Innovative formulae for the estimation of standard liver volume in the era of widespread imaging analysis software.

BACKGROUND: Various formulae have been used for the estimation of standard liver volume (SLV) in preparation for living donor liver transplantation (LDLT). However, these formulae have the disadvantage of being constructed using parameters that are substantially affected by the patient's condition. Here, we aimed to establish more precise formulae that are less affected by the general condition of the patient. METHODS: We analyzed the liver volumes of LDLT donors and patients with normal livers (total: n = 213) using the SYNAPSE VINCENT imaging analysis system, to develop new formulae. The accuracy of the new formulae were compared with those of existing formulae in a separate validation group of healthy patients (n = 200). The new formulae were also validated using 81 LDLT recipients to assess their utility for graft selection in LDLT. RESULTS: Body surface area (BSA) and skeletal muscle mass index (SMI) independently affected total liver volume (TLV). We produced new formulae for SLV incorporating SMI: SLV = 32.2 × L3-SMI-466.9 for men, with R2 .92, and 25.7 × L3-SMI-55.97 for women, with R2 .79 (alongside a BSA formula with R2 .57), which provided the most accurate predictions of TLV in the validation group. A graft volume (GV)/SLV <.35, calculated using the new formulae, predicted the postoperative prognosis, including the development of small-for-size syndrome, sepsis, or acute rejection, significantly more effectively than GV/SLV using the previous formulae. CONCLUSIONS: The newly developed L3-SMI-based formula is more accurate for the estimation of SLV than previously reported formulae, and may thus help to improve the safety of LDLT.

Segmental Hepatic Steatosis Due to Portal Vein Stricture After Pediatric Living Donor Liver Transplantation: A Case Report.

BACKGROUND AND OBJECTIVE: Liver transplantation (LT) is the gold-standard treatment for end-stage liver disease; however, late-onset complications such as fatty liver can occur in the absence of metabolic comorbidities. We report a unique case of post-transplant hepatic steatosis developing in only a part of the liver graft. CASE REPORT: A 1-year-old boy underwent ABO-incompatible living donor liver transplantation (LDLT) with a left lateral liver graft donated from his mother for biliary atresia. The biliary tract was reconstructed by hepaticojejunostomy using the previous Roux-en-Y limb. Liver function tests increased by up to 2-fold of the upper normal limit after the second year. He developed segmental steatosis in a part of the liver graft 2 years after LDLT. Venous blood drained into the area of the liver graft from veins in the Roux-en-Y limb of the jejunum. Pathologic findings from a liver biopsy showed fatty depositions without steatohepatitis, acute rejection, or tumors. Portal vein stricture (PVS) subsequently became apparent, which was complicated by the symptoms of portal hypertension, such as gastrointestinal varices. We treated PVS with 2 sessions of percutaneous transhepatic portal vein angioplasty (PTPA), after which the segmental steatosis disappeared. We hypothesize that PVS caused local hemodynamic anomalies, leading to fatty deposition in a part of the liver graft. CONCLUSION: We experienced a case of post-LT with segmental steatosis that was successfully treated by portal vein flow modification with PTPA. Steatosis of the graft might indicate a vascular abnormality, and further examinations should be performed after LT.

Effect of herbal medicine daikenchuto on oral and enteral caloric intake after liver transplantation: A multicenter, randomized controlled trial.

OBJECTIVE: Postoperative early oral or enteral intake is a crucial element of the Enhanced Recovery After Surgery (ERAS) protocol. However, normal food intake or enteral feeding cannot be started early in the presence of coexisting bowel dysfunction in patients undergoing liver transplantation (LT). The aim of this multicenter, randomized, double-blinded, placebo-controlled trial was to determine the enhancement effects of the Japanese herbal medicine Daikenchuto (DKT) on oral/enteral caloric intake in patients undergoing LT. METHODS: A total of 112 adult patients undergoing LT at 14 Japanese centers were enrolled. The patients were randomly assigned to receive either DKT or placebo from postoperative day (POD) 1 to 14. The primary endpoints were total oral/enteral caloric intake, abdominal distension, and pain on POD 7. The secondary endpoints included sequential changes in total oral/enteral caloric intake after LT, and portal venous flow volume and velocity in the graft. RESULTS: A total of 104 patients (DKT, n = 55; placebo, n = 49) were included in the analyses. There were no significant differences between the two groups in terms of primary endpoints. However, postoperative total oral/enteral caloric intake was significantly accelerated in the DKT group compared with the placebo group (P = 0.023). Moreover, portal venous flow volume (POD 10, 14) and velocity (POD 14) were significantly higher in the DKT group than in the placebo group (P = 0.047, P = 0.025, P = 0.014, respectively). CONCLUSIONS: Postoperative administration of DKT may enhance total oral/enteral caloric intake and portal venous flow volume and velocity after LT and favorably contribute to the performance of the ERAS protocol.

