Alpha-fetoprotein Levels Research Articles

Alpha-fetoprotein level in fetuses, infants, and children with ovarian masses: a literature review.

Alpha-fetoprotein (AFP) is a serum protein highly produced during the fetal period. It is also known as a biomarker of various pathologies. Commonly, tumors requiring diagnosis and monitoring through AFP determination appear during the first year of life, with poorer outcomes when presenting in fetal life. Due to advancements in imaging technology, the detectability of ovarian masses in infants is higher. However, the use of AFP as a biomarker could improve diagnosis in cases when imaging and histological examinations are not sensitive enough to detect tumors. From the outcome of our investigation, it is possible to conclude that there is evidence of an association between increased AFP levels and ovarian masses. However, previous studies have presented contradictory and unverified results, with the authors emphasizing that future research is needed. In this article, an analysis of the available literature on AFP as a biomarker of ovarian masses in children was performed. Two types of literature were reviewed: guidance and published studies (clinical trials, reviews, and systematic reviews). We searched the Embase, PubMed, ScienceDirect, and Web of Science databases to collect essential data.

The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma

PurposeThe GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC.MethodsA total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria.ResultsThe GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001).In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP.ConclusionThe GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.

Validation of Japanese indication criteria for deceased donor liver transplantation for hepatocellular carcinoma: Analysis of US national registry data.

The Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) have been updated based on living donor LT data to include either the Milan criteria (MC) or the 5-5-500 rule, which requires a nodule size of ≤5cm, ≤5 nodules, and an alpha-fetoprotein (AFP) level ≤500ng/mL. We aimed to validate the 5-5-500 rule and the MC for deceased donor LT (DDLT). Using national registry data from the United States from 2010 to 2014, we separated DDLT patients into four groups based on the MC and the 5-5-500 rule. The AFP values were stratified into categories: ≤100, 101-300, 301-500, and >500ng/mL. The 5-year survival rate was significantly lower for patients in the groups within MC/beyond 5-5-500 (56.3%) or beyond MC/5-5-500 (60.7%) than for patients in the groups within MC/5-5-500 (76.2%) and beyond MC/within 5-5-500 (72.3%) (p<0.01). Hepatocellular carcinoma recurrence at 5years was highest for the within MC/beyond 5-5-500 (25.4%) group, followed by the beyond MC/within 5-5-500 (13.1%), beyond MC/5-5-500 (9.6%), and within MC/5-5-500 (7.4%) groups. The stratified 5-year survival rates after DDLT were 76.5%, 72.4%, 58.4%, and 55.6% in the AFP ≤100, 101-300, 301-500, and >500 categories, respectively (p<0.01). The 5-5-500 rule guides the appropriate selection of patients with HCC for DDLT. Patients with AFP levels from 300 to 500ng/mL had inferior outcomes even when they met the 5-5-500 rule, so further investigation is needed to guide their treatment.

Clinicopathological Aspects and Inflammation-Immune Markers in Alcohol and/or Hepatitis C Virus-Induced Hepatocellular Carcinoma Patients Treated With Sorafenib.

Tyrosine kinase inhibitors have been used to treat hepatocellular carcinoma (HCC), but the outcomes of patients under treatment vary. Since the roles of clinicopathological aspects and markers of chronic inflammation/immune homeostasis in the outcome of HCC patients treated with sorafenib are still unclear, these were the aims of this study. Patients with alcohol-induced and/or hepatitis C virus (HCV)-induced HCC (n = 182) uniformly treated with sorafenib were included in the study. Baseline clinicopathological aspects of patients were computed from the medical records. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII) were obtained from the hematological exam performed before the administration of sorafenib. Overall survival (OS) was analyzed using Kaplan-Meier probabilities, log-rank test, and univariate and multivariate Cox proportional hazard ratio (HR) analyses. In multivariate analysis, alpha-foetoprotein (AFP) level and Child-Pugh score were predictors of OS. Patients with AFP levels higher than 157 ng/mL and Child-Pugh B or C had 1.40 (95% confidence interval (CI): 1.03 - 1.91, P = 0.03) and 1.64 (95% CI: 1.07 - 2.52, P = 0.02) more chances of evolving to death than the remaining patients, respectively. NLR, PLR, LMR, SIRI, and SII did not alter the OS of HCC patients. AFP level and Child-Pugh score act as independent prognostic factors in patients with alcohol and/or HCV-induced HCC treated with sorafenib, but markers of chronic inflammation/immune homeostasis seem not to alter the outcome of patients with HCC induced by alcohol and/or HCV.

