Abnormal Alpha-fetoprotein Levels Research Articles

Systems Thinking Approach on Foetal Abnormalities Due to Alpha-Fetoprotein Level

Foetal complications due to abnormal Alpha-Fetoprotein (AFP) levels are becoming a serious matter. The risk of adverse pregnancy outcomes (APOs) is substantially greater in the raised maternal serum-alpha fetoprotein (MS-AFP) group than in the normal MS-AFP groups. The top three APOs in terms of occurrence rate in the increased MS-AFP group were structural foetal abnormalities, spontaneous abortion, and premature delivery. Low levels of AFP in the maternal may indicate a risk of Down syndrome. This is a critical matter that needs to be investigated and dealt with seriously, based on the systems thinking approach. This research aims to investigate screening methods on AFP foetal based on system thinking approach. The main purpose of the study is to provide an analytical and integrated approach to deal with foetal complications due to AFP level. This integrated approach comprises various analytical aspects, including conceptual framework, data analysis, evaluation of the screening methods. How systems thinking can contribute to improve all these aspects of foetal complications will be investigated. The methodology will enable to conduct a detailed explanation to the major problems of AFP in the form of a causal loop diagram based on the holistic view of the systems thinking approach. It is expected that the application of a systems approach could provide an effective method of analysis for understanding and managing the foetal abnormalities by considering all aspects in a holistic manner and clearer methods of intervention to reduce the cases.

Long Non-Coding RNA MAFG-AS1 as a Potential Biomarker for Hepatocellular Carcinoma: Linkage with Tumor Features, Markers, Liver Functions, and Survival Profile

PurposeLong non-coding RNAs musculoaponeurotic fibrosarcoma oncogene family, protein G antisense 1 (lnc-MAFG-AS1) regulates hepatocellular carcinoma (HCC) progression and treatment resistance in multiple ways, while its engagement in HCC clinical management remains obscure. The current study aims to explore the relationship of lnc-MAFG-AS1 with tumor features, liver function indexes, tumor markers, and prognosis in HCC patients.MethodsOne hundred and fifty-two surgical HCC patients who underwent tumor resection were retrospectively analyzed. Their tumor and adjacent tissues were acquired and then proposed to reverse transcription-quantitative polymerase chain reaction to detect lnc-MAFG-AS1 expression.ResultsLnc-MAFG-AS1 expression was increased in HCC tumor tissue than in adjacent tissue [median (interquartile range): 2.730 (1.685–4.198) vs. 0.990 (0.703–1.468), p < 0.001], with a high area under the curve [0.889, 95% confidence interval (CI): 0.854–0.924] to distinguish them via receiver operating characteristic curve analysis. Tumor lnc-MAFG-AS1 was linked with multifocal nodules (p < 0.001), increased Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.018), and elevated China Liver Cancer (CNLC) stage (p = 0.008), which also correlated with an abnormal alpha-fetoprotein (AFP) level (p = 0.004), However, lnc-MAFG-AS1 was not linked with other disease conditions, tumor properties, liver function indexes, or tumor markers (all ps > 0.05). In addition, patients with a high expression of lnc-MAFG-AS1 exhibited worse overall survival than those with a low expression of lnc-MAFG-AS1 [median (95% CI): 34.0 (24.5–43.5) vs. 48.0 (41.5–54.5) months] (p = 0.011), which was further validated by univariate Cox’s analysis [hazard ratio (HR) = 1.827, p = 0.013] and multivariate Cox’s analysis (HR = 1.697, p = 0.040).ConclusionLnc-MAFG-AS1 relates to multifocal nodules, increased BCLC stage, elevated CNLC stage, and abnormal AFP level and predicts pejorative prognosis in HCC patients.

