Serum Alpha-fetoprotein In Patients Research Articles

Prognostic Role of Basal Serum Alpha-Fetoprotein in Patients with Hepatocellular Carcinoma Suitable for Curative Treatment.

Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP's prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child-Pugh class B-C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child-Pugh class B-C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.

The Performance of Serum Alpha-Fetoprotein for Detecting Early-Stage Hepatocellular Carcinoma Is Influenced by Antiviral Therapy and Serum Aspartate Aminotransferase: A Study in a Large Cohort of Hepatitis B Virus-Infected Patients.

Background and aims: Factors associated with abnormally elevated alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-infected patients remain to be studied. We aimed to identify factors associated with elevated serum AFP in patients with non-hepatocellular carcinoma (HCC) and early-stage HCC and their influences on the performance of AFP for detecting early-stage HCC. Methods: This multicenter, retrospective study was conducted in 4401 patients with chronic HBV infection, including 3680 patients with non-HCC and 721 patients with early-stage HCC. Factors associated with elevated AFP were analyzed. Diagnostic performance of AFP for early-stage HCC were compared among groups through area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results: When analyzed by multivariate logistic regression, antiviral therapy was negatively associated with elevated AFP, while hepatitis B e antigen (HBeAg) and aspartate aminotransferase (AST) > 1× upper limit of normal (ULN) were positively associated with elevated AFP both in patients with non-HCC and early-stage HCC (all p < 0.05). The AUCs of AFP for detecting early-stage HCC in patients with antiviral therapy, HBV DNA (−), alanine aminotransferase (ALT) ≤ 1× ULN, and AST ≤ 1× ULN were significantly higher compared to those in non-antiviral therapy, HBV DNA (+), ALT > 1× ULN, and AST > 1× ULN groups, respectively. When categorizing patients into AST ≤ 1× ULN and > 1× ULN, AFP achieved the highest AUCs in patients with AST ≤ 1× ULN regardless of antiviral treatment (AUCs = 0.813 and 0.806, respectively). Furthermore, there were considerable differences in the cut-off values of AFP in detecting early-stage HCC in different subgroups when applying similar sensitivity and specificity. Conclusions: Antiviral therapy and serum AST might be used to help judge and select the specific cut-off values of serum AFP for HCC surveillance in different at-risk populations.

952P Prognostic implication of serum alpha-fetoprotein in patients with unresectable hepatocellular carcinoma treated with regorafenib

Regorafenib is a standard therapy for patients with unresectable hepatocellular carcinoma (uHCC) after progression on sorafenib. However, there is no known reliable factor predictive of clinical outcomes for regorafenib. Serum alpha-fetoprotein (AFP) was reported as a significant predictive factor for the outcome of patients with advanced HCC on sorafenib treatment. In this multinational retrospective cohort study, implication of serum alpha-fetoprotein (AFP) in the prediction of effectiveness of regorafenib in uHCC was investigated.

Signification of Serum Alpha-Fetoprotein Levels in Cases of Compensated Cirrhosis and Hepatitis C Virus without Hepatocellular Carcinoma.

AFP (alpha-fetoprotein) levels are increased during the development of HCC (hepatocellular carcinoma); nonetheless, it can also be produced by non-tumoral hepatocytes in conditions of high cell turnover. Our study aims to provide additional data regarding the causes of elevated AFP in patients with liver cirrhosis due to hepatitis C virus (HCV) infection.We conducted an observational prospective cohort study that included 2068 patients with compensated cirrhosis and chronic hepatitis C genotype 1b infection. The two main inclusion criteria were the presence of advanced liver fibrosis - Metavir stage F4 - diagnosed by FibroMax testing, Fibroscan or liver biopsy, and the presence of detectable HCV RNA in the serum. Plasmatic AFP levels were determined through the electrochemiluminescence method, with a standard value ranging from 0 to 7 ng/ml. All data were obtained from the Romanian National Health Agency.The average AFP serum levels in patients with compensated cirrhosis without HCC were 9.4 ng/ml (range 0.5 ÷ 406 ng/ml); 30.1% of patients had significantly increased levels of AFP (>15 ng/ml). High values of serum AFP in patients with compensated liver cirrhosis without HCC was correlated with more advanced age (p<0.001), severe necroinflammatory activity detected by FibroMax (p<0.001), severe NASH (p<0.001), severe steatosis (p<0.001), low platelets (p<0.001), increased values of AST and ALT (p<0.001).

