Liver transplantation for acute hepatic failure

There are numerous causes of acute hepatic failure (AHF). Cerebral edema, coagulopathy, renal failure, metabolic disturbances and infection are the main clinical sequelae. Patients with AHF should be stabilized when first encountered and transferred to the nearest liver transplant center, as AHF progresses quickly and is often fatal. There are few adequate medical interventions and care of patients with AHF is supportive until spontaneous recovery ensues. If recovery does not appear to occur, most causes of AHF are well accepted indications for liver transplantation.     

Total hepatectomy and liver transplantation as a two-stage procedure for fulminant hepatic failure: A safe procedure in exceptional circumstances

AIM: To evaluate the outcomes of two-stage liver transplant at a single institution, between 1993 and March 2015.METHODS: We reviewed our institutional experience with emergency hepatectomy followed by transplantation for fulminant liver failure over a twenty-year period. A retrospective review of a prospectively maintained liver transplant database was undertaken at a national liver transplant centre. Demographic data, clinical presentation, preoperative investigations, cardiocirculatory parameters, operative and postoperative data were recorded.RESULTS: In the study period, six two-stage liver transplants were undertaken. Indications for transplantation included acute paracetamol poisoning(n = 3), fulminant hepatitis A(n = 1), trauma(n = 1) and exertional heat stroke(n = 1). Anhepatic time ranged from 330 to 2640 min. All patients demonstrated systemic inflammatory response syndrome in the first post-operative week and the incidence of sepsis was high at 50%. There was one mortality, secondary to cardiac arrest 12 h following re-perfusion. Two patients required re-transplantation secondary to arterial thrombosis. At a median follow-up of 112 mo, 5 of 6 patients are alive and without evidence of graft dysfunciton.CONCLUSION: Two-stage liver transplantation represents a safe and potentially life-saving treatment for carefully selected exceptional cases of fulminant hepatic failure.     

Liver transplantation in adults with acute liver failure: Outcomes from the Argentinean Transplant Registry

Introduction and aimLiver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes.Material and methodsData were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998–2005 and 2006–2016). We used survival analysis to evaluate risk of death.ResultsA total of 561 patients were listed for LT (69% female, mean age 39.5 ± 16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p < 0.02) and 1-month post-LT survival rates improved from 70% to 82% (p < 0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02–1.36] and serum creatinine (HR 1.31 [1.01–1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N = 363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06–2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36–1.05]).ConclusionsSurvival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality.     

Diagnostic criteria for acute liver failure due to Wilson disease

AIM: To describe the diagnostic criteria for acute liver failure due to Wilson disease (WD), which is an uncommon cause of acute liver failure (ALF). METHODS: We compared findings of patients presenting with ALF due to WD to those with ALF of other etiologies. RESULTS: Previously described criteria, such as low alkaline phosphatase activity, ratio of low alkaline phosphatase to total bilirubin or ratio of high aspartate aminotransferase (AST) to alanine aminotransferase (ALT), failed to identify patients with ALF due to WD. There were significant differences in low ALT and AST activities (53 ± 43 vs 1982 ± 938, P < 0.0001 and 87 ± 44 vs 2756 ± 2941, P = 0.037, respectively), low choline esterase activity (1.79 ± 1.2 vs 4.30 ± 1.2, P = 0.009), high urine copper concentrations (93.4 ± 144.0 vs 3.5 ± 1.8, P = 0.001) and low hemoglobin (7.0 ± 2.2 vs 12.6 ± 1.8, P < 0.0001) in patients with ALF caused by WD as compared with other etiologies. Interestingly, 4 of 7 patients with ALF due to WD survived without liver transplantation. CONCLUSION: In ALF, these criteria can help establish a diagnosis of WD. Where applicable, slit- lamp examination for presence of Kayser-Fleischer rings and liver biopsy for determination of hepatic copper concentration still remain important for the diagnosis of ALF due to WD. The need for liver transplantation should be evaluated carefully as the prognosis is not necessarily fatal.     

Successful management of acute liver failure in Italian children: A 16-year experience at a referral centre for paediatric liver transplantation

BackgroundIdentifying the causes of acute liver failure (ALF) and predictors of death or liver transplantation (LTX) is crucial to decide its management. We aimed to describe features and outcome of ALF in Italian children.MethodsRetrospective review of cases presenting between 1996–2012. ALF was defined by high transaminases, INR ≥2.0 regardless of hepatic encephalopathy (HE), no evidence of underlying chronic liver disease.Results55 children (median age 2.6 years, range 0.1–15.1; M/F = 31/24) had ALF due to autoimmune hepatitis (AIH) in 10 (18%), metabolic disorders in 9 (17%), paracetamol overdose in 6 (11%), mushroom poisoning in 3 (5%), viral infection in 1 (2%), indeterminate in 26 (47%); 25/55 recovered with supportive management (45%); 28/55 underwent LTX and 2 died on the waiting list (55%). On multivariate analysis severity of HE grade 3–4 and bilirubin ≥12 mg/dl were independent predictors of death or LTX (p < 0.05). After a median follow up of 4 years (range 2–15.0 years) the overall survival rate was 93%.ConclusionChildren with ALF can be managed successfully with combined medical treatment and transplantation, warranting a survival rate similar to children transplanted because of chronic conditions. In our cohort of patients severe HE and high bilirubin on admission were independent predictors of the need of LTX.     

