Home | About IJMPO | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |  Login 
Indian Journal of Medical and Paediatric Oncology
Search Article 
Advanced search 

 Table of Contents      
Year : 2011  |  Volume : 32  |  Issue : 2  |  Page : 71-75  

Lipoprotein(a) as a potential marker of residual liver function in hepatocellular carcinoma

1 Departments of Senescence, Urological & Neurological Sciences, University of Catania, Catania, Italy
2 Department of Surgery, University of Catania, Catania, Italy

Date of Web Publication15-Nov-2011

Correspondence Address:
Mario Uccello
Department of Senescence, Urological and Neurological Sciences, University of Catania, Ospedale Cannizzaro, Viale Messina, 829 - 95125 Catania
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-5851.89775

Rights and Permissions

The residual liver function is a major clinical index in hepatocellular carcinoma (HCC) patients. As the liver plays a crucial role in lipid and lipoprotein metabolism, the significant impairment of the hepatic function occurring during chronic liver diseases, such as HCC, can influence plasma lipoprotein profiles. Although, lipoprotein(a) (Lp(a)) circulating concentrations are mostly determined by genetic factors, in the majority of reports they have shown a correlation with the hepatic status and a significant decrease in HCC and liver cirrhosis patients than among the controls. In such a way, Lp(a) may represent a new additional and useful marker for a more complete assessment and monitoring of the liver function in patients with HCC and liver cirrhosis. Further studies are needed in order to evaluate the clinical significance of Lp(a) in HCC.

Keywords: Chronic liver disease, hepatocellular carcinoma, liver function, lipoprotein(a)

How to cite this article:
Uccello M, Malaguarnera G, Pelligra EM, Biondi A, Basile F, Motta M. Lipoprotein(a) as a potential marker of residual liver function in hepatocellular carcinoma. Indian J Med Paediatr Oncol 2011;32:71-5

How to cite this URL:
Uccello M, Malaguarnera G, Pelligra EM, Biondi A, Basile F, Motta M. Lipoprotein(a) as a potential marker of residual liver function in hepatocellular carcinoma. Indian J Med Paediatr Oncol [serial online] 2011 [cited 2019 Nov 11];32:71-5. Available from: http://www.ijmpo.org/text.asp?2011/32/2/71/89775

  Introduction Top

The liver carries out important biochemical duties on endogenous and exogenous substances including drugs.[1] Therefore, liver function integrity is essential to maintain a physiological metabolism of carbohydrates, lipids, and amino acids.[2],[3] Lipids are insoluble in water, thus they are carried along the plasma with proteins.[4] Most lipids are transported in lipoprotein complexes through the bloodstream.[5] Lipoproteins are globular, high-molecular-weight particles consisting of a core which contains non-polar lipids, triglycerides, and cholesterol esters, and surrounded by a polar surface coat, made of a single layer of phospholipids, unesterified cholesterol, and specific proteins, the so-called apolipoproteins.[4],[5],[6],[7] Apolipoproteins, which are synthesized by liver and gut, are expressed on the surface of lipoproteins and, besides ensuring the structural stability, they influence lipoprotein metabolism by activating specific enzymes and binding to cellular receptors.[8] Since the liver plays a crucial role in lipid and lipoprotein metabolism, the significant impairment of the hepatic function occurring during chronic liver diseases, including hepatocellular carcinoma (HCC), can influence plasma lipid profiles.[3] HCC is a challenging malignancy of global importance and is associated with a high rate of mortality. Nowadays, HCC is representing the fifth most common cancer all over the world and the third most frequent cause of mortality amongst oncological patients. It is responsible for more than 500 000 deaths with over 600 000 new worldwide cases yearly.[9] ,[10] More than 95% of patients with HCC have an underlying chronic liver disease which is most often associated with virus hepatitis B and C.[11] HCC is now the leading cause of death among cirrhotic patients.[12] Cirrhosis is an independent risk factor for the onset of HCC.[13]The best pathogenetic hypothesis points out a process with several stages. In this process, mature hepatocytes acquire further genetic alterations in a microenvironment where the coexistence of hepatic necrosis, inflammation and regeneration leads to the selection of monoclonal populations and the formation of dysplastic nodules.[14] ,[15] The staging systems for HCC take into account the severity of concomitant liver disease and the degree of the residual liver function, which are major conditioning elements for prognosis. The systems so far proposed to measure the liver function are not fully accepted by everyone, therefore the research is still aimed at developing new methods of measurement. A greater number of reports on HCC have shown abnormal plasma patterns of lipids and lipoproteins.[3],[16],[17],[18] This review is focused on the pathophysiological significance and the clinical impact given by fluctuations in lipoprotein(a) (Lp(a)) plasma levels observed during HCC.

