scholarly journals Lung and liver transplantation in patients with alpha-1 antitrypsin deficiency

2021 ◽  
Vol 12_suppl ◽  
pp. 204062232110029
Author(s):  
Martin R. Zamora ◽  
Ali Ataya
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Respiratory Failure ◽  
Lung Transplantation ◽  
Lung Disease ◽  
Cause Of Death ◽  
Treatment Option ◽  
Survival Rates ◽  
Alpha 1 Antitrypsin ◽  
End Stage

Alpha-1 antitrypsin (AAT) augmentation is effective in slowing the progression of emphysema due to AAT deficiency (AATD) but cannot prevent eventual progression to end-stage lung disease and complete respiratory failure, which is the leading cause of death for individuals with severe AATD. When patients develop end-stage lung disease, lung transplantation is the only treatment option available, and this can improve lung physiology and patient health status. The available data suggest that survival rates for lung transplantation are significantly higher for patients with AATD-related chronic obstructive pulmonary disease (COPD) compared with non-AATD-related COPD, but, conversely, there is a higher risk of common post-lung transplant complications in patients with AATD versus non-AATD COPD. Nevertheless, lung transplantation (single and bilateral) is favorable for patients with AATD. After respiratory failure, the second leading cause of death in patients with AATD is liver disease, for example, cirrhosis and hepatocellular carcinoma, caused by the accumulation of mutant forms of AAT retained within the liver. As with lung disease, the only treatment option for end-stage liver disease is liver transplantation. Survival rates for patients with AATD undergoing liver transplantation are also favorable, and patients, particularly pediatric patients, have benefitted from advancements in peri-/post-surgical care. As the majority of AAT is produced by the liver, the AAT phenotype of the recipient becomes that of the donor, meaning that AAT serum levels should be normalized (if the donor is AAT-replete), halting further lung and liver disease progression. However, post-liver transplant respiratory function may continue to decline in line with normal age-related lung function decline. In the most severe cases, where patients have simultaneous end-stage lung and liver disease, combined lung and liver transplantation is a treatment option with favorable outcomes. However, there is very little information available on this procedure in patients with AATD.

Liver Transplantation for HELLP Syndrome

2007 ◽  
Vol 73 (10) ◽  
pp. 1013-1016 ◽  
Author(s):  
Ali Zarrinpar ◽  
Douglas G. Farmer ◽  
R. Mark Ghobrial ◽  
Gerald S. Lipshutz ◽  
Yan Gu ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Liver Failure ◽  
Hellp Syndrome ◽  
Early Recognition ◽  
Survival Rates ◽  
Center Report ◽  
Elevated Liver Enzymes ◽  
The Mean ◽  
End Stage

Of the approximately one in 1000 pregnant women who develop the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP), 2 to 3 per cent develop hepatic complications, including liver failure for which liver transplantation (LT) may be required. Between February 1, 1984, and December 31, 2006, eight women without a history of liver disease underwent LT for complications of HELLP syndrome. All received cadaveric grafts with a mean interval from delivery to LT of 7 days. The mean admission Child-Turcotte-Pugh score was 13.1 (class C), and the mean model for end-stage liver disease score was 40. Manifestations of liver failure included encephalopathy (seven patients), renal failure (four), disseminated intravascular coagulation (three), and respiratory failure (one). There were no intraoperative deaths. Complications of LT included biliary leaks (three patients), reoperation (three), and retransplantation (two). There was one death from sepsis on postoperative day 91 and one death from cholangitis/sepsis more than 5 years postoperatively. After LT, 1-, 5-, and 10-year patient survival rates were 88 per cent, 88 per cent, and 65 per cent; 1-, 5-, and 10-year graft survival rates were 64 per cent, 64 per cent, and 48 per cent. This is the largest single-center report of LT for HELLP. Early recognition and transfer to a transplant center will yield best results with this challenging complication of pregnancy.

scholarly journals COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324879
Author(s):  
Luca Saverio Belli ◽  
Christophe Duvoux ◽  
Paolo Angelo Cortesi ◽  
Rita Facchetti ◽  
Speranta Iacob ◽  
...  
Keyword(s):  
Liver Disease ◽  
Respiratory Failure ◽  
Meld Score ◽  
Decompensated Cirrhosis ◽  
Cox Regression Analysis ◽  
Post Transplant ◽  
End Stage Liver Disease ◽  
Significant Difference ◽  
End Stage ◽  
The Impact

ObjectiveExplore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.DesignData from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.ResultsFrom 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10–30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15–19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44–102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31–170).ConclusionsIncreased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).

