Disease Awaiting Liver Transplantation Research Articles

The assessment of myopenia and muscle biopsy in pediatric patients with liver disease awaiting liver transplantation – A cross-sectional analysis

Little is known about the skeletal muscle characteristics (fibre type proportion and size, location of nuclei, presence of fat infiltration) in children with liver disease with radiologically determined myopenia (low muscle mass). During liver transplantation (LTx) surgery, biopsies from the rectus abdominis muscle were collected. Muscle fibre types (I, I/IIA, IIA, IIA/X, IIX) and CSA index (µm/m2) were determined using immunofluorescence staining. Triacylglycerol (TAG) and phospholipid content of muscle was determined using gas chromatography. Myopenia was defined using study-specific cut offs (skeletal muscle index <-2SD) from age-sex matched healthy control scans. Myopenia was prevalent in 41% of children. Children also had a high prevalence of high muscle adiposity (37%). Children with myopenia were older (8.4 vs. 0.7 yrs; p<0.001), had smaller total (median 595 vs. 844 µm/m2; p=0.04) and hybrid IIA/X (612±143 vs. 993±341 µm/m2; p=0.04) muscle fibre size index, lower prevalence of type I fibres (53 vs. 64%; p=0.01) and higher prevalence of type IIA/X hybrid fibres (median 7.5 vs. 0%; p=0.04). Children with myopenia also had a higher prevalence of elevated TAG content (>75 percentile) within the muscle compared to children without myopenia (36% vs 0%; p=0.009). Percent of muscle fibres with centralized nuclei were not different between groups. In conclusion, children with myopenia experience differences in skeletal muscle biological characteristics when compared to children without myopenia at LTx and these findings may have implications for dietary and exercise rehabilitation pre-and post-LTx.

Sarcopenic obesity in patients awaiting liver transplant: Unique challenges for nutritional recommendations.

Sarcopenic obesity increases the risk of mortality in patients with liver disease awaiting liver transplantation and in the post-transplant period. Nutrition recommendations for individuals with sarcopenia differ from recommendations for patients with obesity or sarcopenic obesity. While these nutrition guidelines have been established in non-cirrhotic patients, established guidelines for liver transplant candidates with sarcopenic obesity are lacking. In this paper, we review existing literature on sarcopenic obesity in patients with chronic liver disease and address opportunities to improve nutritional counseling in patients awaiting liver transplantation.

Portal Hypertension in Malnutrition and Sarcopenia in Decompensated Cirrhosis-Pathogenesis, Implications and Therapeutic Opportunities.

Malnutrition and sarcopenia are highly prevalent in patients with decompensated cirrhosis and are associated with poorer clinical outcomes. Their pathophysiology is complex and multifactorial, with protein-calorie malnutrition, systemic inflammation, reduced glycogen stores and hormonal imbalances all well reported. The direct contribution of portal hypertension to these driving factors is however not widely documented in the literature. This review details the specific mechanisms by which portal hypertension directly contributes to the development of malnutrition and sarcopenia in cirrhosis. We summarise the existing literature describing treatment strategies that specifically aim to reduce portal pressures and their impact on nutritional and muscle outcomes, which is particularly relevant to those with end-stage disease awaiting liver transplantation.

Measurements matter: Assessing outcomes in "lean" patients with nonalcoholic fatty liver disease awaiting liver transplantation.

Measurements matter: Assessing outcomes in "lean" patients with nonalcoholic fatty liver disease awaiting liver transplantation.

Power of mortality prediction in patients awaiting liver transplantation according to the Global Leadership Initiative on Malnutrition criteria and Subjective Global Assessment and Royal Free Hospital Global Assessment scores

