Effect Of Liver Transplantation Research Articles

Liver Transplantation in Children with Advanced Hepatoblastoma: a Systematic Review and Meta-Analysis

AbstractSurgery is a key factor for the curative treatment of hepatoblastoma. Recent evidence suggests that liver transplantation has a strong effect in treating advanced hepatoblastoma. However, there is no consensus on the effects of liver transplantation. This meta-analysis aims to identify the efficacy and safety of liver transplantation for advanced hepatoblastoma, compared with those of conventional liver resection. Electronic databases were searched for relevant studies published prior to June 2022 to evaluate the survival benefit and safety in patients with advanced hepatoblastoma. The primary outcomes were the overall survival and disease-free survival rates, and the secondary outcomes were the complication and tumor recurrence rates. Five relevant clinical studies with a total of 134 participants were included in this meta-analysis. Compared with aggressive liver resection, liver transplantation had similar overall survival rates and disease-free survival rates after 1 year, 3 years, and 5 years (odds ratio (OR) 1 year = 0.89, 95% CI 0.21–3.79, P = 0.88; OR 3 years = 0.54, 95% CI 0.16–1.81, P = 0.32; OR 5 years = 1.24, 95% CI 0.22–6.82, P = 0.81; OR disease-free 1 year = 2.17, 95% CI 0.56–8.42, P = 0.26; OR disease-free 3 years = 1.42, 95% CI 0.48–4.17, P = 0.53; OR disease-free 5 years = 2.91, 95% CI 0.56–8.52, P = 0.26), tumor recurrence rates (OR = 0.62, 95% CI 0.24–1.60, P = 0.32), and complication rates (OR = 1.46, 95% CI 0.48–4.49, P = 0.51). Sensitivity analysis also demonstrated the same outcomes in terms of the tumor recurrence rate, complication rate, and overall and disease-free survival rates after 1 year, 3 years, and 5 years. The funnel plot indicated a low publication bias. Liver transplantation is an excellent option for advanced hepatoblastoma in children with acceptable perioperative complications, which is not inferior to liver resection. And liver transplantation should be considered the primary curative option when liver resection is not possible.

A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation.

Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), whereas data on mucosal microbiota are less consistent. We aimed to use a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT. We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT) and 40 healthy controls (HCs) and performed sequencing of the 16S ribosomal RNA gene (V3-V4) from ileocolonic biopsies. Intraindividual microbial diversity was reduced in both PSC and PSC-LT versus HCs. An expansion of Proteobacteria was more pronounced in PSC-LT (up to 19% relative abundance) than in PSC (up to 11%) and HCs (up to 8%; Q FDR < 0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no-rPSC), increased variability (dispersion) in the PSC group was found. Five genera were associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont, Klebsiella , were associated with reduced LT-free survival. Concomitant IBD was associated with reduced Akkermansia . Consistent mucosal microbiota features associated with PSC, PSC-IBD, and disease severity, irrespective of LT status, highlight the usefulness of investigating PSC and rPSC in parallel, and suggest that the impact of gut microbiota on posttransplant liver health should be investigated further.

Utilization of elderly donors in liver transplantation for patients with hepatocellular carcinoma: A national retrospective cohort study of China

BackgroundProfound organ shortages worldwide have led to the increased utilization of marginal organs from older individuals. However, the effectiveness of liver transplantation (LT) with organs from elderly donors for patients with hepatocellular carcinoma (HCC) remains controversial. The objective of the current study was to assess the overall survival (OS) and disease-free survival (DFS) of patients with HCC following LT using grafts from deceased donors over 60 years old. Material and methodsPatients with HCC who underwent LT between 2015 and 2018 were identified in the China Liver Transplant Registry database. The overall survival and disease-free survival of older liver donors (OLDs) were compared with those of younger liver donors (YLDs) after propensity score matching. ResultsFrom January 2015 to December 2018, a total of 4971 HCC patients were enrolled in the study according to the screening criteria. The absolute and relative utilization of liver grafts from elderly patients over 60 years for HCC patients increased every year, from 65 (9.3%) in 2015 to 268 (14.5%) in 2018. Disease-free survival (DFS) was significantly lower in HCC patients with elderly donors (both P < 0.05) after propensity score matching. The OLD group had worse DFS than YLD group if patients had tumors beyond the Milan criteria (P < 0.05). ConclusionsThe use of older donors for LT has been growing quickly in the last few years in China. Grafts from older donors can be safely used in HCC recipients with similar OS and comparable perioperative complications. However, further investigation into whether older donor has an impact on recurrence is warranted, especially among those with tumors beyond the Milan criteria.

