A Review of Various Techniques of Mouse Liver Transplantation

Objectives

Liver transplantation in a mouse model is a valuable tool for studying transplantation immunobiology and clinic-relevant issues. However, the successful establishment is highly technical and demanding, impeding its widespread use. Herein, the aims of this study were to review and analyze the various techniques of liver transplantation in mice to circumvent pitfalls and minimize the incidence of complications.

Materials and Methods

A search of PubMed was made by using the key words “mouse liver transplantation” for articles published between January 1973 and July 2012. Of the 473 publications identified, 14 were shown to be closely associated with mouse liver transplantation and 4 articles discussed specific microsurgical techniques. Through reviewing these articles, a series of potential factors were collected and analyzed in combination with other murine transplantation models, which might influence successfully establishing a mouse model for liver transplantation.

Results

A mouse liver transplantation model is feasible and practical for experimental studies. Mouse strain, type of anesthesia, type of perfusion and storage solution, and reconstruction of bile duct are relevant factors but not determinants for a successful transplantation. Cold and warm ischemia time should be less than 4.0 hours and 20 minutes, respectively.

Conclusions

The cuff preparation, reconstruction of the hepatic artery, and length of the anhepatic phase play critical roles in successfully establishing a liver transplantation model in mice.     

New method of stent-facilitated arterial reconstruction for orthotopic mouse liver transplantation

Background

Arterialized orthotopic liver transplantation (OLT) in the mouse mimics human liver transplantation physiologically and clinically. The present method of sutured anastomosis for reconstruction of the hepatic artery is complex and is associated with high incidence of complications and failure. This makes the endpoint assessment of using this complex model difficult because of the many variables of the technical aspect.

Methods

A total of 14 pairs of donors and recipients from syngeneic male mice were used for arterialized OLT. The grafts were stored in University of Wisconsin solution at 4°C for less than 4 h, and the recipients underwent OLT using a two-cuff technique. The arterial reconstruction was facilitated by the use of a single stent connecting the donor liver artery segment to the recipient common hepatic artery.

Results

All 14 recipients survived with the time for arterial reconstruction ranging from 4–10 min. Patency of the artery was confirmed by transecting the artery near the graft 2 and 14 d after transplantation. At day 2, five of the six arteries transected were patent and at day 14, seven of the remaining eight were patent for an overall patency rate of 85.7%.

Conclusions

The stent-facilitated arterial reconstruction can be done quickly with a high patency rate. This model expands the translational research efforts to address marginal livers such as steatotic livers.     

Postoperative Enteral Nutrition Improves Survival After Orthotopic Small Bowel Transplantation in Mice

Background

The aim of this study was to assess the effect postoperative enteral nutrition support on the survival after orthotopic small bowel transplantation in mice.

Methods

A model of orthotopic small bowel transplantation used C57BL/6 mice as both donors and recipients.

Results

We demonstrated that postoperative ileus was the deciding complication after transplantation. Postoperative enteral nutritional support resolved this problem and significantly improved survival and growth rates after transplantation.

Conclusion

These data suggest the importance of routine nutritional support after orthotopic small bowel transplantation in mice.     

Interest of BIS monitoring to guide propofol infusion during the anhepatic phase of orthotopic liver transplantation

Objective

The anhepatic phase of orthotopic liver transplantation (OLT) is associated with significant changes in pharmacokinetics. The aim of this study was to compare the influence of this phase on propofol target concentrations during BIS guided target controlled infusion (TCI).

Study design

Prospective study.

Patients and methods

Eight patients aged 25 to 65 years, Child-Pugh status A-B scheduled for OLT were prospectively included. Anesthesia was performed using TCI of propofol (Diprifusor^®, Marsh pharmacokinetic model), sufentanil and cisatracurium. Propofol target concentration was adjusted to maintain BIS values between 40 and 50.

Results

To maintain stable BIS values, propofol target concentrations should be decreased during the anhepatic phase versus the dissection one (2.0 μg/ml ± 0.8 versus 3.0 μg/ml ± 0.9, p < 0.0001).

Conclusion

BIS could be useful to titrate propofol infusion during the anhepatic phase of OLT.     

