Shigehito Miyagi

Risks of donation and quality of donors’ life after living donor liver transplantation

The purpose is to clarify risks of donation and quality of the donors life after living‐related donor liver transplantation (LDLTx). Sixty‐eight donors were classified into four groups: lateral segment group (n = 30); left lobe group (n = 18); left lobe with the middle hepatic vein group (n = 11); right lobe group (n = 9). We investigated (i) the risks of donation, and evaluated the following: blood loss, operation time, postoperative liver function and duration of hospitalization; (ii) quality of donors’ life: donors were mailed a structured questionnaire and the Short‐Form Health Survey (SF‐36), a generic measure assessing quality of life using eight scales. The results were: (i) there were no differences in liver function and duration of hospitalization between four groups; (ii) 48 donors (71%) responded. All donors returned to normalcy. The donors did not regret their decision to donate except two cases whose recipients had died. The donors’ life was almost guaranteed regardless of the lobe we used as the graft.

Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage

Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis.

Effect of portocaval shunt on residual extreme small liver after extended hepatectomy in porcine.

BackgroundWhen residual liver volume is extremely small after extended hepatectomy, postoperative hepatic failure may ensue. The cause of the hepatic failure is likely associated with the portal hypertension after hepatectomy. We investigated the effects of portocaval shunt on portal hypertension in producing sinusoidal microcirculatory injury after extended hepatectomy in pigs.MethodsFourteen pigs were divided into two groups: a group without a shunt, in which extended hepatectomy was carried out (i.e., residual volume was 17% of the whole liver), and a group with a shunt, in which extended hepatectomy was carried out and a portocaval shunt was inserted. The portocaval shunt was placed by side-to-side anastomosis between the portal vein and the inferior vena cava.ResultsIn the group without a shunt, all pigs died of hepatic failure within postoperative day 3. In the group with a shunt, all pigs were alive for more than 4 days, and 4 pigs survived longer than 7 days. Portal vein pressure after hepatectomy was 15.9 ± 3.8 mmHg in the group without a shunt and 10.5 ± 0.6 mmHg in the group with a shunt (P < 0.01). The portal vein flow after 83% hepatectomy in the group without a shunt increased significantly more than at laparotomy and in the group with a shunt (P < 0.01). In the group without a shunt, remarkable destruction of the sinusoidal lining and edema of the portal triad and hydropic change of hepatocytes were observed 1 hour after hepatectomy, but these findings were not observed in the group with a shunt.ConclusionsThese results indicate that, after extended hepatectomy, overload of portal flow is one of the most significant risk factors of hepatic failure by sinusoidal microcirculatory injury.

The Significance of Preserving the Energy Status and Microcirculation in Liver Grafts from Non-Heart-Beating Donor:

To complete a successful liver transplantation (LTx) from non-heart-beating donors (NHBD), it is necessary to both improve the energy status in liver grafts and to reduce the exposure to free radicals. This study investigated the effects of short perfusion with oxygenated buffer on the grafts prior to cold preservation. In addition, the effects of the antioxidant, biliverdin, for reduction of free radicals was investigated. Male Wistar rats were used. Livers were retrieved, preserved in UW solution, and perfused for 60 min with oxygenated Krebs-Henseleit solution. Rats were allocated to six groups as follows (n = 5): i) control group—no warm ischemia (WI) and cold preservation, ii) HBD group—no WI with cold preservation for 6 h; iii) NHBD group—with 30 min of WI and cold preservation, iv) NM group—with WI including nafamostat mesilate infusion before cardiac arrest and cold preservation; v) PRE group—with WI, 30-min pre-cold preservation perfusion with oxygenated buffer after cardiac arrest, and cold preservation, vi) BV group—with the same treatment as the PRE group plus the addition of biliverdin to the pre-cold preservation perfusion. The portal flow volume, bile production, AST, and TNF-α in perfusate, energy charge (EC), and ATP level in the tissue, and histological findings were investigated. The portal flow volume in the NM, PRE, and BV groups were higher than in the NHBD group. The bile production in the PRE and BV groups were also higher than in the NHBD group. The EC and ATP level of the BV group after reperfusion were higher than those of the NHBD group. Pre-cold preservation perfusion and addition of biliverdin to perfusate improved viability of grafts from NHBD. The results indicate that the preservation of the energy status and microcirculation of the graft is important for successful LTx from NHBD.