Plasma osteopontin level as a diagnostic marker of hepatocellular carcinoma in patients with radiological evidence of focal hepatic lesions.

Hepatocellular carcinoma is one of the most aggressive malignant tumors and has limited treatment options. Needle-guided biopsies have been utilized as a tool to diagnose malignant focal hepatic lesions. These techniques are discouraged because of their complications. Nowadays, alpha fetoprotein is the most widely used tumor marker for screening and diagnosis of hepatocellular carcinoma. Nevertheless, this marker has limitations. The diagnostic role of plasma osteopontin as an adjuvant or alternative marker to alpha fetoprotein to detect hepatocellular carcinoma in Egyptian patients with focal hepatic lesions was evaluated in this study. Eighty participants were recruited from the Egyptian National Liver Institute and were self-assigned to three groups, namely, focal hepatic lesions (n = 40), liver cirrhosis (n = 20), and controls (n = 20). Participants' plasma osteopontin and serum alpha fetoprotein levels were determined and were compared across the three groups. The discriminatory ability of plasma osteopontin for hepatocellular carcinoma was lower than that of alpha fetoprotein. Osteopontin and alpha fetoprotein were not correlated with each other. Neither the gender nor the age of the patients showed a significant association with plasma osteopontin level. Measuring plasma osteopontin level alone has no advantage over serum alpha fetoprotein in patients with focal hepatic lesions due to chronic liver disease.

SAT-078 - Prognostic impact of serum alpha-fetoprotein in patients with hepatocellular carcinoma: an international collaborative study

SAT-078 - Prognostic impact of serum alpha-fetoprotein in patients with hepatocellular carcinoma: an international collaborative study

Development and application of a fluorescence protein microarray for detecting serum alpha-fetoprotein in patients with hepatocellular carcinoma.

ObjectiveTo develop a simple, effective, time-saving and low-cost fluorescence protein microarray method for detecting serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC).MethodNon-contact piezoelectric print techniques were applied to fluorescence protein microarray to reduce the cost of prey antibody. Serum samples from patients with HCC and healthy control subjects were collected and evaluated for the presence of AFP using a novel fluorescence protein microarray. To validate the fluorescence protein microarray, serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA).ResultsA total of 110 serum samples from patients with HCC (n = 65) and healthy control subjects (n = 45) were analysed. When the AFP cut-off value was set at 20 ng/ml, the fluorescence protein microarray had a sensitivity of 91.67% and a specificity of 93.24% for detecting serum AFP. Serum AFP quantified via fluorescence protein microarray had a similar diagnostic performance compared with ELISA in distinguishing patients with HCC from healthy control subjects (area under receiver operating characteristic curve: 0.906 for fluorescence protein microarray; 0.880 for ELISA).ConclusionA fluorescence protein microarray method was developed for detecting serum AFP in patients with HCC.

Pigment epithelium-derived factor and matrix metalloproteinase-9 in liver cirrhosis.

Background/Aim:The aim of this study was to assess the role of serum pigment epithelium-derived factor (PEDF) and matrix metalloproteinase-9 (MMP-9) in progression of liver cirrhosis and development of hepatocellular carcinoma (HCC).Patients and Methods:Serum levels of PEDF and MMP-9 were tested in 212 patients with liver cirrhosis and in a control group of 30 healthy volunteers. HCC was diagnosed in 45 of the 212 patients studied (21%).Results:Serum PEDF and MMP-9 were higher in the study group than that in the control group (P < 0.001). In patients with alcoholic or mixed (alcoholic and viral hepatitis-related) cirrhosis, serum PEDF was higher than that in other patients (13970.2 ± 13406.9 ng/ml vs. 8563.5 ± 9602.7 ng/ml, P = 0.008). In patients with viral hepatitis-related cirrhosis, significantly higher PEDF levels were recorded in those with HCC (13429.1 ± 12045.8) than that in patients without HCC (6660.1 ± 7927.1; P = 0.04). There was a trend for higher serum MMP-9 in patients with HCC (5778.7 ± 12426.6 vs. 1389.8 ± 1944.7 in those without HCC; P = 0.07). Significant negative correlation between serum MMP-9 and serum alpha-fetoprotein in patients with HCC was observed (r = −0.54; P = 0.04).Conclusion:Serum PEDF and MMP-9 could be auxiliary markers in diagnosis of HCC, especially in patients with low alpha-fetoprotein level. Alcohol consumption can affect serum PEDF.