The influencing factors for tumor thrombus in patients with hepatocellular carcinoma.

Microvascular invasion (MVI) is considered to be an important factor in the early invasion and metastasis of liver cancer, and the survival rate of patients with MVI is much lower than that of patients without MVI. Therefore, it is crucial to accurately predict the independent predictors of tumor thrombus formation. This study aimed to assess the risk factors for tumor thrombus grades in patients with hepatocellular carcinoma (HCC). Between August 2011 and December 2022, the data of 231 patients diagnosed with HCC were collected and divided into the following three groups: an MVI-negative group, an MVI-positive group, and a portal vein tumor thrombus (PVTT) group. Univariate analysis was used to compare the differences between the three groups in terms of clinical features, pathology, and imaging features. Multiple logistic regression analysis was used to analyze the risk factors associated with tumor thrombus grades, and the cutoff value was finally calculated by using the receiver operating characteristic (ROC) curve. The incidence of MVI and PVTT in the patients with HCC were 10.0% and 6.1%, respectively; univariate analysis revealed statistically significant differences in tumor diameter, alpha fetoprotein level, Ki-67 expression level, gender, tumor quantity, arteriovenous fistula, peritumoral enhancement, and satellite nodules among the three groups (P<0.05). Multiple logistic regression analysis showed that Ki-67 expression level, tumor diameter, and peritumoral enhancement were independent risk factors for tumor thrombus grades (P<0.05). The area under the curve (AUC) of Ki-67 expression level and tumor diameter was 0.713 [95% confidence interval (CI): 0.626-0.800] and 0.753 (95% CI: 0.669-0.837), respectively, and the AUC of the combination analysis was 0.805 (95% CI: 0.723-0.888), with a cutoff value of 17.5% and 4.1 cm, respectively (P<0.05). Tumor diameter, Ki-67 expression level, and peritumoral enhancement can be used as independent predictors of tumor thrombus in patients with HCC. The combination of tumor diameter and Ki-67 expression level can further improve diagnostic efficacy.

Predictive values of sarcopenia and systemic inflammation-based markers in advanced hepatocellular carcinoma after hepatectomy

Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with advanced hepatocellular carcinoma (HCC). However, the effect of sarcopenia combined with systemic inflammation on the prognosis of patients with advanced HCC who underwent hepatectomy is unclear. This study aimed to evaluate the effect of sarcopenia and inflammation on the prognosis of patients with advanced HCC. This retrospective study included 151 patients recruited between July 2010 and December 2022. We defined advanced HCC as that presenting with vascular invasion or tumor size ≥2cm or multiple tumors. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used by calculating the prognostic nutritional index, albumin-globulin ratio (AGR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine the prognostic factors for overall survival. Of 151 patients, sarcopenia occurred in 84 (55.6 %). Sarcopenia was significantly associated with male sex, older age, body mass index (<25kg/m2), and a higher NLR. In the multivariate analysis, AGR <1.25 (hazard ratio [HR], 2.504; 95% confidence interval [CI]: 1.325-4.820; p<0.05); alpha-fetoprotein levels ≥25ng/mL (HR, 1.891; 95% CI: 1.016-3.480; p=0.04); and sarcopenia (HR, 1.908; 95% CI: 1.009-3.776; p<0.05) were independent predictors of overall survival. The sarcopenia and low AGR groups had significantly worse overall survival than either the non-sarcopenia and high AGR or sarcopenia and low AGR groups. Sarcopenia and AGR are independent prognostic factors in patients with advanced HCC. Thus, sarcopenia may achieve a better prognostic value when combined with AGR.

