Utilidad del sistema de recirculación de adsorbentes moleculares en la falla hepática: "diálisis hepática" / Usefulness of the molecular adsorbent recirculating system in liver failure: "liver dialysis"

INTRODUCCIÓN. La falla hepática ya sea aguda o crónica reagudizada representa un reto para el clínico ya que sus complicaciones conllevan una gran mortalidad, esto se ve aún más complicado ya que las opciones terapéuticas son limitadas, incluso muchas veces no se puede acceder a un programa de trasplante hepático oportuno que mejore la sobrevida de estos pacientes, es así que se ha desarrollado un sistema de "diálisis" hepática conocido como sistema de recirculación de adsorbentes moleculares el cual hace un efecto de detoxificación para eliminar sustancias que generan una noxa en el cuerpo humano. OBJETIVO. Entender la utilidad del sistema recirculante molecular adsorbente en la falla hepática, conocer sus indicaciones y complicaciones. METODOLOGÍA. Se realizó una revisión de la literatura con un enfoque descriptivo, retrospectivo cualitativo no experimental, de documentos que tratan sobre la utilización del sistema MARS para tratar la falla hepática, con evidencia desde el año 2004 hasta el 2021. La revisión bibliográfica se llevó a cabo en bases de datos como Pubmed, Embase, BVS, Google Scholar y Elsevier. RESULTADOS. Se identificaron 30 artículos que cumplieron criterios de inclusión de un grupo original de 343 artículos revisados. Se ha determinado que la evidencia sobre este sistema está compuesta sobre todo por reportes de caso y son pocos los ensayos controlados aleatorizados que empleen su uso, sin embargo, se ha podido determinar que este sistema es un puente al trasplante renal mientras se estabiliza al paciente en la Unidad de Cuidados Intensivos, disminuye los marcadores de falla hepática. CONCLUSIÓN. En Latinoamérica su uso es casi nulo de ahí la necesidad de entender el mecanismo de este novedoso sistema.

INTRODUCTION. Hepatic failure, whether acute or chronic, represents a challenge for the clinician since its complications entail a great mortality, this is even more complicated since the therapeutic options are limited, even many times it is not possible to access a timely liver transplant program to improve the survival of these patients, Thus, a hepatic "dialysis" system known as molecular adsorbent recirculation system has been developed, which has a detoxification effect to eliminate substances that generate a noxa in the human body. OBJECTIVE. To understand the usefulness of the molecular adsorbent recirculating system in liver failure, to know its indications and complications. METHODOLOGY. A literature review was performed with a descriptive, retrospective qualitative non-experimental qualitative approach, of papers dealing with the use of the MARS system to treat liver failure, with evidence from 2004 to 2021. The literature review was conducted in databases such as Pubmed, Embase, BVS, Google Scholar and Elsevier. RESULTS. Thirty articles were identified that met inclusion criteria from an original group of 343 articles reviewed. It has been determined that the evidence on this system is mainly composed of case reports and there are few randomized controlled trials that employ its use, however, it has been determined that this system is a bridge to renal transplantation while the patient is stabilized in the Intensive Care Unit, decreasing the markers of liver failure. CONCLUSIONS. In Latin America its use is almost null, hence the need to understand the mechanism of this novel system.

Research advances in the treatment of liver failure with mesenchymal stem cell-derived exosomes / 中华肝脏病杂志

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.

Model selection and curative effect judgment criteria for artificial liver in the treatment of liver failure / 中华肝脏病杂志

Artificial liver is one of the effective methods to treat liver failure. Patients with liver failure are critically ill and have great individualized differences. Therefore, the specific program for the treatment of liver failure with artificial liver should be individualized. The commonly used non-biological artificial liver models include simple plasmapheresis, double filtration plasmapheresis, plasma filtration with dialysis, double plasma molecular adsorption system, molecular absorbent recirculating system, hemodiafiltration, continuous venovenous hemodiafiltration, hybrid, etc. The curative effect should be properly judged from patient's symptoms, laboratory test indicators, survival rate and other aspects after artificial liver therapy.

