Hepatocytes function

Hepatocytes, whether freshly cultured or cryo-preserved, can provide an assessment of not only CYP metabolism but also clearance by other metabolizing enzymes and potentially the role of transporters [51]. The accuracy of the data is of course dependent on how well the proteins in the hepatocytes function after culturing or freezing. 

Albumin and coagulation factors are markers of hepatic synthetic activity and are used to estimate hepatocyte functioning in cirrhosis. 

Guguen-Guillouzo, C., Gripon, P., Vandenbughe, Y., Lamballe, F., Rataanasavanh, D. and Guillouzo, A. (1988). Hepatotoxicity and molecular aspects of hepatocyte function in primary culture. Xenobiotica 18 773-783. 

Van lersel AAJ, Vanholsteijn I, Blaauboer BJ. 1988. Effects of 1,2-dibromoethane on isolated hepatocytes Functional alterations and induction of lipid-peroxidation. Xenobiotica 18 675-683. 

Cell-cell interactions and cell-scaffold interactions have been shown to unprove viability and stabilize function. Complete understanding of the mechanisms required to stabilize hepatocyte function will have a broad impact on this technology. 

Dunn JC, Yarmush ML, Kowbe HG, et al. Hepatocyte function and extracellular matrix geometry long-term culture in a sandwich configuration. FASEB J 1989 3 174-177. 

Hepatocyte function and the role of other cells in the human liver. 

Biopsy results, where available, are invaluable. They may have been taken to help diagnose a disease or to give an indication of its progression. Either way, they enable you to differentiate between a mild hepatitis with an ALT of 100 and cirrhosis with a similar transaminase level. This is very helpful in determining whether or not hepatocyte function is likely to be impaired. It may also demonstrate poor biliary canaliculi or portal tracts which may result in defective bile or blood flow. 

Despite cirrhosis, this patient is maintaining good hepatocyte function (normal albumin, mildly raised INR, normal bilirubin) and the metabolic and excretory capacity of the liver should not be significantly reduced. The patient has portal hypertension, so blood flow to the liver... 

This patient has markedly impaired hepatocyte function and hence reduced metabolic and excretory capacity (raised INR, hyperbili-rubinaemia, encephalopathy). Low extraction drugs (hepatocyte dependent) are likely to accumulate and should be used cautiously. The distribution of highly protein-bound drugs may be affected by hyper-bilirubinaemia, increasing the unbound fraction. Biliary excretion may be impaired. 

Despite cirrhosis, this patient is maintaining good hepatocyte function (normal albumin and bilirubin, mildly raised INR) and the metabolic and excretory capacity of the liver should not be significantly reduced. The patient has portal hypertension, so blood flow to the liver will be impaired, which will reduce the first-pass metabolism of highly extracted drugs (extraction ratio >0.7). This will result in greater bioavailability of oral doses of these drugs. It is important to note that the patient could rapidly deteriorate into a state of decompensation where liver function would be markedly affected. 

POCs could be used in this patient as the liver disease is mild, with normal hepatocyte function. LFTs should be monitored to ensure the hepatitis is not aggravated. 

These various imaging techniques (s. tab. 8.1) - as well as some nuclear medicine-based methods (see chapter 9) - enable key features of benign and malignant tumours to be recognized, including (7.) vascularity, (2.) internal structure, (2.) hepatocyte functions, (4.) biliary tract, (5.) bile secretion, (d.) calcification, and (7.) Kupffer cell activity. 

Bhandari RN, Riccalton LA, Lewis AL, Fry JR, Hammond AH, Tendler SJ, et al. Liver tissue engineering A role for co-culture systems in modifying hepatocyte function and viability. Tissue Eng 2001 7 345-57. 

Bhatia SN, Bahs UJ, Yarmush ML, Toner M. Probing heterotypic cell interactions Hepatocyte function in microfabricated co-cultures. J Biomater Sci Polym Ed 1998 9 1137-60. 

Hepatocytes are attachment-dependent cells [3, 25]. Without adequate extracellular matrix they lose their liver-specific functions. Therefore, it has been studied intensively which types of matrix, hydrogels, and scaffolds support differentiated hepatocyte functions and which are the key properties. One of the first commercially available hydrogels was Matrigel, an extract from mouse sarcoma cells [26]. Later Extragel, another collagen-based hydrogel [27] Alimatrix, a porous 3D scaffold [28] and PuraMatrix... 

Ranucci CS, Kumar A, Batra SP, Moghe PV (2000) Control of hepatocyte function on collagen foams sizing matrix pores toward selective induction of 2-D and 3-D cellular morphogenesis. Biomaterials 21(8) 783-793 Rowley JA, Madlambayan G, Mooney DJ (1999) Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20(1) 45-53... 

Hepatic extraction efficiency decreases with increasing serum bilirubin levels. With impaired hepatocyte function, high plasma concentrations (>8 mg/100 ml) may inhibit uptake of Tc-IDA complexes. As hepatobiliary excretion decreases, renal accumulation of certain " Tc-IDA complexes is observed (Fink-Bennett 1995). 

It is important to distinguish between changes in zinc metabolism which occur as a secondary effect of disease, injury, infection and drug therapy and alterations caused by a primary nutritional zinc deficiency. There is confusion in the literature because a number of unrelated causes can temporarily lower the concentration of zinc in plasma, and this is reported uncritically as evidence of nutritional depletion. Since a high proportion of zinc in plasma is albumin bound, any circumstance which lowers plasma albumin wiil also lower plasma zinc. For example, the changes seen in severe liver disease are primarily caused by a failure of hepatic synthesis of plasma proteins such as albumin. This results in problems in the distribution of zinc and eventual tissue depletion. It is questionable whether zinc supplementation of diet is worthwhile without some restoration of hepatocyte function, by effective treatment of the underlying disease (Mills et al., 1983). 

L. De Bartolo, S. Salerno, E. Curcio, A. Pisdoneri, M. Rende, S. MorelU, F. TasselU, A. Bader, E. DrioU, Human hepatocyte functions in a crossed hollow fiber membrane bioreactor. Biomaterials 30 (13) (2009) 2531-2543. 

Hepatocyte function has been quantitated by histology, morphometric analysis using an Image Technology 3000 Image analyzer and Northern slot blot analysis for albumin specific mRNA of implants. Sixty percent engraftment was seen by this technique compared to three percent engraftment seen before we used this approach(32). 

Mooney DJ, Langer R, Vacanti JP, Ingber DE. Control of hepatocyte function through variation of attachment site densities. 1990 (Abstr.) American Institute of Chemical Engineers. 

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