Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

BACKGROUND: Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. AIMS: To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. METHODS: The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. RESULTS: The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. CONCLUSIONS: Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

Diagnosis of morbid obesity may not impact healthcare utilization for orthotopic liver transplantation: A propensity matched study.

AIM: To study mortality, length of stay, and total charges in morbidly obese adults during index hospitalization for orthotopic liver transplantation. METHODS: The Nationwide Inpatient Sample was queried to obtain demographics, healthcare utilization, post orthotopic liver transplantation (OLT) complications, and short term outcomes of OLT performed from 2003 to 2011 (n = 46509). We divided patients into those with [body mass index (BMI) ≥ 40] and without (BMI < 40) morbid obesity. Multivariable logistic regression analysis was performed to characterize differences in in-hospital mortality, length of stay (LOS), and charges for OLT between patients with and without morbid obesity after adjusting for significant confounders. Additionally, propensity matching was performed to further validate the results. RESULTS: Of the 46509 patients who underwent OLT during the study period, 818 (1.8%) were morbidly obese. Morbidly obese recipients were more likely to be female (46.8% vs 33.4%, P = 0.002), Caucasian (75.2% vs 67.8%, P = 0.002), in the low national income quartile (32.3% vs 22.5%, P = 0.04), and have ≥ 3 comorbidities (modified Elixhauser index; 83.9% vs 45.0%, P < 0.001). Morbidly obese patient also had an increase in procedure related hemorrhage (P = 0.028) and respiratory complications (P = 0.043). Multivariate and propensity matched analysis showed no difference in mortality (OR: 0.70; 95%CI: 0.27-1.84, P = 0.47), LOS (ß: -4.44; 95%CI: -9.93, 1.05, P = 0.11) and charges for transplantation (ß: $15693; 95%CI: -51622-83008, P = 0.64) between the two groups. Morbidly obese patients were more likely to have transplants on weekdays (81.7%) as compared to those without morbid obesity (75.4%, P = 0.029). CONCLUSION: Morbid obesity may not impact in-hospital mortality and health care utilization in OLT recipients. However, morbidly obese patients may be selected after careful assessment of co-morbidities.

Passenger lymphocyte syndrome: a forgotten cause of postliver transplant jaundice and anemia.

A 48-year-old man with cirrhosis secondary to nonalcoholic steatohepatitis and chronic hepatitis C infection underwent a successful orthotopic liver transplant from a B+ donor without intraoperative complications. His postoperative course was complicated by hemolytic anemia, and he was ultimately diagnosed as having passenger lymphocyte syndrome. Passenger lymphocyte syndrome is a complication of both solid-organ and stem cell transplants. It is caused by donor B lymphocyte production of antibodies causing a primary or secondary immune response to recipient erythrocytes. Most commonly, it is in the setting of minor ABO mismatches, such as with a group B liver transplanted into a group AB recipient. Typically, passenger lymphocyte syndrome presents as a mild, self-limiting hemolytic anemia. Laboratory findings are consistent with other forms of hemolytic anemia including decreased hemoglobin and haptoglobin, elevated reticulocyte count, and indirect hyperbilirubinemia There is no definitive treatment for passenger lymphocyte syndrome or strong evidence to favor a particular treatment regimen. Passenger lymphocyte syndrome has been successfully treated with supportive care and blood transfusions matched to the liver donor. It is prudent that physicians caring for patients who receive ABO mismatched organs have a high index of clinical suspicion for passenger lymphocyte syndrome during the early postoperative period when posttransplant patients present with jaundice and anemia.

Preservation solutions used during abdominal transplantation: Current status and outcomes.

Organ preservation remains an important contributing factor to graft and patient outcomes. During donor organ procurement and transportation, cellular injury is mitigated through the use of preservation solutions in conjunction with hypothermia. Various preservation solutions and protocols exist with widespread variability among transplant centers. In this review of abdominal organ preservation solutions, evolution of transplantation and graft preservation are discussed followed by classification of preservation solutions according to the composition of electrolytes, impermeants, buffers, antioxidants, and energy precursors. Lastly, pertinent clinical studies in the setting of hepatic, renal, pancreas, and intestinal transplantation are reviewed for patient and graft survival as well as financial considerations. In liver transplants there may be some benefit with the use of histidine-tryptophan-ketoglutarate (HTK) over University of Wisconsin solution in terms of biliary complications and potential cost savings. Renal grafts may experience increased initial graft dysfunction with the use of Euro-Collins thereby dissuading its use in support of HTK which can lead to substantial cost savings. University of Wisconsin solution and Celsior are favored in pancreas transplants given the concern for pancreatitis and graft thrombosis associated with HTK. No difference was observed with preservation solutions with respect to graft and patient survival in liver, renal, and pancreas transplants. Studies involving intestinal transplants are sparse but University of Wisconsin solution infused intraluminally in combination with an intra-vascular washout is a reasonable option until further evidence can be generated. Available literature can be used to ameliorate extensive variation across centers while potentially minimizing graft dysfunction and improving associated costs.

Preservation solutions for cardiac and pulmonary donor grafts: a review of the current literature.

Hypothermic preservation of donor grafts is imperative to ameliorate ischemia related cellular damage prior to organ transplantation. Numerous solutions are in existence with widespread variability among transplant centers as to a consensus regarding the optimal preservation solution. Here, we present a concise review of pertinent preservation studies involving cardiac and pulmonary allografts in an attempt to minimize the variability among institutions and potentially improve graft and patient survival. A biochemical comparison of common preservation solutions was undertaken with an emphasis on Euro Collins (EC), University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK), Celsior (CEL), Perfadex (PER), Papworth, and Plegisol. An appraisal of the literature ensued containing the aforementioned preservation solutions in the setting of cardiac and pulmonary transplantation. Available evidence supports UW solution as the preservation solution of choice for cardiac transplants with encouraging outcomes relative to notable contenders such as CEL. Despite its success in the setting of cardiac transplantation, its use in pulmonary transplantation remains suboptimal and improved outcomes may be seen with PER. Together, we suggest, based on the literature that the use of UW solution and PER for cardiac and pulmonary transplants, respectively may improve transplant outcomes such as graft and patient survival.

Isolated cardiac metastasis from plasmacytoid urothelial carcinoma of the bladder.

UNLABELLED: A 57-year-old male with a history of hypertension presented with shortness of breath, intermittent substernal chest pain, subjective fevers, and a 30-pound weight loss. He was found to have a bladder mass four months prior to presentation, for which he underwent cystoscopy and surgical removal. Pathology demonstrated high-grade superficial plasmacytoid urothelial carcinoma extending into the submucosa but not the muscularis propria. Given the superficial nature of his bladder cancer, a cystectomy was deferred. He was subsequently lost to follow-up care. On arrival, physical exam was notable for tachycardia, tachypnea, and distant heart sounds. An ECG showed an incomplete right bundle branch block and sinus tachycardia. Computed tomography pulmonary angiography revealed a three-cm pericardial effusion. Transthoracic echocardiography confirmed this finding and revealed a mass in the right ventricle (RV) extending into the outflow tract and infiltrating the free wall. The RV was dilated with an estimated RV systolic pressure of 37 mmHg. Pericardiocentesis yielded nearly one liter of serosanguinous fluid with non-diagnostic cytology. Partial median sternotomy with biopsy showed pathologic findings consistent with metastatic urothelial carcinoma, plasmacytoid variant. A PET scan showed increased uptake exclusively in the heart. The oncology team discussed options with the patient including chemotherapy and palliative care. The patient decided to withhold further therapy and went home with hospice care. He died two months later. DISCUSSION: Bladder cancer is the fourth most common cancer in men in the United States. Most patients (69%) with metastatic bladder cancer have multiple organs involved; conversely, our patient had a PET scan indicating his disease was localized to the heart. Plasmacytoid urothelial carcinoma is a rare subtype of bladder cancer, and is estimated to make up less than three percent of all invasive bladder carcinomas. At the time of this publication we are aware of only three other reported instances of isolated cardiac metastasis with urothelial bladder origin; none of which were the plasmacytoid variant. CONCLUSION: This case highlights a previously unreported presentation of plasmacytoid urothelial carcinoma. Clinicians must remember that even superficial cancers can have significant metastatic potential.