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1.
Am J Transplant ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38692411

ABSTRACT

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

2.
Liver Transpl ; 29(12): 1292-1303, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37540170

ABSTRACT

Hepatic venous outflow obstruction (HVOO) is a rare but critical vascular complication after adult living donor liver transplantation. We categorized HVOOs according to their morphology (anastomotic stenosis, kinking, and intrahepatic stenosis) and onset (early-onset < 3 mo vs. late-onset ≥ 3 mo). Overall, 16/324 (4.9%) patients developed HVOO between 2000 and 2020. Fifteen patients underwent interventional radiology. Of the 16 hepatic venous anastomoses within these 15 patients, 12 were anastomotic stenosis, 2 were kinking, and 2 were intrahepatic stenoses. All of the kinking and intrahepatic stenoses required stent placement, but most of the anastomotic stenoses (11/12, 92%) were successfully managed with balloon angioplasty, which avoided stent placement. Graft survival tended to be worse for patients with late-onset HVOO than early-onset HVOO (40% vs. 69.3% at 5 y, p = 0.162) despite successful interventional radiology. In conclusion, repeat balloon angioplasty can be considered for simple anastomotic stenosis, but stent placement is recommended for kinking or intrahepatic stenosis. Close follow-up is recommended in patients with late-onset HVOO even after successful treatment.


Subject(s)
Angioplasty, Balloon , Budd-Chiari Syndrome , Liver Transplantation , Humans , Adult , Budd-Chiari Syndrome/diagnostic imaging , Budd-Chiari Syndrome/etiology , Budd-Chiari Syndrome/therapy , Liver Transplantation/adverse effects , Constriction, Pathologic/etiology , Constriction, Pathologic/therapy , Living Donors , Treatment Outcome , Stents/adverse effects , Hepatic Veins/diagnostic imaging , Hepatic Veins/surgery , Angioplasty, Balloon/adverse effects
3.
PLoS Pathog ; 17(2): e1009271, 2021 02.
Article in English | MEDLINE | ID: mdl-33524072

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1) spreads through cell contact. Therefore, this virus persists and propagates within the host by two routes: clonal proliferation of infected cells and de novo infection. The proliferation is influenced by the host immune responses and expression of viral genes. However, the detailed mechanisms that control clonal expansion of infected cells remain to be elucidated. In this study, we show that newly infected clones were strongly suppressed, and then stable clones were selected, in a patient who was infected by live liver transplantation from a seropositive donor. Conversely, most HTLV-1+ clones persisted in patients who received hematopoietic stem cell transplantation from seropositive donors. To clarify the role of cell-mediated immunity in this clonal selection, we suppressed CD8+ or CD16+ cells in simian T-cell leukemia virus type 1 (STLV-1)-infected Japanese macaques. Decreasing CD8+ T cells had marginal effects on proviral load (PVL). However, the clonality of infected cells changed after depletion of CD8+ T cells. Consistent with this, PVL at 24 hours in vitro culture increased, suggesting that infected cells with higher proliferative ability increased. Analyses of provirus in a patient who received Tax-peptide pulsed dendritic cells indicate that enhanced anti-Tax immunity did not result in a decreased PVL although it inhibited recurrence of ATL. We postulate that in vivo selection, due to the immune response, cytopathic effects of HTLV-1 and intrinsic attributes of infected cells, results in the emergence of clones of HTLV-1-infected T cells that proliferate with minimized HTLV-1 antigen expression.


Subject(s)
Clone Cells/virology , HTLV-I Infections/immunology , Human T-lymphotropic virus 1/physiology , Leukemia-Lymphoma, Adult T-Cell/immunology , T-Lymphocytes/virology , Adult , Animals , CD8-Positive T-Lymphocytes/immunology , Clone Cells/immunology , Dendritic Cells/immunology , Female , Gene Products, tax/immunology , HTLV-I Infections/transmission , HTLV-I Infections/virology , Hematopoietic Stem Cell Transplantation , Human T-lymphotropic virus 1/immunology , Humans , Leukemia-Lymphoma, Adult T-Cell/virology , Liver Transplantation/adverse effects , Macaca fuscata , Male , Middle Aged , Natural Killer T-Cells/immunology , Proviruses , T-Lymphocytes/cytology , Viral Load , Virus Replication
4.
Liver Transpl ; 28(4): 603-614, 2022 04.
Article in English | MEDLINE | ID: mdl-34989109

