Semipermeable Hollow Fiber Membranes in Hepatocyte Bioreactors: A Prerequisite for a Successful Bioartificial Liver?

Abstract: Recent studies have shown that liver support systems based on viable hepatocytes can prolong life in animal models of acute liver failure. Now the time has come to elucidate the design characteristics that are essential to construct an efficient bioreactor. The gold standard remains the intact liver. Despite the very high cell density in this organ, individual cell perfusion is guaranteed resulting in low diffusional gradients which are essential for optimal mass transfer. These conditions are not met in bioreactors based on hollow fiber membranes. Moreover, the semipermeable membranes can foul and act as a diffusional barrier between the hepatocytes and the blood or plasma of the recipient. We devised a novel bioreactor for use as a bioartificial liver that does not include hollow fiber membranes for blood or plasma perfusion. The device is based on an integral oxygenator and a nonwoven polyester matrix material for hepatocyte culture as small aggregates. The efficacy of this original design was tested in rats with liver ischemia. Preliminary results show statistically significantly improved survival; life was prolonged 100% compared to the control experiments.     

Splanchnic metabolism associated with liver metastasis

Metastatic liver disease can modify the metabolic response to critical illness. Systemic lactic acidosis may arise from an increased production due to inadequate peripheral tissue oxygen transport, altered metabolic function such as depressed pyruvate oxidation or insufficient hepatic clearing capacity due to tumor replacement of functional liver mass. Hepatic venous catheterization in a patient with extensive metastatic melanoma to the liver and adult respiratory distress syndrome indicated a marked disparity between whole body and liver oxygenation which may arise due to a markedly stepped up splanchnic oxygen utilization unmatched by a proportionate rise in regional oxygen delivery. Since some neoplasms may exhibit increased metabolic activity, it is suspected that these metastatic lesions may have contributed to the observed regional hypermetabolism thereby worsening hepatic hypoxia and exacerbating lactic acidosis. This case also illustrates the difficulties in interpreting global indicators of metabolic function and oxygenation in critically ill patients.     

肝硬化患者胰岛素释放试验的临床意义

本文报道46例肝硬化患者口服葡萄糖胰岛素释放试验的结果,并与18名正常人和18名原发性糖尿病患者比较。肝硬化患者糖耐量减低者28例(60.9％),其中29例(43.5％)呈糖尿病型耐量曲线。胰岛素释放高峰值在服糖后2h;释放过多和分泌延迟者32例(69.6％),降低者4例(8.7％)。20例肝源性糖尿病患者的胰岛素释放指数明显高于原发性糖尿患者。笔者认为血浆胰岛素和胰岛素释放指数测定对鉴别这两种类型的糖尿病有很大价值。     

广西百色地区肝病患者及受血者HCV感染现状调查

笔者应用ＥＬＩＳＡ法对广西百色地区１７９例各类肝病患者及４１例受血者血清进行了抗－ＨＣＶ检测。结果各类肝病抗－ＨＣＶ阳性率为１７．９％，受血者抗－ＨＣＶ阳性率为３１．７％。在急性肝炎（急肝）、慢性肝炎（慢肝）、肝硬化和肝癌中，抗－ＨＣＶ阳性率各为４．３％（１／２３）、１２．８％（１０／７８）、２８．６％（１２／４２）和２５．０％（９／３６）。抗－ＨＣＶ阳性率有随肝病慢性比而增高的趋势，肝硬化的抗－ＨＣＶ阳性率明显高于急肝或慢肝（Ｐ＜０．０５），而肝癌的抗－ＨＣＶ阳性率与急肝或慢肝相差不显著（Ｐ＞０．０５或０．１），且发现ＨＢｓＡｇ阴性肝病者的抗－ＨＣＶ阳性率明显高于ＨＢｓＡｇ阳性患者（Ｐ＜０．５），肝病患者抗－ＨＣＶ的检出率与ＡＬＴ活性无关（Ｐ＞０．０５）。在受血者中，抗－ＨＣＶ的检出率与受血次数、ＡＬＴ活性关系非常密切。因此，加强对ＨＣＶ的检测是当前预防输血后肝炎的紧迫任务。     