Repermeabilización portal intrahepática luego de ligadura de rama derecha de vena porta: reporte de un caso / Intrahepathic portal revascularization following right portal vein ligation: a case report / Repermeabilização portal intra-hepática após ligadura do ramo direito da veia porta: relato de caso

Resumen: La ligadura de una rama de la vena porta constituye un procedimiento con buenos resultados para evitar la falla hepática posoperatoria en caso de hepatectomías extremas al provocar la hipertrofia del hígado contralateral. Sin embargo, la repermeabilización de ésta ha sido demostrada por la presencia de anastomosis porto portales intrahepáticas, pudiendo determinar una disminución de la hipertrofia esperada o necesaria. Como objetivo documentamos un caso clínico de repermeabilización intrahepática de la vena porta, evento no deseado de la hepatectomía en dos tiempos para el tratamiento de metástasis hepáticas bilobares de origen colorrectal y describimos alternativas para evitar o tratar dicha repermeabilización.

Summary: Left or right portal vein ligation to prevent post-operative liver failure in the case of extreme hepatectomy constitutes a procedure with a good prognosis, as it causes contralateral liver hypertrophy. However, its revascularization has been proved by intrahepatic porto-portal anastomoses, which could result in a reduction of the expected or required hypertrophy. The study aims to record a clinical case of intrahepatic revascularization of the portal vein, an unwanted event of the two-stage hepatectomy to treat bilobar hepatic metastasis of colorectal origin, and describe alternatives to avoid or treat such revascularization.

Resumo: A ligadura de um ramo da veia porta é um procedimento com bons resultados para evitar a insuficiência hepática pós-operatória em hepatectomias extremas por causar hipertrofia do fígado contralateral. No entanto, sua repermeabilização tem sido demonstrada pela presença de anastomose porto-portal intra-hepática, que pode determinar diminuição da hipertrofia esperada ou necessária. Como objetivo, documentamos um caso clínico de repermeabilização da veia porta intra-hepática, um evento indesejado de hepatectomia em dois estágios para o tratamento de metástases hepáticas bilobares de origem colorretal, e descrevemos alternativas para evitar ou tratar essa repermeabilização.

Guideline for diagnosis and treatment of liver failure / 中华肝脏病杂志

Liver failure is a familiar clinical severe liver disease syndrome with a very high mortality rate. Over the years, scholars from around the world have been exploring the definition, etiology, classification, types, diagnosis and treatment, and prognostic judgment of liver failure. Reflecting changes, that have transpired in recent years at home and abroad relevant to clinical evidence, this guideline updates the information previously published by the Chinese Society of Infectious Diseases, Chinese Medical Association, Liver Failure and Artificial Liver Group, Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Guidelines for Diagnosis and Treatment of Liver Failure (2012 Edition).

Hepatotoxicidad por Amanita lilloi, reporte de primeros casos / Amanita lilloi hepatotoxicity, first cases report

Se presentan dos casos clínicos de intoxicación por A. lilloi, hongos silvestres, que fueron recolectados por quienes los consumieron. Ambas pacientes desarrollaron sintomatología digestiva y evolucionaron a la falla hepática. La consulta tardía retrasó el diagnóstico y el tratamiento, pero igualmente la evolución de ambas pacientes fue favorable.

Two clinical cases of poisoning A. lilloi, wild mushrooms, which were collected by those who consumed themdebe, are presented. Both patients developed gastrointestinal symptoms and progressed to liver failure. The late consultation delayed diagnosis and treatment, but nevertheless the evolution of both patients was favorable.

Clinical implications of advances in liver regeneration

Remarkable advances have been made recently in the area of liver regeneration. Even though liver regeneration after liver resection has been widely researched, new clinical applications have provided a better understanding of the process. Hepatic damage induces a process of regeneration that rarely occurs in normal undamaged liver. Many studies have concentrated on the mechanism of hepatocyte regeneration following liver damage. High mortality is usual in patients with terminal liver failure. Patients die when the regenerative process is unable to balance loss due to liver damage. During disease progression, cellular adaptations take place and the organ microenvironment changes. Portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy are relatively recent techniques exploiting the remarkable progress in understanding liver regeneration. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another major clinical field involving liver regeneration is cell therapy using adult stem cells. The aim of this article is to provide an outline of the clinical approaches being undertaken to examine regeneration in liver diseases.