  Lipoprotein (A): A Suis Generis Molecule Top

Lipoprotein(a), also called Lp(a), is a lipoprotein subclass; it is a "suis generis" molecule consisting of a low-density lipoprotein (LDL)-like particle whose apoB-100 is covalently bound to the apoprotein(a) (apo(a)) through a disulfide bridge. It was first described more than 40 years ago by Berg[19] though it still looks like a mysterious molecule, as its physiological role has not been revealed yet. There is an analogy between the apo(a) and the plasminogen genes: they both have coding sequences for loop structures, stabilized by intrachain disulfide bonds, the so-called kringle (K) domains.[20] Apo(a) contains 10 distinct subclasses of plasminogen kringle IV-like domains (KIV1−KIV10). While apo(a) KIV types 1 and 3−10 are present as single copies, the kringle IV type 2 domain (KIV2) is present in a variable number of identically repeated copies and it is the molecular basis for the observed isoform size heterogeneity of Lp(a).[21]The heterogeneity of apo(a) explains a large fraction of the variability of plasma Lp(a) concentrations, and there is a clear negative correlation between the molecular weight of apo(a) and the plasma Lp(a) concentration.[22],[23],[24] The two main Lp(a) subunits, apo(a) and apoB-100, are independently processed and released by the liver to form covalent particles within the extracellular compartment. The final assembly of Lp(a) occurs trough a two-step mechanism where a noncovalent interaction between apo(a) and apoB-100 precedes the disulfide linkage formation.[25] Lp(a) catabolism still remains unclear, but there is evidence against a great involvement of LDL receptors in this process.[26] The most widely used methods to measure Lp(a) in the clinical laboratory are the commercially available immunoassays (immunoturbidimetric analysis and ELISA method). [27] Lp(a) plasma levels are extremely variable among individuals, from less than 0.2 to more than 200 mg/dl, and their distribution does not follow a Gaussian type curve. Approximately 90% of the population have serum Lp(a) values lower than 300 mg/L though values above 20000 mg/L have occasionally been found.[23] Although Lp(a) circulating concentrations are mostly determined by genetic factors,[21] they may display more or less significant fluctuations, under different physiological and pathological situations or pharmacological agents. Lp(a) levels in postmenopausal women are higher than in premenopausal and perimenopausal women.[28] Lp(a) serum levels are decreased in subjects with liver failure [16] ,[29] or hyperthyroidism.[30] Mink et al.[31] reported that Lp(a) concentrations were significantly higher among the acute phase response patients (infections, postoperative, tumors, and other diseases) than among the controls. The clinical interest around Lp(a) largely springs from the recognition of it as a cardiovascular risk factor. Although it is not counted among the major traditional risk factors, increased Lp(a) levels have shown a correlation with cardiovascular disease in several studies. [32],[33],[34] Moreover, recent data indicate that Lp(a) is a cardiovascular risk factor independent of traditional ones, such as LDL cholesterol, low HDL cholesterol levels, hypertension, diabetes mellitus, obesity, sedentary, and smoking. [35],[36] In some cancer types, apart from HCC, Lp(a) plasma levels have been found to be elevated, but in general few data are still available about Lp(a) concentrations in cancer patients. [37]

