Key challenges of post-liver transplant weight management

Liver transplantation serves as a life-saving intervention for patients with endstage liver disease,yet long-term survival remains a challenge.Post-liver transplant obesity seems to have a significant contribution to this challenge and it emerges as a significant risk factor for graft steatosis,metabolic syndrome and denovo malignancy development.This review synthesizes current literature on prevalence,risk factors and management strategies for post-liver transplant obesity,emphasizing its impact on graft and patient survival.Literature review consultation was conducted in Medline/PubMed,SciELO and EMBASE,with the combination of the following keywords:Weight management,liver transplantation,immunosuppressive therapy,lifestyle interventions,bariatric surgery.Immunosuppressive therapy has a significant influence on long-term survival of liver transplant patients,yet it seems to have lesser effect on post-transplant obesity development than previously thought.However,it significantly contributes to the development of other components of metabolic syndrome.Key predisposing factors for post-transplant obesity development encompass elevated recipient and donor body mass index,a history of alcoholic liver disease,hepatocellular carcinoma,male gender,the absence of cellular rejection and the marital status of the recipient.Tailored immunosuppressive regimens,pharmacotherapy,lifestyle interventions and bariatric surgery represent key components in mitigating post-transplant obesity and improving long-term survival and quality of life in this group of patients.Timely identification and intervention thus hold paramount importance.Further research is warranted to refine optimal management strategies and enhance outcomes in this patient population.

Transplantation and Post-planting Tending and Management Techniques of Olive Trees(Olea europaea L.)

This paper introduced the preparation work before transplanting big olive trees(Olea europaea L.),including key technical measures such as plant excavation,transportation,planting,and post-planting tending.The aim was to provide scientific basis and feasible solutions for adjusting the density of olive trees in Shiyan City,and to assist in the high-quality development of the olive industry.

Post-transplant malignancy:Focusing on virus-associated etiologies,pathogenesis,evidence-based management algorithms,present status of adoptive immunotherapy and future directions

Modern immunosuppression has led to a decrease in rejection rates and improved survival rates after solid organ transplantation.Increasing the potency of immunosuppression promotes post-transplant viral infections and associated cancers by impairing immune response against viruses and cancer immunoediting.This review reflects the magnitude,etiology and immunological characteristics of various virus-related post-transplant malignancies,emphasizing the need for future research.A multidisciplinary and strategic approach may serve best but overall literature evidence targeting it is sparse.However,the authors attempted to provide a more detailed update of the literature consensus for the prevention,diagnosis,management and surveillance of post-transplant viral infections and associated malignancies,with a focus on the current role of adoptive immunotherapy and the way forward.In order to achieve long-term patient and graft survival as well as superior post-transplant outcomes,collaborative research on holistic care of organ recipients is imperative.

COVID-19 and liver injury:Pathophysiology,risk factors,outcome and management in special populations

The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2 is an ongoing health concern.In addition to affecting the respiratory system,COVID-19 can potentially damage other systems in the body,leading to extra-pulmonary manifestations.Hepatic manifestations are among the common consequences of COVID-19.Although the precise mechanism of liver injury is still questionable,several mechanisms have been hypothesized,including direct viral effect,cytokine storm,hypoxic-ischemic injury,hypoxiareperfusion injury,ferroptosis,and hepatotoxic medications.Risk factors of COVID-19-induced liver injury include severe COVID-19 infection,male gender,advanced age,obesity,and underlying diseases.The presentations of liver involvement comprise abnormalities in liver enzymes and radiologic findings,which can be utilized to predict the prognosis.Increased gamma-glutamyltransferase,aspartate aminotransferase,and alanine aminotransferase levels with hypoalbuminemia can indicate severe liver injury and anticipate the need for intensive care units’hospitalization.In imaging,a lower liver-to-spleen ratio and liver computed tomography attenuation may indicate a more severe illness.Furthermore,chronic liver disease patients are at a higher risk for severe disease and death from COVID-19.Nonalcoholic fatty liver disease had the highest risk of advanced COVID-19 disease and death,followed by metabolic-associated fatty liver disease and cirrhosis.In addition to COVID-19-induced liver injury,the pandemic has also altered the epidemiology and pattern of some hepatic diseases,such as alcoholic liver disease and hepatitis B.Therefore,it warrants special vigilance and awareness by healthcare professionals to screen and treat COVID-19-associated liver injury accordingly.

Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions

Patients with liver cirrhosis are susceptible to infections due to various mechanisms, including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine. Bacterial infections are common and represent a reason for progression to liver failure and increased mortality. Fungal infections, mainly caused by Candida spp., are often associated to delayed diagnosis and high mortality rates. High level of suspicion along with prompt diagnosis and treatment of infections are warranted. Bacterial and fungal infections negatively affect the outcomes of liver transplant candidates and recipients, causing disease progression among patients on the waiting list and increasing mortality, especially in the early posttransplant period. Abdominal, biliary tract, and bloodstream infections caused by Gram-negative bacteria [e.g., Enterobacteriaceae and Pseudomonas aeruginosa(P. aeruginosa)] and Staphylococcus spp. are commonly encountered in liver transplant recipients. Due to frequent exposure to broad-spectrum antibiotics, invasive procedures, and prolonged hospitalizations, these patients are especially at risk of developing infections caused by multidrug resistant bacteria. The increase in antimicrobial resistance hampers the choice of an adequate empiric therapy and warrants the knowledge of the local microbial epidemiology and the implementation of infection control measures. The main characteristics and the management of bacterial and fungal infections in patients with liver cirrhosis and liver transplant recipients are presented.

BK viral infection: A review of management and treatment

BK viral infection remains to be a challenging post-transplant infection,which can result in kidney dysfunction.The mainstay approach to BK infection is reduction of immunosuppression.Alterations in immunosuppressive regimen with minimization of calcineurin inhibitors,use of mechanistic target of rapamycin inhibitors,and leflunomide have been attempted with variable outcomes.Over the past few years,investigators have explored potential therapeutic options for BK infection.Fluoroquinolone prophylaxis and treatment was found to have no benefit in kidney transplant recipients.The utility of cidofovir is limited by its nephrotoxicity.Intravenous immunoglobulin is becoming a popular option for treatment and prophylaxis for BK infection,as it increases the neutralizing antibody titers against the most common BK virus serotypes.Virus-specific T cell therapy is an emerging treatment option for BK viremia.In this review,we will explore management and therapeutic options for BK infection and recent evidence available in literature.

Transfusion and coagulation management in liver transplantation

There is wide variation in the management of coagulation and blood transfusion practice in liver transplantation. The use of blood products intraoperatively is declining and transfusion free transplantations take place ever more frequently. Allogenic blood products have been shown to increase morbidity and mortality. Primary haemostasis, coagulation and fibrinolysis are altered by liver disease. This, combined with intraoperative disturbances of coagulation, increases the risk of bleeding. Meanwhile, the rebalancing of coagulation homeostasis can put patients at risk of hypercoagulability and thrombosis. The application of the principles of patient blood management to transplantation can reduce the risk of transfusion. This includes: preoperative recognition and treatment of anaemia, reduction of perioperative blood loss and the use of restrictive haemoglobin based transfusion triggers. The use of point of care coagulation monitoring using whole blood viscoelastic testing provides a picture of the complete coagulation process by which to guide and direct coagulation management. Pharmacological methods to reduce blood loss include the use of anti-fibrinolytic drugs to reduce fibrinolysis, and rarely, the use of recombinant factor VIIa. Factor concentrates are increasingly used; fibrinogen concentrates to improve clot strength and stability, and prothrombin complex concentrates to improve thrombin generation. Non-pharmacological methods to reduce blood loss include surgical utilisation of the piggyback technique and maintenance of a low central venous pressure. The use of intraoperative cell salvage and normovolaemic haemodilution reduces allogenic blood transfusion. Further research into methods of decreasing blood loss and alternatives to blood transfusion remains necessary to continue to improve outcomes after transplantation.