A new liver graft preparation method for uncontrolled non-heart-beating donors,combining short oxygenated warm perfusion and prostaglandin E1

Background

To resolve the shortage of donors associated with liver transplantation, the potential uncontrolled non-heart-beating donor (UNHBD) pool is expected to increase. However, warm ischemia-reperfusion injury leads to inferior survival in transplantation using the grafts from UNHBD compared with those from heart-beating donors. To overcome this problem, we developed a new method for preparation of liver grafts from UNHBDs consisting of a combination of short oxygenated warm perfusion (SOWP) and prostaglandin E1 (PGE1).

Methods

Using an ex vivo perfusion rat model, we examined the effectiveness of this new method.

Results

Using SOWP and PGE1 treatment, the total amount of bile production during reperfusion in UNHBD grafts was increased to the same level as that in the heart-beating donor grafts. The addition of PGE1 to SOWP buffer decreased aspartate aminotransferase/alanine aminotransferase and tumor necrosis factor α levels during 1 h of reperfusion. Necrosis and apoptosis were significantly decreased by SOWP + PGE1 treatment. SOWP + PGE1 ameliorated induction of mitochondrial permeability transition, and the total amount of mitochondrial cytochrome c in the SOWP + PGE1 group after reperfusion was kept significantly higher than that in the no treatment group. Cytosolic c-Jun N-terminal protein kinase activation was significantly suppressed by SOWP + PGE1. Decrease in mitochondrial Bcl-2 was suppressed by SOWP alone and SOWP + PGE1 treatment, and Bax in the mitochondria was significantly suppressed by SOWP + PGE1.

Conclusion

SOWP and PGE1 prior to cold preservation significantly improved the function of liver grafts that underwent warm ischemia-reperfusion injury. Therefore, this method might be useful in liver transplantation using UNHBD grafts.     

Experience of Combined Liver-Kidney Transplantation for Acute-on-Chronic Liver Failure Patients With Renal Dysfunction

Background

The aim of this study was to evaluate the outcomes of orthotopic liver transplantation (OLT) or combined liver-kidney transplantation (CLKT) for acute-on-chronic liver failure (ACLF) patients with renal dysfunction.

Methods

From January 2001 to December 2009, 133 patients underwent OLT for ACLF at our center. Among them, 30 had both ACLF and renal dysfunction. Of the 30 patients, 12 underwent CLKT for end-stage renal disease (ESRD), and the other 18 with hepatorenal syndrome type 1 (HRS1) underwent OLT alone. ACLF was defined according to the Asian Pacific Association for the Study of Liver Consensus Meeting. Clinical data were reviewed for survival outcomes.

Results

The median model for end-stage liver disease score (MELD) of patients with ACLF was 28. Among the 133 patients, all of whom received deceased donor liver grafts, 12 also got the kidney grafts from the same deceased donor. The hospital mortality rate was 21.8% for all patients with ACLF. The 5-year survival rates were 72.8% for patients without renal dysfunction and 70% for patients with renal dysfunction. The results of patients with ESRD who underwent CLKT were better than those of subjects without renal dysfunction or patients with HRS1 who underwent OLT alone.

Conclusions

OLT alone improved renal function in most patients with HRS1, including those requiring short-term hemodialysis. Simultaneous liver-kidney transplantation was an excellent strategy for patients with both ACLF and ESRD. It provided protection to the kidney allograft for liver-based metabolic diseases affecting the kidney. The rate of acute rejection episodes in kidneys was low.     

Ultrasonographic Optic Nerve Sheath Diameter Is Correlated With Arterial Carbon Dioxide Concentration During Reperfusion in Liver Transplant Recipients

Background

Cerebral blood flow and intracranial pressure (ICP) has been known to be increased after graft reperfusion during liver transplantation, which was correlated with arterial carbon dioxide concentration (PaCO₂). Ultrasonographic measurement of optic nerve sheath diameter (ONSD) is a simple and noninvasive method for evaluating ICP. We investigated the correlation between ONSD and the PaCO₂ during reperfusion in liver transplant recipients.

