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Hepatology Communications Oct 2023Surveillance programs are strongly recommended in patients with liver cirrhosis for early detection of HCC development. Six-monthly ultrasound sonography is the most...
BACKGROUND AND AIMS
Surveillance programs are strongly recommended in patients with liver cirrhosis for early detection of HCC development. Six-monthly ultrasound sonography is the most reliable and commonly used technique, especially when associated with serum determination of α-fetoprotein, but different score systems have been proposed to overcome the unsatisfactory diagnostic accuracy of α-fetoprotein. The aim of this 12-year prospective study is to compare the gender, age, AFP-L3, AFP, des-gamma-carboxy prothrombin (GALAD) versus age, gender, bilirubin, albumin, and platelets and albumin-bilirubin scores in predicting HCC onset.
APPROACH AND RESULTS
A cohort of 545 consecutive patients with compensated advanced chronic liver disease without suspected focal lesions was followed up every 6 months by liver imaging and α-fetoprotein to detect HCC occurrence. Harrell's C-index for censored data was employed to evaluate the performance of any parameters or scores helping to predict HCC development. ROC curve analysis showed that the GALAD score was more accurate in evaluating HCC development than albumin-bilirubin and age, gender, bilirubin, albumin, and platelets. The AUC ranged from 0.7268 to 0.6851 at 5 and 10 years, both in the total cohort and in the sub-cohorts (viral hepatitis, NASH, and alcohol). The HCC Risk model was constructed using univariate and multivariate Cox proportional hazard regression analysis, showing a strong association of GALAD with HR > 1, p < 0.05, in the total and sub-cohorts, and a better risk prediction in the alcohol cohort, both alone and standardized with other blood parameters.
CONCLUSIONS
GALAD is the most reliable and accurate score system to detect HCC risk of development in patients with compensated advanced chronic liver disease.
Topics: Humans; alpha-Fetoproteins; Prospective Studies; Carcinoma, Hepatocellular; Liver Neoplasms; Albumins; Bilirubin; Ethanol
PubMed: 37708455
DOI: 10.1097/HC9.0000000000000262 -
Andrology Jan 2023Alfa-fetoprotein (AFP) is a serum glycoprotein highly produced during fetal development. While AFP synthesis drops dramatically after birth, AFP production only persists...
BACKGROUND
Alfa-fetoprotein (AFP) is a serum glycoprotein highly produced during fetal development. While AFP synthesis drops dramatically after birth, AFP production only persists or returns under specific pathological condition.
OBJECTIVE
We sought to investigate the rate of and the potential meaning of high AFP serum levels in men seeking first medical attention for couple's primary infertility.
MATERIALS AND METHODS
Socio-demographic and clinical data from 1803 non-Finnish, White-European primary infertile men were retrospectively analysed. AFP was routinely measured in each patient (high AFP was defined as >7 ng/ml). Men with history of liver diseases, testicular cancer, or other known causes of increased AFP levels were excluded from the final analysis. Semen analyses were based on the 2010 World Health Organization reference criteria. Descriptive statistics and logistic regression models tested the association between serum AFP and clinical variables. Possible nonlinear relationships were graphically explored with locally estimated scatterplot smoothing method.
RESULTS
Overall, high serum AFP level was found in 29 (1.7%) patients. Normal versus high AFP levels patients were comparable in terms of body mass index (BMI), Charlson Comorbidity Index, waist circumference, smoking habits, history of cryptorchidism, testicular volume, and serum hormones (i.e., follicle-stimulating hormone, luteinizing hormone, and total testosterone). Conversely, men with higher AFP levels were older (p = 0.02), had lower sperm concentration (p = 0.003), and were more frequently oligozoospermic and azoospermic (all p ≤ 0.03). At multivariate analysis, high AFP levels were independently associated with oligozoospermia (OR 3.79; p = 0.033) and azoospermia (OR 3.29; p = 0.006). Likewise, if AFP levels increase, patients were found to be older, with higher BMI and to have more comorbidities (all p < 0.05).
DISCUSSION
Unexplained high AFP levels account for almost 2% of cases in primary infertile patients without a previous history of associated disorders. Higher serum AFP levels are linked with aberrant sperm counts, older age, obesity, and a greater amount of comorbid conditions.
