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Metabolic complications following Liver Tx, How to prevent – Prof. Mona El Amir

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Thank you professor sharif for your nice introductions and nice words i hope i deserve these words and many thanks for giving me the chance to be with you today our topic today is metabolic complications following liver transplantation and how to prevent as we all know liver transplantation is the most effective treatment for end stage liver disease resulting

In increased survival and quality of life for the recipients developments in surgical techniques as well as effective immune suppressive regimens have resulted in steady gains in post-transplant outcomes with survival of the recipients reported at one and five years to be 86.9 and 73.9 percent respectively with improvements in short and long-term survival

Following liver transplantation actually new dilemmas particularly metabolic complications and their associated increased cardiovascular disease risk have risen so one of the major challenges facing the transplant community is the increasing metabolic complications that are now affecting quality of life and long-term survival so our agenda is simply to answer two

Important questions what are the metabolic complications post-transplant and how to prevent metabolic complications post-transplant starting with the post-transplant metabolic syndrome it’s a cluster of metabolic derangements associated with insulin resistance and increased risk of cardiovascular mortality estimated to be 44 to 58 the main factors associated with

Ms or metabolic syndrome are post transplant diabetes obesity dyslipidemia and hypertension according to the other treatment panel three definition metabolic syndrome is defined as the presence of this lipidemia obesity glucose intolerance and hypertension and finally okay and this table illustrates the other treatment panel three criteria for metabolic syndrome

And this table illustrates the prevalence of post-transplant metabolic syndrome and its components what about the factors associated with metabolic syndrome immune suppression in the form of cyclosporine acrolyms and desteroids older age of the recipient alcohol related liver disease cryptogenic serosis hsev infection also higher pre-transplant bmi the presence of

Diabetes pre-transplant and the post-transplant changes in bmi and now what about the complications caused by the metabolic syndrome what is the risk of metabolic syndrome we have four main complications the nu nafld two and a half fold increase in cardiovascular disease malignancy and fibrosis fibrosis is specifically in the patients transplanted for hsv cirrhosis

What about mortality this graph shows the main causes of mortality during the first year post-transplant other than the hepatic causes we can find malignancy cardiovascular risk infection and renal problem what’s the rule of metabolic syndrome we can say that metabolic syndrome is a common thread of risk for each of these making the prevalence etiology prevention

And management of post-transplant metabolic syndrome is very important to the transplant community while in hussein the survival of the main causes of death as uh during the first year post transplant in spite no guidelines as regards the prevention and treatment but there is a consensus regarding the need to identify and screen at risk patients for metabolic

Syndrome and tailored clinical approaches taken why to improve the long-term outcomes post-transplant diabetes mellitus unfortunately the patient’s transplant pre-transplanted has have diabetes before transplant unfortunately up to one-third will remain diabetic after transplantation what about the donova diabetes we can find that to 80 percent uh have glucose

Intolerance post transplant but only 20 percent which is which is not only actually it’s a big percentage 20 percent uh develop new onset diabetes post transplant what’s the risk of diabetes why it’s important it increased twofold increase the risk of cardiovascular uh disease not only this but it causes liver related deaths and head has an impact a bad impact or

Negative impact on graft survival through which mechanism or mechanisms unfortunately post transplanted diabetes is associated with increased advanced graft fibrosis it might cause late onset hepatic artery thrombosis as we said recurrent urdu fatty liver disease also it increased the risk over the incidence of acute and the chronic rejection so diabetes not only

Increase the mortality it increase both morbidity and mortality post transplant what about the the role of immune suppression in causing diabetes calcium urine inhibitors cyclosporine and pacrolimus unfortunately associated with risk of post transplant diabetes but that acrolympus is more diabetogenic than the cyclosporine through different mechanisms actually

The calcium inhibitors are diabetogenic inhibiting pancreatic beta cell ability uh peripheral insulin resistance multiple mechanisms actually also corticosteroids lead to insulin resistance increased gluconeogenesis and are diabetogenic or causing post-transplant diabetes other factors as this study shows that hcv infection also in that pre-transplant actually

Impaired fasting glucose pre-transplant family history diabetes male gender acrolym is used as i said and bmi all are risk factors for new onset diabetes after liver transplantation so it’s recommended to screen our patients on weekly basis during the first months then uh every uh three months and our goal when we treat to keep the hemoglobin a1c less than seven

We have to adjust the immune suppression regimen uh to reduce uh hyperglycemia how to take a rapid paper of steroids minimization the doses of steroids the use of cyclosporine rather than the tachrolimus and mmf is less diabetogenic than both than both tachrolimus and cyclospore post-transplant obesity by definition bmi more than 30 risk factors include donor bmi

Acute rejection and the steroid use cyclosporin if we comparing cyclosporine to tachrolimus it might be linked more to post-transplant obesity also not only the the drugs but the dietary mistakes as this study concluded and lack of physical activity may play a major role in uh the increase in the weight uh of the recipient after transplantation uh lifestyle

Modifications exercise and healthy diet are essential for management of obesity in our recipients post-transplant and it’s very important to adjust the our medications as we said and trying to rapid paper with steroids and may shift from one uh to another as we said that the fk is less obesity than the cyclosporine what about the post transplant this

Lipidemia actually this lipidemia is common after transplant affecting 45 to 69 percentages a very big percentage actually risk factors of hypercholesterolemia recipients include pre the presence of pre-transplant hypercholesterolemia cyclosporin used and corticosteroids what about the hypertriglyceridemia predictors of post-transplant hypertriglyceridemia

Including cirrhosis resulting from hcv hbv alcohol cryptogenic cirrhosis and post-transplant renal insufficiency corticosteroids also can lead to this lipidemia by increased hepatic production of lipids although both calcium urine inhibitors cyclosporine and tachrolimus um are associated with post-transplant dyslipidemia but the cyclosporine length is more potent

Through which mechanisms cyclosporine inhibit the hepatic bile acid 26 hydro hydroxylase and through also binding ldl receptors so conversion from cyclosporine to the chronis uh results in improvement in both serum cholesterol and triglyceride levels what about the mtor inhibitor ceramus is associated with post transplant hyper triglyceridemia and increase in

Ldl cholesterol not only this but it’s uh synergistically act with cyclosporine to cause more and more dyslipidemia and this synergistic effect is not seen between ceromas and tacrolimus and this is very important to adjust the immune suppression regimen in our patients if they develop this lipidemia this study highlights the use that the use of mtor containing

Regimens the patients will become at higher risk too to develop this lipidemia post transplant now how to manage weight loss and dietary modifications all we have to know and no adjustment of the blood glucose it might help if the patient have has hyper glycemia or diabetes statin therapy is safe yes it’s considered safe in the liver transplant patient but

Pravastatin and fluvastatin being the preferred agents for patients on uh calcium urine inhibitors why because of lack of interaction with the cytochrome p450 muffled and within the first six months post-transplant um post-transplant hypertension uh different mechanisms increased radial vasoconstriction impert sodium excretion induced by cyclosporine used and

May occur less frequently with tachrollin so malignant molecular melanoid more with cyclosporine than that acrolymps corticosteroids also increase the blood pressure through activation of the rest system why we have to control the hypertension why it’s essential to decrease the development of cardiovascular disease post-transplant this is our main goal we have

To keep the blood pressure lower than 130 over 80. we start with lifestyle modification low salt diet cessation of smoking avoid alcohol a weight loss if all these modifications of no any ineffective we have to start the calcium channel blockers preferred as first line agents we have to again to modify the patient immune suppressive regimens rapid teeth of a

Rapid paper of glucocorticoids transitioned from tachrolimus from cyclosporine to the acrolym switching to mmf or ceramics in the place of calcium urine inhibitors in this table we have to have a look to this table the adverse it summarizes the immune suppressant adverse effects and we can compare each agent um it’s very important tip okay coming to the last

Metabolic complication push transplant which is a post-transplant a non-alcoholic fatty liver disease which is considered as a hepatic manifestation of the metabolic syndrome we mentioned unsurprisingly in manila rates of nafld and nash higher in the recipients undergoing transplantation for nash cirrhosis reported to me 75 percent for nafld and 38 percent for

Nash what about that patience nafld may occur in up to 43 percent of the patients what are the risk factors obesity tacrolimus based immune suppression as we said hyperlipidemia diabetes hypertension um post-transplant non-alcoholic fatty liver disease unfortunately is linked to or contributes to the increase the cardiovascular mortality in our recipients this

Table we can with a rapid look to this table we can know the difference between the recipients transplanted for nasty roses versus non-nash cirrhosis in as regards the incidence of nafld nash and cirrus in spite no concrete guidelines established for monitoring and treatment of nash development or new yani or recurrence however there is expert opinion generally

Encourages more frequent liver biopsy and aggressive risk factor modification in patients in which patients in patients undergoing transplantation for nash serious and now coming to answer the the second question how to prevent while there is a consensus regarding the need to identify and the screen at risk patients for metabolic complications no practice guidance

On the long-term management of those patients but the bridge transplant society recommendations on nash transplanted patients should be followed they these suggest an intensive control of glucose serum levels early steroid withdrawal and low doses of calcium urine inhibitors also tailor the clinical approaches as we said targeting both the individual risk factors

Will features of the metabolic syndrome and other metabolic complications it’s a dynamic challenge we have to know it’s a dynamic challenges a challenge that requires management and understanding the host factors on one side and also the impact of the post-transplant immune suppressive regimen again this table is very important that we have to know the metabolic

Risk of immune suppressants one by one so prevention of metabolic complications requires multiple modalities such as lifestyle modifications early screening and identification of complications and also careful medication selection and titration is very important it’s a multi-disciplinary approach it needs nutrition collaboration of all nutrition pharmacy hepatology

And internal medicine thank you

Transcribed from video
Metabolic complications following Liver Tx, How to prevent – Prof. Mona El Amir By Kasr Al-Ainy EHGC