-
1.
Clinical use of N-acetyl cysteine during liver transplantation: Implications of oxidative stress and inflammation as therapeutic targets.
Ntamo, Y, Ziqubu, K, Chellan, N, Nkambule, BB, Nyambuya, TM, Mazibuko-Mbeje, SE, Gabuza, KB, Orlando, P, Tiano, L, Dludla, PV
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112638
Abstract
Currently, liver transplantation is considered as the definitive treatment option for individuals with complete liver failure. However, the detrimental effects of oxidative stress and inflammation remain the predominant feature that drives hepatic ischemia-reperfusion injury during liver transplantation. As such, therapeutic drugs that hinder oxidative stress and attenuate inflammation, have become ideal targets to curb liver injuries during transplantation. The current review analyses available clinical evidence on the importance of using N-acetyl cysteine (NAC) during liver transplantation. Thus, prominent online search engines such as PubMed and Google Scholar were accessed to retrieve literature from randomized clinical trials reporting on the use of NAC during liver transplantation. Overwhelming evidence suggests that established therapeutic properties of NAC, through enhancing endogenous antioxidants like glutathione to block oxidative stress and attenuate inflammation, remain essential to improve liver function in patients undergoing liver transportation. However, to the contrary, some clinical studies did not show any beneficial effects in patients receiving NAC during liver transplantation. Thus, such controversies, in addition to discussing the implications of oxidative stress and inflammation in relation to hepatic ischemia-reperfusion injury remain the major subject of the current review.
-
2.
The role of the gut microbiome in graft fibrosis after pediatric liver transplantation.
Qin, T, Fu, J, Verkade, HJ
Human genetics. 2021;(5):709-724
-
-
Free full text
-
Abstract
Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.
-
3.
Domino transplantation for pediatric liver recipients: Obstacles, challenges, and successes.
Raghu, VK, Carr-Boyd, PD, Squires, JE, Vockley, J, Goldaracena, N, Mazariegos, GV
Pediatric transplantation. 2021;(8):e14114
-
-
Free full text
-
Abstract
BACKGROUND Domino liver transplantation aims to address the need to increase the liver donor supply. In a domino liver transplant, the domino recipient receives the explanted liver from the recipient of a traditional liver transplant. The domino donor typically requires liver transplant to correct a metabolic disorder; the explanted liver thus has a single gene defect but otherwise normal structure and function. METHODS In this review, we detail the history of domino liver transplantation, appropriate domino donor indications, the technical advances to the surgical approach, current outcomes, and future opportunities. RESULTS Development of de novo disease in the domino recipient has relegated adult domino liver transplant to be considered a source of marginal donor livers. However, pediatric domino liver transplant has leveraged certain metabolic disorders, especially maple syrup urine disease, in which the liver enzyme deficiency can be compensated by the systemic presence of sufficient enzyme. Advances in the surgical aspects of assuring adequate length of vasculature have improved the safety of the procedure in both domino donors and recipients. CONCLUSIONS Pediatric domino liver transplant utilizing domino donors with specific metabolic liver diseases should be considered a viable live donor option for children awaiting liver transplant.
-
4.
Cardiac evaluation of the kidney or liver transplant candidate.
Levy, PE, Khan, SS, VanWagner, LB
Current opinion in organ transplantation. 2021;(1):77-84
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW As the field of transplant has advanced, cardiac events have become the leading cause of morbidity and mortality after liver and kidney transplantation ahead of graft failure and infection. This trend has been bolstered by the transplantation of older and sicker patients who have a higher burden of cardiovascular risk factors, accentuating the need to determine which patients should undergo more extensive cardiac evaluation prior to transplantation. RECENT FINDINGS Computed tomography coronary angiography with or without coronary artery calcium scoring is now preferred over stress imaging in most transplant candidates for assessment of coronary artery disease. Assessment of cardiac structure and function using transthoracic echocardiography with tissue doppler imaging and strain imaging is recommended, particularly in liver transplant candidates who are at high risk of cirrhotic cardiomyopathy, for which new diagnostic criteria were recently published in 2019. SUMMARY Cardiac evaluation of liver and kidney transplant candidates requires a global assessment for both short and long-term risk for cardiac events. Imaging of cardiac structure and function using transthoracic echocardiography with tissue doppler imaging and strain imaging is recommended. Risk stratification should consider both the anatomic and functional consequences of coronary artery disease in transplant candidates. VIDEO ABSTRACT http://links.lww.com/MOT/A27.
