Acute-on-chronic liver failure: a retrospective review of cases at a transplantation center in Brazil.

PURPOSE: Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil. METHODS: Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis. RESULTS: Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively. CONCLUSIONS: ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.

Acute-on-chronic liver failure: a retrospective review of cases at a transplantation center in Brazil

Purpose: Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil. Methods: Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis. Results: Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively. Conclusions: ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.

Exercise training as an intervention for frailty in cirrhotic patients on the liver transplant waiting list: A systematic review.

BACKGROUND: The existing literature suggests that exercise for cirrhotic patients is safe and favours significant improvement to their physical capacity. However, exercise training for this population and how to deliver activities, especially in severe stages of the disease and while waiting for a liver transplant (LT), remain undefined. AIM: To review the existing exercise prescriptions for cirrhotic patients on the waiting list for LT, their results for frailty evolution and their effect on clinical outcomes. METHODS: A systematic review was performed following the Preferred Reporting Review and Meta-Analysis guidelines and searching the PubMed, MEDLINE, and Scopus databases. The keyword "liver transplant" was used in combination with the free terms "frailty" and "exercise" for the literature review. Clinical studies that evaluated the effect of a regular training program, independent of supervision or the duration or intensity of physical exercise, in cirrhotic patients on the waiting list for LT were reviewed. The data on safe physical activity prescriptions following Frequency, Intensity, Time, and Type recommendations were extracted and summarised. RESULTS: Nine articles met the inclusion criteria for this review. Various instruments for frailty assessment were used, frequently in combination. Five studies prescribed physical activity for patients, one in-person and four to be performed remotely and unsupervised. The remaining four studies only used a self-report instrument to assess the level of physical activity. None reported adverse events related to exercise training. The exercise frequency mainly varied from daily to a minimum of twice per week. The intensity depended on frailty and included increasing levels of activity. The type of exercise was predominantly a combination of aerobic and resistance training. The duration of exercise varied from 4 to 12 wk. Three articles evaluated the effect of the exercise program on clinical outcomes, reporting a reduction in 90-d readmission rates post-transplant and improved frailty scores, as well as improved survival of cirrhotic patients waiting for LT. CONCLUSION: Routine frailty assessment is essential for this population. Although more robust evidence is required, the prescription of exercise is safe and can improve patients' functional capacity, improving pre- and post-LT outcomes.

Establishing a HOPE Program in a Real-life Setting: A Brazilian Case Series.

Background: Although hypothermic oxygenated perfusion (HOPE) improves posttransplant outcomes, setting up machine perfusion programs may be subjected to specific obstacles under different conditions. This study aims to describe the establishment of HOPE in a real-life setting in Brazil. Methods: Extended criteria donors in donation after brain death organs preserved by HOPE were accepted for higher-risk candidates needing expedited transplantation, perceived as those who would benefit most from the technique because of its limited availability. Extended criteria donors was defined by the Eurotransplant criteria. High-risk transplant candidates were characterized by suboptimal surgical conditions related to the recipient or the procedure. Results: Six HOPE-preserved grafts were transplanted from February 2022 to August 2022. The mean donor risk index was 1.7 (SD 0.5). One organ was severely steatotic, and 3 had an anticipated cold ischemia time above 12 h. Recipients' mean model for end-stage liver disease was 28.67 (SD 6.79), with 1 case of retransplant, 1 of refractory ascites, and 1 of acute-on-chronic liver failure. The mean cold ischemia time was 5 h 42 min (SD 82 min), HOPE 6 h 3 min (SD 150 min), and total preservation time 11 h 46 min (SD 184 min). No case had early allograft dysfunction. The mean length of hospital stay was 10 d with 100% graft and patient survival and no ischemic cholangiopathies at a median follow-up of 15 mo (min 12, max 18). Costs and country-specific legal regulations for device utilization were the major hurdles to implementing the program. Conclusion: We presented a pathway to introduce and rationalize the use of HOPE in a scenario of challenging donor-recipient matching with good results. These findings may aid in implementing machine perfusion programs, especially in settings with limited resources or complex transplant logistics.

