Safety of anti-TNF agents in patients with compensated cirrhosis: a case-control study

Background: There is limited data on the use of anti-TNF agents in patients with concomitant cirrhosis. The aim of this study is to assess the safety of anti-TNF agents in patients with compensated cirrhosis who used these medications for the treatment of an underlying rheumatologic condition or IBD. Methods: Multicenter, retrospective, matched, case-control study. A one to three case-control match was performed. Adults who received anti-TNF therapy were matched to three adults with cirrhosis who did not receive anti-TNF therapy. Patients were matched for etiology of cirrhosis, MELD-Na and age. Primary outcome was the development of hepatic decompensation. Secondary outcomes included development of infectious complications, hepatocellular carcinoma (HCC), extra-hepatic malignancy, and mortality. Results: Eighty patients with cirrhosis who received anti-TNF agents were matched with 240 controls. Median age was 57.2 years. Median MELD-Na for the anti-TNF cohort was seven and median MELD-Na for the controls was eight. The most common etiology of cirrhosis was NAFLD. Anti-TNF therapy did not increase risk of decompensation (HR: 0.91, 95% CI: 0.64–1.30, p = 0.61) nor influence the time to development of a decompensating event. Anti-TNF therapy did not increase the risk of hepatic mortality or need for liver transplantation (HR: 1.18, 95% CI: 0.55–2.53, p = 0.67). Anti-TNF therapy was not associated with an increased risk of serious infection (HR: 1.21, 95% CI: 0.68–2.17, p = 0.52), HCC (OR: 0.45, 95% CI: 0.13–1.57, p = 0.21), or extra-hepatic malignancy (OR: 0.82, 95% CI: 0.29–2.30, p = 0.71). Conclusions: Anti-TNF agents in patients with compensated cirrhosis does not influence the risk of decompensation, serious infections, transplant free survival, or malignancy

Effects of depression on myocardial perfusion scintigraphy

Introduction: The relationship between depression and coronary artery disease is well established; however assessment of this relationship using functional and semi-quantitative imaging (myocardial perfusion scintigraphy) was lacking. The aim of this study was to assess the relationship between the severity of depression and the severity of myocardial perfusion abnormality. Methods: Patients were assessed with rest/stress 99mTc-MIBI myocardial perfusion scintigraphy using Single Photon Emission Computed Tomography (SPECT) and Beck Depression Inventory (BDI-II). Visual and semi-quantitative assessment of myocardial perfusion score (MPS) in a five-scale measurement for standard 20-segment-model were used. Results: When all patients (n=167) were evaluated, no correlation was found between MPS and BDI-score. Considering only those with significant perfusion abnormality (MPS<90, n=38), negative correlation was found between MPS and BDI score (r= -0.641, p=0.017). Also higher BDI scores were recorded for patients with inferior wall infarction when compared with those with normal or near-normal MPS (MPS>95) (p=0.097), but other myocardial walls failed to show such association. Conclusion: In patients with significant perfusion abnormality, the greater is this abnormality the more severe is the depression. Also patients with inferior wall infarction, have a higher BDI-score as compared with normal subjects

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. Results: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1–124). The median time from pre-operative testing to surgery was 3 months (IQR: 1–4; range: 0–5), and from surgery to post-operative testing, it was 9 months (IQR: 2–22; range: 0.4–112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6–40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/−). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA−/− (n = 1, 10%), and ctDNA−/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. Conclusions: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns