Bruno Jawan

Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy.

Background:Animal and human studies indicate that genetics may contribute to the variability of morphine efficacy. A recent report suggested that cancer patients homozygous for the 118G allele caused by the single nucleotide polymorphism at nucleotide position 118 in the &mgr;-opioid receptor gene require higher doses of morphine to relieve pain. The purpose of the current study was to investigate whether this polymorphism contributes to the variability of morphine efficacy in women who undergo abdominal total hysterectomy. Methods:After informed consent was obtained, 80 female patients (American Society of Anesthesiologist physical status I or II) scheduled to undergo elective total hysterectomy surgery were enrolled in this study. All patients received general anesthesia and were screened for A118G polymorphism by blood sample. Intravenous morphine patient-controlled analgesia was provided postoperatively for satisfactory analgesia. The authors recorded the morphine consumption doses and demand times. Pain at rest and side effects were measured with rating scales. Results:Forty-three women were A118 homozygous, 19 were heterozygous, and 18 were G118 homozygous. Patients homozygous for G118 required more morphine doses (33 ± 10 mg) to achieve adequate pain relief compared with patients homozygous for A118 (27 ± 10 mg) in the first 24 h (P = 0.02). However, there was no statistically significant difference for morphine consumption at 48 h. Conclusion:Genetic variation of the &mgr;-opioid receptor may contribute to interindividual differences in postoperative morphine consumption. In the future, identifying single nucleotide polymorphisms of patients may provide information to modulate the analgesic dosage of opioid for better pain control.

Evaluation of living liver donors.

Preoperative evaluation of donors for living-donor liver transplantation aims to select a suitable donor with optimal graft quality and to ensure donor safety. There are minor variations in the donor selection process among different centers, but the safety of the donor remains central to the entire process. The potential donors are evaluated in a stepwise manner including medical, physical, laboratory, psychosocial, and imaging assessment to disqualify unsuitable donors as early as possible in the evaluation process. The main goal of the imaging study is to provide an accurate picture of liver vascular anatomy and liver volume measurement for surgical guidance or for exclusion of unsuitable donors. All imaging studies can now be obtained using noninvasive modalities, thereby decreasing the risk associated with the donor evaluation process. This article describes the donor selection practice in our center including the details of the imaging evaluation.

Right Lobe Living Donor Liver Transplantation—Addressing the Middle Hepatic Vein Controversy

Objective To describe our approach in the decision-making for taking the middle hepatic vein with the graft or leaving it with the remnant liver in right lobe live donor liver transplantation. Summary Background Data Right lobe living donor liver transplantation has been successfully performed. However, the extent of donor hepatectomy is still a subject of debate and the main considerations in the decision making are graft functional adequacy and donor safety. Methods An algorithm based on donor-recipient body weight ratio, right lobe-to-recipient standard liver volume estimate, and donor hepatic venous anatomy was used to decide the extent of donor hepatectomy. This algorithm was applied in 25 living donor liver transplant operations performed between January 1999 and January 2002. In grafts taken without the middle hepatic vein, anterior segment tributaries draining into it were not reconstructed. Outcomes between right lobe liver transplants with (Group I) and without (Group II) the middle hepatic vein were compared. Results Ten grafts included the middle hepatic vein and 15 did not. The mean graft to recipient standard liver volume ratio was 58% and 64% in Groups I and II, respectively, and the difference was not statistically significant. Donors from both groups had comparable recovery, with 2 complications, 1 from each group, requiring a percutaneous drainage procedure. The recipient outcomes were, likewise, comparable and there was 1 case of structural outflow obstruction in Group I, which required venoangioplasty and stenting. There were 2 recipient mortalities, 1 due to a biliary complication and the other to recurrent hepatitis C. Another patient required retransplantation for secondary biliary cirrhosis. The overall actuarial graft and patient survival rates are 84% and 96%, respectively, at a median follow-up of 16 months. Conclusion Based on certain preoperative criteria, a right lobe graft can be taken with or without the middle hepatic vein with equally successful outcomes in both the donors and recipients. The decision, therefore, of the extent of right lobe donor hepatectomy should be tailored to the particular conditions of each case.

Impact of artificial sunlight therapy on the progress of non-alcoholic fatty liver disease in rats.