Changes in serum alpha fetoprotein in patients with recurrent hepatocellular carcinoma following hepatectomy.

To study the change in serum alpha fetoprotein (AFP) of patients with recurrent hepatocellular carcinoma (HCC) after curative resection and to analyze its effect on the survival. We prospectively collected 981 consecutive patients with post-resectional recurrent HCC between 2005 and 2010 at the Eastern Hepatobiliary Surgery Hospital. According to the change of AFP from the initial stage to recurrent stage, the patients were divided into stable-L (20 ng/mL to 20 ng/mL, n = 296), stable-M (20-400 ng/mL to 20-400 ng/mL, n = 102), stable-H (400 ng/mL to 400 ng/mL, n = 212), decreasing (n = 287), and increasing (n = 84) groups. The overall survival (OS) and recurrence to death survival (RTDS) were analyzed using Kaplan-Meier method. Multivariate analysis was performed by Cox proportional hazards regression. The stable-H/increasing and stable-L/decreasing groups had the lowest and highest 5-year OS and RTDS rates (10.8%/18.8% vs 56.3%/55.0%; 3.4%/5.1% vs 37.7%/33.2%; both P < 0.001), while the stable-M group had the lower rates, which were 29.8% and 23.6% (for OS and RTDS: vs stable-L, P < 0.001 and 0.002; vs deceasing, P = 0.001 and 0.012; vs increasing, P = 0.113 and 0.011; vs stable-H, both P < 0.001). Cox regression analysis showed that AFP inconsistency was an independent factor affecting RTDS (decreasing vs stable-L, hazard ratio: 1.10, 95% confidence interval: 0.79-1.54, P = 0.575; increasing vs stable-L, 2.93, 2.06-4.16, P < 0.001). The AFP inconsistency was an important prognostic factor for recurrent HCC.

Abstract 3247: SAMe versus placebo for the reduction of serum AFP in patients with hepatitis C cirrhosis and moderately elevated AFP: A randomized, placebo-controlled, double-blind phase II trial

Abstract Background: Hepatocellular carcinoma (HCC) is a common complication of hepatitis C virus related cirrhosis (HCV-C). Alpha-fetoprotein (AFP) has been proposed as a biomarker of HCC risk. S-adenosylmethionine (SAMe) is a food supplement that has an excellent safety profile. The use of SAMe as a chemopreventive is based on abnormalities in methionine cycle (with decreased SAMe levels) in patients with cirrhosis, increased risk of HCC in experimental animals deprived of SAMe, and the prevention of liver cancer by SAMe administration in animal models of chemically-induced HCC. Methods: This was a prospective, randomized, placebo-controlled, double-blind phase IIb trial to determine if SAMe (up to 2.4 grams/day) for 24 weeks reduced serum AFP levels in patients with HCV-C. Inclusion criteria: lab evidence of HCV-C (platelet count &amp;lt;150,000/mm3), AFP 15-100 ng/mL (normal less than 9 ng/mL). Exclusion criteria: non-HCV liver diseases, decompensated HCV-C (MELD&amp;gt;15), or history of, or mass suspicious for HCC. Primary outcome was decline in AFP between week 0 and 24. Secondary outcomes: change in other HCC-related markers (des-gamma carboxyprothrombin, AFP-L3), blood tests for HCV RNA, SAMe metabolites, serum markers of oxidative stress, and quality of life. Results: A total of 110 patients were enrolled and 87 completed study. After the 24-week treatment, AFP declined among patients receiving SAMe (-1.9 ng/mL) and increased among patients receiving placebo (+5.9 ng/mL; p=0.16). Neither des-gamma carboxyprothrombin (DCP) nor AFP-L3 changed significantly with SAMe treatment. There were no significant differences in serum HCV RNA between groups. Blood levels of SAMe and S-adenosylhomocysteine (SAH) increased 3-5 fold among patients receiving SAMe and were unchanged in placebo group (p&amp;lt;0.01). Serum glutathione and methionine did not change significantly. Several components of quality of life improved among patients receiving SAMe. There were 5 serious adverse events in the placebo group and 7 in the SAMe group; none were attributable to SAMe. Conclusions: SAMe administration for 24 weeks in patients with HCV-C and elevated AFP did not decrease AFP significantly nor alter liver function. SAMe significantly increased serum SAMe and SAH levels, but did not alter serum glutathione level or serum markers of oxidative stress. Citation Format: Timothy Morgan, Frank L. Meyskens, John Hoefs, Ke-Qin Hu, Tarek Hassanein, Thomas D. Boyer, Neville R. Pimstone, Kathy Osann, Rachel Gonzalez, L M. Rodriguez. SAMe versus placebo for the reduction of serum AFP in patients with hepatitis C cirrhosis and moderately elevated AFP: A randomized, placebo-controlled, double-blind phase II trial. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3247. doi:10.1158/1538-7445.AM2014-3247