  Relationship Between LP(A), Hepatic Status , and HCC Top

Since the majority of HCCs occur in patients with liver cirrhosis, the evaluation of the liver function plays a central role in the fields of therapeutic decision, tumor staging, and prognosis. [38] Liver function can be assessed readily by routine laboratory tests (alanine and aspartate aminotransferase, albumin and bilirubin serum levels, prothrombin and international normalized ratio (INR) values, platelet and white cell counts, blood ammonia level, ferritin), but several factors make the changes in concentration of this analytes difficult to interpret when considered individually. [39] The Child-Pugh classification has incorporated some of these routine laboratory tests, representing thus the first systematic approach to determine the index of the residual liver function. [40] However, it is based on some subjective parameters such as ascites and encephalopathy that make the assessment less accurate. [41] The model for end-stage liver disease (MELD) score, which includes the international normalized ratio (INR) and serum bilirubin and creatinine levels in the calculation, has recently emerged as a very valuable method for the assessment of residual liver function. MELD score has been shown to have significant advantages in clinical practice, especially in those patients who are candidates for liver transplantation. [42],[43] However, it is greatly criticized in some respects. For example, serum creatinine levels and INR show significant discrepancies using different laboratory methodologies. [44],[45] Several studies have reported that the addition of other prognostic factors to those evaluated by MELD score may increase accuracy in evaluating liver function and prognosis. [46],[47],[48] Other methods of liver function estimation, based on the principle of clearance of substrate by the liver, have been developed. The substrates include indocyanin green, lidocaine, galactose, aminopyrine aminoacid, and methacetin. There are also tests based on the principle of energy production by the liver, such as arterial ketone body ratio and AKBR, and others based on the number of receptors for asialoglycoprotein (ASGP-R; technetium-99m-galactosyl human serum albumin; 99mTc-GSA scan). Nevertheless, an accurate, yet practical and cost-effective method of liver function evaluation has not been clearly defined. [49]

The liver is the main site of lipoprotein synthesis.[50] The formation of lipoproteins is a complex and gradual process that begins in the rough endoplasmic reticulum where apolipoproteins are synthesized. In the smooth endoplasmic reticulum, the various lipid fractions link to apolipoproteins. After that, the newly formed lipoproteins get to the tanks of Golgi apparatus where they buy the carbohydrate component required for their secretion. The liver also plays a central role in lipid metabolism. The modification and disposal of the lipid material depends on the liver which can send the circulating lipid material in the form of ketone bodies, triglycerides, phospholipids, and cholesterol, the three last ones being linked to lipoproteins.[7] ,[51],[52],[53],[54]

The liver is the cardinal organ for Lp(a) synthesis.[55] Apo(a) is synthesized by the hepatocytes as a low molecular mass precursor, and then modified in the endoplasmic reticulum and transferred in the Golgi apparatus.[56] It is unclear if the final assembly of Lp(a) takes place inside or outside the cell, probably on the hepatocyte surface, and from there Lp(a) is released into the circulation.[57] Several studies have shown an association between Lp(a) plasma levels and chronic liver diseases. Lp(a) levels decrease as the disease progresses.[16],[55],[58] It has been demonstrated that serum Lp(a) levels in patients with chronic liver diseases, induced by hepatitis viral infections, are significantly reduced when compared to healthy controls.[16],[55],[58],[59],[60] Malaguarnera et al.[55] reported a significant increase of Lp(a) levels occurring after the treatment in patients with chronic active hepatitis C. Only patients who responded fully presented a significant increase in the values of Lp(a). These findings suggest that increased levels of Lp(a) represent an expression of improved liver function. Since the liver is the organ that synthesizes Lp(a), reduced level of Lp(a) during chronic liver diseases may be attributed to the relative decrease in the synthesis by a damaged liver. In the course of HCC and/or cirrhosis, circulating Lp(a) have displayed abnormal patterns.[16],[55],[58],[60] Thus, it is conceivable that the status of hepatic cellular impairments, various cytokines delivered during the disease, and hormone environment may influence the metabolic pathway of Lp(a).[16] Lp(a) plasma levels are influenced early when liver function is impaired, because the half-life of Lp(a) is about 3.3-3.9 days in human plasma.[61],[62] Lp(a) plasma levels, at variance with the other lipoproteins, are not affected by dietary changes.[63] While Basili et al.[64] found elevated levels of Lp(a) in HCC patients, in three different case control studies Lp(a) plasma levels showed a significant decrease in patients with HCC and liver cirrhosis than among the controls.[16] ,[58],[60] Moreover, Motta et al.[16] noticed a significant negative correlation between Lp(a) and Child-Pugh degrees, α-fetoprotein and ferritin values as well as a positive one with albumin and cholinesterase levels calling for a role of Lp(a) as a marker of liver disease also in HCC.

