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Changes in Gc-globulin (Gc) and in alpha-foetoprotein (AFP) have been shown to be related to outcome in patients with acute liver failure (ALF). Gc is a serum protein that complexes with intravascular actin released during cellular necrosis. AFP, also made by hepatocytes, is associated with hepatocellular growth and regeneration. Previously, low absolute levels or decreases over time in either AFP or Gc portended to be a poor outcome.In a retrospective analysis of the double-blind trial of intravenous N-acetylcysteine (NAC) for ALF not because of acetaminophen, sera on days 1 and 3 or days 2 and 4 following admission were available to measure AFP in 70 patients and Gc in 66 patients. Mann-Whitney U tests were performed on the admission values, the absolute change and the fractional change of AFP and Gc to compare TFS (transplant-free survival) and non-TFS (death or transplantation). Logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate the markers in comparison and in addition to King's College Criteria (KCC).Transplant-free survival patients were characterized by increases in AFP, whereas non-TFS had significantly different (negative) absolute and fractional changes (P .01). The addition of declining AFP levels to KCC improved the area under the curve in predicting non-TFS (AUC70%). Gc globulin values did not differ between TFS and non-TFS in the 2-day intervals studied (P .2).In this comparison of two prognostic markers in patients with non-acetaminophen-induced ALF, rising AFP but not rising Gc levels was associated with TFS.ClinicalTrials.gov number NCT00004467.

Background & aims This study investigates the long-term incidences and predictors of developing hepatocellular carcinoma (HCC), cirrhotic events and mortality in cirrhotic patients receiving entecavir (ETV) therapy. Methods We enrolled 481 nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients who had compensated cirrhosis upon entry and had received ETV monotherapy for >12 months. Results The 8-year cumulative incidences of developing HCC, cirrhotic events and liver-related mortality were 26.5%, 8.62% and 10.03% respectively. Multivariate analysis revealed that diabetic mellitus (DM), higher fibrosis-4 (FIB-4) and alpha-foetoprotein (AFP) levels at 12 months of treatment, and FIB-4 increase from baseline to 12 months were independent factors of HCC. FIB-4 and AFP levels at 12 months of treatment were also independent factors of cirrhotic events and mortality. FIB-4 cut-off values of 3, 3 and 5 as well as AFP cut-offs of 5, 5, and 9 ng/mL at 12 months of treatment were optimal for predicting HCC, cirrhotic events and mortality during therapy respectively. The FIB-4 and AFP levels at 12 months of treatment were assessed for the combined risk of developing clinical outcomes. The 8-year incidences of HCC, cirrhotic events and liver-related mortality in the subgroups with low FIB-4 and AFP levels were only 5.95%, 1.03% and 2.43% respectively. DM was an independent predictor of HCC and mortality. Conclusion The combination of FIB-4 and AFP levels at 12 months of treatment is a useful marker for predicting the development of HCC, cirrhotic events and mortality in compensated cirrhotic patients with CHB who are receiving ETV therapy.

Alpha-foetoprotein (AFP), one of the first protein tumour markers discovered, is widely used today in clinical practice. Its application for the screening and diagnosis of hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour, is a matter of extensive debate. In addition to the studies focused on the role of the AFP in the diagnosis of HCC, in recent years AFP has been used to guide the therapeutic choice in HCC and monitor the treatment. Here, we summarize the latest studies that show the interest of AFP quantification in determining the suitability of liver transplantation or to follow-up on patients receiving the targeted treatment sorafenib. We also highlight the recent studies showing the active role of AFP in tumour progression, and the new modes of regulation of this tumour marker. Among these is the regulation of AFP through tumour proteostasis and the Unfolded Protein Response (UPR). We discuss the implications of this new knowledge in the therapeutic context, in terms of interpreting serum levels of AFP, and the new perspectives offered by AFP for the study of tumour proteostasis.