Plasma Osteopontin Level as a Diagnostic Marker of Hepatocellular Carcinoma in Patients with Radiological Evidence of Focal Hepatic Lesions

Hepatocellular carcinoma is one of the most aggressive malignant tumors and has limited treatment options. Needle-guided biopsies have been utilized as a tool to diagnose malignant focal hepatic lesions. These techniques are discouraged because of their complications. Nowadays, alpha fetoprotein is the most widely used tumor marker for screening and diagnosis of hepatocellular carcinoma. Nevertheless, this marker has limitations. The diagnostic role of plasma osteopontin as an adjuvant or alternative marker to alpha fetoprotein to detect hepatocellular carcinoma in Egyptian patients with focal hepatic lesions was evaluated in this study. Eighty participants were recruited from the Egyptian National Liver Institute and were self-assigned to three groups, namely, focal hepatic lesions (n = 40), liver cirrhosis (n = 20), and controls (n = 20). Participants' plasma osteopontin and serum alpha fetoprotein levels were determined and were compared across the three groups. The discriminatory ability of plasma osteopontin for hepatocellular carcinoma was lower than that of alpha fetoprotein. Osteopontin and alpha fetoprotein were not correlated with each other. Neither the gender nor the age of the patients showed a significant association with plasma osteopontin level. Measuring plasma osteopontin level alone has no advantage over serum alpha fetoprotein in patients with focal hepatic lesions due to chronic liver disease.

CSF and serum AFP in patients without gestational or neoplastic AFP-secretion

Background. The measurement of alpha-fetoprotein (AFP) in cerebrospinal fluid (CSF) is important for the diagnosis of intracranial or intraspinal trophoblastic tumors. The current study was performed to establish reference values for AFP in CSF and to explore the relationship of CSF AFP and serum AFP in patients. Material and methods. CSF samples were obtained from 351 inpatients admitted because of various neurological diseases, excluding those who were pregnant, had active liver disease, or who had trophoblastic or other malignant tumors. In 256 of the 351 patients, paired samples of CSF and serum were obtained. Both CSF AFP and serum AFP were measured. The 97.5th percentile and maximum value of CSF AFP were obtained. The CSF AFP and serum AFP concentrations in each of the 256 paired samples were compared. Results. The 97.5th percentile and maximum value of CSF AFP concentration for overall participants were 1.042 and 1.950 g/L, respectively. The CSF AFP concentration was found to be higher than the simultaneous serum AFP concentration only in 1.6% (4/256) of participants. Conclusions. The reference value determined in this study for CSF AFP is significantly lower than that usually used in clinical practice. A CSF AFP concentration higher than the simultaneous serum AFP concentration but lower than the upper reference limit does not necessarily suggest abnormal intrathecal AFP-secretion.