Successful living donor liver transplantation for acute liver failure after acetylsalicylic acid overdose.

A 20-year-old woman was admitted to an emergency hospital after ingesting 66 g of acetylsalicylic acid in a suicide attempt. Although she was treated with gastric lavage, oral activated charcoal, and intravenous hydration with sodium bicarbonate, her hepatic and renal function gradually deteriorated and serum amylase levels increased. Steroid pulse therapy, plasma exchange, and continuous hemodiafiltration did not yield any improvement in her hepatic or renal function, and she was transferred to our hospital for living donor liver transplantation. Nine days after drug ingestion, she developed hepatic encephalopathy: thus, we diagnosed the patient with acute liver failure with hepatic coma accompanied by acute pancreatitis due to the overdose of acetylsalicylic acid. Living donor liver transplantation was immediately performed using a left lobe graft from the patient's mother. Following transplantation, the patient's renal and hepatic function and consciousness improved, and she was discharged. In this report, we describe a rare case of acetylsalicylic acid-induced acute liver failure with acute hepatic coma and concomitant acute pancreatitis and acute renal failure, which were treated successfully with emergency living donor liver transplantation.

A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis E in Liver Transplant Recipients in Japan.

BACKGROUND: Recently, chronic hepatitis E has been increasingly reported in organ transplant recipients in European countries. In Japan, the prevalence of hepatitis E virus (HEV) infection after transplantation remains unclear, so we conducted a nationwide cross-sectional study to clarify the prevalence of chronic HEV infection in Japanese liver transplant recipients. METHODS: A total of 1893 liver transplant recipients in 17 university hospitals in Japan were examined for the presence of immunoglobulin G (IgG), IgM and IgA classes of anti-HEV antibodies, and HEV RNA in serum. FINDINGS: The prevalence of anti-HEV IgG, IgM and IgA class antibodies was 2.9% (54/1893), 0.05% (1/1893) and 0% (0/1893), respectively. Of 1651 patients tested for HEV RNA, two patients (0.12%) were found to be positive and developed chronic infection after liver transplantation. In both cases, HEV RNA was also detected in one of the blood products transfused at the perioperative period. Analysis of the HEV genomes revealed that the HEV isolates obtained from the recipients and the transfused blood products were identical in both cases, indicating transfusion-transmitted HEV infection. INTERPRETATION: The prevalence of HEV antibodies in liver transplant recipients was 2.9%, which is low compared with the healthy population in Japan and with organ transplant recipients in European countries; however, the present study found, for the first time, two Japanese patients with chronic HEV infection that was acquired via blood transfusion during or after liver transplantation.

First two cases of adult-onset type II citrullinemia successfully treated by deceased-donor liver transplantation in Japan.

We report the first two cases of adult-onset type II citrullinemia (CTLN2) successfully treated by liver transplantation from deceased donors in Japan. One patient was a 34-year-old female, who had suffered from depression since the age of 28 years and developed consciousness disturbance at 34 years old. The other patient was a 41-year-old man who began to experience consciousness disturbance with abnormal behavior at 37 years old. Both patients were first treated with non-surgical therapies, including low-carbohydrate diet, arginine granules and sodium pyruvate. However, their therapeutic efficacy was limited and attacks of encephalopathy occurred frequently with elevation of plasma ammonia despite treatment. While both patients and their families desired liver transplantation, no candidate donors for live-donor liver transplantation were available. Fortunately, within a relatively short period after enrollment for liver transplant from deceased donors in Japan (13 and 43 days, respectively), they underwent cadaveric liver transplantation. The clinical courses after the operation were uneventful in both cases and no attacks of hepatic encephalopathy have occurred. Although there have been no reports of good therapies for CTLN2 patients with resistance to non-surgical therapies and no live-donor candidates, our observations indicate that cadaveric liver transplantation can be a promising therapeutic option for CTLN2 patients.

