Frequency of renal impairment in paracetamol overdose compared with other causes of acute liver damage.

In an analysis of 160 patients with fulminant hepatic failure, the frequency of renal failure in the patiens who had taken an overdose of paracetamol was not significantly higher than in those with hepatic failure due to other causes. The same was found in another group of patients with less severe hepatic damage. In both the latter group and the patients with fulminant hepatic failure, the development of renal failure was closely related to the occurrence of endotoxaemia as detected by the Limulus lysate assay. These findings do not support the concept that an overdose of paracetamol has a specific nephrotoxic effect.     

An experimental animal model of fulminant hepatic failure in pigs

The objective of this study was to develop an experimental animal model of fulminant hepatic failure to test the efficacy of the bioartificial liver system. The portal vein and the hepatic artery were clamped intermittently and then the hepatic artery was ligated (ligation group, n=5). Pigs whose hepatic arteries were not ligated after clamping were assigned to the non-ligation group (n=5). The biochemical changes in blood, histologic alterations of the liver and neurologic examination for pigs were checked up. All animals died within 17 hr in the ligation group. On the other hand, all animals survived more than 7 days in the non-ligation group. In the ligation group, the levels of ammonia, lactic acid and creatinine showed a progressively increasing pattern. Prothrombin time was also prolonged gradually. Cytoplasmic condensation and nuclear pyknosis of hepatocytes were detected histologically at autopsy. Neurologic findings such as decreased pain sensation, tachypnea and no light reflex of pupils were observed. The findings shown in the ligation group are similar to the clinical features of fulminant hepatic failure in human and this animal model is reproducible. Therefore, this can be a suitable animal model to evaluate the efficacy of the bioartificial liver system for treating fulminant hepatic failure.     

Serum stimulatory activity and polymorphonuclear leucocyte movement in patients with fulminant hepatic failure.

Serum from 27 patients with fulminant hepatic failure and grade IV encephalopathy had reduced ability to stimulate the movement in vitro of normal polymorphonuclear leucocytes. All patients had a deficiency of serum complement factors C3 and C5 and there was a significant positive correlation between C5 and serum stimulatory activity. However, in addition to this complement defect, serum from 22% of patients contained an antagonist to normal serum stimulatory factors. This antagonism was attributed to at least two different substances in the serum on the basis of differences in heat lability, dialysability and action on complement factor C5a. Polymorphonuclear leucocytes from eight of 13 patients had reduced movement toward serum, but serum from only one patient contained an antagonist acting on the cells; this was probably related to an underlying carcinoma of the breast. During the early stages of clinical recovery, serum stimulatory and complement activity returned to normal. These serum and cellular defects have not been reported previously in patients with fulminant hepatic failure and represent major defects in the body's defenses against bacterial infection.     

Prevalence and severity of acute viral hepatitis and fulminant hepatitis during pregnancy: a prospective study from north India

The present study aimed to find out the prevalence and severity of acute viral hepatitis and fulminant hepatitis during pregnancy in North India. The study was conducted on 97 consecutive pregnant patients in third trimester with acute viral hepatitis (AVH) or fulminant hepatic failure (FHF). The patients were evaluated on the basis of history, examination, liver function profile and serological markers for hepatitis A,B,C and E viruses. Hepatitis E virus (HEV) was the causative agent in 47.4% of the cases of viral hepatitis and 52.6% were caused by non-E viruses(HAV-5.2%,HBV-7.2%,HCV-0%,non A-E 47.4%). HEV was responsible for 36.2% of the cases of AVH and 75% of the cases of FHF. The mortality was 24.7% (24/97). All of them had FHF. Eighteen of 24 cases (75%) who expired were HEV positive. The mortality rate was 39.1% in HEV group and 11.7% in non HEV group. Majority of patients (87.5%) who expired had died undelivered. Hepatitis E was the commonest etiological agent in those who had fulminant disease during pregnancy and was associated with high mortality rate.     