Methods

Twenty liver transplant recipients with end-stage liver disease were enrolled. We measured ONSD and PaCO₂ at 6 time points: preinduction, preanhepatic phase, anhepatic phase, 5 minutes after reperfusion, 30 minutes after reperfusion, and neohepatic phase. Pearson correlation analysis and receiver operating characteristics (ROC) curve analysis were performed.

Results

ONSD measured 5 minutes after reperfusion was significantly higher compared with the other time points. Differences in ONSD between the anhepatic phase and 5 minutes after reperfusion demonstrated significant correlations with both PaCO₂ at the anhepatic phase and 5 minutes after reperfusion (both P < .001). On the ROC curve analysis, PaCO₂ of 35 mm Hg at the anhepatic phase could be used to indicate ≥20% changes in ONSD after reperfusion. There were significant increases in ONSD after graft reperfusion in liver transplant recipients with PaCO₂ ≥ 35 mm Hg at the anhepatic phase (P = .004).

Conclusion

ONSD was increased just after reperfusion, which demonstrated good correlation with PaCO₂ during reperfusion in liver transplant recipients. This finding suggests that the carbon dioxide can play a key role in increasing ONSD during hepatic graft reperfusion.     

Edaravone,a Free Radical Scavenger,Improves the Graft Viability on Liver Transplantation From Non–heart-beating Donors in Pigs

Background

Although liver transplantation from non–heart-beating donors (NHBDs) is an effective way to overcome shortage of donors, primary graft nonfunction is often noted in these grafts. We have previously reported that edaravone, a free radical scavenger, has a cytoprotective effect on warm ischemia-reperfusion injury and improves the function of liver grafts from NHBDs in a rat model of ischemia-reperfusion. The purpose of this study was to investigate the effects of edaravone on liver transplantations from NHBDs.

Methods

Pigs were divided into three groups: (1) a heart-beating (HB) group (n = 5), in which liver grafts were retrieved from HB donors; (2) a non-heart-beating (NHB) group (n = 4), in which liver grafts were retrieved under apnea-induced NHB conditions; and (3) an edaravone-treated (ED) group (n = 5), in which liver grafts were retrieved in the same manner as the NHB group and treated with edaravone at the time of perfusion (3 mg/L in University of Wisconsin [UW] solution), cold preservation (1 mg/L in UW solution), and after surgery (1 mg/kg/d). The grafts from all groups were transplanted after 4 hours of cold preservation.

Results

In the ED group, the 7-day survival rate was significantly higher than that in the NHB group (80% versus 0%, P = .0042, Kaplan-Meier log-rank test). Furthermore, on histologic examination, the structure of sinusoids in the ED group was well preserved and similar to that in the HB group.

Conclusions

Edaravone may improve the viability of liver grafts from NHBDs.     

Results of Liver Transplantation From Old Donors

Introduction

Faced with a shortage of organs for liver transplantation, the use of grafts from older donors is justified. However, there remains little consensus on how this use impacts the graft and patient outcomes after transplantation from these older donors. The aim of the present analysis was to assess the graft and patient outcomes after liver transplantation from deceased donors >60 years of age.

Methods

From January 2007 to January 2011, 505 subjects were identified as liver graft donors after brain death, of which 7.35% were ≥60. To determine the effect of donor age on graft and patient outcomes, we analyzed donor age, recipient age, the Model for End-State Liver Disease (MELD) score of recipients at the time of transplantation, early posttransplant complications, and mortality.

Results

The posttransplant follow-up was 29 ± 25.5 months, and 3-year patient mortality from donors, grouped according to age, was 7.92% with donors <30; 15.78% with donors 30–50, 10.68% with donors 50–60, and 12.50% with donors >60. After analysis of patient and graft survival based on donor graft age, 3-year patient survival according donor age was 89.29% with donors <30, 83.85% with donors 30–50, 89.89% with donors 50–60, and 87.50% with donors >60. Analysis showed overall patient and graft survival rates from older donors were not worse than those from younger donors (P > .1). Among the cases, 3-year patient survival according to MELD score was 91.19% with a MELD of I, 85.37% with a MELD of II, and 67.67% with a MELD of III; differences in graft and patient survival when comparing low MELD I and high MELD III were significantly different (P < .01).