A new procedure for temporary auxiliary partial liver transplantation using living donor graft for patients with familial amyloid polyneuropathy.

To introduce duct-to-duct biliary anastomosis to conventional temporary auxiliary partial orthotopic liver transplantation (APOLT) using living donor graft for patients with familial amyloid polyneuropathy, we modified the conventional APOLT procedure in a manner characterized by the use of the recipient's common hepatic duct for biliary reconstruction and the preservation of the right posterior section alone for the certain placement of a tube into the corresponding biliary tree for external biliary drainage (modified APOLT). This procedure was performed in 3 patients without biliary complications. No complications associated with the external drainage tube occurred. Here we report the techniques and results for this new procedure.

Clinicopathological features of hepatitis C virus disease after living donor liver transplantation: relationship with in situ hybridisation data.

AIMS: Recurrent hepatitis is a significant complication after liver transplantation for hepatitis C virus (HCV) disease. To evaluate responsiveness to treatment of HCV disease after liver transplantation, in situ hybridisation (ISH) was employed. METHODS: Sense and anti-sense probes for HCV were synthesised, and ISH studies were performed on 19 liver biopsy specimens from 19 recipients who had undergone living donor liver transplantation for HCV disease. ISH positive cells and total hepatocytes were counted, and the percentage of positive cells was calculated. Other clinical findings were compared retrospectively with the ISH results. RESULTS: The subjects were divided into three groups: recurrent HCV hepatitis (RHC, n = 11), acute cellular rejection (ACR, n = 5), and recurrent HCV hepatitis with ACR (MIX, n = 3). The percentage of ISH positive cells was almost the same degree (10-20%) in the three groups. The RHC group was subdivided into two sets of patients in whom serum HCV titres decreased (group D, n = 7) or did not decrease (group ND, n = 3) after 1 month of IFN therapy. The percentage of ISH positive cells in group D was significantly lower than that in group ND (p < 0.05) CONCLUSIONS: ISH for the recipients with HCV may be useful for predicting the response to interferon therapy.

Prognosis of adult patients transplanted with liver grafts < 35% of their standard liver volume.

We have previously reported that a graft volume (GV) > 30% of the recipient's standard liver volume (SLV) can meet the recipient's metabolic demands. Here we report our experience with adult-to-adult living donor liver transplantation using left side grafts < 35% of the recipient's SLV. Of 143 adult living donor liver transplants, 13 auxiliary partial orthotopic liver transplants, 8 right side grafts, and 2 retransplantation cases were excluded. The resulting 120 cases were divided into 2 groups: group S consisted of 33 patients who received liver grafts < 35% of their SLV, and group L consisted of 87 patients who received liver grafts > or = 35% of their SLV. Patient characteristics, postoperative liver function, duration of hospital stay, and recipient survival rates were compared between the 2 groups. There were no significant differences between groups in recipient or donor background characteristics. The mean GV/SLV ratio of group S was 31.8%, whereas that of group L was 42.5%. There were no significant differences in the postoperative serum total bilirubin levels, prothrombin time international normalized ratio, daily ascites volume, or duration of postoperative hospital stay between the groups. The 1- and 5-year survival rates in group S were 80.7% and 64.2%, respectively, whereas those of group L were 90.8% and 84.9%, respectively, with no significant difference between groups. In conclusion, graft size was not considered to be the only cause of so-called small-for-size graft syndrome, and left side grafting appears to be the procedure of choice for adult-to-adult living donor liver transplantation because of the lower risk to donors in comparison with right lobe grafting.

De novo autoimmune hepatitis following living-donor liver transplantation for primary biliary cirrhosis.

Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non-autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S-transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk factor for de novo AIH. Here, we report a 33-yr-old woman who presented complaining of marked fatigue and jaundice four yr after living-donor liver transplantation for PBC. On examination, transaminase levels were highly elevated and ANA and antimitochondrial antibody M2 were positive. Histological findings showed zonal necrosis with lymphoplasmacytic infiltration closely resembling AIH. She had pretreatment AIH score of 16 and 19 points after relapse of de novo AIH. Two color fluorescence in situ hybridization with X and Y chromosome-specific probes clearly revealed that the hepatocytes were of donor origin and lymphocytes were of patient origin. The GSTT1 genotype of the patient and the donor were the same null type, suggesting that mechanisms other than GSTT1 mismatches may exist in de novo AIH development. In conclusion, recipient immune cells attacked the allogeneic transplanted liver of the patient via de novo AIH, although the exact participation of autoimmune mechanisms is unclear.

Nonsurgical policy for treatment of bilioenteric anastomotic stricture after living donor liver transplantation.

Biliary complications remain a significant cause of morbidity following living donor liver transplantation. The purpose of this retrospective study was to assess the outcome of nonsurgical management for hepatojejunostomy stricture in our institution. We reviewed 22 patients with hepatojejunostomy stricture among the 231 patients who underwent living donor liver transplantation between June 1990 and December 2005. Hepatojejunostomy stricture was confirmed by percutaneous transhepatic or endoscopic retrograde cholangiography. Anastomotic strictures were treated by balloon dilatation. Percutaneous transhepatic cholangiography was performed on 15 of the 22 patients. Two of 15 patients, with complete obstruction of the anastomosis, were treated successfully by Yamanouchi magnet compression anastomosis. Although another two patients died of infectious disease that was unlikely to have been related to biliary complications, anastomotic patency was maintained in the other 13 patients. Endoscopic retrograde cholangiography was performed on seven of the 22 patients. None of the 22 patients required re-operation or died of biliary complications. The 5-year graft survival rate of 85.6% in the 22 patients with stricture was equivalent to that of the patients without stricture (82.9%, P = 0.98). Advances in intervention techniques have enabled wider application of nonsurgical approaches for this complication, and fair results have been obtained.

Transthyretin-derived amyloid deposition on the gastric mucosa in domino recipients of familial amyloid polyneuropathy liver.

Familial amyloid polyneuropathy (FAP) is a form of hereditary generalized amyloidosis. Liver tissue explanted from FAP patients has normal structure and function, except for the production of amyloidogenic variant transthyretin (TTR), and domino liver transplantation (DLT) using grafts from FAP patients was first performed in 1995. FAP symptoms usually develop in genetically determined individuals after the age of 20, but it is difficult to estimate when FAP symptoms will appear in domino recipients. Concerning this problem, histological findings showing amyloid deposition have recently been obtained in a few domino recipients of FAP livers. This study investigated the presence of de novo amyloid deposition in the gastroduodenal mucosa of domino recipients transplanted at our institution. Biopsy of gastroduodenal mucosa was carried out in 5 recipients of FAP livers and TTR-derived amyloid deposits were detected in 2 patients, both of whom had undergone DLT 47 months previously. In FAP liver recipients, de novo systemic amyloid deposition may begin much sooner than previously supposed. Therefore, careful follow-up of domino recipients of FAP livers is required.

Risk factors contributing to hepatic artery thrombosis following living-donor liver transplantation.

BACKGROUND/PURPOSE: This study was carried out to investigate the risk factors contributing to hepatic artery thrombosis in living-donor liver transplantation. METHODS: Two hundred and twenty-two recipients (113 adults and 109 children) of living-donor liver transplantation were the subjects of this study. The diagnosis of hepatic artery thrombosis was made by color-Doppler ultrasonography and/or hepatic angiography. Parameters for this study were: (1) donor sex, age, and body weight; (2) recipient sex, age, body weight, liver disease, preoperative prothrombin time, and type of arterial reconstruction; and (3) previous liver transplantation. RESULTS: Hepatic artery thrombosis occurred in 12 patients (5.4%) at 3 to 15 days posttransplant. Recipient female sex and metabolic disorder as the original disease were found to be significantly associated with hepatic artery thrombosis. The 5-year patient survival rate in recipients with hepatic artery thrombosis (58.3%) was significantly lower than that in recipients without this complication (84.4%). CONCLUSIONS: Female sex and metabolic disease may be factors contributing to hepatic artery thrombosis after living-donor liver transplantation. More intensive anticoagulation therapy for this patient population might decrease the incidence of hepatic artery thrombosis and, thus, posttransplant recipient mortality.

