The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

BACKGROUND: Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. METHODS: We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. RESULTS: For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. CONCLUSION: The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng/mL. Prospective studies are required to confirm this observation

Abnormal prothrombin (DES-y-Carboxy Prothrombin) in hepatocellular carcinoma

Des-γ-carboxy prothrombin (DCP), a protein induced by vitamin K absence or antagonist-II (PIVKA-II) was measured by an enzyme immunoassay (E-1023) using anti-DCP monoclonal antibody in 92 patients with various hepatobiliary diseases. Thirty-six of the 38 patients (94.7%) with hepatocellular carcinoma (HCC) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml, but only 18 of the 35 patients (51.4%) had AFP greater than 100 ng/ml (suspicious levels for HCC). There was no correlation between plasma or serum DCP and serum alpha-fetoprotein (AFP) levels. Serum alpha fetoprotein was elevated (above 20 ng/ml) in 23 of the 35 patients (65.7%), and DCP was elevated in all of the remaining 12 patients with normal AFP. DCP levels returned to normal levels following curative hepatic resection or orthotopic liver transplantation for HCC. DCP is a useful tumor marker in the diagnosis and postoperative monitoring of patients with HCC

Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease

Copyright @ 2010 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.Background: α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients. Methods: We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-γ. Results: Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child–Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child–Pugh A score and in 46% with a B or C score. Conclusion: These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.Association for International Cancer Research and Polkemmet Fund, London Clinic

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients

OBJECTIVE: As a marker for Hepatocellular Carcinoma (HCC), Protein Induced by Vitamin K Absence II (PIVKA-II) seems to be superior to alpha fetoprotein (AFP). To better characterize the role of PIVKA-II, both AFP and PIVKA-II have been measured in Italian patients with diagnosis of HCC compared with patients affected by non-oncological liver pathologies. MATERIALS AND METHODS: Sixty serum samples from patients with HCC, 60 samples from patients with benign liver disease and 60 samples obtained from healthy blood donors were included in the study. PIVKA-II and AFP were measured by LUMIPULSE(®) G1200 (Fujirebio-Europe, Belgium). We considered as PIVKA-II cutoff 70 mAU/ml (mean +3SD) of the values observed in healthy subjects. RESULTS: The evaluation of PIVKA-II showed a positivity of 70% in patients with HCC and 5% in patients with benign diseases (p < 0.0001) whereas high levels of AFP were observed in 55% of HCC patients and in 47% of patients with benign diseases. The combined Receiver Operating Characteristic (ROC) analysis of the two analytes revealed a higher sensitivity (75%) compared to those observed for the individual biomarkers. In conclusion, we demonstrate that as a marker for HCC, PIVKA-II is more specific for HCC and less prone to elevation during chronic liver diseases. CONCLUSIONS: The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice

Differences Between Alpha-Fetoprotein (AFP) and Prothrombine Induced by Vitamin K Absence or Antagonist II (PIVKA-II) Values as Early Detection Method for Hepatocellular Carcinoma (HCC) and Cirrhosis

Background: Hepatocellular carcinoma is a common cancer worldwide and has a high mortality. Biomarkers could theoretically help to detect the disease at an earlier stage before symptoms occur and improve the treatment outcomes. The first biomarker found was AFP (not very accurate and 30-40% of HCC may be missed). PIVKA-II can be used as an early detection method to diagnose HCC.Method: A cross sectional study on in-patients or out-patients at Saiful Anwar Malang Hospital from July 2016 to October 2016.Results: The p value (p > 0.05) obtained using Kolmogorov-Smirnov was 0.166 for diagnosis of HCC and 0.147 for the diagnosis of hepatic cirrhosis. The p value (p > 0.05) obtained using Shapiro-Wilk was 0.103 for diagnosis of HCC and 0.087 for the diagnosis of cirrhosis. Comparative test using the LSD method showed PIVKA-II serum levels in HCC as compared to hepatic cirrhosis as significant with a p-value less than 0.05 (p < 0.05), that is 0.025. However comparative test using the Tukey HSD method showed that the results obtained were not significant. According to the PIVKA-II cut off value, the sensitivity and specificity to detect cirrhosis and HCC was as large as 100%. According to the AFP cut off value, the sensitivity to detect cirrhosis and HCC was 93.3% and the specificity was 76.92%.Conclusion: Both PIVKA-II and AFP can be used to detect cirrhosis and HCC. However PIVKA-II exhibited better sensitivity and specificity in the detection of cirrhosis and HCC

Demonstration of astrocytes in cultured amniotic fluid cells of three cases with neural-tube defect

We have investigated the origin of rapidly adhering (RA) cells in three cases of neural tube defects (two anencephali, one encephalocele). We were able to demonstrate the presence of glial fibrillary acidic (GFA) protein in variable percentages (4–80%) of RA cells cultured for 4–6 days by use of indirect immunofluorescence with GFA antiserum. Cells cultured from amniotic fluids of normal pregnancies and fetal fibroblasts were completely GFA protein negative. GFA protein is well established as a highly specific marker for astrocytes. Demonstration of astrocytes may prove to be a criterion of high diagnostic value for neural tube defects. The percentage of astrocytes decreased with increasing culture time, while the percentage of fibronectin positive cells increased both in amniotic fluid cell cultures from neural tube defects and normal pregnancies

Assessment of Alpha Fetoprotein Levels and Gamma Glutamyl Transferase Activity in Hepatitis B and Hepatitis C Seropositive Subjects in Nnewi, Nigeria

Hepatitis B and hepatitis C viral infections are the leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. These conditions, which mar the hepatic functional integrity, are characterized by alterations in the liver function markers such as alpha fetoprotein (AFP) and gamma glutamyl tranferase (GGT). In the present study, a total of 90 subjects were recruited. Out of this number, 30 were hepatitis B seropositive subjects, 30 hepatitis C seropositive individuals and the remaining 30 were apparently healthy individuals. The last group served as the control. Serum alpha fetoprotein levels were estimated by the Enzyme Linked Immunosorbent Assay (ELISA) technique and the method adopted for the determination of gamma glutamyl transferase activity was the kinetic-spectrophotometric procedure. The mean serum level of alpha fetoprotein was significantly higher in hepatitis B seropositive subjects compared with the control (P&lt;0.05). The same pattern was observed when the mean serum activity of GGT of the hepatitis B seropositive subjects was compared with that of the control (P&lt;0.05). Furthermore, the mean serum level of AFP and the mean serum GGT activity were significantly higher in hepatitis C seropositive individuals compared with the control (P&lt;0.05). In contrast, no significant difference was observed in the mean serum levels of alpha fetoprotein in hepatitis B seropositive individuals compared with that of hepatitis C seropositive subjects (P&gt;0.05). A positive correlation existed between AFP levels and GGT activity in hepatitis B seropositive subjects (r=0.31) and between AFP levels and GGT activity in hepatitis C seropositive subjects (r=0.25). These findings suggest that evaluation of serum alpha fetoprotein levels and gamma glutamyl transferase activity may be a valuable adjunct in the assessment of disease progression in hepatitis B and hepatitis C seropositive individuals. Keywords: Hepatitis, alpha fetoprotein, glatamyl transferase, disease progression

Resolution of the clinical features of tyrosinemia following orthotopic liver transplantation for hepatoma

The clinical history before transplantation and subsequent clinical and biochemical course of 3 children and one adult with hereditary tyrosinemia treated by orthotopic hepatic transplantation is described. All four patients are now free of their previous dietary restrictions and appear to be cured of both their metabolic disease and their hepatic neoplasm. © 1986 Elsevier Science Publishers B.V. All rights reserved