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Hepatology (Baltimore, Md.) Oct 2023Acute liver failure (ALF) describes a clinical syndrome of rapid hepatocyte injury leading to liver failure manifested by coagulopathy and encephalopathy in the absence... (Review)
Review
Acute liver failure (ALF) describes a clinical syndrome of rapid hepatocyte injury leading to liver failure manifested by coagulopathy and encephalopathy in the absence of pre-existing cirrhosis. The hallmark diagnostic features are a prolonged prothrombin time (ie, an international normalized ratio of prothrombin time of ≥1.5) and any degree of mental status alteration (HE). As a rare, orphan disease, it seemed an obvious target for a multicenter network. The Acute Liver Failure Study Group (ALFSG) began in 1997 to more thoroughly study and understand the causes, natural history, and management of ALF. Over the course of 22 years, 3364 adult patients were enrolled in the study registry (2614 ALF and 857 acute liver injury-international normalized ratio 2.0 but no encephalopathy-ALI) and >150,000 biosamples collected, including serum, plasma, urine, DNA, and liver tissue. Within the Registry study sites, 4 prospective substudies were conducted and published, 2 interventional ( N -acetylcysteine and ornithine phenylacetate), 1 prognostic [ 13 C-methacetin breath test (MBT)], and 1 mechanistic (rotational thromboelastometry). To review ALFSG's accomplishments and consider next steps, a 2-day in-person conference was held at UT Southwestern Medical Center, Dallas, TX, entitled "Acute Liver Failure: Science and Practice," in May 2022. To summarize the important findings in the field, this review highlights the current state of understanding of ALF and, more importantly, asks what further studies are needed to improve our understanding of the pathogenesis, natural history, and management of this unique and dramatic condition.
Topics: Adult; Humans; Prospective Studies; Liver Failure, Acute; Prognosis; Liver Transplantation; Multicenter Studies as Topic
PubMed: 37183883
DOI: 10.1097/HEP.0000000000000458 -
Journal of Hepatology Jun 2023With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic... (Review)
Review
With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic preservation approaches have demonstrated various benefits, including improving liver function and graft survival, and reducing liver injury and post-transplant complications. Consequently, organ perfusion techniques are being used in clinical practice in many countries. Despite this success, a proportion of livers do not meet current viability tests required for transplantation, even with the use of modern perfusion techniques. Therefore, devices are needed to further optimise machine liver perfusion - one promising option is to prolong machine liver perfusion for several days, with ex situ treatment of perfused livers. For example, stem cells, senolytics, or molecules targeting mitochondria or downstream signalling can be administered during long-term liver perfusion to modulate repair mechanisms and regeneration. Besides, today's perfusion equipment is also designed to enable the use of various liver bioengineering techniques, to develop scaffolds or for their re-cellularisation. Cells or entire livers can also undergo gene modulation to modify animal livers for xenotransplantation, to directly treat injured organs or to repopulate such scaffolds with "repaired" autologous cells. This review first discusses current strategies to improve the quality of donor livers, and secondly reports on bioengineering techniques to design optimised organs during machine perfusion. Current practice, as well as the benefits and challenges associated with these different perfusion strategies are discussed.
Topics: Animals; Liver Transplantation; Organ Preservation; Liver; Perfusion; Bioengineering
PubMed: 37208105
DOI: 10.1016/j.jhep.2023.02.009 -
Journal of Hepatology Aug 2023Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.
METHODS
In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI.
RESULTS
Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025).
CONCLUSIONS
Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.
CLINICAL TRIAL REGISTRATION
chictr.org. ChiCTR1900021158.
IMPACT AND IMPLICATIONS
Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.
Topics: Humans; Liver Transplantation; End Stage Liver Disease; Ischemia; Liver; Reperfusion Injury; Perfusion; Organ Preservation
PubMed: 37086919
DOI: 10.1016/j.jhep.2023.04.010 -
Nature Reviews. Gastroenterology &... Oct 2023Nonalcoholic steatohepatitis (NASH) might soon become the leading cause of end-stage liver disease and indication for liver transplantation worldwide. Fibrosis severity... (Review)
Review
Nonalcoholic steatohepatitis (NASH) might soon become the leading cause of end-stage liver disease and indication for liver transplantation worldwide. Fibrosis severity is the only histological predictor of liver-related morbidity and mortality in NASH identified to date. Moreover, fibrosis regression is associated with improved clinical outcomes. However, despite numerous clinical trials of plausible drug candidates, an approved antifibrotic therapy remains elusive. Increased understanding of NASH susceptibility and pathogenesis, emerging human multiomics profiling, integration of electronic health record data and modern pharmacology techniques hold enormous promise in delivering a paradigm shift in antifibrotic drug development in NASH. There is a strong rationale for drug combinations to boost efficacy, and precision medicine strategies targeting key genetic modifiers of NASH are emerging. In this Perspective, we discuss why antifibrotic effects observed in NASH pharmacotherapy trials have been underwhelming and outline potential approaches to improve the likelihood of future clinical success.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Liver; Liver Cirrhosis; Liver Transplantation; End Stage Liver Disease
PubMed: 37268740
DOI: 10.1038/s41575-023-00796-x -
Journal of Hepatology Jun 2023Liver transplantation (LT) is a life-saving treatment for individuals with end-stage liver disease. The management of LT recipients is complex, predominantly because of... (Review)
Review
Liver transplantation (LT) is a life-saving treatment for individuals with end-stage liver disease. The management of LT recipients is complex, predominantly because of the need to consider demographic, clinical, laboratory, pathology, imaging, and omics data in the development of an appropriate treatment plan. Current methods to collate clinical information are susceptible to some degree of subjectivity; thus, clinical decision-making in LT could benefit from the data-driven approach offered by artificial intelligence (AI). Machine learning and deep learning could be applied in both the pre- and post-LT settings. Some examples of AI applications pre-transplant include optimising transplant candidacy decision-making and donor-recipient matching to reduce waitlist mortality and improve post-transplant outcomes. In the post-LT setting, AI could help guide the management of LT recipients, particularly by predicting patient and graft survival, along with identifying risk factors for disease recurrence and other associated complications. Although AI shows promise in medicine, there are limitations to its clinical deployment which include dataset imbalances for model training, data privacy issues, and a lack of available research practices to benchmark model performance in the real world. Overall, AI tools have the potential to enhance personalised clinical decision-making, especially in the context of liver transplant medicine.