C-Reactive Protein-Albumin Ratio (CAR): A More Promising Inflammation-Based Prognostic Marker for Patients Undergoing Curative Hepatectomy for Hepatocellular Carcinoma.

Systemic inflammatory response is a hallmark of cancer and plays a significant role in the development and progression of various malignant tumors. This research aimed to estimate the prognostic function of the C-reactive protein-albumin ratio (CAR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and compare it with other inflammation-based prognostic scores, including the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, systemic immune inflammation index, prognostic index, Glasgow prognostic score, and modified Glasgow prognostic score. Retrospective analysis was conducted on data from 1039 HCC cases who underwent curative liver resection. The prognostic performance of CAR was compared with other scores using the area under the time-dependent receiver operating characteristic (t-ROC) curve. Multivariable Cox regression analyses were performed to confirm independent predictors for disease-free survival (DFS) and overall survival (OS). The area under the t-ROC curve for CAR in the evaluation of DFS and OS was significantly greater than that of other scores and alpha-fetoprotein (AFP). Patients were stratified based on the optimal cut-off value of CAR, and the data revealed that both DFS and OS were remarkably worse in the high-CAR set compared to the low-CAR set. Multivariable Cox analysis demonstrated that CAR was an independent prognostic parameters for assessing DFS and OS. Regardless of AFP levels, all patients were subsequently divided into significantly different subgroups of DFS and OS based on CAR risk stratification. Similar results were observed when applying CAR risk stratification to other scoring systems. CAR also showed good clinical applicability in patients with different clinical features. CAR is a more effective inflammation-based prognostic marker than other scores and AFP in predicting DFS as well as OS among patients with HCC after curative hepatectomy.

Enteroblastic cholangiocarcinoma: An uncommon, underrecognized subtype of bile duct cancer

Enteroblastic carcinoma is clinically characterized by an elevated serum level of alpha-fetoprotein (AFP) and is histologically characterized by cancer cells with a clear cytoplasm and ‘blastic’ coarse chromatin. It sometimes has an element of hepatoid carcinoma; therefore, these two neoplasms are often regarded as sister entities. Although hepatoid carcinoma in the biliary tree has been reported, enteroblastic cholangiocarcinoma is extremely uncommon. In the present study, four cases of enteroblastic cholangiocarcinoma were examined. Tumors were located inside the liver (n = 2) or common bile duct (n = 2). The two intrahepatic cases had a history of primary sclerosing cholangitis, and serum AFP levels were elevated in both. One unresectable case was diagnosed by needle liver biopsy, while the remaining three underwent surgical resection. Histologically, all cases showed similar microscopic features. Cuboidal or polygonal cancer cells with the characteristic clear cytoplasm and subnuclear vacuoles were arranged in a papillary, micropapillary, tubular, or solid architecture. One case had an element of pancreatobiliary-type adenocarcinoma, while a hepatoid carcinoma element was not observed in any cases. All cases were positive for AFP, glypican 3, and SALL4, with SALL4 being the most widely expressed. Heppar-1 and arginase-1 were negative, except for one case, which was positive for Heppar-1. In conclusion, enteroblastic cholangiocarcinoma is an uncommon subtype of biliary tract malignancy. These cases may have been categorized as ‘clear cell’ cholangiocarcinoma. Although enteroblastic cholangiocarcinoma seems to occur more commonly in extrahepatic regions, including the gallbladder, it may also develop in the liver, particularly in patients with primary sclerosing cholangitis.

