How important is donor age in liver transplantation?

The age of liver donors has been increasing in the past several years because of a donor shortage. In the United States, 33% of donors are age 50 years or older, as are more than 50% in some European countries. The impact of donor age on liver transplantation(LT) has been analyzed in several studies with contradictory conclusions. Nevertheless, recent analyses of the largest databases demonstrate that having an older donor is a risk factor for graft failure. Donor age is included as a risk factor in the more relevant graft survival scores, such as the Donor Risk Index, donor age and Model for End-stage Liver Disease, Survival Outcomes Following Liver Transplantation, and the Balance of Risk. The use of old donors is related to an increased rate of biliary complications and hepatitis C virus-related graft failure. Although liver function does not seem to be significantly affected by age, the incidence of several liver diseases increases with age, and the capacity of the liver to manage or overcome liver diseases or external injuries decreases. In this paper, the importance of age in LT outcomes, the role of donor age as a risk factor, and the influence of aging on liver regeneration are reviewed.

Risk of alcohol use relapse after liver transplantation for alcoholic liver disease

AIM To investigate factors, including psychosocial factors, associated with alcoholic use relapse after liver transplantation(LT) for alcoholic liver disease(ALD).METHODS The clinical records of 102 patients with ALD who were referred to Nagoya University Hospital for LT between May 2003 and March 2015 were retrospectively evaluated. History of alcohol intake was obtained from their clinical records and scored according to the HighRisk Alcoholism Relapse scale, which includes duration of heavy drinking, types and amount of alcohol usuallyconsumed, and previous inpatient treatment history for alcoholism. All patients were assessed for eligibility for LT according to comprehensive criteria, including ChildPugh score, Model for End-Stage Liver Disease score, and psychosocial criteria. RESULTS Of the 102 patients with ALD referred for LT, seven(6.9%) underwent LT. One(14.3%) of these seven patients returned to heavy drinking, but that patient was able to successfully quit drinking following an immediate intervention, consisting of psychotherapeutic education and supportive psychotherapy, by a psychiatrist. A comparison between the transplantation/registration(T/R) group, consisting of the seven patients who underwent LT and 10 patients listed for deceased donor LT, and 50 patients who did not undergo LT and were not listed for deceased donor LT(non-T/R group), showed statistically significant differences in duration of abstinence period(P < 0.01), duration of heavy drinking(P < 0.05), adherence to medical treatment(P < 0.01), and declaration of abstinence(P < 0.05).CONCLUSION Patients with ALD referred for LT require comprehensive evaluation, including evaluation of psychosocial criteria, to prevent alcoholic recidivism.

Potential importance of early treatment of SARS-CoV-2 infection in intestinal transplant patient: A case report

BACKGROUND Predispositions for severe coronavirus disease 2019(COVID-19)are age,immunosuppression,and co-morbidity.High levels of maintenance immunosuppression render intestinal transplant(ITx)patients vulnerable for severe COVID-19.COVID-19 also provokes several gastroenterological pathologies which have not been discussed in ITx,so far.CASE SUMMARY During the second European COVID-19 wave in November 2020,an ITx recipient was admitted to the hospital because of electrolyte disturbances due to dehydration.Immunosuppression consisted of tacrolimus,azathioprine,and low-dose corticosteroids.During hospitalization,she tested positive on screening COVID-19 nasopharyngeal polymerase chain reaction swab,while her initial test was negative.She was initially asymptomatic and had normal inflammatory markers.Tacrolimus levels were slightly raised,as Azathioprine was temporarily halted.Due to elevated Ddimers at that time,prophylactic low-molecular weight heparin was started.Seven days after the positive test,dyspnea,anosmia,and C-reactive protein increase(25 mg/L)were noted.Remdesivir was administered during 5 d in total.High stomal output was noted in two consecutive days and several days thereafter.To exclude infection or rejection,an ileoscopy and biopsy were performed and excluded these.Four weeks later,she was discharged from the hospital and remains in good health since then.CONCLUSION Early eradication of severe acute respiratory syndrome coronavirus 2 in ITx recipients may be warranted to prevent acute rejection provocation by it.

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper （Tfh） cells （B220-, CD4＋ CXCR5＋ PD-lhigh）, extrafollicular helper cells （B220-, CD4＋ CXCR5- PD-1＋ and PD-1-） and germinal centre （GC） B cells （B220＋Fas＋ GL7＋） were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.

HVEM,a cosignaling molecular switch,and its interactions with BTLA,CD160 and LIGHT

Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansion and T-cell survival during their differentiation towards effector T cells.Once the inflammatory stimulus is eliminated,effector T cells return to homeostasis after undergoing a contraction phase by activation-induced cell death and the intervention of ligands for coinhibitory receptors,leaving a population of long-term memory T cells.The expression of ligands for coinhibitory receptors on hematopoietic cells and,more importantly,on non-hematopoietic cells of peripheral tissues is a key process in tuning the functional activity of effector T cells to prevent excess tissue inflammation that may lead to immunopathology and subsequent tissue dysfunction.

Correction to: T follicular helper expansion and humoralmediated rejection are independent of the HVEM/BTLA pathway

In this article,one of the grating agencies requested us to incorporate the information,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”,in the acknowledgments section.The correct acknowledgement is as follows:“This work has been supported by grants of the Spanish Ministry of Health(Fondo de Investigaciones Sanitarias,PI13/00029,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”),Department of Education of Castilla and Leon Regional Government(Grant#LE093U13)and Mutua Madrileña Foundation(Basic research grants 2012)to J.I.R.B.;by Miguel Servet National Program(Ministry of National Health)CP12/03063 and by Gerencia Regional de Salud GRS963/A/2014 to M.L.R.G.We are particularly grateful to Mr.Leonides Alaiz for outstanding animal husbandry.”The authors regret the errors.