Alpha-fetoprotein has no prognostic role in small hepatocellular carcinoma identified during surveillance in compensated cirrhosis

Alpha-fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha-fetoprotein in patients with well-compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent. Among the 3,027 patients included in the Italian Liver Cancer study group database, we selected 205 Child-Pugh class A and Eastern Cooperative Group Performance Status 0 patients with cirrhosis with a single HCC ≤ 3 cm of diameter diagnosed during surveillance who were treated with curative intent (hepatic resection, liver transplantation, percutaneous ethanol injection, radiofrequency thermal ablation). Patients were subdivided according to alpha-fetoprotein serum levels (i.e., normal ≤ 20 ng/mL; mildly elevated 21-200 ng/mL; markedly elevated >200 ng/mL). Patient survival, as assessed by the Kaplan-Meier method, was not significantly different among the three alpha-fetoprotein classes (P = 0.493). The same result was obtained in the subgroup of patients with a single HCC ≤ 2 cm (P = 0.714). An alpha-fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve = 0.536, 95% confidence interval = 0.465-0.606) to discriminate between survivors and deceased patients. Alpha-fetoprotein serum levels have no prognostic meaning in well-compensated cirrhosis patients with single, small HCC treated with curative intent.

Predictors of alpha‐fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a–ribavirin combination therapy

Elevated serum alpha-fetoprotein (AFP) levels are noted in patients with chronic hepatitis C (CHC) without hepatocellular carcinoma (HCC). The change in AFP levels after treatment with pegylated interferon and ribavirin (Peg-IFN/RBV) combination therapy is still unknown. The aim of this study was to investigate the predictors of elevated serum AFP in patients with CHC, and its change after Peg-IFN/RBV therapy. A total of 123 patients, intended to receive pegylated interferon alfa-2a plus ribavirin therapy, were enrolled. Eighty-three patients had complete treatment and received follow up for and additional 24 weeks. The factors that may affect the elevation of pretreatment AFP and the normalization of post-treatment AFP were determined. The mean AFP level was 18.5 +/- 63.0 ng/mL (range, 1.3-676.0 ng/mL); 41 (33.3%) of the 123 patients had elevated serum AFP (more than 10 ng/mL) at baseline. A multivariate logistic regression analysis disclosed that older age (odds ratio [OR], 1.093; 95% confidence interval [CI], 1.015-1.177; P = 0.018), more advanced METAVIR fibrosis stage (OR, 5.237; 95% CI, 1.244-22.037; P = 0.024), a higher aspartate aminotransferase (AST) level (IU/L) (OR, 1.020; 95% CI, 1.008-1.033; P = 0.001), and lower platelet count (x10(9)/L, OR, 0.985; 95% CI, 0.968-0.994; P = 0.003) were independent determinants of pretreatment AFP elevation. After treatment, 72 of 83 (86.7%) cases were found to have normal post-treatment AFP levels (<10 ng/mL) at the end of follow up (EOF). Post-treatment negativity of the chronic hepatitis C virus (HCV)-RNA (OR, 10.014; 95% CI, 1.000-100.329; P = 0.050) and the post-treatment platelet count (x10(9)/L) (OR, 1.025; 95% CI, 1.001-1.050; P = 0.040) were associated with normal AFP at EOF. AFP progressively decreased with significant differences starting from the 12th week after treatment to the end of treatment, and was lowest at the EOF date for the sustained viral response (SVR) group. On the contrary, the non-SVR group did not have an AFP change during and after treatment. Older age, low platelet count, higher AST levels, and advanced fibrosis predisposed chronic hepatitis C patients without HCC to have elevated serum AFP levels. After Peg-IFN/RBV combination therapy, a higher platelet count and HCV viral eradication were determinants of normal AFP at EOF. Serial AFP levels decreased after treatment, presenting in a time-dependent manner, specifically for the SVR group.

Serum alpha-fetoprotein levels in patients with advanced hepatitis C: Results from the HALT-C Trial

Alpha-fetoprotein (AFP) has been useful in the diagnosis of hepatocellular carcinoma (HCC) but lacks specificity. We assessed serum AFP among patients with chronic hepatitis C and advanced fibrosis to establish predictors of AFP elevations and changes with antiviral therapy. Serum AFP was measured at baseline and on therapy in patients in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C). AFP levels were correlated with patient demographic and clinical features. Baseline AFP was > or = 20 ng/mL in 191 of 1145 patients (16.6%). Mean AFP values were significantly higher in patients with cirrhosis than in those with bridging fibrosis (22.5 vs. 11.4 ng/mL, P < 0.0001). Factors independently associated with raised serum AFP in patients with cirrhosis were female gender, black race, decreased platelet count, increased serum AST/ALT ratio, serum ferritin, and Mallory bodies in liver biopsies. Serum AFP levels decreased significantly during therapy with pegylated interferon alpha-2a and ribavirin. HCC was identified in six subjects, only three of whom had AFP > 20 ng/mL. Among patients with advanced chronic hepatitis C, serum AFP values are frequently elevated, even in the absence of HCC. Factors associated with raised AFP include severity of liver disease, female gender and black race. Serum AFP levels decline during antiviral therapy.

