Clinical Outcomes of Administration of Rituximab for Desensitization in Liver Transplant Patients with Preformed Donor-Specific Antibodies: A Single-Center Experience.

BACKGROUND The management and fate of liver transplant (LT) recipients with preformed donor-specific antibodies (pDSA) remain controversial. The aim of this study was to evaluate the clinical impact of rituximab desensitization on pDSA in LT recipients. MATERIAL AND METHODS This retrospective observational study enrolled 120 LT patients aged ≥18 years. Patients with pDSA were administered 500 mg/body rituximab 1-21 days before LT, except for those who had an active infection or had insufficient time to receive rituximab. We allocated patients to groups with or without pDSA, and then divided patients with pDSA into rituximab (+) and rituximab (-) groups for further analysis. RESULTS Twenty-three patients (19.2%) with pDSA were identified. Of these, 18 received rituximab and 5 did not receive rituximab. No patients developed adverse events related to rituximab. In both groups, the levels of pDSA class I in all patients were decreased immediately after LT, whereas those of pDSA class II decreased slowly. There were no significant differences in pathology findings and overall survival between patients with pDSA who were rituximab (+) or rituximab (-), and between patients with or without pDSA. CONCLUSIONS Rituximab desensitization for LT patients with pDSA was managed successfully without significant complications. Due to the small sample size, we could not demonstrate the benefit of rituximab desensitization for LT patients compared with the rituximab (-) group. Additionally, clinical outcomes in patients with pDSA, with or without rituximab, were similar to those without pDSA. Rituximab desensitization might be not essential for LT.

Efficacy of rehabilitation initiated in the early phase after simultaneous deceased donor liver and kidney transplantation: A case report.

RATIONALE: The purpose of this case report is to describe a case of successful early rehabilitation intervention for simultaneous liver and kidney transplantation (SLKT). PATIENT CONCERNS: A 51-year-old Japanese man was diagnosed with Caroli disease 27 years ago. Hemodialysis was introduced due to end-stage renal disease 17 years ago. DIAGNOSES: After successful SLKT, the patient was extubated on postoperative day (POD) 1, liberated from dialysis on POD 4, and discharged from the intensive care unit on POD 9. INTERVENTIONS: Supervised rehabilitation was started on POD 2, and the patient was able to walk 100 m on POD 9. Electrical muscle stimulation therapy was started to improve muscle weakness in both legs on POD 16, and aerobic exercise using a cycle-ergometer was started on POD 24. OUTCOMES: The 6-minute walking distance improved from 324 m on POD 14 to 501 m on POD 28. The patient could walk 4000 to 5000 steps per day at hospital discharge, and was discharged home on POD 32. There were no adverse events, including worsening hepatic or renal function, during the rehabilitation period. One month after discharge, the patient was able to perform 30 to 40 minutes of aerobic exercise every day, and returned to work 5 months after discharge. LESSONS: This case shows that early rehabilitation intervention immediately after SLKT safely and rapidly improved physical performance without adverse events. The results in the present case suggest that regular physical assessment and appropriate interventions with a variety of exercise modalities can contribute to improved physical performance in SLKT patients.

Successful living-donor liver transplantation for sustained liver failure even after resolution of infiltrative massive hepatic invasion of stage 4S neuroblastoma: a case report.