-
5.
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.
-
6.
Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy.
Yoshizumi, T, Mori, M
Surgery today. 2020;(1):21-29
-
-
Free full text
-
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.
-
7.
Post-transplantation Outcomes in Patients with PA or MMA: A Review of the Literature.
Yap, S, Vara, R, Morais, A
Advances in therapy. 2020;(5):1866-1896
-
-
Free full text
-
Abstract
INTRODUCTION Liver transplantation is recognised as a treatment option for patients with propionic acidemia (PA) and those with methylmalonic acidemia (MMA) without renal impairment. In patients with MMA and moderate-to-severe renal impairment, combined liver-kidney transplantation is indicated. However, clinical experience of these transplantation options in patients with PA and MMA remains limited and fragmented. We undertook an overview of post-transplantation outcomes in patients with PA and MMA using the current available evidence. METHODS A literature search identified publications on the use of transplantation in patients with PA and MMA. Publications were considered if they presented adequate demographic and outcome data from patients with PA or MMA. Publications that did not report any specific outcomes for patients or provided insufficient data were excluded. RESULTS Seventy publications were identified of which 38 were full papers. A total of 373 patients underwent liver/kidney/combined liver-kidney transplantation for PA or MMA. The most typical reason for transplantation was recurrent metabolic decompensation. A total of 27 post-transplant deaths were reported in patients with PA [14.0% (27/194)]. For patients with MMA, 18 post-transplant deaths were reported [11% (18/167)]. A total of 62 complications were reported in 115 patients with PA (54%) with cardiomyopathy (n = 12), hepatic arterial thrombosis (HAT; n = 14) and viral infections (n = 12) being the most commonly reported. A total of 52 complications were reported in 106 patients with MMA (49%) with viral infections (n = 14) and renal failure/impairment (n = 10) being the most commonly reported. CONCLUSIONS Liver transplantation and combined liver-kidney transplantation appears to benefit some patients with PA or MMA, respectively, but this approach does not provide complete correction of the metabolic defect and some patients remain at risk from disease-related and transplantation-related complications, including death. Thus, all treatment avenues should be exhausted before consideration of organ transplantation and the benefits of this approach must be weighed against the risk of perioperative complications on an individual basis.
-
8.
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.
-
9.
Is Macroscopic Portal Vein Tumor Thrombosis of HCC Really an Exclusion for Liver Transplantation?
Aydin, C, Yilmaz, S
Journal of gastrointestinal cancer. 2020;(4):1137-1140
Abstract
PURPOSE Hepatocellular carcinoma is a heterogenous group of disease with a spectrum of disease presentations that developed on the setting of liver cirrhosis, although the achievements made in the imaging techniques have enabled the early diagnosis in nearly 60% of the cases in cirrhotic patients. However, hepatobiliary centers and tertiary liver transplant centers have to treat patients with advanced hepatocellular carcinoma with portal venous tumor thrombosis. METHODS In this review, liver transplantation results in hepatocellular carcinoma patients with portal vein tumor thrombosis is reviewed. RESULTS Although historically portal venous tumor thrombosis is considered a contraindication for radical surgical procedures such as liver transplantation, current data suggests that patients with hepatocellular carcinoma and macrovascular invasion can achieve favorable outcomes with liver transplantation provided that strict selection criteria is applied. One of the cornerstones of treatment of these patients is development of locoregional therapy such as transarterial chemo and radioembolizations. Transarterial radioembolization is effective in patients if the pretreatment liver failure is mild and the tumor burden including extension to the portal vein is low. Although data is lacking especially radioembolization could even help physicians to differentiate tumors with favorable biologic characteristics. CONCLUSIONS Therefore, these patients should be subject of multimodality treatment, and liver transplantation should be offered whenever objective and significant response is obtained by locoregional therapies.
-
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.