Section 1. Image evaluation of fatty liver in living donor liver transplantation.

Preoperative evaluation of donors for living-donor liver transplantation aims to select a suitable donor with optimal graft quality and to ensure donor safety. Hepatic steatosis, a common finding in living liver donors, not only influences the outcome of liver transplantation for the recipient but also affects the recovery of the living donor after partial hepatectomy. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but it is invasive, and results are vulnerable to sampling error. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. This article describes potential clinical applications for liver fat quantification of imaging methods for fat detection and quantification, with an emphasis on the advantages and limitations of ultrasonography, computed tomography, and magnetic resonance imaging for quantifying liver fat.

Section 8. Management of portal venous complications in pediatric living donor liver transplantation.

Portal vein (PV) complications after living donor liver transplant (LDLT) have been a major concern in pediatric liver transplantation. The incidence of PV complications is more in pediatric (0%-33%) than in adult recipients. Early diagnosis and treatment of PV complications may ensure optimal graft function and good recipient survival. Small preoperation PV size (<4 mm) and slow portal flow (<10 cm/s) combined with lower hepatic artery resistance index (<0.65) are strong warning signs that may predict the development of post LDLT PV complications. Portal vein angioplasty/stenting is conventionally performed through the percutaneous transhepatic approach; however, this can also be performed through transjugular, trans-splenic, and intraoperative approaches. Depending on the situation, using optimal method is the key point to minimize complication (5%) and gain high success rate (80%). PV occlusion of greater than 1 year with cavernous transformation seems to be a factor causing technical failure. Good patency rate (100%) with self-expandable metallic stents was noted in long-term follow-up. In conclusion, PV stent placement is an effective, long-term treatment modality to manage PV complications after pediatric LDLT. Early diagnosis and treatment are essential to maximize the use of stent placement and achieve good success rates.

Liver transplantation for primary biliary cirrhosis in a hepatitis endemic region: a single-center Asian experience.

From March 1984 to November 2008, we performed 539 primary liver transplantations (LTs). Nineteen (19, 3.5%) were transplanted for end-stage liver disease secondary to primary biliary cirrhosis (PBC). There were 17 (89%) female and 2 (11%) male recipients. The overall mean age was 50.3 ± 6.3 yr. The mean model for end-stage liver disease, and Child-Turcotte-Pugh scores were 20.7 ± 2.1, and 11.0 ± 0.5, respectively. There were 2 (11%) United Network for Organ Sharing status 3, 16 (84%) 2B, and 1 (5%) 2A patients. Fourteen patients (14, 73.7%) underwent living donor LT, and five patients (26.3%) received deceased donor LT. The primary immunosuppression consisted of cyclosporine (n = 5) and tacrolimus (n = 14). Liver function returned to normal one month after transplantation. The overall mean follow-up was 5.8 ± 0.8 yr (range, four months to 15.7 yr). The overall one-, three-, and five-yr survival rates were 94.7%, 89.2%, and 89.2%, respectively. Without hepatitis B virus (HBV) prophylaxis, one patient acquired de novo HBV infection after receiving a graft from an anti-HBc(+) donor. Another patient developed recurrent hepatitis C infection and expired 25 months after transplantation. Our results showed that HBV prophylaxis was effective not only against de novo infection, but it also worked on pre-transplant HBV carrier with PBC and helped in virus clearance.

Solitary pulmonary nodule in the liver transplant candidate: importance of diagnosis and treatment.

Our objectives were to define the incidence and etiology of solitary pulmonary nodules (SPNs) in patients undergoing living donor liver transplantation (LDLT), describe a diagnostic approach to the management of SPNs in LDLT, and define the impact of SPNs on the overall survival of adult LDLT recipients. Nine patients (9/152, 5.9%) were diagnosed with an SPN on the basis of chest radiography findings during the pretransplant survey. All were male. The mean age was 52 years. All the patients had hepatitis B virus-related cirrhosis with hepatocellular carcinoma. All were asymptomatic for the lung lesion. All underwent contrast-enhanced chest computed tomography (CT) to verify the presence and possible etiology of the SPNs. In 3 cases, CT was used to definitely determine that there was no pulmonary nodule; in 2, CT led to a definite diagnosis of pulmonary tuberculosis. In 4, CT led to a definite identification of an SPN but not to an etiological diagnosis. Two patients underwent outright thoracoscopy and biopsy of their SPNs. Biopsy showed cryptococcosis in both patients. One received a therapeutic trial of an antituberculosis treatment, and repeat CT after 1 month showed a regression in the size of the SPN. A diagnosis of tuberculosis was made. One patient had an inconclusive whole body positron emission tomography scan and subsequently underwent thoracoscopy where biopsy showed tuberculosis. A concomitant malignancy, either primary lung cancer or metastasis from the liver tumor, was not identified. All patients were surviving with their original grafts and were lung infection-free. The overall mean posttransplant follow-up was 54 months (range = 33-96 months).