Acute respiratory distress syndrome after liver transplantation: etiology, prevention and management

Objective: To study the etiology, prevention andmanagement of acute respiratory distress syndrome(ARDS) after liver transplantation.Methods: The clinical data of 104 patients with end-stage liver diseases who had had liver transplanta-tions were retrospectively reviewed.Results: Seventeen patients (16.3%, 17/104) alto-gether were diagnosed as having ARDS after livertransplantation. Ten of them developed ARDS within24 hours, of whom 1 died during the operation, and7 developed ARDS 3 or 4 days after they were extu-bated and when methylprednisolone was tapered.Fourteen of the 17 ARDS patients (14/17) werefound to have overloaded crystalloid infusion, mas-sive transfusion of blood or blood products such asplasma, platelets, in addition to a prolonged surgicaltime secondary to serious bleeding during the dis-eased liver removal without evidence of active infec-tion. One was found to have serious systemic infec-tion and operatively disseminated intravascular coag-ulation. Four of the recipients developed ARDS sud-denly when intravenous cyclosporine was given on the3rd day after operation. One patient of the 4 had allof the aforementioned conditions. Two patients suf-fered from gastric aspiration. Five (30%, 5/17) ofthem survived ARDS with the combined treatmentconsisting of positive end-expiratory pressure me-chanicai ventilation suctioning as much edema fluidor sputum as possible, administration of diuretics,bolus of corticosteroids, and culture-based antibiot-ics. Hemeodialysis was indicated for patients with ol-iguric renal failure.Conclusions: ARDS is a serious multifactoral compli-cation after liver transplantation with a high mortali-ty and fatality. The most likely cause is fluid over-load from crystalloid liquid infusion or massive trans-fusion. The other predisposing or contributing fac-tors include sepsis, Ⅳ use of cyclosporine, fast ta-pering of corticosteroids, and gastric aspiration.Other factors such as transfusion-related acute lunginjury (TRALI), and reperfusion syndrome of thenewly implanted liver may also contribute. Thoughthe treatment should primarily be supportive in na-ture, it is helpful to understand the predisposing andcontributing factors and to aid in prevention, man-agement and treatment.

Advances in endoscopic management of biliary complications after living donor liver transplantation: Comprehensive review of the literature

Apart from noticeable improvements in surgical techniques and immunosuppressive agents, biliary complications remain the major causes of morbidity and mortality after living donor liver transplantation(LDLT). Bile leakage and stricture are the predominant complications. The reported incidence of biliary complications is 15%-40%, and these are known to occur more frequently in living donors than in deceased donors. Despite the absence of a confirmed therapeutic algorithm, many approaches have been used for treatment, including surgical, endoscopic, and percutaneous transhepatic techniques. In recent years, nonsurgical approaches have largely replaced reoperation. Among these, the endoscopic approach is currently the preferred initial treatment for patients who undergo duct-to-duct biliary reconstruction. Previously, endoscopic management was achieved most optimally through balloon dilatation and single or multiple stents placement. Recently, there have been significant developments in endoscopic devices, such as novel biliary stents, as well as advances in endoscopic technologies, including deep enteroscopy, the rendezvous technique, magnetic compression anastomosis, and direct cholangioscopy. These developments have resulted in almost all patients being managed by the endoscopic approach. Multiple recent publications suggest superior long-term results, with overall success rates ranging from 58% to 75%. This article summarizes the advances in endoscopic management of patients with biliary complications after LDLT.

