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.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care

BACKGROUND Hepatic encephalopathy(HE)is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50%of cirrhotic patients.Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis.AIM To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care.METHODS All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over46-mo(2012–2016)were identified via pharmacy dispensing records.Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded.Medical records were reviewed to determine baseline characteristics and survival.The Kaplan-Meier method was used to calculate survival probability.Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis.The primary outcome was 12-mo mortality following commencement of Rifaximin.RESULTS188 patients were included.Median age was 57 years(IQR 50-65),71%were male and median model for end stage liver disease and Child Pugh scores were 25(IQR 18-31)and 11(IQR 9-12)respectively.The most common causes of cirrhosis were alcohol(62%),hepatitis C(31%)and non-alcoholic fatty liver disease(20%).A precipitating cause for HE was found in 92%patients with infection(43%),GI bleeding(16%),medication non-compliance(15%)and electrolyte imbalance(14%)the most common.During a mean follow up period of 12±13 mo 107(57%)patients died and 32(17%)received orthotopic liver transplantation.Themost common causes of death were decompensated chronic liver disease(57%)and sepsis(19%).The probability of survival was 44%and 35%at 12-and 24-mo respectively.At multivariate analysis a model for end stage liver disease>15 and international normalised ratio reached statistical significance in predicting mortality.CONCLUSION Despite advances made in the management of HE patients continue to have poor survival.Thus,in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

Natural history and outcomes of patients with liver cirrhosis complicated by hepatic hydrothorax

BACKGROUNDHepatic hydrothorax (HH) is an uncommon and difficult-to-manage complicationof cirrhosis with limited treatment options.AIMTo define the clinical outcomes of patients presenting with HH managed withcurrent standards-of-care and to identify factors associated with mortality.METHODSCirrhotic patients with HH presenting to 3 tertiary centres from 2010 to 2018 wereretrospectively identified. HH was defined as pleural effusion in the absence ofcardiopulmonary disease. The primary outcomes were overall and transplant-freesurvival at 12-mo after the index admission. Cox proportional hazards analysiswas used to determine factors associated with the primary outcomes.RESULTSOverall, 84 patients were included (mean age, 58 years) with a mean model forend-stage liver disease score of 29. Management with diuretics alone achievedlong-term resolution of HH in only 12% patients. At least one thoracocentesis wasperformed in 73.8% patients, transjugular intrahepatic portosystemic shuntinsertion in 11.9% patients and 33% patients received liver transplantation within12-mo of index admission. Overall patient survival and transplant-free survival at12 mo were 68% and 41% respectively. At multivariable analysis, current smoking [hazard ratio (HR) = 8.65, 95% confidence interval (CI): 3.43-21.9, P < 0.001) and acute kidneyinjury (AKI) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were associated with a significantly increasedrisk of mortality.CONCLUSIONCirrhotic patients with HH are a challenging population with a poor 12-mo survival despitecurrent treatments. Current smoking and episodes of AKI are potential modifiable factors affectingsurvival. HH is often refractory of diuretic therapy and transplant assessment should beconsidered in all cases.

Hybrid Procedure Utilizing Stent Grafts to Stabilize Distal Flaps after Common and Superficial Femoral Endarterectomy

Background: Endarterectomy has long been the standard for common femoral artery (CFA) occlusive disease. Hybrid procedures utilizing endovascular and open techniques have recently been used for revascularization. The purpose of this study was to evaluate the effectiveness of the use of a stent graft to stabilize the distal flap and prevent further dissection after extensive endarterectomy. Methods: All patients from Monmouth Medical Center in Long Branch, NJ from September 2008 to March 2013 who underwent an extensive common and superficial femoral (SFA) endarterectomy combined with the use of a Viabahn (Gore Medical) stent graft to stabilize the distal flap were included in the study. These stents were deployed in the proximal SFA after extensive endarterectomy, under direct visualization, without the aid of fluoroscopy. Due to the location in the SFA, these flaps were not amenable to suture tacking. Results: Fifteen patients met these criteria and were included in our study. Twelve patients underwent femoral endarterectomy for severe claudication and three patients for limb salvage. Technical success was achieved in all 15 patients. Five patients also had stents placed proximally to increase inflow and one patient had an additional stent placed distally to improve outflow. There were no intraoperative or postoperative complications. Conclusion: Stent graft placement allows a more extensive endarterectomy to be performed by stabilizing the distal flap allowing a safe transition into the true lumen that is not possible with suture tacking.