ABO incompatible (ABO-In) liver transplant remains a controversial solution to acute liver failure in adults. Adult liver recipients with acute liver failure or severely decompensated end-stage disease, intubated and/or in the intensive care unit, were grouped as ABO-In (n = 14), ABO-compatible (n = 29, ABO-C) and ABO-identical (n = 65, ABO-Id). ABO-In received quadruple immunosuppression with antibody-depleting induction agents (except two), calcineurin inhibitors, antimetabolites and steroids. No significant difference of patient and graft survivals was observed among ABO-In, ABO-C and ABO-Id: graft survivals were 64%, 62% and 67%, respectively, in 1 year and 56%, 54% and 60%, respectively, in 5 years; patient survivals 86%, 69% and 67%, respectively, in 1 year and 77%, 61% and 62%, respectively, in 5 years. Three ABO-In grafts were lost (one hyper-acute rejection and two hepatic artery thrombosis). Surgical and infectious complications were similarly distributed between groups, except the hepatic artery thrombosis, more frequent in ABO-In (2, 14%) than ABO-I (1, 1.5%, P
to estimate the effect of decompressive stented drainage of biliary anastomosis on incidence of biliary complications.
294 patients aged from 5 months to 61 years (mean 13.8±0.81) were enrolled. They underwent liver fragments transplantation in the Department of Liver Transplantation of Petrovsky Russian Research Center of Surgery for the period from March 1997 to January 2016. Decompressive stented drainage tubes were used in 28 (9.5%) patients. Reconstruction without drainage was applied in 266 (90.5%) cases. In the group of biliobiliary reconstruction drainage was used in 18 out of 89 cases (20.2%), in the group of biliodigestive reconstruction - in 10 out of 202 cases (4.9%). Incidence of specific biliary complications was assessed.
There was significant direct correlation of stented drainage of biliodigestive anastomosis with various biliary complications including bile leakage (r= -0,1253; p=0.06), obturation of anastomosis (r=0.045; p=0.501), stricture of anastomosis (r= -0.0665; p=0.320), other strictures of intrahepatic bile ducts (r= -0.0291; p=0.664), hepatolithiasis (r=0.0857; p=0.199). However significant direct correation was observed between stented drainage and incidence of intrahepatic bile ducts strictures (r=0.2117; p=0.046) and anastomosis obturation (r=0.2330; p=0.028) in case of biliobiliary reconstruction. Significant correation with other biliary complications was absent (p>0.05).
Unconstrained stented drainage during primary biliary reconstruction is associated with increased incidence of biliary complications and should not be indicated routinely. Clear need for drainage should be determined in further investigations.
BACKGROUND: Blocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver transplantation. METHODS: The orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase (AST), alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)-gamma in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope. RESULTS: Isotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver allografts, and a mean graft survival time (MST) of 10.9 days. Administration of anti 4-1BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-gamma. The histological grade of rejection on day 7 decreased and MST (17.3 days) increased substantially. CONCLUSIONS: These results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.
The transition from regular use of cyclosporine to the newer calcineurin-inhibitors, such as tacrolimus, has been suggested as a contributing factor to the "era effect" of worsening outcomes of post-transplant HCV recurrence. This retrospective medical chart review of 458 patients was undertaken to evaluate the role of immunosuppressant choice (cyclosporine vs. tacrolimus) in determining virologic response and clinical outcomes of post-liver transplant HCV infection recurrence. Our results showed that patients undergoing interferon-based treatment taking cyclosporine have significantly better odds (OR: 2.59, P = 0.043) of presenting a sustained viral response (66.7%) compared to tacrolimus (52.8%). This did not result in a significant effect on post-liver transplantation clinical events including HCV-related deaths, graft loss, fibrosing cholestatic hepatitis, hepatocellular carcinoma or graft rejection. Other variables, which showed a significant relationship with the achievement of sustained viral response included donor age (OR 0.96, P = 0.001) and HCV genotype 1 infection (OR 0.05, P
As opposed to most solid-organ transplant recipients, patients with acute liver failure exhibit a pretransplant health status more comparable with the general population, and any posttransplant cardiovascular risk excess should thus be more attributable to transplantation-related factors alone.
This study compared the cardiovascular risk of 77 consecutive patients with acute liver failure at 5 years after liver transplantation with that of the general population using age, sex, and residence area-standardized prevalence ratios (SPR).