Eleven hours of hypothermic oxygenated machine perfusion (HOPE) for complex liver retransplantation: A case report.

This case report describes the longest reported HOPE treatment ever for an extended criteria donor organ in donation after brain death performed to enable the transplantation of a surgically complex retransplant case. Although further evidence is required, HOPE may facilitate liver retransplantation, expanding the donor organ pool and reducing time constraints on the operation.

Extended criteria brain-dead organ donors: Prevalence and impact on the utilisation of livers for transplantation in Brazil.

BACKGROUND: Despite its association with higher postoperative morbidity and mortality, the use of extended criteria donor (ECD) livers for transplantation has increased globally due to the high demand for the procedure. AIM: To investigate the prevalence of ECD in donation after brain death (DBD) and its impact on organ acceptance for transplantation. METHODS: Retrospective analysis of DBD organ offers for liver transplantation between 2017 and 2020 in a high-volume transplant centre. The incidence of the Eurotransplant risk factors to define an ECD (ET-ECD) among DBD donors and the likelihood of organ acceptance over the years were analysed. The relationship between organ refusal for transplantation, the occurrence, and the number of ET-ECD was assessed by simple and multiple logistic regression adjustment. RESULTS: A total of 1619 organ donors were evaluated. Of these, 78.31% (n = 1268) had at least one ET-ECD criterion. There was an increase in the acceptance of ECD DBD organs for transplantation (1 criterion: from 23.40% to 31.60%; 2 criteria: from 13.10% to 27.70%; 3 criteria: From 6.30% to 13.60%). For each addition of one ET-ECD variable, the estimated chance of organ refusal was 64.4% higher (OR 1.644, 95%CI 1.469-1.839, P < 0.001). Except for the donor serum sodium > 165 mmol/L (P = 0.310), all ET-ECD criteria increased the estimated chance of organ refusal for transplantation. CONCLUSION: A high prevalence of ECD DBD was observed. Despite the increase in their utilisation, the presence and the number of extended donor criteria were associated with an increased likelihood of their refusal for transplantation.

Machine perfusion organ preservation: Highlights from the American Transplant Congress 2022.

The American Transplant Congress 2022, which took place between June 4th and June 8th of 2022, was a hybrid meeting with in-person attendance in Boston-MA and a real-time virtual experience via an online platform. First, we identified abstracts discussing machine perfusion preservation for all organs, a hot topic and approach that may develop into the new gold standard of organ preservation in the near future. A total of 39 abstracts on organ machine preservation were presented at the meeting. Next, we selected abstracts which focus on advances including new approaches to organ preservation, promising biomarkers, ex-situ treatment including cellular therapies, and novel research areas. Here, we summarized the latest developments on machine perfusion preservation in both experimental and clinical studies.

The economic impact of machine perfusion technology in liver transplantation.

INTRODUCTION: Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still underexplored. This review aimed to examine the costs related to machine perfusion and its associated outcomes. METHODS: Expert opinion of several groups representing different machine perfusion modalities. Critical analysis of the published literature reporting the economic outcomes of the most used techniques of machine perfusion in liver transplantation (normothermic and hypothermic ex situ machine perfusion and in situ normothermic regional perfusion). RESULTS: Machine perfusion costs include disposable components of the perfusion device, perfusate components, personnel and facility fees, and depreciation of the perfusion device or device lease fee. The limited current literature suggests that although this upfront cost varies between perfusion modalities, its use is highly likely to be cost-effective. Optimization of the donor liver utilization rate, local conditions of transplant programs (long waiting list times and higher MELD scores), a decreased rate of complications, changes in logistics, and length of hospital stay are potential cost savings points that must highlight the expected benefits of this intervention. An additional unaccounted factor is that machine perfusion optimizing donor organ utilization allows patients to be transplanted earlier, avoiding clinical deterioration while on the waiting list and the costs associated with hospital admissions and other required procedures. CONCLUSION: So far, the clinical benefits have guided machine perfusion implementation in liver transplantation. Albeit there is data suggesting the economic benefit of the technique, further investigation of its costs to healthcare systems and society and associated outcomes is needed.