Fulminant hepatic failure

Abstract Analysis of the first 150 cases collected from 73 centers reporting to the Fulminant Hepatic Failure Surveillance Study showed that 80 patients had presumable viral hepatitis, of whom 62 died. Of 41 patients who had recent surgery, 36 died. In 35 patients massive liver necrosis developed less than three weeks after halothane anesthesia, and 27 (77 per cent) of these had multiple exposures to halothane. The risk from halothane is small, but this complication was present in nearly one quarter of the cases reported in our study. When the use of halothane is desired, multiple exposure should be avoided, if possible. Moreover, postoperative fever after exposure to halothane, otherwise "unexplained," is an important warning sign, and should be thoroughly investigated and taken into consideration when further exposure to this anesthetic is contemplated. The physician prescribing halothane must balance need against risk.

Clinical, Virologic, and Pathologic Significance of Elevated Serum Alpha-fetoprotein Levels in Patients with Chronic Hepatitis C

Elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C is not uncommonly seen, but the pathogenesis of this phenomenon remains unclear. The aims of this study were to assess the prevalence of elevated serum AFP in patients with chronic hepatitis C and to evaluate the clinical, virologic, and histopathologic significance of this phenomenon. One hundred and fifteen Chinese patients with a histologic diagnosis of chronic hepatitis C were enrolled. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 2 years' follow-up. Of the 115 patients, 33 (29%) had elevated serum AFP (more than 12 ng/mL). There was a significantly lower mean serum albumin (4.0 +/- 0.1 vs. 4.3 +/- 0.1 gm/dL, p <0.001) and higher mean scores for periportal necroinflammation (3.3 +/- 0.3 vs. 2.3 +/- 0.2, p = 0.007) and fibrosis (2.3 +/- 0.2 vs. 1.1 +/- 0.1, p < 0.001) in patients with elevated serum AFP when compared with patients without elevated serum AFP. Patients with elevated serum AFP had significantly more incidences of genotype 1b infection when compared with patients without elevated serum AFP (77% vs. 51%, p = 0.021). Mean serum hepatitis C virus (HCV) RNA titer showed no significant difference between the two groups. Multivariate logistic regression analysis showed that as serum albumin of less than 4.2 gm/dL, a histology fibrotic score of more than 3, and HCV genotype 1b infection were significantly independent predictors associated with elevated serum AFP. In conclusion, elevated serum AFP levels were significantly correlated with lower serum albumin levels, advanced fibrosis/cirrhosis, and genotype 1b infection in patients with chronic hepatitis C.

Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour.

Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N-linked, and four were O-linked, to the protein backbone. The structure of the N-linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O-linked glycans (three mucin O-GalNAc type glycans with variable degrees of sialylation, one O-HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O-GalNAc type glycans was supported by the prediction of potential O-GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT. © 1999 Cancer Research Campaign © 1999 Cancer Research Campaign

Radioimmunoassay of serum alpha-fetoprotein in patients with different maliganant tumors.

The level of serum alpha-fetoprotein (AFP) was estimated by radioimmunoassay in 153 normal healthy Malysians of different ethnic groups. The mean level was 7.5 In1/ml (SD 2.28InU/ml). Among 330 patients with malignant tumors, 11 had increased levels of AFP. The only patient who had hepatoma had a very high level of serum AFP. High levels were also found in three of four patients with dysgerminoma of the ovary, in the only two patients with carcinoma of the testis, and in one patient with secondary carcinoma of the humerus of unknown origin. Lower, but significantly increased levels were observed in one patient (of 48) with breast carcinoma, one patient (of 8) with basal cell carcinoma of the nose, one patient (0f 27) with carcinoma of the lung, and one patient (of 59) with nasopharynegeal carcinoma.