Exploratory study of microparticle transcatheter arterial chemoembolization combined with resection for huge hepatocellular carcinoma

To investigate the safety and clinical efficacy of microparticle transcatheter arterial chemoembolization (mTACE) combined with surgical resection for the treatment of huge hepatocellular carcinoma (hHCC; ≥ 10 ​cm). A retrospective descriptive study was conducted to gather the clinical data of nine patients with hHCCs treated with mTACE combined with resection in Beijing Tsinghua Changgung Hospital from December 2016 to July 2020. The outcome were as follows: (1) the excellent effect and adverse reactions of mTACE and (2) the efficacy and safety of perioperative resection. Count data were expressed as absolute numbers and percentages. The measurement data of the normal distribution is represented by X ​± ​S, and the measurement data of the skewed distribution are represented by M (range). A paired t-test was used to compare the data of the same patient. p values <0.05 are considered statistically significant. (1) Regarding the efficacy and safety of mTACE, all nine hHCCs were treated with mTACE one time. The tumor necrosis rate after particle TACE was (77.6 ​± ​15.7)% (51.7%–100%); according to the modified response evaluation criteria in solid tumors, the objective response was partial response in eight patients and complete response in one patient. The alpha fetoprotein (AFP) level was abnormal in six cases (>20 ​ng/mL), of which three cases exceeded the maximum value (>30,000 ​ng/mL) pre-mTACE. In six patients with abnormal AFP levels, the AFP level decreased in five patients, with a median percentage of 74.5% (35.2%–96.0%). The PIVKA-II level in nine patients was > 40 ​mAU/mL before mTACE and decreased to varying degrees after mTACE. The median percentage of decline was 76.0% (4.5%–99.8%). The maximum diameter of the tumor decreased from (13.9 ​± ​1.9) cm (11.0–16.4 ​cm) to (12.8 ± 1.9) ​cm (10.4–15.6 ​cm) ( P ​= ​0.001) before surgical resection. Prior to the surgical resection, the tumor volume decreased from (897 ​± ​244) mL (436–1250 ​mL) to (750 ​± ​291) mL (260–1130 ​mL) ( P ​= ​0.001), and the residual liver volume/standard liver volume increased from (42.8 ​± ​12.8)% (25.8%–61.3%) to (50.2 ​± ​14.9)% (28.8%–67.4%) ( P ​= ​0.008). All patients had embolism syndrome such as fever and abdominal pain in varying degrees, and no serious complications such as liver abscess, liver and kidney failure, or ectopic embolism were noted. (2) For perioperative efficacy and safety, all lesions were successfully resected in (31 ​± ​11) days (14–48 days) after mTACE. The operation time was (395 ​± ​79) min (296–540 ​min), and the amount of intraoperative bleeding was (433 ​± ​158) mL (200–600 ​mL). Complications such as biliary fistula, abdominal bleeding, liver and kidney failure, or abdominal infection were not found. The postoperative hospital stay was (13 ​± ​4) days (9–19 days). No tumor invasion was found at the cutting edge, and hepatic vein invasion was observed in one case. (3) The follow-up ended in November 2021, with a median follow-up of 34 months (16–46 months). Recurrence or distant metastasis occurred in four patients, of which two patients died. The survival times were 18 and 31 months, respectively. The other two patients were followed up for 34 and 41 months. The remaining five patients were followed up for 16–46 months without antitumor treatment or disease progression. mTACE combined with tumor resection is feasible for the treatment of patients with hHCC, which needs to be further confirmed by prospective studies.

GT-Repeat Polymorphism in the HO-1 Gene Promoter Is Associated with Risk of Liver Cancer: A Follow-Up Study from Arseniasis-Endemic Areas in Taiwan.

The induction of heme oxygenase-1 (HO-1) has been shown to have therapeutic potential in experimental models of hepatitis and liver fibrosis, which are closely related to liver cancer. In humans, HO-1 induction is transcriptionally modulated by the length of a GT-repeat [(GT)n] in the promoter region. We aimed to investigate the effect of HO-1 (GT)n variants on liver cancer in a human population. We determined the HO-1 genotype in 1153 study subjects and examined their association with liver cancer risk during a 15.9-year follow-up. Allelic polymorphisms were classified as short [S, <27 (GT)n] or long [L, ≥27 (GT)n]. Newly developed cancer cases were identified through linkage to the National Cancer Registry of Taiwan. Multivariate Cox regression analysis was used to evaluate the effect of the HO-1 (GT)n variants. Alpha-fetoprotein (AFP) and cirrhosis history were also examined. The S/S genotype was found to be significantly associated with liver cancer risk, compared to the L/S and L/L genotypes. The S/S genotype group also had a higher percentage of subjects with abnormal AFP levels than other groups. There were significant percentages of cirrhosis among groups who carried S-alleles. Our findings indicate that short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from liver cirrhosis/cancer.