Un hamartome mesenchymateux (HM) du foie chez une petite fille âgee de sept mois etait associe avec une discrete augmentation du taux serique d'alpha foetoproteine (AFP) (320 pgJL, taux normal < 25 apresl'âge de six mois). L'examen anatomopathologique mettait en evidence un contingent hepatocellulaire abondant a la peripherie de la tumeur. Les hepatocytes tumoraux etaient legerement atypiques et exprimaient l'AFP en immunohistochimie. Chez deux autres petites filles âgees respectivement de 14 mois et deux mois, presentant un HM et un taux augmente d'AFP (320 μg/L et 7500 μg/L, respectivement), le diagnostic preoperatoire d'hepatoblastome a ete pose a tort. L'HM du foie s'accompagnant d'un taux serique augmente d'AFP peut donc simuler un hepatoblastome radiologiquement dans les cas ou les kystes manquent, et un hepatoblastome foetal a l'examen anatomo-pathologique si un prelevement biopsique interesse seulement le contingent hepatocellulaire peripherique de l'HM.

Background & Aims In this study, we investigated the clinical usefulness of AFP and PIVKA-II in subdividing prognostic groups in patients with locally advanced HCC treated locally. Methods Patients who had undergone local treatment for locally advanced HCC between 2001 and 2006 were enrolled. Response to treatment was defined as a reduction in AFP or PIVKA-II by more than 50% from baseline levels at 1 month after the treatment completion. Patients were divided according to their AFP and PIVKA-II response: A↓P↓ [AFP response (+) and PIVKA-II response (+)]; A↓P↑ [AFP response (+) and PIVKA-II response (−)]; A↑P↓ [AFP response (−) and PIVKA-II response (+)]; A↑P↑ [AFP response (−) and PIVKA-II response (−)]. Clinical characteristics and prognosis were compared between groups. Results Patients were subdivided into four groups by the change in the level of the biomarkers AFP and PIVKA-II, and the survival outcomes of each group were distinct. Among patients with an AFP response, further subdivision by PIVKA-II response revealed that those in the A↓P↓ group had a longer median progression-free survival (PFS) and overall survival (OS) compared with those in the A↓P↑ group (PFS: 16.2 vs. 5.1 months, P = 0.009; OS: 26.3 vs. 7.3 months, P = 0.017). Combination of AFP and PIVKA-II response showed a predictive power for PFS and OS comparable to radiological criteria and better than AFP response alone. Conclusions In patients with locally advanced HCC, the use of a combination of two biomarkers, AFP and PIVKA-II, appears useful in predicting treatment outcomes through the subdivision of prognostic groups.

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Serum and urine banks have proved to be useful in the conduct of epidemiological studies. Samples collected as part of a large prospective study can be stored and retrieved later for laboratory analyses, selecting samples from groups of special interest and also from matched controls. The applications of the method are considered under three headings: firstly as a marker of a medical disorder, secondly as a measure of the extent of exposure to a harmful agent and thirdly as a direct measure of a suspected harmful or protective agent. Examples of each are given. Banks of biological samples other than serum or urine, such as hair and nail, are now being formed. The scientific opportunities of these collections are great and it will be of interest to see how they will be used.

An analysis of survival time of 57 West European patients with hepatocellular carcinoma was carried out to define which of several possible factors (age, sex, cirrhosis and raised serum alpha-foetoprotein (AFP)) influenced survival. Although survival was significantly longer in younger patients (P less than 0.02) and in patients with normal serum AFP (P less than 0.01), multivariate analysis showed that significant variation in survival time is better explained by the single factor, the presence of cirrhosis, than by AFP level. This does not seem to apply for patients with this tumour in Africa and the Far East, and there may be a fundamental difference in the natural history of the tumour between high- and low-incidence areas.

Finnstrom, O., Gothefors, L. and Zetterlund, B. (Departments of Paediatrics, University Hospitals, Linkoping and Umea, Sweden). Studies on maturity in newborn infants. VII. Foetal haemoglobin. Acta Paediatr Scand, 64:404, 1975.–Cord blood from 125 newborns of various gestational ages has been analysed for the ratio foetal haemoglobin to total haemoglobin, using an alkali denaturation method. The quotient, percentage of foetal haemoglobin divided by birth weight correlates well with gestational age. Thus the percentage of foetal haemoglobin in cord blood can be used as a method for estimating maturity in newborn infants. Foetal haemoglobin has been compared with other methods for maturity assessments and seems to give the same precision in estimating gestational age as the best of these, which is the scoring of external characteristics. However, the latter method is considerably less time-consuming and more suitable for routine use.

