71%), non-response in 1 patient with genotype 4, and sustained viral response in 4/5 (80%) patients with genotype 2 or 3 and 3/11 (27%) with genotype 1, p<0.05. To conclude, we found that utilizing a low initial daily RBV dose, later increased due to tolerance in combination with peg-IFN alpha-2a 180 microg weekly, was successful. Hence, all patients completed a full treatment course, which also offered a reasonable efficacy.

Hepatitis C impairs survival following liver transplantation irrespective of concomitant hepatocellular carcinoma.

BACKGROUND/AIMS: Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis. METHODS: Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries in a 17-year period were included. For comparison a group of patients with non-viral chronic liver disease (n=1552) was used. RESULTS: Two hundred and fifty-three (90%) patients received a first liver allograft. HCC was found in 38% of the explanted livers. Survival at 1, 3 and 5years was 82%, 69% and 61% vs. 85%, 80% and 76% for the comparison group (p<0.0001), this survival difference was also evident when excluding patients with HCC (p=0.007). HCV patients with HCC had 1, 3 and 5year survival of 73%, 52% and 46% compared with 88%, 80% and 71% for the HCV patients without HCC (p=0.0005). In an intention-to-treat analysis (from time of acceptance to the waiting list) HCV was also associated with an impaired survival. CONCLUSIONS: HCV cirrhosis, which is now also an important indication for LTX in the Nordic countries, and significantly impairs survival following LTX. Concomitant HCC and donor age are the two most important factors contributing to an impaired survival.

Long-term consequences of domino liver transplantation using familial amyloidotic polyneuropathy grafts.

Domino liver transplantation (DLT) using grafts from patients with familial amyloidotic polyneuropathy (FAP) is an established procedure at many transplantation centers. However, data evaluating the long-term outcome of DLT are limited. The aim of the present study was to analyze the risk of de novo polyneuropathy, possibly because of amyloidosis, and the patient survival after DLT. At our department, 28 DLT using FAP grafts were conducted between January 1997 and December 2005. One patient was twice subjected to DLT. Postoperative neurological monitoring of peripheral nerve function was performed with electroneurography (ENeG) in 20 cases. An ENeG index based on 12 parameters was calculated and correlated to age and/or height. Three patients developed ENeG signs of polyneuropathy 2-5 years after the DLT, but with no clinical symptoms. The 1-, 3- and 5-year actuarial patient survival in hepatocellular carcinoma (HCC) patients (n = 12) and non-HCC patients (n = 15) was 67%, 15%, 15% and 93%, 93%, 80%, respectively (P = 0.001). Development of impaired nerve conduction in a proportion of patients may indicate that de novo amyloidosis occurs earlier than previously expected. Survival after DLT was excellent except in patients with advanced HCC.

The Stockholm experience with ABO-incompatible kidney transplantations without splenectomy.

BACKGROUND: ABO-incompatible kidney transplantations have previously only been performed after several pre-operative sessions of plasmapheresis followed by splenectomy, and with the conventional triple-drug immunosuppressive protocol being reinforced with anti-lymphocyte globulin and B-cell-specific drugs. We have designed a protocol without splenectomy, based on antigen-specific immunoadsorption, rituximab and a conventional triple-drug immunosuppressive protocol. METHODS: The protocol called for a 1-month pre-transplantation conditioning period, starting with one dosage of rituximab and followed by full-dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific immunoadsorption was performed on pre-transplantation days -6, -5, -2 and -1. After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was administered. Postoperatively, three more apheresis sessions were given every third day. RESULTS: Twenty-one patients have received transplants with this protocol. The ABO-antibodies (Abs) were readily removed by the antigen-specific immunoadsorption and were kept at a low level post-transplantation by further adsorptions. There were no side effects, and all but one patient have normal renal transplant function. CONCLUSIONS: We conclude that after one infusion each of rituximab and IVIG, and antigen-specific immunoadsorption, blood-group incompatible renal transplantations can be performed with standard immunosuppression and without splenectomy, and with excellent short- and long-term results.