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1.
Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy.
Yoshizumi, T, Mori, M
Surgery today. 2020;(1):21-29
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Abstract
Small-for-size graft (SFSG) syndrome after living donor liver transplantation (LDLT) is the dysfunction of a small graft, characterized by coagulopathy, cholestasis, ascites, and encephalopathy. It is a serious complication of LDLT and usually triggered by excessive portal flow transmitted to the allograft in the postperfusion setting, resulting in sinusoidal congestion and hemorrhage. Portal overflow injures the liver directly through nutrient excess, endothelial activation, and sinusoidal shear stress, and indirectly through arterial vasoconstriction. These conditions may be attenuated with portal flow modulation. Attempts have been made to control excessive portal flow to the SFSG, including simultaneous splenectomy, splenic artery ligation, hemi-portocaval shunt, and pharmacological manipulation, with positive outcomes. Currently, a donor liver is considered a SFSG when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. A strategy for transplanting SFSG safely into recipients and avoiding extensive surgery in the living donor could effectively address the donor shortage. We review the literature and assess our current knowledge of and strategies for portal flow modulation in LDLT.
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OPTN/SRTR 2018 Annual Data Report: Liver.
Kwong, A, Kim, WR, Lake, JR, Smith, JM, Schladt, DP, Skeans, MA, Noreen, SM, Foutz, J, Miller, E, Snyder, JJ, et al
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020;:193-299
Abstract
Data on adult liver transplants performed in the US in 2018 are notable for (1) continued growth in numbers of new waitlist registrants (11,844) and transplants performed (8250); (2) continued increase in the transplant rate (54.5 per 100 waitlist-years); (3) a precipitous decline in waitlist registrations and transplants for hepatitis-C-related indications; (4) increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non-alcoholic fatty liver disease; (5) increased use of hepatitis C virus antibody-positive donor livers; and (6) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity and diabetes. Variability in transplant rates remained by candidate race, hepatocellular carcinoma status, urgency status, and geography. The volume of pediatric liver transplants was relatively unchanged. The highest rate of pre-transplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than in the past, as evidenced by higher model for end-stage liver disease/pediatric end-stage liver disease scores and listings at status 1A and 1B at transplant. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time.
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3.
Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management.
Cigrovski Berkovic, M, Virovic-Jukic, L, Bilic-Curcic, I, Mrzljak, A
World journal of gastroenterology. 2020;(21):2740-2757
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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4.
Management of Recurrent HCC After Liver Transplantation.
Sarici, B, Isik, B, Yilmaz, S
Journal of gastrointestinal cancer. 2020;(4):1197-1199
Abstract
BACKGROUND Liver transplantation is the best treatment option for hepatocellular carcinoma (HCC). Although centers use strict selection criteria, there is a risk of recurrence, reaching up to 20% which are mostly observed within two years following the procedure. The survival after the recurrence is poor and it has been reported to be between 7-16 months. This poor prognosis is due to the systemic course of the recurrence even its presentation is local initially. RESULTS The clinical management and treatment algorithm of recurrence is challenging and there is no guideline regarding the situation. Staging of the disease and multi-disciplinary approach are important. The decision for choice of treatment is given depending on the localization and spread of the recurrence. Adjusting and switching the immunosuppressive therapy should be the first attempt. When the recurrence is limited or confined to resectable regions, surgery should be the choice of treatment. Multiple recurrence sites such as adrenal glands, lung, lymph nodes are not contraindication for curative surgery. Resection of the graft for intrahepatic recurrence is the most beneficial procedure for survival. If resection is not possible due to advanced hepatic disease, loco-regional therapies such as TACE, RF, microwave ablation should be considered. SBRT may be an alternative both for hepatic and extra-hepatic recurrence. In case of systemic disease, sorafenib should be the drug choice.
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5.
Acute kidney injury: A critical care perspective for orthotopic liver transplantation.
MacDonald, AJ, Karvellas, CJ
Best practice & research. Clinical anaesthesiology. 2020;(1):69-78
Abstract
Acute kidney injury (AKI) is associated with high perioperative mortality in patients undergoing liver transplantation (LT). In the era of Model of End-stage Liver Disease score-based allocation, more patients with impaired renal function are receiving LT. The majority of preoperative AKI is secondary to azotemia, including hepatorenal syndrome - a progressive form of renal impairment unique to liver failure. Prompt recognition and initiation of cause-directed therapies are central to improving post-transplant survival. Given that, the healthcare providers must develop an expertise in liver failure-related renal complications, specifically their management and perioperative implications. Notably, AKI may complicate intraoperative course, exacerbating hemodynamic instability, metabolic acidosis, and electrolyte and coagulation abnormalities. Adjunctive intraoperative continuous renal replacement therapy has been employed; however, prospective studies remain necessary to validate potential benefits.
