Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Translation and cross-cultural adaptation of the Kidney Transplant Questionnaire 25 to Greek

BACKGROUND Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients(KTRs)and has been established as the treatment of choice for patients with end-stage kidney disease.Health-related quality of life(HRQoL)has become an important outcome measure.It is highly important to develop reliable methods to evaluate HRQoL with disease-specific questionnaires.AIM To translate the disease-specific instrument Kidney Transplant Questionnaire 25(KTQ-25)to the Greek language and perform a cross-cultural adaptation.METHODS The translation and adaptation of the original English version of the KTQ-25 to the Greek language were performed based on the International Quality of Life RESULTS Eighty-four KTRs(59 males;mean age 53.5±10.7 years;mean estimated glomerular filtration rate 47.7±15.1 mL/min/1.73 m2;mean transplant vintage 100.5±83.2 months)completed the Greek version of the KTQ-25 and the 36-item Short-Form Health Survey,and the results were used to evaluate the reliability of the Greek KTQ-25.The Cronbach alpha coefficients for all the KTQ-25 dimensions were satisfactory(physical symptoms=0.639,fatigue=0.856,uncertainty/fear=0.661,appearance=0.593,emotions=0.718,total score=0.708).The statistically significant correlation coefficients among the KTQ-25 dimensions ranged from 0.226 to 0.644.The correlation coeffi-cients of the KTQ-25 dimensions with the SF-36 physical component summary(PCS)ranged from 0.196 to 0.550;the correlation coefficients of the KTQ-25 with the SF-36 mental component summary(MCS)ranged from 0.260 to 0.655;and the correlation coefficients of the KTQ-25 with the total scores with the SF-36 PCS and MCS were 0.455 and 0.613,respectively.CONCLUSION According to the findings,the Greek version of the KTQ-25 is valid and reliable for administration among kidney transplant patients in Greece.

成人肝移植中的肝动脉搭桥术——澳大利亚Australia National Liver Transplant Unit的经验

目的介绍澳大利亚国家肝移植中心在成人肝移植中应用肝动脉搭桥术的经验。方法对澳大利亚国家肝移植中心(AustraliaNationalLiverTransplantUnit,ANLTU)1986—2003年的31例行肝动脉搭桥的成人肝移植结果进行回顾行分析。31例需行肝动脉搭桥的原因有微小受者肝动脉、肝动脉血栓症、肝门严重粘连、肝动脉壁间动脉瘤、真菌性肝动脉瘤及前次植入肝的肝动脉因胆道出血而结扎。18例为首次移植,13例为再次或多次肝移植。结果术后15例(48.4%)存活,平均存活时间为4.1年,16例(51.6%)死亡,平均存活时间为34.56d。两次和多次肝移植者的死亡率为76.9%,首次肝移植者的死亡率为33.3%(P<0.05)。因肝动脉血栓症而搭桥者的死亡率最高,其次为肝门严重粘连者。死亡原因依次为败血症、围手术期大出血、颅内出血、肝动脉血栓形成、排斥反应、原发病复发以及心跳骤停。结论成人肝移植行肝动脉搭桥的适应证主要是各种原因导致的受者肝动脉不适用,或因肝门部严重粘连而无法解剖者;患者术后转归与肝移植的次数及患者的术前状况有关。

Primary graft dysfunction following lung transplantation:From pathogenesis to future frontiers

Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction.It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant.This review aims to provide an in-depth analysis of the epidemiology,pathophysiology,risk factors,outcomes,and future frontiers involved in mitigating primary graft dysfunction.The current diagnostic criteria are examined alongside changes from the previous definition.We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion.Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality,ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.

Surgical complications after pancreatic transplantation:A computed tomography imaging pictorial review

Pancreatic transplantation is considered by the American Diabetes Association and the European Association for the Study of Diabetes an acceptable surgical procedure in patients with type 1 diabetes also undergoing kidney transplantation in pre-final or end-stage renal disease if no contraindications are present.Pancreatic transplantation,however,is a complex surgical procedure and may lead to a range of postoperative complications that can significantly impact graft function and patient outcomes.Postoperative computed tomography(CT)is often adopted to evaluate perfusion of the transplanted pancreas,identify complications and as a guide for interventional radiology procedures.CT assessment after pancreatic transplantation should start with the evaluation of the arterial Y-graft,the venous anastomosis and the duodenojejunostomy.With regard to complications,CT allows for the identification of vascular complications,such as thrombosis or stenosis of blood vessels supplying the graft,the detection of pancreatic fluid collections,including pseudocysts,abscesses,or leaks,the assessment of bowel complications(anastomotic leaks,ileus or obstruction),and the identification of bleeding.The aim of this pictorial review is to illustrate CT findings of surgical-related complications after pancreatic transplantation.The knowledge of surgical techniques is of key importance to understand postoperative anatomic changes and imaging evaluation.Therefore,we first provide a short summary of the main techniques of pancreatic transplantation.Then,we provide a practical imaging approach to pancreatic transplantation and its complications providing tips and tricks for the prompt imaging diagnosis on CT.

