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Liver dysfunction is the decrease in liver functions, which limits the fulfillment of its main functions such as the elimination of harmful substances from the bloodstream, digestion of food and synthesis of vitamins. When this organ is affected by viruses such as dengue, it can cause enzymatic alterations, inflammation, more serious deficiencies such as acute liver failure. The objective of the research was to describe the association between liver dysfunction and dengue virus infection. A descriptive research with documentary design was carried out, through a systematic review in the electronic databases Pubmed, SciELO, Elsevier and Google Scholar, including articles published in the last four years in English - Spanish languages. Hepatic dysfunction presents in the form of transaminitis with around 65-97% in the cases of patients with dengue. Serious alterations and cases with the presence of acute liver failure due to dengue have been described. Post-mortem studies have revealed viral particles in liver tissue. Based on the analysis of the studies, it is suggested that dengue infection affects tissues and organs, including liver tissue, however, the mechanism of action by which the virus induces damage to liver tissue is not yet well defined, La disfunción hepática es la disminución en las funciones del hígado, lo que limita cumplir con sus principales funciones como es la eliminación de sustancias dañinas del torrente sanguíneo, digestión de alimentos y síntesis de vitaminas. Cuando este órgano es afectado por virus como el dengue, puede causar alteraciones enzimáticas, inflamación, deficiencias más graves. El objetivo de la investigación fue describir la asociación entre la disfunción hepática y la infección por el virus dengue. Se realizó una investigación descriptiva con diseño documental, a través de una revisión sistemática en las bases electrónicas Pubmed, SciELO, Elsevier y Google Académico, incluyendo artículos publicados en los últimos cuatro años en idiomas inglés – español. La disfunción hepática se presenta en forma de transaminitis con alrededor del 65 -97% en los casos de pacientes con dengue. Se han descrito alteraciones graves y casos con presencia de insuficiencia hepática aguda por dengue. Estudios post-mortem han revelado partículas virales en el tejido hepático. En base al análisis de los estudios se sugiere que la infección por dengue afecta tejidos y órganos, entre ellos el tejido hepático, sin embargo, aún no está bien definido el mecanismo de acción por el cual el virus induce daño al tejido&nbsp

Acute paracetamol poisoning due to a single overdose may be effectively treated by the early administration of N-acetylcysteine (NAC) as an antidote. The prognosis may be different in the case of intoxication due to multiple ingestions or when the antidote is started with delay. The aim of this work was to investigate the outcome of paracetamol poisoning according to the pattern of ingestion and determine the factors associated with the outcome. We performed a retrospective analysis over the period 2007⁻2017 of the patients who were referred to a tertiary hospital for paracetamol-related hepatotoxicity. Inclusion criteria were: accidental or voluntary ingestion of paracetamol, delay for NAC therapy of 12 h or more, liver enzymes (ALT) >1000 IU/L on admission. Ninety patients were considered. Poisoned patients following multiple ingestion were significantly older (45 ± 12 vs. 33 ± 14) (p = 0.001), with a higher incidence of liver steatosis (p = 0.016) or chronic ethanol abuse (p = 0.04). In comparison with the subgroup of favorable outcome, the patients with poor outcome were older, had higher values for ALT, bilirubin, lactate, and lower values for factor V and arterial pH. In multivariate analysis, the arterial lactate value was associated with a bad prognosis (p < 0.02) (adjusted odds ratio 1.74 and CI 95:1.09⁻2.77). The risk of poor outcome was greater in the subgroup with staggered overdose (p = 0.02), which had a higher mortality rate (p = 0.01). This retrospective analysis illustrates the different population patterns of patients who were admitted for a single ingestion of a paracetamol overdose versus multiple ingestions. This last subgroup was mainly represented by older patients with additional risk factors for hepatotoxicity; arterial lactate was a good predictor of severity.

This dissertation describes a clinically relevant pig model that provides insight into metabolic changes in severe sepsis and acute hepatic failure. By using new tracer methods, we demonstrate that intestinal and hepatic interorgan metabolism is very complex and dynamic, even under healthy circumstances. It is shown that in severe sepsis, intestinal and hepatic metabolism is more disturbed than muscle metabolism. This information can contribute to the development of new nutritional strategies in illness. In addition, the protein quality of foods is shown to determine the availability of nutrients in the blood circulation. Therefore, the packaging of food products should always contain information about the protein quality.

