Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States

BACKGROUND Early in the coronavirus disease 2019(COVID-19)pandemic,there was a significant impact on routine medical care in the United States,including in fields of transplantation and oncology.AIM To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation(LT)for hepatocellular carcinoma(HCC)in the United States.METHODS WHO declared COVID-19 as a pandemic on March 11,2020.We retrospectively analyzed data from the United Network for Organ Sharing(UNOS)database regarding adult LT with confirmed HCC on explant in 2019 and 2020.We defined pre-COVID period from March 11 to September 11,2019,and early-COVID period as from March 11 to September 11,2020.RESULTS Overall,23.5%fewer LT for HCC were performed during the COVID period(518 vs 675,P<0.05).This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020.Among LT recipients for HCC,concurrent diagnosis of non-alcoholic steatohepatitis significantly increased(23 vs 16%)and alcoholic liver disease(ALD)significantly decreased(18 vs 22%)during the COVID period.Recipient age,gender,BMI,and MELD score were statistically similar between two groups,while waiting list time decreased during the COVID period(279 days vs 300 days,P=0.041).Among pathological characteristics of HCC,vascular invasion was more prominent during COVID period(P<0.01),while other features were the same.While the donor age and other characteristics remained same,the distance between donor and recipient hospitals was significantly increased(P<0.01)and donor risk index was significantly higher(1.68 vs 1.59,P<0.01)during COVID period.Among outcomes,90-day overall and graft survival were the same,but 180-day overall and graft were significantly inferior during COVID period(94.7 vs 97.0%,P=0.048).On multivariable Coxhazard regression analysis,COVID period emerged as a significant risk factor of post-transplant mortality(Hazard ratio 1.85;95%CI:1.28-2.68,P=0.001).CONCLUSION During COVID period,there was a significant decrease in LTs performed for HCC.While early postoperative outcomes of LT for HCC were same,the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Acinar cell injury induced by inadequate unfolded protein response in acute pancreatitis

Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response(UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum(ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP.

Trends and outcomes of liver transplantation among older recipients in the United States

BACKGROUND The average age of recipients and donors of liver transplantation(LT)is increasing.Although there has been a change in the indications for LT over the years,data regarding the trends and outcomes of LT in the older population is limited.AIM To assess the clinical characteristics,age-related trends,and outcomes of LT among the older population in the United States.METHODS We analyzed data from the United Network for Organ Sharing database between 1987-2019.The sample was split into younger group(18-64 years old)and older group(≥65 years old).RESULTS Between 1987-2019,155758 LT were performed in the United States.During this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased(P<0.05)with the highest incidence of LT among older population seen in 2019(1920,23%).Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group,were non-alcoholic steatohepatitis(16.4%vs 5.9%),hepatocellular carcinoma(14.9%vs 6.9%),acute liver failure(2.5%vs 5.2%),hepatitis C cirrhosis(HCV)(19.2%vs 25.6%)and acute alcoholic hepatitis(0.13%vs 0.35%).In older recipient group female sex and Asian race were higher,while model for end-stage liver disease(MELD)score and rates of preoperative mechanical ventilation were lower(P<0.01).Median age of donor,female sex,body mass index(BMI),donor HCV positive status,and donor risk index(DRI)were significantly higher in older group(P<0.01).In univariable analysis,there was no difference in post-transplant length of hospitalization,one-year,three-year and five-year graft survivals between the two groups.In multivariable Cox-Hazard regression analysis,older group had an increased risk of graft failure during the five-year post-transplant period(hazard ratio:1.27,P<0.001).Other risk factors for graft failure among recipients were male sex,African American race,re-transplantation,presence of diabetes,mechanical ventilation at the time of LT,higher MELD score,presence of portal vein thrombosis,HCV positive status,and higher DRI.CONCLUSION While there is a higher risk of graft failure in older recipient population,age alone should not be a contraindication for LT.Careful selection of donors and recipients along with optimal management of risk factors during the postoperative period are necessary to maximize the transplant outcomes in this population.