The importance of second-trimester AFP and preconception TSH levels for predicting the severity of proteinuria in patients with preeclampsia

Objective: This study aimed to investigate the relationships between preconception thyroid stimulating hormone (TSH) and thyroxine (T4) levels, as well as second-trimester alpha-fetoprotein (AFP) levels, and the severity of proteinuria in 24-hour urine samples from patients with preeclampsia.&#x0D; Method: This retrospective analysis focused on preeclampsia patients categorized by proteinuria in 24-hour urine. Inclusion criteria involved patients aged 20-44 with singleton pregnancies diagnosed with preeclampsia and delivery after 20 weeks of gestation. Patients were divided into mild (0.3 to

Surgical management of mediastinal mature cystic teratoma of the elderly remaining asymptomatic

BackgroundMediastinal teratoma is an uncommon disease, nevertheless they represent the most common mediastinal germ cell tumors. It may grow silently for several years and remain undiagnosed until the occurrence of a complication.AimThe main aim of this article is to illustrate the silent evolution of an anterior mediastinal teratoma for over 70 years without presenting any notable complications.Case presentationWe present the case of a 70-year-old female, treated for hypertension referred to our department for managing a voluminous mediastinal mass, discovered fortuitously by a general practitioner in a chest X-ray. The anamnesis didn’t relate any chest pain, cough, dyspnea nor hemoptysis. The clinical examination, in particular pleuropulmonary, was unremarkable. The workup (Chest X-Ray and CT scan) demonstrated a voluminous pleural mass at the expense of the right mediastinal pleura, rounded in shape, with calcified wall and fluid content. Blood tests did not demonstrate eosinophilia, and hydatid IgG serology was negative. serum human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) levels were found to be normal. The patient subsequently underwent a right posterolateral thoracotomy with resection of the lesion. The mass was dissected very carefully and then resected in toto. The macroscopic and microscopic histological examination demonstrated a mature cystic teratoma. Surgical resection was an adequate treatment and the prognosis was excellent for the patient.ConclusionCystic mature teratomas are rare thoracic tumors, often recognized by radiological examination. This article relates the silent evolution that a teratoma could have, and the late appearance of symptoms that it could have.

Prognostic Value of Pathological Response for Patients with Unresectable Hepatocellular Carcinoma Undergoing Conversion Surgery

Plain Language SummaryThe combination of transarterial chemoembolization, lenvatinib, and PD-1 inhibitor is an efficacious conversion therapy for uHCC. In this multicenter retrospective study, we discovered that PR was associated with the prognosis of patients who underwent conversion surgery. Predictors of MPR included neutrophil-to-lymphocyte ratio and alpha-fetoprotein levels.

Analytical and Clinical Evaluation of a Chemiluminescent Immunoassay to Detect Serum Chitinase-3-like Protein 1 in HBV-Related Liver Diseases.

Serum chitinase-3-like protein 1 (CHI3L1) is a diagnostic marker for liver diseases, such as hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the analytical performance of a chemiluminescent immunoassay (CLIA) for the quantitative detection of CHI3L1 and its application in hepatitis B virus (HBV)-related liver diseases. The CLIA for CHI3L1 detection presented good analytical performance, with a linear range of 1.50-2000.00 ng/mL and a detection limit of 0.98 ng/mL. To evaluate its clinical application, serum CHI3L1 levels were detected in 82 patients with chronic hepatitis B (CHB) and in 21 healthy controls. The patients with CHB and HCC had higher CHI3L1 levels than the healthy controls and the patients with CHB without HCC. However, CHI3L1 levels did not change significantly with the increase in liver fibrosis stages. The area under the receiver operating characteristic curve for the diagnosis of HBV-related HCC was 0.808, representing a moderate diagnostic value. Correlation analysis revealed a significant association between CHI3L1 and alpha-fetoprotein (AFP) levels, the fibrosis-4 (FIB-4) index, and the aspartate aminotransferase-to-platelet ratio index (APRI). In conclusion, compared with currently reported methods for CHI3L1 detection, the CLIA has a high sensitivity, a wide linear range, and an acceptable accuracy, precision, and reference intervals, making it valuable in the diagnosis of HBV-related HCC.

The Clinical Significance of Myosteatosis in Survival Outcomes in Patients with Hepatocellular Carcinoma Treated with Sorafenib.

The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0-78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258-2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028-1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105-2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112-2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients.

Comparing resection and stereotactic body radiation therapy for hepatocellular carcinoma with macrovascular invasion: A propensity score matched study.