Routine microsurgical biliary reconstruction decreases early anastomotic complications in living donor liver transplantation.

Biliary reconstruction using a microsurgical technique in living donor liver transplantation was routinely performed on 88 grafts primarily transplanted into 85 patients. All procedures were performed under a microscope by a single microsurgeon. Except for biliary atresia and Alagille syndrome, duct-to-duct reconstruction was performed. Stents were not used. The outcomes with microsurgical biliary reconstruction (MB) were compared with the outcomes of a cohort of 86 grafts in 85 patients that underwent conventional biliary reconstruction (CB). The identification of complications included only up to 12 months of follow-up for each recipient in both groups. The average graft duct sizes were 2.8 mm for MB and 3.4 mm for CB. Most complications occurred in the first 15 cases with MB, and these cases were considered to constitute the learning curve phase. The MB complication rate was 46.7% in the first 15 cases, 20.0% in the next 15 cases, and 5.4% in the last 55 cases. When the learning curve phase was excluded, the overall complication rate over time with MB (8.9%) was significantly lower than that with CB (21.9%). CB increased the risk of biliary complications by 2.5 times (relative risk: 2.5; attributable risk: 128; odds ratio: 2.9). In conclusion, routine MB is a technical innovation that leads to decreased early anastomotic complications in living donor liver transplantation.

Intimal dissection of the hepatic artery following transarterial embolization for hepatocellular carcinoma: an intraoperative problem in adult living donor liver transplantation.

The objective of this study was to describe the relationship between intimal dissection (ID) in the recipient hepatic artery (HA) and transarterial embolization (TAE) and highlight the reconstructive methods for the different types of ID encountered in living donor liver transplantation (LDLT). Fifty-four patients with hepatocellular carcinoma underwent LDLT. ID was classified as mild, moderate, or severe, and this classification was based on the extent of intimal injury. Mild, moderate, or severe ID were defined as ID that was less than one-quarter of the circumference of the HA, had reached one-half of the circumference of the HA, or was more than one-half of the circumference of the HA or involved the entire vessel wall, respectively. The reconstructive methods were based on the severity of ID encountered. Forty patients underwent TAE before LDLT, and 23 of these patients (57.5%) had ID. Nine patients had mild ID, 6 had moderate ID, and 8 had severe ID. In the 14 patients who did not undergo TAE, 4 had ID (28.6%; 3 mild and 1 severe). The other 10 patients (71.4%) had normal HA. In mild and moderate ID, the native HA was used after trimming of the HA until a healthy segment was encountered. In severe ID, the HA was reconstructed with alternative vessels. Two HA thromboses occurred postoperatively. TAE increased the risk of developing ID 2-fold. There was no graft loss or mortality in this series due to HA complications. In conclusion, ID of the HA is associated with pretransplant TAE among hepatocellular carcinoma patients undergoing LDLT. Intraoperative recognition of this complication and trimming until good vessel quality is encountered or using alternative vessels are important.

Dual grafts in adult-to-adult living donor liver transplantation: a single center experience in Taiwan.