Bone morphogenetic proteins-2/4/7 (BMP-2/4/7) are important cytokines in systemic tissue morphogenesis. It has been demonstrated BMPs may have positive effects on liver repair and regeneration after hepatic injury. However, their function in the liver still remains unclear. D-galactosamine (D-gal) is a hepatotoxin used to induce hepatic failure. We employed D-gal and rat hepatoma cell line (1548) to investigate BMP-2/4/7 expression in hepatic injury induced by D-gal and probe their relations with liver repair and regeneration in hepatic injury. LDH release, mRNA and protein expression were detected. Results indicated that BMP-2/4/7 expression was activated by injury of rat hepatoma cells. It is indicative that repair and regeneration of the liver after hepatic injury and morphogenesis in early embryos seem to proceed through the same process. BMPs may be not only associated with hepatic injury after repair and regeneration, but also involved in chronic liver.

Background Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of "liver dialysis". During a 72-h extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (hRBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the hRBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of hRBCs seen during extracorporeal porcine liver xenoperfusion. Methods Ex vivo studies were performed using wild type pig livers perfused with isolated hRBCs for 72-h in the presence of an anti-porcine sialoadhesin antibody or isotype control. Results The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of hRBC over a 72-h period. Sustained liver function was demonstrated throughout the perfusion. Conclusions This study illustrates the role of sialoadhesin in mediating the destruction of hRBCs in an extracorporeal porcine liver xenoperfusion model. © 2013 John Wiley & Sons A/S.

Background/Aims: To identify clinical significances of portal vein embolization (PVE) prior to major hepatectomy, we examined clinical parameters and outcome after right hepatectomy in patients who underwent PVE. Methodology: The subjects were 30 patients who underwent PVE (PVE group), and 52 patients (non-PVE), in whom PVE was considered unnecessary, followed by right hepatectomy for hepatobiliary cancer. Results: Total hepatic volume after PVE (1068±268 ml) tended to increase compared with before PVE (p=0.059). After PVE, the change in hemi-liver volume was 8.9±6.0%. Increases in hepatic volume of non-embolized left liver before and at 4 weeks after hepatectomy between the PVE and non-PVE groups were similar. Changes in hepatic volumes before and after PVE were not significantly influenced by background liver disease. After PVE, the functional liver volume (419±185cm 3) was significantly lower than morphological volume (564±165cm3) in the embolized liver (p<0.05). Although preoperative liver function was worse in the PVE group compared with non-PVE, serious hepatic complications were rarely observed in the PVE group. Conclusions: Marked changes in hepatic volume were noted after PVE in patients with impaired liver function and those who need large-volume right hepatectomy, especially in functional volume, suggesting that PVE is a useful procedure to prevent postoperative liver failure., Hepato-Gastroenterology, 56(91-92), pp.773-777; 2009

