Liver decompensation after rapid weight loss from semaglutide in a patient with non-alcoholic steatohepatitis -associated cirrhosis.

There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonists such as semaglutide worldwide for weight loss and management of non-alcoholic steatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASH cirrhotic population. We report herein the first documented case of liver decompensation and need for liver transplant waitlisting in a patient with NASH-cirrhosis treated with semaglutide. Rapid weight loss led to the development of ascites and hepatic encephalopathy and an increase in the patients Model for Endstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritional supplementation was commenced and the semaglutide was stopped. Over the following months she regained her weight and her liver recompensated and her MELD-Na decreased to 13, allowing her to be delisted from the transplant waitlist. This case serves as a cautionary tale to clinicians using semaglutide in the cirrhotic population and highlights the need for more safety data in this patient group.

Inducible Left Ventricular Outflow Tract Obstruction in Patients Undergoing Liver Transplantation: Prevalence, Predictors, and Association With Cardiovascular Events.

BACKGROUND: Inducible left ventricular outflow tract obstruction (LVOTO) is often encountered in liver transplantation (LT) candidates during cardiac workup. While the impact of LVOTO on adverse cardiovascular hemodynamics is well reported, it is unclear whether it predisposes to perioperative cardiovascular complications. METHODS: Consecutive patients with end-stage liver disease undergoing dobutamine stress echocardiography (DSE) were evaluated at an LT center between 2010 and 2017. Perioperative major adverse cardiovascular events (MACEs) at 30 days and all-cause death were recorded from a prospectively maintained LT database. RESULTS: We evaluated 560 patients who underwent DSE during LT workup, with LVOTO identified in 24.3% (n = 136). Of these, 309 patients progressed to transplant. Patients with LVOTO demonstrated a lower peak systolic blood pressure (SBP) and an overall reduction in SBP on DSE. A total of 85 MACEs were recorded in 72 patients (23.3%) including 3 deaths, 19 cases of heart failure, 11 cardiac arrests, 8 acute coronary syndromes, and 44 arrhythmias. MACE occurred in 15/64 patients (23.4%) with LVOTO and 57/245 (23.3%) without (P = 0.92). There was an increased risk of perioperative cardiac arrest in patients with LVOTO (7.4% versus 2.4%, P = 0.04). Intraoperatively, patients with LVOTO required higher doses of vasopressors (P = 0.01) and received greater volumes of fluid (10.5 ± 8.1 versus 8.4 ± 6.4 L, P = 0.03). CONCLUSIONS: Patients with end-stage liver disease and LVOTO demonstrate a reduction in SBP during physiological stress that may translate to hemodynamic instability during LT. LVOTO was not associated with an increased rate of perioperative MACE or death.

Activity of Inflammatory Bowel Disease After Liver Transplantation for Primary Sclerosing Cholangitis Predicts Poorer Clinical Outcomes.

BACKGROUND: The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS: One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score-Crohn's Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD. RESULTS: Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81-27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55-22.74; P < 0.001). CONCLUSIONS: Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC.

Elevated Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio Predicts Long-Term Mortality in High-Risk Patients.

BACKGROUND: Elevated triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been utilised as a predictor of outcomes in patients with adverse cardiometabolic risk profiles. In this study, we examined the prognostic value of elevated TG/HDL-C level in an Australian population of patients with high clinical suspicion of coronary artery disease (CAD) presenting for coronary angiography. METHODS: Follow-up data was collected for 482 patients who underwent coronary angiography in a prospective cohort study. The primary endpoint was all-cause mortality and the secondary endpoint was a major adverse cardiac event (MACE). Patients were stratified into two groups according to their baseline TG/HDL-C ratio, using a TG/HDL-C ratio cut point of 2.5. RESULTS: The mean follow-up period was 5.1 ± 1.2 years, with 49 all-cause deaths. Coronary artery disease on coronary angiography was more prevalent in patients with TG/HDL-C ratio ≥2.5 (83.6% vs. 69.4%, p = 0.03). On the Kaplan-Meier analysis, patients with TG/HDL-C ratio ≥2.5 had worse long-term prognosis (p = 0.04). On multivariate Cox regression adjusting for established cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was an independent predictor of long-term all-cause mortality (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.04-4.20, p = 0.04). On multivariate logistic regression adjusting for known cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was strongly associated with an increased risk of long-term MACE (odds ratio [OR] 2.72, 95% CI 1.42-5.20, p = 0.002). CONCLUSIONS: Elevated TG/HDL-C ratio is an independent predictor of long-term all-cause mortality and is strongly associated with an increased risk of MACE.