Current and future perspectives on acute-on-chronic liver failure: Challenges of transplantation, machine perfusion, and beyond.

Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation, organ failure and high short-term mortality. Partially due to the lack of universal diagnostic criteria, the actual ACLF prevalence remains unclear; nevertheless, it is expected to be a highly prevalent condition worldwide. Earlier transplantation is an effective protective measure for selected ACLF patients. Besides liver trans-plantation, diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy. Although new clinical specific therapies have been researched, more studies are necessary to assess safety and efficacy. Therefore, future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow. Thus, an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality. In addition, while donor organ quality is meant to be a prognostic factor in the ACLF setting, recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.

Disposal of donor livers in Brazil: how to optimize their utilization rate in transplants?

OBJECTIVE: To understand the professionals´ perception of the use of deceased donor liver for transplantation, the reasons to decline them, and propose strategies to increase their use safely. METHODS: This is a cross-sectional, descriptive qualitative-quantitative study. Professionals working with liver transplantation answered a self-administered, structured, and electronic questionnaire comprising 17 questions distributed into four sessions (demographic factors, perception of use of organs, reasons for disposal, and measures to favor their usage). RESULTS: A total of 42 professionals participated in the study. The rate of use of organs was considered low by 71.43% (n=30) of respondents or very low by 19.05% (n=8). Everyone agreed that it was possible to increase it. Thirty-one (73.81%) participants believed the expansion of the population of extended criteria donors affected this index negatively. Donor-related conditions were the most frequent category of reasons for refusing a liver for transplantation, being the findings during organ retrieval the most frequent reason in clinical practice. Enhanced training of intensive care teams in the treatment of donors was the primary measure selected to favor the use of the organs, followed by investment in new technologies to optimize its preservation/evaluate its function before transplantation. CONCLUSION: Implementation of strategies to increase the rate of acceptance of livers is expected. Improvements in donor intensive care and implementation of new preservation technologies should favor the use of the organs.

Machine perfusion of the liver: Putting the puzzle pieces together.

The realm of extended criteria liver transplantation created the 'adjacent possible' for dynamic organ preservation. Machine perfusion of the liver greatly expanded donor organ preservation possibilities, reaching before unattainable goals, including the mitigation of ischemia-reperfusion injury, viability assessment, and organ reconditioning prior to transplantation. However, current scientific evidence lacks uniformity between studies, perfusion protocols, and acceptance criteria. Construction of collaborative research networks for sharing knowledge should, therefore, enable the development of high-level evidence and guidelines for machine perfusion utilization, including donor acceptance criteria. Finally, this approach shall guarantee conditions for further progress to occur.

Update on the management and treatment of viral hepatitis.

This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.

Disposal of donor livers in Brazil: how to optimize their utilization rate in transplants? / Descarte de fígados de doadores no Brasil: como otimizar sua taxa de utilização em transplantes?

ABSTRACT Objective: To understand the professionals´ perception of the use of deceased donor liver for transplantation, the reasons to decline them, and propose strategies to increase their use safely. Methods: This is a cross-sectional, descriptive qualitative-quantitative study. Professionals working with liver transplantation answered a self-administered, structured, and electronic questionnaire comprising 17 questions distributed into four sessions (demographic factors, perception of use of organs, reasons for disposal, and measures to favor their usage). Results: A total of 42 professionals participated in the study. The rate of use of organs was considered low by 71.43% (n=30) of respondents or very low by 19.05% (n=8). Everyone agreed that it was possible to increase it. Thirty-one (73.81%) participants believed the expansion of the population of extended criteria donors affected this index negatively. Donor-related conditions were the most frequent category of reasons for refusing a liver for transplantation, being the findings during organ retrieval the most frequent reason in clinical practice. Enhanced training of intensive care teams in the treatment of donors was the primary measure selected to favor the use of the organs, followed by investment in new technologies to optimize its preservation/evaluate its function before transplantation. Conclusion: Implementation of strategies to increase the rate of acceptance of livers is expected. Improvements in donor intensive care and implementation of new preservation technologies should favor the use of the organs.

