Long-term outcome after liver transplantation for hepatic schistosomiasis: a single-center experience over 15 years.

Our objective was to study the long-term outcomes of patients who had undergone liver transplantation because of schistosomiasis at our institute over the last 15 years. Four hundred forty-one patients underwent liver transplantation at our institute, and 14 did so for schistosomiasis. The survival of patients who underwent transplantation for schistosomiasis was compared with that of patients who underwent transplantation for other liver diseases. Survival curves were drawn via the Kaplan-Meier method and were compared with the log-rank test. P < 0.05 was considered significant. All 14 patients were male, and the average age was 56.8 ± 8.4 years. The average Model for End-Stage Liver Disease score was 18.2 ± 5.6, and the average Child-Pugh score was 10.6 ± 1.2. All patients had splenomegaly; pretransplant variceal bleeding occurred in 7 patients (50%), and portal vein thrombosis was diagnosed in 5 patients (36%). Patient survival was 75% 1 year after transplantation and 75% at the end of follow-up because no patients were lost after the first year. Patients who underwent transplantation for other causes achieved survival rates of 86% and 76% 1 and 10 years after transplantation, respectively. There was no significant survival difference between the 2 groups (P = 0.66). All patients who survived the early posttransplant period had functioning liver grafts with no reported diagnoses of schistosomiasis in the new grafts. In conclusion, liver transplantation for patients with schistosomiasis has a favorable outcome with no risk of reactivation.

Three-dimensional tumor volume and serum alpha-fetoprotein are predictors of hepatocellular carcinoma recurrence after liver transplantation: refined selection criteria.

Total tumor volume (TTV), as a better predictor of hepatocellular carcinoma (HCC) recurrence after liver transplant, has been explored by our center. Some tumors are not typically spherical but rather ellipsoid or spheroid, and calculating their TTV based on one dimension only may overestimate their volume and exclude them from candidacy for transplantation. Our aim was to study the actual tumor volume (ATV) calculated using the ellipsoid formula and assess its impact on recurrence. HCC patients transplanted between 1990 and 2010 at University of Alberta Hospital were analyzed. Tumor volumes were calculated using both formulas: [(4/3) πr(3)] (r = max. radius) and [(4/3) πabc] (a, b, c = the 3 radiuses). A total of 115 patients were included with a mean follow-up of 4.99 ± 4.23 yr. Five-yr recurrence-free survival was 79.8%. Univariate analysis for predictors of recurrence included: maximum tumor diameter, ATV, TTV, and alpha-fetoprotein (AFP) ≥ 400 ng/mL. Multivariate analysis showed that ATV and AFP ≥ 400 ng/mL were the only predictors of recurrence. Combining both variables provides better predication of recurrence with accuracy that exceeds 80%. Three-dimensional calculation of tumor volume is of critical importance for the group of patients with ellipsoid tumors where volumes are overestimated with the spherical formula and could lead to inappropriate exclusion from transplant.

How do transplant surgeons accomplish optimal portal venous flow during living-donor liver transplantation? Noninvasive measurement of indocyanine green elimination rate.

BACKGROUND: Balancing donor safety and graft volume is difficult. We previously reported that intentional modulation of portal venous pressure (PVP) during living-donor liver transplantation (LDLT) is crucial to overcoming problems with small-for-size grafts; however, detailed studies of portal venous flow (PVF) and a reliable parameter are still required. PATIENTS AND METHODS: The elimination rate (k) of indocyanine green (ICG) was measured in 49 adult LDLT recipients. PVP was controlled during LDLT, with a target of <20 mm Hg. ICG reflects hepatocyte volume and effective PVF. The kICG value is divided by the graft weight to calculate PVF. Recipients were divided into 2 groups: those with severe and/or fatal complications within 1 month after LDLT and those without. RESULTS: Survival rates and postoperative profiles were significantly different between the 2 groups. Univariate analysis showed significant differences in ABO blood group, final PVP, final kICG, and the final kICG/graft weight value; however, multivariate analysis showed that only the kICG/graft weight value was significant. The cutoff level for the final kICG/graft weight value for predicting successful LDLT was 3.1175 × 10(-4)/g. CONCLUSION: Accurate evaluation and monitoring of optimal PVF during LDLT should overcome the use of small-for-size grafts and improve donor safety and recipient outcomes.

Can children catch up in growth after living donor liver transplantation?

