Studies of Vitamin B12 Metabolism in Patients with Chronic Hepatitis and Liver Cirrhosis^[*]

Summary

We have studied the kinetiks of vitamin B₁₂ and especially the liver compartment, in 28 normals and 76 patients with chronic hepatitis and liver cirrhosis.

The study was carried out by means of vitamin B₁₂ ⁵⁸Co, administered per os (alone or followed by “flushing dosis”), vitamin B₁₂ ⁵⁷Co administered intravenously and by double tracer technique.

Our results indicate the Pertubation of intrahepatic storage compartment of radiocobalamine, in patients with chronic hepatitis and especially in patients with active hepatitis and in cirrhotics.

This deficiency can be explained probably, by an alteration of the transport to the liver of the absorbed vitamin B₁₂, by an inadequate chemical forme, by hepatic enzymatic disturbances or by excessive handling and storage in extrahepatic compartment.

Nous avons étudié la cinétique de la vitamine B₁₂ et spécialement le compartiment hépatique chez 28 normaux et 76 malades avec une hépatite chronique ou une cirrhose du foie. L’étude a été effectuée à l’aide de la vitamine B₁₂ ⁵⁸Co, administrée per os (seule ou suivie d’une „flushing dosis”), de la vitamine B₁₂ ⁵⁷Co administrée par voie endoveineuse et par la technique du double traceur.

Nos résultats indiquent une perturbation du compartiment de depot hépatique de la radiocobalamine chez les malades hépatiques et spécialement dans les formes évolutives et dans les cirrhoses.

Ces troubles s’expliquent probablement par une altération du transport de la vitamine B₁₂ absorbée vers le foie, par une forme chimique inadéquate, par des troubles hépatiques enzymatiques et par la fixation extra-hépatique excessive.

Die Kinetik des Vitamin B₁₂, besonders im Lebercompartment, wurde bei 28 Normalen und 76 Leberkranken (chronische Hepatitis und Zirrhose) mit radioaktivem Vitamin B₁₂ untersucht. Es wurde ⁵⁸Co Vitamin B₁₂ per os verabreicht (mit und ohne „flushing dosis”) oder ⁵⁷Co Vitamin B₁₂ injiziert; in einigen Fällen wurden beide Vitamine verabreicht und mit der Doppeltracer-Technik verfolgt.

Die Ergebnisse zeigen eine Störung des Leberdepotcompartments für Radiocobalamine bei den Leberkranken, besonders bei evolutiver Hepatitis und Zirrhose.

Es werden die Bedeutung der Absorptionsstörungen, des Transports zur Leber, der intrahepatischen enzymatischen Bindungen und der großen extrahepatischen Speicherung besprochen, die die Störungen des metabolischen Lebercompartments des Vitamin B₁₂ bei Leberkranken erklären könnten.

^* This work was supported by the International Atomic Energy Agency, under the Research Contract nr. 243 (R 2) R.B.