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor in childhood. Stage 4S neuroblastoma is a unique subset of neuroblastoma characterized by a favorable course and potentially low malignancy with a high rate of spontaneous tumor regression. However, recent reports have shown that there is a subgroup of patients with stage 4S neuroblastoma characterized by MYCN amplification, chromosomal aberrations, age of < 2 months at diagnosis, and significantly poorer outcomes. CASE PRESENTATION: A 1-month-old male infant with a huge abdominal tumor was transferred to our hospital and diagnosed with stage 4S neuroblastoma. The patient showed respiratory distress due to abdominal compartment syndrome secondary to massive hepatic invasion, and he required a silo operation and mechanical ventilation. After chemotherapy using carboplatin and etoposide, the infiltrative massive hepatic invasion was resolved and the abdominal compartment syndrome gradually improved; however, liver dysfunction as evidenced by hyperbilirubinemia, coagulopathy, and hyperammonemia continued. At the age of 3 months, living-donor liver transplantation was performed for treatment of sustained liver failure using a reduced lateral segment graft from the patient's father. Post-transplant liver function recovered immediately. Examination of the explanted liver demonstrated that the majority of liver tissue had been replaced by fibroblastic cells after massive hepatocyte dropout. There were only small areas of residual neuroblastoma cells in the liver specimen. The patient was discharged from the hospital 5 months after transplantation with home intermittent respiratory support. At the time of this writing (23 months after liver transplantation), he was in good condition with no signs of recurrence of neuroblastoma. CONCLUSIONS: We have herein presented a case of successful pediatric living-donor liver transplantation for sustained liver failure even after resolution of infiltrative massive hepatic invasion of stage 4S neuroblastoma. Our case clearly shows that liver transplantation can be added as an appropriate extended treatment option for liver failure after resolution of stage 4S neuroblastoma.

A Successful Living Donor Liver Transplantation Using Hepatic Iron Deposition Graft Suspected by Magnetic Resonance Imaging.

Recently, magnetic resonance imaging (MRI) has been developed as a widely available and noninvasive method for detecting and evaluating hepatic iron overload. This case report presents a successful living donor liver transplantation (LDLT) in which the donor was suspected to have hepatic iron deposition by MRI evaluation. A preoperative donor liver biopsy and genetic examination were performed to exclude hereditary hemochromatosis and other chronic liver diseases. A liver biopsy showed an almost normal liver specimen with a slight deposition of iron in 2-3% of hepatocytes, and a genetic examination of hereditary hemochromatosis revealed no typical mutations in HFE, TFR2, HJV, HAMP, or SLC40A1. Despite the traumatic hemothorax complication caused by the liver biopsy, the liver transplant eligibility was confirmed. Two months after the hemothorax complication, an LDLT donor operation was performed. The donor was discharged from the hospital on postoperative day (POD) #17 with favorable liver function. The recipient's posttransplant clinical course was generally favorable except for acute cellular rejection and biliary complications, and the recipient was discharged from the hospital on POD #87 with excellent graft function. A one-year follow-up liver biopsy of the recipient demonstrated almost normal liver with iron deposition in less than 1% of the hepatocytes, and no iron deposition was identified in the liver graft by MRI examination. Liver biopsy and genetic examination are effective methods to evaluate the eligibility of liver transplant donors with suspected hepatic iron deposition. The living donor with slight hepatic iron deposition, if hereditary hemochromatosis was ruled out, can donate partial liver safely.

Recovery From Severe Systemic Peripheral Neuropathy Secondary to Erythropoietic Protoporphyria by Liver Transplant: A Case Report.

Erythropoietic protoporphyria is a rare inherited metabolic disorder involving the heme biosynthesis pathway and leads to the accumulation of protoporphyrin in the erythrocytes or liver. Although peripheral neuropathy is known to develop occasionally in other types of porphyria, it rarely occurs in patients with erythropoietic protoporphyria. A 16-year-old boy was transferred to our hospital due to end-stage liver disease secondary to erythropoietic protoporphyria. Severe systemic peripheral neuropathy, similar to that presented in Guillain-Barré syndrome, developed; it was promptly managed with mechanical ventilation. Electrophysiological assessment of the presented neuropathy showed no responsiveness, indicating severe axonopathy. Six weeks after the transfer, liver transplant was performed.Postoperatively, hepatorenal syndromes improved immediately, and his erythrocyte protoporphyrin level decreased from 6291 to 174 µg/dL red blood cells.The patient started to move his limbs gradually and was weaned from mechanical ventilation 2 months after liver transplant. Eventually, he was discharged from hospital and was able to ambulate with assistance 10 months after liver transplant. To our knowledge, this is the first report detailing the clinical course in a patient with erythropoietic protoporphyria who recovered from severe systemic peripheral neuropathy after liver transplant.

