Chin-Hsiang Yang

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.

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.

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.

Remnant liver regeneration and spleen volume changes after living liver donation: influence of the middle hepatic vein

Abstract:  Background and objectives:  Graft harvest with or without the middle hepatic vein (MHV) affects venous return and function of the remaining liver. The aims of this study are to compare the remnant liver volume and spleen changes in the donors of different types of graft harvest and to evaluate the influence of resection with or without the MHV on the remnant liver volume regeneration, spleen volume change and serum total bilirubin.

Plasma Exchange Therapy for Thrombotic Thrombocytopenic Purpura in Pediatric Patients With Liver Transplantation

PURPOSE Sporadic cases of thrombotic thrombocytopenic purpura (TTP) have been reported in bone marrow and solid organ transplant patients receiving cyclosporine (CsA). We reported our experience with TTP using plasma exchange (PE) therapy in patients with liver transplantation (OLT). METHODS Between March, 1993, and May, 2007, 400 patients underwent OLT, including 146 pediatric living-donor liver transplantation (LDLT). Four pediatric patients developed TTP after OLT: three were males and one female of mean age at the time of transplantation of 7.8 +/- 3.6 years. The four recipients had the following indications for OLT: two glycogen storage disease, one biliary atresia, and one fulminant hepatic failure. Four patients initially received triple drug immunosuppression consisting of CsA, azathioprine, and steroids. RESULTS Four (1%) patients developed TTP after OLT. All four patients were pediatric in the age group. The mean age at the time of TTP diagnosis was 8.0 +/- 3.2 years, with a mean postoperative interval to TTP of 78.8 +/- 114.2 days. The mean baseline platelet count was 7.0 +/- 7.1 x 10,000. The eventual platelet count was 21.1 +/- 20.8 x 10,000 after PE. These patients received PE 6.0 +/- 4.2. The mean baseline serum creatinine was 0.8 +/- 0.8 mg/dL. The mean peak serum creatinine was 2.3 +/- 2.3 mg/dL. The mean serum CsA level was 717.5 +/- 106.0 ng/mL before TTP diagnosis. Four patients were diagnosed by blood peripheral smears. The causes of TTP were CsA-associated in three patients and venoocclusive disease (VOD) in one patient. Three patients improved their platelet counts after PE therapy. Two patient changed from CsA to FK 506, one underwent reduced CsA dosage, and one stopped CsA. Three patients died of recurrent VOD, infection, and intrapulmonary hemorrhage. Only one patient survived. CONCLUSIONS The incidence of TTP in our series was lower. It only developed in pediatric patients. The causes of TTP were associated with CsA and/or VOD. The mortality was high after the TTP diagnosis. We concluded that TTP was a potentially fatal condition, but an early diagnosis with prompt institution of therapy with invasive PE therapy may reduce its mortal consequences.

Remodeled saphenous vein as interposition graft for portal vein reconstruction in living donor liver transplantation

In this report, we describe a surgical innovation in reconstructing the portal vein (PV) in a recipient with portal vein thrombosis (PVT) using a remodeled triplesheet great saphenous vein (GSV) from the recipient as a vascular interposition graft. A 36-year-old Taiwanese male diagnosed with endstage alcoholic cirrhosis and hepatocellular carcinoma was referred for possible liver transplantation. He had profound hypoalbuminemia (albumin, 1.2 g/dL) and massive ascites (Child-Pugh B, Model for End-Stage Liver Disease 12, and United Network for Organ Sharing status 2B). Preoperative imaging modalities showed a 3-cm hepatocellular carcinoma in segment 8. The computed tomography angiography demonstrated a narrowed distal (hilar) PV. However, the proximal PV at the splenomesenteric junction measured 10 mm. There were prominent, engorged mesenteric collateral veins (Fig. 1). The patient underwent living donor liver transplantation (LDLT) with a right lobe graft without the middle hepatic vein (graft weight, 632 g; graft-to-recipient weight ratio, 0.99) coming from his wife. The segment 5 and 8 veins were reconstructed with a cryopreserved deceased donor iliac vein graft. For PV reconstruction, the measured length of interposition graft required was 5 cm. A 20-cm GSV was harvested from the recipient’s thigh with the conventional open technique for vein harvest in vascular surgery. The distal and proximal portions being noted, the vein was hydrostatically distended by hand injection with a normal saline solution and was checked for leaks. The vein was opened longitudinally. After being opened, the vein was divided into 3 sheets with an equal length of 6 cm each. The sheets of GSV were fashioned and sewn side by side with a polypropylene 6-0 continuous suture along their longitudinal axes. Upon completion of this side-by-side anastomosis, the vein was remodeled to form a hollow tube by sewing together from the farthest ends of the sheets using polypropylene 6-0 continuous suture along their longitudinal axes (Fig. 2). The diameter of the remodeled GSV measured 1.3 cm. This remodeled GSV was used as an interposition graft connecting the graft PV to the recipient’s native splenomesenteric junction (Fig. 3). The narrowed PV segment was resected without an attempt at PV thrombectomy because of circumferential subintimal thrombosis noted intraoperatively. Intraoperative Doppler ultrasound showed that the remodeled GSV interposition graft diameter measured 8.3 mm and the PV flow velocity was 31 cm/second after reconstruction. The PV flow volume was 161 mL/min/100 g of liver tissue. Routine daily postoperative Doppler ultrasound to check vascular patency showed that the mean PV size measured 8.4 mm (range, 7.5-9.5) with a mean PV flow velocity of 28.5 cm/second (range, 12.7-46) during the first week. At 1 month post transplant, the remodeled GSV-PV measured 12 mm with a flow velocity of 16.8 cm/second. The remodeled GSV-PV remained patent to the latest follow-up. Postoperative antithrombosis management included heparin infusion (200 units/kg of body

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 Childs 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 [</=4 mm], medium [5-9 mm], or large [>/=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.

Impact of late conversion from C0 to C2 monitoring of microemulsified cyclosporine in pediatric living donor liver transplant recipients

Abstract:  The efficacy and feasibility of 2‐h post‐dose level (C2) monitoring of cyclosporine in long‐term living donor liver transplantation (LDLT) is not clear. The aim of this study was to investigate the impact of late conversion from conventional trough‐level (C0) monitoring to C2 monitoring of a microemulsion form of cyclosporine (Neoral) in pediatric LDLT recipients. From June 1994 to August 2002, we performed 116 LDLTs in 115 patients. Initially, we adapted conventional C0 monitoring of Neoral, which was converted to C2 monitoring starting in January 2002. The 60 patients who were enrolled in the study had the following characteristics: they were younger than or equal to 15 yr at transplantation, and they had survived LDLT, and they had received a Neoral‐based immunosuppression regimen, and they underwent conversion to C2 more than 1 month after transplantation. We evaluated the impact of conversion on doses, blood levels, rejection, adverse effects, and patient/graft outcome. In the long‐term patients, the mean C2 levels immediately after conversion were higher than the target levels at any time point selected after transplantation; thus, 34 patients (57%) finally required a dose reduction of Neoral. The current mean C2 level was significantly lower than that observed immediately after conversion (584.6 ± 262.8 ng/ml vs. 893.1 ± 260.2 ng/ml, mean ± SD, p < 0.0001) with a mean follow‐up period of 7.4 ± 0.6 months (range: 5–8 months) after conversion. Only one patient encountered rejection after conversion (1.7%), and no de novo infection or adverse effects were observed. Traditional C0 monitoring of Neoral was safely replaced by C2 monitoring without an increase in the rejection rate or any adverse effects in pediatric LDLT patients. C2 monitoring contributed to the dose reduction of Neoral, which may lead to the avoidance of long‐term complications due to immunosuppression.

Low-Dose Dantrolene Is Effective in Treating Hyperthermia and Hypercapnia, and Seems Not to Affect Recovery of the Allograft After Liver Transplantation: Case Report

Dantrolene is the drug of choice in treatment of malignant hyperthermia. However, dantrolene is hepatotoxic; thus prolonged use is not recommended in patients with active hepatic disease such as acute hepatitis or active cirrhosis because it may result in fatal hepatic failure. Use of dantrolene in a patient with end-stage liver disease undergoing liver transplantation (LTx) in whom suspected malignant hyperthermia developed has been reported rarely. Its effect on the liver allograft, which has sustained cold, warm, and reperfusion injuries, is currently unknown. We report a case in which low-dose dantrolene administered intravenously during LTx was effective in treating hyperthermia, hypercapnia, and hyperkalemia. Furthermore, its reported hepatotoxic effect seemed to not affect recovery of the allograft after LTx.