Several studies have shown improved growth after liver transplantation, but long-term follow-up data have been lacking. This study was aimed at evaluating the ability of children to catch up in height after living donor liver transplantation (LDLT) and at clarifying factors affecting growth. Growth was assessed by serial height measurements performed during follow-up. Standardized height scores (z scores) were calculated for each patient preoperatively (at the baseline) and at 1, 2, 3, 5, 10, and 15 years after LDLT. The risk potential of several preoperative and postoperative variables was evaluated. A total of 237 patients, including 159 females (67.1%), met the inclusion criteria. The mean age at the time of transplant was 3.89 +/- 0.28 years. The mean z score was -1.70 +/- 0.09, whereas the baseline height deficit was -6.50 +/- 0.39 cm. After LDLT, the z score improved significantly and reached -0.64 +/- 0.14 by the end of the first year. The best height improvement was seen after 10 years (-0.33 +/- 0.16). However, significant growth retardation remained at 15 years (-0.47 +/- 0.17). Height showed 3 distinct phases after transplantation: a growth spurt, a plateau phase, and a late declining phase. Univariate and multivariate analyses showed that children under 2 years and those with the most growth retardation at the time of LDLT achieved the best height gain in the first year. Late growth retardation was related to the baseline z score, ABO-incompatible grafts, and graft dysfunction. In conclusion, children have the potential ability to catch up in growth to normal levels after LDLT; they can show impressive height gains in the first year followed by protracted improvement over 10 years and then late growth retardation. Young age is a determinant for early height gain, whereas ABO-incompatible grafts and graft dysfunction are determinants for late growth retardation. In contrast, the baseline z score is a determinant for both.

Portal pressure <15 mm Hg is a key for successful adult living donor liver transplantation utilizing smaller grafts than before.

To prevent small-for-size syndrome in adult-to-adult living donor liver transplantation (A-LDLT), larger grafts (ie, right lobe grafts) have been selected in many transplant centers. However, some centers are investigating the benefits of portal pressure modulation. Five hundred sixty-six A-LDLT procedures using right or left lobe grafts were performed between 1998 and 2008. In 2006, we introduced intentional portal pressure control, and we changed the graft selection criteria to include a graft/recipient weight ratio >0.7% instead of the original value of >0.8%. All recipients were divided into period I (1998-2006, the era of unintentional portal pressure control; n = 432) and period II (2006-2008, the era of intentional portal pressure control; n = 134). The selection of small-for-size grafts increased from 7.8% to 23.9%, and the selection of left lobe grafts increased from 4.9% to 32.1%. Despite the increase in the number of smaller grafts in period II, 1-year patient survival was significantly improved (87.9% versus 76.2%). In 129 recipients in period II, portal pressure was monitored. Patients with a portal pressure <15 mm Hg demonstrated better 2-year survival (n = 86, 93.0%) than patients with a portal pressure >or=15 mm Hg (n = 43, 66.3%). The recovery from hyperbilirubinemia and coagulopathy after transplantation was significantly better in patients with a portal pressure <15 mm Hg. In conclusion, our strategy for A-LDLT has changed from larger graft-based A-LDLT to controlled portal pressure-based A-LDLT with smaller grafts. A portal pressure <15 mm Hg seems to be a key for successful A-LDLT.

Pediatric living-donor liver transplantation for acute liver failure: analysis of 57 cases.

We reviewed 57 pediatric patients admitted with acute liver failure to Kyoto University Hospital in Japan over a period of 15 years to compare the etiology and the long-term outcome of infants and children after living donor liver transplantation (LDLT). Patients were divided into two groups according to age at the time of liver transplantation, infants group (<1 year, n = 20), and children group (1-18 years, n = 37). The overall survival rates were 73.6%, 69.5% and 67.2% at 1, 5, and 10 years after LDLT respectively. Age of recipients at the time of LDLT had a strong impact on their outcome, Children had significantly better outcome than infants (P = 0.001). Surgical complications were comparable between both groups. Infants had higher rates of acute cellular rejection (ACR), which was associated with features of hepatitis in many cases. Refractory ACR was the leading cause of death in eight out of 12 infants, while it resulted in loss of one child only. Cox's proportional hazard regression model was used to examine potential risk factors for graft loss and it shows that age <1 year was associated with high risk of graft loss [hazard ratio (HR) = 11.393; CI = 1.961-76.1763] (P < 0.05). In conclusion, Infants had poorer prognosis than children and refractory ACR was the leading cause of death. Using additional immunosuppressant for cases with severe and atypical rejections is recommended.

Two different methods for donor hepatic transection: cavitron ultrasonic surgical aspirator with bipolar cautery versus cavitron ultrasonic surgical aspirator with radiofrequency coagulator-A randomized controlled trial.