P-215 Liver transplantation for hilar cholangiocarcinoma: A systematic review and meta-analysis

Both liver transplantation and surgical resection are available for selected patients with hilar cholangiocarcinoma. However, the effect of liver transplantation vs liver resection for patients with this disease remains uncertain. The aim of our study was to evaluate the relative efficacy between liver transplantation and surgical resection in patients with hilar cholangiocarcinoma.

Donor with HLA-C2 is associated with acute rejection following liver transplantation in Southern Chinese.

Apart from presenting peptides to T cells, class I HLA molecules serve as ligands for killer cell immunoglobulin-like receptor (KIRs) and regulate the response of natural killer (NK) cells. The role played by HLA and KIR in the acute rejection (AR) following liver transplantation has been controversial. In this retrospective study, we assessed the influence of class I HLA alleles, HLA matching between donor-recipient pairs, recipient KIR and donor HLA ligands on AR following liver transplantation in southern Chinese. In total, 143 recipients and 78 donors obtained from a single transplant center were included in the study cohort. Thirty-three recipients with histologically confirmed AR were observed. We found that the incidence of AR did not correlate with donor or recipient class I HLA alleles and HLA matching. Neither recipient KIR gene nor the KIR genotype was associated with AR, moreover, high-resolution genotyping of 14 functional KIR genes of recipients showed that no KIR allele was independently associated with AR. However, the frequency of HLA-C2+ donor significantly increased in AR group compared with NAR group (52.9% vs. 24.6%, p=0.03). In the presence of HLA-C2 by the donor allograft, AR was more frequently observed in recipients with normal expressed KIR2DS4 (43.8% vs. 15.0%, p=0.03). Donor with HLA-C2 is therefore a major determinant of AR, which can confer risk effect in liver transplantation. Our findings can provide valuable clues for better understanding pathogenesis of AR and have important clinical implications in liver transplantation for Chinese.

The «microbiome» of post-liver transplant complications

This paper reviews modern literature and presents a brief analysis of our own data on one of the most pressing issues in modern transplantology and, in particular, transplant hepatology – the role and place of gut-liver axis (GLA) in the early post-transplant period.Objective: to compare the correlation between gut microbiome palette and incidence of certain early postoperative complications in liver transplantation.Materials and methods. The study design is presented as a pilot, prospective, observational, double-blind study based on investigation of the composition of the microbiome residing in the large intestinal in patients that underwent orthotopic liver transplantation (OLTx). The primary cohort of patients consisted of 12 patients who underwent OLTx from a postmortem donor. To assess the gut microbiome palette, biomaterial was collected from all patients in the preand post-transplant period followed by next-generation sequencing. The study was conducted as primary study results registered under number NCT04281797.Results. In the preoperative period, differences close to statistically reliable in relation toActinobacteriawere observed in patients included in the liver transplant waiting list for cirrhosis (LC) and hepatocellular carcinoma (HCC) in cirrhosis. However, due to the pilot nature of the study, this study cohort was limited to an extremely small sample. In turn, in the post-transplant period, there was a statistically significant difference in the taxonomic range ofActinobacteria(p &lt; 0.05) between the above groups, indicating a possible effect of liver transplantation on the gut microbiome. In addition, in the early post-transplant period, there was a marked difference in the microbiome palette between patients with and without acute cellular rejection.Conclusion. GLA and the gut microbiome play a critical role in many liver diseases, and may also have a significant impact on the post-transplant period. In this regard, further research in this direction will not only characterize the predictors and risk factors of bacterial infection and rejection episodes, but will also allow us to form a completely new approach to the treatment tactics for certain complications, including through formation of a microbiota-oriented pharmacotherapy.

Effects of liver transplantation on sexual function and quality of life

ABSTRACT This descriptive study aimed to determine patients’ sexual dysfunction and quality of life before and after liver transplantation. The study was conducted with 64 patients who underwent liver transplantation at a university hospital between January 2015 and 2017. The patients were aged 18 or over, able to answer relevant questions and volunteered to participate in the study. The population of the study included patients who underwent liver transplantation on the specified dates and agreed to participate in the study. Descriptive Characteristics Form, Short Form-36 (SF-36), Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF) were used for data collection. A significant increase was found in all subscale scores of males on the IIEF scale after transplantation (p = 0.000). The total FSFI score of the females was 24.27 ± 18.60 before transplantation and 29.62 ± 25.19 after transplantation. The results were not statistically significant (p = 0.072). After transplantation, a highly significant increase was observed in the Physical Component Summary and Mental Component Summary subscale scores of the SF-36 both in males and females (p = 0.000). An increase was observed in the sexual functions of males and females after transplantation. A statistically significant increase was found in the mean scores of both males and females on the quality of life after transplantation (p = 0.000). This study concluded that sexual functions of male (p < 0.05) and female (p > 0.05) patients improved after transplantation.

