Increased plasma homocysteine in liver cirrhosis

Bosy‐Westphal, Anja; Petersen, Sven; Hinrichsen, Holger; Czech, Norbert; Müller, Manfred J.

doi:10.1016/s1386-6346(00)00119-4

Cited by 46 publications

(44 citation statements)

References 31 publications

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“…However, our present data on hyperhomocysteinemia in cirrhosis has been confirmed in other human and experimental studies in which hyperhomocysteinemia was not associated with altered plasma levels of the abovementioned vitamins. 25,26 We also observed a decrease in MAT1A expression in cirrhotic liver, which contributes to the reported hypermethioninemia and impairment of AdoMet synthesis in this condition. 5 We have previously shown that AdoMet treatment of cirrhotic rats reduces elevated plasma Hcy.…”

Section: Discussionsupporting

confidence: 60%

Hyperhomocysteinemia in Liver Cirrhosis

et al. 2001

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Abstract-Numerous clinical and epidemiological studies have identified elevated homocysteine levels in plasma as a risk factor for atherosclerotic vascular disease and thromboembolism. Hyperhomocysteinemia may develop as a consequence of defects in homocysteine-metabolizing genes; nutritional conditions leading to vitamin B 6 , B 12 , or folate deficiencies; or chronic alcohol consumption. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver. Impaired liver function leads to altered methionine and homocysteine metabolism; however, the molecular basis for such alterations is not completely understood. In addition, the mechanisms behind homocysteineinduced cellular toxicity are not fully defined. In the present work, we have examined the expression of the main enzymes involved in methionine and homocysteine metabolism, along with the plasma levels of methionine and homocysteine, in the liver of 26 cirrhotic patients and 10 control subjects. To gain more insight into the cellular effects of elevated homocysteine levels, we have searched for changes in gene expression induced by this amino acid in cultured human vascular smooth muscle cells. We have observed a marked reduction in the expression of the main genes involved in homocysteine metabolism in liver cirrhosis. In addition, we have identified the tissue inhibitor of metalloproteinases-1 and ␣1(I)procollagen to be upregulated in vascular smooth muscle cells and liver stellate cells exposed to pathological concentrations of homocysteine. Taken together, our observations suggest (1) impaired liver function could be a novel determinant in the development of hyperhomocysteinemia and (2)

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Section: Discussionsupporting

confidence: 60%

Hyperhomocysteinemia in Liver Cirrhosis

et al. 2001

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“…Hyperhomocysteinemia may also be induced by liver damage per se, because it has been reported that homocysteine metabolism may be altered in cirrhosis. 31,32 However, the data do not support this hypothesis in this setting of patients, because the levels of homocysteine were not significantly higher in patients with cirrhosis than those observed in CHC with high levels of fibrosis. Furthermore, we cannot exclude an interaction between HCV or HCV components with the homocysteine metabolism, which could be particularly significant in subjects with a favorable genetic background.…”

Section: Discussionmentioning

confidence: 59%

Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients

Adinolfi

Ingrosso

Cesaro³

et al. 2005

Hepatology

118

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The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r ‫؍‬ 0.367; P ‫؍‬ .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 mol/L, respectively (P ‫؍‬ .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P ‫؍‬ .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR ‫؍‬ 7.1), HAI (OR ‫؍‬ 3.8), liver fibrosis (OR ‫؍‬ 4.0), and HCV genotype 3 (OR ‫؍‬ 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P ‫؍‬ .03), HAI (P ‫؍‬ .0001), and steatosis (P ‫؍‬ .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. ( H epatic steatosis frequently occurs in hepatitis C virus (HCV) infection, more so than in subjects with hepatitis B virus. 1 The prevalence of fatty infiltration in the livers of chronic hepatitis C (CHC) has been reported to average around 50%, with a range of 30% to 70%. 2-4 For HCV genotype 3 infection, it has been suggested that the virus exerts a direct steatogenic effect, supported by correlation of steatosis with the levels of HCV RNA, and by the reversal of steatosis as the result of antiviral therapy. [5][6][7][8] Moreover, the degree of steatosis has been related to the extent of hepatic fibrosis in CHC. 5,[9][10][11][12] The mechanisms involved in HCV-associated steatosis are unknown. Several host (body mass index [BMI], insulin resistance, hypertrigliceridemia) and viral factors may be implicated. Among viral factors, at least two HCV proteins-core and NS5A-have been credited with the ability to alter lipid metabolism in infected cells, thus causing hepatic steatosis in the absence of immune response. 13,14 In the transgenic mouse model, it has also been shown that the HCV core protein induces steatosis. 15 Transgenic mice expressing HCV co...

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“…Patients with a chronic liver disease may present with homocysteine concentrations 3.4 to 6.2µmol/L higher than healthy controls (126). The level of hyperhomocysteinemia corresponds to the level of hepatic damage (126,127). Loss of hepatic function is associated with impairment of the transsulfuration pathway and decreased methionine adenosyltransferase III activity (128).…”

Section: Hepatic and Renal Functionmentioning

confidence: 99%

Effect of Nitrous Oxide Exposure During Surgery on the Homocysteine Concentrations of Children

Pichardo¹,

Luginbuehl²,

Shakur³

et al. 2013

Survey of Anesthesiology

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In this study we determined the effect of nitrous oxide (N 2 O) on homocysteine concentrations in children and whether blood levels of folate, vitamin B12, B6, methylmalonic acid (MMA) and methylenetetrahydrofolate reductase C6777T genotype affected this relationship. Homocysteine was measured before and after N 2 O. Vitamin levels, MMA and genotype were determined preoperatively. Median age of the 32 participants was 11 months (3-126 months). All children had folate and B6 levels above deficiency values (7.4, 20nmol/L respectively). Five children had MMA levels indicating deficiency (≥0.21µmol/L). Postexposure homocysteine concentrations increased by 25% (P= <0.001). Duration of exposure and initial homocysteine concentrations were predictors of the increase (r 2 = 0.821, P= <0.001).Vitamin B12 and initial homocysteine concentrations were inversely associated (r 2 = 0.277, P= 0.004). Folate, vitamin B6 and genotype showed no effect. In conclusion, N 2 O exposure leads to increased homocysteine in children. Studies investigating benefit of pre-surgical vitamin B12 supplementation may prove worthwhile.iii ACKNOWLEDGMENTS

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Increased plasma homocysteine in liver cirrhosis

Cited by 46 publications

References 31 publications

Hyperhomocysteinemia in Liver Cirrhosis

Hyperhomocysteinemia in Liver Cirrhosis

Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients

Effect of Nitrous Oxide Exposure During Surgery on the Homocysteine Concentrations of Children

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