ABSTRACT

Domino liver transplantation (DLT) using grafts from donors with familial amyloid polyneuropathy is an acceptable procedure for expanding the donor pool. The vascular and biliary reconstructions in living donor DLT (LDDLT) are technically demanding, and data on the short-term and long-term surgical outcomes of domino donors and recipients in LDDLT are limited. In this study, we identified 25 domino recipients from our liver transplantation program (1999-2018), analyzed the vascular and biliary reconstructions performed, and evaluated the surgical outcomes, including graft survival. Piggyback technique was adopted in all 25 domino donors. The only surgical complication in domino donors was hepatic vein (HV) stenosis with an incidence rate of 4%. In 22 domino recipients, right HV and middle/left HV were reconstructed separately. A total of 10 recipients had 2 arteries anastomosed, and 18 underwent duct-to-duct biliary anastomosis. HV stenosis and biliary stricture had incidence rates of 8% and 24%, respectively, in the recipients, but none of them developed hepatic artery thrombosis. The 1-year and 5-year graft survival rates were 100% each in the domino donors, and 84.0% and 67.3% in the domino recipients, respectively. In conclusion, LDDLT has acceptable outcomes without increasing the operative risk in donors despite the demanding surgical technique involved.


Subject(s)
Amyloid Neuropathies, Familial , Liver Transplantation , Amyloid Neuropathies, Familial/surgery , Constriction, Pathologic , Humans , Liver Transplantation/methods , Living Donors , Treatment Outcome
5.
Pediatr Surg Int ; 38(2): 201-208, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34779867

ABSTRACT

BACKGROUND: The impact of pediatric liver transplantation on intellectual development has yet to be determined. We investigated the intellectual outcomes of school-aged patients after living donor liver transplantation for biliary atresia in infancy. METHODS: The Wechsler Intelligence Scale for Children-fourth edition test was administered to 20 patients who survived [Formula: see text] 5 years after living donor liver transplantation. Borderline full scale intelligence quotient was defined as ≤ 85. Pre-, peri-, and postoperative data were compared between patients with > 85 and ≤ 85 to identify predictive factors of borderline performance. RESULTS: The one-sample t test demonstrated that the mean full scale intelligence quotient of patients after transplantation for biliary atresia was significantly lower than that of the general population (91.8 vs. 100.0, p = 0.026) and 7 (35%) were classified as intellectual borderline functioning. Multivariable logistic regression models were unable to identify any factors predictive of full scale intelligence quotients of ≤ 85. CONCLUSION: This is the first study to indicate that the mean full scale intelligence quotient among school-aged patients who underwent living donor liver transplantation for biliary atresia in infancy is significantly lower than that of the general population.


Subject(s)
Biliary Atresia , Liver Transplantation , Biliary Atresia/surgery , Child , Humans , Living Donors , Logistic Models , Postoperative Period
6.
Liver Transpl ; 27(6): 854-865, 2021 06.
Article in English | MEDLINE | ID: mdl-33346927

ABSTRACT

Portal vein complications (PVCs) after adult living donor liver transplantation (LDLT) are potentially lethal. We categorized PVCs by the time of onset (early versus late, <1 month versus ≥1 month, respectively) and deformity patterns (portal vein stenosis [PVS], portal vein thrombosis [PVT], and portal vein occlusion [PVO]) to establish optimal treatment strategies. Overall, 35/322 (10.9%) recipients developed PVCs between 2000 and 2019. Pretransplant PVT (odds ratio [OR], 15.20; 95% confidence interval [CI], 3.70-62.40; P < 0.001) was the only independent risk factor for PVS. In contrast, male sex (OR, 5.57; 95% CI, 1.71-18.20; P = 0.004), pretransplant PVT (OR, 4.79; 95% CI, 1.64-14.00; P = 0.004), and splenectomy (OR, 3.24; 95% CI, 1.23-8.57; P = 0.018) were independent risk factors for PVT. PVS was successfully treated with interventional radiology regardless of its time of onset. On the other hand, late PVT and PVO had significantly lower treatment success rates (2/15, 13%) compared with those that occurred in the early period (10/11, 91%) despite aggressive intervention (P < 0.001). Deformity patterns had a significant impact on the 5-year cumulative incidence of graft loss as a result of PVC (PVO + Yerdel grades 2-4 PVT group [n = 16], 41% versus PVS + Yerdel grade 1 PVT group [n = 19], 0%; P = 0.02). In conclusion, late grades 2 to 4 PVT and PVO are refractory to treatment and associated with poor prognoses, whereas PVS has a good prognosis regardless of time of onset. A tailored approach according to the time of onset and deformity patterns of PVC is essential.