Effect of liver transplantation on QT-interval prolongation and impact on mortality

BackgroundQT-interval prolongation is considered the electrophysiological hallmark of cirrhotic cardiomyopathy. However, the significance of QT-interval prolongation and how it is affected by liver transplantation (LT) remains unclear. MethodsConsecutive inpatients undergoing LT between 2010 and 2017 at a state-wide liver transplant center in Australia were included. Preoperative, early postoperative and long-term follow-up corrected QT-intervals (QTc) were manually measured by a cardiologist. QTc was calculated using the Bazett formula and QTc ≥440 milliseconds (ms) was considered prolonged. ResultsOverall, 1111 ECG tracings among 408 patients (mean age 57 ± 12 years) were assessed. Pre-LT, 265 patients (65.0%) had QTc ≥440 ms and 24 patients (5.9%) had QTc ≥500 ms. In the early postoperative period, there was a significant increase in QTc compared to pre-LT (471 ± 39 vs. 452 ± 31 ms, p < 0.001) and 80 patients (20.3%) had QTc ≥500 ms. At a median of six months post-LT, there was significant reduction in mean QTc compared to pre-LT (430 ± 32 vs. 452 ± 31 ms; p < 0.001) with the QTc shortening in 73% of patients. QT-interval prolongation was not associated with postoperative complications or mortality at any time-point. ConclusionQT-interval prolongation is common in patients with liver cirrhosis and this metric normalized in the majority within six months post-LT. A significant increase in QTc was noted early post-LT, with over 20% demonstrating QTc ≥500 ms. QT-interval prolongation was not associated with post-transplant complications or mortality. Resolution of QT-interval prolongation suggests that this feature of cirrhotic cardiomyopathy may reverse post-transplantation.

The long-term outcomes of deceased-donor liver transplantation for primary biliary cirrhosis: a two-center study in China

Background & AimsFactors that influence the outcomes after deceased-donor liver transplantation (DDLT) for primary biliary cirrhosis (PBC) are not well known. We aimed to clarify these effects on the outcomes after DDLT.MethodsWe retrospectively analyzed patients with PBC who underwent DDLT from March 2006 to July 2018 at the organ transplantation center of the First Hospital of Jilin University and the First Central Hospital of Tianjin. Changes in liver function were assessed posttransplantation. Recurrence, survival rate, and complications were recorded at follow-up. The effect of liver transplantation on survival and recurrence was evaluated using univariate and/or multivariate Cox regression analyses.ResultsIn total, 69 patients with PBC undergoing DDLT were included in this study. At 4 weeks posttransplant, all liver function tests were normal. During a median follow-up time of 32 months, 5-year overall survival and recurrence rates were estimated as 95.1% and 21.8%, respectively. A recipient aspartate aminotransferase-to-platelet ratio index (APRI) greater than 2 was negatively associated with survival (P = 0.0018). Multivariate regression analysis demonstrated that age younger than 48 years was an independent risk factor for recurrent PBC in recipients undergoing liver transplantation (hazard ratio 0.028, 95% confidence interval 0.01–0.71, P = 0.03). Posttransplant infections (62%) and biliary tract complications (26%) were the most common complications.ConclusionLiver transplantation is an effective treatment for patients with PBC. Liver function normalizes by 4 weeks posttransplant. Although posttransplant survival rate is high, recurrence is possible. To some extent, survival rate and recurrence rate can be predicted by APRI and age, respectively.

Effect of liver transplantation on intestinal permeabilityand correlation with infection episodes.

BackgroundLiver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections.MethodsLT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA).ResultsThe median 51Cr-EDTA excretion was found to be higher in 35 LT recipients as compared with that in the healthy controls [4.77% (2.79–6.03) vs. 2.07% (1.57–2.42), p<0.0001], and comparable to that in the cirrhotic patients [3.69% (2.34–6.57), p = 0.445]. 51Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections [infection/no infection: 4.97% (3.14–7.03) vs 4.62% (2.79–5.82), p = 0.938].ConclusionLT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted.

The effect of liver transplantation on patient-centred outcomes: A propensity-score matched analysis

The effect of liver transplantation on patient-centred outcomes: A propensity-score matched analysis

The Observer Effect in Liver Transplantation Exemplified by Unintended Consequences of Regulation and Selected Outcome Metrics.

The Observer Effect in Liver Transplantation Exemplified by Unintended Consequences of Regulation and Selected Outcome Metrics.