At least one cardiovascular risk factor developed in 92% of patients. Treated hypertension, observed in 71% of patients at 5 years, was more common among patients than controls (SPR, 2.73; 95% confidence interval [CI], 2.06-3.55), whereas the 61% prevalence of dyslipidemia and 3% prevalence of impaired fasting glucose were significantly less frequent among patients (SPR, 0.69; 95% CI, 0.51-0.92 and SPR, 0.29; 95% CI, 0.04-1.00). The 5-year prevalence of diabetes (10%), overweight (32%), and obesity (13%) deviated nonsignificantly from controls (SPR 1.90, 0.85, and 0.58). Antibody therapy associated with a 1.49-fold increase in the risk of hypertension (95% CI, 1.15-1.94) and a 6.43-fold increase in the risk of diabetes (95% CI, 1.18-34.9). Immunosuppression-type, steroids, acute rejection, retransplantation, or graft steatosis revealed nonsignificant risk alterations.
Liver transplantation and associated immunosuppression evidently cause hypertension, and possibly elicit diabetes in susceptible individuals. Conversely, the often reported transplantation-associated increased burden of overweight/obesity and dyslipidemia might relate mostly to other factors.
In patients with familial amyloidotic polyneuropathy (FAP), heart complications are prognostic factors for mortality and morbidity after liver transplantation (LT). However, only a few studies have analyzed the development of arrhythmia in transplant patients with FAP. We investigated the development of arrhythmia requiring pacemaker insertion (PMI) in Swedish transplant patients with FAP, and we related the findings to gender, age at disease onset, and survival. One hundred four transplant patients with the amyloidogenic transthyretin Val30Met mutation were included in the study. Twenty-six (25%) received a pacemaker during the observation period (a median of 11 years after disease onset). This frequency was comparable to that noted in a previous study describing the natural course of FAP. No significant differences in PMI between early-onset cases (
Recent studies of liver transplanted (LTx) familial amyloidotic polyneuropathy (FAP) patients have shown a progression of cardiomyopathy in some patients after LTx, but knowledge of the underlying factors remains limited.
Seventy-five patients, who had undergone LTx from 1996 to 2008, were included. They had all been examined by echocardiography 1-16 months before LTx. Fifty-four had been re-examined 7-34 months, and forty-two 36-137 months after LTx.
A significant increase in interventricular septum (IVS) thickness occurred after LTx (p
Liver transplantation is a highly effective treatment for end-stage liver disease. However, there is debate over the practice of liver transplantation in older recipients (age = 60 years) given the relative shortage of donor grafts, worse post-transplantation survival, and concern that that older patients may utilize excess resources postoperatively, thus threatening the economic feasibility of the procedure.
To determine if patients = 60 years of age utilize more health resources following liver transplantation compared with younger patients.
Consecutive adult patients who underwent primary liver transplantation (n = 208) at a single center were studied over a 2.5-year period. Data were collected on clinico-demographic characteristics and resource utilization. Descriptive statistics, including means, standard deviations, or frequencies were obtained for baseline variables. Patients were stratified into 2 groups: age = 60 years (n = 51) and
The non-improvement in >1-year post-liver transplant (LT) survival and diminishing importance of hepatitis C (HCV) with modern antivirals justify identification of early factors predictive of long-term outcome post-LT in HCV-negative recipients.
This nationwide study included all 631 HCV-negative adult patients transplanted in Finland 1982-2013 with at least 1-year graft survival (6311 person-year follow-up). We tested 37 variables, including immunosuppression, for their association with >1-year combined graft loss/mortality, late rejection, cancer, or infections.
Significant multivariate predictors of graft loss/mortality were male gender (HR 2.40, P = 0.001), pretransplant hepatocellular (HR 2.92, P = 0.001) or biliary cancer (HR 12.7, P
*Department of Pediatric Research, Women and Children's Division †Department of Radiology, Rikshospitalet, Oslo University Hospital ‡Department of Paediatric Medicine, Women and Children's Division, Oslo University Hospital, Oslo, Norway.
The aim of the present study was to assess whether the complication rate after ultrasound-guided percutaneous liver biopsies in children is affected by how frequently the procedure is performed by the operator.
Medical charts and ultrasound descriptions of 311 ultrasound-guided percutaneous liver biopsy procedures performed by 18 radiologists at a single center from 2000 to 2011 were reviewed. Postbiopsy ultrasound the following day was performed after 97% of the procedures.
There were no differences in the procedure-associated rate of major bleeding incidents (2.2% vs 0.8%, P = 0.38), minor bleeding incidents (15.2% vs 10.2%, P = 0.31), or abdominal pain (13.0% vs 10.6%, P = 0.61) among operators who performed =10 procedures and those who performed >10 procedures during the study period. A higher rate of minor bleeding incidents were recorded after liver biopsy when operators had performed 20 pediatric liver biopsies during the study period (odds ratio 3.4 [1.3-9.1], P = 0.02). No association between the number of biopsies performed by the operator during the 2 years preceding the date of the biopsy and complications was found.
Major complications are infrequent after pediatric liver biopsies and no relation between operator experience and major complications was found. We found a significant, but minor, effect of operator procedure frequency on the rate of minor bleeding incidents after ultrasound-guided pediatric liver biopsies.