Clinical characteristics and predictors of outcomes in patients with fibrolamellar carcinoma: An eleven-year analysis of the National Cancer Database (NCDB).

413 Background: Fibrolamellar carcinoma (FLC) is a very rare liver tumor, comprising only 1% of all primary liver tumors in the United Sates. There is no standard of care for unresectable disease. Current practices are based on small retrospective studies and case series. We aim to analyze the clinicopathologic factors and treatment modalities affecting overall survival (OS) in FLC. Methods: Using the National Cancer Data Base (NCDB), we identified 496 patients diagnosed with FLC between 2004 and 2015. Simple descriptive statistics were created for all covariates. Survival data was available on 461 patients. Kaplan Meier Survival analysis was used for unadjusted results, and Cox proportional hazards model was used for multivariable analysis. The objective of the study is to identify predictors of survival in FLC. Results: The median age at diagnosis was 32 (range 18-90) years. Fifty-six percent were males. Stage distribution included 114 (31.2%), 43 (11.8%), 89 (24.3%) and 120 (32.8%) patients for stages I, II, III and IV, respectively. Median follow-up was 24 months. Surgery of the primary site was performed on 282 (56.9%) of patients, 146 (51.2%) of which had regional lymph node dissection. Seventy (47.9%) patients had pN+ disease. Among patients with available serum alpha fetoprotein (AFP) data, 146 (42.5%) had abnormal AFP levels (&gt; 20 ng/mL). Median OS by stage were 78.5, 87.2, 18.6, and 10.6 months for stages I, II, III, and IV, respectively. Multivariate analysis showed that age (HR 1.01, p &lt; 0.0001), pN+ (HR 2.31, p = 0.0003), and abnormal AFP (HR 1.69, p = 0.0003) were negative predictors of survival. Among metastatic patients, 57 (11.4%) had metastatectomy. Metastatectomy improved overall survival in stage IV FLC, HR 0.51 (95% CI 0.29-0.89). Conclusions: Independent predictors of decreased OS in patients with FLC include age, pN+ and abnormal AFP. Metastatectomy improved OS. FLC is a rare disease entity that warrants further investigations to better delineate optimal treatment approaches.

Serum angiopoietin-2 level as a predictor of tumor invasiveness in patients with hepatocellular carcinoma

Background. Because hepatocellular carcinoma (HCC) has important angiogenic activity, the expression of angiopoietin-2 (Ang-2) may have a pathogenic role. The information about the influence of serum Ang-2 (sAng-2) in patients with HCC is scarce. Aims. The aim was to assess the association between sAng-2 levels and characteristics of tumor and liver disease in patients with HCC. Methods. sAng-2 concentrations in peripheral (sAng-2-P) and hepatic (sAng-2-H) veins were analyzed by ELISA in 33 patients with chronic liver disease who underwent a splanchnic hemodynamic study. Thirty-two patients received treatment for HCC. Results. The median age was 61 years and 79% were male. Hepatitis C infection (70%) was the main etiology. Most patients were Child-Pugh grade A (72.7%). sAng-2-P and sAng-2-H were well correlated (r = 0.95; p < 0.0001). A significant association was found between sAng-2-H and lobar tumor extension, vascular thrombosis, BCLC staging, infiltrating pattern, abnormal alpha-fetoprotein level, fulfillment of the Milan criteria, and performance of nonsystemic treatment. sAng-2-H also showed a significant correlation with the MELD score (r = 0.49; p = 0.007), albumin (r = -0.63; p < 0.001), and HVPG (r = 0.44; p = 0.02). Eleven patients received treatment with radiofrequency ablation and eight with transarterial chemoembolization. HCC treatment did not influence the sAng-2 concentration while the necrosis response to treatment was not influenced by previous sAng-2 levels. Conclusions. Ang-2 seems to play an important role in the angiogenic processes of HCC and its serum levels are associated with tumor characteristics and invasive behavior. Our results suggest that Ang-2 is not related with treatment response and its level is not modified by treatment.