Subject(s)
Liver Transplantation , Venous Thrombosis , Adult , Humans , Liver Transplantation/adverse effects , Living Donors , Male , Portal Vein/diagnostic imaging , Retrospective Studies , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/epidemiology
7.
BMC Gastroenterol ; 20(1): 378, 2020 Nov 12.
Article in English | MEDLINE | ID: mdl-33183260

ABSTRACT

BACKGROUND: Hepatic artery dissection after liver transplantation is an uncommon morbidity. The onset mechanism and management for this disorder remain unclear. The present report describes the cases of two patients with hepatic artery dissection after living-donor liver transplantation (LDLT) with simultaneous splenectomy and provides new insight into the onset mechanism of this disorder. CASE PRESENTATION: CASE 1: A 51-year-old man with liver cirrhosis caused by hepatitis B virus underwent LDLT with a right lobe graft and splenectomy simultaneously. The recipient's right hepatic artery had partial dissection at the anastomosis site; therefore, his left hepatic artery was anastomosed. Contrast-enhanced computed tomography (CT) on postoperative day (POD) 27 showed dissection from his celiac artery to his left hepatic artery with bleeding in the false lumen. There was a risk of rupture of the false lumen; therefore, emergency interventional radiology and coil embolization of the false lumen were performed. The patient was doing well at 6 months after LDLT. CASE 2: A 58-year-old woman with liver cirrhosis caused by primary biliary cholangitis underwent LDLT with a left lobe graft and splenectomy simultaneously. Her hepatic artery had a dissection that extended from her left hepatic artery to the proper hepatic artery. The gastroduodenal artery was anastomosed. Contrast-enhanced CT on POD 8 revealed dissection from the celiac artery to the common hepatic artery as well as a pseudoaneurysm at the celiac artery. We managed the patient with conservative treatment and performed daily follow-ups with Doppler ultrasonography examination and serial contrast-enhanced CT. At the time of writing this report, the patient was doing well at 34 months after LDLT. CONCLUSIONS: Patients who have an intimal dissection at the anastomosis site and/or simultaneous splenectomy are at a higher risk of hepatic artery dissection. Most patients with asymptomatic hepatic artery dissections can be treated conservatively. Blood flow in the intrahepatic artery should be checked frequently using Doppler ultrasonography or contrast-enhanced CT soon after diagnosis.


Subject(s)
Liver Transplantation , Dissection , Female , Hepatic Artery/diagnostic imaging , Hepatic Artery/surgery , Humans , Liver Transplantation/adverse effects , Living Donors , Male , Middle Aged , Splenectomy
8.
J Immunol ; 198(4): 1718-1728, 2017 02 15.
Article in English | MEDLINE | ID: mdl-28062700

