Allan M. Concejero

Association of μ‐opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty

Background:  Morphine consumption after a given surgical procedure can vary considerably. Studies show that single nucleotide polymorphism involving the nucleotide position 118 at exon 1 of the μ‐opioid receptor gene (OPRM1) may play a role in mediating the effects of opioids. This study was performed to correlate the A118G polymorphism at OPRM1 with morphine consumption in patients undergoing total knee arthroplasty.

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.

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.

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.

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. Liver Transpl 15:1766–1775, 2009.

Liver graft-to-recipient spleen size ratio as a novel predictor of portal hyperperfusion syndrome in living donor liver transplantation.

Portal hyperperfusion in a small‐size liver graft is one cause of posttransplant graft dysfunction. We retrospectively analyzed the potential risk factors predicting the development of portal hyperperfusion in 43 adult living donor liver transplantation recipients. The following were evaluated: age, body weight, native liver disease, spleen size, graft size, graft‐to‐recipient weight ratio (GRWR), total portal flow, recipient portal venous flow per 100 g graft weight (RPVF), graft‐to‐recipient spleen size ratio (GRSSR) and portosystemic shunting. Spleen size was directly proportional to the total portal flow (p = 0.001) and RPVF (p = 0.014). Graft hyperperfusion (RPVF flow >250 mL/min/100 g graft) was seen in eight recipients. If the GRSSR was <0.6, 5 of 11 cases were found to have graft hyperperfusion (p = 0.017). The presence of portosystemic shunting was significant in decreasing excessive RPVF (p = 0.059). A decrease in portal flow in the hyperperfused grafts was achieved by intraoperative splenic artery ligation or splenectomy. Spleen size is a major factor contributing to portal flow after transplant. The GRSSR is associated with posttransplant graft hyperperfusion at a ratio of <0.6.

Liver graft regeneration in right lobe adult living donor liver transplantation.

Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital‐Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight‐to‐recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty‐five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 ± 12.6% (range, 58–151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.

Electroporative interleukin-10 gene transfer ameliorates carbon tetrachloride-induced murine liver fibrosis by MMP and TIMP modulation

AbstractAim:Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Effective therapies for liver fibrosis are lacking. Interleukin-10 (IL-10) is a cytokine that downregulates pro-inflammatory responses and has a modulatory effect on hepatic fibrogenesis. The aim of this study was to investigate whether electroporative IL-10 gene therapy has an hepatic fibrolytic effect on mice.Methods:Hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) for 10 weeks in mice. The human IL-10 expression plasmid was delivered via electroporation after hepatic fibrosis was established. Histopathology, reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and gelatin zymography were used to investigate the possible mechanisms of action of IL-10.Results:Human IL-10 gene therapy reversed CCl4-induced liver fibrosis in mice. RT-PCR revealed that IL-10 gene therapy attenuated liver TGF-β1, collagen α1, fibronectin, and cell adhesion molecule mRNA upregulation. Following gene transfer, both the activation of α-smooth muscle actin and cyclooxygenase-2 were significantly attenuated. Furthermore, IL-10 significantly inhibited matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase (TIMP) activation after CCl4 intoxication.Conclusions:We demonstrated that IL-10 gene therapy attenuated CCl4-induced liver fibrosis in mice. IL-10 prevented upregulated fibrogenic and pro-inflammatory gene responses. Its collagenolytic effect may be attributed to MMP and TIMP modulation. IL-10 gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use.

Electroporative α-MSH gene transfer attenuates thioacetamide-induced murine hepatic fibrosis by MMP and TIMP modulation

Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino-acid peptide with potent anti-inflammatory effects. We have previously demonstrated that α-MSH gene therapy protects against thioacetamide (TAA)-induced acute liver failure. Therefore, the aim of this study is to investigate whether α-MSH gene therapy possesses antihepatic fibrogenic effect. Liver fibrosis was induced by long-term TAA administration in mice. α-Melanocyte-stimulating hormone expression plasmid was delivered via electroporation after liver fibrosis was established. Our results showed that α-MSH gene therapy attenuated liver fibrosis in TAA-treated mice. Reverse transcription polymerase chain reaction revealed that α-MSH gene therapy attenuated the liver transforming growth factor-β1, collagen α1 and cell adhesion molecule mRNA upregulation. Following gene transfer, the expression of α-smooth muscle actin and cyclooxygenase-2 were both significantly attenuated. Further, α-MSH significantly increased matrix metalloproteinase (MMP), while tissue inhibitors of matrix metalloproteinase (TIMPs) were inactivated. In summary, α-MSH gene therapy reversed established liver fibrosis in mice and prevented the upregulated fibrogenic and pro-inflammatory gene responses after TAA administration. Its collagenolytic effect might be attributed to MMP and TIMP modulation. Hence, α-MSH gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use.

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. Liver Transpl 15:1553–1556, 2009.