Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally. Most patients present with late diagnosis, leading to poor prognosis. This narrative review explores novel biomarkers for early HCC detection. We conducted a comprehensive literature review analyzing protein, circulating nucleic acid, metabolite, and quantitative proteomics-based biomarkers, evaluating the advantages and limitations of each approach. While established markers like alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, and AFP-L3 remain relevant, promising candidates include circulating tumor DNA, microRNAs, long noncoding RNAs, extracellular vesicle, and metabolomic biomarkers. Multi-biomarker panels like the GALAD score, Oncoguard, and Helio liver test show promise for improved diagnostic accuracy. Non-invasive approaches like urine and gut microbiome analysis are also emerging possibilities. Integrating these novel biomarkers with current screening protocols holds significant potential for earlier HCC detection and improved patient outcomes. Future research should explore multi-biomarker panels, omics technologies, and artificial intelligence to further enhance early HCC diagnosis and management.

INTRODUCTION: Hepatocellular carcinoma (HCC) surveillance is underused in clinical practice, and few contemporary data have assessed patients' perceptions of surveillance effectiveness and net benefit. METHODS: We conducted a survey study among adult patients with cirrhosis at 7 health systems in the United States. The survey was based on validated measures, when available, and assessed patient knowledge about HCC surveillance, attitudes regarding surveillance benefits and harms, perceived HCC risk, and trust in their doctors. RESULTS: Respondents (n = 665; median age 60; 46.5% female) were knowledgeable about HCC surveillance, with no significant differences across sociodemographic groups; however, approximately 1 in 5 patients had knowledge gaps about the need and benefit of surveillance. Over three fourths of patients believed that surveillance improves early HCC detection (80.3%) and survival (77.9%). While 74.0% of patients reported that doctors had discussed surveillance benefits, only 54.2% recalled a discussion about potential harms. Patients placed greater importance on surveillance benefits, but expressed harms should be measured when assessing the net benefit of surveillance programs. Based on a pictogram depicting current estimates for surveillance benefits and harms, 93.2% of patients chose to undergo surveillance, with no significant differences by race, perceived surveillance benefits, or fear of dying from HCC. Study limitations include response and nonresponse biases, which may result in an overestimation of reported surveillance benefits and patient acceptance. DISCUSSION: Most patients with cirrhosis followed at academic health systems have high knowledge about HCC surveillance, believe that it is beneficial, and express interest in undergoing surveillance after being counseled about the benefits and harms.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer death, and existing HCC risk stratification models in cirrhosis poorly identify patients at the highest risk. We evaluated whether baseline antinuclear antibody (ANA) status is independently associated with incident HCC and whether adding ANA improves risk prediction. We conducted a single-center, retrospective cohort of adults (age ≥18 years) with established cirrhosis and clinically obtained ANA testing within 12 months of cirrhosis diagnosis. Follow-up began at the cirrhosis index date; the primary outcome was incident HCC. Associations were assessed using cause-specific Cox models with prespecified clinical covariates. We compared discrimination for a clinical model with and without ANA and performed inverse-probability–weighted and immunologic (IgG/neutrophil-to-lymphocyte ratio) sensitivity analyses in complete cases. Among 1,023 participants [mean age 53.7 years (SD 10.9); 57% male], 102 developed incident HCC over a median 4.7 years of follow-up. HCC incidence was lower in ANA-positive versus ANA-negative patients (1.10 vs. 3.73 per 100 person-years; log-rank P < 0.001). ANA positivity was associated with lower HCC risk in multivariable models (HR, 0.32; 95% CI, 0.20–0.52). Adding ANA improved discrimination (C-index 0.727–0.750) and model fit (likelihood-ratio P < 0.001). Findings were consistent in weighted and laboratory-complete sensitivity analyses. In cirrhosis, baseline ANA positivity is independently associated with lower incident HCC risk and provides incremental prognostic information beyond routine clinical factors. Prospective validation and mechanistic studies are warranted. Significance: Natural autoantibodies (ANA) are routinely measured, inexpensive, and widely accessible, yet their prognostic value in cirrhosis is not used for HCC risk stratification. In this retrospective cohort, baseline ANA positivity was independently associated with lower incident HCC risk and improved model discrimination beyond clinical factors. These findings support repurposing a common clinical test to refine individualized surveillance intensity and motivate prospective validation and mechanistic studies.

Purpose: This study analyzes the characteristics and prognosis of patients with de novo and recurrent metastatic gastric cancers.Methods: This retrospective study included 301 advanced, pathologically confirmed gastric cancer patients who received palliative chemotherapy between 2012 and 2022. The de novo cohort included patients who presented with distant metastasis at diagnosis, and the recurrent metastatic cohort was composed of patients with metastasis after curative gastrectomy. We analyzed prognostic association by Cox regression and compared survival time of both cohorts using the Kaplan-Meier survival analysis.Results: The study included 167 de novo and 112 recurrent patients. No differences were noted among the patients with de novo disease and recurrent metastatic disease concerning age, sex, Eastern Cooperative Oncology Group scores, primary cancer location, and pathologic features. Patients in the recurrent group versus the de novo group had a longer duration of chemotherapy (1.16±1.18 years vs. 0.85±0.84 years, P= 0.01) and lower mean body mass index (20.22±2.78 kg/m2 vs. 21.93±3.38 kg/m2, P< 0.001). The median overall survival in the de novo group was 11.6 versus 14.4 months in the recurrent group (P= 0.02).Conclusion: De novo and recurrent metastatic gastric cancer are characterized by distinct subpopulations. Advanced gastric cancer patients with recurrence have significantly better survival versus those in the de novo cohort. The differences between de novo and recurrent gastric cancer patient outcomes could facilitate discussions about the selection of the clinical trial of each patient and help with their personalized treatment.

HCC-free survival in MASLD cirrhosis by ANA status

Sensitivity analysis – complete-case multivariable Cox model with IgG and NLR.