CONCLUSION
Despite the need for additional validation, these data suggest that serum AFP measurement might have a multifaceted role over the diagnostic work-up of males presenting for couple's infertility.
Topics: Humans; Male; Testicular Neoplasms; alpha-Fetoproteins; Sperm Motility; Infertility, Male; Retrospective Studies; Semen; Sperm Count; Testosterone; Follicle Stimulating Hormone
PubMed: 36116018
DOI: 10.1111/andr.13297 -
Scientific Reports Sep 2022Metastasis is crucial for the prognosis of hepatocellular carcinoma (HCC). Distinguishing the potential risk factors for distant metastasis in small HCC...
Metastasis is crucial for the prognosis of hepatocellular carcinoma (HCC). Distinguishing the potential risk factors for distant metastasis in small HCC (diameter ≤ 5 cm) is of great significance for improving the prognosis. HCC patients in the Surveillance, Epidemiology and End Results (SEER) registry with tumors ≤ 5 cm in diameter between January 2010 and December 2015 were retrieved. Demographic and clinicopathological metrics were extracted, including age, sex, race, marital status, tumor size, histological grade, T stage, N stage, M stage, alpha-fetoprotein (AFP), and liver fibrosis score. Univariate and multivariate logistic regression analyses were used to identify independent risk factors correlated with extrahepatic metastasis in small HCC. Propensity score matching (PSM) analysis was performed to balance the confounding factors in baseline characteristics. A total of 4176 eligible patients were divided into a non-metastasis group (n = 4033) and a metastasis group (n = 143) based on metastasis status. In multivariate analysis, larger tumor size, poor histological differentiation, regional lymph node metastasis, and elevated serum AFP levels were identified as independent risk factors for distant metastasis (P < 0.05), while age, sex, race, marital status, and liver fibrosis score were not associated with extrahepatic metastasis. After propensity score analysis, the AFP level was no longer associated with metastatic risk. The present study provided no evidence for a correlation between the clinical threshold of AFP and metastasis in small hepatocellular carcinoma.
Topics: Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Prognosis; alpha-Fetoproteins
PubMed: 36127436
DOI: 10.1038/s41598-022-19531-8 -
International Journal of Surgery... Dec 2023In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver...
Incorporation of protein induced by vitamin K absence or antagonist-II into transplant criteria expands beneficiaries of liver transplantation for hepatocellular carcinoma: a multicenter retrospective cohort study in China.
INTRODUCTION
In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver transplantation (LT) is essential. As a crucial diagnostic biomarker for HCC, protein induced by vitamin K absence or antagonist-II (PIVKA-II) has become one of the key indicators for assessing tumor recurrence risk after LT. This study aims to investigate the role of PIVKA-II in recipient selection and prognostic stratification.
METHODS
The clinicopathologic data of HCC patients undergoing LT from 2015 to 2020 in six Chinese transplant centers were collected. Univariate and multivariate analyses were performed to determine risk factors for disease free survival (DFS). Based on these risk factors, survival analysis was made by Kaplan-Meier method and their value in prognostic stratification was assessed.
RESULTS
A total of 522 eligible HCC patients with pre-LT PIVKA-II records were finally included in this study. Tumor burden>8 cm, α-fetoprotein>400 ng/ml, histopathologic grade III and PIVKA-II>240 mAU/ml were identified as independent risk factors for DFS. DFS of patients with PIVKA-II≤240 mAU/ml ( N =288) were significantly higher than those with PIVKA-II>240 mAU/ml ( N =234) (1-year, 3-year, and 5-year DFS: 83.2, 77.3, and 75.9% vs. 75.1, 58.5, and 50.5%; P <0.001). Compared with Hangzhou criteria ( N =305), incorporating PIVKA-II into Hangzhou criteria (including tumor burden, α-fetoprotein, and histopathologic grade) increased the number of patients with eligibility for LT by 21.6% but achieved comparable DFS and overall survival.
CONCLUSIONS
Incorporating PIVKA-II into existing LT criteria could increase the number of eligible HCC patients without compromising post-LT outcomes.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Transplantation; Liver Neoplasms; Biomarkers; Retrospective Studies; Neoplasm Recurrence, Local; Living Donors; Vitamin K; Biomarkers, Tumor
PubMed: 37988413
DOI: 10.1097/JS9.0000000000000729 -
BMC Gastroenterology May 2023Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and rare extrahepatic tumor. The prognosis is controversial because of its rarity and the lack of...