RESUMO Objetivo: Compreender a percepção dos profissionais acerca do uso de fígado de doadores falecidos para transplante e os motivos para sua recusa, além de propor estratégias para ampliar sua utilização com segurança. Métodos: Estudo do tipo transversal, descritivo qualiquantitativo.Profissionais que trabalhavam com transplante hepático responderam a um questionário autoaplicável, estruturado e eletrônico, composto de 17 questões distribuídas em quatro seções (fatores demográficos, percepção sobre a utilização dos órgãos, razões para o descarte e medidas para favorecer sua utilização). Resultados: Participaram do estudo 42 profissionais. A taxa de utilização dos órgãos foi considerada baixa por 71,43% (n=30) dos respondentes ou muito baixa por 19,05% (n=8). Todos concordaram que era possível aumentá-la. Trinta e um (73,81%) participantes acreditavam que a expansão da população de doadores de critérios estendidos impacta negativamente nesse índice. Condições relacionadas ao doador foi a categoria mais frequente de razões para a recusa de um fígado para transplante, sendo os achados durante a cirurgia de extração o motivo mais frequente na prática clínica. O melhor treinamento das equipes da terapia intensiva nos cuidados com os doadores foi a principal medida selecionada para favorecer a utilização dos órgãos, seguido pelo investimento em novas tecnologias para otimizar sua preservação/avaliar sua função antes do transplante. Conclusão: A efetivação de estratégias para aumentar a taxa de aceite de fígados de doadores é aguardada. Melhorias no cuidado intensivo do doador e a implementação de novas tecnologias de preservação devem favorecer a utilização desses órgãos.

Tubulovillous adenoma of the duodenal papilla: radiological-endoscopic and anatomopathological correlation in the surgical proposal.

Tubulovillous adenomas of the duodenal ampulla are rare neoplasms. The present report describes a case with radiological-endoscopic and pathological correlation in which the patient underwent duodenal pancreatectomy with good postoperative progression. With advanced imaging methods, especially magnetic resonance and endoscopic ultrasound, locoregional aspects and extraluminal, lymphovascular, and metastatic invasion have been increasingly discussed as contributors to therapeutic decision making. This progression improves lesion staging and is especially useful in selecting eligible candidates for endoscopic treatment.

Prospects for the ex situ liver machine perfusion in Brazil.

Brazil, like most countries in the world, experiences the expansion of extended criteria donors, mainly due to the aging of the population and the obesity epidemic. Concerns regarding the quality of these organs along with the vast territorial areas of the country compromise the utilization rate of livers from donors and aggravate the discrepancy between the number of liver transplants performed and the needed. Ex situ liver machine perfusion offers superior preservation for livers from extended criteria donors, limiting cold ischaemia time and offering the possibility of evaluation of their function before transplantation as well as the reconditioning of marginal organs. Objections such as the financial cost, difficulty in transporting the device between hospitals, and demand of trained professionals in the handling of the device must be pondered with the possibility of increasing the number of transplants and the utilisation rate of donor organs. The optimal use of this resource, through the careful selection of donors and the appropriate technical and scientific knowledge, can ensure an effective and successful implementation of this technology.