Conclusions

A more advanced age of a donor should not be a contraindication for liver transplantation. The present analysis shows that liver grafts from donors >60 can be used safely in older recipients who presented with relatively low MELD scores. Analyses also indicate that high MELD obtained before transplantation may be an important prognostic factor for graft and patient survival.     

Hepatitis B prophylaxis in hepatitis B-negative recipients transplanted with donor grafts positive for hepatitis B core antibodies

Background and aims

Use of grafts from hepatitis B (HBV) core antibody (HBcAb⁺) individuals is a routine transplant practice. Herein, we have reported the results of 20 HBV-negative patients transplantated with a HBcAb-positive liver grafts in order to access the efficacy of HBV prophylaxis using immunoglobulin (IE) and antiviral drugs.

Methods

From January 2004 to December 2009, we performed 168 liver transplantations including 38 HBcAb-positive grafts (22.6%) in 18 cases of HBV-positive recipients and 20 HBV-negative recipients. Histological data obtained from these last 20 grafts during retrieval showed an Ishak 1 score in three and no fibrosis in the other cases. HBV prophylaxis included infusion of 10,000 UI IG during the anhepatic phase and every 24 hours for the first 7 days irrespective of the antibody titer as well as lamivudin (100 mg) administred daily. Once discharged, outpatient management provided modulated IG infusions according to when the antibody titer was lower than 400 UI.

Results

No patient displayed an HBV infection. The overall survival was 80%. Two patients died within the first month after transplantation due to septic complications; one patient succumbed at 24 months after transplantation because of a lymphoproliferative malignancy and another died due to an aggressive hepatitis C virus recurrence at 6 months post transplant.

Conclusion

By using appropriate anti-HBV prophylaxis, HBcAb-positive grafts can be used safely for HBcAb-negative recipients.     

Chronic Immune-Mediated Reaction Syndrome as the Cause of Late Graft Mortality in Living-Donor Liver Transplantation for Primary Biliary Cirrhosis

Introduction

Few studies to date have investigated the causes of late graft mortality after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC).

Patients and Methods

Fifty-five LDLTs for PBC were retrospectively reviewed. Factors prognostic of graft survival after LDLT were investigated, and histologic findings in patients with late graft loss were assessed.

Results

The 1-, 5-, and 10-year cumulative graft survival rates were 85.1%, 82.5%, and 66.9%, respectively. Multivariate Cox regression analysis found that male donor and ≥4 HLA mismatches were independently associated with poor graft survival. Among the 13 grafts lost, 5 were lost >1 year after LDLT, including 1 each due to chronic rejection, veno-occlusive disease, and obliterative portal venopathy, and 2 to other causes. Pathologic reviews of the serial biopsy specimens and explanted grafts from these 5 patients, with graft rejections from “chronic immune-mediated reaction syndrome,” showed reciprocal changes over time. No patient died of recurrent PBC.

Conclusions

Male donor and ≥4 HLA mismatches were independent factors associated with poor graft survival. Late graft mortality after LDLT for PBC in some patients was due to chronic immune-mediated reaction syndrome, including chronic rejection, veno-occlusive disease, and obliterative portal venopathy, but not to recurrent PBC.     

Risk Factors for Inadvertent Hypothermia During Adult Living-Donor Liver Transplantation

Background

Hypothermia (core temperature <35°C) causes multiple physiologic disturbances, including coagulopathy and cardiac dysfunction. Patients undergoing liver transplantation are at risk of inadvertent hypothermia and might be more vulnerable to its adverse effects. We sought to identify the factors contributing to hypothermia during living-donor liver transplantation (LDLT), which have not yet been studied in depth.

Methods

Medical records of 134 recipients who underwent adult-to-adult LDLT were reviewed. Core temperature at the following time points were taken: anesthetic induction, skin incision, start and end of the anhepatic phase, and hourly after hepatic reperfusion.

Results

Of 134 recipients, 29 (21.6%) developed hypothermia during surgery. Four independent risk factors for hypothermia were identified: small body weight–to–body surface area ratio, acute hepatic failure, high Model for End-Stage Liver Disease (MELD) score, and low graft-to-recipient weight ratio. The amount of core temperature drop was positively correlated with the number of involved risk factors. Each risk factor had a respective contribution according to the operative phases: body weight–to–body surface area ratio and the MELD score for the preanhepatic phase, acute deterioration of hepatic failure for the anhepatic phase, and graft-to-recipient weight ratio was for the postreperfusion phase.

Conclusions

Hypothermia was independently associated with the recipient's morphometric characteristics, emergency of end-stage liver disease, MELD score, and graft volume. These factors showed a cumulative effect, and the role of each factor was different according to the operative phase. These results should aid in the development of an optimal thermal strategy during LDLT.     

Clinical Evaluation of Hepatic Transection on Pediatric Liver Transplantation

Objectives

Liver transplantation is an effective technique in the treatment of end-stage liver disease. The aim of this study was to evaluate the impact of hepatic transection, an advanced surgical technique able to tailor size to generate two grafts to from a single donor.

Materials and Methods

A retrospective study between January 2000 and September 2013, reviewing 91 pediatric patients who underwent 96 liver transplants from deceased donors. Patients were distributed into two groups: whole organ (WO, n = 39) and transected liver grafts (TLG, n = 57). The following were evaluated: etiology, anthrophometric parameters (age, weight, height, z score weight/age, and height/age), model for end-stage liver disease (MELD) or pediatric end-stage liver disease (PELD), previous surgeries, transfusion of blood components, 1-year survival rate, preoperative laboratory testing, from the second and seventh postoperative days, lactate during surgery, postoperative complications, duration of surgery, duration of cold and warm ischemia, types of biliary reconstruction, and laboratory testing of the donor.

Results

The anthropometric values showed significant differences (P < .05) between the groups. The average age was 124.7 months in the WO group and 33.6 months in the TLG group (P < .0001), while the weight was 28.0 kg and 7.4 kg, respectively (P < .0001). The analysis of z score weight/age showed that the TLG had greater acute and chronic malnutrition, probably due to the etiology of liver disease, present from birth in patients as young. Red blood transfusion was higher in the TLG group (P < .0006) due to the cut surface of the graft, emphasizing the use and improvement of hemostatic techniques.

Conclusion

Despite differences between the groups, clinical and surgical complications were similar, showing that liver transection injury didn't change the results of transplantation. There was no impact on liver function, graft, or 1-year patient survival after liver transection. Second postoperative lactate is a predictive factor of death. Transection liver transplantation is an effective method as an alternative to pediatric liver transplantation.     

Recipient-Donor Age Matching in Liver Transplantation: A Single-Center Experience

Objective

The aim of this study was to investigate whether donor age was a predictor of outcomes in liver transplantation, representing an independent risk factor as well as its impact related to recipient age-matching.

Methods

We analyzed prospectively collected data from 221 adult liver transplantations performed from January 2006 to September 2009.

Results

Compared with recipients who received grafts from donors <60 years old, transplantation from older donors was associated with significantly higher rates of graft rejection (9.5% vs 3.5%; P = .05) and worse graft survival (P = .021). When comparing recipient and graft survivals according to age matching, we observed significantly worse values for age-mismatched (P values .029 and .037, respectively) versus age-matched patients. After adjusting for covariates in a multivariate model, age mismatch was an independent risk factor for patient death (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.1–4.17; P = .027) and graft loss (HR 3.86, 95% CI 1.02–15.47; P = .046).

Conclusions

The results of this study suggest to that optimized donor allocation takes into account both donor and recipient ages maximize survival of liver-transplanted patients.     

Ex Vivo Lung Perfusion Increases the Pool of Lung Grafts: Analysis of Its Potential and Real Impact on a Lung Transplant Program

Background

Among the strategies to increase the number of lung transplants, ex vivo lung perfusion (EVLP) represents a novel technique to expand the donor pool.

Methods

Data from donors referred to our center were retrospectively analyzed to identify grafts that could potentially be potentially reconditioned by EVLP and for comparison with those obtained by clinical application of EVLP program in our center.