ABSTRACT

Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence is accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal that guides neutrophils to sites of inflammation. This study aimed to investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response to FPR1 blockade during hepatic I/R. LysM-eGFP mice were subjected to partial warm hepatic I/R. They were pretreated with an FPR1 antagonist, cyclosporine H (CsH), or formyl peptide, fMLF. Liver was imaged after hepatic laser irradiation or I/R using the TPLSM technique. CsH treatment alleviated hepatic I/R injury, as evidenced by decreased serum transaminase levels, reduced hepatocyte necrosis/apoptosis, and diminished inflammatory cytokine, chemokine, and oxidative stress. In contrast, systemic administration of fMLF showed few effects. Time-lapse TPLSM showed that FPR1 blockade inhibited the accumulation of neutrophils in the necrotic area induced by laser irradiation in vivo. In the CsH-treated I/R group, the number and crawling velocity of neutrophils in the nonperfused area were lower than those in the control group. Meanwhile, FPR1 blockade did not affect monocyte/macrophage recruitment. Hepatic I/R promoted the retention of neutrophils and their active behavior in the spleen, whereas CsH treatment prevented their changes. Intravital TPLSM revealed that formyl-peptide-FPR1 signaling is responsible for regulating neutrophil chemotaxis to allow migration into the necrotic area in hepatic I/R. Our findings suggest effective approaches for elucidating the mechanisms of immune cell responses in hepatic I/R.


Subject(s)
Liver/immunology , Liver/pathology , Neutrophil Infiltration , Receptors, Formyl Peptide/metabolism , Reperfusion Injury/immunology , Reperfusion Injury/physiopathology , Animals , Apoptosis , Chemokines/immunology , Chemotaxis, Leukocyte , Cyclosporine/administration & dosage , Cytokines/immunology , Intravital Microscopy/methods , Liver/diagnostic imaging , Liver/drug effects , Male , Mice , Monocytes/immunology , Necrosis , Neutrophils/immunology , Receptors, Formyl Peptide/antagonists & inhibitors , Receptors, Formyl Peptide/deficiency , Reperfusion Injury/diagnostic imaging
9.
Pediatr Transplant ; 23(6): e13522, 2019 09.
Article in English | MEDLINE | ID: mdl-31210388

ABSTRACT

HVOO is a rare complication after LT and an important cause of graft failure. Balloon venoplasty is the first-line treatment for HVOO, but the effect of repeated balloon venoplasty and stent placement for HVOO recurrence after pediatric LDLT remains unclear. Between 1998 and 2016, 147 pediatric patients underwent LDLT in our institution. Among them, the incidence of HVOO and the therapeutic strategy were retrospectively reviewed. Ten patients were diagnosed with HVOO. All the patients underwent LLS grafts. Median age at the initial endovascular intervention was 2.7 years (range, 5 months-8 years). The median interval between the LDLT and the initial interventional radiology was 2.7 months (range, 29 days-35.7 months). Four patients experienced no recurrence after a single balloon venoplasty; 6 underwent balloon venoplasty more than 3 times because of HVOO recurrence; and 2 underwent stent placement due to the failure of repeated balloon venoplasty. All patients are alive with no symptoms of HVOO. The HVOO recurrence-free period after the last intervention ranged from 20 days to 15.5 years (median, 8.9 years). Repeated balloon venoplasty may prevent unnecessary stent placement to treat recurrent HVOO after pediatric LDLT.


Subject(s)
Endovascular Procedures/adverse effects , Hepatic Veins/surgery , Liver Transplantation/adverse effects , Liver/blood supply , Living Donors , Child , Child, Preschool , Female , Humans , Immunosuppression Therapy , Infant , Infant, Newborn , Male , Recurrence , Reoperation , Retrospective Studies , Risk Factors , Stents , Treatment Outcome
10.
Ann Surg ; 267(2): 332-337, 2018 02.
Article in English | MEDLINE | ID: mdl-27811506

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of hepatopancreaticoduodenectomy (HPD) for patients with biliary cancer. BACKGROUND: HPD is thought to be the only curative treatment for widespread bile duct cancer and for some advanced cases of gallbladder cancer; however, HPD has not yet been accepted as a standard operative procedure because of concerns over morbidity and mortality. METHODS: Fifty-two patients undergoing HPD were retrospectively reviewed. The patient and tumor characteristics, preoperative treatments, operative results, and survival outcomes were investigated. RESULTS: Preoperative biliary drainage and portal vein embolization were applied for all patients undergoing right-sided HPD or a left trisectionectomy. A major hepatectomy was performed in 42 patients, and a 2-stage pancreaticojejunostomy was selected in all the cases. The 90-day mortality was 0; however, 1 patient died because of a liver abscess 230 days after surgery. Postoperative significant complications (grade III or greater) and liver insufficiency were observed in 19 (37%) and 2 (3.8%) patients, respectively, and no abdominal bleeding events after the formation of a pancreatic fistula were encountered. The 5-year overall survival rate was 44.5%, and a significant difference was not observed between patients with bile duct cancer and those with gallbladder cancer. The operative procedure was switched to an HPD in 13 patients based on intraoperative findings, and the recurrence-free survival rate for these patients was poorer than that for patients who did not require a switch in operative procedure (P = 0.004). CONCLUSIONS: HPD can be safely performed using the presently reported surgical strategies with acceptable short and long-term outcomes. A precise assessment of the extent of tumor spread might improve patient outcome.