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Effect of the proton-pump Inhibitor pantoprazole on MycoPhenolic ACid exposure in kidney and liver transplant recipienTs (IMPACT study): a randomized trial.
Sunderland, A, Russ, G, Sallustio, B, Cervelli, M, Joyce, D, Ooi, E, Jeffrey, G, Boudville, N, Chakera, A, Dogra, G, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(6):1060-1070
Abstract
BACKGROUND Mycophenolic acid (MPA) is widely utilized as an immunosuppressant in kidney and liver transplantation, with reports suggesting an independent relationship between MPA concentrations and adverse allograft outcome. Proton-pump inhibitors (PPIs) may have variable effects on the absorption of different MPA formulations leading to differences in MPA exposure. METHODS A multicentre, randomized, prospective, double-blind placebo-controlled cross-over study was conducted to determine the effect of the PPI pantoprazole on the MPA and its metabolite MPA-glucuronide (MPA-G) area under the curve (AUC) >12 h (MPA-AUC12 h) in recipients maintained on mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). We planned a priori to examine separately recipients maintained on MMF and EC-MPS for each pharmacokinetic parameter. The trial (and protocol) was registered with the Australian New Zealand Clinical Trials Registry on 24 March 2011, with the registration number of ACTRN12611000316909 ('IMPACT' study). RESULTS Of the 45 recipients screened, 40 (19 MMF and 21 EC-MPS) were randomized. The mean (standard deviation) recipient age was 58 (11) years with a median (interquartile range) time post-transplant of 43 (20-132) months. For recipients on MMF, there was a significant reduction in the MPA-AUC12 h [geometric mean (95% confidence interval) placebo: 53.9 (44.0-65.9) mg*h/L versus pantoprazole: 43.8 (35.6-53.4) mg*h/L; P = 0.004] when pantoprazole was co-administered compared with placebo. In contrast, co-administration with pantoprazole significantly increased MPA-AUC12 h [placebo: 36.1 (26.5-49.2) mg*h/L versus pantoprazole: 45.9 (35.5-59.3) mg*h/L; P = 0.023] in those receiving EC-MPS. Pantoprazole had no effect on the pharmacokinetic profiles of MPA-G for either group. CONCLUSIONS The co-administration of pantoprazole substantially reduced the bioavailability of MPA in patients maintained on MMF and had the opposite effect in patients maintained on EC-MPS, and therefore, clinicians should be cognizant of this drug interaction when prescribing the different MPA formulations.
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7.
Energy Balance and Nutrition Status: A Prospective Assessment of Patients Undergoing Liver Transplantation.
Ribeiro, HS, Coury, NC, de Vasconcelos Generoso, S, Lima, AS, Correia, MITD
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2020;(1):126-132
Abstract
BACKGROUND Energy balance (EB) and its relation to nutrition status throughout the perioperative period of liver transplantation (LTx) patients has been poorly reported in the literature, and this is the primary objective of the current study. METHODS A prospective observational study was conducted with patients undergoing LTx, who were assessed before and after the operation. Resting energy expenditure, total energy expenditure (TEE), dietary intake, and EB were evaluated, as well as anthropometry, handgrip strength, and standard phase angle (SPA). The presence of complications after the operation, length of intensive care unit and hospital stay, and death were registered. A P-value < 0.05 was considered statistically significant. RESULTS The average age was 54.1 ± 11.5 years; 79.3% of the patients were male, and the mean model for end-stage liver disease (MELD) score was 16.7 ± 4.6. Negative EB was seen in 71.4% and 77.8% of patients before and after LTx, respectively. Food intake further decreased after the operation, leading to a significantly more negative EB. The prevalence of malnutrition ranged from 17.2% to 57.7% pretransplantation and 30.8% to 86.4% postoperatively, according to the different methods used. Increased preoperative TEE (0.040) and age (0.039) were predictive factors for complications, and low SPA was a predictive factor of death (0.038). CONCLUSION Negative EB was prevalent, and this was associated with high rates of malnutrition. These data reinforce the importance of individual nutrition assessment, including dietary intake, to tailor early nutrition interventions.
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8.
Glomerular filtration rate in liver transplant for unresectable hepatoblastoma.