  Conclusions Top

With its complexity, Lp(a) could act as a marker of residual liver function. Its structure is indeed an expression of lipid (LDL-like particle) and protein (apoB-100) metabolism, and of coagulation state (apo(a)) as well. Since in the overall population Lp(a) blood concentrations are extremely variable from a subject to another, cohort studies would be more appropriate than case control studies at evaluating the relationship between Lp(a) and HCC. In such a way, it would be possible to evaluate the fluctuations of Lp(a) levels over time, with serial measurements with the progression of the disease and the consequent deterioration of the liver function. The presence of HBV or HCV infection, generalized inflammatory state or other conditions could be confounding factors though they have not been analyzed separately in any study. Lp(a) may supply useful additional information for a more complete assessment and monitoring of the liver function in patients with HCC and liver cirrhosis. Further investigations are needed in order to verify Lp(a) accuracy at measuring the residual liver function in HCC patients, especially in comparison with other methods of liver function evaluation.

  Acknowledgment Top

The authors wish to thank Alessia Trovato for her work in drafting the article and for her contribution to language revision.

  References Top

1.Prescott LF, Forrest JA, Adjepon-Yamoah KK, Finlayson ND. Drug metabolism in liver disease. J Clin Pathol Suppl (R Coll Pathol) 1975;9:62-5.  Back to cited text no. 1
2.Bell AW. Lipid metabolism in liver and selected tissues and in the whole body of ruminant animals. Prog Lipid Res 1979;18:117-64.  Back to cited text no. 2
3.Jiang J, Nilsson-Ehle P, Xu N. Influence of liver cancer on lipid and lipoprotein metabolism. Lipids Health Dis 2006;5:4.  Back to cited text no. 3
4.Wasan KM, Cassidy SM. Role of plasma lipoproteins in modifying the biological activity of hydrophobic drugs. J Pharm Sci 1998;87:411-24.  Back to cited text no. 4
5.Shepherd J, Packard CJ. Lipid transport through the plasma: the metabolic basis of hyperlipidaemia. Baillieres Clin Endocrinol Metab 1987;1:495-514.  Back to cited text no. 5
6.Ginsberg HN, Taskinen MR. New insights into the regulation of lipoprotein metabolism: Studies in procaryocytes, eukaryocytes, rodents, pigs, and people. Curr Opin Lipidol 1997;8:127-30.  Back to cited text no. 6
7.Cooper AD. Hepatic lipoprotein metabolism: Recent molecular insights. Prog Liver Dis 1995;13:173-200.  Back to cited text no. 7
8.Dixon JL, Ginsberg HN. Hepatic synthesis of lipoproteins and apolipoproteins. Semin Liver Dis 1992;12:364-72.  Back to cited text no. 8
9.Bosch FX, Ribes J, Cléries R, Díaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis 2005;9:191-211.  Back to cited text no. 9
10.Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.  Back to cited text no. 10
11.Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907-17.  Back to cited text no. 11
12.Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, et al. Morbidity and mortality in compensated cirrhosis type C: A retrospective follow-up study of 384 patients. Gastroenterology 1997;112:463-72.  Back to cited text no. 12
