Preexisting atrial fibrillation and cardiac complications after liver transplantation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with increased cardiovascular morbidity and all-cause mortality. Our aim was to determine the impact of preexisting AF on patients undergoing liver transplantation (LT). A retrospective case-control study was performed. Records from patients who underwent LT between January 2005 and December 2008 at Mayo Clinic Florida were reviewed. Patients with preexisting AF were identified and matched to patients who did not have a diagnosis of AF. Thirty-two of 717 LT recipients (4.5%) had AF before LT. These patients were compared to a control group of 63 LT recipients. Pre-LT left ventricular hypertrophy (P = 0.03), a history of congestive heart failure (P = 0.04), and a history of stroke or transient ischemic attack (P = 0.03) were significantly more prevalent in patients with AF versus controls. Intraoperative adverse cardiac events (P = 0.02) and AF-related adverse postoperative events (P < 0.001) were more common in the recipients with known AF. Six patients with paroxysmal AF (19%) developed chronic/persistent AF postoperatively. Graft survival and patient survival were similar in the groups. Although patients with AF had a higher incidence of intraoperative cardiac events, a higher cardiovascular morbidity rate, and a complicated postoperative course, this did not affect overall graft and patient survival.

Reversible non-ischaemic cardiomyopathy and left ventricular dysfunction after liver transplantation: a single-centre experience.

BACKGROUND & AIMS: Non-ischaemic cardiomyopathy (NIC) is an early complication of liver transplantation (LT). Our aims were to define the prevalence, associated clinical factors, and prognosis of this condition. METHODS: A retrospective study was performed on patients undergoing LT at our institution from January 2005 to December 2012. Patients who developed NIC were identified. Data collected included demographic and clinical data. RESULTS: A total 1460 transplants were performed in this period and seventeen patients developed NIC. Pretransplant median QTc interval was 459 (range, 405-530), and median E/A ratio was 1 (range, 0.71-1.67). Fourteen patients (82%) were severely malnourished and required nutritional support. Thirteen patients (76%) had renal insufficiency. Median time to onset was 2 days post-transplant (range, 0-20). Echocardiograms showed global left ventricular hypokinesis and a decrease in ejection fraction (EF) from a median of 65% (range, 50-81) pretransplant to a median of 21% (range, 15-32). Median raw model for end-stage liver disease (MELD) score was 29 in patients with NIC vs. 18 in patients without cardiomyopathy (P = 0.01). There was no significant difference between recipients with NIC vs. recipients without cardiomyopathy regarding donor age, donor risk index, and cold and warm ischaemia time. Recovery of cardiac function occurred in 16 patients, with a median EF of 44% (range, 25-65%) at the time of discharge. The last echocardiogram available showed a median EF of 59% (range, 49-73%). One-year survival of NIC patients was 94.1%. CONCLUSION: Non-ischaemic cardiomyopathy is a rare complication after LT. Patients with NIC are critically ill, with high MELD score, and severe malnutrition.

Gastroparesis: from concepts to management.

While the symptoms of gastroparesis are common, an accurate diagnosis is based on a combination of those symptoms with a documented delay in gastric emptying. Typical symptoms include nausea, vomiting, early satiety, postprandial fullness, bloating, and abdominal discomfort. Patients with gastroparesis face many diagnostic and therapeutic challenges. The most common origins of gastroparesis are idiopathic causes and diabetes mellitus. The increased use of certain medications in medicine today, including opiates and drugs with anticholinergic properties, can alter gastrointestinal functions and mimic symptoms of gastroparesis. Accordingly, alternative explanations for symptoms and altered gastrointestinal function need to be considered. Numerous clinical sequelae, including weight loss and severe protein-calorie malnutrition, may be seen in advanced stages of gastroparesis. This article provides an overview of gut sensorimotor function to help the reader better understand the clinical presentation of patients with dyspepsia and those who may have accompanying delayed gastric emptying that meets criteria for gastroparesis. Techniques available for diagnosing motor dysfunction and the principles of gastroparesis management are reviewed. Nutrition recommendations and a review of pharmacologic agents, nonpharmacologic techniques, and novel treatment modalities are provided.

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors.