Liver transplantation as a management of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common cancers worldwide and has a poor prognosis if untreated. It is ranked the third among the causes of cancer-related death. There are multiple etiologic factors that can lead to HCC. Screening for early HCC is challenging due to the lack of well specific biomarkers. However,early diagnosis through successful screening is very important to provide cure rate. Liver transplantation(LT) did not gain wide acceptance until the mid-1980 s,after the effective immunosuppression withcyclosporine became available. Orthotopic LT is the best therapeutic option for early,unresectable HCC. It is limited by both,graft shortage and the need for appropriate patient selection. It provides both,the removal of tumor and the remaining cirrhotic liver. In Milan,a prospective cohort study defined restrictive selection criteria known as Milan criteria(MC) that led to superior survival for transplant patients in comparison with any other previous experience with transplantation or other options for HCC. When transplantation occurs within the established MC,the outcomes are similar to those for nonmalignant liver disease after transplantation. The shortage of organs from deceased donors has led to the problems of long waiting times and dropouts. This has led to the adoption of extended criteria by many centers. Several measures have been taken to solve these problems including prioritization of patients with HCC,use of pretransplant adjuvant treatment,and living donor LT.

Collagen matrix scaffolds:Future perspectives for the management of chronic liver diseases

Approximately 1.5 billion chronic liver disease(CLD)cases have been estimated worldwide,encompassing a wide range of liver damage severities.Moreover,liver disease causes approximately 1.75 million deaths per year.CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process,cell death,over deposition of extracellular matrix proteins,and dysregulated regeneration.Overall,these processes impair the correct function of this vital organ.Cirrhosis and liver cancer are the main complications of CLD,which accounts for 3.5%of all deaths worldwide.Liver transplantation is the optimal therapeutic option for advanced liver damage.The liver is one of the most common organs transplanted;however,only 10%of liver transplants are successful.In this context,regenerative medicine has made significant progress in the design of biomaterials,such as collagen matrix scaffolds,to address the limitations of organ transplantation(e.g.,low donation rates and biocompatibility).Thus,it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.

Is there any difference in anesthetic management of different post-OLT stage patients undergoing nontransplant organ surgery?

BACKGROUND: Little information is available about anesthesia management of nontransplant organ surgery of recipients after adult liver transplantation. The aim of this study was to discuss the anesthesia management of recipients for different stages after liver transplantation. METHODS: The medical records of 16 patients were reviewed after OLT scheduled for elective nontransplant organ surgery at our institution from September 2002 to October 2005. The patients were divided into perioperative stage (group A) and mid-term and long-term stage (group B) groups according to post-OLT time. The data of 16 patients preoperation, intraoperation and postoperation were analyzed. RESULTS: The measurements of alanine transaminase (ALT), total bilirubin (TB), prothrombin time (PT), and lung infection were significantly higher in group A than in group B (P<0.05). The incidence of hyperglycaemia was significantly higher in group B than in group A (P<0.05). During operation the incidence of hypotension was significantly higher in group A than in group B (P<0.05). After operation, the number of patients in ICU was significantly larger and the extubation time was longer in group A than in group B. General anesthesia was induced in 14 patients, and regional anesthesia in 2 patients. CONCLUSIONS: Regional or general anesthesia can be safely delivered to adult OLT recipients except for contraindications. Special considerations include protection of the function of important organs, correction of hemodynamic instability in perioperative stage patients after OLT, and measurement of the side-effects of immunosuppression in mid-term and long-term stage patients.

Swine model in transplant research: Review of anaesthesia and perioperative management

Pigs are one of most common animal species to be used in biomedical models due to their many anatomical visceral similarities with humans, particularly with regards to transplantation. Despite this use, in many of the researches in which pigs are selected for transplantation, the anaesthesia used is an adaptation of human anaes-thesia and presents some limitations such as a reduced analgesia a limited control in perioperative period. In this review we show some of the most important conditions in the preanaesthetic management and of swine as well as we review of anaesthetic protocols for the most common types of swine model of transplantation.

