Liver Transplantation - Science topic

Subject: Invitation to Join Dailyplanet.Club and Recommendations for Publishing Your Case Report

Dear Zuhair Ali Rizvi,

I hope this message finds you well.

I would like to invite you to join us at www.Dailyplanet.Club, a vibrant community of researchers, professionals, and innovators who collaborate on groundbreaking work across various fields, including medicine. Your question about publishing a case report on anesthesia in liver transplant recipients is of particular interest, and I believe you would find valuable connections and support within our network.

Regarding your query, here are a few journals with good acceptance rates and early response times that specialize in medical case reports:

I would love to explore more publishing opportunities with you and support your work at Dailyplanet.Club. We would be thrilled to have you as part of our community!

Best regards, MJ CEO, Dailyplanet.Club MJHSA Ltd.

"Prevalence" is the number of occurrences in the whole population studied. Individual rates could still be subdivided between arterial vs. venous, stenotic vs. thrombotic, whole organ vs. live donor, whatever so longas population size remains adequate for analysis. "Incidence" is the number of NEW events in a population under study. You might check with your institutions' statistician, but I believe incidence is not a retrospective descriptor. Looking back over time for vascular events will give you the PREVALENCE in the (sub)population studied. Finding associations explaining prevalence in your retrospective study (perhaps using analysis of variance) could lead to changes in operative strategy to reduce the incidence of that problem moving forward. For example: suppose the "prevalence" of arterial thrombosis was 5% overall, but 10% with a greater than 4mm diameter mismatch between donor and recipient. Changing surgical technique would hopefully reduce the "incidence" of this complication moving forward. But that's another study...

The transplantation team must select these patients very cautiously because the risk of neoplastic relapse into the new liver, is very high

Alemtuzumab, sold under the brand name Campath among others, is a medication used to treat chronic lymphocytic leukemia (CLL) and multiple sclerosis.

We prefer a single stage, same anesthesia, lap chole with intraoperative cholangiogram and if common bile duct stone (s) is confirmed, ERCP during the same procedure. If endoscopist cannot do it, we proceed with laparoscopic exploration of the CBD and/or rendez-vous. Anyway, we try to complete the procedure at the same OR time.

This is a prevalent problem—the analysis of multicentre clinical trials when there is heterogeneity between centers.

Irradiation preferentially kills rapidly dividing cells, including bone marrow and epithelial cells of the gut and other organs. The most common application of rodent irradiation is to destroy the bone marrow and other hematopoietic progenitors (myeloablation), either for immunosuppression or before replacing the immune system with donor grafts.

Perioperative mortality after Oliver transplantaron must be included within 30 days of the intervención, short term survival must be included living less than 3 months and long-xterm survival living more than 5 years after grafting

Our institute has the largest team of liver transplant surgeons in Turkey. 13 recipient and 10 donor hepatectomy surgeons works in synchrone.

We have 36 ICU beds, 12 operating rooms in our institute.

I think ours is the only institute in the world that dedicated for only liver surgery and research.

We perform over than 250 live donor liver transplantation a year, some years over 300.

So, we can perform 2 LDLT a day routinely.

Thanks for your replies.

My be one of the highest level of serum bilirubin reached

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Data on the matter in question may relate to many factors e.g. magnitude of alcohol related problems in a country [data from countries where alcohol is social or religious taboo will be very different from those that are not], alcohol related diseases [psychiatric, injuries, liver etc] alcohol related liver disease [which further include decompensated liver disease, acute on chronic liver failure, alcoholic hepatitis etc] and each of which will be different in different regions of the world. Added to this it must remembered that the above mentioned points may occur in unison which also affect outcomes depending on the multidisciplinary medical infrastructure in a country devoted to diagnosing and treating alcohol related problems [which is dismal in India] Alcohol problems are also under reported most times.

Considering liver disease, data in meagre in India [for relapse rates check article: Narendra S. Choudhary, Naveen Kumar, Sanjiv Saigal,⁎ Rahul Rai, Neeraj Saraf, and Arvinder S. Soin. Liver Transplantation for Alcohol-Related Liver Disease. J Clin Exp Hepatol. 2016 Mar; 6(1): 47–53.] Data will vary according to nature of alcohol related liver disease that is being treated. I also personally feel that much of these data are biased in favour of selection of patients who have chance of better outcome on pretransplant check up. Also the follow up period is very variable and most studies do not report long term outcome.