521 Background: Macrovascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor. Current guidelines endorse systemic therapy for MVI. Local therapies present a potential for obliteration of MVI and improved survival. Surgery has been the standard local therapy at our institution, and stereotactic body radiotherapy (SBRT) has emerged as an alternative local therapy for this patient population. Methods: In this retrospective study, one-to-one optimal pair propensity score matching was used to compare outcomes of HCC patients with MVI who underwent surgery or received SBRT. Matching was done based on sex, age, ECOG, cirrhosis presence, Child-Pugh class, number of tumours, tumour volume, alpha-fetoprotein level, ALBI score, Japanese Classification of portal vein invasion, and hepatic vein invasion. Overall survival was estimated using the Kaplan-Meier method and between group differences determined using the log-rank test. The cumulative incidence of recurrence, accounting for the competing risk of death, was compared using Gray’s test. Results: Ninety of 193 patients were included after matching (45 patients in both the surgery and SBRT groups) (Table). The SBRT group had a median OS of 15 months (95% CI: 10-38), while in the surgery group it was 24 months (95% CI: 11-81). Comparing the 12-, 36-, and 60-month overall survival (OS) rates between the SBRT group (57%, 33%, 15%) and the surgery group (58%, 37%, 34%), there was no statistically significant differences (p=0.16); the 5-year OS was double in the surgical resection group. The 12-, 36-, and 60-month cumulative incidence of HCC recurrence in the SBRT group (47%, 73%, 75%) was comparable to the surgery group (69%, 69%, 69%) (p=0.89). Conclusions: Long term survival is possible in patients with HCC and MVI in a substantial minority of patients with HCC and MVI treated with local therapies. There was no statistical difference in outcomes; however, surgical resection resulted in numerically longer survival outcomes compared to SBRT after propensity score adjustment. There is rationale for investigating both local therapies with systemic therapies in future clinical trials. [Table: see text]

Agrin as a prognostic biomarker in hepatocellular carcinoma.

559 Background: Hepatocellular carcinoma (HCC), the predominant form of hepatic cancer is associated with high mortality rates, both in the United States &amp; globally. Alpha-fetoprotein (AFP) &amp; Glypican-3 have been proposed as biomarkers for HCC, although they do not offer any prognostic benefit to model disease progression. Immunotherapy combinations increase patient survival to ~18 months but are not selected based on biomarkers. Agrin, a secreted proteoglycan is frequently overexpressed &amp; secreted in HCC &amp; plays a prominent role in liver tumor microenvironment to promote hepatocarcinogenesis. In this single center, retrospective study using banked materials, we assessed the role of agrin as a prognostic biomarker in HCC. Methods: With IRB approval, we studied 90 newly diagnosed unresectable hepatobiliary cancer patients, &amp; compared them to healthy controls matched for age, gender, &amp; BMI between February 2006 &amp; September 2013. Serum concentration (conc.) of agrin was assessed using enzyme-linked immunosorbent assay (ELISA). We correlated the level of agrin with AFP, a known biomarker in hepatocellular cancer. Comparisons between groups were made using Mann-Whitney U &amp; Kruskal Wallis tests. Survival analysis used both univariate &amp; multivariate Cox regression models to investigate the relationship between survival outcomes &amp; agrin concentration, in comparison to AFP. Results: Mean circulatory plasma agrin levels were higher in HCC patients (n=79) (7.97 ng/ml, SD 5.8) when compared to controls (4.27 ng/ml, SD 1.03). ECOG PS &gt; 2 was linked to higher agrin conc. (mean: 10.5 ng/ml, p 0.007). While agrin levels in healthy individuals did not change with smoking history, the mean agrin levels were significantly higher in smokers (9.49 ng/ml) vs non-smokers (6.84 ng/ml) (p 0.0001) amongst HCC patients. Agrin displayed a strong positive correlation with AFP (correlation coefficient (r) 0.31944, p 0.0137). Multivariate cox regression models indicated that agrin conc. of &gt; 9.3 ng/ml had greater predictable survival outcomes (Hazard ratio (HR) 8.51, p &lt;0.001) when compared to elevated AFP levels (HR 1.55, p 0.25) (Table). HCC patients with lower agrin conc. (4.9 to 6.3 ng/ml) exhibited a one-year survival rate of 63% &amp; a median survival time of 16 months, while those with higher agrin conc. exceeding 9.3 ng/ml had significantly lower one-year survival rate of 14% &amp; significantly shorter median survival time of 3 months (p 0.002). Conclusions: Our results suggest that agrin levels as a prognostic indicator fare better than AFP levels. Thus, further studies should be done to explore this as a therapeutic target and as a biomarker of response to targeted therapies. [Table: see text]