The aim of this study was to compare the Cavitron ultrasonic surgical aspirator (CUSA) with bipolar cautery (BP) to CUSA with a radiofrequency coagulator [TissueLink (TL)] in terms of efficacy and safety for hepatic transection in living donor liver transplantation. Twenty-four living liver donors (n = 12 for each group) were randomized to undergo hepatic transection using CUSA with BP or CUSA with TL. Blood loss during parenchymal transection and speed of transection were the primary endpoints, whereas the degree of postoperative liver injury and morbidity were secondary endpoints. Median blood loss during liver transection was significantly lower in the TL group than in the BP group (195.2 +/- 84.5 versus 343.3 +/- 198.4 mL; P = 0.023), and liver transection was significantly faster in the TL group than in the BP group (0.7 +/- 0.2 versus 0.5 +/- 0.2 cm(2)/minute; P = 0.048). Significantly fewer ties were required during liver transection in the TL group than in the BP group (15.8 +/- 4.8 versus 22.8 +/- 7.9 ties; P = 0.023). The morbidity rates were similar for the 2 groups. In conclusion, CUSA with TL is superior to CUSA with BP for donor hepatectomy in terms of blood loss and speed of transection with no increase in morbidity.

Living-related liver transplantation in patients with variceal bleeding: outcome and prognostic factors.

BACKGROUND: Liver transplantation currently represents the ultimate therapy for bleeding esophageal varices in patients with liver cirrhosis. It is the only therapy that cures both portal hypertension and the underlying liver disease. The outcome of liver transplantation is thought to be correlated with several factors. In this study, the clinical outcome of living-related liver transplantation (LRLT) was evaluated in patients with variceal bleeding, and the prognostic indicators of short-term survival in these patients were identified. METHODS: We reviewed retrospectively 121 patients with a history of variceal bleeding who had received LRLT from 1998 to 2006. The clinical outcomes were analyzed, and the risk factors for short-term survival were defined. RESULTS: The 3-month survival rate of patients with variceal bleeding was 83.4%, while that of non-bleeders was 87%. Sepsis was the commonest cause of death in both groups. Portal vein diameter and blood transfusion were the only independent prognostic factors for short-term survival among variceal bleeders. CONCLUSION: The outcome of LRLT in recipients with variceal bleeding is based on the improvement of portal hemodynamics, by minimizing intraoperative blood loss and subsequent blood transfusion.

Is biliary bile acid a good predictor for acute cellular rejection in living donor liver transplantation?

BACKGROUND: In liver transplantation, acute cellular rejection (ACR) is still a major complication that can lead to mortality. Bile secretion has been considered as a marker of early graft function. METHODS: The study included 41 adults who received living donor liver transplantation (LDLT) at Kyoto University Hospital between April 2007 and February 2008. The patients were stratified according to the presence or absence of ACR. Bile samples were collected from donors once and from recipients every other day for the first 2 weeks after transplantation. Total bile acid (BA) and taurine-conjugated bile acid (TCBA) in bile were measured by magnetic resonance spectroscopy. The recipient/donor (R/D) BA ratio and R/D TCBA ratio were calculated. RESULTS: The ACR group (n=12) showed a greater decrease in BA post-transplantation than the non-ACR group, but this difference was not statistically significant. On both day 7 and day 9 post-transplantation the R/D TCBA was significantly different between the two groups (P=0.038 on day 7 and P=0.036 on day 9). The R/D TCBA ratio >or=0.5 on days 7 and 9, and >or=0.38 on day 11 post-transplantation were associated with better ACR-free survival. CONCLUSION: The recipient/donor TCBA ratio can be a predictor for ACR after LDLT as early as post-transplantation day 7.

Incidence, Characteristics, and Prognosis of Incidentally Discovered Hepatocellular Carcinoma after Liver Transplantation.

Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants. Methods. We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma. Results. Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P < 0.001). There was no significant difference between groups regarding patient survival; 5-year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P = 0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P = 0.016). Conclusions. iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC.

Outcome of critically-ill children after living-donor liver transplant.