The patient underwent heart transplantation on December 2017. Post-operative chilothorax was treated by thoracic duct ligation and low-fat diet. After a transitory acute kidney insufficiency, treated by CVVH, the renal function is now optimal. Colchicine was used to treat the tendency to anasarcatic state due to AKI and lymphatic stasis secondary to thoracic duct ligation and chronic venous ipertension due to Fontan circulation. No problems related to liver function were evidenced. The patient was discharged and we plan to check his liver in the next months. I'll let you know the results. Thanks to all for the suggestions.

Ithink there are no connection between the two

For what purpose you want to fulfill a partial model of hepatectomy - regeneration, studies of drugs etc? What degree of resection plan: 60-70% or more? There are lots of old simple methods remove a large lobe and the right or the left (depending on surgical approach) by ligating the base shares without overlapping the Central bile ducts. To minimize injury to the animals using flat tweezers grip, which is convenient to pull the lobe with no damage and the risk of bleeding. In young animals (mice up to 3 months) the liver is delicate and easily damaged.

Dear Sezin,

The important issue is the time point of injection. Please try to do your experiment at late afternoon, if you work on rodents. You will get considerable results depending on the experimental time or you have to fasten the animals at least 8 hours before the injection.

Relif of causes is the best option

Dear Timothy

I understand that your company as you stated above "We manufacture hepatocytes for therapeutic purposes and are in clinical trials right now.  " is using discarded livers from TX to use them as a source for hepatocytes transplantation.

This is a very salutable goal, due to the scarcity of livers and linked to the possibility to use in some diseases- especially pediatric- hepatocytes TX instead of split livers of whole livers TX.

I wish you good luck with the clinical trials as well as with fulfilling the regulatory hurdles and the tight GMP demands for it.

I did not quite understand the second part of your question, stated below:

"I wanted to know if you have the need for a source of non-transplantable organs (heart, lung, pancreas, kidney, intestine and liver).  If so, we might be able to help you source the raw material."

As you mentionned it, you are in contact with different OPOs in the USA who are able to provide you with non transplantable organs as listed above.

The regulatory legislation for organ procurement as well as the use of discarded ogans from TX in Europe is a bit different from USA and each country has its own legislation regarding the use of human cells or tissues for research purposes.

Thus, I am afraid your offer to help researchers with the tissue or cells from discarded organs from RX will be limited to US centers.

Kind regards, Michaela

Here, I would like to describe the molecular pathophysiology and promising therapeutic strategy for hepatic encephalopathy (HE). This review states that astrocytic glutamine synthetase makes glutamine from glutamate, one of excitotoxic neurotransmitters, and ammonia.1 The source of glutamate in the edematous brain of HE is from the cystine-glutamate antiporter, referred to as system xc−, which exchanges extracellular cystine for intracellular glutamate.2,3 The system xc− is a heterodimeric complex composed of catalytic light chain xCT and regulatory heavy chain 4F2hc, which is crucial for membrane localization of xCT.3 Both damaged oligodendrocytes and activated microglia are responsible for the dysregulated system xc− in HE.3,4 Elevated glutamine release from astrocytes which is promoted by microglia-induced neuroinflammation causes oligodendrocyte excitotoxicity via AMPA receptor activation. That is why NSAIDs have been shown to exhibit partial therapeutic effect. 4 Furthermore, excessive amount of ammonia due to hepatic failure can act as a toxic agent only after the modification with glutamate.1,2 Given that system xc− ameliorates the HE, the development of system xc− inhibitors which can penetrate through BBB should be warranted.

(175 words)

References

1. Wijdicks EF. Hepatic Encephalopathy. N Engl J Med. 2016;375:1660-1670.

2. Aldridge DR, Tranah EJ, Shawcross DL. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol. 2015;5:S7-S20.

3. Bridges RJ, Natale NR, Patel SA. System xc⁻ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS. Br J Pharmacol. 2012;165:20-34.

4. Zemtsova I, Görg B, Keitel V, Bidmon HJ, Schrör K, Häussinger D. Microglia activation in hepatic encephalopathy in rats and humans. Hepatology. 2011;54:204-15.

You have in my book with titel Transplantation KIidney and pancreas clninical immunoology  aspects and  pharmacotherapy on my paper on Researchgate in chapter 8. Protocols for kidney transplantation, chapter 10 Protocols for pancreas transpntation  and chapter 11. General guidlines for translant patients!I told you to put ResearchGATE in electronic form can be found here and talk about the protocol of the oral cavity before and after the transplant!

The percentage of false positivity with Fibroscan is very low (less than 3%)

Hi,

 I have not found or know any specific markers for Th3 cells.

However they should secrete TGF-b, so if you want to characterize them with flow cytometry one could block secretion of cytokines with a GolgiStop and do an intracellular fowcytometry for TGF along with other surface markers like CTLA-4 and CD25.

You could also refer to this paper. It can guide you to differentiate Tregs from Th3 cells

Not aware of this being an issue post liver transplantation-

Years ago when we were using it in the setting of poor initial graft function in the liver transplant recipient it was an observation that hypotension could be an issue leading to the PGE1 having to be ceased.

Dr. Hussein,

my experience with intraomental transplantation of various tissues taught me that tissue fragments up to 5 mm can survive until some angiogenesis occurs (3-4 Days). However, I did not do think this will decrease AST or ALT as these will be degraded naturally. Tissue degradation will occur thourgh ischemia and/or necrosis and inflammation not enzymatically. Hard to quantify the function of this transplanted tissue as initially it will not support the animal - that will be done by the remnant tissue which will grow in its turn. Histology may be needed. 

Yes, we used it. It was succesful. The patients flares were well controlled. Crp levels decreased to normal levels. 

I don't feel its a good choice to freeze down any samples for ROS estimations..as there maybe significant changes in ROS levels during thawing and processing..also to check energy levels..please try checking ATP, NADH, NADPH and ion levels like Ca2+ etc..i suggest doing them immediately or not delaying it beyond 10-12 h after sample collection when snap frozen cryogenically..

Trials of non-biologic support including two controlled trials published last year have failed to show a survival benefit.  These are very difficult to do because patients are very ill and frail - you may cause as much harm as good.  Biologic devices have suffered from poor design - Vital Therapies changed the original design and cell line, and then seemed surprised that the results were not as good as the animal models and initial studies had suggested.  Adding the complexity and cost of an extracoporeal circulation to a critically ill patient is just more complicated than you think.

Below are several PDFs and links to resources including a 20 year national survey in Argentina. These transplants seem to take a great deal of time. One study from a surgical center found the median wait time between BDI and liver transplant was 11 years. 

Let me know if these weren't the kind of resources you were looking for or if you need more information. Happy to help in any way I can.

This lady aborted a fetus due to infection with hepatitis E, which has bad outcomes in pregnancy. However the outcomes improve if the fetus is delivered which is the case with this lucky lady. Further her bilirubin and INR has improved. Since her renal parameters are normal, inj. Mannitol can be given to reduce brain edema and improve her GCS. Ammonia lowering agents can be tried like L-Ornithine-L-Aspartate. However my experience is that such patients take pretty long time for improvement. Also since she is having seizures, a gynaecology consult may be done to rule out two dreaded complication -- eclampsia and acute fatty liver of pregnancy both of which have far poorer outcomes

I'm sure Deepthi Gadu is no fault by performing the assay. The test repetition will reproduce the anomaly.

I observed such results several times, always when conjugated bilirubin is very high.

I assumed that the adjuvants intended to promote the reaction of unconjugated bilirubin with the diazo slowed in this case its answer,  while the conjugated bilirubin reacts quickly with diazo: a kinetic modified of the reaction of the  two types of bilirubin with diazo?

Here s a movie made by me. It s the procedure of a Dual Living Donor Liver Transplant.

Left lobe + left lateral section.

HA was made with interposition of a deceased donor iliac artery graft. - minute 7:40 in the movie.

https://www.youtube.com/watch?v=CoPIbBIwYgE 

One other avenue you may wish to pursue is to apply to join the Liver Transplantation & Hepatobiliary group on Linked In (you must have a Linked In profile), and then post the same question there.

Hepatic diseases: hepatitis C, recurrent HCC, recurrent alcoholism and fatty liver.

Extrahepatic diseases: Cardiovascular risk factors and renal failure are very important problems, but malignancy is a growing problem in most transplant centers.

Not sure where you can get this test performed.  I'd suggest asking Ronen Arnon (Pediatrics Liver) since PFIC patients are seen mostly in the Pediatrics practice.