ObjectivesThis study aimed to analyze the performance of the Global Leadership Initiative on Malnutrition (GLIM) criteria and Subjective Global Assessment (SGA) and Royal Free Hospital Global Assessment (RFH-GA) scores in predicting 12-mo mortality in patients awaiting liver transplantation. MethodsThis is a longitudinal observational study, carried out between March 2019 and November 2021. Clinical data were collected and nutritional assessment was performed through anthropometry and application of validated instruments, such as the SGA, GLIM criteria, and RFH-GA. A Cox regression model was carried out, in which the dependent variable was mortality in 1 y, and the independent variables were the classifications of nutritional status by the different methods. ResultsThe sample consisted of 126 patients, most of them male (56.35%). Malnutrition was diagnosed in 85.71% of the patients according to the RFH-GA, 62.70% according to the SGA, and 56.31% according to the GLIM criteria. Malnutrition assessed by GLIM was related to a 3.79-fold increase in the chance of mortality over time in patients awaiting liver transplantation. Moreover, the GLIM criteria had good discriminatory power in identifying mortality in patients awaiting liver transplantation, compared with the initial and final SGA and RFH-GA scores and the Model for End-stage Liver Disease–Sodium (MELD-Na) index. ConclusionsThe GLIM criteria were a good predictor of increased risk of mortality in malnourished patients with chronic liver disease awaiting liver transplantation, compared with the SGA and RFH-GA scores and the MELD-Na index.

Cryptogenic hepatitis patients have a higher Bartonella sp.-DNA detection in blood and skin samples than patients with non-viral hepatitis of known cause.

BackgroundThis study aimed to assess the prevalence of Bartonella sp.-DNA detection in blood and skin samples from patients with non-viral end-stage liver disease awaiting liver transplantation.Methodology/Principal findingsBlood samples and healthy skin fragments from 50 patients were tested using microbiological and molecular methods. Fifteen patients had cryptogenic hepatitis (CH) and 35 had alcoholic, drug-induced or autoimmune liver disease. DNA was extracted from whole blood and liquid culture samples, isolates, and skin fragments. Thirteen of the 50 patients (26%) had Bartonella henselae DNA detection in their blood (9/50) and/or skin (5/50) samples. Colonies were isolated in 3/50 (6%) and infection was detected in 7/50 (14%) of the 50 patients. B. henselae-DNA detection was more prevalent in patients with CH than in other patients (p = 0.040). Of 39 patients followed-up for at least two years, a higher mortality rate was observed among patients with CH infected with B. henselae (p = 0.039).Conclusions/SignificanceFurther studies assessing the role of B. henselae infection in the pathogenesis of hepatitis patients must be urgently conducted.

Coronavirus Disease 2019 and Liver Transplantation: Lessons from the First Year of the Pandemic.

Over the last year, the novel coronavirus disease 2019 (COVID‐19) has continued to spread across the globe, causing significant morbidity and mortality among transplantation candidates and recipients. Patients with end‐stage liver disease awaiting liver transplantation and patients with a history of liver transplantation represent vulnerable populations, especially given the high rates of associated medical comorbidities in these groups and their immunosuppressed status. In addition, concerns surrounding COVID‐19 risk in this patient population have affected rates of transplantation and general transplantation practices. Here, we explore what we have learned about the impact of COVID‐19 on liver transplantation candidates and recipients as well as the many key knowledge gaps that remain.

Low Rates of Advance Care Planning (ACP) Discussions Despite Readiness to Engage in ACP Among Liver Transplant Candidates.

Patients with end-stage liver disease awaiting liver transplantation (LT) are seriously ill and experience fluctuating periods of clinical decompensation. Discussion of a patient's advance care planning (ACP) wishes early in their dynamic disease course is critical to providing value-aligned care while awaiting LT. We aimed to evaluate current ACP documentation and assess readiness to engage in ACP in this population. We conducted a retrospective study of adults undergoing LT evaluation from January 2017 to June 2017 and assessed characteristics associated with documentation using logistic regression. We then administered a survey to LT candidates from March 2018 to May 2018 to determine self-reported readiness to engage in ACP (range 1 = not at all ready to 5 = very ready). Among 170 LT candidates, median (interquartile range) age was 58 (53-65), 65% were men, MELDNa was 15 (11-21), and Child-Pugh A/B/C were 33/38/29%. Nine percent reported completing ACP prior to LT evaluation, but 0% had legal ACP forms or end-of-life wishes documented in the medical record. A durable power of attorney (DPOA) was discussed with 10%. In univariable analysis, white race (OR 4.16, p = 0.03) and female sex (OR 3.06, p = 0.04) were associated with ACP documentation, but Child-Pugh score and MELDNa were not. Of the 41 LT candidates who completed the ACP survey, 93% were ready to appoint a DPOA and 85% were ready to discuss end-of-life care. There is a paucity of ACP documentation and identification of DPOA among LT candidates, despite patients reporting readiness to complete ACP and appoint a DPOA. These results reveal an opportunity for tools to facilitate discussions around ACP between clinicians, patients, and their caregivers.