Results

Among 75 rejected lungs, 23 organs have been identified as potentially treatable with EVLP with a hypothetic increase of lung transplant activity of 53%. After the introduction of the EVLP program in our center, lung transplantation with reconditioned grafts was performed in 7 (23%) patients with a 30% increase in transplant procedures.

Conclusion

Although less than expected, EVLP increased the number of lungs suitable for transplantation.     

Atrial Fibrillation in Patients Undergoing Liver Transplantation—A Single-Center Experience

Background

As the prevalence of atrial fibrillation rises with age and older patients increasingly receive transplants, the perioperative management of this common arrhythmia and its impact on outcomes in liver transplantation is of relevance.

Methods

Retrospective review of 757 recipients of liver transplantation from January 2002 through December 2011.

Results

Nineteen recipients (2.5%) had documented pre-transplantation atrial fibrillation. Sixteen patients underwent liver and 3 a combined liver-kidney transplantation. Three patients died within 30 days (84.2% 1-month survival) and another 3 within 1 year of transplantation (68.4% 1-year survival). Compared with patients without atrial fibrillation, the relative risk of death in the atrial fibrillation group was 5.29 at 1 month (P = .0034; 95% confidence interval [CI], 1.73–16.18) and 3.28 at 1 year (P = .0008; 95% CI, 1.63–6.59). Time to extubation and intensive care unit (ICU) and hospital readmissions were not different from the control cohort. Rapid ventricular response requiring treatment occurred in 4 patients during surgery and 7 after surgery, resulting in 3 ICU and 3 hospital readmissions.

Conclusions

The results suggest that patients with atrial fibrillation may be at increased risk of mortality after liver transplantation. Optimization of medical therapy may decrease ICU and hospital readmission due to rapid ventricular response.     

Contribution of human adipose tissue–derived stem cells and the secretome to the skin allograft survival in mice

Background

Despite considerable evidence showing the immunosuppressive properties of mesenchymal stem cells (MSCs) in vitro, such properties have not been fully demonstrated in vivo. The aim of this study was to evaluate the effect of MSCs and/or MSC secretome in inducing tolerance in a mouse skin transplantation model.

Methods

After receiving full-thickness skin allotransplantation on the back of the mouse, the recipient mice were infused with phosphate-buffered saline, adipose tissue–derived stem cells (ASCs), conditioned media (CM), and control media. Specifically, ASCs (1.0 × 10⁶/0.1 mL) were transplanted to ASC-infused mice and 25-fold concentrated CM, which had been obtained from ASC culture were infused to CM-infused mice. Graft survival rates and the parameters reflecting immunologic consequences were assessed.

Results

The serum level of proinflammatory cytokine interleukin 6 decreased in mice treated with ASCs or CM compared with the control groups after infusion (P < 0.05). Interferon gamma, interleukin 10, and tumor necrosis factor alpha messenger RNA levels in the skin graft seemed to be decreased in the ASC-infused mice and CM-infused mice. Hyporesponsiveness was identified in mixed lymphocyte reaction assay at 30-d posttransplantation in ASC- or CM-infused mice. And, administering ASCs and CM markedly increased skin allograft survival compared with control animals (P < 0.001).

Conclusions

These findings suggest that ASCs and their secretome have the potential to induce immunologic tolerance. Moreover, our results demonstrate that the immunosuppressive properties of ASCs are mediated by the ASC secretome. Our approach could provide insights into a promising strategy to avoid toxicities of chemical immunosuppressive regimen in solid organ transplantation.     

Monitoring of Intrasplenic Hepatocyte Transplantation for Acute-on-Chronic Liver Failure: A Prospective Five-Year Follow-Up Study

Background

Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of chronic liver disease. Intrasplenic hepatocyte transplantation is increasingly recognized as a treatment for liver failure and genetic metabolic liver diseases. We describe our experience of intrasplenic hepatocyte transplantation in a small cohort of patients as bridge therapy or as an alternative to orthotopic liver transplantation (OLT).

Methods

Seven patients with ACLF with an expected survival of less than 8 weeks were enrolled into the study. The donor hepatocytes were collected from 2 healthy males and cryopreserved. Donor hepatocytes were transplanted into the spleen of recipients via catheterization of the femoral artery. All patients were followed up for 5 years or to death.

