Serum Α-fetoprotein Research Articles

Abstract No. 552 GALAD score predicts hepatocellular carcinoma recurrence in patients with normal serum α-fetoprotein levels following transarterial radioembolization

Abstract No. 552 GALAD score predicts hepatocellular carcinoma recurrence in patients with normal serum α-fetoprotein levels following transarterial radioembolization

Ultrasound features of immature ovarian teratomas: Case series and review of literature.

Immature ovarian teratomas are rare but account for 10-20% of ovarian cancers in women under the age of 20 years. This study aimed to characterise immature ovarian teratomas using grey-scale and Doppler ultrasonography and review the literature to refine the diagnosis of immature ovarian teratomas. Patients with a confirmed histological diagnosis of immature ovarian teratoma from years 2006-2018, who had undergone a transvaginal ultrasound at two large teaching hospitals, were identified. The imaging was retrieved from the centres clinical databases. Ultrasound scans were performed by experienced ultrasound examiners and described according to International Ovarian Tumour Analysis criteria. Eight patients were identified in total with a mean age of 26 years (range 13-35). Half of the patients had a past history of a mature ovarian teratoma (3 ipsilateral, 1 contralateral). The cysts were generally large (median 115 mm), fast growing unilateral lesions with a single, peripheral predominantly solid component arising from the cyst wall. The solid component was hyperechoic with multiple foci of fibrosis and numerous small cysts. The cystic component typically formed less than 75% of the lesion and the cyst fluid was of low-level echogenicity. Subjective assessment of vascularity of the solid part of the tumours varied between scores of 1 and 2. Tumour markers showed a raised serum a-fetoprotein level in 42% of these patients. Although there were no ultrasound features that were pathognomonic of immature teratoma, the diagnosis should be suspected in a young woman with a large ovarian cyst with a fibrotic, microcystic solid component, particularly if she has a past history of a dermoid cyst.

Mixed Germ Cell Tumor of the Endometrium: A Case Report and Literature Review.

Germ cell tumors (GCTs) localized extragonadally are rare, with only 14 reported cases of a yolk sac tumor in the endometrium. Here we report a case of mixed endometrium GCTs in a 65-year-old postmenopausal woman with abnormal vaginal bleeding. An ultrasound examination showed an oval-shaped mass in the patient’s uterine cavity. Biochemical examination revealed elevated serum α-fetoprotein (AFP) at 359 ng/mL, whereas the tumor markers CA-125, CA-199, and CEA were all within normal range. Total hysterectomy and bilateral salpingo-oophorectomy were performed;. a histological examination revealed that the malignant components contained a yolk sac tumor, embryonal carcinoma, and focal immature teratoma. Immunohistochemical staining showed that AFPs were diffusively distributed in both the yolk sac tumor and embryonal carcinoma. The stem cell marker OCT3/4 was positive in the embryonal carcinoma component and that the pan-cytokeratin AE1/AE3 staining was positive in glandular areas. GFAPs (Glial Fibrillary Acidic Proteins) were positive in neuroectodermal tubules; the Ki-67 protein was positive in 90% of the tumor cells, whereas CD117 and placental alkaline phosphatase (PLAP) were negative. The cumulative evidence indicated mixed GCTs of endometrium as the final histopathological diagnosis. The patient received three courses of adjunct chemotherapy that provided good therapeutic efficacy as evidenced by the decreased serum AFP level. Our report on this rare case of mixed GCTs of the endometrium, supported by associated histological patterns and immunophenotypes and successful adjunct chemotherapy after surgery, could provide insight on future treatment of this rare but lethal disease.

Coenzyme Q10 attenuates rat hepatocarcinogenesis via the reduction of CD59 expression and phospholipase D activity.

