{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:39:43Z","timestamp":1790858383773,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,2,7]],"date-time":"2005-02-07T00:00:00Z","timestamp":1107734400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:p><jats:bold>Abstract: Background\/Aims: <\/jats:bold> The liver plays a key role in sulphur aminoacid metabolism hence, homocysteine metabolism may be impaired in chronic liver diseases. The aim of this study was to investigate, in patients affected by chronic liver diseases, (1) the prevalence of hyperhomocysteinaemia and (2) the role of its determinants such as the stage and the aetiology of disease, vitamin status, genetic documented alterations (methylenetetrahydrofolate reductase deficiency) and presence\/absence of documented malignant evolution (hepatocellular carcinoma).<\/jats:p><jats:p><jats:bold>Material and Methods: <\/jats:bold> One hundred and thirty patients with chronic liver disease (34 with chronic active hepatitis, 12 with fatty liver and 88 with liver cirrhosis) and 50 healthy age\u2010matched control subjects were included into the study.<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> Hyperhomocysteinaemia was defined as homocysteine plasma levels greater than 12.6\u2003\u03bcmol\/l. Hyperhomocysteinaemia prevalence in liver cirrhosis group was 40.9%, significantly higher (all <jats:italic>P<\/jats:italic>&lt;0.01) with respect to controls (12%), chronic active hepatitis (14.7%) and fatty liver (25%) groups and increased with Child\u2013Pugh stage [Child A: 22.2%, Child B (50%); Child C (58.3%)]. In chronic\u2010active hepatitis and liver cirrhosis, the prevalence of subjects with methylenetetrahydrofolate reductase C677\u2192T mutation (both as CT and as TT) and hyperhomocysteinaemia results in significantly higher levels with respect to controls. Methylenetetrahydrofolate reductase C677\u2192T mutation and disease stage showed to be the most important predictive factors of hyperhomocysteinaemia in liver cirrhosis whereas the influence of homocysteine\u2010related vitamin status seems to have a secondary role.<\/jats:p><jats:p><jats:bold>Conclusions: <\/jats:bold> In conclusion hyperhomocysteinaemia is highly prevalent in liver cirrhosis but not in other chronic liver diseases; it may contribute to fibrogenesis and vascular complication of liver cirrhosis.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2005.01042.x","type":"journal-article","created":{"date-parts":[[2005,2,7]],"date-time":"2005-02-07T13:34:12Z","timestamp":1107783252000},"page":"49-56","source":"Crossref","is-referenced-by-count":51,"title":["Hyperhomocysteinaemia in chronic liver diseases: role of disease stage, vitamin status and methylenetetrahydrofolate reductase genetics"],"prefix":"10.1111","volume":"25","author":[{"given":"Paolo","family":"Ventura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Abbati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Marchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Grandone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Vergura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Tremosini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Zeneroli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,2,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/77.5.1094"},{"key":"e_1_2_6_3_2","first-page":"1217","article-title":"Hyperhomocysteinemia in liver cirrhosis","volume":"38","author":"Garcia\u2010Tevijano E R","year":"2001","journal-title":"mechanisms and role in vascular and hepatic fibrosis"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/003655200750023255"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80122-1"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(81)90489-3"},{"key":"e_1_2_6_7_2","first-page":"322","article-title":"Vitamin B12 and vitamin B12 binding proteins in liver diseases","volume":"8","author":"Areekul S","year":"1977","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840060324"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540460039030"},{"key":"e_1_2_6_10_2","first-page":"1149","article-title":"Hyperhomocysteinemia","volume":"324","author":"Clarke R","year":"1991","journal-title":"an independent risk factor for vascular disease"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530130055028"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.81.6.2004"},{"key":"e_1_2_6_13_2","first-page":"1202","article-title":"Homocysteine and cardiovascular disease","volume":"325","author":"Wald D S","year":"2002","journal-title":"evidence on causality from a meta-analysis"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.14.7.1080"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603213341203"},{"key":"e_1_2_6_16_2","first-page":"874","article-title":"Hyperhomocysteinemia and venous thrombosis","volume":"80","author":"Den Heijer M","year":"1998","journal-title":"a meta-analysis"},{"key":"e_1_2_6_17_2","first-page":"566","article-title":"Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism","volume":"80","author":"Eichinger S","year":"1998","journal-title":"Thromb Haemost"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1650680"},{"key":"e_1_2_6_19_2","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/S0016-5085(84)80077-3","article-title":"Formation of hilar collaterals or cavernous transformation after portal vein obstruction by hepatocellular carcinoma. Observations in ten patients","volume":"87","author":"Ohnishi K","year":"1984","journal-title":"Gastroenterology"},{"key":"e_1_2_6_20_2","first-page":"397","article-title":"Portal vein thrombosis in hepatocellular carcinoma","volume":"124","author":"Pirisi M","year":"1998","journal-title":"age and sex distribution in an autopsy