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Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients.
Hepatology. 2005 May; 41(5):995-1003.Hep

Abstract

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 micromol/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.

Authors+Show Affiliations

Division of Internal Medicine and Hepatology, Second University of Naples, Faculty of Medicine, Naples, Italy. luigielio.adinolfi@unina2.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15834927

Citation

Adinolfi, Luigi E., et al. "Hyperhomocysteinemia and the MTHFR C677T Polymorphism Promote Steatosis and Fibrosis in Chronic Hepatitis C Patients." Hepatology (Baltimore, Md.), vol. 41, no. 5, 2005, pp. 995-1003.
Adinolfi LE, Ingrosso D, Cesaro G, et al. Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. Hepatology. 2005;41(5):995-1003.
Adinolfi, L. E., Ingrosso, D., Cesaro, G., Cimmino, A., D'Antò, M., Capasso, R., Zappia, V., & Ruggiero, G. (2005). Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. Hepatology (Baltimore, Md.), 41(5), 995-1003.
Adinolfi LE, et al. Hyperhomocysteinemia and the MTHFR C677T Polymorphism Promote Steatosis and Fibrosis in Chronic Hepatitis C Patients. Hepatology. 2005;41(5):995-1003. PubMed PMID: 15834927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. AU - Adinolfi,Luigi E, AU - Ingrosso,Diego, AU - Cesaro,Giuseppe, AU - Cimmino,Amelia, AU - D'Antò,Maria, AU - Capasso,Rosanna, AU - Zappia,Vincenzo, AU - Ruggiero,Giuseppe, PY - 2005/4/19/pubmed PY - 2005/6/2/medline PY - 2005/4/19/entrez SP - 995 EP - 1003 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 41 IS - 5 N2 - 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 micromol/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. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/15834927/Hyperhomocysteinemia_and_the_MTHFR_C677T_polymorphism_promote_steatosis_and_fibrosis_in_chronic_hepatitis_C_patients_ L2 - https://doi.org/10.1002/hep.20664 DB - PRIME DP - Unbound Medicine ER -