Results

A total of (4.2–6.0) × 10¹⁰ hepatocytes were harvested from the 2 donors' livers and their survival after recovery from the frozen stock was 63% ± 2.8% and 73.5% ± 3.2%, respectively. Following intrasplenic hepatocyte transplantation, 3 patients fully recovered from liver failure, 1 survived and subsequently underwent OLT, and the remaining 3 patients died between 2.5 and 12 months after intrasplenic hepatocyte transplantation. At month 48 post–intrasplenic hepatocyte transplantation, living hepatocyte signals were observed in the spleen using magnetic resonance imaging (MRI) with gadobenate dimeglumine (Gd-BOPTA).

Conclusions

Intrasplenic hepatocyte transplantation is a promising therapy for liver failure that may reduce mortality rates among patients with end-stage liver disease awaiting OLT. Conceivably, intrasplenic hepatocyte transplantation may be considered an alternative to OLT for patients with acute liver failure. MRI (Gd-BOPTA) is a useful tool for detecting living hepatocytes in the spleen after intrasplenic hepatocyte transplantation.     

Complications Analysis of Polytetrafluoroethylene Grafts Used for Middle Hepatic Vein Reconstruction in Living-Donor Liver Transplantation

Background

We previously showed that ringed polytetrafluoroethylene (PTFE) grafts combined with small allograft patches showed high patency rates similar to those of iliac vein grafts and therefore that they can be used for middle hepatic vein (MHV) reconstruction. Although such use of PTFE graft showed high patency rates, its long-term safety regarding infection and other types of complications were not presented. In this study, we investigated the actual risk of complications directly associated with PTFE graft interposition for MHV reconstruction.

Methods

During the study period of 30 months, we performed 215 cases of adult living-donor liver transplantation with modified right lobe graft and PTFE grafts. We classified the potential complications directly associated with PTFE graft interposition as infectious and surgical complications. The medical records of study patients were retrospectively reviewed.

Results

MHV graft patency rate was 76.3% at 6 months and 36.7% at 12 months. Their 1-year graft and patient survival rates were 92.6% and 93.5%, respectively. The 1-year actual incidences of infectious complication and surgical complication were near zero and 1 case (0.5%), respectively. In 1 recipient, the PTFE graft penetrated into the stomach wall 6 months after transplantation, but the patient did not complain of any specific symptoms. The PTFE graft was removed with the use of laparotomy, and the patient recovered uneventfully.

Conclusions

Although the incidence of PTFE graft–associated complication rate is very low, we suggest that it is necessary to closely monitor the PTFE graft, because unexpected complications can happen during long-term follow-up.     

Sirolimus Reduces the Risk of Significant Hepatic Fibrosis After Liver Transplantation for Hepatitis C Virus: A Single-Center Experience

Introduction

Hepatitis C virus (HCV) recurrence following orthotopic liver transplantation is an expected outcome in all patients transplanted for a primary diagnosis of HCV. HCV recurrence has been shown to be associated with graft fibrosis and graft loss. Recent studies suggest that sirolimus (SRL) therapy may slow or inhibit hepatic fibrosis following liver transplant in patients positive for HCV at the time of transplant.

Methods

Among 313 patients who underwent orthotopic liver transplantation for HCV between 2000 and 2009, 251 qualified for inclusion in the study. Per protocol liver biopsies were performed on all patients at 1 year following liver transplantation and/or at the time of a clinical diagnosis of HCV recurrence. Biopsies were scored for fibrosis using the Batts-Ludwig staging system (0–4); significant fibrosis was defined as fibrosis ≥ stage 2.

Results

Overall, there was no difference in overall survival or graft loss in the SRL compared with the control group. Multivariate analysis revealed SRL therapy to be associated with decreased odds of significant hepatic fibrosis at year 1 postoperatively and over the study duration.

Conclusions

This retrospective, single-center study showed sirolimus-based immunosuppression to be associated with a lower risk of significant graft fibrosis, both at year 1 and throughout the study period, following liver transplantation in HCV-infected recipients.