BACKGROUND & AIMS Non-alcoholic steatohepatitis (NASH) is recognized as the most severe form of non-alcoholic fatty liver disease, with likely progression to liver cirrhosis and hepatocellular carcinoma. However, there is no unified standard for diagnosis and therapeutics. This study aimed to characterize lipid transfer/metabolic proteins as non-invasive diagnostic markers, and to evaluate the therapeutic effects of phototherapy on the progression of NASH in rats. METHODS Lewis rats given a choline-deficient and iron-supplemented l-amino acid-defined (CDAA) diet and Zucker fa/fa rats were used as a diet-induced and an obesity-related NASH models, respectively, with or without phototherapy. RESULTS Serum apolipoprotein E and low molecular weight-adiponectin levels were gradually reduced and reached the lowest level at fatty liver/NASH stage both in CDAA diet-induced NASH model and in genetically obese model. Total-adiponectin levels were dramatically elevated after NASH was established in CDAA diet-induced NASH model. Phototherapy ameliorated hepatocyte apoptosis, inflammation, fibrosis, and insulin/leptin resistance caused by CDAA diet with alteration of the levels of lipid transfer/metabolic proteins and elevation of the circulating active form of vitamin D(3). Vitamin D(3) supplementation ameliorated NASH progression in CDAA diet-induced NASH model. However, phototherapy failed to ameliorate the obesity and steatosis, suggesting that phototherapy may possess anti-inflammatory/fibrotic activity rather than anti-obesity/steatotic activity. CONCLUSIONS These results suggest that serum lipid transfer/metabolic proteins and vitamin D(3) status may be effective biomarkers for non-invasive diagnosis of NASH progression, and that phototherapy may be a good complementary therapy for NASH because of its regulation of lipid transfer/metabolic proteins and vitamin D(3).

Minimal blood loss living donor hepatectomy.

BACKGROUND Donor hepatectomy with maximal safety while preserving graft viability is of principal concern in living donor liver transplantation. There are compelling reasons for avoiding blood transfusion, even with autologous blood, to avoid the potential risks it imposes on healthy donors. This study aims to describe the surgical technique and clinical outcomes of living donor hepatectomy with minimal blood loss requiring no blood transfusion. METHODS Donor hepatectomy was performed in 30 living donors according to a detailed preoperative imaging study of the vascular and biliary anatomy. Liver parenchymal transection was carried out with strict adherence to a meticulous surgical technique without vascular inflow occlusion to either side of the liver. Pre-, intra-, and postoperative data were gathered, and factors related to blood loss were analyzed retrospectively. RESULTS The intraoperative blood loss ranged from 20 to 300 ml with a mean of 72.0+/-58.9 ml (median, 55 ml), and neither homologous nor autologous blood transfusion was required in any of the donors intra- and postoperatively. All 30 donors were discharged with minimal complications, and remain well at a mean follow-up of 24 months after donation. Excellent graft viability was verified by the fact that all 30 recipients are alive and well with a few manageable complications. The actual graft and patient survival are both 100% at the time of writing. CONCLUSIONS Regardless of the extent of donor hepatectomy, blood loss can and should be kept to a minimum, and living donor hepatectomy without blood transfusion is a realistic objective.

Living Donor Liver Transplantation for Biliary Atresia: A Single-Center Experience with First 100 Cases

The aim of this study is to present our institutional experience in living donor liver transplantation (LDLT) as a treatment for end‐stage liver disease in children with biliary atresia (BA). A retrospective review of transplant records was performed. One hundred BA patients (52 males and 48 females) underwent LDLT. The mean follow‐up period was 85.5 months. The mean age was 2.4 years. The mean preoperative weight, height, and computed GFR were 12.2 kg, 82.5 cm, and 116.4 ml/min/1.73 m2, respectively. Twenty‐seven patients were below 1 year of age, and 49 patients were below 10 kg at the time of transplantation. Ninety‐six had had previous Kasai operation prior to transplant. The mean recipient operative time was 628 min. The mean recipient intraoperative blood loss was 176 ml. Thirty‐five did not require blood or blood component transfusion. The left lateral segment (64) was the most common type of graft used. There were 27 operative complications which included 3 reoperations for postoperative bleeding, 9 portal vein, 4 hepatic vein, 4 hepatic artery, and 7 biliary complications. There was one in‐hospital mortality and one retransplantation. The overall rejection rate was 20%. The overall mortality rate was 3%. The 6‐month, 1‐year and 5‐year actual recipient survival rates were 99%, 98% and 98%, respectively.

Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors

Abstract: Exclusion of liver grafts from hepatitis B core antibody (anti‐HBc) positive donors to prevent de novo hepatitis B virus (HBV) infection after liver transplantation is not feasible in areas highly endemic for HBV virus like Taiwan, where approximately 80% of adults are anti‐HBc(+). The efficacy of lamivudine monotherapy to prevent de novo HBV infection after living donor liver transplantation (LDLT) using grafts from anti‐HBc(+) donors remains to be elucidated. From June 1994 to August 2000, LDLT was performed in 42 recipients. Twenty‐four of the 42 donors were anti‐HBc(+) (57%). Pre‐transplant HBV vaccination was given to all recipients irrespective of anti‐HBc status at monthly intervals for 3 months. Until December 1997, eight recipients received liver grafts from anti‐HBc(+) donors without prophylaxis. Since January 1998, prophylaxis with lamivudine monotherapy was given to 16 recipients receiving liver grafts from anti‐HBc(+) donors. De novo HBV infection occurred in three of the eight recipients (37.5%) who did not receive prophylaxis, while none of the 16 recipients given lamivudine developed de novo HBV infection after a mean follow‐up of 25 months. Two of the three recipients with de novo HBV infection were anti‐HBs(–) and one recipient was anti‐HBs(+). Lamivudine was well tolerated, and no side effects were noted. These results suggest that lamivudine monotherapy for recipients receiving anti‐HBc(+) liver grafts is a simple, relatively inexpensive and effective prophylactic regimen for prevention of de novo HBV infection. The additive protection provided by vaccine‐induced or natural immunity is uncertain.

Intraoperative blood loss is a risk factor for complications in donors after living donor hepatectomy

Complications in a donor are a distressing but inevitable occurrence, since graft procurement is a major undertaking. Although the technique for procurement has some similarities to hepatic resection, a donor is very unlike a patient with malignancy. The risk factors identified in these patients cannot be extrapolated to donors. Donor hepatectomy carried out from June 1995 to March 2005 in Chang Gung Memorial Hospital, Kaohsiung Medical Center was reviewed with the aim of identifying risk factors for complications. There were 204 living donor liver transplants, with 205 donor hepatectomies, as 1 living donor liver transplantation was a dual graft. Ten donors (4.88%) suffered complications. There was no difference in terms of age, gender, body weight, operation, and parenchymal time between those who had complications and those who did not. There was also no difference in liver function tests between the 2 groups of donors, but the total bilirubin was significantly higher in donors with complications. The graft weight and remnant liver volume were also similar. The proportion of donors with fatty liver was the same between the 2 groups. The mean blood loss in donors with complications was 170 ± 79 mL, and that for donors without complications was 95 ± 77 mL. There was a statistically significant greater blood loss in donors with complications (P < 0.05). The number of segments removed in donors with complications was also higher compared to donors without complications (P < 0.03). Using multivariate analysis, intraoperative blood loss and the number of segments removed were found to be independent risk factors for donor complications. Intraoperative blood loss during graft procurement must be kept low to minimize complications in donors. Liver Transpl 12:950–957, 2006.

Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.

This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty received grafts from anti‐HBc(+) donors, and another 30 received grafts from anti‐HBc(−) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti‐HBc(+) grafts for about 2 years. Forty‐seven (78%) recipients achieved high levels of anti‐HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti‐HBc(−) graft and another received an anti‐HBc(+) graft. Both recipients were in the lower anti‐HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow‐up period was 51 months in recipients with anti‐HBc(−) grafts and 57 months in those with anti‐HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti‐HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT.

Outflow tract reconstruction in living donor liver transplantation.

Background. Hepatic venous reconstruction is critical in living donor liver transplantation because outflow obstruction may lead to graft dysfunction or loss. We describe our e-perience and analyze outcomes with a technique of creating a single outflow tract using venoplasties of the graft and recipient hepatic veins. Patients and Methods. A retrospective study was done on 38 consecutive living donor liver transplants performed from June 1994 to March 2000. The grafts included 36 left-side grafts and 2 right-side grafts. Nine grafts had multiple hepatic veins and required a venoplasty of two or three hepatic veins to create a single outflow orifice. Triple recipient hepatic venoplasty was performed in 32 patients, double venoplasty in 5 and none in 1. Results. There were four cases of outflow obstruction, three occurring in patients with a double recipient venoplasty. Two of the problems were remedied intraoperatively by adjusting the position of the graft although two were structural in nature and required the insertion of expandable metallic vascular stents. All donors and recipients with their original grafts are alive at a mean follow-up period of 27 months. Conclusion. A triple recipient venoplasty with a matching venoplasty of multiple graft hepatic veins to create a single wide outflow orifice is recommended in living donor liver transplantation using left side grafts.