• References

• 1 Armstrong B.K., Woodliff H.J.. Vitamin B₁₂ absorption studies, Comparison of ⁵⁸Co vitamin B₁₂ Schilling test and ⁵⁷Co vitamin B₁₂ plasma level test. Med. J. Austral. 1: 709 1966;
• 2 Belcher E.H., Anderson B.B., Robinson C.J.. The measurement of gastrointestinal absorption of ⁵⁸Co labelled vitamin B₁₂, by whole body counting. Nucl. Medizin 3 (04) 349 1963;
• 3 Booth C.C., Mollin D.L.. Plasma, tissue and urinary radioactivity after oral administration of ⁵⁸Co-labelled vitamin B₁₂ . Brit. J. Haemat. 2: 223 1956;
• 4 Booth C.C.. The site of absorption of vitamin B₁₂ in man. Lancet 1: 18 1959;
• 5 Doscherholmen A., Hägen P.S., Lin M.. Radioactive vitamin B₁₂ absorption studies: Results of direct measurement of radioactivity in the blood. Blood 12: 336 1957;
• 6 Doscherholmen A.. Studies in the metabolism of vitamin B₁₂ . The University of Minnesota Press; (Minneapolis): 1965
• 7 Ganatra R.D., Sundaram K., Desai K.B., Gaitonde B.B.. Determination of absorption of vitamin Bt, by a double isotope tracer technique. J. Nucl. Med. 6: 459 1965;
• 8 Gazet J.C., McColl I.. Absorption of vitamin B₁₂ from the small intestine. Study in man, monkey, cat and dog. Brit. J. Surg. 54 (02) 128 1967;
• 9 Glass G.B.J., Boyd L.J., Gellin G.A., Stephanson L.. Uptake of radioactive vitamin B₁₂ by the liver in humans: Test for measurement of intestinal absorption of vitamin B₁₂ and intrinsic factor activity. Arch. Biochem. 51: 251 1954;
• 10 Glass G.B.J., Boyd L.J., Stephanson L.. Intestinal absorption of vitamin B₁₂ in man. Science 120: 74 1954;
• 11 Glass G.J.B.. Intestinal absorption and hepatic uptake of vitamin B₁₂ in disease of the gastro-intestinal-tract. Gastroenterology 30: 37 1956;
• 12 Glass G.J.B., Boyd L.J., Ebin L., Schaffer H., Schwartz G.. Radioactive vitamin B₁₂ in the liver. I Hepatic uptake of ⁶⁰Co B₁₂ in liver diseases. J. Lab. Clin. Med. 52: 849 1958;
• 13 Göthe C.J.. Influence of liver function on the excretion of vitamin B₁₂ . Scand. J. Clin. Lab. Invest. 17: 99 1965;
• 14 Heyssel R.M., Bozian R.C., Darby W.J., Bell M.C.. Vitamin B₁₂ turnover in man. Amer. J. Clin. Nutrit. 18: 176 1966;
• 15 Lawrence C.. The binding of vitamin B₁₂ by serum proteins in normal and B₁₂ deficient subjects. Brit. J. Haemat. 12 (05) 569 1966;
• 16 McCurdy P.R.. The detection of intestinal absorption of ⁵⁷Co tagged vitamin B₁₂, by serum counting. Ann. Int. Med. 62: 97 1965;
• 17 Meintyre P.A., Wagner Jr H.N.. Comparison of the urinary excretion and 8 hour plasma tests for vitamin B₁₂ absorption. J. Lab. Clin. Med. 68 (06) 966 1966;
• 18 Nelson R.S., Doctor V.M.. Hepatic and serum vitamin B₁₂ content in liver disease. Gastroenterology 38: 188 1960;
• 19 Okuda K.. Intestinal absorption of vitamin B₁₂ in liver cirrhosis. Yamaguchi med. Sch. 9: 19 1962;
• 20 Rachmilewitz M., Stein Y., Aronovitsch J., Grossowicz N.. The clinical significance of serum cyanocobalamin (vitamin B₁₂) in liver disease. Arch. Int. Med. 101: 1118 1958;
• 21 Reizenstein P.G., Cronkite E.P., Cohn S.A.. Measurement of absorption of vitamin B₁₂ by whole-body gamma spectrometry. Blood 18: 95 1961;
• 22 Reizenstein P.G., Cronkite E.P., Cohn S.A.. Plasma clearance and whole body turnover of injected and absorbed radioactive vitamin B₁₂ in man. J. Lab. and Clin. Med. 62: 255 1963;
• 23 Schilling R.F.. Intrinsic factor studies. II. The effect of gastric juice on the urinary excretion of radioactivity after the oral administration of radioactive vitamin B₁₂ . J. Lab. Clin. Med. 42: 860 1953;
• 24 Spârchez T., Gheorghescu B., Jovin G., Merculiev El., Timis E.. Vitamin B₁₂ metabolism in patients with chronic hepatitis, cirrhosis and liver cancer as studied with ⁵⁸Co vitamin B₁₂ . Proceedings of 3rd World Congress of gastroenterology. Tokyo: 1966. vol. III 204.
• 25 Stein O., Stein Y., Aronovitsch J., Grossowicz N., Rachmi-lewitz M.. Effect of liver damage and regeneration on vitamin B₁₂ concentration in rat liver. J. Lab. and Clin. Med. 54: 545 1959;
• 26 Stützel M., Romics L.. Die Rolle des Dünndarms in der Speicherung und Ausscheidung des intravenös gegebenen Vitamins B₁₂, ⁵⁸Co bei Ratten. Int. Z. Vitaminforsch. 36 (03) 322 1966;
• 27 Weisberg H., B.Glass G.J.. A rapid quantitative method for measuring intestinal absorption of vitamin B₁₂ in man, using double label hepatic uptake test. J. Lab. Clin. Med. 68 (01) 163 1966;
• 28 Woodliff M.J., Armstrong B.K.. Vitamin B₁₂ absorption studies. Comparison of ⁵⁷Co vitamin B₁₂ plasma levels, urinary excretion and fecal excretion. Med. J. Austral. 1: 1023 1966;