Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study

BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)metformin.During a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related mortality.Statin,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Variability in conflict of interest disclosures by physicians presenting trauma research

AIM To quantify the variability of financial disclosures by authors presenting orthopaedic trauma research. METHODS Self-reported authorship disclosure information published for the 2012 American Academy of Orthopaedic Surgeons(AAOS) and Orthopaedic Trauma Association(OTA) meetings was compiled from meeting programs. Both the AAOS and OTA required global disclosures for participants. Data collected included:(1) total number of presenters;(2) number of presenters with financial disclosures;(3) number of disclosures per author;(4) total number of companies supporting each author; and(5) specific type of disclosure. Disclosures made by authors presenting at more than one meeting were then compared for discrepancies.RESULTS Of the 5002 and 1168 authors presenting at the AAOS and OTA annual meetings, respectively, 1649(33%) and 246(21.9%) reported a financial disclosure(P < 0.0001). At the AAOS conference, the mean number of disclosures among presenters with disclosures was 4.01 with a range from 1 to 44. The majority of authors with disclosures reported three or more disclosures(n = 876, 53.1%). The most common cited disclosurewas as a paid consultant(51.5%) followed by research support(43.0%) and paid speaker(34.8%). Among the 256 physicians with financial disclosures presenting at the OTA conference, the mean number of disclosures was 4.03 with a range from 1 to 22. Similar to the AAOS conference, the majority of authors with any disclosures at the OTA conference reported three or more disclosures(n = 140, 54.7%). Most authors with a disclosure had three or more disclosures and the most common type of disclosure was paid consulting. At the OTA conference, the most commonly cited form of disclosure was paid consultant(54.3%) followed by research support(46.1%) and paid speaker(42.6%). Of the 346 researchers who presented at both meetings, 112(32.4%) authors were found to have at least one disclosure discrepancy. Among authors with a discrepancy, 36(32.1%) had three or more discrepancies. CONCLUSION There were variability and inconsistencies in financial disclosures by researchers presenting orthopaedic trauma research. Improved transparency of conflict of interest disclosures is warranted among trauma researchers presenting at national meetings.