Gomathy Narasimhan

Liver retransplantation for primary nonfunction: Analysis of a 20-year single-center experience†

Initial graft function following liver transplantation is a major determinant of postoperative survival and morbidity. Primary graft nonfunction (PNF) is uncommon; however, it is one of the most serious and life‐threatening conditions in the immediate postoperative period. The risk factors associated with PNF and short‐term outcome have been previously reported, but there are no reports of long‐term follow‐up after retransplant for PNF. At our institution, 52 liver transplants had PNF (2.22%) among 2,341 orthotopic liver transplants in 2,130 patients from 1984 to 2003. PNF occurred more often in the retransplant setting. Female donors, donor age, donor days in the intensive care unit, cold ischemia time, and operating room time were significant factors for PNF. Patient as well as graft survival of retransplant for PNF was not different compared to retransplant for other causes. However, PNF for a second or third transplant did not demonstrate long‐term survival, and hospital mortality was 57%. In conclusion, retransplant for PNF in the initial transplant can achieve relatively good long‐term survival; however, if another transplant is needed in the setting of a second PNF, the third retransplant should probably not be done due to poor expected outcome. Liver Transpl 13:227–233, 2007.

Late acute rejection after liver transplantation impacts patient survival.

Abstract:  Hepatic allograft rejection still remains an important problem following liver transplantation. Early acute rejection, occurring within three months of transplant, is a common event and usually of lesser significance with respect to prognosis than other non‐immune‐related post‐transplant morbidities. However, little is known about late acute rejection (LAR) including factors affecting its occurrence and long‐term outcome. In this study, we analyzed LAR including the incidence, clinical risk factors, patient survival, and graft survival. LAR was defined as acute cellular rejection later than six months after liver transplant. Adult patients who had a minimum of 24 months of graft survival were included in this study. A total of 1604 case records of consecutive adult patients (over age 18 yr) who underwent liver transplant between 1985 and 2003 were reviewed. Of the 1604 patients, 305 (19.0%) developed LAR. Patients with primary diagnoses of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis had higher incidences of LAR, while patients with metabolic disease and retransplant had lower incidence of LAR (p = 0.0024). The LAR group had more female and younger recipients than the no LAR group (p = 0.0026, p = 0.0131, respectively). Patient survival as well as graft survival were significantly lower in the LAR group (p = 0.0083, p = 0.0075, respectively). PTLD was the only significant independent predictor of late rejection. The careful management and treatment of PTLD, especially immunosuppressive management, is important to prevent LAR, which is related to poorer patient survival.

Liver transplantation for cystic fibrosis in adults.

PurposeTo expand our knowledge on liver transplantation for cirrhosis associated with cystic fibrosis in adults.MethodsFive patients who underwent a liver transplantation due to cystic fibrosis were reviewed. The outcome of the patients in terms of age, immunosuppression regimen, patient and graft survival, and pre- and post-transplant complications were investigated.ResultsFive adult liver transplant patients had cystic fibrosis (0.2%). These included 4 men and 1 woman with a mean age of 31 ± 10, ranging from 22 to 52 years old at the time of transplantation. All patients had lung problems. Four patients had exocrine and two had endocrine pancreatic insufficiency. Two are currently alive with a follow-up of 5.8 years and 4 months after transplantation, respectively. There were three deaths from pulmonary embolism at 4.5 years, myocardial infarction with cyclosporine nephrotoxicity at 10.7 years, and lymphoproliferative disorder at 5 months after transplantation. No deaths occurred from lung infection. Only one patient had postoperative pulmonary infectious complications, which were successfully treated with antibiotics and did not result in mortality.ConclusionAdult liver transplantation for end-stage liver disease associated with cystic fibrosis offers encouraging results with a rapid general improvement after surgery and it is now considered to be a safe and acceptable treatment for this disease population.

Liver transplantation in India.

Liver transplantation as an established form of treatment for end‐stage liver disease has gained acceptance in India over the last 10 years. Liver transplantation in India has unique features that have contributed to the growth of both deceased donor and living donor transplantations of which living donor currently dominates the picture. Living donor contributes to 80% and deceased donor to 20% of the liver transplants currently performed in India. The majority of these transplants are performed within the private sector with public sector hospitals lagging behind significantly. This article gives an overview of the evolution of liver transplantation in India and the potential future challenges. Liver Transplantation 22 1019–1024 2016 AASLD

Successful combined liver and kidney transplant for COACH syndrome and 5-yr follow-up

Abstract:  The COACH syndrome is a very rare disorder with cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. Nineteen cases with COACH diagnosis have been reported. Neurologic abnormalities are the first symptoms in most cases. Complications of the hepatopathy [portal hypertension, esophageal varices, and gastrointestinal (GI) bleeding] contribute extensively to the morbidity and lethality in the course of the disease. We describe a 28‐yr‐old female with COACH syndrome resulting in chronic renal and hepatic insufficiency. The patient was found to have significant mental retardation, truncal ataxia, motor abnormality and occulomotor abnormality. She began to develop GI bleeding and encephalopathy because of biopsy‐confirmed cirrhosis. We performed combined liver and kidney transplant after challenging discussion. Her postoperative course was uneventful, and she was discharged on the ninth postoperative day (POD). She has not had any problems at 1, 3 and 5‐yr follow‐up with excellent liver and renal function. This is the first description of successful combined liver and kidney transplant with long‐term follow‐up. The decision for transplant is challenging because COACH syndrome is rare with only descriptive characterization and patients have non‐progressive ataxia and mental retardation. However, our case shows that liver and kidney transplant can be medically successful, and the individuals achieve long‐term success if they have a stable neurological condition and an excellent support system.

Death of a living liver donor: Opening Pandora's box

Living donor liver transplantation (LDLT) is an established modality of treatment for end-stage liver disease and is the predominant form of transplantation in most Asian countries. The benefit to the recipient, who would otherwise die waiting for a cadaveric organ, is undisputed. Although a period of 23 years has passed since the first case of LDLT was reported, the LDLT/deceased donor liver transplantation debate continues and is focused heavily on 2 aspects of LDLT: donor mortality and the ethics of LDLT (specifically issues related to donor autonomy and transplant commercialism). Both, sadly, have been underreported. We present the details of a LDLT case at our institution in which the unfortunate occurrence of the donor’s death led to the revelation of facts related to the ethics of LDLT that otherwise would not have come to light.

Preserving double equipoise in living donor liver-kidney transplantation for primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive metabolic disorder caused by deficiency of pyridoxal phosphate–dependent peroxisomal alanine: glyoxalate aminotransferase (AGT) in the liver resulting in increased levels of serum oxalate. The kidneys excrete oxalate where it crystallizes within renal tubules causing nephrocalcinosis and renal failure. As the glomerular filtration rate (GFR) decreases because of progressive renal involvement, oxalate saturates the plasma and accumulates in bone and other body tissues causing systemic oxalosis. When diagnosed early, patients are managed medically (pyridoxine, citrates, hydration), but once the GFR falls below a critical level of 30 to 60 mL/ minute/1.73 m, preemptive liver transplantation (LT) may be considered. LT alone may be performed for selected patients with GFR between 15 and 30 mL/ minute/1.73 m, but the likelihood of having to undergo a subsequent kidney transplant is high. Once GFR drops below approximately 15 mL/minute/ 1.73 m, renal function is not salvageable after LT, and combined liver-kidney transplantation (CLKT) is the ideal treatment. CLKT is well accepted as the treatment of choice for patients with PH1 and end-stage renal disease. In the deceased donor liver transplantation (DDLT) setting, simultaneous CLKT from the same cadaver donor is ideal when the size and general condition of the recipient permit, with the remaining patients undergoing sequential CLKT. The infantile form of PH1 manifests as acute renal failure in the first few months of life. In this situation, where the abdominal cavity of the infant is unable to accommodate simultaneous CKLT, split LT is performed first, followed by a sequential kidney transplant if renal function remains inadequate. Compagnon et al., presenting the French national experience with such patients, reported better kidney graft survival (88% versus 10% at 10 years), less rejection, and a 78% 10-year survival rate without increased short-term mortality risk with CKLT compared to kidney transplantation alone. Others report similar results, mostly from countries where cadaveric organ donation is well established. In such a scenario, CKLT from the same deceased donor is feasible and offers immunological advantages with the liver graft providing renal immunoprotection because of immunogenetic identity. Sequential liverkidney transplantation (LKT) is only performed in small children in whom the abdominal cavity would be unable to accommodate both grafts simultaneously or in patients deemed clinically unfit to undergo combined grafts. In South Asia and the Far East where deceased donor organs are in very short supply, and living donor liver transplantation (LDLT) predominates, the familial nature of PH1, the need for 2 donor organs, and the variable severity of the disease in the recipient present special challenges (Table 1). In this scenario, the decision regarding whether to perform simultaneous or sequential LKT on PH1 patients with established renal failure is largely influenced by the availability of living donors for both organs—most commonly parents or siblings of the patient. Parents are most likely to be heterozygous carriers of the disease. We, along with other centers, assume that if they have reached adulthood without developing renal stones or nephrocalcinosis, they are unlikely to be homozygous for any of the AGT mutations. Data from the Japanese Multicenter Registry determined that heterozygous carriers of autosomal recessive diseases can safely donate their organs for transplantation without risk to either themselves or the recipient. Although these data did not include patients with PH1, Sasaki et al. recently found low to intermediate levels of liver AGT (30%-70% of normal) in living related donors for PH1 patients, suggesting they might be heterozygous carriers, without any adverse effects on either the donor or recipient. Sibling donors, however, tend to be younger, may not yet have manifested disease, and have a 25% chance of being homozygous for AGT mutations. We therefore

Combined Liver and Kidney Transplantation: Perioperative Management

Common indications for combined liver and kidney transplants (CLKT) in children are the following: Primary hyperoxaluria (PH) type 1 Congenital hepatic fibrosis with polycystic kidney Methylmalonic acidemia (MMA) Atypical hemolytic uremic syndrome

Complete remission of refractory hepatoblastoma after liver transplantation in a child with sorafenib monotherapy: A new hope?

Hepatoblastoma (HB) is the most common liver tumor in children, with an annual incidence of 1.2–1.5/million population/year.1 HB has excellent outcomes with chemotherapy and surgery in standard risk cases, while patients with high-risk and/or recurrent HB have limited options.2,3 We report complete remission (CR),4 defined as the lack of evidence of residual disease and normal levels of alfa-fetoprotein (AFP) as per the Response Evaluation Criteria in Solid Tumours (RECIST),4 in recurrent metastatic HB on sorafenib monotherapy. A 5-year-old female child of Sri Lankan nationality presented with abdominal distension of 1-month duration and was detected to have multiple space-occupying lesions in right and left hepatic lobes with AFP levels of 140,000 international units (IU)/ml. Biopsy was consistent with HB. The pretreatment extension (PRETEXT)5 stage of the lesion was 3. She was treated with six cycles of cisplatin and doxorubicin initially, but inoperability of the tumor and poor therapeutic response prompted change of chemotherapy regimen to cisplatin and irinotecan. There was no clinical or radiological response. She underwent living donor liver transplantation (LT) 1 year after the initial diagnosis and the explant liver showed HB with fetal and embryonal pattern (Supplementary Figs. S1A and S1B). She received two cycles of carboplatin as postoperative chemotherapy. AFP levels gradually increased from a baseline of 6 IU/ml after LT to 10,300 IU/ml in 14 months. Computed tomography (CT) and 18fluorodeoxyglucose positron emission tomographic (FDG–PET) scan revealed recurrence of tumor in the pericardium and diaphragm (Supplementary Fig. S2A). The lesion was excised completely and the histopathology showed fetal, embryonal, and focal macrotrabecular pattern (Supplementary Figs. S1C and S1D). Child received irinotecan and vincristine following resection but due to severe adverse reactions chemotherapy was discontinued.

Use of two expanded-criteria-donor renal allografts in a single patient

The disparity between the number of available renal donors and the number of patients on the transplant waiting list has prompted the use of expanded-criteria-donor (ECD) renal allografts to expand the donor pool. ECD allografts have shown good results in appropriately selected recipients, yet a number of renal allografts are still discarded. The use of dual renal transplantation may lower the discard rate. Additionally, the use of perfusion systems may improve acute tubular necrosis rates with these allografts. We report a successful case of a dual transplant with ECD allografts using a perfusion system. The biopsy appearance and the pump characteristics were suboptimal for these kidneys, making them unsuitable for single transplantation; however, the pair of transplanted kidneys provided increased nephron mass and functioned well. We recommend that ECD kidneys that are individually nontransplantable be evaluated for potential dual renal transplantation. Biopsy criteria and perfusion data guidelines must be developed to improve the success rates with ECD dual renal allografts. Finally, recipient selection is of utmost importance.