The current study aimed to test the profile of serum lipids, phospholipase D (PLD) activity, and CD59 expression pattern in rat hepatocellular carcinoma (HCC) after therapeutic treatment with Coenzyme Q10 (CoQ10). Three rat groups were allocated as normal control, untreated HCC, and treated HCC (HCC + CoQ10). The levels of serum α-fetoprotein (AFP) and tumour necrosis factor (TNF)-α were assessed using enzyme-linked immunosorbent assay (ELISA), while proliferating cell nuclear antigen (PCNA) was detected using immunohistochemistry (IHC). Serum lipids, classical (CH50), and alternative (APH50) pathways of complement activation, the liver cell HMG-CoA reductase (HMGCR), and PLD activities were assayed colorimetrically. The protein expression of CD59, scavenger receptor class B type 1 (SRB1), B cell lymphoma-2 (Bcl2), and cleaved Caspase-3 (Casp-3) were detected using western blotting, while the level of serum CD59 (sCD59) was assessed using dot-blot. CoQ10 reduced the cell proliferation, histological alterations, and the levels of AFP and TNF-α but increased lipids, CH50, and sCD59 in serum. In the liver cell, CoQ10 decreased and increased PLD and HMGCR enzyme activities, respectively. In addition, reduction of liver CD59, Bcl2, and SRB1 vs increased cleaved Casp-3 expressions was observed. Statistical correlation indicated an inverse relationship between CH50 and each of CD59 expression and PLD activity after treatment with CoQ10. In conclusion, CoQ10 could protect against rat HCC through increased lipids and the reduction of CD59 expression and PLD activity. SIGNIFICANCE OF THE STUDY: To our knowledge, this study is the first to describe the attenuating effect of antitumour natural product like Coenzyme Q10 (CoQ10) via the reduction of CD59 expression and phospholipase D (PLD) activity. This illustrates the important role of CD59 and PLD in relation to lipids in cancer prevention.

Radiomic Features at Contrast-enhanced CT Predict Recurrence in Early Stage Hepatocellular Carcinoma: A Multi-Institutional Study.

Background Early stage hepatocellular carcinoma (HCC) is the ideal candidate for resection in patients with preserved liver function; however, cancer will recur in half of these patients and no reliable prognostic tool has been established. Purpose To investigate the effectiveness of radiomic features in predicting tumor recurrence after resection of early stage HCC. Materials and Methods In total, 295 patients (median age, 58 years; interquartile range, 50-65 years; 221 men) who underwent contrast material-enhanced CT and curative resection for early stage HCC that met the Milan criteria between February 2009 and December 2016 were retrospectively recruited from three independent institutions. Follow-up consisted of serum α-fetoprotein level, liver function tests, and dynamic imaging examinations every 3 months during the first 2 years and then every 6 months thereafter. In the development cohort of 177 patients from institution 1, recurrence-related radiomic features were computationally extracted from the tumor and its periphery and a radiomics signature was built with least absolute shrinkage and selection operator regression. Two models, one integrating preoperative and one integrating pre- and postoperative variables, were created by using multivariable Cox regression analysis. An independent external cohort of 118 patients from institutions 2 and 3 was used to validate the proposed models. Results The preoperative model integrated radiomics signature with serum α-fetoprotein level and tumor number; the postoperative model incorporated microvascular invasion and satellite nodules into the above-mentioned predictors. In both study cohorts, two radiomics-based models provided better predictive performance (concordance index ≥0.77, P < .05 for all), lower prediction error (integrated Brier score ≤0.14), and larger net benefits, as determined by means of decision curve analysis, than rival models without radiomics and widely adopted staging systems. The radiomics-based models gave three risk strata with high, intermediate, or low risk of recurrence and distinct profiles of recurrent tumor number. Conclusion The proposed radiomics models with pre- and postresection features helped predict tumor recurrence for early stage hepatocellular carcinoma. © RSNA, 2020 Online supplemental material is available for this article.

Elevated Serum α-Fetoprotein is Associated with Abbreviated Survival for Patients with Fibrolamellar Hepatocellular Carcinoma Who Undergo a Curative Resection.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare variant of hepatocellular carcinoma (HCC), with most clinical data stemming from single-institution series. The variability in the literature lends support for analysis using a large national dataset. In doing so, we sought to (1) define the characteristics and outcomes of patients with FLC; (2) determine factors associated with survival in patients undergoing resection; and (3) compare the overall survival (OS) of patients with FLC with a matched group of patients with HCC. The National Cancer Database was queried for patients with FLC, and their clinicopathologic features were recorded. Univariate and multivariate analyses were performed to delineate factors associated with survival. Between 2004 and 2015, 496 patients were diagnosed with FLC, 229 of whom underwent a curative resection. The median OS for patients with FLC undergoing curative resection was 78.5months. Factors associated with abbreviated OS in this surgical cohort include multiple tumors [hazard ratio (HR) 3.15, p = 0.025], positive regional lymph nodes (HR 2.83, p = 0.023), and elevated serum α-fetoprotein (AFP; HR 2.81, p = 0.034). When the OS of patients with FLC was compared with a matched group of patients with HCC, no difference was detected (p = 0.748); however, patients with FLC and elevated AFP had abbreviated OS compared with patients with HCC and elevated AFP (43 vs. 82months, p ≤ 0.001). Elevations in serum AFP occur more frequently than previously documented for patients with FLC and are associated with abbreviated OS. AFP levels may help guide the decision for operative intervention in patients with FLC.

