Successful Liver Transplantation Research Articles

The Balance between CD8+ T Cell-Mediated Clearance of AAV-Encoded Antigen in the Liver and Tolerance Is Dependent on the Vector Dose

The liver continuously receives antigens from circulation and the gastrointestinal tract. A complex immune regulatory system has evolved in order to both limit inflammation and promote tolerance in the liver. Although insitu immune tolerance mechanisms enable successful gene therapy and liver transplantation, at the same time they facilitate chronic infections by pathogens such as hepatitis viruses. It is, however, poorly understood why hepatocytes infected with hepatitis viruses or transduced with adeno-associated virus (AAV)-based vectors may be rejected by CD8+ Tcells several months later. We found that hepatic transfer of limited doses of an AAV-ovalbumin vector rapidly induced antigen-specific CD8+ Tcells that only became functionally competent after >2months. At this time, CD8+ Tcells had downregulated negative checkpoint markers, e.g., the programmed death 1 [PD-1] receptor, and upregulated expression of relevant cytokines. At further reduced vector dose, only intrahepatic rather than systemic CD8+ Tcell responses occurred, showing identical delay in antigen clearance. In contrast, PD-1-deficient mice rapidly cleared ovalbumin. Interestingly, higher vector dose directed sustained transgene expression without CD8+ Tcell responses. Regulatory Tcells, IL-10 expression, and Fas-L contributed to high-dose tolerance. Thus, viral vector doses profoundly impact CD8+ Tcell responses.

Tolerability of Switch to Macitentan from Bosentan in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease that can be treated with several medications. Macitentan, an endothelin receptor antagonist (ERA), has received approval as a PAH therapy. We report our data regarding the tolerability in patients with PAH who were switched from bosentan to macitentan. At the Baylor Pulmonary Hypertension Program, 24 patients with PAH who had been taking bosentan and were switched to macitentan were identified in this retrospective study. Data from these patients who switched from bosentan 125 mg orally twice per day to macitentan 10 mg orally daily (between October 2013 and February 2015) when macitentan became commercially available were collected. Patients were advised to take their last evening dose of bosentan and then take the first dose of macitentan the following morning within 12 to 24 hours of the last bosentan dose. Baseline data and postswitch data, including 6-minute walk distance, brain naturietic peptide, alanine transaminase (ALT) and aspartate transaminase (AST) levels, World Health Organization Functional Class (WHO FC), Borg dyspnea score, presence of peripheral edema. At the time of the switch, the mean age was 58 ± 13 (mean ± standard deviation) years, the duration of disease was 6.6 ± 4.4 years, 21 patients were women, 54% were white, and 25% had idiopathic PAH. The mean duration of follow-up after the switch was 5.7 ± 1.5 months. The 6-minute walk distance was 344 ± 106 m preswitch and 319 ± 85 m postswitch (P = 0.18). Brain naturietic peptide levels were 91 ± 170 pg/mL preswitch and 90 ± 137 pg/mL postswitch (P = 0.93). At the time of the switch, 42% were WHO FC II and 50% had edema, and 55% had edema. AST and ALT remained unchanged postswitch. Two patients did not tolerate the switch to macitentan and had to be returned to bosentan: one patient with portopulmonary hypertension developed elevated AST and ALT and the second patient's macitentan was stopped because of malaise and tachyarrhythmia. One patient who underwent a successful liver transplant had macitentan stopped following the transplant. A rapid switch from bosentan to macitentan was well tolerated and safe with maintained WHO FC, with no significant change in edema and liver enzyme levels. The switch from bosentan to macitentan eliminates the need for monthly liver function test monitoring and removes the potential for bosentan treatment interruption.

The Association between Oxygen Consumption of the Liver Graft and Post-transplant Outcome

The association between oxygen consumption of the liver graft after reperfusion and post-transplant outcome has been studied from 1950s. The lack of significant progress is because oxygen consumption of the liver graft is determined by various factors, including the donor condition, status of the graft preservation, cold ischemia time, and hepatic blood flow after reperfusion. However, metabolic alterations, such as oxygen consumption and glucose metabolism in the liver grafts are reliable predictors of subsequent the liver graft function, and may help the decision of re-transplantation for the patients with failed liver graft. Appropriate organ preservation reduces oxygen consumption of the liver grafts, and low oxygen consumption might reflect less histological damage after preservation and reperfusion. In contrast, systemic oxygen consumption after reperfusion in patients with successful liver transplantation was higher than systemic oxygen consumption in those with primary non-function and graft dysfunction. This review summarizes association between oxygen consumption of the liver graft and post-transplant outcome.

A Case of Hepatic Artery Thrombosis after Liver Transplantation

Introduction: Hepatic artery thrombosis (HAT) is the most serious vascular complication after liver transplantation. The most common presentation is elevation of liver function tests. When the diagnosis of hepatic arterial thrombosis is established, prompt intervention should be performed.Case Presentation: In this case report, we present a 37-year-old male with Chronic Hepatitis B infection who underwent a successful liver transplantation, and later developed multiple complications. The most significant of which is hepatic artery thrombosis. He underwent revascularization, supported by heparin and prostaglandin infusion. Succeeding doppler ultrasound surveillance showed patency of right hepatic artery flow. Conclusion: Early identification of hepatic artery thrombosis should be paid attention after liver transplantation to prevent its complications. Once the diagnosis is established, prompt intervention such as retransplantation or revascularization should be performed.

Hepatopulmonary syndrome and liver transplantation: the review and a case report

Hepatopulmonary syndrome is a liver disease complication characterized by the clinical triad of an advanced chronic liver disease, a pulmonary vascular dilatation, and a reduced arterial oxygenation (hypoxemia: PaO2 less than 70 mm Hg at rest) in the absence of intrinsic cardiopulmonary disease. Precapillary vasodilatation, intrapulmonary angiogenesis and hyperdynamic circulation lead to arteriovenous shunting and reduced gas diffusion. In case of detecting macroscopic shunts, the pulmonary artery branch embolization could be performed. However, the hepatopulmonary syndrome can be cured nowadays by means of liver transplantation only. A 5-year survival in these patients is about 70%. The observed mortality is the highest during the surgery or early after, especially in patients with PaO2 lower than 50 mm Hg. It ranges from 8.5 to 29%. A prolonged oxygenation support is often required after liver transplantation using invasive or non-invasive ventilation, or even extracorporeal membrane oxygenation. In this review, we have focused on the recent advances in this field as described in available literature and have presented a case report of successful liver transplantation in a patient with a severe hepatopulmonary syndrome.

Fourteen Years of Experience of Liver Transplantation for Wilson’s Disease; a Report on 107 Cases from Shiraz, Iran

Background and AimLiver transplantation is a potential cure for liver damage from Wilson’s disease but the course of neuropsychiatric manifestations after transplantation remains undetermined.Material and methodsIn this study, data on all patients who’d received a liver transplant for Wilson’s disease at the Shiraz Organ Transplantation Center between December 2000 and March 2014 were reviewed and compared to data on a control group who’d received a liver transplant over the same period but due to other causes.ResultsOut of 2198 patients who’d received a liver transplant in the period; 107 patients were diagnosed with Wilson’s disease (21 with fulminant hepatic failure); age of patient ranged from 5 to 59 years; 56.07% of patients in this series had some type of neuropsychiatric manifestation before transplantation, of which 66.67% showed improvement after the procedure. 18 patients had aggravation of neuropsychiatric symptoms after transplantation. These neuropsychiatric symptoms were mostly for anxiety, tremor and depression but there were four cases of new onset dysarthria, rigidity and ataxia in various combinations. Survival rates of 1-month, 1-year, and 5-years for patients with Wilson’s disease were 88%, 86%, 82%, respectively, evaluations were not statistically different from that of the control group.ConclusionsLiver transplantation showed good long-term results in patients with Wilson’s disease, even in those presenting fulminant hepatic failure. Neuropsychiatric manifestations normally show improvement after transplantation but in some cases new onset of manifestations occurred after successful liver transplantation.

The liver transplant: “a tricky, tricky thing”

The liver transplant: “a tricky, tricky thing”

Liver transplantation in transthyretin amyloidosis: Characteristics and management related to kidney disease.

Orthotopic liver transplantation (LT) was implemented as the inaugural disease-modifying therapy for hereditary transthyretin (ATTR) amyloidosis, a systemic amyloidosis mainly affecting the peripheral nervous system and heart. The first approach to pharmacologic therapy was focused on the stabilization of the TTR tetramer; following that new advent LT was assumed as the second step of treatment, for those patients whose neuropathy becomes worse after a course of pharmacologic therapy. The renal disease has been ignored in hereditary ATTR amyloidosis. The low level of proteinuria or slight renal impairment does not suppose such a heavy glomerular and vascular amyloid deposition. Moreover, severity of renal deposits does not consistently parallel that of myelinated nerve fiber loss. These are pitfalls that limit the success of LT and suggest troublesome criteria for pharmacological therapy or LT. An algorithm of evaluation concerning renal disease and treatment options is presented and some bridges-to-decision are exposed. In stage 4 or 5 kidney disease, the approach remains to deliver combined or sequential liver-kidney transplantation in eligible patients. However, in the majority, hemodialysis is the only option even in the presence of a well-functioning liver graft. In this review, we highlight useful information to aid the transplant hepatologist in the clinical practice.

Family Members, Transplantation Candidates, and Patients Who Underwent Liver Transplantation Had Insufficient Information About the Procedure.

Adherence to treatment is essential for a successful liver transplantation (LT) because LT requires information, abilities, and competencies of patients and family members. This study sought to identify whether the information received about the LT process was enough for either patients or family members who attended a liver transplant center in a school hospital. This was a transversal study using questionnaires to verify received information on LT. It included 50 patients on the waiting list for LT, 50 transplanted patients, and 50 family members. There was a prevalence of men (82%) among patients, age range from 19 to 67 years (average: 46.87 ± 10.99), and of women (74%) among family members, age range from 18 to 80 years (average: 43.5 ± 11.77). The majority of subjects (88%) had a low education level. The most frequent etiology of hepatic cirrhosis was viral hepatitis associated with alcohol. A significant number of the listed and transplanted patients as well as all family members reported insufficient information about the process of the transplantation. The kind of insufficient information varied according to the period of treatment. The best way to obtain information, as reported by patients and family members, was a combination of oral and written information. Our data show the need for improvement in the means of delivering information to patients and family members, and an explanatory manual was created from this study.

Outcomes of transjugular intrahepatic portosystemic shunt creation for flow-enabled dissolution of spleno-mesenterico-portal venous thrombosis.

To evaluate the outcomes of transjugular intrahepatic portosystemic shunt (TIPS) for flow-enabled clearance of portal (PVT), splenic (SVT) and/or superior mesenteric (MVT) vein thrombosis. In this single-center study, 12 patients underwent TIPS using Viatorr covered stent-grafts (W.L.Gore & Associates, Flagstaff, AZ, USA) from 2008-2014 for PVT as a primary (n=8) or secondary (n=4) indication. TIPS were not accompanied by pharmacomechanical clot disruption; rather, shunts served to increase portal blood flow to allow flow-mediated physiologic clot dissolution. Pre- and post-TIPS cross-sectional imaging were used to assess clot location, size, and clearance, defined by resolution (vessel patency with no clot), reduction (decrease in clot size), stability (no change in clot size), or extension (increase in clot size). The cohort included 5 men and 7 women (median age 63 years, range 45-73 years, median MELD score 15) with 30 non-occlusive and asymptomatic thrombi spanning main or intrahepatic PVT (n=15/30, 50%), SVT (n=6/30, 20%), and MVT (n=9/30, 30%). TIPS were generally created with 10mm covered stent-grafts; mean final portosystemic pressure gradient was 8mmHg. At mean 190 days post-TIPS, 58% (n=7/12) had clot resolution, 33% (n=4/12) had clot reduction, and 8% (n=1/12) had stable clot; there were no cases of clot extension. Resolution rate was 67% for PVT (10/15), SVT (4/6), and MVT (6/9). Two of 12 (17%) patients underwent successful liver transplant post-TIPS. TIPS prompts dissolution of or decrease in PVT, SVT, and MVT in cirrhotic patients. This may be a useful approach notwithstanding omission of pharmacomechanical methods.

A Persistent Left-Sided Superior Vena Cava With Agenesis of the Right Superior Vena Cava in a Patient Who Underwent Liver Transplantation: A Case Report

The persistent left-sided superior vena cava (PLS-SVC) is the most frequent congenital anomaly of the mediastinal veins system. The concomitant agenesis of the right-sided superior vena cava (RS-SVC) is much less frequent. This variant is often discovered incidentally and could be mistaken for other findings or complicated intravascular accesses. A 29-year-old Caucasian woman presented with a decompensated autoimmune cirrhosis and hyperbilirubinemia. After a successful liver transplantation, a central venous catheter (CVC) was placed through the right jugular and a chest X-ray examination demonstrated its position into the left subclavian vein. After some days, it has been replaced by another CVC positioned from the left jugular vein. Using ultrasonography during the positioning maneuvers, we observed the metallic guide of the CVC in what seemed to be the dilated coronary sinus (CS). Subsequent chest X-ray examination demonstrated the catheter’s tip in the left paramediastinal position. In order to confirm the catheter’s exact position, we chose to inject contrast medium through the CVC under fluoroscopic guidance; the examination confirmed the presence of a PLS-SVC. These findings were also visible in a computed tomography (CT) examination previously performed in another hospital, which demonstrated the agenesis of the RS-SVC as well. We demonstrated a rare case of young patient with a PLS-SVC and agenesis of RS-SVC who underwent major surgery (liver transplantation) without any intra- or post-operative complications, even if advanced venous accesses with high flow catheters were used. J Med Cases. 2016;7(7):253-257 doi: http://dx.doi.org/10.14740/jmc2487w

Liver transplantation for pediatric inherited metabolic disorders: Considerations for indications, complications, and perioperative management.

LT is an effective therapeutic option for a variety of IEM. This approach can significantly improve the quality of life of patients who suffer from severe disease manifestations and/or life-threatening metabolic decompensations despite medical/dietary management. Due to the significant risks for systemic complications from surgical stressors, careful perioperative management is vital. Even after LT, some disorders require long-term dietary restriction, medical management, and monitoring of metabolites. Successful liver transplant for these complex disorders can be achieved with disease- and patient-specific strategies using a multidisciplinary approach. In this article, we review indications, complications, perioperative management, and long-term follow-up recommendations for IEM that are treatable with LT.

High Frequency of Arterial Hypertension in Patients After Liver Transplantation

BackgroundCardiovascular diseases are among the most frequent causes of patient death after liver transplantation. The aim of this retrospective clinical study was to estimate the prevalence of arterial hypertension among patients after successful liver transplantation and the role of immunosuppressive drugs in the pathogenesis of hypertension in these patients. Patients and MethodsA total of 88 patients (age 47 .5 ± 12.1 years; 33 women and 55 men) who had undergone successful liver transplantation and completed 24 months follow-up were studied. The results are presented as means with standard deviations. ResultsAt 1, 12, and 24 months after liver transplantation, the prevalences of hypertension were 44.3%, 54.5%, and 62.5%, respectively. Systolic and diastolic blood pressure in these months were 124.1 ± 14.8, 132.8 ± 19.1, and 135.2 ± 17.3 mm Hg and 83.3 ± 12.0, 87.3 ± 11.1, and 87.9 ± 11.1 mm Hg, respectively. The estimated glomerular filtration rates were 77.8 ± 32.3, 80.3 ± 30.8, and 78.8 ± 29.1 mL/min/1.73 m2, respectively. Arterial hypertension was significantly more frequent in patients treated with cyclosporine A than in those treated with tacrolimus (P = .004) or everolimus (P = .005). In patients treated with tacrolimus, a positive correlation was found between tacrolimus blood concentration and systolic blood pressure (R = 0.34; P = .01) and a negative correlation was found between estimated glomerular filtration rate and systolic blood pressure (R = −0.28; P = .02). ConclusionsBased on study findings, the following conclusions were drawn: arterial hypertension occurs in more than 50% of patients after liver transplantation (significantly higher frequency than in the general population); calcineurin inhibitors may participate in the pathogenesis of arterial hypertension in patients after successful liver transplantation; and the clinical importance of these findings and the influence on cardiovascular outcome of the liver transplant recipients need further investigation.

Research advances in liver ischemia reperfusion injury

Hepatic ischemia reperfusion injury (IRI) is a continuous process of damage of liver cells, which could cause a series of clinic reactions. Early owing to IRI, organ failure reaches 10%, and easily leads to acute and chronic liver transplantation rejection. Therefore, study on the treatment method of IRI is very important. Decreasing the adverse effect of IRI could significantly increase the amount of successful liver transplantation. This paper will explore mainly on the pretreatment methods of IRI. Key words: Liver transplantation; Ischemia reperfusion injury; Pretreatment methods

Pathological characteristics and clinical effect of autoimmune hepatitis after liver transplantation

Objective To investigate the pathological characteristics and clinical effect of autoimmune (AIH) after liver transplantation. Methods The retrospective descriptive cross-sectional study was adopted. The clinicopathological data of 14 patients with AIH who underwent liver transplantation at the First Affiliated Hospital of Xi′an Jiaotong University between June 2011 and December 2015 were collected. Fourteen patients underwent orthotopic liver transplantation, specimens of total liver resection from 14 patients and aspiration specimens from liver allografts of 6 patients with severely abnormal liver function after liver transplantation were collected and detected by hematoxylin-eosin (HE) staining. Specimens of total liver resection continued to detect by reticular fiber staining and immunohistochemistry. The tissues construction was observed by light microscopy. Observation indicators included (1) intra- and post-operative situations, (2) results of pathological examination, (3) follow-up. The follow-up using outpatient examination and telephone interview was performed to detect the situations of immuno-suppressive therapy and survival of patients up to March 2016. Measurement data were represented as average (range). Results (1) Intra- and post-operative situations: all the 14 patients with AIH underwent successful liver transplantation without perioperative death. The operation time, duration of anhepatic period of liver transplantation, volume of intraoperative blood loss and duration of hospital stay were 402 minutes (range, 353-405 minutes), 50 minutes (range, 42-60 minutes), 2 800 mL (range, 1 325-4 050 mL) and 19 days (range, 12-24 days), respectively. Of 14 patients with AIH after liver transplantation, 6 were complicated with pulmonary infection, 2 with acute rejection, 2 with bile duct strictures and 1 with acute renal failure, and they were improved by symptomatic treatment. (2) Results of pathological examination: HE staining of specimens of total liver resection showed that different levels of hepatitis were detected in 14 patients, lymphocytes penetration phenomena in 14 patients, lymphoplasmacytic interface hepatocyte necrosis in 9 patients, infiltration of plasma cells in 9 patients, spotty and piecemeal necroses in 5 patients and rosettes-like structure in 4 patients. HE staining of specimens of liver allografts showed that lymphoplasmacytic interface hepatocyte necroses were detected in 4 patients, rosettes-like structure in 4 patients, cholestatic cirrhosis in 3 patients, mildly acute rejection in 2 patients and recurrence of AIH in 1 patient. Reticular fiber staining: fibrous tissues were proliferative in the portal area and then separated and surrounded hepatocytes to form pseudolobule structure. Immunohistochemistry: inflammatory cells infiltrated by liver tissues were composed of T cells with mainly positive CD3 and CD8 and with few positive CD4. (3) Follow-up: 14 patients were followed up for 26 months (range, 3-57 months). Fourteen patients received regular immuno-suppressive therapy. During follow-up, 1 patient was complicated with primary transplants nonfunction, 2 had AIH recurrence and 3 were dead. Conclusions Patients with AIH should enhance hormone therapy due to high incidences of bile duct complications and pulmonary infection after liver transplantation. Lymphoplasmacytic interface hepatocyte necrosis and rosettes-like structure probably have worse prognosis. Dysfunction of Regulatory T cells (T-reg) may be a prognosis predictor for AIH after liver transplantation. Key words: Autoimmune hepatitis; Liver transplantation; Pathology; Prognosis

Risk of Liver Injury Associated with Green Tea Extract in SLIMQUICK(®) Weight Loss Products: Results from the DILIN Prospective Study.

Herbal and dietary supplements (HDS) have been increasingly recognized as a cause for acute liver injury (Navarro et al. Hepatology 60(4):1399-1408, 2014; Bailey et al. J Nutr 141:261-266, 2011). HDS products frequently contain numerous ingredients, and are marketed under various product names. A perusal of marketed weight loss products indicates that green tea extract (GTE) is a common ingredient in many. We aimed to describe the course and outcome of six patients who developed liver injury attributed to SLIMQUICK(®) weight loss products. Patients with suspected drug-induced liver injury were enrolled in a prospective study of the Drug-Induced Liver Injury Network (DILIN) and causality was assessed by a panel of hepatologists. During the period under study, 6 of 1091 cases of liver injury were attributed to a SLIMQUICK(®) product and were assigned causality scores of probable, highly likely, or definite. Six cases of acute liver injury attributed to SLIMQUICK(®) products were enrolled in the DILIN prospective study between 2007 and 2011. All were women aged 22 to 58years. Two had a normal body weight and four were mildly obese (body mass index 22.9-32.2kg/m(2)). All were taking SLIMQUICK(®) products for weight loss and no patient reported prior use. Laboratory tests revealed a hepatocellular pattern of injury, with initial alanine aminotransferase (ALT) levels above 1000U/L in all but one patient. Three patients were hospitalized and one underwent successful liver transplantation. No patients died of liver injury. GTE and/or its component catechins were listed among the ingredients for five of the six products. SLIMQUICK(®) products can lead to severe acute hepatocellular liver injury, which may result in transplantation. Given the frequency of GTE as a component in weight loss products, this ingredient should be studied further as a possible cause for liver injury.

Use of a pressure wire to evaluate right heart pressures in a pre-liver transplant recipient through a peripheral IV.

Use of a pressure wire to evaluate right heart pressures in a pre-liver transplant recipient through a peripheral IV.

Rescue management of early complications after liver transplantation-key for the long-term success.

Postoperative complications may have not only immediate but also long-term effects on the outcomes. Here, we analyzed the effect of postoperative complications requiring a reoperation (grade 3b) within the first 30days on patients' and graft survival following liver transplantation. Graft and patient survival in relation to donor and recipient variables and the need of reoperation for complications of 277 consecutive liver transplants performed from January 2007 to December 2012 were analyzed. Two hundred seventy-seven liver transplants were performed in 252 patients. Overall patient and graft survival at 1, 2, and 3years were significantly reduced in patients requiring a reoperation. The labMELD score was significantly elevated (p = 0.04) and cold ischemia time was prolonged (p = 0.03) in recipients undergoing reoperations. Kaplan-Meier curves indicate that complications impact the outcome primarily within the first 3months after transplantation. In multivariate analyses, the actual need of reoperation (p < 0.001), the labMELD score (p = 0.05), cold ischemia time (p = 0.02), and the need for hemodialysis pre-transplant (p = 0.05) were the only variables which correlated with the overall survival. Postoperative complications resulting in reoperations have a significant impact on the outcome primarily in the early phase after liver transplantation. Successful management of postoperative complications is key to every successful liver transplant program.

Intragastric balloon as a novel modality for weight loss in patients with cirrhosis and morbid obesity awaiting liver transplantation.

In extreme obesity, bariatric surgery or weight loss by lifestyle modification is often not possible because of presence of decompensated cirrhosis. Endoscopic intragastric balloon placement may be used as minimal invasive technique to promote weight loss and make them better candidates for liver transplantation surgery; however, there is no literature in this regard. Patients with body mass index (BMI) >40kg/m(2) or BMI between 35 and 40 (with a low graft to recipient weight ratio) were considered for weight reduction modalities including dietary counseling and intragastric balloon placement when feasible. Intragastric balloon placement was done in six males and two females, age 46 ± 5years, BMI 43.5 ± 6.9kg/m(2). All patients (except one with hepatocellular carcinoma) had decompensated liver disease, mean Child score was 8.5 ± 1.6. Five of them had successful liver transplantation (three deceased and two living donor liver transplantation) after weight loss, while three are waiting. All these five patients had uneventful post-transplant course. All patients had transient vomiting except one, in whom volume of balloon was decreased due to persistent vomiting. All patients except one had weight loss. None of patients had any serious complications. Three of five patients maintained weight loss post-transplant also. Intragastric balloon placement is a useful modality for promoting short-term weight loss and thereby making morbidly obese recipients fit for liver transplantation surgery.

Acute Metabolic Crises in Maple Syrup Urine Disease After Liver Transplantation from a Related Heterozygous Living Donor.

Maple syrup urine disease (MSUD) is an autosomal recessive disorder associated with impaired metabolism of branched-chain amino acids (BCAA) leucine, isoleucine, and valine. Children with MSUD suffer from bouts of metabolic decompensation, which may lead to neurological damage. Liver transplantation from unrelated deceased donors has been considered curative. The natural history of the disease following transplantation using a haploidentical (obligate heterozygous) living donor is still unclear, although previously described as favorable. We describe acute metabolic crises in a 20-month-old child with MSUD type II. The first well-documented one occurred 5 months after a successful liver transplantation from his mother. The patient developed encephalopathy with progressive lethargy and seizures after an episode of gastroenteritis with dehydration. Plasma levels of leucine, isoleucine, and valine were markedly elevated and alloisoleucine was detected. He promptly responded to dialysis and BCAA-free dietetic management and subsequently could resume a normal diet. Since then he has had another symptomatic metabolic crisis with seizures. This case strongly suggests that some recipients of liver transplantation from a haploidentical parent possess limited capacity to oxidize BCAA at the time of catabolic stress and dehydration and remain at risk of severe metabolic crises. Thus, careful metabolic monitoring and prompt treatment post liver transplantation are still required to avoid neurological sequelae of MSUD, particularly if the donor is heterozygous for MSUD.