Subject(s)
Bile Duct Neoplasms/surgery , Gallbladder Neoplasms/surgery , Hepatectomy/methods , Pancreaticoduodenectomy/methods , Aged , Aged, 80 and over , Bile Duct Neoplasms/mortality , Female , Follow-Up Studies , Gallbladder Neoplasms/mortality , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Survival Analysis , Treatment Outcome
11.
BMC Med ; 16(1): 83, 2018 06 05.
Article in English | MEDLINE | ID: mdl-29871683

ABSTRACT

In real-world clinical practice, the acceptance of anticoagulation therapy in the management of portal vein thrombosis (PVT) in patients with cirrhosis is limited by the fear of an increased bleeding risk. Additionally, accumulating evidence indicates that spontaneous recanalization of PVT may occur in the absence of antithrombotic treatment. Therefore, risk stratification based on outcomes in such patients is crucial for determining a therapeutic strategy. In this paper, we draw attention to the distinct clinical entity, "transient PVT" by introducing two cases with PVT that spontaneously recanalized in the absence of antithrombotic treatment. We reviewed the available data regarding the probability of and predictors for spontaneous recanalization of PVT. Available data suggest singling out transient thrombosis in the natural history of PVT in patients with cirrhosis because of its prognostic and management implications.


Subject(s)
Anticoagulants/therapeutic use , Liver Cirrhosis/complications , Portal Vein/abnormalities , Venous Thrombosis/etiology , Adult , Anticoagulants/pharmacology , Female , Humans , Liver Cirrhosis/pathology , Male , Prognosis , Treatment Outcome , Venous Thrombosis/mortality , Venous Thrombosis/pathology
12.
Pediatr Transplant ; 22(5): e13221, 2018 08.
Article in English | MEDLINE | ID: mdl-29761829

ABSTRACT

LT is a practical therapeutic alternative for unresectable hepatoblastoma; however, deciding when to perform LT is difficult. The aim of this study was to optimize the timing of LT for hepatoblastoma using pretransplant trends in AFP levels. Trends in pretransplant AFP levels and their influence on post-transplant outcomes were retrospectively evaluated. All patients who underwent living donor LT for hepatoblastoma in our institution since 2002 were included. Variables analyzed included history of prior tumor resection, pretransplant AFP responses to chemotherapy, metastatic disease at diagnosis, and post-transplant chemotherapy. Eight patients (seven boys and one girl; median age, 35 months; range, 15 months-12 years) were transplanted. The overall post-transplant recurrence-free survival rate was 62.5% (5/8) with a mean follow-up of 77 months. Patients with post-transplant recurrence showed a 0.573 log increase in AFP levels after the last chemotherapy session before LT. This was significantly higher than the 0.279 log decrease observed in patients without post-transplant recurrence (P = .024). Because the AFP response cannot be accurately predicted before each cycle of chemotherapy, it may be appropriate to perform LT when AFP levels do not decrease after the last cycle and before they are found to be elevated again.