Is renal replacement therapy necessary in deceased donor liver transplantation candidates with hepatorenal syndrome?: a 2-year experience at a high-volume center.

PurposeHepatorenal syndrome (HRS) is a fatal complication in patients with end-stage liver disease awaiting liver transplantation (LT). HRS often develops in patients with high model for end-stage liver disease (MELD) score. This study investigated the outcomes of peritransplant management of HRS in a high-volume LT center in Korea for 2 years.MethodsA total of 157 recipients that deceased donor liver transplantation (DDLT) from January 2017 to December 2018 were included. In-hospital mortality (IHM) was analyzed in relation to pre- and posttransplant application of renal replacement therapy (RRT).ResultsPrimary diagnoses for DDLT were alcoholic liver disease (n = 61), HBV-associated liver cirrhosis (n = 48), retransplantation for chronic graft failure (n = 24), and others (n = 24). Mean MELD score was 34.6 ± 6.2 with 72 patients at Korean Network for Organ Sharing MELD status 2 (45.9%), 43 at status 3 (27.4%), 36 at status 4 (22.9%), and 6 at status 5 (3.8%). Pretransplant RRT was performed in 16 patients (10.2%) that did not show IHM. Posttransplant RRT was performed in 69 patients (44.0%), for whom IHM incidence was 15.9%. In 53 patients that had undergone de novo posttransplant RRT, IHM incidence increased to 20.8%. IHM in the 88 patients not requiring RRT was 2.3%.ConclusionThe majority of adult DDLT recipients in Korean MELD score-based allocation system have very high MELD scores, which is often associated with HRS. Pretransplant RRT appears to improve posttransplant survival outcomes. We thereby recommend that, if indicated, pretransplant RRT be performed while awaiting DDLT.

Effect of vitamin D levels and osteoporosis on survival in patients with chronic liver disease awaiting liver transplantation

Effect of vitamin D levels and osteoporosis on survival in patients with chronic liver disease awaiting liver transplantation

A selective oral vasopressin V2-receptor antagonist for patients with end-stage liver disease awaiting liver transplantation: a preliminary study

Administration of the selective arginine vasopressin V2 receptor antagonist tolvaptan to cirrhotic patients is controversial. There are no reports of tolvaptan use for patients with far-advanced end-stage liver disease (ESLD) and refractory ascites awaiting liver transplantation. Between 2013 and 2016, 64 patients awaiting adult-to-adult living donor liver transplantation (LDLT) were screened for enrollment. Patients with refractory ascites and on dual conventional diuretics (≥ 50 mg/day of spironolactone and ≥ 20 mg/day of a loop diuretic) were enrolled and assigned to the tolvaptan (TOL) group (n = 10), and low-dose tolvaptan, 3.75 mg/day, was started. The remaining patients who had no or little ascites on conventional diuretic therapy (CDT) were assigned to the CDT group (n = 23). The median model for end-stage liver disease and Child-Pugh scores were 16 (range 7-41) and 10 (7-15), respectively. The median dose of spironolactone in the TOL group was 88 mg (range 50-200) vs. 50 (0-100) in the CDT group (p < 0.01). The median dose of loop diuretics in the TOL group was 70 mg (20-120) vs. 20 (0-80) in the CDT group (p = 0.03). No significant liver damage was detected during tolvaptan therapy. Tolvaptan demonstrated favorable effects in 60% (6/10) of the patients, decreasing the body weight by at least 1.5 kg during the 7 day treatment. These findings suggest that low-dose of tolvaptan may be safe for patients having far-advanced ESLD patients with apparent and refractory ascites taking dual conventional diuretics for a short period before LDLT.