BACKGROUND
Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and rare extrahepatic tumor. The prognosis is controversial because of its rarity and the lack of multi-center cohort studies, especially on the influence of serum Alpha-fetoprotein (AFP) level on prognosis. We aimed to analyze the clinicopathological characteristics and prognosis of HAS, particularly the effect of serum AFP on the prognosis of HAS.
METHODS
We retrospectively reviewed clinical data of one HAS patient treated at our institution in 2019 and of 252 patients reported between 1984 and 2020 in research databases.
RESULTS
Among these patients, 60.1% were > 60 years, 51% had lesions in the gastric antrum, and 51.0% (73/143) had the ulcerative lesion type. The preoperative elevated levels of serum alpha-fetoprotein (AFP) were detected in most patients (76.7%). Lymph-node (84.6%) and preoperative liver metastasis (39.1%) were often found. The high-AFP group was characterized by a higher rate of stage IV (P = 0.000682) and liver metastasis (P = 0.000068). The 1-, 3-and 5-year progression-free survival(PFS) rates were 41%, 18%, and 0%, and the 1-, 3-, and 5-year overall survival (OS) rates were 64%, 26%, and 21%, respectively. The survival analysis showed that OS was significantly shorter for HAS with high-AFP (> 300 ng/ml) than with low-AFP (≤ 300 ng/ml) (P = 0.023). The univariate analysis indicated that the OS of HAS was associated with tumor location, pTNM stage, lymph-node metastasis, surgical resection, and serum AFP > 300 ng/ml. However,the prognostic factors for PFS was only pTNM stage and surgical resection. The multivariate analysis confirmed that the independent prognostic factor affecting OS of HAS included pTNM stage and surgical resection.
CONCLUSIONS
Liver metastasis was increasingly more likely with increasingly higher serum AFP, but the prognosis of HAS is not necessarily poor. Serum AFP level is an important prognostic indicator in HAS and should be monitored.
Topics: Humans; Retrospective Studies; alpha-Fetoproteins; Adenocarcinoma; Stomach Neoplasms; Liver Neoplasms
PubMed: 37161409
DOI: 10.1186/s12876-023-02773-9 -
International Journal of Molecular... Nov 2023Hepatocellular carcinoma (HCC) accounts for more than 75% of primary liver cancers, which are the second leading cause of cancer-related deaths. The GALAD (gender, age,...
BACKGROUND
Hepatocellular carcinoma (HCC) accounts for more than 75% of primary liver cancers, which are the second leading cause of cancer-related deaths. The GALAD (gender, age, AFP-L3, AFP, and des-carboxy-prothrombin) score is a diagnostic tool developed based on gender, age, alpha-fetoprotein, alpha-fetoprotein L3, and des-gamma-carboxy prothrombin, originally designed as a diagnostic tool for HCC in high-risk patients.
METHODS
We analyzed 212 patients with and without cirrhosis. The population study was divided into patients with liver cirrhosis without evidence of HCC at the time of serum sample collection for GALAD score determination and patients with liver cirrhosis and a confirmed diagnosis of HCC at the time of serum sample collection for GALAD score determination. Patients were followed up until death or liver transplantation. The association between variables and HCC mortality risk was performed, and the results were presented as hazard ratio (HR). The receiver operating characteristic (ROC) curve was used to assess the performance of the GALAD HCC diagnosis. The survival probability was explored using the non-parametric test, and the equality of survival amongst categories was assessed with the log-rank test.
RESULTS
Biomarkers were higher in the HCC group compared to cirrhosis. Kaplan-Meier survival probability analysis for individual GALAD categories revealed that a high GALAD level was associated with decreased survival during follow-up, and the difference between the curves was statistically significant ( = 0.01).
CONCLUSIONS
Our findings suggest that the GALAD score has promise as a prognostic tool, with implications for improving patient management and treatment strategies for HCC.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Biomarkers, Tumor; Prognosis; Biomarkers; ROC Curve; Liver Cirrhosis; Prothrombin
PubMed: 38003675
DOI: 10.3390/ijms242216485 -
Bioscience Reports Feb 2017α-fetoprotein (AFP) is an early serum growth factor in foetal embryonic development and hepatic oncogenesis. A growing number of investigations of AFP as a...