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Logistic regression models were used in the univariate and multivariate analyses of predictors for the development of IC. Additional analyses using Cox regression models were performed to identify predictors of graft survival and to compare outcomes for DCD and DBD graft recipients. In our series, the patient survival rates for the DCD and DBD groups at 1, 3, and 5 years was 92.6%, 85%, and 80.9% and 89.8%, 83.0%, and 76.6%, respectively (P = not significant). The graft survival rates for the DCD and DBD groups at 1, 3, and 5 years were 80.9%, 72.7%, and 68.9% and 83.3%, 75.1%, and 68.6%, respectively (P = not significant). In the DCD group, 5 patients (2.5%) had primary nonfunction, 7 patients (3.5%) had hepatic artery thrombosis, and 3 patients (1.5%) experienced hepatic necrosis. IC was diagnosed in 24 patients (12%), and 11 of these patients (5.5%) required retransplantation. In the multivariate analysis, the asystole-to-cross clamp duration [odds ratio = 1.161, 95% confidence interval (CI) = 1.021-1.321] and African American recipient race (odds ratio = 5.374, 95% CI = 1.368-21.103) were identified as significant factors for predicting the development of IC (P < 0.05). This study has established a link between the development of IC and the asystole-to-cross clamp duration. Procurement techniques that prolong the nonperfusion period increase the risk for the development of IC in DCD liver grafts.

Age is not a contraindication for orthotopic liver transplantation: a single institution experience with recipients older than 75 years.

INTRODUCTION: Transplant community has arbitrary age limit for liver transplantation based on the increased comorbidities in aging population. There has been an increased demand to consider older patients to have access to liver transplantation as the US population continues to live longer with better health. METHODS: This is a single institution, retrospective review of patients, who were age 75 or over underwent liver transplantation. RESULTS: There were 13 patients, who were 75 years or older at the time of orthotopic liver transplantation. There were no intraoperative or perioperative deaths. Seven of 13 patients are still alive (53.8%) with a mean survival of 65 months. CONCLUSION: Our study demonstrates that a with proper evaluation and careful consideration of risk factors, individuals older than 75 years of age can undergo this life-saving procedure with acceptable long-term survival.

Recurrent liver failure caused by IgG4 associated cholangitis.

Immunoglobulin G4 associated cholangitis (IAC) is an autoimmune disease associated with autoimmune pancreatitis (AIP). It presents with clinical and radiographic findings similar to primary sclerosing cholangitis (PSC). IAC commonly has a faster, more progressive onset of symptoms and it is more common to see obstructive jaundice in IAC patients compared to those with PSC. One of the hallmarks of IAC is its responsiveness to steroid therapy. Current recommendations for treatment of AIP demonstrate excellent remission of the disease and associated symptoms with initiation of steroid therapy followed by steroid tapering. If untreated, it can progress to irreversible liver failure. This report describes a 59 year-old female with undiagnosed IAC who previously had undergone a pancreaticoduodenectomy for a suspected pancreatic cancer and later developed liver failure from presumed PSC. The patient underwent an uncomplicated liver transplantation at our institution, but experienced allograft failure within five years due to progressive and irreversible bile duct injury. Radiology and histology suggested recurrence of PSC, but the diagnosis of IAC was suspected based on her past history and confirmed when IgG4 positive cells were found within the intrahepatic bile duct walls on a liver biopsy. A successful liver retransplantation was performed and the patient is currently on triple immunosuppressive therapy. Our experience in this case and review of the current literature regarding IAC management suggest that patients with suspected or recurrent PSC with atypical features including history of pancreatitis should undergo testing for IAC as this entity is highly responsive to steroid therapy.

Use of liver grafts from donation after cardiac death donors for recipients with hepatitis C virus.

Hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation in the United States. Although studies have addressed the use of expanded criteria donor organs in HCV(+) patients, to date the use of liver grafts from donation after cardiac death (DCD) donors in HCV(+) patients has been addressed by only a limited number of studies. This retrospective analysis was undertaken to study the outcomes of DCD liver grafts used in HCV(+) recipients. Seventy-seven HCV(+) patients who received DCD liver grafts were compared to 77 matched HCV(+) patients who received donation after brain death (DBD) liver grafts and 77 unmatched non-HCV patients who received DCD liver grafts. There were no differences in 1-, 3-, and 5-year patient or graft survival among the groups. Multivariate analysis showed that the Model for End-Stage Liver Disease score [hazard ratio (HR) = 1.037, 95% confidence interval (CI) = 1.006-1.069, P = 0.018] and posttransplant cytomegalovirus infection (HR = 3.367, 95% CI = 1.493-7.593, P = 0.003) were significant factors for graft loss. A comparison of the HCV(+) groups for fibrosis progression based on protocol biopsy samples up to 5 years post-transplant did not show any difference; in multivariate analysis, HCV genotype 1 was the only factor that affected progression to stage 2 fibrosis (genotype 1 versus non-1 genotypes: HR = 2.739, 95% CI = 1.047-7.143, P = 0.040). In conclusion, this match-controlled, retrospective analysis demonstrates that DCD liver graft utilization does not cause untoward effects on disease progression or patient and graft survival in comparison with DBD liver grafts in HCV(+) patients.