Case report of hemorrhagic shock from spontaneous gallbladder rupture in a patient with advanced liver disease awaiting liver transplant

Case report of hemorrhagic shock from spontaneous gallbladder rupture in a patient with advanced liver disease awaiting liver transplant

Role of Nutrition and Feeding for the Chronically Ill Pediatric Liver Patient Awaiting Liver Transplant.

This article reviews the essential role of nutrition in optimizing care for pediatric patients with liver disease awaiting liver transplant. A review of growth and overall principles of feeding for pediatric patients, from infancy through childhood and into adolescence, is provided including the role of macro- and micronutrients, nutrient distribution, and nutrition supplementation. The importance of a thorough nutrition assessment is reviewed, including focus areas the nurse can address with patients and families such as diet histories, growth, and dietary modifications. Suggestions for monitoring and implementing nutrition strategies are provided.

Sa1644 Acute Kidney Injury Severity Predicts Mortality and Response to Terlipressin in Patients With End Stage Liver Disease Awaiting Liver Transplantation

Sa1644 Acute Kidney Injury Severity Predicts Mortality and Response to Terlipressin in Patients With End Stage Liver Disease Awaiting Liver Transplantation

Association of serum zinc levels with liver function and survival in patients awaiting liver transplantation

Purpose: Zinc is an important trace element with catalytic and defensive functions. We assessed the impact of zinc deficiency in patients with end-stage liver disease awaiting liver transplantation.

Clinician assessments of health status predict mortality in patients with end-stage liver disease awaiting liver transplantation.

The US liver allocation system effectively prioritizes most liver transplant candidates by disease severity as assessed by the Model for End-Stage Liver Disease (MELD) score. Yet, one in five dies on the wait-list. We aimed to determine whether clinician assessments of health status could identify this subgroup of patients at higher risk for wait-list mortality. From 2012-2013, clinicians of all adult liver transplant candidates with laboratory MELD≥12 were asked at the clinic visit: 'How would you rate your patient's overall health today (0 = excellent, 5 = very poor)?' The odds of death/delisting for being too sick for the transplant by clinician-assessment score ≥3 vs. <3 were assessed by logistic regression. Three hundred and forty-seven liver transplant candidates (36% female) had a mean follow-up of 13 months. Men differed from women by disease aetiology (<0.01) but were similar in age and markers of liver disease severity (P > 0.05). Mean clinician assessment differed between men and women (2.3 vs. 2.6; P = 0.02). The association between clinician-assessment and MELD was ρ = 0.28 (P < 0.01). 53/347 (15%) died/were delisted. In univariable analysis, a clinician-assessment score ≥ 3 was associated with increased odds of death/delisting (2.57; 95% CI 1.42-4.66). After adjustment for MELD and age, a clinician-assessment score ≥ 3 was associated with 2.25 (95% CI 1.22-4.15) times the odds of death/delisting compared to a clinician-assessment score < 3. A standardized clinician assessment of health status can identify liver transplant candidates at high risk for wait-list mortality independent of MELD score. Objectifying this 'eyeball test' may inform interventions targeted at this vulnerable subgroup to optimize wait-list outcomes.

No association between BMD and prevalent vertebral fractures in liver transplant recipients at time of screening before transplantation.