13.Shibata M, Morizane T, Uchida T, Yamagami T, Onozuka Y, Nakano M, et al. Irregular regeneration of hepatocytes and risk of hepatocellular carcinoma in chronic hepatitis and cirrhosis with hepatitis-C-virus infection. Lancet 1998;351:1773-7.  Back to cited text no. 13
14.Wong CM, Ng IO. Molecular pathogenesis of hepatocellular carcinoma. Liver Int 2008;28:160-74.  Back to cited text no. 14
15.Moradpour D, Blum HE. Pathogenesis of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2005;17:477-83.   Back to cited text no. 15
16.Motta M, Giugno I, Ruello P, Pistone G, Di Fazio I, Malaguarnera M. Lipoprotein (a) behaviour in patients with hepatocellular carcinoma. Minerva Med 2001;92:301-5.  Back to cited text no. 16
17.Ooi K, Shiraki K, Sakurai Y, Morishita Y, Nobori T. Clinical significance of abnormal lipoprotein patterns in liver diseases. Int J Mol Med 2005;15:655-60.   Back to cited text no. 17
18.Ahaneku JE, Taylor GO, Olubuyide IO, Agbedana EO. Abnormal lipid and lipoprotein patterns in liver cirrhosis with and without hepatocellular carcinoma. J Pak Med Assoc 1992;42:260-3.  Back to cited text no. 18
19.Berg K. A new serum type system in man - the Lp system. Acta Pathol Microbiol Scand 1963;59:369-82.  Back to cited text no. 19
20.McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, et al. cDNA sequence of human apolipoprotein (a) is homologous to plasminogen. Nature 1987;330:132-7.  Back to cited text no. 20
21.Utermann G, Weber W. Protein composition of Lp(a) lipoprotein from human plasma. FEBS Lett 1983;154:357-61.  Back to cited text no. 21
22.Utermann G. The mysteries of lipoprotein(a). Science 1989;246:904-10.  Back to cited text no. 22
23.Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest 1992;90:52-60.  Back to cited text no. 23
24.Galvano F, Malaguarnera M, Vacante M, Motta M, Russo C, Malaguarnera G, et al. The physiopathology of lipoprotein (a). Front Biosci (Schol Ed) 2010;2:866-75.  Back to cited text no. 24
25.Guevara J Jr, Valentinova NV, Garcia O, Gotto AM, Yang CY, Legal S, et al. Interaction of apolipoprotein[a] with apolipoproteinB-100 Cys3734 region in lipoprotein[a] is confirmed immunochemically. J Protein Chem 1996;15:17-25.  Back to cited text no. 25
26.Knight BL, Perombelon YF, Soutar AK, Wade DP, Seed M. Catabolism of lipoprotein(a) in familial hypercholesterolaemic subjects. Atherosclerosis 1991;87:227-37.  Back to cited text no. 26
27.Levine DM, Sloan BJ, Donner JE, Lorenz JD, Heinzerling RH. Automated measurement of lipoprotein(a) by immunoturbidimetric analysis. Int J Clin Lab Res 1992;22:173-8.  Back to cited text no. 27
28.Kim CJ, Kim TH, Ryu WS, Ryoo UH. Influence of menopause on high density lipoprotein-cholesterol and lipids. J Korean Med Sci 2000;15:380-6.  Back to cited text no. 28
29.Malaguarnera M, Giugno I, Trovato BA, Panebianco MP, Restuccia N, Ruello P. Lipoprotein(a) in cirrhosis. A new index of liver functions? Curr Med Res Opin 1996;13:479-85.  Back to cited text no. 29
30.Kung AW, Pang RW, Lauder I, Lam KS, Janus ED. Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism. Clin Chem 1995;41:226-31.  Back to cited text no. 30