重组腺病毒介导的BCL-Xl基因过表达治疗急性肝衰竭大鼠的研究

目的 明确肝细胞凋亡与急性大鼠肝衰竭模型肝组织损伤程度的关系;明确BCL-Xl过表达对急性肝衰竭大鼠肝脏的治疗保护作用.方法 将60只Wistar大鼠随机分为正常对照组、模型组、处理组三组.正常对照组及模型组给予门静脉注射生理盐水,处理组予门静脉注射重组BCL-Xl腺病毒.预处理7 d后模型组及处理组予D-氨基半乳糖+脂多糖建立肝衰竭模型,观察各组大鼠的BCL-Xl蛋白的表达、ALT、AST水平、肝细胞凋亡率及死亡率.结果 BCL-Xl基因在处理组的表达高于在模型组中的表达;建立大鼠肝衰竭后6 h,处理组的血清ALT、AsT水平低于模型组(P<0.05).处理组的肝细胞凋亡率低于模型组(P<0.05).处理组的大鼠死亡率低于模型组(P<0.05).结论 在急性肝衰竭大鼠中,肝细胞的凋亡率与大鼠的死亡率呈正相关;BCL-Xl在肝组织中的过表达能减少急性肝衰竭模型大鼠的肝细胞凋亡率,降低急性肝衰竭大鼠的死亡率.     

重组腺病毒介导的BCL-Xl基因过表达治疗急性肝衰竭大鼠的研究

目的 明确肝细胞凋亡与急性大鼠肝衰竭模型肝组织损伤程度的关系;明确BCL-Xl过表达对急性肝衰竭大鼠肝脏的治疗保护作用.方法 将60只Wistar大鼠随机分为正常对照组、模型组、处理组三组.正常对照组及模型组给予门静脉注射生理盐水,处理组予门静脉注射重组BCL-Xl腺病毒.预处理7 d后模型组及处理组予D-氨基半乳糖+脂多糖建立肝衰竭模型,观察各组大鼠的BCL-Xl蛋白的表达、ALT、AST水平、肝细胞凋亡率及死亡率.结果 BCL-Xl基因在处理组的表达高于在模型组中的表达;建立大鼠肝衰竭后6 h,处理组的血清ALT、AsT水平低于模型组(P<0.05).处理组的肝细胞凋亡率低于模型组(P<0.05).处理组的大鼠死亡率低于模型组(P<0.05).结论 在急性肝衰竭大鼠中,肝细胞的凋亡率与大鼠的死亡率呈正相关;BCL-Xl在肝组织中的过表达能减少急性肝衰竭模型大鼠的肝细胞凋亡率,降低急性肝衰竭大鼠的死亡率.     

重组腺病毒介导的BCL-Xl基因过表达治疗急性肝衰竭大鼠的研究

目的 明确肝细胞凋亡与急性大鼠肝衰竭模型肝组织损伤程度的关系;明确BCL-Xl过表达对急性肝衰竭大鼠肝脏的治疗保护作用.方法 将60只Wistar大鼠随机分为正常对照组、模型组、处理组三组.正常对照组及模型组给予门静脉注射生理盐水,处理组予门静脉注射重组BCL-Xl腺病毒.预处理7 d后模型组及处理组予D-氨基半乳糖+脂多糖建立肝衰竭模型,观察各组大鼠的BCL-Xl蛋白的表达、ALT、AST水平、肝细胞凋亡率及死亡率.结果 BCL-Xl基因在处理组的表达高于在模型组中的表达;建立大鼠肝衰竭后6 h,处理组的血清ALT、AsT水平低于模型组(P<0.05).处理组的肝细胞凋亡率低于模型组(P<0.05).处理组的大鼠死亡率低于模型组(P<0.05).结论 在急性肝衰竭大鼠中,肝细胞的凋亡率与大鼠的死亡率呈正相关;BCL-Xl在肝组织中的过表达能减少急性肝衰竭模型大鼠的肝细胞凋亡率,降低急性肝衰竭大鼠的死亡率.     

Adult-to-adult living donor liver transplantation at the Asan Medical Center

Between February 1997 and December 2003, 580 adult-to-adult living donor liver transplants (A-A LDLTs) were performed at the Asan Medical Center for patients above 20 years of age. Indications for A-A LDLT were: chronic hepatitis B (309), chronic hepatitis C (18), hepatocellular carcinoma (144), alcoholic cirrhosis (20), Wilson's disease (4), autoimmune hepatitis (4), hepatic tuberculosis (1), cholangiocarcinoma (2), cryptogenic cirrhosis (5), secondary biliary cirrhosis (7), primary biliary cirrhosis (2), fulminant hepatic failure (18), primary sclerosing cholangitis (2), vanishing bile duct syndrome (1) and re-transplantation (4). Of 580 A-A LDLTs, 119 were of high medical urgency, 96 were for acute on chronic liver failure, 18 were for acute and subacute hepatic failure, 1 was for Wilson's disease, and 4 were for re-transplantation. Recipient age ranged from 20 to 69 years. The age of the donors ranged from 16 to 63 years. There was no donor mortality. Implanted liver grafts were categorized into seven types: 307 modified right lobes (MRL), 85 left lobes, 44 left lobe plus caudate lobes, 41 right lobes, 93 dual grafts, 5 extended right lobes, 4 posterior segments, and 1 extended left lateral segment. In the MRL, the tributaries of the middle hepatic vein were reconstructed by interpositioning a vein graft. Indication for dual graft implantation was the same as single graft A-A LDLT, and seventeen of 93 were emergency cases. As a right-sided graft, 47 received left lobes; 31 received a extended left lateral segment or a lateral segment; 13 received a right lobe with or without the reconstruction of middle hepatic vein tributaries; and 2 received a posterior segment. Graft volume ranged from 26.5% to 83% of the standard liver volume of the recipients. There were 46 (8.0%) one year mortalities among the 576 patients after 580 A-A LDLTs. Of the 119 patients who received emergency transplants, 108 (90.8%) survived. These encouraging results justify the expansion of A-A LDLT to adjust to increasing demands, even in urgent situations. We have aimed establish the efficacy of A-A LDLT in various end-stage chronic and acute liver diseases, as well as new technical advances to overcome the small-for-size graft syndrome by using dual-graft implantation and MRL, both of which were first developed in our department.     