Subject(s)
Hepatoblastoma/surgery , Liver Neoplasms/surgery , Liver Transplantation , Neoplasm Recurrence, Local/diagnosis , alpha-Fetoproteins/metabolism , Child , Child, Preschool , Female , Follow-Up Studies , Hepatoblastoma/blood , Hepatoblastoma/diagnosis , Humans , Infant , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Liver Transplantation/methods , Living Donors , Male , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/etiology , Preoperative Period , Retrospective Studies , Treatment Outcome
13.
Prog Transplant ; 28(1): 91-92, 2018 03.
Article in English | MEDLINE | ID: mdl-29226766

ABSTRACT

Hepatitis E virus (HEV) infection which may become fulminant, especially in elderly people is more common than previously recognized in develop countries. Here we report successful living-donor liver transplantation (LDLT) in a case of acute liver failure due to HEV. A 63-year-old Japanese man with no previous history of liver disease was admitted for severe acute hepatitis. Detection of anti-HEV immunoglobulin A established a diagnosis of this virus-related liver failure. The patient suffered from hepatic encephalopathy 10 days after symptom onset and underwent LDLT. The patient had an uneventful course. The HEV RNA showed spontaneous negative conversion 10 weeks after LDLT. LDLT led to a successful outcome in a patient with acute liver failure due to HEV infection and regular testing for HEV RNA should be performed until HEV RNA is undetectable.


Subject(s)
Hepatitis Antibodies/blood , Hepatitis E/surgery , Hepatitis E/virology , Liver Failure, Acute/surgery , Liver Failure, Acute/virology , Liver Transplantation/methods , Asian People , Humans , Living Donors , Male , Middle Aged , Treatment Outcome
14.
Ann Surg ; 265(1): 166-172, 2017 01.
Article in English | MEDLINE | ID: mdl-28009742

ABSTRACT

OBJECTIVE: The aim of the study was to investigate the association between platelet count/prothrombin time early after transplant and short-term outcomes among living-donor liver transplant (LDLT) recipients. BACKGROUND: Postoperative platelet count and prothrombin time-international normalized ratio (PT-INR) were critical biomarkers in LDLT. METHODS: The study participants consisted of 445 initial LDLT recipients, and perioperative variables, including platelet count and PT-INR, were assessed for their association with severe complications (Clavien-Dindo classification grade IIIb/IV) and mortality within 90 days after operation. RESULTS: Severe complications and operative mortality occurred in 161 (36%) and 23 patients (5%), respectively. Cox regression analysis revealed that a high body mass index [hazard ratio (HR) 1.2; 95% confidence interval (CI), 1.1-1.4; P = 0.004] and low platelet count on postoperative day (POD)3 (HR 0.88; 95% CI, 0.57-0.97; P < 0.001) were independent predictors for grade IIIb/IV complications after LDLT, whereas high PT-INR on POD5 (HR 1.1; 95% CI, 1.1-1.3; P = 0.021) was the only independent factor for operative mortality. In addtion, the progonostic scoring with low platelet count (<50 × 10/L) and prolonged prothrombin time (PT-INR >1.6) within POD5, 1 point for each, was demonstrated to be useful in predicting the development of Clavien-Dindo grade IIIb/IV/V complications after LDLT (30% for score 0, 46% for score 1, and 72% for score 2: 0 vs 1, P = 0.004; 0 vs 2, P < 0.001; 1 vs 2, P = 0.002). CONCLUSIONS: PT-INR above 1.6 and platelet count below 50 × 10/L within POD5 were useful predictors of mortality and severe complications after LDLT.


Subject(s)
International Normalized Ratio , Liver Transplantation/mortality , Living Donors , Platelet Count , Postoperative Complications/diagnosis , Prothrombin Time , Adult , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Postoperative Complications/blood , Postoperative Complications/epidemiology , Prognosis , Proportional Hazards Models , Retrospective Studies , Severity of Illness Index
15.
Hepatol Res ; 47(11): 1147-1154, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28002876