Effects of Neuromuscular Electrical Stimulation on Lower Limb Muscle Strength After Living Donor Liver Transplant: A Case-Control Study.

BACKGROUND: Early mobilization after liver transplant (LT) plays an important role in postoperative recovery and complication prevention; however, patients undergoing LT cannot achieve early mobilization because of mechanical ventilation and poor preoperative physical performance. We investigated the effect of neuromuscular electrical stimulation (NMES) on lower limb muscle strength after living donor liver transplant (LDLT). METHODS: Adult patients who underwent LDLT between December 2016 and January 2019 at a university hospital were recruited. A consecutive series of patients who underwent LDLT without NMES therapy before the clinical trial (April 2014-May 2016) were enrolled as the non-NMES (control) group. Patients in the NMES group received NMES on the quadriceps muscles starting 1 day post LDLT for 4 weeks. The study was conducted in accordance with the Declaration of Helsinki, and all patients provided informed consent. RESULTS: Twenty-four patients in the NMES group and 16 patients in the non-NMES group were analyzed. There was no significant difference between groups regarding changes in any outcome. CONCLUSIONS: The application of NMES in patients with LDLT did not yield greater improvement of muscle strength, functional capacity, activities of daily living, or length of hospital stay 4 weeks postoperatively compared with the control group. However, developing a novel NMES device and confirming whether additional NMES is effective for other body areas may yield different results.

Psychosocial characteristics of alcoholic and non-alcoholic liver disease recipient candidates in liver transplantation: a prospective observational study.

BACKGROUND: There are long-standing controversies about the transplant indications for alcoholic liver disease (ALD), because of the recognition that ALD is fundamentally self-inflicted. However, it is unclear whether psychosocial characteristics of ALD are different from that of non-alcoholic liver disease (NALD) in the selection of liver transplantation (LT) recipients. We aimed to clarify the psychosocial characteristics of ALD recipients (ALD-R)/ALD recipient candidates (ALD-RC) and NALD recipients (NALD-R)/ NALD recipient candidates (NALD-RC). METHODS: From 2011 to 2019, 75 patients were enrolled in this prospective observational study (ALD-RC, n = 19; NALD-RC, n = 56), LT were carried out as follow; ALD-R, n = 6; NALD-R, n = 52. We evaluated psychosocial characteristics in the preoperative period and 3, 12 months after LT (ALD-R, n = 3/3; NALD-R, n = 28/25). The following scales were used to evaluate psychosocial characteristics: Visual Analogue Scale, Alcohol Use Disorders Identification Test, Hospital Anxiety and Depression Scale, Beck Depression Inventory, Brief Evaluation of Medication Influences and Beliefs, Social Support Questionnaire (SSQ), Temperament and Character Inventory, Parental Bonding Instrument (PBI), the Short Form Health Survey (SF-36). RESULTS: When evaluating on the basis of abstinence rule, a comparison of ALD-RC and NALD-RC in the preoperative period identified similar patterns of psychosocial characteristics, except that the NALD-RC scored higher on the PBI item "overprotection from mother" (P < 0.05). The only significant difference between ALD-R and NALD-R after liver transplantation was in SSQ scores at 3 months. CONCLUSION: The psychosocial characteristics of ALD-RC and NALD-RC may be similar when evaluated on the basis of Japan's abstinence rule. This result also imply that the psychosocial characteristics of ALD-RC may differ from the previously reported psychosocial characteristics of alcohol dependent patients. These findings have the potential to provide helpful information for the evaluation of ALD-RC.

The impact of chronic Epstein-Barr virus infection on the liver graft of pediatric liver transplant recipients: A retrospective observational study.