Volume mismatch is encountered when a single live donor cannot provide adequate graft volume to the recipient with a remnant liver volume which is safe for donation. Our objective is to present our experience in living donor liver transplantation using dual grafts. Record review of 4 dual graft recipients was done. The results were compared with 122 consecutive patients who received a single right lobe. All dual graft recipients were surviving with satisfactory liver function at a median follow-up of 21 months. Two recipients received 1 right and 1 left lobe graft, while the other 2 recipients received 2 left lobe grafts. One donor developed biloma and was managed by percutaneous drainage. The first recipient required re-laparotomy for postoperative bleeding. The second recipient underwent re-laparotomy for bile leak. The third recipient developed grade II decubitus ulcers due to a prolonged sedentary position. When compared with recipients who received a single right lobe, the operative time was prolonged in the dual graft group. There was no apparent increase in the rate of vascular and biliary complications or the incidence of acute cellular rejection. Actuarial patient survivals were comparable in both groups. Dual graft transplantation provides sufficient volume in the recipient without jeopardizing donor safety.

Involvement of autoimmunity against nuclear histone H1 in liver transplantation tolerance.

BACKGROUND: Our recent studies suggested that anti-histone H1 autoantibody (auto-Ab) plays an important role in experimental and clinical liver allograft tolerance as a natural immunosuppressive factor. The present study aimed to explore how the autoimmune response against histone H1 is involved in tolerance induction. METHODS: The measurement of anti-histone H1 auto-Ab and immunohistochemical analysis were performed in serum and liver allografts after orthotopic liver transplantation (OLT). To compare the auto-Ab response against histone H1 between the recipients of rejector (DA-LEW) and tolerogenic (DA-PVG) OLT models, naïve recipients were immunized with calf thymus histone H1. The immunosuppressive state of histone H1-immunized rats was assayed by mixed lymphocyte reaction (MLR). RESULTS: Anti-histone H1 Ab titer was transiently increased during the rejection phase after OLT (days 7-21) in the DA-PVG combination, while no such response was confirmed in the DA-LEW acute rejection model. Nuclear histone H1 antigens were found in the cytoplasm and the extracellular environment in liver allografts at the rejection phase in the tolerogenic model but not in the rejector model, resulting from the transient induction of anti-histone H1 auto-Ab in recipient PVG rats after OLT. Low dose and short-term immunization with histone H1 upregulated the anti-histone H1 Ab titer in naïve PVG rats, which exhibited a low allogeneic immune response, while no such response was found in naïve LEW rats. CONCLUSIONS: These results suggest that the sensitivity to nuclear antigens such as histone H1 may be a key factor determining the acceptance or rejection of donor liver grafts, at least in DA-PVG and DA-LEW combinations.

A simple and inexpensive technique of upper abdominal wall retraction in pediatric liver surgery and transplantation.

In majority of centers, pediatric liver surgery and transplantation involves a team of four at any given time: the surgeon, the first and second assistants, and the instrument nurse. This creates considerable crowding around both operative field and operating table. Mechanical devices have been occasionally employed to solve this problem, but most table-mounted devices are designed for adult patients. Based on our experience with pediatric living donor liver transplantation, we developed a simple, safe, and inexpensive method of upper abdominal wall retraction to facilitate surgical exposure and avoid over-crowding in the sterile field. The key points of this technique are the use of the Mercedes incision for liver transplantation or right subcostal incision with upper abdominal midline extension for hepatic resection and an adult-designed Kent retractor. A pediatric-designed Kent retractor is expensive, unnecessary, and may even cause complications as rib fractures and nerve paralysis. We used this technique in 142 consecutive pediatric living donor liver transplants and 16 major hepatectomies in children without any complication resulting from the exposure. The presented technique is simple, safe, reliable, and inexpensive. It can be used in pediatric liver surgery, as well as general pediatric upper abdominal operations.

Living donor liver transplantation for hepatocellular carcinoma: a single-center experience in Taiwan.

BACKGROUND: Living donor liver transplantation (LDLT) demonstrates certain survival benefits over deceased donor liver transplantation for hepatocellular carcinoma (HCC) but there is no consensus on criteria for the use of LDLT for HCC for hepatocellular carcinoma (HCC) taking into account strategies to improve survival. METHODS: Thirty-five patients (89% men) underwent LDLT for HCC. The mean age was 51 years (range, 22-61). The median disease severity scores were B, 11-20, and 2B for Child-Turcotte-Pugh, Model for End-stage Liver Disease, and United Network for Organ Sharing, respectively. The transplant records were retrospectively analyzed. RESULTS: All were within Milan criteria at time of transplantation. A novel approach to downstaging tumors initially beyond the Milan criteria was evaluated using transarterial embolization or percutaneous ethanol injection. Our initial results were encouraging as recipients whose tumors had been downstaged had not had recurrence to date. Seven (20%) patients underwent hepatectomy for HCC before undergoing transplant. The overall mean posttransplant follow-up in this series was 40.3 months (range, 23-75). The overall posttransplant complication rate requiring intervention was 11%. There was only one malignancy recurrence for an overall recurrence rate of 3%. Vascular invasion and small- for-size transplants did not seem to influence tumor recurrence. The nonestimated recipient 1-year, 3-year, and 5-year survivals were 98%, 96%, and 90%, respectively. CONCLUSION: This review emphasizes the need for early disease recognition and prompt intervention when Milan criteria are met to improve survival from HCC after LDLT.

Atrial septal defect in end-stage liver disease children before and after liver transplantation.

BACKGROUND AND OBJECTIVE: Atrial septal defect (ASD) is a common congenital heart defect. The course and impact of hemodynamically insignificant ASD in end-stage liver disease (ESLD) patients remains to be elucidated. Our objective is to present our experience in live donor liver transplantation in children with secundum type of ASD and to find out whether ASD has an impact on the outcome of liver transplantation. PATIENTS AND METHODS: Fourteen recipients (7 male, 7 female) whose median age was 14.2 months (range, 8-28) were included. The diagnosis of secundum type of ASD was confirmed by transthoracic 2-dimensional Doppler echocardiography preoperatively. The mean Child's score was 9.9, and the mean Pediatric End-stage Liver Disease Score was 14.7. The ASD were classified based on physiologic-hemodynamic (insignificant vs significant) and structural size (small [/=10 mm]) parameters. Only 1 patient showed hemodynamically significant ASD based on echocardiography and cardiac catheterization findings. RESULTS: Six small ASD spontaneously closed during the waiting period for transplantation. Four small ASD spontaneously closed posttransplant. The medium- and large-sized ASD persisted or increased in size posttransplantation. There were no perioperative cardiac complications. There were no neurologic complications. All patients are alive with the original grafts. The median follow-up was 49.7 months (range, 19.8-79.4). CONCLUSION: Hemodynamic insignificant ASD seems to not impact the outcome of liver transplantation in children with ESLD. Further, this series demonstrated that transplantation can be successfully and safely performed in the presence of hemodynamically stable patients with small- to large-sized ASD.

The effects of suplatast tosilate (IPD-1151T) on innate immunity and antigen-presenting cells.

We previously demonstrated that the anti-allergic drug, suplatast tosilate (IPD-1151T), prolonged rat survival after heterotopic heart transplantation (HHT) and suppressed mixed lymphocyte reaction (MLR). In the present study, we investigated the effects of suplatast on T cells, lipopolysaccharides (LPS), or peptidoglycan (PGN)-stimulated cells and dendritic cells (DCs). The addition of suplatast to concanavalin A (ConA) blasts inhibited the proliferation of cells in which the gene expression of T-helper-1 (Th1) and T-helper-2 (Th2) cytokines including interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 were down-regulated with decreased concentration of the IFN-gamma and IL-10 in the supernatants of ConA blast cells. Suplatast also showed down-regulation of the toll-like receptor (TLR)2, TLR4, and CD14 gene expressions on splenocytes stimulated by LPS and PGN, TLR2 or TLR4 agonist, respectively. DCs treated with suplatast expressed lower levels of CD40, CD80, and CD86 and reduced IL-12 production. These results suggest that suplatast may modulate the TLRs on antigen-presenting cells (APCs) and thus block the pathway of Th1/Th2 cytokine production.

Hepatic pseudotumor in long-standing biliary atresia patients undergoing liver transplantation.

