Pathogenesis of hepatic encephalopathy in acute liver failure

Hepatic encephalopathy (HE) in acute liver injury signifies a serious prognosis. Brain edema and intracranial hypertension are major causes of death in this syndrome. Comparison of HE in acute liver failure (ALF) with that of cirrhosis allows recognition of important differences and similarities. A key role for ammonia in the pathogenesis of both HE and brain edema is now firmly supported by clinical and experimental data. Additional factors, such as infection, products of the necrotic liver, and synergistic toxins, may contribute to an altered mental state. A low plasma osmolarity, high temperature, and both high and low arterial pressure may affect brain water content. A combined derangement of cellular osmolarity coupled with cerebral hyperemia can explain the development of brain edema in ALF. Increasingly, study of the mechanisms responsible for brain swelling provides critical information for understanding the pathogenesis of HE.     

急性胰腺炎肝损伤的发病机制和治疗

急性胰腺炎(acute pancreatitis,AP)是临床常见的急腹症,常常引起胰外器官损伤,肝脏是主要受损器官之一,其损害的不断加重可导致胰腺炎病情恶化,目前认为肝脏损伤的机制主要有细胞因子、胰酶、氧化应激、微循环障碍、细胞凋亡和胰腺炎相关性腹水等.目前AP肝损伤的治疗也主要从上述各方面着手,但更多的方法仍仅仅局限于动物实验,临床应用还需进一步研究.     

Acute kidney injury in acute on chronic liver failure

Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.     

Acute kidney injury in acute liver failure: a review

Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.     

Mechanisms of hepatocyte injury, multiorgan failure, and prognostic criteria in acute liver failure

Acute liver failure (ALF) occurs when the rate and extent of liver cell death are not adequately balanced by regenerative activity. Two forms of liver cell death are recognized: apoptosis and necrosis. A number of causes of ALF have been shown, predominantly in experimental animal models, to induce one or the other form of liver cell death. Nonetheless, an insult capable of inducing apoptosis may cause cell death by necrosis, particularly if the degree of mitochondrial damage is sufficient to exhaust stores of adenosine triphosphate. Here we consider mechanisms of liver cell injury in ALF, including evolving knowledge of signaling pathways leading to hepatocellular apoptosis and necrosis. Factors that have an impact on the adequacy of hepatic regeneration along with the pathophysiology of complicating multiorgan failure are also reviewed. Prognostic criteria are discussed, especially in relation to current concepts of mechanisms of liver cell death and multiorgan dysfunction.     

Acute liver injury,acute liver failure and acute on chronic liver failure: A clinical spectrum of poisoning due to Gyromitra esculenta

Gyromitra esculenta, also known as “false morel” is one of the most poisonous mushrooms. This species is found all over the world, growing in coniferous forest in early spring time. Common manifestation of poisoning includes gastrointestinal symptoms which include varied degrees of liver impairment.We describe three cases: acute liver injury, acute liver failure and acute-on-chronic liver failure due to G. esculenta poisoning. At admission patients presented with encephalopathy and features of liver failure. Two of them recovered completely following supportive management while the remaining patient who also had preexisting liver disease developed multiorgan failure and subsequently died.Although a rare occurrence, G. esculenta poisoning should be considered in the differential diagnosis of acute liver failure.     

Renal failure in acute liver failure.

Renal failure develops in approximately 55% of all patients referred to specialized centres with acute liver failure. The renal failure may be secondary to the liver failure itself (and is termed the hepatorenal syndrome) or the renal failure may be a secondary insult that directly affects both liver and kidney alike (for example paracetamol overdose). The pathogenesis of the hepatorenal syndrome involves the development of a hyperdynamic circulation, with a lowering of renal perfusion pressure, the activation of the sympathetic nervous system, which renders the kidneys more susceptible to modest decreases in perfusion pressure, and increased synthesis of a variety of vasoactive mediators. These mediators can cause renal vasoconstriction, but more importantly they can also decrease the glomerular capillary ultrafiltration coefficient (Kf), thus causing a decline of glomerular filtration rate over and above that caused by renal vasoconstriction alone. The treatment of the renal failure in acute liver failure involves the optimization of renal haemodynamics and haemofiltration. Renal failure will always recover when there is recovery of liver function, and in the absence of a spontaneous hepatic recovery, liver transplantation will reverse the hepatorenal syndrome.     

Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow

BACKGROUND/AIMS: The study aims were to determine the role of inflammation in the pathogenesis of increased intracranial pressure (ICP) in patients with acute liver failure (ALF) and its interplay with cerebral blood flow (CBF) and ammonia. METHODS: Twenty-one patients with ALF were studied from the time they were ventilated for grade 4 encephalopathy until receiving specific treatment for increased ICP. Depending upon the ICP, the patients were divided into two groups; those that required specific treatment (ICP>20 mmHg, group 1: n=8, ICP: 32 (28-54) mmHg); and those that did not (ICP< or =20 mmHg, group 2: n=13, ICP: 15 (10-20) mmHg). RESULTS: Inflammatory markers, arterial ammonia and CBF were significantly higher in the group 1 patients. TNFalpha levels correlated with CBF (r=0.80). Four patients from group 2 developed surges of increased ICP (32 (15-112) hours from enrolment). These were associated increases in markers of inflammation and TNFalpha, and an increase in CBF. There was no change in these inflammatory markers, CBF or ICP in the other 9 group 2 patients. CONCLUSIONS: The results of this study suggest that inflammation plays an important synergistic role in the pathogenesis of increased ICP possibly through its effects on CBF.     