Meningeal cryptococcosis in a pancreas transplant recipient requiring grafectomy: A case report

BACKGROUND Through continuous improvement in transplantation medicine,a wider range of solid organ transplant(SOT)recipients is considered suitable for complex procedures.Despite advances in modern transplantation practice,transpiring invasive fungal infections pose a substantial threat for SOT recipients.To our knowledge,cryptococcal infection confined amidst sole pancreas SOT recipients has not been described to date.Enforcement of a multidisciplinary transplant team approach in the management of pancreas SOT recipients presenting with complex cryptococcal complications is fundamental in improving patient outcomes.CASE SUMMARY We present the case of a female pancreas transplant recipient,with confirmed meningeal cryptococcosis,referred to our institution for further evaluation and treatment from the Regional Center for Infectious Diseases.On admission,the patient was weaned from the protocolized immunosuppression therapy for two consecutive weeks,in addition to tapering systemic corticosteroid remedial treatment.Our novel multidisciplinary transplant team approach embodied exhaustive discussions of possible complex and diverse multiple organ system physiologic and pathologic challenges associated with distinct management strategies in pancreas transplant recipients.Owing to the potentially devastating impact of invasive cryptococcosis in terms of morbidity and mortality,a definitive surgical intervention of pancreas transplant grafectomy was reinforced,as a pathway towards secure access to early meaningful expertise care.The patient was discharged to the Regional Center for Infectious Diseases 2 mo after the admittance further advancing to a clinical improvement.CONCLUSION The precision transplantation approach by tailoring complex medical interventions to individual needs proved indispensable in improving our patient’s outcomes.

Innovative management of the open abdomen:ultrasound Doppler-guided gradual abdominal wall closure after pediatric liver transplantation

Objective:Primary abdominal wall closure can be difficult after liver transplantation(LT),mostly in cases involving an oversized liver graft with edema of the intestine.Conventional closure with extensive tension may compromise graft perfusion.An open abdomen significantly increases the risk of infection and fluid loss.

Endoscopic management of biliary strictures post-liver transplantation

Biliary complications play a significant role in morbidity of liver transplant recipients. Biliary strictures occur between 10%-25% of patients with a higher incidence in living donor recipients compared to deceased donors. Strictures can be classified as either anastomotic or non-anastomotic and may be related to ischemic events. Endoscopic management of biliary strictures in the posttransplant setting has become the preferred initial approach due to adequate rates of resolution of anastomotic and non-anastomotic strictures(NAS).However, several factors may increase complexity of the endoscopic approach including surgical anatomy, location, number, and severity of bile duct strictures.Many endoscopic tools are available, however, the approach to management of anastomotic and NAS has not been standardized. Multi-disciplinary techniques may be necessary to achieve optimal outcomes in select patients. We will review the risk factors associated with the development of bile duct strictures in the posttransplant setting along with the efficacy and complications of current endoscopic approaches available for the management of bile duct strictures.

Challenges related to clinical decision-making in hepatocellular carcinoma recurrence post-liver transplantation: Is there a hope?

Hepatocellular carcinoma(HCC)is a common liver malignancy and represents a serious cause of cancer-related mortality and morbidity.One of the favourable curative surgical therapeutic options for HCC is liver transplantation(LT)in selected patients fulfilling the known standard Milan/University of California San Francisco criteria which have shown better outcomes and longer-term survival.Despite careful adherence to the strict HCC selection criteria for LT in different transplant centres,the recurrence rate still occurs which could negatively affect HCC patients’survival.Hence HCC recurrence post-LT could predict patients’survival and prognosis,depending on the exact timing of recurrence after LT(early or late),and whether intra/extrahepatic HCC recurrence.Several factors may aid in such a complication,particularly tumour-related criteria including larger sizes,higher grades or poor tumour differentiation,microvascular invasion,and elevated serum alpha-fetoprotein.Therefore,managing such cases is challenging,different therapeutic options have been proposed,including curative surgical and ablative treatments that have shown better outcomes,compared to the palliative locoregional and systemic therapies,which may be helpful in those with unresectable tumour burden.To handle all these issues in our review.