Osteoporosis and fractures are prevalent after orthotopic liver transplantation (OLT), but data on these skeletal complications are scarce in patients with end-stage liver disease awaiting liver transplantation. To evaluate the prevalence of vertebral fractures (VFs) in OLT recipients at the time of screening for transplantation and to establish the association between bone mineral density (BMD) and these fractures before transplantation. We conducted a retrospective study of consecutive OLT recipients at the Leiden University Medical Centre between 2000 and 2011 at the time of screening for transplantation. Clinical, laboratory, and BMD data were extracted from electronic hospital records. Conventional spinal radiographs were assessed for VF by two independent observers using Genant's semiquantitative method. In total, 162 of the 223 OLT recipients (median age, 51 y; 75% men) who had available BMD and spinal radiographs but who were not receiving bone-modifying treatment at screening for OLT were included in the study. Association between BMD and VF before transplantation. Osteoporosis and osteopenia were prevalent at the lumbar spine in 19 and 38% of subjects, respectively, and in 10 and 42 % at the femoral neck. VFs, mostly grade 1, were prevalent in 56% of the subjects. There was no association between BMD and prevalent VF before transplantation. VFs were prevalent in liver transplant recipients at the time of screening for transplantation, but there was no association between BMD and prevalent fractures. Spinal radiographs should be routinely performed as part of screening protocols before liver transplantation to enable identification of VF and allow timely intervention to potentially decrease or prevent skeletal morbidity after transplantation.

Genetic variation in TNFA predicts protection from severe bacterial infections in patients with end-stage liver disease awaiting liver transplantation

Augmented susceptibility to infections increases mortality in patients with end-stage liver disease (ESLD). We sought to determine the contribution of selected genetic variants involved in inflammatory signalling downstream of the Toll-like receptor 4 (TLR4) to severe bacterial infections (SBIs) in patients with ESLD. We retrospectively assessed incidence of SBIs in 336 adult ESLD patients enlisted for orthotopic liver transplantation (OLT) and genotyped them for TLR4 c.+1196C/T, CD14 c.-159C/T, TNFA c.-238G/A, TNFA c.-863C/A, IL1B c.-31C/T and IL1RN variable number of tandem repeats allelic variants. Principal findings were validated in an independent cohort of 332 ESLD patients. Thirty-four percent of patients from the identification cohort and 40% of patients from the validation cohort presented with SBI while enlisted for OLT. The presence of the variant allele TNFA c.-238A (rs361525) was associated with lower serum levels of TNF-α, and with significantly decreased risk of SBI in both cohorts. Multivariate analysis showed that the relative protection from SBI associated with this allele almost completely negated the increased susceptibility to SBI owed to advanced ESLD. Although not predictive of overall mortality, the presence of the TNFA c.-238A allele was associated with a complete prevention of SBI-related pre-transplant deaths. Our results suggest that genetic variability in inflammatory signalling is associated with the development of SBI in patients with ESLD. Specifically, we identified the importance of the TNFA c.-238A allele as a strong predictor of protection from SBI, and as a genetic marker associated with significantly improved pre-transplant survival in patients with SBI.

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Portal Vein Thrombosis in Patients with End Stage Liver Disease Awaiting Liver Transplantation: Outcome of Anticoagulation

The prevalence of portal vein thrombosis (PVT) increases with the severity of liver disease. Development of PVT is often accompanied by increased rate of morbidity and mortality and may affect patient candidacy for liver transplant. There is limited data regarding the role of anticoagulation therapy in patients with PVT and liver cirrhosis. The aims of this study were to describe the prevalence of hypercoagulable disorders in patients with liver cirrhosis and PVT, and to describe the outcome of anticoagulation in patients with liver cirrhosis and PVT. A retrospective chart review was conducted of patients with liver cirrhosis awaiting liver transplant who were diagnosed with PVT between January 2005 and November 2011. During the study period, 537 patients were evaluated for liver transplant. Sixty-nine (13 %) patients were diagnosed with portal vein thrombosis. Chronic hepatitis C was the cause of liver disease in 24/69 (35 %) patients, and hepatocellular carcinoma was present in 39 % of patients. In 22 patients screened for hypercoagulable disorders, hypercoagulable disorder was diagnosed in one patient (5 %). Twenty-eight (28/69) patients were treated during the study period with warfarin: PVT resolved in 11/28 (39 %), no change in 5/28 (18 %), and 12/28 (43 %) patients showed partial resolution of thrombus. Eight patients received liver transplant while on anticoagulation, and operative notes confirmed patency of PV in all eight patients. PVT is frequently seen in patients with end stage liver disease with prevalence of 13 %. Hypercoagulable disorder was detected in 5 % of the patients screened. Careful use of anticoagulation is safe and effective in patients with PVT.