Ten years of experience with liver transplantation for familial amyloid polyneuropathy in Japan: outcomes of living donor liver transplantations.

OBJECTIVE: We summarize 10 years of experience with liver transplantation for FAP patients in Japan and review the current opinions regarding this treatment for FAP. METHODS AND PATIENTS: All basic report data on patients at the time of transplantation were registered with the Japanese Liver Transplantation Society (JLTS). Based on the JLST report data, more detailed information on FAP patients was requested from each center. RESULTS: Living donor liver transplantation (LDLT) for FAP patients was first performed in Japan in 1993. LDLT has since been performed in 41 FAP patients, including nine cases of temporary auxiliary partial orthotopic liver transplantation (APOLT). Orthotopic liver transplantation (OLT) from cadaveric donors for FAP patients began in 1999, but only one FAP patient has subsequently undergone this procedure. Of these total of 43 FAP patients, 36 are currently alive: the one-year survival rate of patients after transplantation was 93%, and the five-year survival rate of these cases was 77%. Preoperative clinical severity and the nutritional status of patients are correlated with their outcome after liver transplantation. Domino (sequential) liver transplantation has been carried out in 20 domino recipients with end-stage liver diseases. Of the 20 domino recipients, 12 are currently alive. CONCLUSION: For FAP patients, these outcomes after the operation were very similar to those of OLT from cadaveric donors reported in other countries. Therefore, we concluded that for the treatment of FAP, LDLT from a living donor is equally effective as OLT from a cadaveric donor.

Feasibility of auxiliary partial orthotopic liver transplantation from living donors for patients with adult-onset type II citrullinemia.

More than 20 patients with adult-onset type II citrullinemia have undergone liver transplantation, showing dramatic therapeutic effects. In Japan, living donor liver transplantation is the standard technique of liver transplantation because of the rare availability of cadaveric donors. The feasibility of auxiliary partial orthotopic liver transplantation (APOLT) for adult-onset type II citrullinemia to overcome the problem of a small-for-size graft in living donor liver transplantation has not been defined. We recently performed APOLT for patients with type II citrullinemia. Here, we present 2 patients: patient 1 was a 32-year-old man and patient 2 was a 43-year-old woman. Both patients suffered from hepatic encephalopathy, and laboratory data showed highly elevated plasma levels of ammonia and citrulline. In patient 1, the liver graft was obtained from a patient with familial amyloid polyneuropathy as a domino liver transplant. In patient 2, APOLT was performed after graft donation from her husband. The postoperative clinical courses of both patients were uneventful, and the neurological symptoms were completely resolved. The plasma concentrations of ammonia and citrulline normalized rapidly in both patients. APOLT can provide an adequate hepatocyte mass to correct the underlying enzyme deficiency in adult patients with type II citrullinemia. In addition, APOLT can be carried out safely to overcome the limitation of graft volume in living donor liver transplantation.

Osteonecrosis of the femoral head in Japanese adults after liver transplantation: a preliminary report.

Patients who are treated with high-dose corticosteroids as an immunosuppressive therapy are at high risk of developing osteonecrosis, especially in the femoral head. We examined whether symptomatic osteonecrosis of the femoral head (ONFH) would be a clinical problem after liver transplantation. From June 1990 to December 2001, a total of 169 patients underwent liver transplantation at the Shinshu University Hospital. Within this group, 65 patients were more than 18 years old at the time of surgery, and all were enrolled in the present study. All patients were referred to the Orthopaedic Department of Shinshu University Hospital when they experienced musculoskeletal symptoms, including hip or groin pain. In addition, they were informed of the potential risk of osteonecrosis associated with immunosuppressive therapy after the liver transplant. As result, the patients were advised to have a magnetic resonance imaging (MRI) check for osteonecrosis after transplant surgery. In terms of outcomes, none of the patients presented with symptomatic hip difficulties due to osteonecrosis. Additional clinical investigation revealed that of the 18 patients who underwent MRI screening, only one was found to have asymptomatic unilateral ONFH. In conclusion, ONFH after liver transplantation has not been a clinical problem for our patients.

Von Willebrand factor--cleaving protease activity in thrombotic microangiopathy after living donor liver transplantation: a case report.

Defective plasma activity of Von Willebrand factor (VWF)-cleaving protease (CP) and/or the inhibitors against this protease has been shown to have a pathological role in several forms of thrombotic microangiopathy (TMA). This report describes a patient for whom a diagnosis of TMA was made immediately after living donor liver transplantation. In this patient, activity of VWF-CP and its inhibitor were analyzed serially. At the onset of the disease, VWF-CP activity was quantified as 17%. Inhibitor against this protease was positive, with a titer of 0.6 Bethesda U/mL, and its inhibitory activity was quantified as 3.8 Bethesda U/mg immunoglobulin G. Laboratory parameters and clinical features were significantly improved after induction of plasma exchange (PE) with fresh frozen plasma and concurrent cessation of tacrolimus therapy. The inhibitors disappeared after one session of PE. However, VWF-CP activity after a transient increase and again decreased to subnormal levels after completion of PE. Nevertheless, this did not result in disease recurrence. In view of sustained VWF-CP activity at disease onset and the absence of definite correlations between levels of this protease and clinical features, abnormality of this enzyme system had no essential role in the pathogenesis of TMA in this case. Clinical findings suggest that TMA was tacrolimus-induced.

Living liver donation: preoperative assessment, anatomic considerations, and long-term outcome.

BACKGROUND: A major prerequisite for living donor liver transplantation (LDLT) as an acceptable treatment modality is thoughtful consideration of the donor. However, there has been no comprehensive audit of living liver donation focusing on issues such as donor selection, anatomic surveys, and long-term outcome. METHODS: Between June 1990 and January 2002 at our institution, 160 LDLTs were performed and 177 patients were referred for LDLT. For these patients, a total of 203 potential donors were screened. The process of donor selection, safety of donor hepatectomy, and postoperative morbidity were investigated. Additionally, an anonymous questionnaire was administered to 100 donors who had undergone LDLT more than 3 years previously. RESULTS: Thirty-eight (19%) of the 203 donor candidates were excluded. Precise estimation of the hepatic anatomy was indispensable for donor safety. None of the donors showed prolonged postoperative liver dysfunction nor developed complications requiring reoperation or readmission. There was no donor mortality. The responses to the questionnaire indicated that 95% of the living donors had not felt coerced to donate and that 5% were neutral about coercion pressure. There were no severe postoperative aftereffects, but minor problems were reported by 51% of the respondents. CONCLUSIONS: Our appraisal of the perioperative and long-term postoperative course of LDLT donors revealed that although most donors are satisfied after undergoing LDLT, there is a need for strict attention to the process of donor selection and long-term postoperative follow-up. The outcome of the present series seems to confirm the safety of donor hepatectomy.

Peripheral nerve function in patients with familial amyloid polyneuropathy after liver transplantation.

To evaluate the therapeutic efficacy of liver transplantation in patients with ATTR Val30Met familial amyloid polyneuropathy (FAP), were repeatedly examined the neurophysiological function of peripheral nerves in nine patients. The maximal motor and sensory conduction velocities (MCV and SCV) of the ulnar and tibial nerves, size of compound muscle action potential (CMAP), terminal latency of CMAP, skin temperature of extremities, CVR-R, blood pressure, heart rate, and Schellong's test were examined before and every 6 months after the operation. Although there were no changes in CVR-R, blood pressure, or heart rate, the skin temperature of foot and hand increased soon after surgery and did not decrease during the period of observation. The temperature-adjusted MCV of tibial nerve gradually increased, but the MCV of ulnar nerve showed no change. The temperature-adjusted tibial nerve SCV worsened slightly soon after transplantation and remained at that level in the distal part. The ulnar nerve SCV worsened and subsequently improved. Liver transplantation is very effective for halting the progression of this type of FAP, but the recovery of peripheral nerve function in patients seems to be very slow and limited, especially the function of large diameter myelinated fibers.