31.Min WK, Lee JO, Huh JW. Relation between lipoprotein(a) concentrations in patients with acute-phase response and risk analysis for coronary heart disease. Clin Chem 1997;43:1891-5.  Back to cited text no. 31
32.Smolders B, Lemmens R, Thijs V. Lipoprotein (a) and stroke: A meta-analysis of observational studies. Stroke 2007;38:1959-66.   Back to cited text no. 32
33.Cheng SW, Ting AC, Wong J. Lipoprotein (a) and its relationship to risk factors and severity of atherosclerotic peripheral vascular disease. Eur J Vasc Endovasc Surg 1997;14:17-23.  Back to cited text no. 33
34.Takagi H, Manabe H, Kawai N, Goto SN, Umemoto T. Circulating lipoprotein(a) concentrations and abdominal aortic aneurysm presence. Interact Cardiovasc Thorac Surg 2009;9:467-70.  Back to cited text no. 34
35.Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 2009;361:2518-28.  Back to cited text no. 35
36.Trégouët DA, König IR, Erdmann J, Munteanu A, Braund PS, Hall AS, et al. Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nat Genet 2009;41:283-5.  Back to cited text no. 36
37.Lippi G, Franchini M, Salvagno GL, Guidi GC. Lipoprotein(a) and cancer: anti-neoplastic effect besides its cardiovascular potency. Cancer Treat Rev 2007;33:427-36.  Back to cited text no. 37
38.Manizate F, Hiotis SP, Labow D, Roayaie S, Schwartz M. Liver functional reserve estimation: state of the art and relevance to local treatments. Oncology 2010;78:131-4.  Back to cited text no. 38
39.Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician 1999;59:2223-30.  Back to cited text no. 39
40.Albers I, Hartmann H, Bircher J, Creutzfeldt W. Superiority of the Child-Pugh classification to quantitative liver function tests for assessing prognosis of liver cirrhosis. Scand J Gastroenterol 1989;24:269-76.  Back to cited text no. 40
41.Dohmen K. Many staging systems for hepatocellular carcinoma: evolution from Child-Pugh, Okuda to SLiDe. J Gastroenterol Hepatol 2004;19:1227-32.  Back to cited text no. 41
42.Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001;33:464-70.  Back to cited text no. 42
43.Ahmad J, Downey KK, Akoad M, Cacciarelli TV. Impact of the MELD score on waiting time and disease severity in liver transplantation in United States veterans. Liver Transpl 2007;13:1564-69.  Back to cited text no. 43
44.Cholongitas E, Marelli L, Kerry A, Senzolo M, Goodier DW, Nair D, et al. Different methods of creatinine measurement significantly affect MELD scores. Liver Transpl 2007;13:523-29.  Back to cited text no. 44
45.Trotter JF, Brimhall B, Arjal R, Phillips C. Specific laboratory methodologies achieve higher model for endstage liver disease (MELD) scores for patients listed for liver transplantation. Liver Transpl 2004;10:995-1000.  Back to cited text no. 45
46.Jiang M, Liu F, Xiong WJ, Zhong L, Xu W, Xu F, et al. Combined MELD and blood lipid level in evaluating the prognosis of decompensated cirrhosis. World J Gastroenterol 2010;16:1397-401.  Back to cited text no. 46
47.Sheng QS, Lang R, He Q, Yang YJ, Zhao DF, Chen DZ. Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis. Hepatobiliary Pancreat Dis Int 2009;8:46-9.  Back to cited text no. 47
48.Ruf AE, Kremers WK, Chavez LL, Descalzi VI, Podesta LG, Villamil FG. Addition of serum sodium into the MELD score predicts waiting list mortality better than MELD alone. Liver Transpl 2005;11:336-43.  Back to cited text no. 48
49.Fan ST. Liver functional reserve estimation: State of the art and relevance for local treatments: The Eastern perspective. J Hepatobiliary Pancreat Sci 2010;17:380-4.  Back to cited text no. 49
50.Davis RA. Lipoprotein synthesis and secretion by cultured hepatocytes. Methods Enzymol 1986;129:272-83.  Back to cited text no. 50
51.Theriault A, Wang Q, Van Iderstine SC, Chen B, Franke AA, Adeli K. Modulation of hepatic lipoprotein synthesis and secretion by taxifolin, a plant flavonoid. J Lipid Res 2000;41:1969-79.  Back to cited text no. 51
52.Samuels ME. Genetics of cholesterol and lipoprotein metabolism. Recent Pat Cardiovasc Drug Discov 2007;2:195-204.  Back to cited text no. 52
53.Beisiegel U. Lipoprotein metabolism. Eur Heart J 1998;19:A20-3.  Back to cited text no. 53
54.Illingworth DR. Lipoprotein metabolism. Am J Kidney Dis 1993;22:90-7.  Back to cited text no. 54
55.Malaguarnera M, Giugno I, Trovato BA, Panebianco MP, Siciliano R, Ruello P. Lipoprotein(a) concentration in patients with chronic active hepatitis C before and after interferon treatment. Clin Ther 1995;17:721-8.  Back to cited text no. 55
56.White AL, Rainwater DL, Lanford RE. Intracellular maturation of apolipoprotein[a] and assembly of lipoprotein[a] in primary baboon hepatocytes. J Lipid Res 1993;34:509-17.  Back to cited text no. 56
57.White AL, Lanford RE. Cell surface assembly of lipoprotein(a) in primary cultures of baboon hepatocytes. J Biol Chem 1994;269:28716-23.  Back to cited text no. 57
58.Samonakis DN, Koutroubakis IE, Sfiridaki A, Malliaraki N, Antoniou P, Romanos J, et al. Hypercoagulable states in patients with hepatocellular carcinoma. Dig Dis Sci 2004;49:854-8.  Back to cited text no. 58
59.Irshad M. Serum lipoprotein (a) levels in liver diseases caused by hepatitis. Indian J Med Res 2004;120:542-5.  Back to cited text no. 59
60.Jiang J, Zhang X, Wu C, Qin X, Luo G, Deng H, et al. Increased plasma apoM levels in the patients suffered from hepatocellular carcinoma and other chronic liver diseases. Lipids Health Dis 2008;7:25.  Back to cited text no. 60
61.Malaguarnera M, Trovato G, Restuccia S, Giugno I, Franzé CM, Receputo G, et al. Treatment of nonresectable hepatocellular carcinoma: review of the literature and meta-analysis. Adv Ther 1994;11:303-19.  Back to cited text no. 61
62.Krempler F, Kostner GM, Roscher A, Haslauer F, Bolzano K, Sandhofer F. Studies on the role of specific cell surface receptors in the removal of lipoprotein (a) in man. J Clin Invest 1983;71:1431-41.  Back to cited text no. 62
63.Albers JJ, Adolphson JL, Hazzard WR. Radioimmunoassay of human plasma Lp(a) lipoprotein. J Lipid Res 1977;18:331-8.  Back to cited text no. 63
64.Basili S, Andreozzi P, Vieri M, Maurelli M, Cara D, Cordova C, et al. Lipoprotein (a) serum levels in patients with hepatocarcinoma. Clin Chim Acta 1997;262:53-60.  Back to cited text no. 64

