Determinants of hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation.
BACKGROUND
Homocysteine metabolism may be impaired in chronic liver disease, possibly contributing to fibrogenesis and disease complications.


OBJECTIVE
The goal was to investigate the prevalence and determinants of basal and postprandial hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation (OLT).


METHODS
This was a cross-sectional study of 323 patients with chronic liver disease (93 with hepatitis, 8 with fatty liver, 168 with cirrhosis, and 54 after OLT) and 25 healthy control subjects. Portohepatovenous gradients of total homocysteine (tHcy) and methionine and postload methionine and tHcy kinetics before and after 10 d of supplementation with folate plus vitamin B-6 were investigated in subgroups.


RESULTS
Basal hyperhomocysteinemia was observed in all patient groups (34% of patients with hepatitis, 50% with fatty liver, 54% with cirrhosis, and 52% after OLT). It was more frequently seen in patients with elevated plasma creatinine concentrations and at advanced stages of liver disease. Mean plasma folate was normal in patients with liver disease, but vitamin B-12 was elevated in cirrhosis and vitamin B-6 was low after OLT. There were significant negative associations between tHcy and folic acid or vitamin B-12 concentrations in control subjects and in patients with hepatitis and after OLT. No systematic association between portohepatovenous differences in tHcy and methionine concentrations was found. Cirrhosis was accompanied by impaired methionine clearance. After vitamin supplementation, the area under the tHcy curve improved in cirrhosis at nearly unchanged basal tHcy concentrations.


CONCLUSIONS
Basal hyperhomocysteinemia is seen in approximately 50% of patients with cirrhosis and after OLT. Basal tHcy concentrations do not change significantly after supplementation with folate and vitamin B-6, but postprandial Hcy metabolism improves.
Bosy-Westphal
Anja
A
Institut für Humanernährung und Lebensmittelkunde, Universität Kiel, Kiel, Germany.
Ruschmeyer
Martina
M
Czech
Norbert
N
Oehler
Gerd
G
Hinrichsen
Holger
H
Plauth
Matthias
M
Lotterer
Erich
E
Fleig
Wolfgang
W
Müller
Manfred James
MJ
D000328:Adult; D019540:Area Under Curve; D016022:Case-Control Studies; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000453:epidemiology* / Q000378:metabolism; D008107:Liver Diseases / Q000097:blood* / Q000188:drug therapy; D016031:Liver Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008715:Methionine / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000008:administration & dosage / Q000097:blood
D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D008715:Methionine; D003404:Creatinine; D014805:Vitamin B 12