A 60-year-old man without any history of cardiac disease was admitted for fulminant hepatic failure (FHF) with coma which revealed severe dilated cardiomyopathy.The patient improved with an adapted medical treatment and was finally discharged from the hospital. Congestive heart failure is a rare cause of FHF, but an important differential diagnosis because it has a specific and potentially efficient treatment., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Conventional diagnostic procedures and therapy of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) focus on to identify triggering events of the acute deterioration of the liver function and to avoid them. Further objectives are to prevent the development respectively the progression of secondary organ dysfunctions or organ failure. Most of the times the endocrinological function of the liver can to a wide extent be compensated, but the removal of toxins can only marginally be substituted by conventional conservative therapy. To improve this component of the liver function is the main objective of extracorporal liver support systems. The following principles of liver support systems can be differentiated: Artificial systems, bioartifical systems and extracorporal liver perfusion systems. This HTA report focuses on artificial systems (e.g. BioLogic-DT/-DTPF, MARS, Prometheus), because only these approaches currently are relevant in the German health care system. In 2004 a category "Extracorporal liver assist device" was introduced in the list of "additional payments" in the German DRG-system, which makes reimbursement for hospitals using the technology in inpatient care possible, based on an hospital's individual contract with statutory sickness funds. Objectives To report the present evidence and future research need on medical efficacy and economic effectiveness of extracorporal liver support devices for treatment of patients with ALF or ACLF based on published literature data. Are artificial liver support systems efficient and effective in the treatment of ALF or ACLF? Methods An extensive, systematic literature search in medical, economic, and HTA literature data bases was performed. Relevant data were extracted and synthesised. Results Relevant controlled trials were detected for BioLogic-DT and MARS. No randomised controlled trial on Prometheus was found. None of the included studies on BioLogic-DT showed advantages of the technolo, Hintergrund Die konventionelle Diagnostik und Therapie des akuten Leberversagens (Acute Liver Failure = ALF) sowie der akuten Dekompensation einer chronischen Lebererkrankung (Acute-On-Chronic Liver Failure = ACLF) ist fokussiert auf die Identifikation und Behebung der auslösenden Ereignisse des Leberversagens. Ferner gehören die Vermeidung der Entstehung bzw. die Therapie bereits vorhandener sekundärer Organdysfunktionen bzw. -versagen zu ihren primären Aufgaben. Die Funktionen der versagenden Leber sind dabei für den Bereich Synthese und Stoffwechselregulation zeitweilig meist gut zu substituieren. Die Leberentgiftungsfunktion ist allerdings mit konservativen Mitteln kaum zu ersetzen. Hier liegt der primäre Ansatzpunkt der extrakorporalen Leberunterstützungsverfahren. Unterscheiden lassen sich artifizielle Verfahren, bioartifizielle Verfahren sowie Ansätze zur extrakorporalen Leberperfusion (ECLP). Der vorliegende HTA untersucht schwerpunktmäßig die artifiziellen Verfahren (insbesondere: BioLogic-DT/-DTPF, MARS, Prometheus), da allein diese in Deutschland gegenwärtig und auf absehbare Zeit Relevanz haben. Seit 2004 wurde erstmals in diesem Land über die Definition der Zusatzleistung "Extrakorporale Leberersatztherapie (Leberdialyse)" eine krankenhausindividuelle Vergütung im System der gesetzlichen Krankenversicherung (GKV) möglich. Ziele Der HTA-Bericht legt die Datenlage und den Forschungsbedarf zur medizinischen Wirksamkeit und zur Wirtschaftlichkeit der extrakorporalen Leberunterstützungsverfahren bei ALF oder einer ACLF dar. Sind die extrakorporalen Leberunterstützungsverfahren von leberpflichtigen Stoffwechselprodukten wirksame Verfahren zur Therapie eines ALF oder einer ACLF? Methoden Zur Erschließung des Datenmaterials wurde eine systematische, breit angelegte Literaturrecherche in den gängigen medizinischen, ökonomischen und HTA-Datenbanken sowie in weiteren Medien durchgeführt. Ergebnisse Lediglich zu den Verfahren BioLogic-DT und Molecular Adsorbent Rec

Objective: In physiological conditions, the liver plays an important role in the regulation of plasma arginine concentrations by taking up large amounts of arginine from the hepatic circulation. When hepatic failure is present, arginine metabolism may be disturbed. Therefore, we hypothesized high arginine plasma concentrations in critically ill patients suffering from hepatic failure. Design: We prospectively collected blood samples from a cross-section of intensive care unit patients. Setting: Surgical intensive care unit of a Dutch university medical center. Subjects: A total of 52 critically ill patients with clinical evidence of dysfunction of more than two organs were recruited. Measurements: Plasma arginine concentrations were determined by HPLC. We identified correlations of arginine concentrations with organ failure scores and laboratory variables by univariate and multiple regression analyses. Results: High plasma arginine concentrations were found in critically ill patients developing organ failure. Patients who were in the highest quartile of plasma arginine concentrations had significantly lower fibrinogen concentrations, higher lactic acid concentrations, and longer prothrombin time. Stepwise multiple regression analysis showed that concentrations of arginine were independently associated with the presence of hepatic failure (P = 0.03) and renal failure (P = 0.048). In addition, lactic acid proved to be an independent determinant of plasma arginine concentration (P = 0.014). Conclusions: Critically ill patients who suffer from hepatic failure have elevated plasma arginine concentrations. Additional arginine in the treatment of these patients can be harmful, and therefore should not be used as a standard nutritional regimen until further evaluation.

In fulminant hepatic failure, survival is not possible without recovery of sufficient hepatocyte mass. Remarkably, only a few studies exist that provide insight into the mechanisms that control proliferation of residual hepatocytes after extensive hepatocyte loss. In this regard, the role of growth-regulatory factors, including pro-inflammatory cytokines such as interleukin-6 (IL-6), is not well understood. In the present study we show that in rats with critically low (10%) hepatocyte mass, whether with or without ongoing liver cell necrosis, inhibition of liver regeneration is associated with early and sustained increase in blood IL-6 levels. Under these conditions, the signal transducer and activator of transcription (Stat3) DNA binding activity was lowered at the time of G1/S cell-cycle transition. We further demonstrate that the protein inhibitor of activated Stat3 (PIAS3) and the suppressor of cytokine signaling (SOCS-1) were upregulated early after induction of liver failure (6-12 h), In vitro, IL-6 induced PIAS3 expression in HGF stimulated rat hepatocytes. These findings suggest that after massive hepatocyte loss, an early and rapid rise in blood IL-6 levels may weaken the hepatic regenerative response through up-regulation of Stat3 inhibitors PIAS3 and SOCS-1.