体外静脉—静脉转流下原位肝移植围术期酸碱,生化的变化

目的:观察体外静脉转流下原位肝移植围术期酸碱和生化的变化。方法:7例病人行原位肝移植术,在无肝期行体外静脉-静脉转流,监测围术期酸碱和生化指标。结果:(1)与术前相比,pH各期有所下降,但仍维持在正常范围,BE和SBC在转流60分钟及关腹时降低;与转流前期相比。pH以后各期变化不大。术期pH在7.35～7.45范围之内;(2)血糖在各期都升高,血钙降低,体温逐渐降低;(3)血钾在肝血管开放后一过性增高,由3.17mmol/L升至3.53mmol/L。结论;体外静脉转流下原位肝移植术,术中酸碱和生化变化轻微,避免了明显的代谢性酸中毒和高血钾,但体温和血糖变化明显。     

Gadoteridol dose dependence in MR imaging of a liver abscess model

A necrotic liver abscess model was studied with magnetic resonance (MR) imaging at 1.5 T before and after intravenous administration of gadoteridol at doses of 0.1, 0.25, and 0.5 mmol/kg in 24 rabbits. Enhancement characteristics and lesion delineation were assessed with both breath-hold and non-breath-hold imaging techniques. Lesion delineation, as assessed both by signal intensity measurements and evaluations by two image readers blinded to imaging technique, was greatest on high-dose (0.5 mmol/kg) breath-hold images. Lesion rim enhancement was seen consistently only on postcontrast images obtained at a dose of 0.5 mmol/kg and progressed with time after injection of contrast material.     

Percutaneous transhepatic stenting by wallstents of portal vein and bile duct stenoses caused by immunoblastic sarcoma in a liver transplantation

Posttransplant lymphoproliferative disorders are infrequent tumors related to chronic immunosuppressive therapy. We present a liver transplant recipient who developed such a tumor in the porta hepatis that provoked obstruction of the entire portal triad. Treatment consisted of systemic chemotherapy, percutaneous dilatation, and placement of Wallstent endoprostheses across both biliary and portal vein stenoses. The patient died 3 weeks later of pneumonia and sepsis. At necropsy, the tumor was completely necrosed and the prostheses in both the common bile duct and the portal vein were patent.     

Pre- and post-transplant assessment of liver function in paediatric liver transplantation

The pre-operative risk of paediatric liver transplantation candidates (n=41) was assessed in a prospective study by means of clinical symptoms, conventional static and liver blood flow dependent dynamic liver function tests. Nine patients died during the 365-day waiting period. The data were subjected as covariates to a survival analysis in the Cox proportional hazards model. There was a significant relationsship between the results of mono-ethylglycinexylidide (MEGX) formation and ICG test and the 365-day survival rate. In the stepwise analysis, none of the remaining parameters improved the predictive ability when added to the dynamic liver function test results. The assessment of post-transplantation liver function was studied in 27 patients during the first 28 postoperative-day period. In addition, liver function was studied in a cross-sectional study 1–7 years after successful liver transplantation in children with complete or partial rehabilitation. In the early postoperative period severe organ damage was indicated by both static and dynamic liver function tests. In the later course after transplantation no deterioration of liver function measured with MEGX formation was to be observed. These findings demonstrate the usefulness of dynamic liver function tests in the pre- and post-transplant assessment of liver function.     

Choledochoenterostomy with an anti-reflux mechanism

A new technique of choledochoenterostomy was devised to solve some of the problems of enterobiliary anastomosis with a normal calibre. The distal extremity of the common bile duct is completely surrounded by the bowel mucosa to a length of 3 cm after seromyectomy of a bowel wall rectangle of 4 × 1 cm. Experimental studies in rats and dogs demonstrated that this procedure prevents the risks of anastomotic disruption and functions like a mechanical unidirectional valve, which has great efficacy in stopping enterobiliary reflux. Studies in ten patients with obstructive jaundice with an extrahepatic biliary dilation less than 1.2 cm diameter submitted to this procedure Confirmed the experimental results. All patients were asymptomatic, without jaundice and with normalization of the liver enzymes after 2 months. The permeability of the valvular anastomosis studied by cholangiography, the HIDA ^99mTc test and manometry was quite similar to other classical biliary-enteric anastomosis. In contrast, anti-reflux efficacy was only demonstrated in patients with a valvular anastomosis.