Timing of recurrence in relation to firs resection as well as signs of microvascular invasion and AFP level are crucial information in order to make an optimal assessment. If the time frame is less than 12 months, it may well be that this is not recurrence but a staging error due to the fact that microscopic tumors will not be possible to diagnose on the original imaging.  If no vascular invasion, and a short interval, salvage transplantation is a viable option

Have you reviewed these papers?

Gavalda, J., Len, O., San Juan, R., Aguado, J. M., Fortun, J., Lumbreras, C., ... & Pahissa, A. (2005). Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study. Clinical infectious diseases, 41(1), 52-59.

Fortún, J., Martín‐Dávila, P., Moreno, S., de Vicente, E., Nuño, J., Candelas, A., ... & García, M. (2002). Risk factors for invasive aspergillosis in liver transplant recipients. Liver transplantation, 8(11), 1065-1070.

Pappas, P. G., Alexander, B. D., Andes, D. R., Hadley, S., Kauffman, C. A., Freifeld, A., ... & Chiller, T. M. (2010). Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clinical Infectious Diseases, 50(8), 1101-1111.

Singh, N., Avery, R. K., Munoz, P., Pruett, T. L., Alexander, B., Jacobs, R., ... & Linden, P. (2003). Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients. Clinical infectious diseases, 36(1), 46-52.

Well, I think that in liver transplantation there is no prospective, independent and randomised mutlicenter study which is large enough and has enough power to show that cyclosporin or any form of tarcrolimus has superior results for the patients - used as induction therapy or long term. If somebody thinks there is, I would like to see one.

Again, we would use The TEG to monitor changes, try to explain abnormal blessings or effects of heparin (extrinsic and intrinsic) - not as a pre-emptic tool before clinical signs appear.

Hepatic blood volume in anaesthetized normel pig is about 25% (Munk OL, Bass L, Roelsgaard K, Bender D, Hansen SB, Keiding S. Liver kinetics of glucose analogs measured in pigs by PET: Importance of dual-input blood sampling. J Nucl Med 2001;42:795-801). We have data from on-going studies in pigs and healthy human subjects that confirm these results.

Maybe a  better question to ask is: do you use Stereotactic body radiotherapy (SBRT) aka Cyberknife, for treatment of any liver tumors?  There has been a wealth of experience from Asia that SBRT is as effective and less toxicity than TACE or RFA.

We would be interested as well and could probably organize the whole Nordic Liver group to participate

I thank all for the responses.

I think, that rapid deterioration or “critically ill cirrhotic” could be regarded as acute decompensation and as acute-on-chronic liver failure (ACLF).

ACLF is potentially reversible, but acute decompensation could also be potentially reversible condition. ACLF usually results following a precipitating event (bacterial infection, GI bleeding, HBV etc.), and the AD develops because of the same events.

It is important to know, why one patient is tolerant to accelerating events, but others are not.

Excellent research CANONIC has given us the tool for stratification of risk for critically ill cirrhotic (CLIF-SOFA score).

Identification of risk defines early specific treatments and intensive management.

In line with very old data by Medawar on tolerogenic signals, I believe that any deleting T-cell agent given after transplantation or given as a too long course, will effect the T-regs negatively. The T-regs in ATG use will appear only if you give a high dose before or at the time of transplantation. Prolonged treatment after transplantation will kill also the T-regs, that have enough "room" to act after a depleting agent. In other words, the action of basiliximab will certainly depend on the baseline immunosuppressive protocol.

Unfortunately, baby died.

Thank you

Thank you - this makes sense and may explain why we concluded that the higher incidence of GVHD after liver transplant appeared to be correlated with the use of Simulect.  Given that memory T cells appear to reconstitute faster in the homeostatic proliferative environment, this may explain this finding.  The fact that we have not seen a single case after stopping simulect induction further supports the correlation.

Yang et al reported in July issue of Liver Transplantatin the relative contributions of necrotic and apoptotic biomarkers in liver ischemic reperfusion injury in mice. "Biomarkers Distinguish Apoptotic and Necrotic Cell Death During Hepatic Ischemia-Reperfusion Injury in Mice". See abstract at: http://www.ncbi.nlm.nih.gov/pubmed/25046819

A nice recent (2012) review article on pathophysiology of ischemic reperfusion liver injury full text available at:

It can happen sometimes after liver transplantation. This demonstrates that hepatocytes show a genetic dependant response to the the virus.  But it is not clear if this spontaneous clearence is associated with kidney transplantation. However, interestingly, the previous decompensation might be the cause of the clearence. The damage to the liver caused by HCV is essentially due to an inflammatory response to the virus by our immune system.  In a chronic HCV infected patient , this response changes during a timeline, sometimes is very strong and acute, sometimes just stable.  Maybe (and just maybe) the decompensation was caused by a very strong immune reaction to the virus, which caused the decompensation and the clearence at the same time, and then it ended spontaneously.