Carbohydrate antigen 19-9 as a serum marker of hepatocellular carcinoma: Comparison with alpha-foetoprotein

Ten preparations containing various levels of alpha-foetoprotein have been assayed by eight different laboratories in an international collaborative study of the W.H.O. alpha-foetoprotein standard. Included among the preparations, all of which were analyzed by the radioimmunoassay technique, were normal serum, sera from women before and after delivery, sera from teratoblastoma, alcoholic cirrhosis, and primary liver cancer patients, and amniotic fluid. The study establishes the validity of the W.H.O. standard for specimens with a wide range of AFP titer. Results have lower variability when expressed in comparison with the W.H.O. standard than when compared with the local standard used in each laboratory. Within-laboratory variability was some 2·5 times as great using the local standard but both standards show important differences between laboratories; the worst laboratory had more than 10 times greater within-laboratory variance (of the log concentration) than the best after all assays failing a rigorous test of technical validity had already been removed. Agreement between laboratories was better for preparations with more than 45 international units of alpha-foetoprotein/ml such as sera from women in the second half of gestation. For preparations with very low AFP content, such as normal human sera, only one laboratory was capable of providing dose-response curves parallel to that of the standard. A statistical technique (cubic splines) is discussed which allows useful information to be extracted from poor or oddly shaped assay curves. It is also noted, however, that an experienced laboratory worker is often even more effective in recovering results from bad assays.

Localization of αfp independent of the presence of serum was demonstrated only in a limited number of tumour cells in αfp-positive hepatocellular carcinomas. These cells usually formed three-dimensional groups with a definite tendency to localize near blood vessels and capillaries. Haematoxylin-eosin staining did not reveal any morphological difference between αfp-positive and -negative tumour cells. Etude par Immunofluorescence de L'a-αFetoproteine (afp) Dans le Foie et les Tumeurs Hepatiques. II. Localisation de L'afp Dans les Tissus de Sujets Atteints de Cancer Primitif du Fote L'αfp n'a pu ětre localisee independamment de la presence de serum que dans un petit nombre de cellules tumorales de carcinomes hepatocellulaires αfp-positifs. Ces cellules forment en general des groupes tridimensionnels et ont nettement tendance a se localiser pres des vaisseaux sanguins et des capillaires. La coloration a l'hematoxylineeosine n'a pas revele de differences morphologiques entre les cellules tumorales αfp-positives et αfp-negatives.

ABOUT 1000of testicular germ-cell tumoursoccurinmen treated formaldescended testes(Whitaker, 1970). The risk oftesticular tumourinmenwithmaldescended testes hasbeenestimated at35 timesthatofnormalmen (Whitaker, 1970). Recently 2 case-control studies confirmed theincreased riskoftesticular tumourinmaldescended testes (Morrison, 1976;Henderson etal., 1979). Testicular germ-cell (TGC) tumoursmaybepreceded bycarcinoma insituinabiopsy several yearsbefore(Skakkebaek, 1972,1978). Raisedconcentrations ofserumo-foetoprotein (AFP)andserumhumanchorionic gonadotropin :subunit (hCG)often precededothersignsofrelapse innonseminomatous TGC tumours(Waldmann &McIntire, 1974). SerumAFP and serum hCG were measured asascreen forTGCtumoursin menwithmaldescended testes, inaddition tophysical examination andtesticular biopsy. Thehistological findings ofthe first 50menbiopsied haverecently been reported elsewhere (Krabbe etal., 1979). Inthis paperwereport theresults ofthe tumourmarkers. Twohundred andseventy men aged18to35yearswhohadbeen treated formaldescended testeswere askedbyletter totakepartinthestudy. During childhood theyhadeither orchido

THE use of immunochemical methods for studying the composition of foetal human blood serum proteins led to the discovery of, in addition to the known alpha foetoprotein1–8, other embryospecific globulins with electrophoretic mobility of beta1 (refs. 5, 6, 9) and beta2 globulins9. Alpha foetoprotein is a relatively constant component of foetal blood serum. Embryospecific beta1 globulin was discovered in about 75 per cent9,10 and embryospecific beta2 globulin in 50 per cent of the cases9.