scholarly journals The Autophagy Pathway: A Critical Route in the Disposal of Alpha 1-Antitrypsin Aggregates That Holds Many Mysteries

2021 ◽  
Vol 22 (4) ◽  
pp. 1875
Author(s):  
Celine Leon ◽  
Marion Bouchecareilh
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Therapeutic Option ◽  
Ubiquitin Proteasome System ◽  
Therapeutic Benefit ◽  
Cellular Functions ◽  
Precise Control ◽  
New Therapeutic Approaches ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

The maintenance of proteome homeostasis, or proteostasis, is crucial for preserving cellular functions and for cellular adaptation to environmental challenges and changes in physiological conditions. The capacity of cells to maintain proteostasis requires precise control and coordination of protein synthesis, folding, conformational maintenance, and clearance. Thus, protein degradation by the ubiquitin–proteasome system (UPS) or the autophagy–lysosomal system plays an essential role in cellular functions. However, failure of the UPS or the autophagic process can lead to the development of various diseases (aging-associated diseases, cancer), thus both these pathways have become attractive targets in the treatment of protein conformational diseases, such as alpha 1-antitrypsin deficiency (AATD). The Z alpha 1-antitrypsin (Z-AAT) misfolded variant of the serine protease alpha 1-antitrypsin (AAT) is caused by a structural change that predisposes it to protein aggregation and dramatic accumulation in the form of inclusion bodies within liver hepatocytes. This can lead to clinically significant liver disease requiring liver transplantation in childhood or adulthood. Treatment of mice with autophagy enhancers was found to reduce hepatic Z-AAT aggregate levels and protect them from AATD hepatotoxicity. To date, liver transplantation is the only curative therapeutic option for patients with AATD-mediated liver disease. Therefore, the development and discovery of new therapeutic approaches to delay or overcome disease progression is a top priority. Herein, we review AATD-mediated liver disease and the overall process of autophagy. We highlight the role of this system in the regulation of Z-variant degradation and its implication in AATD-medicated liver disease, including some open questions that remain challenges in the field and require further elucidation. Finally, we discuss how manipulation of autophagy could provide multiple routes of therapeutic benefit in AATD-mediated liver disease.

Low psoas muscle index as an unfavorable factor in children with end‐stage liver disease undergoing liver transplantation

2021 ◽  
Author(s):  
Settapong Jitwongwai ◽  
Chatmanee Lertudomphonwanit ◽  
Thitiporn Junhasavasdikul ◽  
Praman Fuangfa ◽  
Pornthep Tanpowpong ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Psoas Muscle ◽  
End Stage Liver Disease ◽  
End Stage

scholarly journals RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Guomin Xie ◽  
Li Liang ◽  
Hui Liu ◽  
Jing Pan ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Poor Prognosis ◽  
Alcoholic Cirrhosis ◽  
Normal Liver ◽  
Neutrophil Infiltration ◽  
Meld Score ◽  
End Stage Liver Disease ◽  
Cirrhotic Patients ◽  
End Stage

Alcoholic cirrhosis is an end-stage liver disease with impaired survival and often requires liver transplantation. Recent data suggests that receptor-interacting protein kinase-3- (RIPK3-) mediated necroptosis plays an important role in alcoholic cirrhosis. Additionally, neutrophil infiltration is the most characteristic pathologic hallmark of alcoholic hepatitis. Whether RIPK3 level is correlated with neutrophil infiltration or poor prognosis in alcoholic cirrhotic patients is still unknown. We aimed to determine the correlation of RIPK3 and neutrophil infiltration with the prognosis in the end-stage alcoholic cirrhotic patients. A total of 20 alcoholic cirrhotic patients subjected to liver transplantation and 5 normal liver samples from control patients were retrospectively enrolled in this study. Neutrophil infiltration and necroptosis were assessed by immunohistochemical staining for myeloperoxidase (MPO) and RIPK3, respectively. The noninvasive score system (model for end-stage liver disease (MELD)) and histological score systems (Ishak, Knodell, and ALD grading and ALD stage) were used to evaluate the prognosis. Neutrophil infiltration was aggravated in patients with a high MELD score (≥32) in the liver. The MPO and RIPK3 levels in the liver were positively related to the Ishak score. The RIPK3 was also significantly and positively related to the Knodell score. In conclusion, RIPK3-mediated necroptosis and neutrophil-mediated alcoholic liver inflammatory response are highly correlated with poor prognosis in patients with end-stage alcoholic cirrhosis. RIPK3 and MPO might serve as potential predictors for poor prognosis in alcoholic cirrhotic patients.

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