Liver Transplantation in the Elderly: An Evidence Based Review on Patient Outcome, Selection and Management Strategies

There has been a steady increase in the age of potential recipients for liver transplantation over the past two decades. While patients older than age 60, on average, did not do as well as younger patients after transplantation, optimizing patient selection could minimize this discrepancy. It is appropriate to evaluate functional elderly patients without significant medical comorbidities for liver transplantation for the same indications as younger patients. For elderly patients with hepa-tocellular carcinoma and otherwise compensated liver disease, however, it is important to consider alternative treatment modalities that could provide similar survival. Elderly candidates who became too ill should be compassionately counseled away from transplantation based on existing prognostic models that can accurately predict post-transplant mortality. Finally, elderly transplant candidates and recipients may benefit from a more tailored management strategy in terms of donor risk matching and less immunosuppression.

Usefulness of Monitoring Stroke Volume Variations for Fluid Management During Pediatric Living-Donor Liver Transplantation

Purpose: Central venous pressure (CVP) is considered to be unsuitable as preload parameter. Stroke volume variation (SVV) has recently been reported to be effective as a preload and fluid responsiveness parameter, and its usefulness for fluid management during living-donor liver transplantation (LDLT). However, use of SVV has not been reported in children. Our aim is to evaluate the use of SVV as a target parameter of circulating blood volume during pediatric LDLT. Methods: This retrospective study was conducted in 40 consecutive patients aged between 5 and 109 months who underwent elective LDLT. Twenty patients underwent LDLT without FloTrac? (C group) and the rest patients underwent LDLT with the FloTrac? monitoring (F group). As a fluid management target, CVP was maintained at 10 mmHg in the C group and SVV at 10% in the F group. We compared MAP and CVP at the times of the greatest decrease within 5 minutes after reperfusion. Results: MAP after reperfusion was significantly decreased in both groups (P < 0.01), with the magnitude of decrease significantly greater in the C group compared with the F group (P = 0.02). MAP before and after reperfusion did not significantly differ between the groups. After reperfusion, CVP was nearly the same in both groups, with that in the C group slightly decreased and nearly no change in the F group. SVV after reperfusion was significantly increased (P < 0.001). Conclusion: When used as a target parameter for fluid management during pediatric LDLT, hemodynamic changes was less when SVV was used as the parameter of circulating blood volume.

Effect of cardiac output-guided hemodynamic management on acute lung injury in pediatric living donor liver transplantation

BACKGROUND Acute lung injury(ALI)after liver transplantation(LT)may lead to acute respiratory distress syndrome,which is associated with adverse postoperative outcomes,such as prolonged hospital stay,high morbidity,and mortality.Therefore,it is vital to maintain hemodynamic stability and optimize fluid management.However,few studies have reported cardiac output-guided(CO-G)management in pediatric LT.AIM To investigate the effect of CO-G hemodynamic management on early postoperative ALI and hemodynamic stability during pediatric living donor LT.METHODS A total of 130 pediatric patients scheduled for elective living donor LT were enrolled as study participants and were assigned to the control group(65 cases)and CO-G group(65 cases).In the CO-G group,CO was considered the target for hemodynamic management.In the control group,hemodynamic management was based on usual perioperative care guided by central venous pressure,continuous invasive arterial pressure,urinary volume,etc.The primary outcome was early postoperative ALI.Secondary outcomes included other early postoperative pulmonary complications,readmission to the intense care unit(ICU)for pulmonary complications,ICU stay,hospital stay,and in-hospital mortality.RESULTS The incidence of early postoperative ALI was 27.7%in the CO-G group,which was significantly lower than that in the control group(44.6%)(P<0.05).During the surgery,the incidence of postreperfusion syndrome was lower in the CO-G group(P<0.05).The level of intraoperative positive fluid transfusions was lower and the rate of dobutamine use before portal vein opening was higher,while the usage and dosage of epinephrine during portal vein opening and vasoactive inotropic score after portal vein opening were lower in the CO-G group(P<0.05).Compared to the control group,serum inflammatory factors(interleukin-6 and tumor necrosis factor-α),cardiac troponin I,and N-terminal pro-brain natriuretic peptide were lower in the CO-G group after the operation(P<0.05).CONCLUSION CO-G hemodynamic management in pediatric living-donor LT decreases the incidence of early postoperative ALI due to hemodynamic stability through optimized fluid management and appropriate administration of vasopressors and inotropes.