Analysis of urinary donor-derived DNA in renal transplant recipients with acute rejection.

Abstract: In renal transplantation we usually diagnose an acute rejection by based on the results of a needle biopsy; however, this takes time and findings in some cases are not definite. We analysed the urine of renal recipients for the presence of donor DNA in an attempt to establish a diagnostic means of acute rejection. Sixty‐four renal transplant recipients were examined. Thirty‐seven patients had no trouble after transplantation and 22 patients developed acute rejection, diagnosed based on serum creatinine levels and/or needle biopsy findings of the graft. Five patients had drug‐induced renal dysfunction. In female recipients with a male graft we examined urine for the presence of Y‐chromosome (SRY and DYZ‐1) and in recipients receiving a HLA mismatched graft we investigated the HLA‐DR gene (DRB1) by the polymerase chain reaction (PCR) method. Among female recipients with a male graft there were 14 patients with stable renal function and SRY and DYZ‐1 on Y‐chromosome were negative in 13 (93%) and positive in one, whereas SRY and DYZ‐1 of urine were positive in the four female patients with acute rejection and these DNA fragments disappeared in three after rejection therapy. One patient was subjected to haemodialysis. Among 23 recipients of a graft from HLA mismatched donors with stable renal function, DRB1 was negative in 21(91%). Among 18 patients with acute rejection DRB1 was positive in 16 (93%) and negative in two. These DNA fragments disappeared in 13 patients after rejection therapy. In all patients with drug‐induced renal dysfunction donor‐derived DNA was negative. Presence of donor‐specific DNA in the urine of the recipient is associated strongly with acute rejection and analysis of DNA derived from donor cells in urine might be an effective and accurate method for the diagnosis of acute rejection of a renal transplant.

Quality of Life and Problems Affecting Recipients More Than 10 Years After Living Donor Liver Transplantation

BACKGROUND We initiated living donor liver transplantation (LDLT) in 1991, allowing us to examine issues related to long-term survival. The aim of this study was to review the long-term outcomes of LDLT in children. PATIENTS AND METHODS We performed 116 LDLT from 1991 to present, including 17 recipients who survived >10 years. They were evaluated for growth, immunosuppressive therapy, complications, and quality of life (QOL). RESULTS The average age at LDLT was 5.4 years (range, 6 months to 17 years), with a present average age of 17.2 years (range, 11-28 years). At the time of LDLT, 6 recipients had growth retardation with body weights low for age by 2 standard deviations (SD). However, 4 of 6 recipients who underwent LDLT before age of 2 years caught up, reaching average heights and body weights for their ages. Among 6 recipients who were diagnosed with acute rejections by biopsy >5 years after LDLT, 5 improved after steroid pulse therapy. One recipient with a steroid-resistant acute rejection was administered deoxyspergualin after steroids. Chronic rejection was not observed in this series. One recipient has not required immunosuppressive therapy for >4 years with a good present condition. CONCLUSION The majority of LDLT recipients achieved a good QOL during long-term survival; they are pursuing normal studies.

Microsurgical Back Wall Support Suture Technique With Double Needle Sutures on Hepatic Artery Reconstruction in Living Donor Liver Transplantation

OBJECTIVES In living-donor-liver transplantation (LDLT), microsurgical reconstruction of the hepatic artery is an essential but challenging issue. Especially using a living donor graft, the hepatic artery is short, the intimal damage may be severe, and the usable vessel grafts are limited compared with cadaveric donors. Thus, sometimes it is difficult to use a conventional twist reconstruction technique in which one needs to turn over the hepatic artery. METHODS To overcome these difficulties, we began to use a back wall support suture technique. From July 1991 to June 2007, we performed 110 LDLTs. In 87 cases, we used the conventional twist technique. In the most recent 23 cases, we used a back wall support suture technique. To put it briefly, we placed 2 sutures at the deepest, most difficult points in the artery for backside support. Each stitch was placed from the inner side of the arterial wall to the outer side with double needle sutures. The subsequent sutures were placed forward on either side adjacent to the previous suture. RESULTS The total ratio of hepatic artery thrombosis (HAT) was 8.2% (9/110). In the conventional twist technique group, HAT occurred in 8 cases (9.2%). In the new technique group, it occurred in only 1 case that had an intimal dissection in the recipient artery (4.3%). Thus there was no HAT associated with the arterial anastomosis in the new technique group. CONCLUSION Our technique allows for safe intimal adaptation without turning over the artery. In conclusion, this back wall support suture technique may contribute to more satisfactory results.

