Genetic risk score correlates with immune profile and risk of HCC and cirrhosis development in Hispanics with MASLD
Bibliographic record
Abstract
Background & Aims: Genetic risk score and immune dysregulations have been separately associated with the development of hepatocellular carcinoma (HCC) and cirrhosis in the context of metabolic dysfunction-associated steatotic liver disease (MASLD). Latin America has the highest prevalence of MASLD worldwide. However, the relationship between genetic risk scores, immune dysregulation, and MASLD has not been explored. Methods: rs72613567 in samples from a cohort of 972 Latin American individuals (HCC = 267, non-HCC = 705). The four SNPs were later combined into a genetic risk score and calculated in patients with MASLD (cirrhotic HCC = 133, cirrhosis = 242, non-cirrhotic liver disease (NCLD) = 113). A total of 28 cytokines were analyzed in a subgroup of these samples (cirrhotic HCC = 107, cirrhosis = 111). Results: = 0.004) compared with those with a score of 0-2. Cytokine profiles differed by genetic risk score in MASLD-related HCC and cirrhosis. Patients with HCC with high scores had lower levels of interferon-gamma and CCL8 (false discovery rate <0.05), whereas patients with cirrhosis with high scores showed higher matrix metallopeptidase 2 (MMP2) levels (false discovery rate <0.05). Conclusions: In Latin America, genetic risk score 6-8 in patients is strongly associated with an increased risk of MASLD-related HCC and cirrhosis. Additionally, patients with HCC and cirrhosis showed distinct immune profiles across high and low genetic risk score groups. Impact and implications: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) and cirrhosis is rising, with Hispanics having the highest MASLD rates. However, large-scale studies examining the association between genetic risk score, immune profiles, and the progression of MASLD-related HCC and cirrhosis are still lacking. In our study, we found that patients with MASLD-related HCC and cirrhosis who had higher genetic risk score were more likely to show higher odds ratios compared with those with lower genetic risk score. Additionally, genetic risk scores were found to be associated with immune profiles, as reflected by cytokine levels. These findings could assist clinicians in identifying high-risk groups of patients with MASLD-related HCC and cirrhosis and provide valuable insights into the potential immune changes in these individuals.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".