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

BACKGROUND/AIMS: The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). METHODS: Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. RESULTS: In the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. CONCLUSIONS: A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

Albumina humana: usos e abusos / Human albumin: uses and abuses

A relevância da utilização de albumina em pacientes com doença aguda ou crônica permanece controversa. Apesar da importância fisiológica e dos potenciais efeitos benéficos, sua utilização é baseada na prática clínica e não sustentada nas evidências dos estudos clínicos. Resultados promissores de seu uso são confirmados na falência hepática, no infarto cerebral e, talvez, em situações de exceção na reposição volêmica de pacientes críticos.

The relevance of human albumin administration remains controversial. Albumin infusion has not proven to achieve clinical benefit in many acute and chronic disease states with a few exceptions in liver failure, cerebral infarction and may be in acute hypovolemia in the critical patients.

Journey from hepatocyte transplantation to hepatic stem cells: a novel treatment strategy for liver diseases.

Acute liver failure (ALF) carries high morbidity and mortality (>80%) even in the best centres. Orthotopic liver transplantation (OLTx) is the only viable approach to the treatment of ALF. This has significantly improved the survival in these patients. The major limitations of OLTx are non availability of the donor liver, requirement of a major surgical procedure, high cost and longterm immunosuppression. Isolated hepatocyte transplantation is emerging as an appealing method for the treatment of ALF because of its technical simplicity and easy availability of cells. Transplantation of allogenic/xenogenic hepatocytes transplantation in experimentally induced ALF has shown an increased survival rate. Clinical studies in acute, chronic liver failure and metabolic disorders have also been undertaken in a few centres and have shown encouraging results. To maintain the continuous supply of cells, xenogenic source of hepatocytes (porcine, rabbit, canine) have offered a hope. A major concern regarding the use of xenogenic donors is the risk of transmission of zoonosis and immunogenicity. Recently, Porcine endogenous retrovirus (PERV) has been shown to infect human tissue in vitro. The problem of immunogenicity of xenogenic hepatocytes can be overcome to some extent by immunoisolation, encapsulation technique, which may also provide protection to the hepatocytes during cryopreservation. The knowledge of adult hepatic stem from tissue offered a new hope for the treatment of various chronic and metabolic diseases. Further, the transdifferentiation potentiality of haematopoietic stem cells to hepatic lineage has strengthened cell therapy.

Bioartificial liver support for fulminant hepatic failure.

Mortality from fulminant hepatic failure (FHF) is high (50%-80%), although survivors have absolutely normal liver function. The only treatment option that is curative is liver transplantation. However, because of shortage of cadaveric organ donors and/or delay in their availability, only 10% of FHF patients ultimately receive a transplant. This has led to development of artificial liver support systems with an idea to bridge the time to transplantation and/or recovery from FHF. Initial support systems were based on the principles of hemodialysis, hemofiltration, plasma-exchange, and hemoperfusion through adsorbent media (e.g., charcoal). However, lack of clinical efficacy, problems of bioincompatibility and fear of loss of circulating hepatocyte-regeneration factors led to the search for alternate strategies. With the successful long-term propagation and culturing of human and pig hepatocytes, and the development of adequate biocompatible microcarrier modules, it is now possible to achieve sufficient density of hepatocytes per unit volume to develop bioartificial liver systems. These can be implanted transperitoneally but are subject to early destruction because of inadequate vascularization and immune attack from the host. Thus the major thrust is now to develop bioreactors, e.g., Extracorporeal Liver Assist Device (ELAD), Bioartificial Liver (BAL), etc. These contain human or pig hepatocytes implanted on hollow-fiber ultrafiltration cartridges. The patient's blood or plasma circulates through these bioreactors and after clearance of toxic compounds (via ultrafiltration and metabolism in hepatocytes) and addition of synthesized products, is returned to the patient. This article reviews the genesis, the pros and cons, and the clinical experience of BAL support for FHF.