儿童肝衰竭临床特征的研究

目的 探讨儿童肝衰竭的临床特征。方法 应用EXCELL 2000软件和t检验分析了本院收治的105例儿童肝衰竭临床资料。结果 (1)急性肝衰竭9例，亚急性肝衰竭38例，慢性肝衰竭58例。(2)发病人数最多的是学龄期7-12岁儿童组43例(41．0％)；其次是婴儿组30例(28．6％)。(3)婴儿组中13例(43．3％)病因不明，占第1位；其次为CMV感染9例(30．0％)。1岁以上组病因以HBV感染最多，有22例(29．3％)；病因不明21例(28．0％)；肝豆状核变性15例(20．0％)；HAV感染10例(13．3％)。(4)合并症中71例(67．6％)合并腹水，合并自发性腹膜炎34例，占有腹水病例的47．9％。合并其他部位感染的有35例(33．3％)，感染最多的是肺部感染，其次则是败血症。51例(48．6％)合并电解质紊乱，低钾见于所有电解质紊乱的病例。48例(46．2％)合并肝性脑病，肝性脑病在儿童中有其特殊的临床表现。(5)本组77．2％(71／92)患儿合并低血糖。结论 儿童肝衰竭病因与年龄有较大的关系。在婴儿组中主要是由CMV感染引起。但近一半病因不明。年长组以HBV和HAV感染为主，但在引起儿童肝衰竭的其他因素中肝豆状核变性是最常见的。在临床中必须注意儿童肝性脑病的特殊表现，积极预防和及时发现腹膜炎及除自发性腹膜炎以外的其他部位感染、电解质紊乱和低血糖等肝衰竭的合并症。     

重组腺病毒介导的BCL-X1基因过表达治疗急性肝衰竭大鼠的研究

目的明确肝细胞凋亡与急性大鼠肝衰竭模型肝组织损伤程度的关系;明确BCL—X1过表达对急性肝衰竭大鼠肝脏的治疗保护作用。方法将60只Wistar大鼠随机分为正常对照组、模型组、处理组三组。正常对照组及模型组给予门静脉注射生理盐水,处理组予门静脉注射重组BCL-Xl腺病毒。预处理7d后模型组及处理组予D-氨基半乳糖＋脂多糖建立肝衰竭模型,观察各组大鼠的BCL-X1蛋白的表达、ALT、AST水平、肝细胞凋亡率及死亡率。结果BCL．XI基因在处理组的表达高于在模型组中的表达;建立大鼠肝衰竭后6h,处理组的血清ALT、AST水平低于模型组（P〈0．05）。处理组的肝细胞凋亡率低于模型组（P〈0．05）。处理组的大鼠死亡率低于模型组（P〈0．05）。结论在急性肝衰竭大鼠中,肝细胞的凋亡率与大鼠的死亡率呈正相关;BCL-XI在肝组织中的过表达能减少急性肝衰竭模型大鼠的肝细胞凋亡率,降低急性肝衰竭大鼠的死亡率。     

暴发性肝损伤肝性脑病大鼠血浆及脑游离氨基酸变化的相关分析

本文测定了D-氨基半乳糖所致暴发性肝损伤肝性脑病大鼠血浆及脑勺浆游离氨基酸含量的变化,并作相应的相关分析。结果表明,正常大鼠血浆及脑内各种氨基酸含量间均无相关。肝性脑病大鼠血浆及脑勺浆多种氨基酸水平均有增高,脑内大多数氨基酸含量与血浆相应氨基酸的变化无相关关系,但一些与肝性脑病发生相关的氨基酸水平与其相应的血浆含量呈显著相关。提示肝性脑病的发生与血脑屏障氨基酸转运功能选择性改变有关。     

