Exercise training as an intervention for frailty in cirrhotic patients on the liver transplant waiting list:A systematic review

BACKGROUND The existing literature suggests that exercise for cirrhotic patients is safe and favours significant improvement to their physical capacity.However,exercise training for this population and how to deliver activities,especially in severe stages of the disease and while waiting for a liver transplant(LT),remain undefined.AIM To review the existing exercise prescriptions for cirrhotic patients on the waiting list for LT,their results for frailty evolution and their effect on clinical outcomes.METHODS A systematic review was performed following the Preferred Reporting Review and Meta-Analysis guidelines and searching the PubMed,MEDLINE,and Scopus databases.The keyword“liver transplant”was used in combination with the free terms“frailty”and“exercise”for the literature review.Clinical studies that evaluated the effect of a regular training program,independent of supervision or the duration or intensity of physical exercise,in cirrhotic patients on the waiting list for LT were reviewed.The data on safe physical activity prescriptions following Frequency,Intensity,Time,and Type recommendations were extracted and summarised.RESULTS Nine articles met the inclusion criteria for this review.Various instruments for frailty assessment were used,frequently in combination.Five studies prescribed physical activity for patients,one in-person and four to be performed remotely and unsupervised.The remaining four studies only used a self-report instrument to assess the level of physical activity.None reported adverse events related to exercise training.The exercise frequency mainly varied from daily to a minimum of twice per week.The intensity depended on frailty and included increasing levels of activity.The type of exercise was predominantly a combination of aerobic and resistance training.The duration of exercise varied from 4 to 12 wk.Three articles evaluated the effect of the exercise program on clinical outcomes,reporting a reduction in 90-d readmission rates post-transplant and improved frailty scores,as well as improved survival of cirrhotic patients waiting for LT.CONCLUSION Routine frailty assessment is essential for this population.Although more robust evidence is required,the prescription of exercise is safe and can improve patients’functional capacity,improving pre-and post-LT outcomes.

Delayed referral for liver transplant evaluation worsens outcomes in chronic liver disease patients requiring inpatient transplant evaluation

BACKGROUND Indications to refer patients with cirrhosis for liver transplant evaluation(LTE)include hepatic decompensation or a model for end stage liver disease(MELDNa)score≥15.Few studies have evaluated how delaying referral beyond these criteria affects patient outcomes.AIM To evaluate clinical characteristics of patients undergoing inpatient LTE and to assess the effects of delayed LTE on patient outcomes(death,transplantation).METHODS This is a single center retrospective cohort study assessing all patients undergoing inpatient LTE(n=159)at a large quaternary care and liver transplant center between 10/23/2017-7/31/2021.Delayed referral was defined as having prior indication(decompensation,MELD-Na≥15)for LTE without referral.Early referral was defined as referrals made within 3 mo of having an indication based on practice guidelines.Logistic regression and Cox Hazard Regression were used to evaluate the relationship between delayed referral and patient outcomes.RESULTS Many patients who require expedited inpatient LTE had delayed referrals.Misconceptions regarding transplant candidacy were a leading cause of delayed referral.Ultimately,delayed referrals negatively affected overall patient outcome and an independent predictor of both death and not receiving a transplant.Delayed referral was associated with a 2.5 hazard risk of death.CONCLUSION Beyond initial access to an liver transplant(LT)center,delaying LTE increases risk of death and reduces risk of LT in patients with chronic liver disease.There is substantial opportunity to increase the percentage of patients undergoing LTE when first clinically indicated.It is crucial for providers to remain informed about the latest guidelines on liver transplant candidacy and the transplant referral process.

Follicular dendritic cell sarcoma of the liver:unusual presentation of a rare tumor and literature review

BACKGROUND:Hepatic follicular dendritic cell (FDC) sarcoma is an extremely rare neoplasm.Most commonly,FDC sarcoma presents as a solitary mass in lymph nodes,however,several extra-nodal locations have been identified.METHODS:We report a case of a 53-year-old female who presented with symptoms of abdominal pain,fever,anemia,and jaundice.After an extensive review of the literature,we have found only 12 cases of hepatic FDC sarcoma.RESULTS:The tumor was 11.5 cm in diameter and composed of spindle and epithelioid cells with ovoid nuclei and associated with mixed inflammatory infiltrate.Immunohistochemical stains were positive for CD35 and CD21.The patient underwent a left hepatic lobectomy.CONCLUSIONS:Liver follicular dendritic cell sarcoma is a very rare tumor.Most cases present with abdominal pain and weight loss,and most of them can be managed by hepatic resection with excellent short-term outcomes.