study"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(85)90327-0"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-199010000-00030"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-198603000-00012"},{"key":"e_1_2_6_24_2","first-page":"902","article-title":"Portal vein thrombosis associated with cirrhosis","volume":"114","author":"Sarfeh I J.","year":"1979","journal-title":"clinical importance"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1996.0053"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614438"},{"key":"e_1_2_6_27_2","first-page":"1285S","article-title":"Homocysteine and hemostasis","volume":"126","author":"Harpel P C","year":"1996","journal-title":"pathogenic mechanisms predisposing to thrombosis"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118776"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(00)91403-3"},{"key":"e_1_2_6_30_2","first-page":"12","article-title":"Induction of TIMP\u20101 expression in rat hepatic stellate cells and hepatocytes","volume":"1455","author":"Torres L","year":"1999","journal-title":"a new role for homocysteine in liver fibrosis"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10588"},{"key":"e_1_2_6_32_2","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1093\/clinchem\/36.12.2137","article-title":"Concentrations of total homocysteine in plasma in chronic renal failure","volume":"36","author":"Soria C","year":"1990","journal-title":"Clin Chem"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(93)80432-4"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.12.3277"},{"key":"e_1_2_6_35_2","first-page":"862","article-title":"5,10\u2010Methylenetetrahydrofolate reductase gene variants and congenital anomalies","volume":"151","author":"Botto L D","year":"2000","journal-title":"a HuGE review"},{"key":"e_1_2_6_36_2","first-page":"111","article-title":"A candidate genetic risk factor for vascular disease","volume":"10","author":"Frosst P","year":"1995","journal-title":"a common mutation in methylenetetrahydrofolate reductase"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800600817"},{"key":"e_1_2_6_38_2","first-page":"866","article-title":"Long\u2010term diuretic therapy in hypertensive patients","volume":"92","author":"Morrow L E","year":"1999","journal-title":"effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11596"},{"key":"e_1_2_6_40_2","first-page":"1279","volume-title":"Metabolic Bases of Inherited Diseases","author":"Mudd S H L H","year":"1995"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.19.1.217"},{"key":"e_1_2_6_42_2","first-page":"142","article-title":"Thermolabile 5,10\u2010methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia","volume":"56","author":"Engbersen A M","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.3.569"},{"issue":"3","key":"e_1_2_6_44_2","first-page":"S208","article-title":"Genetic determinants of hyperhomocysteinaemia","volume":"159","author":"Blom H J.","year":"2000","journal-title":"the roles of cystathionine beta-synthase and 5,10-methylenetetrahydrofolate reductase"},{"key":"e_1_2_6_45_2","first-page":"131","article-title":"Polygenic in fatty liveruence on plasma homocysteine","volume":"149","author":"Tsai M Y","year":"2000","journal-title":"association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase, with lowered plasma homocysteine levels"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(98)00271-8"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/58.4.468"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1992.tb17100.x"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb09916.x"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(98)01041-8"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6346(00)00119-4"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/77.5.1269"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.1998.10718752"},{"key":"e_1_2_6_54_2","first-page":"266","article-title":"Blood vitamin status (B1, B2, B6, folic acid and B12) in patients with alcoholic liver disease","volume":"52","author":"Majumdar S K","year":"1982","journal-title":"Int J Vitam Nutr Res"},{"key":"e_1_2_6_55_2","first-page":"105","article-title":"The methylenetetrahydrofolate reductase (MTHFR) gene in colorectal cancer","volume":"30","author":"Ryan B M","year":"2001","journal-title":"role in tumor development and significance of allelic loss in tumor progression"},{"key":"e_1_2_6_56_2","first-page":"423","article-title":"Polymorphisms in genes involved in folate metabolism and colorectal neoplasia","volume":"159","author":"Sharp L","year":"2004","journal-title":"a HuGE review"},{"key":"e_1_2_6_57_2","first-page":"3748S","article-title":"Folate, methyl\u2010related nutrients, alcohol, and the MTHFR 677C\u2013>T polymorphism affect cancer risk","volume":"133","author":"Bailey L B.","year":"2003","journal-title":"intake recommendations"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(02)00633-X"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021843019755"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310213"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1478-3231.2005.01042.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1478-3231.2005.01042.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1478-3231.2005.01042.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T13:36:03Z","timestamp":1697117763000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1478-3231.2005.01042.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,2]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,2]]}},"alternative-id":["10.1111\/j.1478-3231.2005.01042.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1478-3231.2005.01042.x","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,2]]}}}