Bile acids and the risk for hepatocellular carcinoma in primary biliary cholangitis
Bibliographic record
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer.1 The most frequent risk factors include chronic viral hepatitis (types B and C), alcohol intake and aflatoxin exposure. However, it has been reported that HCC occurs in 1-6% of patients with primary biliary cholangitis (PBC) per year. In addition HCC surveillance with abdominal imaging and α-fetoprotein is recommended every 6-12 months for patients. Furthermore, some studies suggested that risk factors for the development of HCC in patients with PBC include older age, male sex, presence of portal hypertension, advanced histological stage, and poor response to ursodeoxycholic acid (UDCA).2,3 We read with a great interest the article by Trivedi, et al.4 on the stratification of HCC risk in PBC. The risk for HCC in patients with PBC has been reported in previous publications and it has also been demonstrated by Liang, et al.5 in a systematic review and meta-analysis, suggesting that PBC is significantly associated with an increased risk for HCC. Two major risk factors have been suggested to predispose patients with PBC to develop HCC. The first one is gender and the second the biochemical non-response to UDCA. In the present study the univariate analysis showed that male sex (unadjusted HR 2.91, p < 0.0001) is one the factors at PBC diagnosis associated with future HCC development.4 The reason for increased hepatocarcinogenesis in men compared to women remains yet to be defined, but a role of estrogen-related differences in inflammatory cytokine production has been suggested.6 Here we would like to suggest a hypothesis to explain in part the increased risk in men with PBC for HCC. Both risk factors gender and non-response to treatment may be related to each other and increase HCC susceptibility. PBC is more frequent in women than men. However, men are more prone to the development of HCC. Currently the gold standard for treatment of PBC is UDCA.7 This bile acid constitutes < 5% of the bile acid pool under physiological conditions. After oral administration of UDCA an enrichment of bile with this hydrophilic bile acid occurs, which represents the requirement for treatment response in patients with chronic cholangiopathies. The mechanism of action of UDCA is multifactorial8 and involves replacement of endogenous cytotoxic bile acids [chenodeoxycholic (CDCA) and deoxycholic (DCA) acid] by the non-cytotoxic bile acid UDCA; one of the mechanisms is likely to be competition for active ileal transport. Interestingly, it has been suggested that gender has a major effect on fasting plasma concentrations of individual bile acids in healthy individuals. In fact, Xiang, et al.9 reported that fasting plasma concentrations of individual bile acids are 111% higher in men than in women. Consequently, the mean concentration of total bile acids is about 50% higher in men than in women. These differences were also observed in the 70’s by Bennion, et al.10 in healthy male subjects whose chenodeoxycholic acid pool sizes were larger than in women. In addition, Diger, et al.11 reported that PBC patients differ from healthy individuals The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for Study of the Liver and the Canadian Association for the Study of the Liver
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".