α1-Antitrypsin deficiency and hepatocellular cancer

Alpha 1-antitrypsin levels and phenotypes and hepatitis B serology in liver cancer

“…Individuals who are homozygous for the Z allele (and perhaps other alleles associated with a1AT deficiency) have an increased risk for HCC, and many of them have the characteristic globular bodies in their livers. However, it is not clear whether individuals who B are heterozygous for these alleles are at increased risk for HCC; many studies have noted modest associations but several others have not, even though heterozygotes have consistently the same characteristic globules in their livers (studies reviewed by Sharp, 1976;Kew et al, 1978;Morse, 1978;Kelly et al, 1979;Sizaret et al, 1981;Spech & Liehr, 1982 Kew et al, (1978), Chio &Oon (1979), andMatsuzaki et al (1981). Our findings confirm the results of the earlier investigations and indicate that the elevation is sufficiently marked to be aetiologically intriguing and diagnostically useful.…”

“…Alpha1-antitrypsin (a]AT) is one of nine distinct plasma proteins which have been characterized as protease inhibitors (Harpel, 1983); it is a glycoprotein synthesized in the liver and it is responsible for about 90 per cent of the tryptic inhibitory capacity of human serum (Sharp, 1976;Kew et al, 1978;Morse, 1978;Chio & Oon, 1979). i1AT is under genetic control, and more than 30 codominant alleles at a single chromosomal locus have been identified (Chapuis-Cellier, 1975;Cox, 1978;Morse, 1978).…”

“…Some of these alleles (particularly the alleles Z, I, S, and perhaps P and other less common ones) have been associated with serum cz1AT deficiency of varying degree (ChapuisCellier, 1975;Morse, 1978;Chapuis-Cellier & Arnaud, 1979) and with the presence in the liver of periodic acid-Schiff(PAS)-positive, diastase-resistant globules (Sharp, 1976;Morse, 1978;Palmer et al, 1980). There appears to be an intriguing link between a1AT and hepatocellular carcinoma (HCC) but the evidence is not clear cut (Sharp, 1976;Kew et al, 1978;Morse, 1978;Kelly et al, 1979). We have studied the association between e1AT and HCC in a large group of HCC cases and matched controls, using adequate laboratory procedures "blindly" (with respect to disease status), in a European population with an unusually high incidence of HCC (Trichopoulos et al, 1982).…”

α1-antitrypsin and survival in hepatocellular carcinoma

“…Individuals who are homozygous for the Z allele are at an increased risk for hepatocellular carcinoma (HCC) (Eriksson et al, 1986), but there is no convincing evidence that individuals who are heterozygous for the Z allelle, and other alleles associated with mjAT deficiency, are over-represented among cases of HCC (Govindarajan et al, 1981;Sparos et al, 1984;Eriksson, 1985;Marwick et al, 1985;Schneider et al, 1986). Interestingly, several authors have confirmed the observation of Kew et al (1978) that HCC cases have elevated levels of serum a,AT, an increase which is found across several a,AT phenotypes (Chio & Oon, 1979;Matsuzaki et al, 1981). In 1984 we reported the results of a relatively large epidemiological study in Greece exploring, among other issues, the association between a,AT levels and HCC, by hepatitis B virus (HBV) serological status (Sparos et al, 1984).…”

“…identified (Cox, 1978;Morse, 1978;Kuhnl & Spielmann, 1979;Buffone et al, 1983;Dykes et al, 1984). The association between a,AT and HCC is complex and intriguing, and may reflect both the pathophysiological role of a,AT (Eriksson, 1985;Garver et al, 1986) and its production by the liver (Glasgow et al, 1982).…”