Effects of liver transplantation on health-related quality of life in patients with primary biliary cholangitis.

Patients with primary biliary cholangitis (PBC) have decreased health-related quality of life (HRQoL). Here, we investigate HRQoL in two cohorts of transplanted patients with PBC and compare their results to healthy subjects. We used generic SF-36 and disease-specific PBC-40 questionnaires to evaluate HRQoL in 26 patients with PBC (23 females, age 59.4±5.7years) before and after liver transplantation (LT), and in 107 patients with PBC (99 females, age 62.8±6.7years) who were previously transplanted. The control group was comprised of 60 healthy controls (55 females, age 54.6±8.8years). Health-related quality of life improved after LT in 85% of PBC patients. The SF-36 measure showed significant (all P<0.05) improvements in the majority of domains after LT, and in the summary scores both physical and mental. We also documented significant improvements in pruritus andfatigue after LT (all P<0.01). However, liver graft recipients had significantly worse physical functioning, physical role, and emotional role domains, and physical component score (all P<0.001), as compared to healthy subjects. No differences in HRQoL were detected between patients evaluated after short and prolonged post-LT periods (P>0.05). Liver transplantation substantially improves most aspects of life quality in PBC patients. Nevertheless, their HRQoL remains worse in comparison to healthy individuals, mainly in physical aspects.

Intravenous Anesthetic Protects Hepatocyte from Reactive Oxygen Species-Induced Cellular Apoptosis during Liver Transplantation In Vivo.

Background Liver transplantation leads to liver ischemia/reperfusion (I/R) injury, resulting in early graft dysfunction and failure. Exacerbations of oxidative stress and inflammatory response are key processes in the development of liver I/R injury. Intravenous anesthetic propofol potent effects on free radical scavenging and protects livers against I/R injury. However, the role and mechanism of propofol-mediated hepatic protection in liver transplantation is poorly understood. The aim of this study was to evaluate the role of propofol postconditioning in the liver I/R injury after liver transplantation. Methods Forty-eight rats were randomly divided into six groups: rats receiving either sham operation or orthotopic autologous liver transplantation (OALT) in the absence or presence of propofol (high dose and low dose) postconditioning or intralipid control or VAS2870 (Nox2 special inhibitor). Eight hours after OALT or sham operation, parameters of organ injury, oxidative stress, inflammation, and NADPH-associated proteins were assessed. Results After OALT, severe liver pathological injury was observed that was associated with increases of serum AST and ALT, which were attenuated by propofol postconditioning. In addition, especially high dose of propofol postconditioning reduced TNF-α, IL-1β, IL-6, TLR4, and NF-κB inflammatory pathway, accompanied with decrease of neutrophil elastase activity, MPO activity, 8-isoprotane, p47phox and gp91phox protein expressions, and increase of SOD activity. Inhibition of Nox2 by VAS2870 conferred similar protective effects in liver transplantation. Conclusion Liver transplantation leads to severe inflammation and oxidative stress with NADPH oxidase activation. Propofol postconditioning reduces liver I/R injury after liver transplantation partly via inhibiting NADPH oxidase Nox2 and the subsequent inflammation and oxidative stress.

The weekend effect in liver transplantation.

BackgroundThe weekend effect describes a phenomenon whereby patients admitted to hospitals on weekends are at higher risk of complications compared to those admitted during weekdays. However, if a weekend effect exists in orthotopic liver transplantation (oLT).MethodsWe analyzed oLT between 2006 and 2016 and stratified patients into weekday (Monday to Friday) and weekend (Saturday, Sunday) groups. Primary outcome measures were one-year patient and graft survival.Results364 deceased donor livers were transplanted into 329 patients with 246 weekday (74.77%) and 83 weekend (25.23%) patients. Potential confounders (e.g. age, ischemia time, MELD score) were comparable. One-year patient and graft survival were similar. Frequencies of rejections, primary-non function or re-transplantation were not different. The day of transplantation was not associated with one-year patient and graft survival in multivariate analysis.ConclusionsWe provide the first data for the Eurotransplant region on oLT stratified for weekend and weekday procedures and our findings suggest there was no weekend effect on oLT. While we hypothesize that the absent weekend effect is due to standardized transplant procedures and specialized multidisciplinary transplant teams, our results are encouraging showing oLT is a safe and successful procedure, independent from the day of the week.