Significance of a preoperative tumor marker gradient for predicting microvascular invasion in cases of hepatocellular carcinoma.

Although vascular invasion is an important factor in the progression and treatment of hepatocellular carcinoma (HCC), it remains difficult to determine, on the basis of preoperative imaging alone, whether vascular invasion, especially microvascular invasion, has occurred. The current retrospective study enrolled 292 patients who, between 2004 and 2014, underwent curative hepatectomy as an initial treatment for HCC. The patients were divided between those with (n=70) and those without (n=222) microvascular invasion. Whether tumor-marker-based prediction of microvascular invasion was possible was assessed by comparing the preoperative serum α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II concentrations between two groups of patients. The AFP concentration was significantly higher in patients with microvascular invasion compared with patients without microvascular invasion (P=0.0019). Stepwise logistic regression analysis demonstrated the AFP concentration and the logarithmic conversion ratio of the AFP gradient (log AFP grad) to be useful (P=0.0019; 0.0424) for predicting microvascular invasion. The serum AFP concentration and log AFP grad appear to be clinically useful in predicting microvascular invasion in patients with HCC.

Vicenin-2 Treatment Attenuated the Diethylnitrosamine-Induced Liver Carcinoma and Oxidative Stress through Increased Apoptotic Protein Expression in Experimental Rats.

Liver cancer or hepatocellular carcinoma is considered to be the third leading cause of death among all other cancers. The rate of liver cancer occurrence is high, and the rate of recovery is low. In this study, we investigated the therapeutic efficacy of vicenin-2 against the diethylnitrosamine-induced liver carcinoma in experimental rats. Diethylnitrosamine was widely employed as a carcinogenic agent to stimulate the cancer in animal models. Our results indicated that vicenin-2 administration effectively attenuates the diethylnitrosamine-induced physiological and pharmacological alterations in the experimental rats. Vicenin-2 treatment significantly enhanced the pathological lesions and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and α-fetoprotein (AFP) in serum. We also observed that vicenin-2 reduced the production of reactive oxygen species, decreased the liver weight, upregulated expression of apoptotic proteins, and decreased the histological changes in the liver, which are induced by the diethylnitrosamine in rats. Moreover, vicenin-2 downregulates antiapoptotic Bcl-2 and Bcl-xL, and upregulates the proapoptotic Bax and caspase. Hence, our results suggested that vicenin-2 had a highly therapeutic effect in reversing diethylnitrosamine-induced liver carcinoma in rats, which might be related to the apoptosis induced by vicenin-2. Therefore vicenin-2 could be a good candidate for future therapeutic use to inhibit chemically induced liver cancer.

The clinical significance of serum miRNA-224 expression in hepatocellular carcinoma.

Aim of the studyMicro-ribonucleic acids (miRNA) are small single stranded RNA molecules. They act as key regulators of several cellular processes such as proliferation, apoptosis, tumor differentiation, invasion and metastasis. Hepatocellular carcinoma (HCC) represents the most common primary liver cancer. miRNA-224 is an oncomiR that is highly upregulated in HCC tissues. The aim of the present study was to measure the relative expression of circulating miRNA-224 in the serum of patients with HCV-related liver cirrhosis and HCC and to assess its usefulness in the diagnosis of HCC.Material and methodsForty-eight patients were classified into two groups: 24 HCV-related HCC patients (HCC group), and 24 HCV-related liver cirrhosis patients (LC group). A third group included 24 healthy volunteers (control group). Clinical examination, imaging studies and routine laboratory investigations, including serum α-fetoprotein (AFP), were done. Quantification of serum miRNA-224 expression was performed using real time reverse transcription polymerase chain reaction (RT-PCR).ResultsThe relative expression of serum miRNA-224 was significantly higher in HCC patients compared to LC patients and healthy control subjects. Its level correlated positively with the serum concentration of AFP and with Barcelona Clinic Liver Cancer (BCLC) stage of HCC. By combining miRNA-224 relative expression with AFP, their diagnostic sensitivity, specificity and accuracy increased significantly (95.0%, 92.1% and 93.2%, respectively) compared with either of the two markers alone in discriminating HCC from liver cirrhosis.ConclusionsSerum miRNA-224 relative expression may aid in the diagnosis of HCC. Better diagnostic performance is obtained if miRNA-224 is combined with other tumor markers such as AFP.