In my view the answer is a clear no.

ROTEM/TEG are excellent tests to guide treatement in acute trauma/bleeding and perioperatively. The are even some RCT published on that and more on the way.

There is little if no RCT data on anticoagulation and ROTEM/TEG. Possibly the problem is the signal to noise ratio. ROTEM/TEG mostly used as whole blood tests. In whole blood the hematocrit increases the signal to noise ratio. You can have a patient anticoagulated therapeutically on vitmain K antagonists or even heparin and not see it on ROTEM/TEG.

Anticoagulation in transplant patients rarely is an emergency decision. Time is sufficient to guide therapy by thrombin time, aPTT, antiFXa or the test of your choice. There are also some POCT devices emerging, which still need clinical validation. 

I am very impressed for the good outcomes of that patients due to an immediate laparotomy and bleeding control. However, I am sure that the purpose of the question was how to prevent such a potential life-threatening accident. The first idea involves a careful preoperative imaging study: for example, it could have shown some vascular abnormalities of hepatic veins confluence. Moreover, I am strongly convinced that the crucial point is the use of an intraoperative ultrasonography probe managed by one of the robotic arm. This technology is also able to show the liver (and other major vascular structures) vascularization through a "picture in picture" image in the surgeon's console. This real time imaging device is able to best guide any liver resection or vessel dissections.

Very difficult unless the donor pool is expanded.  Nevertheless, the advantage of HCC seems that they have more MELD points with otherwise more liver reserve.  For a non-HCC to reach same score means their disease is more advanced and probably decompensated with ascites

In this era of Value Based Care, one important measure that takes many clinical and social issues into consideration is the overall cost for the first year of care.  This should include pre-transplant costs from listing as another metric.  This will take into account decision to list, management on the waiting list, surgical care, medical care, immunosuppression regimen costs, readmissions and costs of managing complications.  These should then be risk stratified and combined with standard survival outcomes for a composite score.

Clearly other important metrics you refer to, such as eGFR, HCC recurrence rates, etc. are also important.  The problem is that the FDA and industry want short term measures.  If you look at our H2304 Everolimus in liver transplant study, the impressive retention of renal function as measured by eGFR up to 4 years should be enough incentive to move to a lower dose tacrolimus with everolimus immunosuppressive regimen.

A carefull evaluation is needed about the different options as at present we need to take into account the high costs. In our experience 30- 40% of patients  were able to eradicate the Hepatitis C virus with the standard treatment after (6-12 months) and they never show recidivism. Relapser and non-responder need to be the first to be considered for the new DAA.

sincerely

I would think liver transplant. There was one case of liver transplant in a patient with Niemann Pick Type A in the literature.

Am J Med Genet. 1977;1(2):229-39.

Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick disease type A.

Daloze P, Delvin EE, Glorieux FH, Corman JL, Bettez P, Toussi T.

Abstract

Liver homotransplantation was attempted as replacement therapy in a 2-year-old patient with near total absence of sphingomyelinase activity of Niemann-Pick disease type A. Satisfactory function of the graft was observed until the death of the recipient from respiratory complication 2 years after transplantation. The clinical stigmata of the disease became less severe during the first 6 months after transplantation, with no further improvement thereafter. Sphingomyelinase activity was restored to near normal levels in serum, was present in cerebrospinal fluid and was maintained in the graft at normal or supranormal levels. No accumulation of sphingomyelin was observed in the transplanted organ as evaluated by histopathological and chromatographic studies. These findings support the interest of organ transplantation for long-term enzyme replacement in Niemann-Pick disease type A and similar lysosomal deficiencies.

Before any extensive workup, I would do a thorough workup for Stongyloidiasis. Antibodies may be less likely to be positive given immune suppression but given the ongoing symptoms I would test serology and stool O&P. Bacterial overgrowth is a diagnosis of exclusion in this scenario. Clues for strongy would also be occult bacteremia especially with a gram negative enteral bug. Hope this helps.