BACKGROUND: Chronic high Epstein-Barr virus loads (CHEBV) are commonly observed in pediatric liver transplant patients. However, it is unclear how CHEBV impacts the liver graft. The aim of this study was to clarify the clinical and pathological impacts of CHEBV on the liver graft. METHODS: From 2012 to 2020, we retrospectively investigated 46 pediatric liver transplant patients (under 16 years) who survived ≥6 months. The patients were divided into two groups: CHEBV group (EBV DNA >10 000 IU/ml of whole blood for ≥6 months) and nonchronic high EBV (NCHEBV) group (patients who did not meet CHEBV criteria). Tacrolimus was reduced to <3.0 ng/ml in patients with EBV DNA >5000 IU/ml. Blood biochemistry data and pathological findings, obtained at the time of protocol and episodic biopsies, were compared between the two groups. RESULTS: Out of 46 patients, 28 CHEBV and 18 NCHEBV patients were enrolled. The blood biochemical examination did not show a significant difference between the two groups. In addition, no significant differences between the two groups were found in the pathological findings, including frequency of late acute rejection and the progression of fibrosis at the time of both protocol and episodic biopsies. Appropriate adjustment of immunosuppression for CHEBV management may have contributed to the prevention of the progression of fibrosis. CONCLUSION: CHEBV had little adverse effect on the liver graft. Graft fibrosis might have been avoided through optimal dose modification of tacrolimus. Further long-term monitoring is necessary because CHEBV may affect the pediatric liver graft in the long term.

A novel anatomic variation of the intrahepatic biliary tree in live liver donor surgery: A case report.

INTRODUCTION: Anatomic variations of the biliary tree are common, making precise anatomic evaluation important before hepatobiliary surgery. PRESENTATION OF CASE: A 52-year-old woman with no medical history was admitted to our hospital for a live-liver donation to her husband. During her evaluation, magnetic resonance cholangiopancreatography (MRCP) revealed a previously unknown anatomic variation in her biliary system. Segment 2 of the bile duct (B2) independently drained into the posterior branch and formed a common channel (B2+posterior) before joining the anterior branch. Then, bile duct segments 3 and 4 (B3+4) drained into this B2+posterior+anterior channel to form a common hepatic duct. The computerized overlay features shown by MRCP and three-dimensional computed tomography clarified this anatomic variation. A right lobe donor graft was then obtained successfully, with intraoperative cholangiography confirming that the donated graft had two bile duct orifices (i.e., posterior and anterior branches). We thus avoided surgical missteps that would have disallowed bile drainage of B2 and B3+4 into the common hepatic duct. DISCUSSION: Precise evaluation is mandatory for hepatobiliary surgical planning to rule out, or discover, challenging bile duct anatomy. CONCLUSION: Preoperative computerized overlay visualization of MRCP and computed tomography allowed definition of a previously unknown biliary tree variation.

Clinical Features and Long-Term Outcomes of Living Donors of Liver Transplantation Who Developed Psychiatric Disorders.

BACKGROUND In the field of living donor liver transplantation (LDLT), it is important to ensure donor's psychological well-being. We report on clinical features and long-term outcomes of LDLT donors who developed psychiatric disorders after their donor operations. Additionally, we compare patient backgrounds, as well as surgical and perioperative aspects between LDLT donors with and without postoperative psychiatric complications. MATERIAL AND METHODS Between November 1998 and March 2018, we identified 254 LDLT donors at our hospital. Among these, we investigated those who had newly developed psychiatric complications and required psychiatric treatment after donor operation. RESULTS The median duration of follow-up was 4 years. Sixty-five donors were lost to follow-up. Eight donors (3.1%) developed postoperative psychiatric complications, including major depressive disorder in 4, panic disorder in 2, conversion disorder and panic disorder in 1, and adjustment disorder in 1. The median duration from donor surgery to psychiatric diagnosis was 104.5 days (range, 12 to 657 days) and the median treatment duration was 18 months (range, 3 to 168 months). Of those, 3 donors required psychiatric treatment over 10 years, and 4 donors remained under treatment. The duration of hospital stay after donor operation was significantly longer and perioperative complications with Clavien classification greater than grade IIIa were more frequent in donors with psychiatric complications than in those without psychiatric complications (P=0.02 and P=0.006, respectively). CONCLUSIONS Accurate diagnosis and appropriate treatment for psychiatric disorders by psychiatrists and psychologists are important during LDLT donor follow-up. Minimization of physiological complications might be important to prevent postoperative psychiatric complications in LDLT donors.