Prenatal Genetic Diagnosis of Congenital Nephrotic Syndrome

Congenital nephrotic syndrome (CNS) of the Finnish type is an autosomal recessive disorder caused by mutations in the gene encoding nephrin (NPHS1). A 31-year-old primigravida woman from the Philippines was referred to Seoul St. Mary’s Hospital with an abnormally elevated maternal serum α-fetoprotein (MSAFP) level of 8.5 multiples of the median (MoM) at 16+1 weeks gestation. The MSAFP level was 11.25 MoM when measured at Seoul St. Mary’s Hospital. The amniotic fluid tested negative for acetylcholine esterase and had an α-fetoprotein level of 41.09 MoM. The karyotype was normal. Analysis of the NPHS1 gene in amniotic fluid by massively parallel sequencing revealed mutations associated with CNS. Cesarean delivery was performed at 37+4 weeks gestation due to transverse presentation. The neonate was not severely affected; there was no evidence of proteinuria or renal failure. However, because symptoms usually appear within 2 weeks to 1 month of age, close monitoring that includes regular blood and urine testing should be conducted.

Genomic Profiles of a Patient of Pulmonary Hepatoid Adenocarcinoma With High AFP Level: A Case Report

Hepatoid adenocarcinoma of lung (HAL) is a rare and aggressive tumor. The current study reported a new HAL case in the right lower lung with high serum α-fetoprotein (AFP) level in a 71-year-old male patient. After the confirmation of morphology and immunohistochemistry, the patient was diagnosed clinically with HAL and treated with radio-frequency ablation. However, the patient whose disease progressed eventually died 4 months after diagnosis. Whole genome sequencing analysis identified a driver gene mutation in the FAT atypical cadherin 1 gene (FAT1) and the copy number loss. The tumor was microsatellite-stable and tumor mutation burden (TMB) was 1.69 mutations/Mb. PD-L1 expression was negative by IHC. Our finding provide further clues for the molecular basis of HAL and the efficacy of immunotherapy needs to be explored.

Ultrasound-Guided Microwave Ablation of Unresectable Hepatocellular Carcinoma: Short Term Response and Predictors of Success

Abstract Background: Microwave ablation (MWA) refers to all electromagnetic methods of inducing tumor destruction. Aim of Study: The aim of this study was to evaluate the outcome of ultrasound-guided microwave ablation of unre-sectable hepatocellular carcinoma using cold shaft antenna. Material and Methods: A total of 65 patients with Hepa-tocellular carcinboma (HCC) were referred to interventional Radiology Department for ablation of presumed non resectable tumor. The study group included 49 (75.4%) male and 16 (24.6%) female, with an average age (±SD) of 55±7.2 years (range, 48-72 years). Conventional gray scale ultrasound and triphasic computed tomography were performed for all patients before ablation. The microwave system used was HS AMICA (apparatus for microwave ablation, hospital service, Rome, Italy), with electronically controlled microwave generator. A 14 Gauage cooled shaft electrode named AMICA-probe was used to deliver microwave power to the liver tissue. The patients were then followed-up with contrast enhanced com-puted tomography (CT) and serum a-fetoprotein levels. Results: Among the 65 patients, complete ablation was achieved in 60 patients after initial treatment (92.3%). Initial complete ablation rates in patients with nodules 5cm were 100%, 92.1%, and 85.7% respectively. The probability of achieving a complete ablation was signif-icantly greater in patients with tumor size of <5cm. Conclusion: Sonographically guided MWA is an effective ablative method that can be applied in unresectable HCC of various sizes and different locations with reasonable safety.

The clinical significance of lipopolysaccharide binding protein in hepatocellular carcinoma.