Tubulovillous adenoma of the duodenal papilla: radiological-endoscopic and anatomopathological correlation in the surgical proposal

SUMMARY Tubulovillous adenomas of the duodenal ampulla are rare neoplasms. The present report describes a case with radiological-endoscopic and pathological correlation in which the patient underwent duodenal pancreatectomy with good postoperative progression. With advanced imaging methods, especially magnetic resonance and endoscopic ultrasound, locoregional aspects and extraluminal, lymphovascular, and metastatic invasion have been increasingly discussed as contributors to therapeutic decision making. This progression improves lesion staging and is especially useful in selecting eligible candidates for endoscopic treatment.

RESUMO Os adenomas túbulo-vilosos da ampola duodenal são neoplasias raras. Neste trabalho apresentamos um caso com correlação radiológico-endoscópica e patológica, tendo a paciente sido submetida à duodenopancreatectomia com boa evolução pós-operatória. Com os avanços dos métodos de imagem, em especial da ressonância magnética e ultrassonografia endoscópica, aspectos locorregionais, além da invasão extraluminal, linfovascular e metastática, têm sido discutidos de maneira crescente como contribuintes na decisão terapêutica. Essa evolução contribui para o melhor estadiamento destas lesões e é especialmente útil para selecionar candidatos elegíveis ao tratamento endoscópico.

Preventing Tumour Recurrence after Liver Transplantation: The Role of Machine Perfusion.

Tumour recurrence is currently a hot topic in liver transplantation. The basic mechanisms are increasingly discussed, and, for example, recurrence of hepatocellular carcinoma is often described in pre-injured donor livers, which frequently suffer from significant ischemia/reperfusion injury. This review article highlights the underlying mechanisms and describes the specific tissue milieu required to promote tumour recurrence after liver transplantation. We summarise the current literature in this field and show risk factors that contribute to a pro-tumour-recurrent environment. Finally, the potential role of new machine perfusion technology is discussed, including the most recent data, which demonstrate a protective effect of hypothermic oxygenated perfusion before liver transplantation.

Prospects for the ex situ liver machine perfusion in Brazil / Perspectivas para a máquina de perfusão hepática ex situ no Brasil

ABSTRACT Brazil, like most countries in the world, experiences the expansion of extended criteria donors, mainly due to the aging of the population and the obesity epidemic. Concerns regarding the quality of these organs along with the vast territorial areas of the country compromise the utilization rate of livers from donors and aggravate the discrepancy between the number of liver transplants performed and the needed. Ex situ liver machine perfusion offers superior preservation for livers from extended criteria donors, limiting cold ischaemia time and offering the possibility of evaluation of their function before transplantation as well as the reconditioning of marginal organs. Objections such as the financial cost, difficulty in transporting the device between hospitals, and demand of trained professionals in the handling of the device must be pondered with the possibility of increasing the number of transplants and the utilisation rate of donor organs. The optimal use of this resource, through the careful selection of donors and the appropriate technical and scientific knowledge, can ensure an effective and successful implementation of this technology.

RESUMO O Brasil, como a grande parte dos países no mundo, convive com a expansão de doadores de órgãos de critério estendido, principalmente devido ao envelhecimento da população e à epidemia de obesidade. Dúvidas em relação à qualidade desses órgãos juntamente com as longas extensões territoriais do país comprometem a taxa de utilização de fígados de doadores e agravam a discrepância entre o número de transplantes hepáticos realizados e o necessário. A máquina de perfusão hepática oxigenada ex situ oferece preservação superior para fígados de doadores de critério estendido, limitando o tempo de isquemia fria e oferecendo a possibilidade de avaliação da função antes do transplante bem como o recondicionamento de órgãos de qualidade limítrofe. Objeções como o custo financeiro, dificuldade de transporte do dispositivo entre hospitais e a demanda de profissionais treinados para o manuseio devem ser apreciadas diante da possibilidade do aumento do número de transplantes e a maior taxa de utilização de órgãos de doadores. A otimização na utilização desse recurso, por meio da seleção cuidadosa de doadores, e o conhecimento técnico-científico adequado podem garantir a implementação eficaz e bem sucedida dessa tecnologia.