FRI-044 - Effects of liver transplantation (LTx) on health-related quality of life (HRQoL) in patients with PBC

FRI-044 - Effects of liver transplantation (LTx) on health-related quality of life (HRQoL) in patients with PBC

The center effect in liver transplantation in the Eurotransplant region: a retrospective database analysis

Apart from donor and recipient risk factors, the effect of center-related factors has significant impact on graft survival after liver transplantation (LT). To investigate this effect in Eurotransplant, a retrospective database analysis was performed, including all LT's in adult recipients (≥18years) in the Eurotransplant region from 1.1.2007 until 31.12.2013. Additionally, a survey was sent out to all transplant centers requesting information on surgeons' experience and exposure. In total, 10265 LT's were included (median follow-up 3.3years), performed in 39 transplant centers. Funnel plots showed significant differences in graft survival between the transplant centers. After correction for donor and recipient risk, with the Eurotransplant donor risk index (ET-DRI) and the simplified recipient risk index (sRRI) and random effects, these differences diminished. Mean historical volume (in the preceding 5years) was a significant (P<0.001), nonlinear marker for graft survival in the multivariate analysis. This study demonstrates that funnel plots can be used for benchmarking purposes in LT. Case-mix correction can be performed with the use of the ET-DRI and sRRI. The center effect encompasses the entire complex process of preoperative workup, operation to follow-up.

Progression of myocardial sympathetic denervation assessed by 123I-MIBG imaging in familial amyloid polyneuropathy and the effect of liver transplantation

IntroductionFamilial amyloid polyneuropathy (FAP) is a rare disease caused by systemic deposition of amyloidogenic variants of the transthyretin (TTR) protein. The TTR-V30M mutation is caused by the substitution of valine by methionine at position 30 and mainly affects the peripheral and autonomic nervous systems. Cardiovascular manifestations are common and are due to autonomic denervation and to amyloid deposition in the heart. Cardiac sympathetic denervation detected by iodine-123 labeled metaiodobenzylguanidine (MIBG) is an important prognostic marker in TTR-V30 M FAP. Liver transplantation, widely used to halt neurological involvement, appears to have a varying effect on the progression of amyloid cardiomyopathy. Its effect on the progression of cardiac denervation remains unknown. MethodsIn this observational study, patients with the TTR-V30 M mutation underwent annual cardiac assessment and serial MIBG imaging with quantification of the late heart-to-mediastinum (H/M) ratio. ResultsWe studied 232 patients (median age 40 years, 54.7% female, 37.9% asymptomatic at the time of inclusion) who were followed for a median of 4.5 years and underwent a total of 558 MIBG scans. During follow-up, 47 patients (20.3%) died. MIBG scintigraphy at inclusion was a strong predictor of prognosis, with the risk of death increasing by 27.8% for each one-tenth reduction in the late H/M ratio. The late H/M ratio decreased with age (0.082/year, p<0.001), but progression of cardiac denervation was so slow that annual repetition of MIBG imaging did not increase its prognostic accuracy. During follow-up, 70 symptomatic patients underwent liver transplantation. The late H/M ratio decreased by 0.19/year until transplantation but no statistically significant differences were detected after the procedure. ConclusionsCardiac denervation is common during the progression of TTR-V30 M FAP and quantification of the late H/M ratio on MIBG scintigraphy is valuable for prognostic stratification of these patients. Liver transplantation stabilizes cardiac denervation, without recovery or further deterioration in cardiac MIBG uptake after the procedure.

FRI-504 - Effects of liver transplantation on cardiac function in patients transplanted for NASH cirrhosis

FRI-504 - Effects of liver transplantation on cardiac function in patients transplanted for NASH cirrhosis

The effect of Liver Transplantation on the quality of life of the recipient's main caregiver – a systematic review

Liver transplantation (LT) is a transformative, life-saving procedure with life-long sequale for patients and their caregivers. The impact of LT on the patient's main caregiver can be underestimated. We carried out a systematic review of the impact of LT on the Health-Related Quality of Life (HRQL) of LT patients' main caregivers. We searched 13 medical databases from 1996 to 2015. We included studies with HRQL data on caregivers of patients following LT then quality assessed and narratively synthesized the findings from these studies. Of 7076 initial hits, only five studies fell within the scope of this study. In general, they showed caregiver burden persisted in the early period following LT. One study showed improvements, however, the other four showed caregiver's levels of stress, anxiety and depression, remained similar or got worse post-LT and remained above that of the normal population. It was suggested that HRQL of the patient impacted on the caregiver and vice versa and may be linked to patient outcomes. No data were available investigating which groups were at particular risk of low HRQL following LT or if any interventions could improve this. The current information about LT caregivers' needs and factors that impact on their HRQL are not adequately defined. Large studies are needed to examine the effects of LT on the patients' family and caregivers to understand the importance of caregiver support to maximize outcomes of LT for the patient and their caregivers.