Efficacy of immune checkpoint inhibitors in patients with HIV-associated unresectable HCC (uHCC): Propensity-score matched analyses from two international consortia.

442 Background: HIV-associated HCC is an incompletely characterized disease with poor prognosis. People living with HIV (PWH) are commonly excluded from clinical trials, leading to a paucity of high-level evidence for optimal management. Whether ICIs are tolerated and effective in HIV-associated uHCC remains unclear. Methods: Using data from the CATCH-IT consortium and from a global dataset recruiting patients with HCC from 14 centers in 3 continents, we selected patients with HIV-associated uHCC treated with ICIs and compared their outcomes with a matched cohort of HIV negative (HIV-) patients. Primary endpoints were overall (OS) and progression-free survival (PFS). Propensity score matching (PSM) between the two groups was performed for the following variables: age, sex, HCC aetiology, Child-Pugh class (CP-C), ECOG-PS, BCLC stage, alpha-fetoprotein (AFP) levels, treatment line, portal vein tumor thrombosis (PVTT), and extrahepatic spread (EHS). Restricted mean survival time (RMST) difference analyses stratified by HIV status were performed for OS and PFS at 3, 6 and 9 months. Results: We accrued 46 PWH and 400 HIV-, treated mostly in the first-line setting (58.7% vs. 43.7%) with either atezolizumab plus bevacizumab (28.3% vs 17.5%) or anti-PD-1 monotherapy. Median age at ICI start was 62 (38-76) and 64 (18-87); viral hepatitis (HCV: 58.7%; HBV: 34.8%) were the prevalent aetiologies in PWH, non-viral (46%) was the most common in HIV-; most patients had BCLC-C HCC (84.8% and 82.3%). In PWH, median CD4 count was 345 cells/mm3 (IQR: 200-465); viral load was undetectable in 45 patients, all were established on combined anti-retroviral therapy. Following PSM, 44 PWH and 117 HIV- were included. Median OS was 7.5 months (95%CI: 5.2-NR) in PWH and 10.8 months (95%CI: 7.3-19.5) in HIV- (HR: 0.89; 95%CI: 0.56-1.42; p=0.58). Presence of PVTT, AFP&gt;400 ng/mL, and ECOG-PS=1 but not HIV status were associated with worse OS in uni- and multivariable models. Median PFS was 2.8 months (95%CI: 2.6-4.8) for PWH vs 3.0 months (95%CI: 2.4-5.3) for HIV- (HR: 0.83-95%CI:0.56-1.24 ;p=0.38); HIV status was not associated with worse PFS. RMST confirmed no OS or PFS differences based on HIV status. In matched cohorts, neither ORR (21% vs. 19.1%, p=0.97) nor DCR (44.7% vs. 55.4%, p=0.19) were associated with HIV status. All grade immune-related adverse events (irAEs) were more frequent in HIV (44.0% vs 21.7%, p=0.003), with similar incidence of grade ≥3 irAEs (22.2% vs 13.0%). PWH had lower incidence of dermatological toxicities (4.3% vs 22%, p=0.003) and a trend towards lower incidence of hepatotoxicity (6.5% vs 18%, p=0.059). Conclusions: This study provides practice-informing evidence to support the use of ICIs in PWH and uHCC. Our findings encourage the inclusion of patients with well-controlled HIV in prospective clinical trials.