ABSTRACT

AIM: The development of direct-acting oral agents has dramatically changed the treatment strategy of hepatitis C virus (HCV) infection. Here we aimed to reveal the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) for recurrent HCV genotype 1 infection after liver transplantation (LT). METHODS: A retrospective study was undertaken on nine patients who underwent a 24-week DCV/ASV treatment regimen for recurrent HCV genotype 1 infection. Five of the patients were men; four had failed treatment with pegylated interferon (Peg-IFN)/ribavirin, two had failed simeprevir/Peg-IFN/ribavirin, one had the resistance-associated variant Y93H in the NS5A region, and one underwent maintenance dialysis. RESULTS: Median time to treatment initiation following LT was 70 months. Of the nine patients treated with DCV/ASV, eight (88.9%) achieved a sustained viral response 12 weeks after completion of therapy (SVR12). The patient with virologic failure had failed simeprevir/Peg-interferon/ribavirin therapy 4 months before undergoing the DCV/ASV treatment regimen. In addition, a resistance-associated variant D168E in the NS3 region was detected in the patient after discontinuation of the DCV/ASV regimen. The trough level of tacrolimus tended to decrease, and renal function showed no significant changes during treatment. Adverse events occurred in two patients (22.2%), but no severe adverse events occurred during treatment. CONCLUSIONS: The DCV/ASV regimen was well tolerated, resulting in high rates of sustained viral response 12 weeks after completion of therapy for LT patients with recurrent HCV genotype 1 infection.

16.
Pediatr Transplant ; 21(7)2017 Nov.
Article in English | MEDLINE | ID: mdl-28834141

ABSTRACT

Acute GVHD is a rare complication after liver transplantation that has a high mortality rate. We experienced an infant case complicated with acute GVHD. An 8-month-old infant with biliary atresia underwent LDLT with a graft obtained from his mother. Their HLAs showed a donor-dominant one-way match, not at HLA-DR but at HLA-A, HLA-B, and HLA-C (recipient; A 31/33, B 51/54, C 1/14, DR 9/11, donor; A 31/-, B 51/-, C 14/-, DR 8/11). The patient exhibited a high fever, skin rash, and diarrhea, and was diagnosed with acute GVHD based on the blood chimerism test. Despite immunosuppression treatment with prednisolone and tacrolimus, plasma exchange, blood transfusion including cord blood transplantation, and antibiotics, the child died on postoperative day 126. Donor-dominant one-way matching at HLA class 1 can be a high-risk factor for acute GVHD despite HLA class 2 mismatching.


Subject(s)
Graft vs Host Disease/immunology , HLA-DR Antigens/immunology , Histocompatibility , Liver Transplantation , Living Donors , Fatal Outcome , Humans , Infant , Male
17.
Pathol Int ; 67(3): 163-170, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28139862

ABSTRACT

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma.


Subject(s)
B7-H1 Antigen/biosynthesis , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/pathology , Occupational Diseases/pathology , Programmed Cell Death 1 Receptor/biosynthesis , Adult , Aged , Apoptosis/physiology , B7-H1 Antigen/analysis , Bile Duct Neoplasms/chemically induced , Bile Duct Neoplasms/immunology , Cholangiocarcinoma/chemically induced , Cholangiocarcinoma/immunology , Female , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Japan , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Occupational Diseases/etiology , Occupational Diseases/immunology , Occupational Exposure/adverse effects , Precancerous Conditions/pathology , Printing , Programmed Cell Death 1 Receptor/analysis , Solvents/adverse effects
18.
Surg Today ; 47(11): 1405-1414, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28434081

ABSTRACT

PURPOSE: Liver retransplantation is the only therapeutic option for patients with graft failure after liver transplantation. The aim of this study is to evaluate the outcomes of pediatric retransplantation from living donor at a single center. METHODS: Between December 1998 to August 2015, retransplantation from a living donor was performed for 14 children (<18 years of age) at Kumamoto University Hospital. The characteristics of the retransplantation recipient and the clinicopathological factors between primary transplantation and retransplantation were analyzed to detect the prognostic factors. RESULTS: In retransplantation, the operative time was longer and the amount of blood loss was greater in comparison to primary transplantation. The 1-, 3-, and 5-year survival rates from the date of retransplantation were 85.7, 85.7, and 78.6%, respectively. The rates of re-laparotomy after primary transplantation, bile leakage and postoperative bleeding after retransplantation were higher than after primary transplantation. Among the three patients who died after retransplantation, the operative time, the rate of re-laparotomy after primary transplantation and the incidence of gastrointestinal complications were higher in comparison to the surviving patients. CONCLUSION: Pediatric retransplantation from a living donor is an acceptable procedure that could save the lives of recipients with failing allografts when organs from deceased donors are scarce. To ensure good results, it is essential to make an appropriate assessment of the cardiopulmonary function and the infectious state of the patients before Re-LDLT.


