Historical Perspective

For many years it has been assumed that the majority of toxins which cause coma in hepatic failure are small dialyzable molecules. As a result, most liver support systems and therapeutic regimens relied primarily on blood detoxification. However, the pathogenesis of acute liver failure is complex and many investigators, including ourselves, have argued that isolated viable hepatocytes should be used to construct a liver support system to provide not only detoxification, but also missing liver synthetic functions. This suggests that a clear distinction should be made between systems designed to strictly "purify" patient blood from toxins and devices incorporating liver tissue preparations to carry out detoxification and provide synthetic function. The former are based on the artificial kidney principle; a classic example is hemodialysis, which was first applied by Kiley et al, and hemoperfusion, which was first tried by Schechter et al using cationic resins and several years later by Yatzidis and Chang et al using activated charcoal.1-4 The latter include biological components (isolated hepatocytes, liver tissue slices) and are thus truly "bioartificial". In our opinion, the prefix "hybrid" should be used when both living, e.g., isolated hepatocytes and mechanical, e.g., adsorptive column, parts are used in combination to design a liver support system.

Charcoal hemoperfusion has been used to treat severe acute liver failure with mixed results. Although there is clear experimental evidence that the technique has some beneficial effects, a controlled prospective clinical trial has failed to demonstrate significant clinical benefits of the technique.5 Other methods that relied primarily upon blood detoxification showed limited success as well. It would appear that, due to the complexity and vast number of metabolic and physiologic functions provided by the liver, construction of an extracorporeal liver support system requires utilization of viable isolated hepatocytes rather than specific cell components or enzymes. Sorrentino was the first investigator to use the term "artificial liver" while describing a series of in vitro experiments in which he demonstrated that fresh liver tissue homogenates can metabolize salicylic and barbituric acids and ketone bodies and produce urea from ammonia.6 At approximately the same time, Sugie and Hori advanced the concept of cross-hemodialysis between man and dog.7 A case report was soon published by Kimoto, and studies on hemodialysis against various canine liver tissue preparations were published by Nose et al.8-10 The first clinical use of a device loaded with isolated liver cells was by Matsumura fourteen years later.11 Rapid recovery from hepatic coma was accompanied by a significant decrease in blood ammonia levels. In the meantime, use of liver cells to construct a liver assist system was being studied extensively by Eiseman et al.12,13 During the past forty years, artificial liver devices utilizing liver tissue preparations and isolated liver cells were described by Mikami et al,9 Wolf and Munkelt,14 Eiseman et al,12>13>15>16 Nose et al,10 Kawarabata et al,17 Hager et al,18 Takahashi et al,19 Wada and Ohshim,20 Kimura et al,21 Lie et al,22 Kawamura et al,23 Demetriou et al,24 Kasai et al,25,26 Saito et al,27 Uchino et al,28 Yanagi et al,29 Margulis et al,30 Matsumura et al,11 Jauregui et al,31,32 Arnaout et al,33 Shnyra et al,34 Takahashi et al,35 Nyberg et al,36-39 Sussman et al,40-42 Fremond et al,43 Li et al,44 and by Rozga et al.45-49 Several new systems are currently in various stages of laboratory development, including the novel hepatocyte bioreactors of Flendrig et al,53 Wang et al,54 Suda et al,55 Gerlach et al,56 Ekevall et al,57 Qiang et al,58 Mazariegos et al,59 and Sajiki et al.60 Most of these devices were tested in vitro and in animals with chemically and surgically induced hepatic insufficiency. In some studies, significant levels of detoxification and liver support were achieved. Patient data, however, are scarce and most of these devices were never used clinically.

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Detox Diet Basics

Detox Diet Basics

Our internal organs, the colon, liver and intestines, help our bodies eliminate toxic and harmful  matter from our bloodstreams and tissues. Often, our systems become overloaded with waste. The very air we breathe, and all of its pollutants, build up in our bodies. Today’s over processed foods and environmental pollutants can easily overwhelm our delicate systems and cause toxic matter to build up in our bodies.

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