Basal and post-methionine serum homocysteine and lipoprotein abnormalities in patients with chronic liver disease.
BACKGROUND
Lipoprotein abnormalities are commonly found in chronic liver diseases (CLDs), particularly hypercholesterolemia in primary biliary cirrhosis (PBC). However, affected patients may not be at increased risk of coronary heart disease. Cirrhotic patients display impaired methionine clearance, and an increased level of homocysteine, a methionine metabolite, is an independent risk factor for coronary heart disease. Thus, we hypothesized that the low risk of coronary heart disease in patients with CLD may be related to low serum levels of homocysteine. The aim of this study was to test this hypothesis after methionine load and to describe the serum lipoprotein profile in patients with PBC and in patients with hepatocellular liver disease.


METHODS
Fifteen female patients (mean age, 58.2 +/- 11.7 years) with PBC, 15 female patients (mean age, 54.5 +/- 9.6 years) with other causes of CLD, and 15 healthy sex- and age-matched controls were given L-methionine (50 mg/kg of ideal body weight). Basal fasting serum homocysteine level and 2, 4, and 6 hours of post-methionine load were determined using high-performance liquid chromatography with a fluorometric detector. Levels of fasting serum cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein (a) (Lp(a)), and apoprotein B were also determined.


RESULTS
Results showed that mean basal and post-methionine load (6 hours) serum homocysteine levels were statistically significantly higher in the patients with PBC and with CLD than in the control group (P=0.04) and that levels of serum cholesterol, LDL, HDL, and apoprotein B were significantly higher in the PBC patients than in the other two groups (P < or = 0.05). There was no correlation between any of these parameters and the severity of liver disease. Serum HDL was significantly lower in the CLD group (P < or = 0.05) and correlated with severity of liver disease. There was no significant difference in serum cholesterol, LDL, or apoprotein B between the CLD group and the controls. Serum triglyceride and Lp(a) levels were similar for all three groups.


CONCLUSIONS
In contrast to previous reports, the site of the methionine metabolic impairment was found to be below the homocysteine synthesis level. For most patients with CLD, factors other than serum homocysteine or Lp(a) are responsible for the reduction in the risk of coronary heart disease. Further studies with larger samples are needed.
Ben-Ari
Z
Z
Department of Medicine, Rabin Medical Center, Petah Tiqva, Israel.
Tur-Kaspa
R
R
Schafer
Z
Z
Baruch
Y
Y
Sulkes
J
J
Atzmon
O
O
Greenberg
A
A
Levi
N
N
Fainaru
M
M
D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D002908:Chronic Disease; D003327:Coronary Disease / Q000209:etiology; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications; D008107:Liver Diseases / Q000097:blood* / Q000150:complications; D008715:Methionine / Q000008:administration & dosage*; D008875:Middle Aged; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D017270:Lipoprotein(a); D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D006710:Homocysteine; D002784:Cholesterol; D008715:Methionine