Lipopolysaccharide binding protein (LBP) has been reported to be associated with prognosis in colorectal carcinoma and renal cell carcinoma; however, the clinical significance of LBP in human primary hepatocellular carcinoma (HCC) is inconclusive. We aimed to investigate the clinical significance and prognostic value of LBP in human primary HCC. In the present study, 346 patients with HCC who underwent curative resection were retrospectively analyzed. LBP protein expression was evaluated using western blot analysis and immunohistochemistry. LBP scores collected from immunohistochemical analysis were obtained by multiplying staining intensity and the percentage of positive cells. An outcome-based best cutoff-point was calculated by X-tile software. Moreover, Kaplan-Meier curves and Cox regressions were used for prognosis evaluation. LBP was frequently overexpressed in HCC compared with that in peritumor tissues (five pairs by western blot analysis, P=0.0533; 77 pairs by immunohistochemistry, P=0.0171), and LBP expression was positively associated with tumor-node-metastasis stage and tumor differentiation. Patients who had high LBP expression had decreased overall survival and time to recurrence compared with patients with low LBP expression. Furthermore, patients who were both serum α-fetoprotein positive and had high LBP expression had poor prognoses. Univariate and multivariate Cox analyses indicated that this combination was an independent prognostic factor [overall survival: Hazard ratio (HR), 1.458; 95% confidence interval (CI), 1.158–1.837; P=0.001; time to recurrence: HR,1.382; 95% Cl, 1.124–1.700; P=0.002]. In conclusion, LBP is highly expressed in HCC, and high LBP expression combined with serum α-fetoprotein may predict poor outcomes in patients with HCC following curative resection.

Whey protein concentrate and lactoferrin alleviated anaemia, immunotoxicity, and biochemical alterations in a mouse model of early hepatocarcinogenesis

Diethylnitrosamine (DEN), a natural carcinogen, is widely used in basic research to develop hepatocellular carcinoma in the experimental animals. The present study evaluated/compared the modulatory activities of bovine whey protein concentrate (WPC, 300 and 600 mg kg−1 body weight) and lactoferrin (30 and 60 mg kg−1 body weight), given orally/daily and concurrently for 14 weeks with DEN, in a mouse model of early hepatocarcinogenesis. The results showed that both WPC and lactoferrin (especially at the higher doses) improved the body weight, lymphoid organs cellularity, blood cell counts, and serum proteins, as well as alleviated significantly (P < 0.001) the elevation in clotting time, serum aminotransferases activities, serum α-fetoprotein and tumour necrosis factor-α concentrations, and hepatic malondialdehyde and nitric oxide concentrations in the DEN-treated mice. In conclusion, WPC and lactoferrin were effective under the experimental conditions in decreasing the markers of liver injury/carcinoma, anaemia, and immunotoxicity in DEN-induced hepatocarcinogenic mice.

Joining the dots for better liver cancer treatment.

In 2019, powerful single-cell analyses were applied to liver cancer biology at an unprecedented level. In parallel with this achievement was the identification of serum α-fetoprotein as a biomarker for patient selection in the use of ramucirumab for liver cancer and that β-catenin activation can distinguish between liver cancer immunotherapy responders and non-responders.

Diagnosis and Management of Placental Mesenchymal Disease. A Review of the Literature.

To review what is currently known about placental mesenchymal dysplasia (PMD) including imaging techniques for diagnosis and differentiation from a molar pregnancy, genetics, maternal/fetal effects, and management. A literature search by research librarians at 2 universities was undertaken using the search engines PubMed and Web of Science. The search terms used were "etiology" OR "cause" OR "risk" OR "risks" OR "epidemiology" OR "diagnosis" OR "therapy" OR "prognosis" OR "management" AND "placental mesenchymal dysplasia" OR "placenta" AND "mesenchymal dysplasia." No limit was put on the number of years searched. The etiology of PMD remains uncertain, although there are a number of theories on causation. An elevated maternal serum α-fetoprotein level, slightly elevated human chorionic gonadotropin level, normal karyotype, multicystic lesions on ultrasound, and varying degrees of flow within cysts using color Doppler (stained-glass appearance) are helpful in making the diagnosis. On pathologic examination of the placenta, PMD is differentiated from molar pregnancy by the absence of trophoblastic hyperplasia. Fetal complications of PMD include hematologic disorders, Beckwith-Wiedemann syndrome, liver tumors, fetal growth restriction, preterm delivery, and intrauterine fetal demise. Maternal complications include gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver function tests, low platelets) syndrome, and eclampsia. Accurate diagnosis of PMD is imperative for appropriate management and surveillance to minimize adverse maternal and fetal outcomes. The importance of a correct diagnosis of PMD is important because it can be misdiagnosed as a partial molar pregnancy or a complete mole with coexisting normal fetus, and this can result in inappropriate management.

Comprehensive Metabolomic Search for Biomarkers to Differentiate Early Stage Hepatocellular Carcinoma from Cirrhosis.