Subject(s)
Liver Transplantation , Living Donors , Primary Graft Dysfunction/surgery , Adolescent , Allografts , Child , Child, Preschool , Female , Humans , Infant , Male , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/etiology , Reoperation , Treatment Outcome
19.
Ann Surg ; 263(3): 529-37, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25563884

ABSTRACT

OBJECTIVE: To establish a strategy for surgical resection of hepatic malignancies confined to segment VII. BACKGROUND: Various surgical procedures can be used to resect hepatic malignancies in segment VII, the deepest region of the liver, by open and/or laparoscopic approaches: nonanatomic wedge resection (WR), segmentectomy VII, right lateral sectionectomy (RLS), and right hepatectomy. METHODS: WR and segmentectomy VII were applied as first-line surgical procedures for colorectal liver metastasis (CRLM) and hepatocellular carcinoma (HCC), respectively. RLS and right hepatectomy were indicated only when tumor infiltration to the proximal Glissonian sheath was suspected. Operative outcomes were evaluated in 200 consecutive patients who underwent hepatic resection for HCC (n = 120) or CRLM (n = 80). RESULTS: WR, segmentectomy VII, RLS, and right hepatectomy were performed in 104 (52.0%), 57 (28.5%), 22 (11.0%), and 17 (8.5%) patients, respectively. Local hepatectomy (WR and segmentectomy VII) led to shorter operation times and lower blood loss volumes than did extensive hepatectomy (RLS and right hepatectomy). Thoracotomy was performed in half of the WR and two-thirds of the segmentectomy VII procedures. The availability of a laparoscopic approach was 40% (8 patients) after its application in October 2012. CONCLUSIONS: Even for hepatic malignancies located in segment VII, WR and segmentectomy should be prioritized over extensive hepatectomy to preserve the postoperative functional hepatic volume. Full mobilization of the right liver and a good surgical field provided by a large thoracoabdominal or abdominal incision or a laparoscopic approach are key factors for safe performance of deep hepatic transection.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Diagnostic Imaging , Female , Humans , Laparoscopy/methods , Liver Function Tests , Liver Neoplasms/pathology , Male , Middle Aged , Treatment Outcome
20.
Clin Transplant ; 30(8): 880-5, 2016 08.
Article in English | MEDLINE | ID: mdl-27146588

ABSTRACT

BACKGROUND: Several clinical factors are reportedly correlated with acute cellular rejection (ACR) after liver transplantation. However, the factors that determine the response to rescue therapies remain unclear. METHODS: A prospective database of 413 consecutive adult patients who underwent living donor liver transplantation (LDLT) was reviewed. RESULTS: Ninety-nine (24%) patients developed ACR after LDLT. A multivariate analysis revealed that a positive T-lymphocytotoxic test (odds ratio [OR], 3.85; P=.017), HLA-DR mismatch (OR, 2.99; P=.013), autoimmune disease (OR, 2.61; P=.001), and a younger recipient age (OR, 0.60 for +10 years; P<.001) were independent risk factors for ACR. Among these, autoimmune disease was significantly correlated with refractoriness to the standard rescue therapy (53% vs 30%, P=.02) and relapse of cellular rejection (34% vs 16%, P=.04). After rescue therapy, 98 of the 99 (99%) patients eventually recovered from ACR and graft loss was observed in only one patient. None of the risk factors for ACR impaired both graft survival and overall survival after LDLT. CONCLUSIONS: Autoimmune liver disease is associated with refractoriness to rescue therapy for ACR and the relapse of rejection. However, ACR does not affect the long-term outcomes of LDLT if it is well controlled.


Subject(s)
Graft Rejection/prevention & control , Immunosuppression Therapy/methods , Liver Transplantation/adverse effects , Adolescent , Adult , Aged , Allografts , Female , Follow-Up Studies , Graft Rejection/diagnosis , Graft Rejection/epidemiology , Graft Survival , Histocompatibility Testing , Humans , Incidence , Japan/epidemiology , Liver/pathology , Living Donors , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Treatment Outcome , Young Adult
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