SCOPUS: re.j, info:eu-repo/semantics/published

The authors prepared D-galactosamine (Gal) hepatic failure rats and hepatic failure dogs induced by hepatic ischemia and studied the correlation between the progress of hepatic failure and amount of trace metal in liver measured of the rats and dogs. After Gal was given, the rats rapidly fell into hepatic failure condition. They were sacrificed with the lapse of time and their zinc (Zn) content in liver was measured, which showed a decrease in relation to hepatic injury reaching a minimum of 67. 2 ± 3. 8 μg/g dry weight (that of control group: 149. 1 ± 23. 4, p<0. 05) 48 hr later. The hepatic failure dogs induced by hepatic ischemia also fell into hepatic failure after hepatic ischemia and died 17.5-112 hr (average 57.1 ± 38. 2) later. Positive correlation between the Zn. content in liver immediately after death and the survival time (r= 0. 653, p<0. 01). As a result, it is suggested that the Zn content in liver can be used as an index to the degree of hepatocyte injury and prognosis of hepatic failure.

The findings made in the presented study suggest that one or more still unknown factors inherent in the experimental models currently in use are of critical importance and that only a certain limited type of model of acute hepatic failure is suitable for the evaluation of the effectiveness of methods intended to promote regeneration of diseased livers. It does not seem unreasonable to conclude that 40 x 106 liver cells injected into the abdominal cavity or the spleen would not improve survival, since ca. 300xlo6 (representing 30% of a normal liver) did not do so. It is conceivable that in a given model the use of hepatocytes and/or hepatocyte fractions triggers a non-specific reaction leading to survival. It is then also conceivable that when the hepatocytes or hepatocyte fractions are injected, the ongoing damage caused by galactosamine is arrested before it becomes lethal. This means that in cases of real fulminant hepatic failure the only chance of survival lies in the ability of the graft either to induce regeneration in the diseased liver or to take over all of the functions of the damaged liver. Because of the excessive risk associated with waiting to see whether the organ will recover is too great, it is preferable to aim at a transplantation enabling the graft to take over functions of the host's liver completely

A rat model of fulminant hepatic failure induced by D-galactosamine (Gal) was given glucagon and insulin. The amount of Zn contained in its liver was measured and investigated for use as an index to the progress of hepatic failure and to the hepatic regeneration. The results showed that the Zn content in the rat's liver had been rapidly reduced to the lowest value 48 hours after Gal was given before the morphological change occurred. Also, a significant improvement was observed in the Zn content in liver by giving glucagon and insulin. As a result, it is suggested that the Zn content can be used as an index to the degree of hepatocyte injury and regeneration.

Plasma taken from hepatic failure rats induced by D-galactosamine was used to observe the variatiation in its chromatogram obtained by conducting a high performance gel-chromatography (TSK G2000SW used). The progress of hepatic failure caused distinct increase in the 12 abnormal peaks, especially peak b contained middle molecular weight substances, which showed a good correlation with the condition of progressing hepatic failure. Thus, the measurement of variation in gel-chromatogram, especially, in peak b, is effectives as a parameter of hepatic failure in progress.

Hepatic failure dogs induced by hepatic ischemia were prepared from mongrel dogs by occluding their hepatic and gastroduodenal arteries without anesthesia 48 hours after operation of their end to side port-ca val anastomosis. During the process, they were divided into two groups; the 60-minute temporary hepatic ischemia group and the continuous hepatic ischemia group. The plasma was sampled with the lapse of time from the above dogs after their hepatic ischemia and was analyzed using a high performance gel-chromatography (TSK G2000SW). The progress of hepatic failure caused distinct increase in the 12 abnormal Peaks a-1, of which Peak a and b fell in a region of middle molecular weights on the chromatography. Especially, Peak b increased greatly showing a good correlation with the condition of progressing hepatic failure. Therefore, it is considered that the measurement of variation of such peaks, especially of Peak b, by the high performance gel-chromatography will prove to be a parameter indicating the degree of hepatic failure in progress.