Explanted liver inflammatory grade predicts fibrosis progression in hepatitis C recurrence.

UNLABELLED: Factors present prior to liver transplantation (LT) that predict fibrosis progression in recurrent hepatitis C infection (HCV) after LT would be important to identify. This study sought to determine if histologic grade of HCV in the explant predicts fibrosis progression in recurrent HCV. The clinical and histologic data of all 159 patients undergoing their first LT for HCV at our center from 1998 to 2001 were retrospectively reviewed with follow-up through June 2008. Twenty-five cases were excluded for: non-HCV-related graft loss <90 days (19), recidivism (4), or unavailable explant or follow-up biopsies (2). A single pathologist scored (Ishak) explants in a blinded fashion. Patients were grouped by explant inflammatory grade ≤ 4 (group1) and >4 (group 2). Prospectively scored liver biopsies (protocol months 1 and 4, annually, and as indicated clinically) were reviewed for development of advanced fibrosis (bridging or cirrhosis). Cox proportional hazard regression was used to analyze the association of explant grade, donor, viral and LT factors with progression to advanced fibrosis. The groups were well-matched for patient, viral, donor, and transplant factors. Five-year advanced fibrosis-free survival in group 1 versus group 2 was 63% versus 28%, P < 0.001. Explant grade >4 was associated with increased HCV-related graft loss at 1 (6% versus 3%) and 5 (36% versus 14%) years post-LT (P = 0.003). On univariate and multivariate Cox regression analysis, predictors of advanced fibrosis were explant grade >4 (hazard ratio [HR] = 3.3, 95% confidence interval [CI] = 1.9-5.6, P < 0.001) donor age >50 (HR = 3.3, 95% CI = 1.9-5.7, P < 0.001) and viral load at LT of >158,730 IU/mL (HR = 1.8, 95% CI = 1.05-3.1, P = 0.03). CONCLUSION: Explant histologic grade can identify patients requiring more aggressive monitoring and intervention for HCV recurrence post-LT.

Improving graft survival for patients undergoing liver transplantation.

Liver transplant (LT) outcomes are reported to be improving in non-HCV recipients but not for those infected with HCV. Our aim was to evaluate graft survival and predictors of outcome in HCV and non-HCV patients before and after 2003. Patients with primary LT between February 1, 1998, and December 31, 2005, were included. Patients were divided into Era 1 (1998-2002) and Era 2 (2003-2005) with follow-up through May 31, 2009. Graft survival was compared for HCV, non-HCV, and all patients. There was significant improvement in graft survival in Era 2 for HCV patients. Graft survival in Era 2 of HCV patients was equivalent to non-HCV patients. The most significant improvement between eras was in outcomes of grafts from donors ≥60 yr with three-yr graft survival 58.6 (51.3-65.9) vs. 75.4 (68.9-81.9), p = 0.002. The use of donors ≥60 did not change between eras: 31% vs. 34%; however, utilization in HCV recipients decreased from 36% to 3% (p < 0.001). In conclusion, graft survival of HCV patients has improved significantly since 2003 and was comparable to non-HCV patients up to three yr. The change in management of donor organs into HCV and non-HCV patients likely contributed to this outcome.

Nutritional support in head injury.

Nutritional support is imperative to the recovery of head-injury patients. Hypermetabolism and hypercatabolism place this patient population at increased risk for weight loss, muscle wasting, and malnutrition. Nutrition management may be further complicated by alterations in gastrointestinal motility. Resting energy expenditure should be measured using indirect calorimetry and protein status measured using urine urea nitrogen. Providing early enteral nutrition within 72 hours of injury may decrease infection rates and overall complications. Establishing standards of practice and nutrition protocols will assure patients receive optimal nutrition assessment and intervention in a timely manner.

Long term survival and complications after liver transplantation in patients with chronic hepatitis B.

BACKGROUND: Following introduction of effective antiviral prophylaxis, recurrent hepatitis B after liver transplantation (LT) has become a rare event. MATERIAL/METHODS: From 1998 to 2001, 402 patients underwent 467 LTs at our center including 24 individuals (28 LTs) with chronic hepatitis B. All patients received HBIg prophylaxis; 23 in combination with lamivudine and one (YMDD mutant) received adefovir. RESULTS: Eleven patients (46%) had HCC (five outside the Milan criteria); only one died from tumor recurrence four years post LT. The one-year graft and patient survival were 87% and 92%, respectively. Currently 19 patients (79%) are alive with well functioning grafts (minimum follow up of >7 years). No patient developed recurrent hepatitis B; 12 currently receive lamivudine/HBIg, 3 lamivudine monotherapy, 3 discontinued antivirals. Follow up liver biopsies showed minimally active or no active hepatitis and negative HBV immunostains in all patients. Long term comorbid conditions included hypertension (77%), chronic renal failure (50%), diabetes mellitus (77%), hyperlipidemia (36%), obesity (55%), malignancies (37%) and neuropsychiatric disorders (55%). During the study period, 24 individuals (6%) were transplanted for chronic hepatitis B as opposed to only 38 individuals (3.3%) from 2002 to 6/2008 (1298 LTs in 1162 patients). CONCLUSIONS: LT for chronic HBV produced excellent long term results despite inclusion of patients with HCC outside the Milan criteria. Long term medical complications must be considered. Indication for LT for chronic HBV is declining but long term development of resistance remains a matter of concern.

HCV recurrence in HIV-infected patients after liver transplant.

Patients coinfected with hepatitis C virus (HCV) and HIV undergoing liver transplantation (LT) are at risk of early, aggressive HCV recurrence. This study investigates the use of frequent protocol-driven biopsies to identify HCV recurrence post LT in coinfected patients. Five consecutive HIV/HCV-coinfected patients underwent LT. Liver biopsies were obtained post LT at 1 hour; days 7, 120, and 365; then annually; and as clinically indicated. Stage 2 (Ishak) or higher fibrosis occurred in 4 of the 5 patients by 60, 120, 270, and 365 days. Two patients died of HCV recurrence and liver failure at 6 and 35 months post LT. Three patients survived more than 4 years after LT, 2 having sustained virologic responses to anti-HCV treatment. Another has histologic recurrence not responding to treatment. Hepatitis C virus recurrence can be rapid and aggressive after LT in HIV-coinfected patients. Serial biopsies identify recurrence early, allowing for prompt initiation of treatment.

Liver transplantation and pancreatic resection: a single-center experience and a review of the literature.

Liver transplantation may occasionally be indicated in patients with unique clinical scenarios. Little is known regarding the outcomes of patients who have had a pancreatic resection prior to, in combination with, or after liver transplantation. A retrospective review of all patients undergoing liver transplantation from March 1998 to March 2008 identified 17 patients who also underwent pancreatic resection. An additional literature review was performed. Five underwent pancreatic resection prior to liver transplantation (1.7, 3.6, 3.8, 6.8, and 8.1 years), another 9 underwent pancreatic resection together with liver transplantation, and 3 underwent pancreatic resection after liver transplantation (2.2, 2.6, and 3.8 years). Indications for pancreatic resection included cholangiocarcinoma (n = 6), neuroendocrine tumor (n = 5), pancreatic cancer (n = 2), gastrointestinal stromal tumor (n = 1), periampullary adenocarcinoma (n = 1), duodenal adenomas (n = 1), and benign pancreatic mass (n = 1). Indications for liver transplantation were metastatic neuroendocrine tumor disease (n = 5), primary sclerosing cholangitis (n = 5), hepatitis C virus (n = 2), metastatic gastrointestinal stromal tumor (n = 1), Klatskin tumor (n = 1), alcohol cirrhosis (n = 1), alpha-1 antitrypsin deficiency (n = 1), and chemotherapy-induced cirrhosis (n = 1). One patient died intraoperatively, 7 patients died of tumor recurrence, 2 patients died from transplant complications, and 7 patients are still alive. Pancreatic resection-related complications included 4 pancreatic fistulas. A literature review confirmed liver transplantation/pancreatic resection-related complications. In conclusion, liver transplantation and pancreatic resection remain uncommon, and a good outcome can be achieved. Recurrence of malignant disease is the main factor limiting survival, and specific morbidity may be related to pancreatic resection and liver transplantation.