α-fetoprotein (AFP) is an early serum growth factor in foetal embryonic development and hepatic oncogenesis. A growing number of investigations of AFP as a tumour-specific biomarker have concluded that AFP is an important target for cancer treatment. AFP also plays an immunomodulatory role in the treatment of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis and thyroiditis. In an effort to support biochemical screening and drug design and discovery, we attempted to express and purify human AFP in a Bac-to-Bac system. Two key factors affecting the expression of recombinant human AFP (R-AFP), namely the infectious baculovirus inoculum volume and the culturing time post-infection, were optimized to maximize the yield. We achieved a high yield of approximately 1.5 mg/l of harvested medium with a 72-96 h incubation period after infection and an inoculum volume ratio of 1:100. We also assessed the role of R-AFP in the proliferation of the human liver cancer cell line Bel 7402, and the results indicated that R-AFP promoted the growth of hepatoma cells. We concluded that this method can produce high yields of R-AFP, which can be used for studies related to AFP.
Topics: Animals; Baculoviridae; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Culture Media; Drug Design; Drug Evaluation, Preclinical; Humans; Immunologic Factors; Insecta; Recombinant Proteins; alpha-Fetoproteins
PubMed: 27913752
DOI: 10.1042/BSR20160161 -
British Journal of Cancer Oct 2023Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is...
BACKGROUND
Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs.
METHODS
The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells.
RESULTS
Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination.
CONCLUSIONS
Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; In Situ Hybridization, Fluorescence; Prognosis; Polyploidy
PubMed: 37715023
DOI: 10.1038/s41416-023-02408-6 -
Clinical Gastroenterology and... Jan 2022Professional societies recommend abdominal ultrasound (US) with or without alpha fetoprotein (AFP) for hepatocellular cancer (HCC) surveillance; however, there are...
BACKGROUND AND AIMS
Professional societies recommend abdominal ultrasound (US) with or without alpha fetoprotein (AFP) for hepatocellular cancer (HCC) surveillance; however, there are several emerging surveillance modalities, including abbreviated MRI and blood-based biomarker panels. Most studies have focused on provider perspectives for surveillance logistics, but few have assessed patient preferences. We aimed to measure preferences among patients with cirrhosis regarding HCC surveillance modalities.
METHODS
We conducted a choice-based conjoint survey to patients with cirrhosis at four institutions. Participants were provided 15 scenarios in which they were asked to choose surveillance modalities based on five test attributes: benefits, i.e. sensitivity for early HCC (range: 35-95%), physical harm, i.e. false positives requiring additional testing (range: 10-40%), financial harm, i.e. out-of-pocket costs (range: $10-100), test logistics and convenience, i.e. duration of testing (range: 10-60 min). Hierarchical Bayes discrete choice conjoint analysis was used to derive attribute importance, and preference shares were determined by simulation.
RESULTS
In total 91% (182/199) of approached patients consented to participate in the study and 98% (n=179) successfully completed the survey. Surveillance benefits (importance: 51.3%, 95%CI: 49.0-53.4%) were valued more than risk of physical harm (importance: 7.6%, 95%CI 7.0-8.2%), financial harm (importance: 15.2%, 95%CI 14.0-16.3%), convenience (importance: 9.3%, 95%CI 8.5-10.1%) and test logistics (importance: 16.7%, 95%CI 15.4-18.1%). Based on simulations including all possible tests, patients preferred abbreviated MRI (29.0%), MRI (23.3%), or novel blood-based biomarkers (20.9%) to ultrasound alone (3.4%) or with AFP (8.8%).
CONCLUSIONS
Patients with cirrhosis prioritize early HCC detection over potential surveillance-related harms or inconvenience.
Topics: Bayes Theorem; Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Patient Preference; alpha-Fetoproteins
PubMed: 33618022
DOI: 10.1016/j.cgh.2021.02.024 -
World Journal of Gastroenterology Jan 2016The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV).... (Review)
Review
The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.
Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Hepatitis B; Hepatitis C; Humans; Liver Neoplasms; Prognosis; Protein Precursors; Prothrombin; alpha-Fetoproteins
PubMed: 26755875
DOI: 10.3748/wjg.v22.i1.262