Disseminated Trichosporon beigelii infection after orthotopic liver transplantation

A 25-year-old male, who received an orthotopic liver transplant for fulminant hepatic failure resulting from hepatitis B, had disseminated Trichosporon beigelii infection develop. Of the 55 cases of disseminated T. beigelii that have been reported in the English-language medical literature, most have occurred in patients who were both neutropenic and had compromised cell-mediated immunity. Mortality has ranged from 60 to 78%. Outcome appears to depend significantly on leukocyte recovery. Histologically, Trichosporon can be confused with Candida; however, recognition of the arthroconidia and pleomorphic hyphae and pseudohyphae of Trichosporon should allow their differentiation.     

暴发性肝衰竭血脑屏障通透性改变对肝性脑病发生发展的影响

采用硫代乙酰胺所致大鼠暴发性肝衰模型，以脑组织浸泡液中Ｅｖａｎｓ蓝含量为血脑屏障通透性指标。结果表明，在肝性脑病初期血脑屏障通透性就已增加，至脑病晚期则明显增加，并伴脑水肿发生，脑组织浸泡液中Ｅｖａｎｓ蓝含量与血浆内毒素呈正相关。以上结果提示，暴发性肝衰竭时，肝性脑病发生发展与内毒素所致血脑屏障通透性增加密切相关。     

Circulating lysosomal enzymes and acute hepatic necrosis.

The activities of the lysosomal enzymes acid and neutral protease, N-acetylglucosaminidase, and acid phosphatase were measured in the serum of patients with fulminant hepatic failure. Acid protease (cathepsin D) activity was increased about tenfold in patients who died and nearly fourfold in those who survived fulminant hepatic failure after paracetamol overdose, whereas activities were increased equally in patients with fulminant hepatic failure due to viral hepatitis whether or not they survived. A correlation was found between serum acid protease activity and prothrombin time, and the increase in cathepsin D activity was sustained over several days compared with aspartate aminotransferase, which showed a sharp early peak and then a fall. Circulating lysosomal proteases can damage other organs, and measurement of their activity may therefore be of added value in assessing prognosis in this condition.     

Malarial hepatopathy

Jaundice is a common clinical presentation in severe malaria, seen in approximately 2.5% patients with falciparum infection but hepatitis is unusual. Although hepatic dysfunction is unusual and hepatic encephalopathy is almost never seen in malaria, yet, cases of hepatic dysfunction are being increasingly reported in patients with P.falciparum infection, from different parts of world. The extent of hepatocellular dysfunction varies from mild abnormalities in liver function tests to hepatic failure. Patients with hepatocellular dysfunction in malaria are more prone to develop complications, but have a favorable outcome if hepatic involvement is recognized early and managed properly. It is important to meticulously look for hepatic dysfunction in patients with severe malaria, distinguish it from fulminant hepatic failure and manage it aggressively.     

The role of hepatic venous congestion and endotoxaemia in the production of fulminant hepatic failure secondary to congestive heart failure

The present study was undertaken to clarify the role of congestion of the liver and endotoxemia in the production of fulminant hepatic failure secondary to congestive heart failure. Induction of congestion of the liver, i.e. an elevation of hepatic venous pressure, in rats was accomplished by partial obstruction of the inferior vena cava. A close relationship was demonstrated between venous pressure and serum levels of transaminases as a measure of hepatic dysfunction. Hepatic dysfunction was mild in rats with venous hypertension alone, and only centrilobular congestion was seen on microscopy. In contrast, severe abnormalities of hepatic function were induced by venous hypertension and endotoxaemia. Histologically, the liver revealed bridging centrilobular necrosis as seen in patients with congestive heart failure who develop fulminant hepatic failure. These data suggest that coexistence of endotoxaemia and congestion of the liver may induce fulminant hepatic failure, and that the latter alone is associated only with slight hepatic dysfunction and liver damage.     

左旋肉碱治疗肝硬化并显性肝性脑病的效果观察

目的 探讨左旋肉碱治疗肝硬化并显性肝性脑病患者的临床疗效。方法 选择2011年3月~2018年6月天津市宝坻区人民医院收治的84例肝硬化并发肝性脑病显性症状,且住院治疗＞1周的患者作为研究对象,随机分为左旋肉碱组和对照组,每组42例。对照组接受常规治疗,左旋肉碱组在常规治疗基础上联合应用左旋肉碱。比较治疗7 天时两组患者肝性脑病West-Haven分级、NCT-A时间、血氨情况,以及两组住院天数、随访6周时肝性脑病复发情况。结果 治疗7天时左旋肉碱组NCT-A时间为（52.31±17.92）s ,低于对照组的（61.32±18.24）s（P＜0.05）;空腹静脉血氨水平为（45.23±27.42）μmol/L,低于对照组的 （60.44±25.43）μmol/L（P＜0.05）;左旋肉碱组HE分级为（1.47±0.51）,与对照组的（1.43±0.54）比较,差异无统计学意义（P＞0.05）。两组患者平均住院日［（8.32±3.60）d vs（9.12±5.81）d］及随访6周肝性脑病早期复发率（35.71% vs 28.57%）分别比较,差异均无统计学意义（P＞0.05）。结论 左旋肉碱虽能降低肝硬化并显性肝性脑病患者血氨水平、改善NCT-A时间,但不能改善肝性脑病严重程度分级、降低住院日及肝性脑病复发率,其在肝硬化并显性肝性脑病中的应用价值有待进一步证实。     

Fulminant hepatic failure in the elderly: a clinicopathological study of autopsy cases aged over 65 years

The pathology of fulminant hepatic failure (FHF) in the elderly is little known because of its very low frequency. Thirteen autopsy cases, all above 65 years of age (mean ± SD, 72 ± 6 years), and 10 younger control cases, all below 40 years of age (30 ± 7 years), were analyzed. The elderly group comprised 10 cases with subacute FHF and three cases with acute FHF, while the younger group comprised seven cases with subacute FHF and three cases with acute FHF. The most predominant pathological type in the elderly group was submassive hepatic necrosis (10 cases), followed by acute hepatitis with bridging hepatic necrosis (AH-BHN; two cases) and massive hepatic necrosis (one case). In two cases of submassive hepatic necrosis, hepatic regeneration seemed to be insufficient for the suggested history. The underlying diseases and terminal complications were significantly more frequent in the elderly group than in the younger group. In conclusion, the immune response in the elderly group is found to be strong enough to cause massive or submassive hepatic necrosis. However, impaired hepatic regeneration is occasionally observed in the elderly cases and AH-BHN is often lethal because of frequent underlying diseases and severe complications.     

Bioartificial liver: implanted artificial cells microencapsulated living hepatocytes increases survival of liver failure rats

Suspension of living hepatocytes were microencapsulated inside 300 micron mean diameter alginate artificial cells. The galactosamine fulminant hepatic failure rat model was used. 48 hours after the injection of galactosamine, grade II coma hepatic failure rats were divided into pairs. One of the pair was randomly chosen for the control group, and the other for the treated group. Each rat in the control group received one peritoneal injection of microcapsules containing no hepatocytes. Each rat in the treated group received one peritoneal injection of microcapsules containing hepatocytes. The survival of the treated group is significantly higher than the control group.     

左肝蒂阻断行腹腔镜左半肝切除术治疗肝内胆管结石疗效研究

目的 探讨腹腔镜左肝蒂阻断左半肝切除术治疗肝内胆管结石患者的疗效。方法 回顾性分析2016年10月~2018年3月在承德医学院附属医院肝胆外科行手术治疗的67例肝内胆管结石患者的临床资料,其中35例行左肝蒂阻断腹腔镜左半肝切除术治疗设为腔镜组,32例行传统开腹左半肝切除术治疗设为开腹组,比较两组的手术时间、术中出血量、术后镇痛时间、胃肠恢复时间、术后住院时间、住院费用、术后并发症和术后第7天的白蛋白（ALB）、总胆红素（TBIL）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）变化情况。结果 腔镜组手术时间较开腹组长[（269.11±54.43） min vs（211.72±31.64） min],术后疼痛缓解时间 [（2.89±1.41） d vs（4.81±1.58） d],术后排气时间[（24.80±6.31） h vs（45.13±9.80）h],术后住院时间[（9.51±2.38） d vs（14.19±2.86） d]均优于开腹组, 差异均具有统计学意义（P＜0.05）;两组患者手术出血量、并发症和住院总费用比较,差异无统计学意义（P＞0.05）;治疗后两组肝功能指标比较,差异无统计学意义（P＞0.05）。结论 腹腔镜下左肝蒂阻断左半肝切除术治疗肝内胆管结石的疗效与安全性是肯定的,与以往开腹肝切除术相比,腹腔镜左肝蒂阻断左半肝切除术创伤更小,并发症更少,术后恢复更快。