OBJECTIVES: The outcome of children who had living-donor liver transplant was analyzed according to their status before transplant, and we analyzed the outcome of critically ill patients. MATERIALS AND METHODS: This was a retrospective analysis of children who received primary living-donor liver transplant at Kyoto University Hospital. According to the criteria of the United Network for Organ Sharing, we divided patients into 3 groups: Group A patients had been admitted to the intensive care unit before living-donor liver transplant; Group B patients were hospitalized but did not require intensive care unit stay; and Group C patients were living at home and underwent elective transplant. RESULTS: A total 685 patients met inclusion criteria. Children in Group A were younger than Group B and received liver grafts from younger donors than Group B and C. Group A patients had marked impairment in liver and renal function and coagulation profile and needed higher volumes of fresh frozen plasma transfusions. Group A patients had significantly worse outcomes and early patient death than the other group; Group A patient survival was 68.3%, 63.2%, 60.1%, and 56.1% at 1, 5, 10, and 15 years after living-donor liver transplant (P < .0001). Group A had worse graft survival than other groups (P < .0001), and Group A graft survival was 68.3%, 65.9%, 54.1%, and 49.9% at 1, 5, 10, and 15 years. Low gamma-glutamyl transpeptidase was an independent risk factor for patient death in Group A (hazard ratio, 1.004; 95% confidence interval, 1.0-1.007) (P < .05). Group A patients had a higher rate of multidrug-resistant hospital-acquired infections. CONCLUSIONS: Children who were admitted to the intensive care unit prior to living-donor liver transplant had marked impairment of pretransplant laboratory parameters and worse outcome than other groups.

Occult hepatitis B virus infection in Egypt.

The emerging evidence of the potentially clinical importance of occult hepatitis B virus (HBV) infection (OBI) increases the interest in this topic. OBI may impact in several clinical contexts, which include the possible transmission of the infection, the contribution to liver disease progression, the development of hepatocellular carcinoma, and the risk of reactivation. There are several articles that have published on OBI in Egyptian populations. A review of MEDLINE database was undertaken for relevant articles to clarify the epidemiology of OBI in Egypt. HBV genotype D is the only detectable genotype among Egyptian OBI patients. Higher rates of OBI reported among Egyptian chronic HCV, hemodialysis, children with malignant disorders, and cryptogenic liver disease patients. There is an evidence of OBI reactivation after treatment with chemotherapy. The available data suggested that screening for OBI must be a routine practice in these groups of patients. Further studies needed for better understand of the epidemiology of OBI among Egyptian young generations after the era of hepatitis B vaccination.

Recovery of locked-in syndrome following liver transplantation with calcineurin inhibitor cessation and supportive treatment.

BACKGROUND: Locked-in syndrome represents the most severe form of central pontine myelinolysis (CPM) and has been associated with a dismal outcome. CASE REPORT: In this report we describe a case of severe locked-in syndrome after liver transplantation with spontaneous recovery with cessation of calcneurin inhibitor therapy and supportive treatment. A 54-year old male received deceased-donor liver transplantation and developed decreased level of consciousness with spastic quadriplegia. A diagnosis of central pontine myelinolysis with extrapontine manifestations was confirmed by magnetic resonance imaging. His immunosuppresion was modified by switching from tacrolimus to sirolimus and addition of prednisone. The patient started to recover from symptoms fourth months after transplantation. CONCLUSIONS: Tacrolimus is known to have neurotoxic side effects and it may precipitate CPM in patients who have predisposing factors. Sirolimus and steroids should be considered as safe and an effective alternative for immunosuppression in the setting of CPM after liver transplantation.

Pre transplant serum magnesium level predicts outcome after pediatric living donor liver transplantation.

BACKGROUND: Hypomagnesaemia is a frequent complication after liver transplantation (LTx) however; magnesium is not routinely replaced in the perioperative period. MATERIAL/METHODS: The incidence of hypomagnesaemia before and after pediatric LTx was studied in 673 pediatric patients who underwent living-donor liver transplantation (LDLT). RESULTS: The mean serum Mg levels before LTx was normal, 2.03 ± 0.28 mg/dl, exhibited marked decrease on 5th postoperative (PO) day, 1.79 ± 0.45, p<0.001, comparing with the pre-transplant value. It reached its nadir in the 1st PO month, p<0.001. Up to the 5th PO year, serum Mg did not achieve the lower limit of normal, 1.77 ± 0.24, p<0.001 and incidence of hypomagnesaemia was 60.7% (242/399). Univariate analyses of variables that can predict graft loss and patient death after LDLT demonstrated that recipient factors, pre and post transplant serum Mg and blood product transfusions were potentially risk factors significantly affected the outcome. Multivariate analysis of potential risk factors showed that pre transplant serum Mg <1.8 mg/dl, (Hazard ratio (HR) 2.362 [confidence interval (CI) 1.350-4.133]; p=0.003) and pre transplant BUN, (HR 1.046 [CI 1.014-1.079]; p=0.005) were independent predictors of graft loss and patient death. CONCLUSIONS: hypomagnesaemia is common before and after pediatric LDLT. Pre transplant hypomagnesaemia and high BUN are independent risk factors for graft loss or patient death. Pre transplant hypomagnesaemia patients exhibited decreased survival of their graft. Post transplant hypomagnesaemia was a potentially risk factor for graft loss.