Higher long-term adherence to statins in rural patients at high atherosclerotic risk.

BACKGROUND: Rural patients with atherosclerotic cardiovascular disease (ASCVD) experience greater cardiovascular morbidity and mortality than their urban counterparts. Statin therapy is a key component of ASCVD treatment. The extent to which there may be regional differences in long-term adherence to statins is unknown. OBJECTIVE: To assess long-term rates of adherence to statins in a high-risk ASCVD cohort, and whether regional differences exist between rural and urban patients. METHODS: Follow-up was conducted in patients who underwent coronary angiography at a single tertiary center between 2009 and 2013. Adherence was defined as consumption of prescribed statin ≥6 days per week. Patients were divided into remoteness areas (RAs), classified as RA1 (major city), RA2 (inner regional), and RA3 (outer regional) based on the Australian Standard Geographical Classification. RESULTS: Five hundred twenty-five patients (69% male, mean age 64 ± 11 years) were followed-up after a median of 5.3 years. Baseline characteristics were similar between RAs. Overall adherence was 83%; however, rural patients were significantly more adherent to their statin therapy (80% in RA1, 83% in RA2, and 93% in RA3, P = .04). Living in RA3 independently predicted greater statin adherence than living in RA1 (odds ratio: 2.75, 95% CI: 1.1-7.8, P = .03). All-cause mortality was significantly higher in RA3 than other regional areas (6% RA1, 12% RA2, and 18% RA3, P = .01). CONCLUSIONS: Despite higher all-cause mortality, rural patients with ASCVD demonstrate significantly greater long-term adherence to statins than urban patients. Other factors, such as reduced access to health care and delayed diagnosis may explain the gap in outcomes between rural and urban patients.

Usefulness of Platelet-to-Lymphocyte Ratio to Predict Long-Term All-Cause Mortality in Patients at High Risk of Coronary Artery Disease Who Underwent Coronary Angiography.

Platelet-to-lymphocyte ratio (PLR) has recently been studied as a biomarker in patients with established coronary artery disease (CAD). The association between PLR and long-term all-cause mortality is unclear in patients at high risk of CAD who undergo coronary angiography for various indications. Follow-up was completed for 514 patients who underwent coronary angiography in a prospective study cohort. The primary end point was all-cause mortality. Patients were classified into tertiles based on preangiography PLR and also dichotomized based on the optimal cutoff at a PLR of 137, determined from the receiver operating characteristic curve analysis. The mean follow-up period was 5.0 ± 1.3 years, with 50 all-cause deaths. On the Kaplan-Meier analysis, patients in Tertile 3 (PLR > 145) had worse prognosis than patients in Tertiles 1 (PLR ≤ 106) and 2 (PLR 106.1 to 145) (p = 0.0075), and patients with PLR ≥ 137 had a significantly higher rate of all-cause mortality than those with PLR < 137 (p = 0.0006). On multivariate Cox regression adjusting for known cardiovascular risk factors, PLR was a strong, independent predictor of long-term all-cause mortality on the tertile analysis (Tertile 3 vs Tertile 1: hazard ratio 2.52, 95% confidence interval 1.18 to 5.39, p = 0.017) and based on the cutoff at a PLR of 137 (PLR ≥ 137 vs <137: hazard ratio 2.25, 95% confidence interval 1.21 to 4.20, p = 0.011). In conclusion, elevated PLR is associated with long-term all-cause mortality in patients at high risk of CAD who undergo coronary angiography, and PLR may be a useful prognostic biomarker in this population.