Computational Fluid Dynamics-Based Blood Flow Assessment Facilitates Optimal Management of Portal Vein Stenosis After Liver Transplantation.

BACKGROUND: Portal vein stenosis develops in 3.4-14% of split liver transplantation1-3 and its early detection and treatment are essential to achieve long-term graft survival,2-5 although the diagnostic capability of conventional modalities such as Doppler ultrasound and computed tomography is limited.1,4,5 METHODS: This study used computational fluid dynamics to analyze portal vein hemodynamics in the management of post-transplant portal vein stenosis. To perform computational fluid dynamics analyses, three-dimensional portal vein model was created using computed tomographic DICOM data. The inlet flow condition was set according the flow velocity measured on Doppler ultrasonography. Finally, portal vein flow was simulated on a fluid analysis software (Software Cradle, Japan). RESULTS: An 18-month-old girl underwent liver transplantation using a left lateral graft for biliary atresia. At the post-transplant 1-week evaluation, the computational fluid dynamics streamline analysis visualized vortices and an accelerated flow with a velocity ratio < 2 around the anastomotic site. The wall shear stress analysis revealed a high wall shear stress area within the post-anastomotic portal vein. At the post-transplant 6-month evaluation, the streamline analysis illustrated the increased vortices and worsening flow acceleration to reach the proposed diagnostic criteria (velocity ratio > 3:1).3,5 The pressure analysis revealed a positive pressure gradient of 3.8 mmHg across the stenotic site. Based on the findings, the patient underwent percutaneous transhepatic portal venoplasty with balloon dilation. The post-treatment analyses confirmed the improvement of a jet flow, vortices, a high wall shear stress, and a pressure gradient. DISCUSSION: The computational fluid dynamics analyses are useful for prediction, early detection, and follow-up of post-transplant portal vein stenosis and would be a promising technology in post-transplant management.

Decreased long-term graft survival in persistent biliary complications after right-lobe living-donor liver transplantation.

BACKGROUND: Long-term outcomes after endoscopic treatment of post-transplant biliary complications have not been fully understood. This study aimed to evaluate the impact of biliary complications on graft survival after right-lobe living-donor liver transplantation (R-LDLT). METHOD: From a single-institutional prospectively maintained database, all patients who underwent R-LDLT between 1999 and 2017 were included. Data on patient demographics, complications, endoscopic treatment, and graft survival were retrieved for analyses. RESULTS: Among 111 patients who underwent R-LDLT, 33 (29.7%) developed biliary complications; of these, 19 (17.1%) were treated with biliary stenting, and the stent was removed following resolution of biliary complications in 8 of the 19 (42.1%) patients. The graft survival rate was 88.0% and 85.6% at 5- and 10-year follow-up, respectively, in patients without biliary complications, which was similar to that of the patients with resolved biliary complications (81.3% at 5- and 10-year follow-up, P = .68) but higher than that of patients having persistent (unresolved) biliary complications (61.4% and 49.1% at 5- and 10-year follow-up, respectively, P = .04). CONCLUSION: Post-transplant persistent biliary complications, unresolved after endoscopic management and requiring prolonged biliary stenting, are associated with inferior graft survival. However, patients with resolved biliary complications achieve a favorable long-term survival similar to patients without biliary complications.

Budd-Chiari Syndrome Associated With Hypereosinophilic Syndrome Treated by Deceased-Donor Liver Transplantation: A Case Report.

INTRODUCTION: Budd-Chiari syndrome (BCS) associated with hypereosinophilic syndrome (HES) is very rare, and only a few reports have described its treatment. Furthermore, no report to date has described the performance of liver transplantation for the treatment of BCS associated with HES. We herein describe a 54-year-old man who underwent deceased-donor liver transplantation (DDLT) for treatment of BCS associated with HES. CASE: A 54-year-old man was found to have an increased eosinophil count during a medical check-up. After exclusion of hematopoietic neoplastic diseases and secondary eosinophilia, idiopathic hypereosinophilia was diagnosed. Oral prednisolone was administered to the patient, and his eosinophil count immediately decreased to a normal level. He had an uneventful course without complications for 11 months but then presented with bloating and malaise. Imaging studies including ultrasonography, enhanced computed tomography, and angiography revealed BCS associated with HES. Transjugular intrahepatic portosystemic shunt failed because of complete obstruction of the hepatic veins. Therefore, the patient was introduced to our hospital for liver transplantation. DDLT was performed with venovenous bypass 1 month after the patient was placed on the DDLT waiting list. The explanted hepatic veins were completely occluded and organized. The patient's eosinophil count was maintained at a normal level with prednisolone treatment after DDLT. CONCLUSIONS: Liver transplantation can be a treatment option for BCS associated with HES if neoplastic diseases and secondary eosinophilia have been excluded. Life-long oral steroid therapy is required to control HES even after liver transplantation.

Preventive Effect of Antioxidative Nutrient-Rich Enteral Diet Against Liver Ischemia and Reperfusion Injury.

BACKGROUND: Liver ischemia and reperfusion injury (IRI) is a major problem associated with liver surgery. This study is aimed to compare the preventive effect of an antioxidative nutrient-rich enteral diet (Ao diet) with an ordinal enteral diet (control diet) against liver IRI. METHODS: The Ao diet was an ordinary diet comprising polyphenols (catechin and proanthocyanidin) and enhanced levels of vitamins C and E. Male C57BL/6 mice were fed the Ao or control diet for 7 days before ischemic insult for 60 minutes, followed by reperfusion for 6 hours. The levels of inflammatory cytokines, chemokines, and antioxidant enzymes and oxidative stress were evaluated. RESULTS: After 7 days of pretreatment with the Ao diet, the serum levels of vitamins C and E in mice were markedly elevated. The levels of serum aspartate aminotransferase and alanine aminotransferase, as well as the scores of liver necrosis caused by ischemia and reperfusion, were significantly lower in the Ao diet group than in the control diet group. The gene expression levels of inflammatory cytokines and chemokines, such as interleukin-6 and CXCL1, were significantly lower in the Ao diet group. In the liver, the levels of antioxidant enzymes superoxide dismutase 1 (SOD1) and SOD2 were significantly higher and the malondialdehyde levels were significantly lower in the Ao diet group. Cell adhesion molecule expression was significantly lower, and neutrophil and macrophage infiltration was less in the Ao diet group. CONCLUSIONS: Antioxidative nutrient supplementation to an ordinary enteral diet may mitigate liver IRI by causing an antioxidant effect and suppressing inflammation.

Pretransplant replacement of donor liver grafts with recipient Kupffer cells attenuates liver graft rejection in rats.

BACKGROUND AND AIM: Rejection of liver grafts is a difficult issue that has not been resolved. Preoperative replacement of liver cells in the graft with cells from the intended recipient may attenuate rejection. We investigated whether preoperative transplant of recipient bone marrow cells (BMCs) to the donor replaced liver allograft cells and attenuated rejection. METHODS: We used a rat model of allogeneic liver transplant (LT) from Dark Agouti (DA) to Lewis (LEW) rats. In BMC group, DA rats received BMC transplants from LacZ-transgenic LEW rats at 1 week before LT. In the control group, DA rats received no preoperative treatment. We evaluated graft damage at 7 days after LT and the survival of the recipient rats. RESULTS: Rats in the BMC group experienced prolonged survival that was abrogated by the administration of gadolinium chloride to donors at 24 h before LT. Serum concentrations of total bilirubin and hyaluronic acid on day 7 were significantly lower in the BMC group, and histopathological analyses revealed that rejection of the liver graft was attenuated. X-gal staining and immunohistostaining of the liver graft revealed that BMCs engrafted in the sinusoidal space differentiated into Kupffer cells. CONCLUSIONS: Preoperative transplant of recipient BMCs to LT donors replaced donor Kupffer cells and attenuated post-LT rejection, indicating that this strategy may increase the success of LT.