Thrombopoietin in acute liver failure

Thrombopoietin (TPO) is the primary regulator of platelet production. TPO is produced in the liver and levels are low in patients with cirrhosis. Because thrombocytopenia is common in patients with acute liver failure (ALF), we measured TPO concentrations (normal TPO range, 31 to 136 pg/mL) in 51 patients with ALF to determine if low levels were associated with thrombocytopenia. TPO levels from hospital day 2 were elevated in 43% of patients, normal in 47%, and decreased in 10% of patients. Levels were higher in acetaminophen-induced than in non-acetaminophen-induced ALF, 160 (12 to 549) pg/mL versus 73 (18 to 563) pg/mL, respectively, P =.031. TPO levels did not correlate with platelet count and were not related with survival or infection. We analyzed daily TPO levels for the first week of hospitalization in 12 patients with acetaminophen-induced ALF and observed a gradual increase from a median admission level of 50 (5 to 339) pg/mL to a median peak level of 406 (125 to 1,081) pg/mL occurring on day 5 (3 to 6). Platelets were reduced in 11 of the 12 patients with a nadir platelet count of 52 (19 to 156) x 10(9) cells/L occurring on day 5.5 (1 to 6). The peak TPO level did not correlate with the nadir platelet count (P =.43). In conclusion, the normal inverse relationship between platelet count and TPO levels was not observed in ALF. Despite severe hepatic dysfunction, serum TPO levels were initially normal and increased during hospitalization in acetaminophen-induced ALF, but did not prevent the development of thrombocytopenia.     

急性出血坏死性胰腺炎肺损伤的发病机制

0 引言急性胰腺炎(AP)的研究进展较大,然而急性出血坏死性胰腺炎(AHNP)早期容易并发多器官功能衰竭(MODS),尤其是呼吸功能障碍在75%的急性胰腺炎(AP)患者中发生,临床症状从较轻的低氧血症到成人呼吸窘迫综合征(ARDS)均可出现.AHNP 相关的 ARDS 在临床表现和病理特征上均与其他原因如败血症、严重创伤所引起的 ARDS 相似,但是其发病机制还不清楚.最新的研究表明,AP 是一种全身炎症反应综合征,其发病机制复杂,与多种因素有关.近年来经大量研究,许多学者对 AP 相关肺损伤的发病机制有了较多的认识,其中包括胰酶、补体系统和激肽的作用,循     

Role of liver transplantation in acute liver failure

Orthotopic liver transplantation is employed as salvage therapy for individuals who are unable to recover from acute liver failure. Prognostic models are helpful but not entirely accurate in predicting those who will eventually require liver transplantation. There are specific criteria for United Network for Organ Sharing category 1a (urgent) listing of these patients. Unfortunately, clinical deterioration develops rapidly and many require removal from the waiting list prior to transplantation. With advances in critical care management and surgical technique, 1-year post-transplant survival rates have improved to 60 to 80%. Alternatives to conventional orthotopic liver transplantation include living donor liver transplantation, ABO-incompatible grafts, and auxiliary liver transplantation. There are many ethical and psychosocial issues inherent to transplanting these sick patients due to the urgent nature of acute liver failure. Fortunately, the long-term survival and quality of life in these transplant recipients is good.     

新型冠状病毒肺炎合并肝损伤的发生机制

新型冠状病毒肺炎已对全球公共卫生造成了重大威胁。除呼吸系统外,部分患者可出现不同程度的肝损伤。基于相关文献,对病原学特征及其致病机制进行分析,初步探讨导致新型冠状病毒肺炎合并肝损伤出现的原因可能有病毒的直接作用、炎性细胞因子风暴、药物性肝损伤、低氧性肝损伤及免疫功能障碍等。建议临床可选择合理药物进行护肝治疗,减少肝损伤的发生。     

急性/亚急性肝衰竭合并急性肾损伤的临床特征分析

目的初步明确急/亚急性肝衰竭(ALF/SALF)合并急性肾损伤(AKI)患者的临床特征。方法回顾性分析解放军第三〇二医院2015年1月-2016年12月收治的115例ALF/SALF患者临床资料,根据是否发生AKI分为AKI组(n=36)和无AKI组(n=79)。比较两组患者的年龄、性别、肝功能、外周血WBC水平、凝血功能、MELD评分及并发症发生情况等,观察发生AKI患者的预后情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果导致ALF/SALF的病因以药物性最为多见(49.57%),其次为不明原因(28.70%)。115例ALF/SALF患者中共36例合并AKI,AKI发生率为31.3%,其中1、2及3期发生率分别为11.30%、14.78%、5.22%。与未发生AKI的患者相比,AKI组患者年龄、WBC、中性粒细胞比值、腹水、腹腔和肺部感染率以及MELD评分均显著增高,血清Alb水平显著降低(P值均<0.05)。发生AKI的患者无效/死亡率明显高于无AKI患者(69.4%vs38.0%,χ2=9.815,P=0.002),且随AKI严重程度的增高,病死率升高,1、2及3期AKI患者无效/死亡的比例分别为61.5%、70.6%和83.3%。结论肝衰竭患者发生AKI时多存在感染或炎症反应,且AKI的发生与肝衰竭患者的病死率相关。