Karen L. Krok

Reduction of Immunosuppression as Initial Therapy for Posttransplantation Lymphoproliferative Disorder

Reduction of immunosuppression (RI) is commonly used to treat posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients. We investigated the efficacy, safety and predictors of response to RI in adult patients with PTLD. Sixty‐seven patients were managed with RI alone and 30 patients were treated with surgical excision followed by adjuvant RI. The response rate to RI alone was 45% (complete response—37%, partial response—8%). The relapse rate in complete responders was 17%. Adjuvant RI resulted in a 27% relapse rate. The acute rejection rate following RI‐containing strategies was 32% and a second transplant was feasible without relapse of PTLD. The median survival was 44 months in patients treated with RI alone and 9.5 months in patients who remained on full immunosuppression (p = 0.07). Bulky disease, advanced stage and older age predicted lack of response to RI. Survival analysis demonstrated predictors of poor outcome—age, dyspnea, B symptoms, LDH level, hepatitis C, bone marrow and liver involvement. Patients with none or one of these factors had a 3‐year overall survival of 100% and 79%, respectively. These findings support the use of RI alone in low‐risk PTLD and suggest factors that predict response and survival.

Trends in post-liver transplant survival in patients with hepatitis C between 1991 and 2001 in the United States

It has been suggested that the post–liver transplantation (LT) survival rate of patients with hepatitis C virus infection (HCV) has declined in recent years. To compare the outcome of LT in patients with HCV at various time intervals between 1991 and 2001, we used United Network for Organ Sharing data to compare the post‐LT survival of adult patients (age >18 years) with HCV with those without HCV. Of the 37,101 patients who underwent LT during the study period, 28,193 patients (HCV 7,459 and 20,734 non‐HCV) were eligible for the study. On the basis of the time of transplantation, patients were divided into 3 groups: 1991‐1993 (period 1), 1994‐1997 (period 2), and 1998‐2001 (period 3). The patient and graft survival rates were adjusted for other known confounding variables that influenced outcomes. The 3‐year patient survival rate was lower in HCV patients compared with non‐HCV recipients (78.5% vs. 81.4%, hazard ratio 1.14, 95% confidence interval 1.05‐1.23, P = 0.001). The graft (72.8%, 71.0%, and 69.8%) and patient (77.4%, 79.6%, and 78.5%) survival of HCV patients remained unchanged during study periods 1‐3, respectively. However, the graft and patient survival rates of non‐HCV recipients improved markedly during study periods 2 and 3 compared with period 1. The graft and patient survival has remained unchanged between 1991 and 2001 in HCV recipients, but during the same period, there was a great improvement in survival among non‐HCV recipients. Liver Transpl 13:719–724, 2007.

Impact of the Hepatopulmonary Syndrome MELD Exception Policy on Outcomes of Patients After Liver Transplantation: An Analysis of the UNOS Database

BACKGROUND & AIMS Patients with hepatopulmonary syndrome (HPS) are prioritized for liver transplantation (given exception points) due to their high pre- and post-transplantation mortality. However, few studies have evaluated the outcomes of these patients. METHODS We performed a retrospective cohort study using data submitted to the United Network for Organ Sharing in a study of the effects of room-air oxygenation on pre- and post-transplantation outcomes of patients with HPS. We identified thresholds associated with post-transplantation survival using cubic spline analysis and compared overall survival times of patients with and without HPS. RESULTS From 2002 through 2012, nine hundred and seventy-three patients on the liver transplant waitlist received HPS exception points. There was no association between oxygenation and waitlist mortality among patients with HPS exception points. Transplant recipients with more severe hypoxemia had increased risk of death after liver transplantation. Rates of 3-year unadjusted post-transplantation survival were 84% for patients with PaO2 of 44.1-54.0 mm Hg vs 68% for those with PaO2 ≤ 44.0 mm Hg. In multivariable Cox models, transplant recipients with an initial room-air PaO2 ≤ 44.0 mm Hg had significant increases in post-transplantation mortality (hazard ratio = 1.58; 95% confidence interval [CI]: 1.15-2.18) compared with those with a PaO2 of 44.1-54.0 mm Hg. Overall mortality was significantly lower among waitlist candidates with HPS exception points than those without (hazard ratio = 0.82; 95% CI: 0.70-0.96), possibly because patients with HPS have a reduced risk of pre-transplantation mortality and similar rate of post-transplantation survival. CONCLUSIONS Although there was no association between pre-transplantation oxygenation and waitlist survival in patients with HPS Model for End-Stage Liver Disease exception points, a pre-transplantation room-air PaO2 ≤ 44.0 mm Hg was associated with increased post-transplantation mortality. HPS Model for End-Stage Liver Disease exception patients had lower overall mortality compared with others awaiting liver transplantation, suggesting that the appropriateness of the HPS exception policy should be reassessed.

Endoscopic Management of Biliary Complications After Liver Transplantation

Complications of the biliary tract are an important cause of morbidity and mortality after liver transplantation. The most frequent complications are anastomotic biliary tract strictures, bile leaks, and bile duct stones. The estimated incidence of these complications ranges between 5% and 25%, although rates have been decreasing in recent years. Most complications can be managed successfully with endoscopic retrograde cholangiography. This article reviews the various biliary complications after liver transplantation (both deceased donor and living-related donor) and their endoscopic management.

Colorectal cancer in inflammatory bowel disease.

Purpose of reviewPatients with inflammatory bowel disease, either Crohn disease or ulcerative colitis, are at an increased risk for developing colorectal carcinoma. Recent findingsSurveillance colonoscopy, although never formally evaluated in a prospective controlled trial, is performed in an effort to reduce this risk. Novel methods of detecting dysplasia are constantly being evaluated, including chromoendoscopy and biomarkers of carcinoma, in an attempt to stratify patients who are at a higher risk of developing high-grade dysplasia or carcinoma. SummaryBecause of the potential impact on quality of life and life expectancy, an optimal strategy for reducing the risk of developing colorectal cancer in patients with inflammatory bowel disease needs to be defined.

Nutrition in Crohn disease.

Nutrition plays an important role in the pathogenesis, treatment, and morbidity of Crohn disease. Approximately two thirds to three fourths of hospitalized patients with active disease and one fourth of outpatients with Crohn disease are malnourished. Malnutrition, which can be present even when Crohn disease is in remission, can affect growth, cellular and humoral immunity, bone density, and wound healing. Decreased nutrient intake, malabsorption, drug–nutrient interactions, anorexia, and protein-losing enteropathy can all contribute to the protein-calorie malnutrition and other specific nutrient deficiencies seen in Crohn disease. Therefore, by preventing and correcting nutrient deficiencies, nutritional therapy is an important component in the overall management of patients with Crohn disease.

Single-center outcomes of combined heart and liver transplantation in the failing Fontan

Long‐term outcomes of the Fontan operation include Fontan failure and liver disease. Combined heart‐liver transplantation (CHLT) is an option for select patients although limited data exist on this strategy. A retrospective review of Fontan patients 18 years or older referred for cardiac transplant evaluation between 2000 and 2013 at the Hospital of the University of Pennsylvania was performed. All patients were considered for potential CHLT. Clinical variables such as demographics, perioperative factors, and short‐term outcomes were reviewed. Of 17 referrals for cardiac transplantation, seven Fontan patients underwent CHLT. All patients who underwent CHLT had either advanced fibrosis or cirrhosis on liver biopsy. There were no perioperative deaths. The most common postoperative morbidity was acute kidney injury. Short‐term complications include one episode of acute liver rejection but no cardiac rejection greater than 1R. CHLT is an acceptable therapeutic option for patients with failing Fontan physiology who exhibit concomitant advanced liver fibrosis. However, optimal patient selection is currently undefined, and long‐term outcomes are not known.

Combined heart-liver transplantation; implications for liver-alone wait list mortality.

Combined heart-liver (HL) transplants are increasingly performed as the definitive treatment for patients with dually failing organs (1). The scarcity of organs however, raises ethical concern about allocating two life-saving organs to a single patient (2,3). The principle of equitable distribution is further challenged by the current rules governing multi-organ allocation, which permit the primary organ, allocated based upon the recipients wait list priority, to automatically sequester a second organ from the same donor, regardless of wait list priority specific to the second organ (4). This rule applies to all solid organs, with the exception that kidneys are always allocated secondarily (5). Latent wait list attrition resulting from multiple organ allocation to one recipient has not been quantified, but is of concern to the transplant community.

Perioperative and postoperative use of immunosuppressive agents in liver transplantation.

Immunosuppression after liver transplantation is essential for graft and patient survival. At the inception of solid organ transplantation over 50 years ago, drug regimens were limited, the toxicities were high, and the efficacy and specificity of each agent was low. Transplant physicians now have more drugs in their armamentarium, but there is no gold standard or optimal protocol for immunosuppression across transplant centers. Each transplant program uses its own regimen, based on its own personal clinical experience and published scientific and clinical data. In addition, each transplant center individualizes the choice of immunosuppressive drugs, either as monotheraphy or combination therapy, and arbitrarily decides the optimal dosages and target trough blood levels. The decision to use induction therapy, the type of induction therapy, and the timing of instituting a therapy after liver transplantation also is often arbitrary. But the goal at each center is the same—to achieve graft acceptance without substantially increasing the risk of infection and malignancy. Most immunosuppressive regimens will use a combination of agents during the early postoperative period, and by implementing drugs with different modes of actions and toxicities, a lower dose of each individual drug can be used. A majority of patients could be managed with monotherapy 6 to 12 months after transplantation. In the early years of liver transplantation, corticosteroids and azathioprine were the backbone of any immunosuppression regimen. With the introduction of calcineurin inhibitors (cyclosporine in the early 1980s and tacrolimus in the early 1990s), and the use of other agents, such as mycophenolate mofetil (MMF) and sirolimus, the transplant team now has a wider array of drugs to choose from to manipulate the immune system, control rejection, and allow the development of tolerance.

Portal Hypertension: An Underestimated Entity?

Objective:The aim of this study is to evaluate portal hypertension as an independent risk factor in general surgical procedures. Background:Data on the impact of portal hypertension in general surgical outcomes has been limited. Published literature has focused mainly on its effect in liver surgery. The Child Pugh score and Model for End Stage Liver Disease are utilized for surgical risk assessment in liver disease but they do not accurately reflect degree of portal hypertension. Methods:From 2005 to 2012, patients with esophageal varices (EV) in the National Surgical Quality Improvement Program (NSQIP) formed the portal hypertension cohort, and were case matched to patients without esophageal varices (NEV) based on sex, age, surgery type, and year of operation. Thirty day mortality and morbidity were analyzed using generalized estimating equations for binary outcomes. EV patients were also dichotomized by Model for End Stage Liver Disease (MELD) score (⩽15 vs >15) and compared with NEV patients. Results:One thousand five hundred and seventy-four EV patients were matched to 3148 NEV patients. In multivariable analysis, EV patients had a 3.01 higher odds of 30 day mortality (P < 0.001) and 1.28 higher odds of complications (P < 0.001) compared with NEV patients. EV patients with MELD >15 had 4.64 higher odds of death within 30 days (P < 0.001) and had 1.75 higher odds of complications within 30 days (P < 0.001) compared with NEV patients; EV patients with MELD 15 or less had 1.95 higher odds of 30 day mortality (P < 0.001) compared with NEV patients. Conclusions:Portal hypertension is associated with a significant mortality and morbidity risk in general surgery, and should not be underestimated even in patients with MELD 15 or less where the early mortality risk remained significant.