Risk stratification of renal transplant recipients using routine parameters: Implication of learning from SARS-CoV-2 into transplant follow-up program

BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In the course of acute SARS-CoV-2 infection,various laboratory markers have been identified as predictors for high risk of mortality.AIM To risk stratify renal transplant recipients(RTxR)using general demographic parameters,comorbidities and routine laboratory markers for the severity of the disease and its outcomes.We believe that learning about these routinely monitored parameters can help us plan better strategies for the RTxR follow-up program.METHODS This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021.We recorded the basic demographics,comorbidities and routine laboratory markers.We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality.RESULTS From 505 RTxRs in our renal transplant follow-up program,29(7.75%)RTxRs had PCR-positive SARS-CoV-2 infection.We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6%but a significant 27.6%mortality in SARS-CoV-2 positive recipients.Age more than 68 years,non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability;P≤0.001.<0.001 and<0.0001 respectively.87.5%of the deceased were diabetic;P≤0.0.0001.Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2,serum albumin less than 20 g/L,Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality;P=0.0128,<0.001,<0.0001 and 0.0061 respectively.CONCLUSION This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity.This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.

Patients with hepatocellular carcinoma that die during the first year of liver transplantation have high blood sFasL concentrations

BACKGROUND Fas ligand(FasL)is one ligand that activates extrinsic apoptosis pathway.High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation(LT).No high blood concentrations of soluble FasL(sFasL)have been found in patients with acute LT rejection;however,the samples size of those studies was small.AIM To determine whether patients with hepatocellular carcinoma(HCC)that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample size.METHODS Patients underwent LT due to HCC were included in this retrospective study.Serum sFasL levels prior to LT were measured and one-year LT mortality was registered.RESULTS Non-surviving patients(n=14)showed higher serum sFasL levels[477(269-496)vs 85(44-382)pg/mL;P<0.001]than surviving patients(n=113).Serum sFasL levels(pg/mL)were associated with mortality(OR=1.006;95%CI=1.003-1.010;P=0.001)independently of age of LT donor in the logistic regression analysis.CONCLUSION We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.

Machine learning in liver surgery:Benefits and pitfalls

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of interest.However,we must be cautious with the results.In this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the future.Although the future faces significant challenges,it also holds a great potential.

Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Perioperative thrombotic complications in liver transplantation

Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation(OLT),the possible cohesion of an underestimated intrinsic hypercoagulative state during and after the transplant procedure may pose a major threat to both patient and graft survival.Thromboembolism during OLT is characterized not only by a complex aetiology,but also by unpredictable onset and evolution of the disease.The initiation of a procoagulant process may be triggered by various factors,such as inflammation,venous stasis,ischemia-reperfusion injury,vascular clamping,anatomical and technical abnormalities,genetic factors,deficiency of profibrinolytic activity,and platelet activation.The involvement of the arterial system,intracardiac thrombosis,pulmonary emboli,portal vein thrombosis,and deep vein thrombosis,are among the most serious thrombotic events in the perioperative period.The rapid detection of occlusive vascular events is of paramount importance as it heavily influences the prognosis,particularly when these events occur intraoperatively or early after OLT.Regardless of the lack of studies and guidelines on anticoagulant prophylaxis in this setting,many institutions recommend such an approach especially in the subset of patients at high risk.However,the decision of when,how and in what doses to use the various chemical anticoagulants is still a difficult task,since there is no common consensus,even for highrisk cases.The risk of postoperative thromboembolism causing severe hemodynamic events,or even loss of graft function,must be weighed and compared with the risk of an important bleeding.In this article we briefly review the risk factors and the possible predictors of major thrombotic complications occurringin the perioperative period,as well as their incidence and clinical features.Moreover,the indications to pharmacological prophylaxis and the current treatment strategies are also summarized.

Platelet-to-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer: A systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on platelet-to-lymphocyte ratio(PLR) as a risk factor for post-transplant hepatocellular cancer(HCC) recurrence. METHODS A systematic literature search was performed using PubM ed. Participants of any age and sex, who underwent liver transplantation for HCC were considered following these criteria:(1) studies comparing pre-transplant low vs high PLR values;(2) studies reporting post-transplant recurrence rates; and(3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measure was set for HCC recurrence after transplantation. RESULTS A total of 5 articles, published between 2014 and 2017, fulfilled the selection criteria. As for the quality of the reported studies, all the investigated articles presented an overall high quality. A total of 899 cases were investigated: 718 cases(80.0%) were males. Three studies coming from European countries and one from Japan presented HCV as the main cause of cirrhosis. On the opposite, one Chinese study presented a greater incidence of HBV-related cirrhotic cases. In all the studies apart one, the PLR cut-off value of 150 was reported. At meta-analysis, high PLR value was associated with a significant increase in recurrence after transplantation(OR = 3.33; 95%CI: 1.78-6.25; P < 0.001). A moderate heterogeneity was observed among the identified studies according to the Higgins I^2 statistic value.CONCLUSION Pre-transplant high PLR values are connected with an increased risk of post-operative recurrence of hepatocellular cancer. More studies are needed for better clarify the biological mechanisms of this results.