Liver transplantation for acute-on-chronic liver failure

Purpose  

To evaluate the outcome of liver transplantation for acute-on-chronic liver failure.     

Liver transplantation for acute liver failure: outcome analysis

Summary. Acute liver failure (ALF) remains a major cause of morbidity and mortality. Before the availability of liver transplantation only 20% of patients with ALF survived. The clinical dilemma relates to the prognostication of these patients, as early liver transplantation has been associated with better outcomes. The eligibility for liver transplantation must therefore be quickly established. The patient's age, aetiology of disease, interval between the onset of jaundice and encephalopathy, blood pH, prothrombin time, serum bilirubin and serum creatinine levels has been identified as useful prognostic markers. The degree of hepatocyte necrosis on liver biopsy and estimated hepatic volume by computed tomography may also be valuable predictors of survival; however, further studies are needed.     

对肝功能衰竭的猪行异位部分肝移植的效果评价

目的 探讨在猪急性缺血性肝功能衰竭时行辅助性异位部分肝移植的作用。 方法在缩窄门静脉8 5％以上的同时,对结扎及不结扎肝动脉的家猪体内配对开展辅助性异位部分肝移植,监测受体存活情况、肝功能、肝脏血流情况、病理及供肝胆汁分泌情况。 结果 在缩窄门静脉85％以上并结扎肝动脉的受体肝脏体积缩小,病理提示大片肝细胞坏死,在缩窄门静脉85％以上而未结扎肝动脉的受体肝脏色泽正常,病理肝细胞无明显异常;植入肝体积增大,病理提示肝细胞存活良好并有分裂增生。 结论 受体肝动脉结扎、门静脉缩窄可以造成急性肝功能衰竭模型;辅助性异位部分肝移植能纠正肝功能衰竭;保留受体肝脏动脉血供、减少门静脉血供对受体肝脏功能无严重影响。     

Parvovirus B19 induced hepatic failure in an adult requiring liver transplantation

Parvovirus B19 induced acute hepatitis and hepatic failure have been previously reported, mainly in children. Very few cases of parvovirus induced hepatic failure have been reported in adults and fewer still have required liver transplantation. We report the case of a 55-year-old immunocompetent woman who developed fulminant hepatic failure after acute infection with Parvovirus B19 who subsequently underwent orthotopic liver transplantation. This is believed to be the first reported case in the literature in which an adult patient with fulminant hepatic failure associated with acute parvovirus B19 infection and without hematologic abnormalities has been identified prior to undergoing liver transplantation. This case suggests that Parvovirus B19 induced liver disease can affect adults, can occur in the absence of hematologic abnormalities and can be severe enough to require liver transplantation.     

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, how ever, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.     

背驮式肝移植治疗急性肝衰竭15例

目的探讨肝移植治疗急性肝衰竭（ALF）的临床疗效，总结移植前处理、手术时机的选择以及术中关键技术应用的经验。方法回顾性分析了1999年9月2006年2月采用背驮式肝移植治疗15例ALF患者的临床资料。结果患者均获随访，术后1年生存率87％（13／15）。其中2例急性肝衰竭型威尔逊氏病患者术后角膜K—F环消失，血清铜蓝蛋白恢复正常。1例术后第11天死于多系统器官功能衰竭，1例患者术后第6天死于严重肺部感染，其余11例HBsAg转阴。结论肝移植是治疗ALF的有效方法，能提高ALF患者的生存率；年龄不应作为ALF患者肝移植的禁忌证；充分的术前准备和恰当的移植时机选择以及术中关键技术的使用是提高术后生存率的关键。     

儿童急性肝衰竭的肝移植治疗

儿童急性肝衰竭(PALF)是一种罕见的综合征,致死率高。肝移植仍然是目前PALF唯一疗效肯定的治疗方法。近年来,我国儿童肝移植技术日趋成熟,已显著改善PALF预后。但PALF进行肝移植仍存在许多问题,充分讨论PALF患儿行肝移植术术前、术中和术后存在的客观问题,将进一步改善PALF患儿的整体预后。     

Celecoxib-induced cholestatic liver failure requiring orthotopic liver transplantation

Selective cyclooxygenase-2 （COX-2） inhibitors are widely used due to their efficacy and good safety profile. However, recent case reports have described varying degrees of liver injudes associated with the use of COX-2 inhibitors. We report the case of a patient who developed acute cholestatic hepatitis progressing to hepatic failure requiring liver transplantation, following a 3-d course of celecoxib for treatment of generalized muscle aches and pains. The clinical presentation, the laboratory data, as well as the liver histopathology were supportive of the putative diagnosis of drug induced liver injury.     

Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg·d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg·d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α (TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438±102 vs 841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNPa (indomethacin vs N/S: 22±5 vs 10±1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure.