Liver transplant in Turkey

Liver Transplant Operation | Reasons, conditions and risks

Liver transplantation is the definitive surgical treatment for patients with end-stage liver disease and patients with acute liver failure that improves liver function and survival after transplantation.

Liver transplantation is a final solution to many liver problems, as this process saves the lives of patients with acute liver failure, andLiver transplant side effects It can be avoided with the progress of medicine in Turkey.

What is the success rate of a liver transplant? How many hours does the liver donation process take? What are the contraindications and conditions for liver transplantation? Is liver donation dangerous? Find out with us the answer to these questions in the following article.

An introduction to the liver transplant process

The first liver transplant was performed in 1963 in the United States by surgeon Thomas Starzl. Today, this operation is the most effective treatment for end-stage and acute liver failure. Liver transplantation has been performed on more than 80,000 patients with Chronic liver failure in the world.

Over the past three decades, liver transplantation has become an option for saving the lives of patients with end-stage liver disease, liver malignancies, metabolic diseases with liver damage, or acute liver failure. The purpose of the transplant is to prolong the life of the recipient and improve their quality of life.

The survival rates after liver transplantation have increased dramatically in recent times, as the one-year survival rate is 96% and the ten-year survival rate is 71% after transplantation. The operation, advances in postoperative care and immunosuppressive therapies increase long-term survival success after liver transplantation.

conditions for liver transplantation

Three underlying principles dictate which patients should be referred for and potentially undergo transplant.

  1. The recipient must have acute or chronic liver disease that cannot be cured and is expected to be fatal without a liver transplant.
  2. The patient must be able to survive during and around the surgery.
  3. The patient should be expected to have a good survival and quality of life benefit after liver transplantation.

What are the reasons for a liver transplant?

  1. Acute liver failure: The most common cause is an overdose of acetaminophen 39%.
  2. Hepatic artery thrombosis within 14 days of liver transplantation.
  3. cirrhosisWith decompensation (variceal bleeding, hepatic encephalopathy, or ascites), or with pulmonary hepatorenal syndrome or pulmonary hypertension.
  4. Primary hepatocellular carcinomas: hilar cholangiocarcinoma fHepatocellular carcinoma.
  5. Congenital metabolic diseases: cystic fibrosis associated with lung and liver disease, primary hyperoxaluria type I with Renal insufficiency Large, familial amyloid neuropathy.
An image showing the stages of liver damage that ends in cirrhosis and thus transferring the patient to liver transplantation
Stages of liver damage that end in cirrhosis and thus refer the patient to liver transplantation

Contraindications for liver transplantation

Absolute contraindications are:

  • Active extrahepatic malignancy
  • Intrahepatic cholangiocarcinoma
  • Hepatocellular carcinoma outside Milan criteria or metastatic
  • Severe cardiopulmonary disease
  • Uncontrolled infections
  • Active alcohol or illicit substance abuse
  • Acquired Immunodeficiency Syndrome (AIDS)
  • Persistent non-compliance or lack of social support
  • Technical and/or anatomic barriers to liver transplantation

Relative contraindications:

  • advanced age
  • Portal venous thrombosis
  • Human immunodeficiency virus (HIV) infection
  • Morbid obesity (body mass index [BMI] ≥ 40)
  • Poor medical compliance or social support
  • Active psychiatric comorbidities (3)

Evaluation of the recipient's condition prior to a liver transplant

LT entails the physical and hemodynamic demands of a major surgery, a potentially protracted recovery period, the risks of chronic immunosuppression, and increased psychosocial stress. As such, the pre-transplant evaluation process is designed to screen for patients who are:

  • Is in sufficient physical health to survive the liver transplant and the period around it.
  • Adherent with medical recommendations to ensure compliance with postoperative care.
  • Have a secure psychosocial support system. (3)

Laboratory tests for a liver transplant

The main purpose of these pre-transplant examinations is to confirm blood type (which must be matched with a donor organ), assess liver and kidney function status, and rule out associated infections that may require treatment or could affect post-transplant care or outcome. This includes:

  • ABO and Rh blood typing
  • Basic metabolic panel
  • Complete blood count
  • Liver-associated enzymes and coagulation parameters
  • Calcium and Vitamin D
  • Urinalysis
  • Urine drug screen
  • Serological testing for hepatitis A, hepatitis B, hepatitis C, HIV, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and screening for tuberculosis(3)

Hepatic Imaging

Adequate CT scans for surgical planning should be performed prior to liver transplantation. Triphasic CT or gadolinium-enhanced MRI are the most common and may help identify potential technical barriers to liver transplantation including portal vein thrombosis, varicose veins around the liver, and anatomical abnormalities in the liver. liver, and sequelae of previous abdominal surgeries. (3)

If a CT or MRI scan cannot be obtained prior to liver transplantation, ultrasound with Doppler flow assessment may be sufficient. Hepatic radiography is particularly critical for the accurate diagnosis of patients with intrahepatic malignancy in order to confirm their candidacy for liver transplantation. .(3)

Cardiac Evaluation

Heart tests before liver transplantation aim to screen for coronary artery disease, valvular disease, and/or cardiomyopathy if present. Specific therapeutic interventions can be performed before or during liver transplantation as needed. If there is advanced heart disease, it may be performed. Liver transplant cancellation (3)

Malignancy Screening

An age-appropriate cancer examination should be performed in all patients, given that the presence of a metastasis outside the liver is a definite contraindication to a liver transplant.

Bone Density Testing

Advanced liver disease promotes osteoporosis through relative inactivity, hypogonadism, reduced vitamin D levels, impaired intestinal calcium absorption, and, in certain patients, the direct effects of alcohol, steroids, or iron overload. (3)

Infectious Diseases Considerations

Due to hepatocellular dysfunction, LT candidates are at increased risk of a variety of infections, including spontaneous bacterial peritonitis, aspiration pneumonia, urinary tract, and catheter-associated bloodstream infections. Active infection needs to be adequately treated before LT can be attempted. (5)

Vaccinations

Patients should be vaccinated against hepatitis A and B if serologies do not demonstrate immunity. Tetanus, diphtheria, and pertussis vaccinations should be up to date, as well as immunization against influenza and pneumococcus. (3)

Pulmonary Hypertension

Pulmonary hypertension, an elevation of the mean pulmonary artery pressure (MPAP)_≥25 mmHg, occurring in the presence of portal hypertension, is referred to as portopulmonary hypertension (POPH), and is detected in 4-8% of LT candidates. Mild POPH (MPAP<35 mmHg) is not of major concern but moderate (MPAP≥35 mmHg) and severe POPH (MPAP≥45 mmHg) are predictors of increased mortality following LT. (5)

Tobacco Consumption

Cigarette smoking is implicated in a number of adverse outcomes in LT recipients including cardiovascular mortality and an increased incidence of hepatic artery thrombosis. Oropharyngeal and other neoplasms following LT are also linked to cigarette smoking and can result in significant potentially avoidable long-term mortality. (5)

There are compelling reasons to prohibit all tobacco use in LT candidates, and indeed some programs make cigarette cessation a condition for listing for LT and require negative serial nicotine screens for documenting tobacco cessation. (5)

The Liver Transplantation Operation steps

The liver transplant process in Turkey has four steps, which are:

Excise the recipient liver and prepare for transplantation

Hepatectomy of the native liver is the first step of the operation. This can be a challenging procedure due to the intimate anatomical relationship of the liver with the retrohepatic inferior vena cava (IVC) in the setting of coagulopathy and portal hypertension. (6)

Hepatectomy can be performed using one of two techniques, but no study in the literature has proven superiority of one technique over the other:

The conventional technique: the native retrohepatic IVC is removed en bloc with the liver. The conventional technique requires complete occlusion of the vena cava. Consequently, some surgeons prefer to use a veno-venous bypass during the anhepatic phase to avoid hemodynamic instability caused by total caval occlusion. (6)

The piggyback technique: the liver is completely dissected from the IVC, which is therefore preserved and only partially clamped at completion of the hepatectomy. One of the major advantages of this technique is that the venous return is preserved during the anhepatic phase. This is the only technique possible when the IVC is not present in the graft (i.e., in living donors and split livers). (6)

Portal vein anastomosis

After completing the IVC anastomosis, portal vein anastomosis is performed in an end-to-end fashion and the liver is reperfused. Reperfusion is one of the most critical parts of transplantation. This can be characterized by profound hemodynamical instability (bradycardia and hypotension) and is the result of the sudden introduction in the systemic circulation of cold and cytokine-rich graft effluent. To avoid that, the liver is flushed with room temperature saline and then with systemic blood from either the portal vein or the IVC to wash and warm the graft just prior to formal reperfusion. (6)

Hepatic artery anastomosis

The most common and durable approach to hepatic artery reconstruction is an end-to-end anastomosis between the donor’s celiac axis and the recipient’s common hepatic artery just at the confluence with the gastroduodenal artery. Depending on surgeon preference and anatomical factors the level of the reconstruction may vary. The focus of the reconstruction is to allow for only one simple anastomosis in the recipient. The easiest and most common reconstruction technique is the anastomosis of the separate right hepatic branch to the stump of the donor gastroduodenal artery. (6)

Biliary anastomoses

Following the vascular anastomosis and the establishment of good hemostasis is the donor cholecystectomy and biliary reconstruction. The preferred anastomosis is duct-to-duct between the donor and recipient common bile ducts. When there is unacceptable duct size mismatch or the recipient bile duct is unusable (primary sclerosing cholangitis), a hepatico-jejunostomy is performed. (6)

Shapes and locations of surgical incisions made during liver transplantation

Postoperative care of liver transplantation

A patient who has had a liver transplant requires special care and must follow the doctor's recommendations completely.

Hemodynamic monitoring after liver transplantation

Monitoring hemodynamics after liver transplantation is critical in the postoperative setting. Acute changes in hemodynamics that are not properly diagnosed or treated can result in impaired graft function, prolonged ICU stay, and increased mortality. Postoperative management of hemodynamics begins with a thorough understanding of the underlying pathophysiology. (7)

End-stage liver disease typically results in high cardiac output and low systemic vascular resistance. Following successful transplantation this process begins to reverse, leading to a reduction in cardiac output and an increase in systemic vascular resistance with improved maintenance of systolic blood pressure. (7)

Early endotracheal extubation after liver transplantation

Early extubation after liver transplant is often possible due to improvements in both surgical and anesthetic techniques. The concept of early postoperative tracheal extubation began with cardiac surgery and was applied to select liver transplant patients in the late 1990s. Proponents argued that early extubation reduced the risk of ventilator associated pneumonia and improved both splanchnic and hepatic blood flow. Early extubation has been shown to decrease ICU length of stay. (7)

Liver transplant patients who are not candidates for early extubation in the operating room are common, particularly among patients with pre-existing pulmonary pathology. A subset of patients will require prolonged mechanical ventilation and may develop additional pulmonary complications in the postoperative period. It is critical to recognize these patients and work to prevent ventilator associated lung injury. (7)

Pain management after liver transplant

Liver transplant is a major surgical procedure and may be accompanied by significant postoperative surgical pain. Pain control intra- and postoperatively is usually achieved with fentanyl, via infusion or intermittent bolus. Other opioids such as morphine and hydromorphone are avoided if possible due to their prolonged half-lives in liver failure. (7)

Some patients may require use of a patient-controlled analgesia (PCA) pump along with longer acting agents, or transition to around-the-clock oral medications if pain persists. Thoracic epidurals are beneficial for pain control following abdominal surgery; however, they are not routine for liver transplant patients. (7)

Monitoring blood electrolytes after liver transplantation

Adequate management of electrolytes can be challenging in posttransplant patients. The patients often have numerous abnormalities that should be closely monitored and corrected. (7)

Hyperkalemia may be the most lethal electrolyte abnormality due to the rapid progression of arrhythmias and death. The causes of hyperkalemia in the posttransplant patient are often multifactorial. Many liver transplant patients either have pre-existing renal dysfunction or will develop transient renal dysfunction in the perioperative period which can impair mechanisms of potassium homeostasis. (7)

Hypocalcemia is frequently identified in liver transplant patients. However, it is important to remember that these patients often have low albumin levels and the total calcium is not necessarily reflective of free calcium levels. Ionized calcium levels are more accurate in this situation. Low calcium levels can result from chelation with the anticoagulant citrate, found in blood products and renal replacement therapy infusions. Hypocalcemia should be suspected in a patient with hypotension despite adequate resuscitation. (7)

Hypocalcemia is frequently diagnosed in liver transplant patients, and it is important to remember that these patients often have low levels of albumin and that total calcium does not necessarily reflect free calcium levels so ionic calcium levels are more accurate in this case.
Low calcium levels can result from chelation with the citrate anticoagulant in blood products and dialysis agents, and hypocalcaemia should be suspected in a hypotensive patient despite adequate resuscitation. (7)

Blood sugar levels after liver transplantation are of great importance for both prognosis and complications. Hypoglycaemia in the postoperative period may be a sign of bacteremia or impaired liver graft function, while hyperglycemia (which is more common postoperatively) may be a sign of celiac disease. Latent diabetes or in response to stress or steroids.
Severe hyperglycemia (glucose >200 mg/dL) is associated with an increased risk of liver transplant rejection, operative site infections, and increased mortality (7).

Coagulation disorders after liver transplantation

Coagulation disorders do not improve immediately after liver transplantation and often persist in the intensive care period after surgery. This is due to a multifactorial etiology that can include excessive fibrinolysis, disseminated intravascular coagulopathy, thrombocytopenia, platelet retention in the liver graft, The presence of heparin-like effect.
Some patients also suffer from hypercoagulability after liver transplantation, which complicates the evaluation of their coagulation status. The cause of hypercoagulability is not completely clear, but it may result from poor synthesis of antithrombin by the liver. (7)

Immunosuppression after liver transplantation

Posttransplant immunosuppression is necessary to prevent rejection of the donor organ. However, immunosuppression must be balanced with the maintenance of other immunologic functions, especially the prevention or recurrence of infection and malignancy. The rejection of transplanted livers occurs less frequently than in other organs, so lower dosages can be used. (7)

Steroids are used for induction and maintenance during the first year following transplant, and also for treating episodes of acute rejection. Concern exists for the use of high-dose corticosteroids accelerating rates of HCV recurrence, HCC recurrence, and hepatic fibrosis. (7)

Avoiding the use of steroids for immunosuppression has not been shown to benefit HCV-positive recipients. Common severe side effects of steroids in high doses include:

  • Blood pressure
  • glucose intolerance
  • Agitation/restlessness
  • risk of infection
  • Poor wound healing

Most of these signs and symptoms can be controlled, so steroid use is rarely discontinued. (7)

Rehabilitation after a liver transplant

Rehabilitative approaches may help patients with liver disease and transplant recipients to improve quality of life by increasing muscle strength, prevent excessive fatigue, enhance aerobic capacity and increase physical activity level. In accordance with this purpose, specific physiotherapeutic interventions structured according to patients’ needs in any phase of the disease process should be properly defined by the professions working in related fields. Physiotherapy in liver transplant recipients could mainly be divided into three periods: Preoperative physiotherapy, early post-operative physiotherapy and late post-operative physiotherapy. (8)

Indications and contraindications for participation in rehabilitation process should be well-clarified. Any sign of acute rejection of the transplanted organ, acute hemorrhage, electrolyte imbalance, physiological instability, severe neurologic complications and severe cardiovascular co-morbidities may further effect the implementation of specific techniques and exercises. Therefore phase-dependent specialized assessment procedures should be carried out before planning the exercise programs. (8)

Physiotherapeutic evaluation should include the assessment of muscle strength and endurance, aerobic capacity, physical activity level, independency in daily life activities and health-related quality of life. Neurologic, metabolic or musculoskeletal co-morbidities, level of pain and fatigue, smoking and alcohol habits should also be recorded within the context of the assessment procedure. (8)

Risks and complications of a liver transplant

Liver transplantation has many complications, but we will go through it in detail and explain its cause to know its treatment and how to avoid it, and among the risks and complications:

Respiratory problems after a liver transplant

Pulmonary complications can be very common in the postoperative setting. Many liver transplant patients will have a tenuous respiratory status requiring care ranging from close observation to prolonged mechanical ventilation. Predisposing factors in the pre-operative setting include underlying pulmonary disease and smoking. In addition, patients intubated pre-operatively are at risk for mechanical ventilation needs postoperatively due to the underlying disease. (7)

Hepatopulmonary syndrome is a complication of cirrhosis that adds unique concerns to the postoperative course. The presence of hepatopulmonary syndrome can lead to increased postoperative mortality, particularly for severe cases of hepatopulmonary syndrome (PaO 2 < 50 mmHg on room air). The complication most commonly seen in patients with hepatopulmonary syndrome is prolonged hypoxia in the postoperative setting. (7)

Infectious complications after liver transplantation

Infections are the leading cause of morbidity and mortality after liver transplantation, and the early period after transplantation (the first month) is often complicated by incisional and hospitalization-related infections including urinary tract infections, pneumonia, septicaemia, and pseudomembranous colitis (7).

Patients’ post-liver transplant are at particular risk for developing bacterial infections of the liver and surgical site including abscesses, cholangitis, and peritonitis. Standard perioperative antibiotic prophylaxis should be used to reduce the risk of infections. (7)

Renal complications after liver transplantation

Renal insufficiency following liver transplant is a common occurrence. Some studies report up to a 50 % incidence, though numbers vary widely due to the lack of a uniform definition. Acute ischemic tubular necrosis (ATN) is the most common cause of early renal failure following liver transplant. (7)

There are a number of factors that contribute to an increased risk of developing renal disorders after liver transplantation. These include:

  • Hepatorenal syndrome
  • Hepatitis C
  • diabetes
  • Hemodynamic instability during and after surgery
  • Large blood transfusions
  • Intravenous infusion of vasoconstrictors
  • infections
  • Repeated radiological procedures
  • Immunosuppressants and kidney-damaging antibiotics (7)

Thrombocytopenia after liver transplantation

Low platelet counts are a commonly seen abnormality in the posttransplant patient. The etiology for the thrombocytopenia is varied but is related to decreased circulation and decreased production.

With severe cirrhosis, there is often significant sequestration of platelets in the spleen due to portal hypertension, and the new graft will also sequester platelets. There is decreased platelet production because of low thrombopoietin levels in liver failure patients. In the postoperative period, massive blood transfusions can result in a dilutional thrombocytopenia. (7)

Graft rejection after liver transplant

After liver transplantation, there are many types of graft rejection that may occur. Rejection of the allograft can be hyperacute, acute, chronic, or graft-versus-host (GVHD). (7)

Graft rejection can be from T-cell mediated or antibody-mediated processes. The process predominantly targets interlobular bile ducts and vascular endothelia, including portal veins and hepatic venules, and occasionally the hepatic artery and its branches. (9)

Hyperacute rejection, mediated by antibodies, occurs within minutes to hours after the transplant procedure. Sixty percent of the cases of hyperacute rejection are due to ABO-incompatible allografts. In the presence of ABO-incompatible transplants, plasmapheresis, splenectomy, and the CD20 monoclonal antibody, rituximab, have been reported to prevent hyperacute rejection, but immediate retransplantation is often the only lasting option. (7)

To learn more about rituximab, you can review the article Hodgkin's lymphoma treatment orNo Hodgkin.

Acute rejection is mediated by T cells. Acute rejection is usually seen within days or weeks of the transplant and occurs in 36–75 % of liver transplant patients. Acute rejection is characterized by mononuclear inflammation and active cell damage, and episodes refractory to antirejection medications can progress to chronic rejection. (7)

GVHD occurs in 1–2 % of liver transplant recipients and associated with an 85% mortality rate. In the case of solid organ transplant, donor lymphocytes remaining in the parenchyma become detectable in the recipient weeks after transplant. These immunocompetent cells react against the different cellular antigens found in the host. GVHD is divided between acute (occurring within 100 days of transplant) and chronic (after 100 days) presentations. (7)

Outcome of liver transplant

The outcomes for liver transplant patients continue to improve due to the optimization of both surgical techniques and immunosuppressive regimens and due to better management of infections and post-transplant complications. The lack of donors remains, however, arguably the biggest challenge facing the liver transplant community today. (2)

Given the high rates of morbidity and mortality associated with end-stage liver disease, essential that physicians caring for such patients have a valid, reproducible system for staging disease severity and prognosis. Ideally, this system would be useful in determining those who need a transplant. (2)

Physiological rather than chronological age determines the possibility of accepting an older patient for liver transplantation with careful attention to comorbidities and functional status. Overall results are acceptable in recipients over 70 years of age although they are of lower quality compared to younger age groups.(4)

Quality of life has been considered at 10 and 30 years after LT, and patients’ perception of their QoL was generally good, being reduced only in older individuals who can develop a reduction in their ability to carry out physical activity in comparison with the general population. Usually no difference in terms of post-transplant QoL between male and female patients is seen, but a study reported a higher degree of overall QoL in male compared with female recipients. (4)

In the end, we find that the liver transplant is one of the best operations in Turkey to solve liver problems once and for all, and the cost of the liver transplant in Turkey is much lower than in other countries, and with almost the same quality and expected results, and that many patients talked about my experience with liver transplant In Turkey, all comments were positive and promising, even after a long period of liver donation or liver transplantation.


Sources:

  1. Bulur A and Sevmiş M. Clinical, surgical and histopathological characteristics of liver transplant recipients: An analysis of a large sample from Turkey. Gulhane Medical Journal 2022;64:60-66.
  2. Ionescu, VA, Diaconu CC, Bungau S, Jinga V, Gheorghe G. Current Approaches in the Allocation of Liver Transplantation. J.Pers. Med. 2022;12,1661.
  3. Mahmod N. Selection for Liver Transplantation: Indications and Evaluation. Current Hepatology Reports 2020;19:203-212.
  4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Liver transplantation. Journal of Hepatology 2016;64:433-485.
  5. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alono-Coello P, et al. Evaluation for Liver Transplantation in Adults: 2013 Practice Guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. BMJ 2008;336:924-926.
  6. Miller C and Diago Uso T. The Liver Transplant Operation. Clinical Liver Disease 2013; 2,(4):192-196.
  7. Parekh KN, et al. Postoperative Care of the Liver Transplant Recipient. Springer 2017;29:365-384.
  8. Yıldırım MS, Yurdalan SU Physiotherapy in Liver Transplantation. InTech 2012;21:445-454.
  9. Zhu JH, et al. Medical complications of liver transplantation. AME Medical Journal 2018;3:1-10.

Frequently Asked Questions:

There are a group of complications that can occur after liver transplantation, including respiratory and renal complications, infections, and rejection of the liver graft. Infections are the main cause of morbidity and mortality after liver transplantation.

Recently, survival rates after transplantation have increased considerably, with 96% in 1 year and 71% in 10 years after transplantation.

In general, it varies according to the degree of the center and if there is hepatitis B, but the cost ranges between 40 thousand and 80 thousand US dollars.

The liver transplant is performed in four steps and takes about several hours.

Three underlying principles dictate which patients should be referred for and potentially undergo transplant.

First, the recipient should have irreversible liver disease that is expected to be fatal without transplantation. This disease may be acute or chronic in nature.

Second, the patient should have sufficient reserve to survive the operative and perioperative period.

Third, the patient should be expected to have a good survival and quality of life after liver transplantation.

The best hospitals for liver transplantation in Turkey are Koç Hospital, Turgut Ozal and Research Hospital in Ankara, in addition to several other hospitals.

Physiological, not chronological, age determines whether an older patient can be accepted for LT, with careful attention to comorbidities and functional status. Overall outcomes are acceptable in recipients >70 years of age, although they are inferior to those in younger age groups.

The donor and the recipient can come with three people to Turkey for liver transplantation.

Absolute contraindications are:

  • Active extrahepatic malignancy
  • Intrahepatic cholangiocarcinoma
  • Hepatocellular carcinoma outside Milan criteria or metastatic
  • Severe cardiopulmonary disease
  • Uncontrolled infections
  • Active alcohol or illicit substance abuse
  • Acquired Immunodeficiency Syndrome (AIDS)
  • Persistent non-compliance or lack of social support
  • Technical and/or anatomic barriers to liver transplantation

Over the past three decades, liver transplantation has become a life-saving option for patients suffering from end-stage liver disease, malignant liver tumors, metabolic diseases associated with liver damage, and acute liver failure. Transplants aim to extend the life of the recipient and improve his quality of life, especially in Turkey. Recently where the best doctors have been trained with the hospital's latest constructionorgan transplant In general, and liver transplantation in particular, as Turkey has become a destination for many patients around the world for organ transplantation and stem cell treatment.

If you are planning for treatment in Turkey
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