Thank you Dr Riley. I agree about the best reference is Lee et al at Gastroenterology. We use NAC for all FHF patients, starting at level II of HE in dosis for acetaminophen intoxication. After 48h we discontinue NAC. Some patients recover the liver function at this time, or the option of liver tx may have a better decision with a better condition.

Outcomes will improve because graft survival improves when the graft isn't infected with HCV (e.g. http://www.ncbi.nlm.nih.gov/pubmed/15996238), and treatment pre- or post-transplant will be much better tolerated with interferon-free therapy. These benefits should be at least as apparent in HIV/HCV co-infected individuals. Whether additional sites engage with this population is multifactorial, but improved outcomes (and treatment options) can only help.

There is no biological marker for differentiating between active TB and latent TB in countries where TB is endemic. IGRT ( quantiferon Gold assay) has failed to diagnose latent TB infection in India.

Part of the answer depends on the state of the patient going into combined liver and kidney transplant. Critically ill patients with high MELD scores that may be hemodynamic unstable after transplant with significant coagulopathy would benefit from less steroids, delayed tacrolimus - those patients would possibly get basiliximab with iv MMF for up to 5 days and then start with low dose tacrolimus and convert to oral MMF when taking po. For those that are highly sensitized combined liver and kidney transplant recipient, would use thymoglobulin with steroids and start tacrolimus within 1-2 days, adding MMF when taking po. For straight forward combined liver and kidney that are not sensitized, would use either thymoglobulin or basiliximab with steroids and MMF and start tacrolimus after 3-5 days when kidney function and liver function are good. I would wean steroids first, then MMF and keep these patients on mono therapy with tacrolimus.

Yes, indeed. You may find the answer in a recent article from the A2ALL study which was published in Hepatology in 2011: "Liver Transplant Recipient Survival Benefit with Living Donation in the Model for Endstage Liver Disease Allocation Era" by Carl L. Berg et al.

Since we used to have our own cryo-bank we used iliac grafts from other donors. With the new european regulation regarding the handling of tissue, the use of vessels is only allowed for the same recipient. In older days we always had grafts to use. nowadays we dont. We are not used to keep the iliacs for 10 days wthich is indeed possible. We use in the rare cases for the arterie a biosynthttic prothesis calles omniflow. For the venous vessels we use pericard patches preparde as a tube to get the rigt diameter.

It is difficult to perform a comparison of the outcomes in the published literature due to the heterogeneity in practice of LDLT versus DDLT around the world. It all comes down to context and hence the availability of donor livers via either route. The HongKong liver transplant programme does publish outcome data for both LDLT and DDLT. Look for publications fro Albert C Chan or otherwise look up either ST Fan or CM Lo on Medline.

In one situation I had to perform Aorto-Femoral arterial prosthetic bypass. Then I anastomosed Donor Renal Transplant Artery to the prothetic arterial bypass. This patient 's distal aorta and iliac felt like a lead pipe / egg shell. Patient did very well. However, I agree about what has been said re avoid prosthetics in transplant setting if possible.

Thank you for your answer Mohamed.

So, in case you have a patient with known severe Ig A deficiency which has a previous history of transfusion reaction due to anti-IgA: Would you use Ig A deficient blood components during liver transplantation?.

At the U. of Miami, we do not have an age cut off, but those patients above 70 years old are evaluated and subsequently discussed in our Extreme Risk Board. If the patient is considered to be biologically strong enough, we place them in the list and reassess them periodically until transplantation time. At some point, we used extended criteria donor livers on some of those patients, but the results were not excellent

RAG knockout mice would be an alternative. This is a good model as CD4 KO, CD8 KO and B cell (mu) KO mice are available on the same background (C57/Bl6). If you can get the animals they are much easier to look after. We have used a heterotopic heart transplant model as described:

Chen Z. (1991) A technique of cervical heterotopic heart transplantation in mice. Transplantation 52: 1099-1101

The Transplantation Society has stated in the Declaration of Istanbul that efforts to initiate or enhance deceased donor transplantation are essential to minimize the burden on living donors. Legislation should be developed and implemented by each country or jurisdiction to govern the recovery of organs from deceased and living donors and the practice of transplantation, consistent with international standards.

a. Policies and procedures should be developed and implemented to maximize the number of organs available for transplantation, consistent with these principles;

b. The practice of donation and transplantation requires oversight and accountability by health authorities in each country to ensure transparency and safety;

c. Oversight requires a national or regional registry to record deceased and living donor transplants;

d. Key components of effective programs include public education and awareness, health professional education and training, and defined responsibilities and accountabilities for all stakeholders in the national organ donation and transplant system.

