Liver transplantation: Current status and challenges

Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death(DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function.

Hepatitis E in solid organ transplant recipients:A systematic review and meta-analysis

BACKGROUND Hepatitis E virus(HEV)infection is underdiagnosed due to the use of serological assays with low sensitivity.Although most patients with HEV recover completely,HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death.AIM To demonstrate the prevalence of HEV infection in solid organ transplant(SOT)recipients.METHODS We searched Ovid MEDLINE,EMBASE,and the Cochrane Library for eligible articles through October 2020.The inclusion criteria consisted of adult patients with history of SOT.HEV infection is confirmed by either HEV-immunoglobulin G,HEV-immunoglobulin M,or HEV RNA assay.RESULTS Of 563 citations,a total of 22 studies(n=4557)were included in this metaanalysis.The pooled estimated prevalence of HEV infection in SOT patients was 20.2%[95%confidence interval(CI):14.9-26.8].The pooled estimated prevalence of HEV infection for each organ transplant was as follows:liver(27.2%;95%CI:20.0-35.8),kidney(12.8%;95%CI:9.3-17.3),heart(12.8%;95%CI:9.3-17.3),and lung(5.6%;95%CI:1.6-17.9).Comparison across organ transplants demonstrated statistical significance(Q=16.721,P=0.002).The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries.The pooled estimated prevalence of de novo HEV infection was 5.1%(95%CI:2.6-9.6)and the pooled estimated prevalence of acute HEV infection was 4.3%(95%CI:1.9-9.4).CONCLUSION HEV infection is common in SOT recipients,particularly in middle-income countries.The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants.More studies examining the clinical impacts of HEV infection in SOT recipients,such as graft failure,rejection,and mortality are warranted.

Revisiting the liver’s role in transplant alloimmunity

The transplanted liver can modulate the recipient immune system to induce tolerance after transplantation.This phenomenon was observed nearly five decades ago.Subsequently,the liver’s role in multivisceral transplantation was recognized,as it has a protective role in preventing rejection of simultaneously transplanted solid organs such as kidney and heart.The liver has a unique architecture and is home to many cells involved in immunity and inflammation.After transplantation,these cells migrate from the liver into the recipient.Early studies identified chimerism as an important mechanism by which the liver modulates the human immune system.Recent studies on human T-cell subtypes,cytokine expression,and gene expression in the allograft have expanded our knowledge on the potential mechanisms underlying immunomodulation.In this article,we discuss the privileged state of liver transplantation compared to other solid organ transplantation,the liver allograft’s role in multivisceral transplantation,various cells in the liver involved in immune responses,and the potential mechanisms underlying immunomodulation of host alloresponses.

In-hospital mortality of hepatorenal syndrome in the United States:Nationwide inpatient sample

BACKGROUND Hepatorenal syndrome(HRS)is a life-threatening condition among patients with advanced liver disease.Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited.AIM To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States.METHODS We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014(weighted sample of 23973 admissions).The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality.We estimated odds ratios from multilevel mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality.RESULTS Overall hospital mortality was 32%.Hospital mortality decreased from 44%in 2005 to 24%in 2014(P<0.001),while there was an increase in the rate of liver transplantation(P=0.02),renal replacement therapy(P<0.001),length of hospital stay(P<0.001),and hospitalization cost(P<0.001).On multivariable analysis,older age,alcohol use,coagulopathy,neurological disorder,and need for mechanical ventilation predicted higher hospital mortality,whereas liver transplantation,transjugular intrahepatic portosystemic shunt,and abdominal paracentesis were associated with lower hospital mortality.CONCLUSION Although there was an increase in resource utilizations,hospital mortality among patients admitted for HRS significantly improved.Several predictors for hospital mortality were identified.