Xanthogranulomatous cholecystitis mimicking gallbladder cancer and causing obstructive cholestasis

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a destructive inflammatory disease of the gallbladder that can mimic gallbladder carcinoma. METHODS: We present the case of a 35-year-old Hispanic male complaining of right upper quadrant pain and jaundice for 2 months prior to admission. He denied a history of fever, nausea/ vomiting, and weight loss. The past medical history was relevant only for diabetes. He had no previous history of jaundice or previous operations. RESULTS: CA19-9 was slightly elevated (52 U/mL). Abdominal ultrasonography showed an irregular thickening of the gallbladder wall and no gallstones were detected. CT scan also revealed an irregular thickening of the wall of the gallbladder body suggestive of malignancy. At laparotomy, the mass was adherent to the duodenum and colon, and although the frozen section biopsy was negative, the intraoperative findings were suggestive of malignancy, and the patient underwent left liver trisegmentectomy, resection of the common bile duct and Roux-en-Y hepaticojejunostomy. Pathological examination unexpectedly revealed XGC without malignancy. CONCLUSIONS: Preoperative and intraoperative differential diagnosis of XGC from gallbladder carcinoma remains a challenge when it is associated with inflammatory involvement of surrounding tissues. Since gallbladder carcinoma and XGC may coexist, radical resection is justified when malignancy cannot be completely ruled out.

Liver graft vascular variant with 3 extra-hepatic arteries

Vascular anatomy of the liver is varied,and the 'standard'anatomy is seen in 55%-80%of cases.It is very important that extrahepatic arteries are identified precisely at the time of graft procurement to avoid injuries that might compromise the liver function.In the present case the liver donor had the vascular anatomy of Michels typeⅦ,e.g.a hepatic artery originating from the celiac trunk and going to the left lobe,an accessory left hepatic artery coming from the left gastric artery,and a replaced right hepatic artery coming from the superior mesenteric artery.This pattern of vascular supply is uncommon,representing less than 5%of cases.The replaced hepatic artery was reconstructed in the back-table with polypropylene suture 7.0 by connecting it to the stump of the splenic artery,and the celiac trunk of the graft was anastomosed to the recipient common hepatic artery.

Potential approaches to improve the outcomes of donation after cardiac death liver grafts

There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death(DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods:(1) different ex vivo perfusion techniques;(2) persufflation with oxygen; and(3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft's for transplantation, improve the outcomes, and decrease the mortality on the waiting list.

Therapeutics administered during ex vivo liver machine perfusion:An overview

Although the use of extended criteria donors has increased the pool of available livers for transplant,it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury(IRI),as these"marginal"organs are particularly vulnerable to IRI during the process of procurement,preservation,surgery,and post-transplantation.In this review,we explore the current basic science research investigating therapeutics administered during ex vivo liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation process.These various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway,utilizing defatting cocktails,and administering classes of agents such as vasodilators,anti-inflammatory drugs,human liver stem cell-derived extracellular vesicles,and δ-opioid agonists in order to reduce the damage of IRI.Ex vivo machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ,effectively deliver substrates and oxygen required for cellular metabolism,therapeutically administer pharmacological or cytoprotective agents,and continuously monitor organ viability during perfusion.The use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science studies.While novel therapeutic approaches to combat IRI are being developed through basic science research,their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.

Impact of recipient functional status on 1-year liver transplant outcomes

BACKGROUND The Karnofsky Performance Status(KPS)scale has been widely validated for clinical practice for over 60 years.AIM To examine the extent to which poor pre-transplant functional status,assessed using the KPS scale,is associated with increased risk of mortality and/or graft failure at 1-year post-transplantation.METHODS This study included 38278 United States adults who underwent first,non-urgent,liver-only transplantation from 2005 to 2014(Scientific Registry of Transplant Recipients).Functional impairment/disability was categorized as severe,moderate,or none/normal.Analyses were conducted using multivariableadjusted Cox survival regression models.RESULTS The median age was 56 years,31%were women,median pre-transplant Model for End-Stage for Liver Disease score was 18.Functional impairment was present in 70%;one-quarter of the sample was severely disabled.After controlling for key recipient and donor factors,moderately and severely disabled patients had a 1-year mortality rate of 1.32[confidence interval(CI):1.21-1.44]and 1.73(95%CI:1.56-1.91)compared to patients with no impairment,respectively.Subjects with moderate and severe disability also had a multivariable-adjusted 1-year graft failure rate of 1.13(CI:1.02-1.24)and 1.16(CI:1.02-1.31),respectively.CONCLUSION Pre-transplant functional status is a useful prognostic indicator for 1-year posttransplant patient and graft survival.

Machine perfusion of the liver:Putting the puzzle pieces together

The realm of extended criteria liver transplantation created the'adjacent possible'for dynamic organ preservation.Machine perfusion of the liver greatly expanded donor organ preservation possibilities,reaching before unattainable goals,including the mitigation of ischemia-reperfusion injury,viability assessment,and organ reconditioning prior to transplantation.However,current scientific evidence lacks uniformity between studies,perfusion protocols,and acceptance criteria.Construction of collaborative research networks for sharing knowledge should,therefore,enable the development of high-level evidence and guidelines for machine perfusion utilization,including donor acceptance criteria.Finally,this approach shall guarantee conditions for further progress to occur.