Peña Zavala, R, Marzouki, M, Beaunoyer, M, Alvarez, F
Pediatric transplantation. 2020;(6):e13746
Abstract
Most children with hepatoblastoma manifest, at the time of LT, a decrease in renal function due to chemotherapy that could be further deteriorated by the use of calcineurin inhibitors. The purpose of this work was to examine the long-term follow-up of renal function in a cohort of children transplanted for unresectable hepatoblastoma. We present a retrospective observational study of 10 pediatric patients who received a LT for unresectable hepatoblastoma between 1996 and 2016. All patients included in this study were followed up on a regular basis and were assessed for GFR before transplantation and at least once a year during follow-up. All patients received standardized chemotherapy treatment for hepatoblastoma and immunosuppression according to hospital protocols. There was a marked decrease in GFR at the time of the LT in five patients presenting renal complications during the pretransplant cycles of chemotherapy. Three patients, one of them with prior kidney involvement, presented complications after LT, namely acute kidney failure and decrease in GFR. Those patients who presented with the lowest GFR at the time of LT eventually recovered renal function at levels similar to the rest of the group on follow-up. Chemotherapy-induced nephrotoxicity is a concern in patients treated for hepatoblastoma. Some individuals will develop low GFR after chemotherapy; therefore, strict follow-up is recommended, as low GFR may affect the doses of subsequent chemotherapy and immunosuppression. Stabilization of GFR levels and occasional improvement can be observed in the post-transplant period.
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9.
Effects of both Pro- and Synbiotics in Liver Surgery and Transplantation with Special Focus on the Gut-Liver Axis-A Systematic Review and Meta-Analysis.
Kahn, J, Pregartner, G, Schemmer, P
Nutrients. 2020;(8)
Abstract
The gut-liver axis is of upmost importance for the development of infections after surgery. Further bacterial translocation due to surgery-related dysbiosis is associated with limited detoxification function of the liver compromising outcome of surgical therapy. After liver surgery, about 30% of patients develop a bacterial infection, with the risk of bacteremia or even sepsis-associated liver failure and mortality in >40%. The potential benefit of pro-/synbiotics given before surgery is still under debate. Thus, a systematic literature search on trials comparing patients with or without supplementation and outcome after liver resection or transplantation was performed. Our search strategy revealed 12 relevant studies on perioperative administration of pro-/synbiotics in liver surgery. The pro-/synbiotic combinations and concentrations as well as administration timeframes differed between studies. Five studies were performed in liver transplantation and 7 in liver resection. All studies but one reported lower infection rates (pooled RR: 0.46, 95% CI: 0.31-0.67) with pro-/synbiotics. Liver function was assessed after LT/LR in 3 and 5 studies, respectively. Pro-/synbiotics improved function in 1/3 and 2/5 studies, respectively. Concluding, perioperative pro-/synbiotics clearly reduce infection after liver surgery. However, standard protocols with both well-defined probiotic strain preparations and administration timeframes are pending.
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10.
Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: a case report and literature review.
Tohyama, T, Sakamoto, K, Tamura, K, Nakamura, T, Watanabe, J, Wakisaka, H, Takada, Y
World journal of surgical oncology. 2020;(1):109
Abstract
BACKGROUND The most common sites of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been reported to be the liver, lung, bone, and adrenal glands, but there have also been many reports of cases of multiple recurrence. The prognosis after recurrence is poor, with reported median survival after recurrence of HCC ranging from 9 to 19 months. Here, we report a case of long-term survival after recurrence of pharyngeal metastasis following living-donor liver transplantation (LDLT) for HCC within the Milan criteria, by resection of the metastatic region and cervical lymph node dissection. CASE PRESENTATION A 47-year-old man with a Model End-stage Liver Disease (MELD) score of 11 underwent LDLT for HCC within the Milan criteria for liver cirrhosis associated with hepatitis B virus infection, with his 48-year-old elder brother as the living donor. One year and 10 months after liver transplantation, he visited a nearby hospital with a chief complaint of discomfort on swallowing. A pedunculated polyp was found in the hypopharynx, and biopsy revealed HCC metastasis. We performed pharyngeal polypectomy. Two years later, cervical lymph node metastasis appeared, and neck lymph node dissection was performed. Although recurrence subsequently occurred three times in the grafted liver, the patient is still alive 12 years and 10 months after recurrence of pharyngeal metastasis. He is now a tumor-free outpatient taking sorafenib. CONCLUSION It is necessary to recognize that the nasopharyngeal region is a potential site of HCC metastasis. Prognostic improvement can be expected with close follow-up, early detection, and multidisciplinary treatment, including radical resection.