A pseudotumor, giant regenerative nodule, or macroregenerative nodule is an unusual benign hepatic lesion in biliary atresia (BA) patients. This tumor may mimic malignant transformation and may preclude liver transplantation (LT). The clinical and imaging surveillance of patients after the Kasai procedure is therefore an important aspect of management of BA patients. Our objective is to report our experience and describe the incidence, imaging, and pathologic features of pseudotumors in BA patients awaiting LT. From August 1990 to December 2006, 133 LTs for BA were performed. Five (3.8%; 4 female, 1 male) patients were diagnosed with pseudotumor. The patients' records were reviewed. The diagnostic imaging modalities used were abdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI). Histologic confirmation of the lesions was obtained in all cases. All underwent the Kasai operation in early infancy. Six of 7 lesions in 4 of 5 patients were demonstrated by pretransplant imaging. Two of 7 tumors were detected by US. Five of 7 lesions were detected by CT, and 5 of 7 lesions were demonstrated by MRI. In 1 patient, the lesion was not seen in the US, CT, or MRI but was found during surgery and confirmed by histology. An additional tumor was found incidentally during histologic examination in a patient previously diagnosed to have 2 tumors by CT and MRI. In another patient diagnosed to have 2 tumors on imaging, pathology revealed only a single tumor. In conclusion, although unusual, pseudotumor should be included in the differential diagnosis of liver masses in BA children.

Living donor liver transplantation in children with congenital heart disease.

BACKGROUND: The occurrence of congenital heart disease (CHD) with congenital biliary disease is uncommon. Our aim is to present our experience in living donor liver transplantation (LDLT) as treatment for end-stage liver disease (ESLD) in children with CHD. METHODS: A review of transplant records from June 1994 to December 2004 was performed. Twenty-three LDLT (13 males, 10 females) recipients were diagnosed to have both CHD and ESLD. RESULTS: CHD diagnoses were made preoperatively using transthoracic two-dimensional color flow Doppler echocardiography. The mean age was 22.3 months. There were 20 (87%) biliary atresia, two (9%) neonatal hepatitis, and one (4%) glycogen storage disease patients. Isolated CHD associated with ESLD included atrial septal defect (11, 48%), pulmonary stenosis (including 2 Alagille syndrome; 4, 17%), patent foramen ovale (4, 17%), ventricular septal defect (1, 4%), and mitral valve prolapse (1, 4%). Complex CHD included atrial septal defect + patent ductus arteriosus + patent foramen ovale (1, 4%), and atrial septal defect + pulmonary stenosis (1, 4%). The median Child's and Pediatric End-stage Liver Disease scores were 9, and 17, respectively. In all, 70% presented with varying degrees of pulmonary congestion pretransplant. There were no perioperative cardiac complications. Posttransplant, the patent foramen ovale in four recipients and atrial septal defect in four recipients closed spontaneously; and two recipients with pulmonary stenosis had their stenoses resolved spontaneously. The overall rejection rate was 17%. There was no mortality. The overall recipient and graft survivals at 1 and 5 years were both 100%. CONCLUSION: LDLT is a safe procedure in a select group of ESLD patients with CHD.

Long-term results of living donor liver transplantation for glycogen storage disorders in children.

Liver transplantation (LT) may be indicated in glycogen storage disorders (GSD) when medical treatment fails to control the metabolic problems or when hepatic adenomas develop. We present our institutional experience with living donor LT (LDLT) for children with GSD. A total of 244 patients underwent primary LDLT at our institution from June 1994 to December 2005. A total of 12 (5%) children (8 female and 4 male) were afflicted with GSD and were not responsive to medical treatment. Nine patients had GSD type I and 3 had GSD type III. The median age at the time of transplantation was 7.27 yr (range, 2.4-15.7). All patients presented with metabolic abnormalities, including hypoglycemia, and lactic acidosis. In addition, 4 patients presented with growth retardation. A total of 11 patients received left lobe grafts and 1 received a right lobe graft. The mean graft-to-recipient weight ratio was 1.25 (range, 0.89-1.61). Two patients had hepatic vein stenoses that were treated by balloon dilatation; 1 patient had bile leak, which settled spontaneously. The overall surgical morbidity rate was 25%. Three patients had hepatic adenomas in the explanted liver. There was a single mortality at 2 months posttransplantation due to acute pancreatitis and sepsis. The mean follow up was 47.45 months. The metabolic abnormalities were corrected and renal function remained normal. In patients with growth retardation, catch-up growth was achieved posttransplantation. In conclusion, LDLT is a viable option to restore normal metabolic balance in patients with GSD when medical treatment fails. Long-term follow-up after LT for GSD shows excellent graft and patient survival.