Treatment of primary liver cancer using highly-conformal radiotherapy with kv-image guidance and respiratory control

PurposeTo implement a reliable, practical and reproducible treatment procedure, based on in-room kV-image guidance and respiratory control, for liver cancer patients treated with high dose conformal radiotherapy using a commercially available treatment system. Materials and methodsCT stimulation was conducted under voluntary breath hold or gating using the Varian Real-time Position Management™ (RPM) System. Treatments were delivered daily under kV image guidance to verify the diaphragmatic or lipiodol-defined tumor position. ResultsThirty-three patients with liver confined hepatocellular carcinoma were treated between May 2006 and Dec 2009. After a median follow-up period of 16.5months (range: 3.5–40.7), all but 2 patients demonstrated radiological tumor regression. Eight patients (24%) achieved complete remission. The median tumor shrinkage was 42% (27–100%). Subsequent in-field tumor progression was observed in only three patients (10%). For the 23 patients with abnormal alpha fetoprotein level, 22 of them showed biochemical response with a median AFP level drop of 78%. The treatment was well tolerated: Grade 3 toxicities occurred in 5 patients (1 leucopenia, 1 elevated liver enzyme and 3 elevated bilirubin level) but there was no grade 4 toxicity or treatment related death. The 1year overall survival rate is 71.7% and median survival time is 17.2months (3.5–40.7months). ConclusionsExcellent treatment results with minimal toxicities could be achieved in a clinical environment with a commercially available highly sophisticated radiotherapy system.

Substitution of amino acid 70 in the hepatitis C virus core region of genotype 1b is an important predictor of elevated alpha‐fetoprotein in patients without hepatocellular carcinoma

Previous studies identified amino acid (aa) substitutions of the hepatitis C virus core region of genotype 1b (HCV-1b core region) and elevated serum alpha-fetoprotein (AFP) levels as predictors of poor virologic response to pegylated interferon (PEG-IFN) plus ribavirin (RBV), and also as risk factors for hepatocarcinogenesis. The present study evaluated the impact of aa substitutions of HCV-1b core region on AFP, as a surrogate marker of hepatocarcinogenesis, on AFP levels in 569 Japanese patients with HCV-1b but without HCC, and investigated the predictive factors of elevated AFP (> or =11 microg/L). High AFP levels were detected in 27.4% of the patients. The rate of hepatocarcinogenesis in a group of 109 patients who received IFN monotherapy and followed-up for 15 years, was significantly higher in patients with abnormal than normal AFP. Multivariate analysis of 569 patients identified fibrosis stage (F3,4), aspartate aminotransferase (> or =76 IU/L), substitution of aa 70 (glutamine or histidine), and platelet count (<15.0 x 10(4)/microl) as significant determinants of elevated AFP. In 49 patients with abnormal AFP levels and substitutions at aa 70 who were treated with PEG-IFN + RBV, the rate of normalization of AFP was significantly lower in non-virological responders (28.6%) than in transient (71.4%) and sustained (100%) virological responders. The results indicated that substitution of aa 70 of HCV-1b core region is an important predictor of elevated AFP in non-HCC patients, and that eradication of the mutant virus normalizes AFP. The results highlight the importance of eradication of mutant type virus of aa 70 for reducing the risk of hepatocarcinogenesis.

Perinatal outcome after prenatal diagnosis of placental abnormalities and abnormal alpha-fetoprotein levels