The established biomarker for hepatocellular carcinoma (HCC), serum α-fetoprotein (AFP), has suboptimal performance in early disease stages. This study aimed to develop a metabolite panel to differentiate early-stage HCC from cirrhosis. Cross-sectional metabolomic analyses of serum samples were performed for 53 and 47 patients with early HCC and cirrhosis, respectively, and 50 matched healthy controls. Results were validated in 82 and 80 patients with early HCC and cirrhosis, respectively. To retain a broad spectrum of metabolites, technically distinct analyses (global metabolomic profiling using gas chromatography time-of-flight mass spectrometry and targeted analyses using liquid chromatography with tandem mass spectrometry) were employed. Multivariate analyses classified distinct metabolites; logistic regression was employed to construct a prediction model for HCC diagnosis. Five metabolites (methionine, proline, ornithine, pimelylcarnitine, and octanoylcarnitine) were selected in a panel. The panel distinguished HCC from cirrhosis and normal controls, with an area under the receiver operating curve (AUC) of 0.82; this was significantly better than that of AFP (AUC: 0.75). During validation, the panel demonstrated significantly better predictability (AUC: 0.94) than did AFP (AUC: 0.78). Defects in ammonia recycling, the urea cycle, and amino acid metabolism, demonstrated on enrichment pathway analysis, may reliably distinguish HCC from cirrhosis. Compared with AFP alone, the metabolite panel substantially improved early-stage HCC detection.

The role of preoperative albumin-bilirubin grade for oncological risk stratification in liver transplant patients with hepatocellular carcinoma.

Albumin-bilirubin (ALBI) score was shown to correlate with liver function and tumor recurrence after hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to assess the prognostic value of ALBI grade in liver transplantation (LT) patients with HCC. Pre-LT available independent predictors of recurrence-free survival (RFS) and microvascular tumor invasion (MVI) were determined in 123 patients with HCC. Posttransplant HCC recurrence rates were 10.5%, 15.9%, and 68.2% in ALBI grade 1, 2, and 3, respectively (P < .001). Along with serum α-fetoprotein (AFP) and C-reactive protein (CRP) levels, ALBI grades 1 or 2 was identified as an independent predictor of RFS (hazard ratio, 3.52; 95% confidence interval [CI], 1.577-7.842; P = .002). Furthermore, ALBI grade 3 proved to be the strongest indicator of MVI (odds ratio, 11.59; 95% CI, 3.412-39.381; P < .001). A novel oncological risk score-based on AFP, CRP, and ALBI grade provided the best discriminative capacity (c-statistic 0.806) in selecting liver recipients with low oncological risk profile. Preoperative ALBI grade seems to be valuable for refinement of oncological risk stratification at LT for HCC.

PD-1 Antibody + XELOX in 1st Line Serum A-fetoprotein (AFP)-Elevated Gastric or Gastroesophageal Junction Adenocarcinoma

PD-1 Antibody + XELOX in 1st Line Serum A-fetoprotein (AFP)-Elevated Gastric or Gastroesophageal Junction Adenocarcinoma

An Albumin-Bilirubin (ALBI) Grade-based Prognostic Model For Patients With Hepatocellular Carcinoma Within Milan Criteria.

The Milan criteria are recommended as the major reference for liver transplantation in patients with small hepatocellular carcinoma (HCC). However, alternative anticancer treatments are often utilized due to severe donor organ shortage. This study aimed to develop and validate an albumin-bilirubin (ALBI) grade-based prognostic model to stratify survival in patients within Milan criteria undergoing nontransplant therapy. A total of 1655 patients were assigned into the derivation and validation cohort according to treatment modalities. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort. An ALBI-based model was evaluated in the validation cohort. In the Cox multivariate model, age 65 years or older (hazard ratio [HR]=1.576, P<0.001), serum α-fetoprotein (AFP) level >100 ng/mL (HR=1.671, P<0.001), ascites (HR=1.808, P<0.001), performance status 1 to 4 (HR=1.738, P<0.001), ALBI grade 2 (HR=1.827, P<0.001), and ALBI grade 3 (HR=3.589, P<0.001) were independent predictors of poor survival in the derivation cohort. An ALBI-based prognostic model with a total of 0 to 6 points was derived with the sum of 5 variables: 1 point each for age 65 years or older, AFP >100 ng/mL, presence of ascites, performance status 1 to 4, and ALBI grade 2, and 2 points for ALBI grade 3. This model can accurately predict long-term outcome in the validation cohort (P<0.001) and discriminate survival in patients stratified by curative and noncurative treatments (both P<0.001). The proposed ALBI grade-based model is feasible in predicting survival in HCC patients within the Milan criteria, and helps identify high-risk patients who need timely liver transplantation.