Topics: Humans; Liver Transplantation; Artificial Intelligence; Deep Learning; End Stage Liver Disease; Machine Learning
PubMed: 37208107
DOI: 10.1016/j.jhep.2023.01.006 -
Transplant International : Official... 2024
Topics: Humans; Liver Transplantation; Transplants; Perfusion; Organ Preservation; Graft Survival; Liver
PubMed: 38544563
DOI: 10.3389/ti.2024.12853 -
Tidsskrift For Den Norske Laegeforening... Nov 2023Primary sclerosing cholangitis is a severe liver disease and a leading cause of liver transplantation in Scandinavia. This clinical review article examines recently... (Review)
Review
Primary sclerosing cholangitis is a severe liver disease and a leading cause of liver transplantation in Scandinavia. This clinical review article examines recently revised recommendations on diagnosis, follow-up and treatment of patients with this disease. Treatment of symptoms, assessment of fibrosis and monitoring for the development of cancer in the liver and bowel are central.
Topics: Humans; Cholangitis, Sclerosing; Liver Transplantation; Scandinavian and Nordic Countries
PubMed: 37987062
DOI: 10.4045/tidsskr.23.0156 -
The Korean Journal of Gastroenterology... Nov 2023Hepatorenal syndrome (HRS) is a critical and potentially life-threatening complication of advanced liver disease, including cirrhosis. It is characterized by the... (Review)
Review
Hepatorenal syndrome (HRS) is a critical and potentially life-threatening complication of advanced liver disease, including cirrhosis. It is characterized by the development of renal dysfunction in the absence of underlying structural kidney pathology. The pathophysiology of HRS involves complex interactions between systemic and renal hemodynamics, neurohormonal imbalances, and the intricate role of vasoconstrictor substances. Understanding these mechanisms is crucial for the timely identification and management of HRS. The diagnosis of HRS is primarily clinical and relies on specific criteria that consider the exclusion of other causes of renal dysfunction. The management of HRS comprises two main approaches: vasoconstrictor therapy and albumin infusion, which aim to improve renal perfusion and mitigate the hyperdynamic circulation often seen in advanced liver disease. Additionally, strategies such as liver transplantation and renal replacement therapy are essential considerations based on individual patient characteristics and disease severity. This review article provides a comprehensive overview of hepatorenal syndrome, focusing on its pathophysiology, diagnostic criteria, and current management strategies.
Topics: Humans; Hepatorenal Syndrome; Kidney; Vasoconstrictor Agents; Liver Cirrhosis; Liver Transplantation
PubMed: 37997218
DOI: 10.4166/kjg.2023.108 -
Nutrients Aug 2023The liver is a key organ that is responsible for the metabolism of proteins, fats, and carbohydrates and the absorption and storage of micronutrients. Unfortunately, the... (Review)
Review
The liver is a key organ that is responsible for the metabolism of proteins, fats, and carbohydrates and the absorption and storage of micronutrients. Unfortunately, the prevalence of chronic liver diseases at various stages of advancement in the world population is significant. Due to the physiological function of the liver, its dysfunction can lead to malnutrition and sarcopenia, and the patient's nutritional status is an important prognostic factor. This review discusses key issues related to the diet therapy of patients with chronic liver diseases, as well as those qualified for liver transplantation and in the postoperative period.
Topics: Humans; Liver Diseases; Nutritional Support; Liver Transplantation; Malnutrition
PubMed: 37630830
DOI: 10.3390/nu15163640 -
Hepatology Communications Sep 2023Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring...
Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.
Topics: Humans; Liver Diseases; Invasive Fungal Infections; Liver Transplantation; Cytology; Hepatitis, Alcoholic
PubMed: 37639701
DOI: 10.1097/HC9.0000000000000216