ITIES AND ABNORMAL ALPHA-FETOPROTEIN LEVELS WILLIAM DOBAK, NORA DOYLE, DIAN FOGLE, METHODIUS TUULI, CHRISTINE L. PROUDFIT, PATRICE L. BASANTA-HENRY, TAMULA M. PATTERSON-THOMAS, CHRISTOPHER D. HARVEY, KHADEJA HAYE, EMAD I. ATTA, Emory University, Gynecology & Obstetrics, Atlanta, Georgia OBJECTIVE: Elevated levels of alpha-fetoprotein have been associated with obstetric complications such as neural tube defects, growth restriction, abruption, preterm delivery, fetal demise and preeclampsia. Prior studies have shown that the higher the level of alpha-fetoprotein, the greater the risk for adverse outcome. We sought to identify among patients with abnormal placentas, the correlation of alpha-fetoprotein levels with adverse perinatal outcomes. STUDY DESIGN: Cases of placental abnormalities diagnosed prenatally on ultrasound were identified. Alph-fetoprotein levels for each patient were abstracted from results of the serum quadruple screen. Information on maternal demographics, prenatal sonographic findings, pregnancy complications, antenatal intervention, and perinatal outcomes were obtained by reviewing the medical records and our perinatal database. Perinatal outcomes among patients with both placental abnormalities and high alpha-fetoprotein levels (O2MOM) and those with only placental abnormalities were compared. Chi square, Fisher’s exact test, ANOVA, T –test and logistic regression analysis were performed where appropriate with p less than 0.05 considered significant. RESULTS: In the 6 year period from November 2000 – June 2006 , 184 patients with abnormal placentas were diagnosed prenatally. Of these 71 had AFP values for analysis. Preterm birth (31.4%, p!0.05) and incidence of IUFD (8%, p!0.05) were significantly higher in the group with high AFP values as compared to those with normal AFP. No significant differences in chronic hypertension or cesarean delivery rate between the two groups was noted. CONCLUSION: Placental abnormalities are associated with an increased risk of pregnancy complications, the most common being IUGR, fetal loss, and preterm delivery. From our study the presence of high alpa-fetoprotein levels further increases these risks. Prenatal diagnosis of these two abnormalities may allow for identification and appropriate interventions to reduce these adverse perinatal outcomes. More studies are needed.

An Intensive Surveillance Program Detected a High Incidence of Hepatocellular Carcinoma Among Hepatitis B Virus Carriers With Abnormal Alpha-Fetoprotein Levels or Abdominal Ultrasonography Results

To study the incidence and treatment outcomes of hepatocellular carcinoma (HCC) detected in an intensive surveillance program (ISP) of hepatitis B virus (HBV) carriers. We screened 1,018 HBV carriers by serum alpha-fetoprotein (AFP) measurement and abdominal ultrasonography (AUS). Patients with an abnormal AFP level or AUS result were enrolled in an ISP that included Lipiodol computed tomography followed by AFP measurement/AUS every 3 months for 2 years and then every 6 months thereafter. The rest were on routine surveillance for 2 years. A total of 9,849 serum AFP measurements and 3,053 AUSs were performed. After a median follow-up of 4.12 years, we diagnosed 24 HCCs among 78 patients with abnormal screening test results at enrollment (group A); 23 HCCs among 93 patients with only abnormal surveillance test results during follow-up (group B); and nine HCCs among 847 patients with 2 years of normal surveillance (group C). Annual incidence of HCC in the ISP was 760.2 (95% CI, 538.4 to 1,073.7) per 100,000. Mean tumor sizes were 3.02, 2.91, and 4.82 cm in groups A, B, and C, respectively (P = .01). Tumor resection rate of the ISP was 36.2%, although another 29.8% of the patients were eligible for locoregional ablative therapy. This study illustrated that a high incidence of relatively small HCCs may be detected by using intensive surveillance of high-risk HBV carriers. However, the surgical resection rate was low, and we were not able to demonstrate clinical benefit with the early detection. Future surveillance studies should consider incorporation of therapy aimed at long-term control of small-sized tumors.

Pattern Analysis of Serum alpha-fetoprotein in the Early Diagnosis of Hepatocellular Carcinoma in Liver Cirrhosis

In a surveillance program for hepatocellular carcinoma (HCC), serum alpha-fetoprotein (AFP) was determined every 4 months in 164 patients with liver cirrhosis. Ultrasonography (US) was performed yearly or as dictated by abnormal AFP levels. During a follow-up of 32.5 +/- 20.8 months HCC was identified by US in 16 patients. In 9 of them the AFP levels rose steadily over 4 months, increasing 7, 8 and 12 months in 3 cases before the lesion became detectable by US. In 4 patients tumors developed despite persistently normal AFP levels. Nine more patients showed abnormal fluctuations of AFP but HCC was not detected. AFP sensitivity was higher at a low cut-off point (40 ng/ml) while specificity of the test appeared higher at the 200 ng/ml cut-off point. An AFP value rising steeply over a few months appeared more reliable than a fixed preset threshold in indicating carcinomatous transformation. Screening for AFP can be expected to uncover about 3/4 of HCC developing in cirrhotics with few false-positive reactions. The test may have a unique role in identifying a subset of liver tumors whose early expression is AFP production.