In addition, we have written about the minimum requirements from an institutional and professional standpoint to support living liver donation, I attach that document for you but the reference is: Malago M, Testa G, Marcos A, Fung JJ, Siegler M, Cronin DA, Broelsch CE: Ethical considerations and rationale of adult-to-adult living donor liver transplantation. Liver Transpl 7(10):921-927, October, 2001.

Atta, excellent question. In biliary disorders, the literature suggests a cholangiocyte origin of increased serum GGT. However, in non-biliary chronic alcohol liver disorder, the origini of increased serum GGT is more likely the injured hepatocyte, disruption and extrusion of GGT into the canalicular region, and eventual absorption into the bloodstream. See excellent study by Irie et al:

"Hepatic expression of gamma-glutamyltranspeptidase in the human liver of patients with alcoholic liver disease" Hepatology Research (Nov 2007) 37(11):966-973. Abstract at: http://www.ncbi.nlm.nih.gov/pubmed/17854466

I cannot find a weblink for the full article. Here is Abstract:

Background: Gamma-glutamyltranspeptidase (GGT) has been recognized as an enzyme that converts glutathione into cysteine, and it is localized predominantly within the liver. Serum GGT is clinically recognized as the most useful marker for diagnosis of alcoholic liver disease (ALD). Methods: GGT localization within the liver was examined immunohistochemically using an anti-GGT antibody and was visualized by confocal laser scanning microscopy in ALD and normal livers. Double immunostaining for GGT and dipeptidylpeptidase-IV (DPP-IV) was carried out to evaluate GGT localization in greater detail. Results: Expression of GGT protein and mRNA was studied with immunoblot analysis and in situ hybridization, respectively. Immunohistochemically, the expression of GGT in the normal liver was faintly demonstrated in the bile canaliculi of hepatocytes and in biliary epithelial cells. In ALD livers, GGT was clearly demonstrated at the same sites. Double immunostaining demonstrated that GGT and DPP-IV were colocalized in hepatocytes in the ALD liver. In situ hybridization clearly demonstrated GGT-mRNA within the cytoplasm of hepatocytes and biliary epithelial cells. Immunoblot analysis revealed that GGT protein expression was increased in the ALD livers compared with that seen in the normal livers. Conclusion: These findings indicate that GGT in control and alcoholic livers is synthesized in hepatocytes and biliary epithelial cells, and is localized within the bile canalicular membrane and the luminal membrane in those cells, respectively. In conclusion, GGT synthesis and protein expression are increased in ALD livers, leading to the elevation of serum levels of GGT that are commonly noted in patients with the disease

For source of increased serum GGT in biliary cholestasis disorder, see Bulle at:

"Mechanism of gamma-glutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: a histochemical, biochemical and molecular approach." in Hepatology. 1990 Apr;11(4):545-50 Abstract on web at:

I do not use targeted antibiotics. However, I use prophylactic broad spectrum antibiotics, 2nd generation cephalosporin with or without cifloxacin, in case of high risk patient

James Guarrera at Columbia University in the US is perfusing livers. Clinical outcomes so far are limited and indicate it is not harmful with some biochemical benefits to the tissue. Longer term follow up and longer perfusion times (>4 hrs) will be needed. These livers are extended criteria grafts. The solution is a new UW clone with some other additives in it. I'm waiting to see any effects on preservation cholangiopathy.

We have a high load liver tranplantation program in shiraz transplant center, Shiraz, Iran, under supervision of Dr Seyed Ali Malekhosseini with more than 350 procedure per year. For a short period we used HTK as the main preservation solution insteadof UW. But very soon our mortality and morbidity incresed considerably and Dr Malekhosseini abondoned the use of HTK. During that short period many of our patient had enzymatic changes consistent with preservation injury and also we had 3 cases of primary nonfunction of unknown cause but we didn't published our results. We strongly recommend the use ofUW solution until a better solution is introduced becauseof the high cost and disaterous complications of liver transplantation failure for the patients.