Whey-hydrolyzed peptide-enriched immunomodulating diet prevents progression of liver cirrhosis in rats.

OBJECTIVE: Liver fibrosis and subsequent cirrhosis is a major cause of death worldwide, but few effective antifibrotic therapies are reported. Whey-hydrolyzed peptide (WHP), a major peptide component of bovine milk, exerts anti-inflammatory effects in experimental models. A WHP-enriched diet is widely used for immunomodulating diets (IMD) in clinical fields. However, the effects of WHP on liver fibrosis remain unknown. The aim of this study was to investigate the antifibrotic effects of WHP in a rat cirrhosis model. METHODS: Progressive liver fibrosis was induced by repeated intraperitoneal administration of dimethylnitrosamine (DMN) for 3 wk. Rats were fed either a WHP-enriched IMD (WHP group) or a control enteral diet (control group). The degree of liver fibrosis was compared between groups. Hepatocyte-protective effects were examined using hepatocytes isolated from rats fed a WHP diet. Reactive oxygen species and glutathione in liver tissue were investigated in the DMN cirrhosis model. RESULTS: Macroscopic and microscopic progression of liver fibrosis was remarkably suppressed in the WHP group. Elevated serum levels of liver enzymes and hyaluronic acid, and liver tissue hydroxyproline content were significantly attenuated in the WHP group. Necrotic hepatocyte rates with DMN challenge, isolated from rats fed a WHP-enriched IMD, were significantly lower. In the DMN cirrhosis model, reactive oxygen species were significantly lower, and glutathione was significantly higher in the WHP group's whole liver tissue. CONCLUSION: A WHP-enriched IMD effectively prevented progression of DMN-induced liver fibrosis in rats via a direct hepatocyte-protective effect and an antioxidant effect through glutathione synthesis.

How to successfully resect 70 % of the liver in pigs to model an extended hepatectomy with an insufficient remnant or liver transplantation with a small-for-size graft.

An insufficient remnant in extended hepatectomy and small-for-size graft in liver transplantation are critical matters in the field of liver surgery, and reliable and reproducible animal models that can provide clinically relevant and reliable data are needed. We herein describe our detailed surgical procedures for performing 70 % hepatectomy in pigs, and discuss the critical anatomical features, key techniques and pitfalls based on our experience. The porcine liver is divided into four lobes. The right lateral lobe (RLL) accounts for 30 % of the liver volume. Important points, such as selective temporal clamping of the arterial branch, confirmation of a related demarcation line, a two-step process to skeletonize Glisson's capsules during liver resection and selective ligation of the portal venous branch to the right medial lobe without inducing any subtle injuries to Glisson's capsules from the RLL to common bile duct, are discussed.

Effect of cold ischemia/reperfusion injury and/or shear stress with portal hypertension on the expression of matrix metalloproteinase-9.

BACKGROUND: Matrix metalloproteinase (MMP)-9 plays an important role in liver regeneration after liver surgery. MMP-9 behavior is complicated in cold ischemia/warm reperfusion injury (CIWRI) and/or shear stress with portal hypertension. Small-for-size grafts (SFSGs) are also an issue. MATERIALS AND METHODS: We used a rat model to examine MMP-9 expression 6 h after laparotomy, a temporal clamp (Pringle maneuver), orthotopic liver transplantation (OLT) with a whole-liver graft (100% OLT), partial hepatectomy without the Pringle maneuver (60% hepatectomy) and split orthotopic liver transplantation (SOLT) with a SFSG (40% SOLT) were investigated. Four liver samples were collected in each group. RESULTS: The normalized ratio of MMP-9 was not significantly different with a temporal clamp (P = 0.1963), 100% OLT (P = 0.1781) and 60% hepatectomy (P = 0.2367), but it was significantly higher with 40% SOLT compared to that with laparotomy (P = 0.0159). CONCLUSION: Forty percent SOLT is accompanied by not only CIWRI but also shear stress. This fatal damage results in increased MMP-9 expression.