Neoplastic disease after liver transplantation: focus on de novo neoplasms

De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma(HCC) recurrence have been reported with the use of m TOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs m TOR-inhibitorfree immunosuppression is more efficacious in reducing HCC recurrence.

Risk factors, surgical complications and graft survival in liver transplant recipients with early allograft dysfunction

Background: Early allograft dysfunction (EAD) is a severe complication after liver transplantation. The associated risk factors and complications have re-gained recent interest. This study investigated risk factors, survival and complications associated with EAD in a large liver transplant center in Latin America. Methods: Retrospective, unicenter, cohort, based on data from adult patients undergoing first deceaseddonor liver transplant from January 2009 to December 2013. EAD was defined by one or more of the following:(i) bilirubin ≥10 mg/dL on postoperative day 7;(ii) international normalized ratio ≥1.6 on postoperative day 7, and (iii) alanine aminotransferase or aspartate aminotransferase > 2000 IU/L within the first seven days after transplant. Results: A total of 602 patients were included;of these 34.2% developed EAD. Donor risk factors were male ( P = 0.007), age between 50 and 59 years ( P = 0.034), overweight ( P = 0.028) or grade I obesity ( P = 0.012), sodium > 157 mmol/L ( P = 0.002) and grade IV ischemia/reperfusion injury ( P = 0.002). Cold ischemia time ≥10 h ( P = 0.008) and warm ischemia time ≥40 min ( P = 0.013) were the surgical factors. Male ( P < 0.001) was the only recipient protective factor. Compared with the non-EAD group, patients with EAD were submitted to more reoperations (24.3% vs. 13.4%, P = 0.001) and had higher graft loss rates (37.9% vs. 21.2%, P < 0.001), with similar patient survival rates ( P = 0.238). Conclusions: EAD risk factors are related to donor, surgical procedure and recipient. Donor risk factors for EAD were male, age between 50 and 59 years, donor overweight or grade Ⅰ obesity, sodium > 157 mmol/L and grade Ⅳ ischemia/reperfusion injury. Cold ischemia time ≥10 h and warm ischemia time ≥40 min were the surgical risk factors. Male was the only recipient protective factor. Patients with EAD had higher reoperations and graft loss rates.

Liver transplantation for hepatocellular carcinoma:Role of inflammatory and immunological state on recurrence and prognosis

Criteria for liver transplantation(LT)for hepatocellular carcinoma(HCC)and post-LT indicators of prognosis are historically based on the measurement of the tumor mass.Recently,high throughput technologies have increased the prediction of recurrence,but these tools are not yet routinely available.The interaction between HCC and the immune system has revealed an imbalance of lymphocyte phenotypes in the peritumoral tissue,and the increase of regulatory T cells with respect to cytotoxic lymphocytes has been linked to a higher rate of post-LT HCC recurrence.Moreover,some inflammatory markers have shown good reliability in predicting cancer reappearance after surgery,as a result of either a systemic inflammatory response or a decreased capacity of the organism to control the tumor growth.Among these markers,the neutrophil-tolymphocyte ratio appears to be the most promising and easily available serum parameter able to predict HCC recurrence after LT and following other types of treatment,although the exact mechanisms determining its elevation have not been clarified.Post-LT immunosuppression may impact on cancer control,and the exposure to high levels of calcineurin inhibitors or other immunusuppressants has recently emerged as a negative prognostic factor for HCC recurrence and patient survival.Despite the absence of prospective randomized trials,inhibitors of the mammalian target of rapamycin have been shown to be associated with lower rates of tumor recurrence compared to other immunosuppressors,suggesting their use especially in patients with HCC exceeding the conventional indication criteria for LT.

Liver transplantation in acute liver failure:A challengingscenario

Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, intervalbetween jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation.

Strategies to optimize the use of marginal donors in liver transplantation

Liver transplantation is the treatment of choice for end stage liver disease, but availability of liver grafts is still the main limitation to its wider use. Extended criteria donors(ECD) are considered not ideal for several reasons but their use has dramatically grown in the last decades in order to augment the donor liver pool. Due to improvement in surgical and medical strategies, results using grafts from these donors have become acceptable in terms of survival and complications; nevertheless a big debate still exists regarding their selection, discharge criteria and allocation policies. Many studies analyzed the use of these grafts from many points of view producing different or contradictory results so that accepted guidelines do not exist and the use of these grafts is still related to non-standardized policies changing from center to center. The aim of this review is to analyze every step of the donationtransplantation process emphasizing all those strategies, both clinical and experimental, that can optimize results using ECD.

Liver transplantation for viral hepatitis in 2015

Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus(HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus(HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.

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.