Risk Factors for Hepatic Artery Thrombosis After Microsurgical Vascular Reconstruction in Liver Transplantation

OBJECTIVE In liver transplantation, microsurgical reconstruction of a hepatic artery is essential but requires challenging techniques. Especially in living-donor liver transplantation, the recipient artery is short and located deep in the abdominal cavity. Furthermore, hepatic artery thrombosis (HAT) can be a lethal complication. This study sought to uncover the risk factors for HAT after microsurgical vascular reconstruction. METHODS From 1991 to 2011, we performed 151 microsurgical vascular reconstructions, including 3 deceased-donor liver transplantations. We retrospectively investigated the cases, performing univariate and multivariate analyses to identify independent risk factors for HAT. The patients had undergone ultrasonographic examinations for HAT over the first 14 days after transplantation. RESULTS Upon univariate analysis, the risk factors identified to be associated with P < .20 were young age (P = .0484), low body weight (P = .0466), short height (P = .0128), high graft-to-recipient weight ratio (P = .0031), small liver graft volume (P = .0416), small amounts of gabexate mesilate infusion (P = .0516), and the conventional technique (without a back-wall support suture; P = .1326). A multiple logistic regression analysis identified low body weight to be the only independent risk factor for HAT. CONCLUSION On the univariate analysis, we found that using the back-wall support suture technique contributed to the reduction of HAT, whereas on multivariate analysis, the only independent risk factor for HAT was low body weight.

The Use of Recipient Superficial Femoral Vein as a Venous Graft for Portal Vein Reconstruction in Right Lobe Living Donor Liver Transplantation

In living donor liver transplantation (LDLT), portal vein thrombosis (PVT) in the recipient is frequently regarded as a contraindication. To reconstruct the PV of a right-lobe liver graft (RLG) using an interposition or jump graft from the splenomesenteric junction, various vein grafts and technical modifications have been introduced. The internal jugular, external iliac, or great saphenous veins have been utilized in such reconstructive procedures. However, the superficial femoral vein (SFV) is preferable to the autologous vein grafts in terms of caliber, wall thickness, and length. We employed the recipient SFV to reconstruct PVT among 40 adult LDLT using RLG. Thirty-three were reconstructed by single end-to-end anastomosis with the right or left recipient PV. Three patients were transplanted with a RLG using 2 separated PVs reconstructed by double anastomoses with both the right and left PVs of the recipient. The remaining 4 patients required venous grafting for portal reconstruction. We used the recipient SFV as an interposition or jump graft from the splenomesenteric junction to the graft PV. There were 2 cases of anastomotic PV stenosis; 1 in portal reconstruction without a venous graft and the other with a SFV graft. Both were treated successfully by balloon angioplasty. The recipient SFV is an excellent size match for the PV reconstruction as a long interposition or jump conduit when the venous system from the deceased donor is not available. The indication for LDLT in patients with complete PVT should be carefully decided before transplantation in terms of portal reconstruction.

Long-term outcome of ABO-incompatible living-donor liver transplantation: a single-center experience

PURPOSE We report the long-term outcome of ABO-incompatible living donor liver transplantation (LDLT) performed in our hospital. METHODS We started the LDLT program in 1991 and from that year up to now (2008) 11 patients have received an ABO-incompatible graft. RESULTS Nine out of the 11 cases have survived from 3.7 years to 13.9 years (mean 7.3 years) and they are in good conditions at present. Seven patients were subjected to preoperative apheresis. Eight patients experienced acute rejection and of them, 6 experienced steroid-resistant rejection that was treated with deoxyspergualin and apheresis. One patient who suffered rapidly progressing rejection died due to liver failure. Three patients who were administered rituximab did not suffer severe rejection nor adverse effects. During the long-term follow up 5 recipients had major complications such as postoperative lymphoproliferative disease, post-transplantation diabetes mellitus, portal vein occlusion and biliary stenosis. But those complications were controlled under stable conditions. CONCLUSIONS We concluded that long-term survival can be expected after ABO-incompatible LDLT provided perioperative complications such as humoral rejection are overcome.