Prognostic value of the timing of immune checkpoint inhibitors infusion in patients with advanced hepatocellular carcinoma.

457 Background: Experimental and clinical data in melanoma and lung cancer suggest that the response to immune checkpoint inhibitors (ICI) may be influenced by circadian rhythms. However, similar findings are lacking in hepatocellular carcinoma (HCC). The aim of this study was to assess the impact of infusion timing of atezolizumab, an ICI, associated or not with bevacizumab, as first line systemic treatment in advanced HCC. Methods: We retrospectively analyzed all consecutive patients, who received, as first line systemic treatment, at least two cycles of atezolizumab +/- bevacizumab for advanced HCC in Paul Brousse Hospital, Villejuif, France, between January 2020 and October 2022. We split them in two groups: 1) patients receiving the first two cycles after 1 pm (afternoon group); 2) patients receiving at least one of the two first cycles before 1 pm (morning or mixed group). Cox regression models were used to assess the prognostic value of ICI infusion timing for the overall survival (OS). Results: A total of 131 patients were analyzed. 119 patients (90.8%) were male, with a median age of 70 years [35; 88]; 40 patients (31%) had performance status (PS) ≥ 1. 103 patients (79%) had cirrhosis; 61 patients (46.6%) had portal hypertension. 49 patients (37.4%) had metastatic HCC and 52 patients (40.6%) had portal vein thrombosis at diagnosis. The mean initial level of alpha-fetoprotein was 5,212.8 ng/mL (SD: 18,681.8). 36 patients (27.5%) received only atezolizumab. 41 patients were included in the first group and were compared to 90 patients included in the second group. There were no significant clinical differences between the two groups. The median OS was significantly lower in the afternoon group compared to the morning or mixed group (11.5 months vs 18.7 months, p = 0.015). In univariate analysis, PS ≥ 1 (p = 0.025), initial level of alpha-fetoprotein (p = 0.030), monotherapy by atezolizumab (p = 0.004) and the first two cycles of ICI infusion after 1 pm (p = 0.018) were significantly correlated with OS. The first two cycles of ICI infusion after 1 pm remains an independent factor significantly associated with OS in the multivariate Cox model, with HR 2.29, 95% CI: 1.27-4.14, p = 0.005 (Table). Conclusions: Our results suggest that the afternoon infusion of the first two cycles of ICI is associated with lower outcomes in patients with advanced HCC, independently of other prognostic factors. There may be confounding factors due to the variability of administration of further perfusions. Larger data are needed to confirm such findings. [Table: see text]

Radiographic and serologic response in patients with unresectable hepatocellular carcinoma receiving systemic antineoplastic treatments: A trial-level analysis.

In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC. After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated. Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates. PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier.

Fetal and Placental Causes of Elevated Serum Alpha-Fetoprotein Levels in Pregnant Women.

The most common association related to alpha-fetoprotein (AFP) is fetal neural tube defect (NTD), and indeed, this is where the international career of this protein began. In times when ultrasonography was not yet technically advanced, the detection of high levels of AFP in maternal serum (MS-AFP) and amniotic fluid was the basis for suspecting neural tube defects. In cases where there was no confirmation of NTD, other causes were sought. It has been established that high titers of MS-AFP could originate in other defects or diseases, such as (1) increased proteinuria in severe fetal kidney diseases; (2) pathological overproduction in liver diseases; (3) penetration through the membranes of gastrointestinal organs exposed to amniotic fluid; (4) passage through the walls of skin vessels; and as a side effect of (5) hepatic hematopoiesis and increased transfer through the edematous placenta in fetal anemia. This article provides a review of the current literature on congenital defects and genetic diseases in the fetus where an elevated level of MS-AFP may serve as the initial diagnostic clue for their detection.

The Prognostic Value of Alpha-Fetoprotein Ratio in Patients With Resectable Alpha-Fetoprotein-Negative Hepatocellular Carcinoma.

This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC). We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1week before surgery to the level 20-40days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). The study found that a cutoff value of 1.6ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS. The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients.