Hyperhomocysteinemia is associated with severity of cirrhosis and negative impact after liver transplantation

Bhanji, Rahima A.; Ma, Mang; Bain, Vincent G.; Montano‐Loza, Aldo J.

doi:10.1111/liv.12979

Cited by 13 publications

(6 citation statements)

References 38 publications

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“…In addition, among the patients with liver cirrhosis, the severity of liver disease is often in parallel with the prevalence of HHcy. 18,21 Similarly, the present study found that patients with Child-Pugh class B/C had a higher proportion of HHcy, and Child-Pugh score positively correlated with HHcy.…”

Section: Discussionsupporting

confidence: 77%

No Association of Homocysteine, Anticardiolipin Antibody, and Anti-β2 Glycoprotein I Antibody With Portal Venous System Thrombosis in Liver Cirrhosis

Wang

Guo

et al. 2021

Clin Appl Thromb Hemost

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Portal venous system thrombosis (PVST), a common complication of liver cirrhosis, is closely associated with thrombophilia. To explore the association of homocysteine (Hcy), anticardiolipin antibody (aCL), and anti-β2 glycoprotein I antibody (aβ2GPI), which are possible thrombophilic factors, with PVST in liver cirrhosis. Overall, 654 non-malignant patients (219 with and 435 without liver cirrhosis) admitted between January 2016 and June 2020 were retrospectively evaluated. Presence of PVST, degree of main portal vein (MPV) thrombosis, and clinically significant PVST were identified. Hcy level, hyperhomocysteinemia (HHcy), aCL positivity, and aβ2GPI positivity were compared according to the presence of liver cirrhosis and PVST. Positive aβ2GPI was significantly more frequent in patients with liver cirrhosis than those without, but Hcy level and proportions of HHcy and positive aCL were not significantly different between them. PVST could be evaluated in 136 cirrhotic patients. Hcy level [10.57 μmol/L (2.71-56.82) versus 9.97 μmol/L (2.05-53.44); P = 0.796] and proportions of HHcy [4/44 (9.1%) versus 13/81 (16.0%); P = 0.413] and positive aCL [1/23 (4.3%) versus 10/52 (19.2%); P = 0.185] and aβ2GPI [9/23 (39.1%) versus 21/52 (40.4%); P = 0.919] were not significantly different between cirrhotic patients with and without PVST. There was still no significant association of Hcy level, HHcy, aCL, or aβ2GPI with PVST based on Child-Pugh classification, MPV thrombosis >50%, and clinically significant PVST. Hcy, aCL, and aβ2GPI may not be associated with PVST in liver cirrhosis, suggesting that routine screening for Hcy, aCL, and aβ2GPI should be unnecessary in such patients.

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Section: Discussionsupporting

confidence: 77%

No Association of Homocysteine, Anticardiolipin Antibody, and Anti-β2 Glycoprotein I Antibody With Portal Venous System Thrombosis in Liver Cirrhosis

Wang

Guo

et al. 2021

Clin Appl Thromb Hemost

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“…A previous study 25 found that the mean plasma Hcy concentration was elevated in liver cirrhosis patients than in the control group. A recent study 26 found an association between HHcy and the severity of liver cirrhosis, and HHcy was related to a lower survival rate in patients post-liver transplantation. Additionally, animal experiments revealed that HHcy promoted LF in mice by activating the aromatic hydrocarbon receptor/CD36 pathway.…”

Section: Discussionmentioning

confidence: 96%

Plasma Levels of Homocysteine is Associated with Liver Fibrosis in Health Check-Up Population

Lv¹,

Wang²,

Ji³

et al. 2021

IJGM

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Object Studies have shown a link between homocysteine (Hcy) and heart diseases, kidney diseases, cerebrovascular diseases, liver diseases, and other pathological conditions. However, the relationship between Hcy and liver fibrosis (LF) is unclear. Here, we studied the link between plasma Hcy concentration and LF. Methods We determined and recorded the plasma Hcy concentration, general biochemical parameters, and liver stiffness measurement (LSM) in 1582 subjects, followed by statistical data analyses. Results During different stages of LF, we found a considerable difference ( p <0.001 unless specified) in body mass index (BMI), sex, age, Hcy, the levels of alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT; P = 0.012), triglycerides (TG; P = 0.006), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBS), and platelet count (PLT). There was a strong association between the plasma Hcy concentration and the serum biomarkers of LF ( P <0.001) and the values of LSM ( P <0.001). Conclusion The plasma Hcy concentration was substantially different among different stages of LF. The higher the plasma Hcy concentration, the more evident was the degree of LF.

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“…That working hypothesis should be confirmed by the demonstration of a negative correlation between rising Hcy values and declining TTR plasma levels [ 25 , 26 ] in aged subjects. The liver may similarly endure toxic exposure and varying inflammatory, autoimmune, and degenerative processes associated with HHcy states, as described in viral hepatitis [ 62 ], cirrhosis [ 63 ], and nonalcoholic steatosis [ 64 ]. The replacement of normal parenchymal cells by fatty, fibrotic, or inflammatory material would lead to marked intrahepatic dysregulation of Met metabolism, as recently documented in mouse experiments showing that diet-induced steatofibrosis is associated with HHcy status and a 30% depletion of the intrahepatic Met pool size [ 65 ].…”

Section: Salvage Mechanisms For Methionine Homeostasismentioning

confidence: 99%

Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis

Ingenbleek¹

2017

Nutrients

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Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value.

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Hyperhomocysteinemia is associated with severity of cirrhosis and negative impact after liver transplantation

Abstract: Hyperhomocysteinemia is frequently present in patients with cirrhosis and is associated with severe liver disease and reduced graft and patient survival after liver transplantation. The negative impact hyperhomocysteinemia has on graft and patient survival is not related to thrombosis.

Cited by 13 publications

References 38 publications

No Association of Homocysteine, Anticardiolipin Antibody, and Anti-β2 Glycoprotein I Antibody With Portal Venous System Thrombosis in Liver Cirrhosis

No Association of Homocysteine, Anticardiolipin Antibody, and Anti-β2 Glycoprotein I Antibody With Portal Venous System Thrombosis in Liver Cirrhosis

Plasma Levels of Homocysteine is Associated with Liver Fibrosis in Health Check-Up Population

Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis

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