This article has been cited by
1 Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
Sunjae Lee,Adil Mardinoglu,Cheng Zhang,Doheon Lee,Jens Nielsen
Nucleic Acids Research. 2016; : gkw462
[Pubmed] | [DOI]
2 The miR-573/apoM/Bcl2A1-dependent signal transduction pathway is essential for hepatocyte apoptosis and hepatocarcinogenesis
Yan-Wei Hu,Zhi-Ping Chen,Xiu-Mei Hu,Jia-Yi Zhao,Jin-Lan Huang,Xin Ma,Shu-Fen Li,Yu-Rong Qiu,Xiao-Juan Wu,Yan-Hua Sha,Ji-Juan Gao,Yan-Chao Wang,Lei Zheng,Qian Wang
Apoptosis. 2015; 20(10): 1321
[Pubmed] | [DOI]
3 Protective activity of probiotic bacteria against 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PhIP) – anin vitrostudy
Adriana Nowak,Agata Czyzowska,Malgorzata Stanczyk
Food Additives & Contaminants: Part A. 2015; 32(11): 1927
[Pubmed] | [DOI]
4 An unusual cause of gastric extraluminal compression: Fibrolamellar hepatocellular carcinoma
Dilettoso, S. and Uccello, M. and Dilettoso, A. and Gelardi, S. and Dilettoso, B.
Central European Journal of Medicine. 2013; 8(2): 182-184
5 Lipoprotein(a) plasma levels and the risk of cancer: The PRIME study
Marrer, E. and Wagner, A. and Montayed, M. and Luc, G. and Amouyel, P. and Dallongeville, J. and Ducimetiere, P. and Bingham, A. and Arveiler, D. and Velten, M.
European Journal of Cancer Prevention. 2013; 22(3): 286-293
6 Serum markers of intrahepatic cholangiocarcinoma
Malaguarnera, G. and Paladina, I. and Giordano, M. and Malaguarnera, M. and Bertino, G. and Berretta, M.
Disease Markers. 2013; 34(4): 219-228
7 Lipoprotein(a) plasma levels and the risk of cancer
Émilie Marrer,Aline Wagner,Michèle Montaye,Gérald Luc,Philippe Amouyel,Jean Dallongeville,Pierre Ducimetiere,Annie Bingham,Dominique Arveiler,Michel Velten
European Journal of Cancer Prevention. 2013; 22(3): 286
[Pubmed] | [DOI]
8 An unusual cause of gastric extraluminal compression: fibrolamellar hepatocellular carcinoma
Salvatore Dilettoso,Mario Uccello,Alessandra Dilettoso,Salvatore Gelardi,Benedetto Dilettoso
Central European Journal of Medicine. 2013; 8(2): 182
[Pubmed] | [DOI]
9 Centenarians and supercentenarians: A black swan. Emerging social, medical and surgical problems
Vacante, M. and Dagata, V. and Motta, M. and Malaguarnera, G. and Biondi, A. and Basile, F. and Malaguarnera, M. and Gagliano, C. and Drago, F. and Salamone, S.
BMC Surgery. 2012; 12(SUPPL. 1)
10 Neurotoxicity in cadmium-exposed workers
Alessandria, I. and Pennisi, M. and Cataudella, E. and Frazzetto, P.M. and Malaguarnera, M. and Rampello, L. and Rampello, L.
Acta Medica Mediterranea. 2012; 28(3): 253-526
11 Centenarians and supercentenarians: a black swan. Emerging social, medical and surgical problems
Marco Vacante,Velia D’Agata,Massimo Motta,Giulia Malaguarnera,Antonio Biondi,Francesco Basile,Michele Malaguarnera,Caterina Gagliano,Filippo Drago,Salvatore Salamone
BMC Surgery. 2012; 12(Suppl 1): S36
[Pubmed] | [DOI]
12 Lipoprotein(A) in cerebral stroke: A review
Russo, C. and Vacante, M. and Malaguarnera, G. and Drago, F. and Dæagata, V. and Rampello, L. and Bella, R. and Pennisi, M. and Malaguarnera, M. and Rampello, L.
Acta Medica Mediterranea. 2012; 28(3): 201-205
13 Pesticides exposure and the management of acute hepatic injury
Cataudella, E. and Malaguarnera, G. and Gagliano, C. and Condorelli, G. and Antic, T. and Rampello, L. and Erdogan, Ö. and Rampello, L. and Malaguarnera, M.
Acta Medica Mediterranea. 2012; 28(3): 245-252


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Lipoprotein (A):...
   Relationship Bet...

 Article Access Statistics
    PDF Downloaded301    
    Comments [Add]    
    Cited by others 13    

Recommend this journal