Unexplained and prolonged perioperative hypotension after orthotopic liver transplantation: undiagnosed systemic mastocytosis.

Arterial vasodilation is common in end-stage liver disease, and systemic hypotension often may develop, despite an increase in cardiac output. During the preparation for and the performance of orthotopic liver transplantation, expected and transient hypotension may be caused by induction agents, anesthetic agents, liver mobilization, or venous clamping. A mild decrease of the already low systemic vascular resistance is often observed, and intermittent use of short-acting agents for vasopressor support is not uncommon. In this report, we describe a patient with unexpected and prolonged hypotension due to vasodilation during and after orthotopic liver transplantation. The preoperative end-stage liver disease evaluation, intraoperative events, and intensive care unit course were reviewed, and no cause for the vasodilation and prolonged hypotension was evident. The explant pathology report was later available and showed systemic mastocytosis. We hypothesize that the unexpected hypotension and vasodilation were caused by mast cell degranulation and its systemic effects on arterial tone.

Liver transplantation using young pediatric donor grafts in adults with hepatitis C infection.

BACKGROUND: The impact of using grafts from donor's age less than or equal to 13 years on adult hepatitis C virus (HCV) recipients in terms of survival and HCV recurrence is undefined. To determine if adults undergoing liver transplantation for HCV who receive a graft from a donor age less than or equal to 13 years have similar outcomes to recipients of organs from 18- to 35-year-old donors. METHODS: Records from adult HCV patients undergoing liver transplantation between April 1998 and April 2004 who received whole grafts from non-HCV donors less than 35 years old after brain death were reviewed. Patients with donor age less than or equal to 13 years (group 1) and 18 to 35 years (group 2) were compared for patient and graft survival, allograft rejection, biliary complications, and HCV recurrence. RESULTS: Fifty-one HCV patients were analyzed. The two groups were similar except that group 1 donors and recipients were smaller in size. One year patient and graft survival for groups 1 vs. 2 were 93% vs. 94% and 93% vs. 83%, respectively (P=NS). Biliary complications, HCV recurrence, and advanced fibrosis free survival were not significantly different. CONCLUSION: Whole liver grafts from donors age less than or equal to 13 years can potentially be used in selected size-matched adult HCV patients in the absence of an acceptable pediatric recipient.

Long-term outcomes of donation after cardiac death liver allografts from a single center.

Organ shortage continues to be a major challenge in transplantation. Recent experience with controlled non-heart-beating or donation after cardiac death (DCD) are encouraging. However, long-term outcomes of DCD liver allografts are limited. In this study, we present outcomes of 19 DCD liver allografts with follow-up >4.5 years. During 1998-2001, 19 (4.1%) liver transplants (LT) with DCD allografts were performed at our center. Conventional heart-beating donors included 234 standard criteria donors (SCD) and 214 extended criteria donors (ECD). We found that DCD allografts had equivalent rates of primary non-function and biliary complications as compared with SCD and ECD. The overall one-, two-, and five-yr DCD graft and patient survival was 73.7%, 68.4%, and 63.2%, and 89.5%, 89.5%, and 89.5%, respectively. DCD graft survival was similar to graft survival of SCD and ECD in non hepatitis C virus (HCV) recipients (p > 0.370). In contrast, DCD graft survival was significantly reduced in HCV recipients (p = 0.007). In conclusion, DCD liver allografts are durable and have acceptable long-term outcomes. Further research is required to assess the impact of HCV on DCD allograft survival.

Dual hepatitis virus infections in liver transplant: case report and a review of the literature.

BACKGROUND: Liver transplantation (LT) using grafts from anti-HBVcore antibody-positive (anti-HBVcAB+) donors carry risk for development of hepatitis B virus (HBV) infection. The long-term course of hepatitis C virus (HCV) patients receiving anti-HBVcAB+ grafts is poorly understood. PATIENTS AND METHODS: A patient with chronic hepatitis C received an anti-HBVc+ graft and developed de novo hepatitis B after four months. We describe the 14 HCV patients who received antiHBVc+ grafts and the condition of disease. RESULTS: Hepatitis B was treated successfully with lamivudine. One year later, breakthrough infection developed with a lamivudine-resistant mutant. Addition of adefovir led to HBV surface antigen to surface antibody seroconversion after two yr, which was maintained long term. Antiviral therapy was discontinued. Liver biopsy revealed minimal histologic changes up to eight yr post-LT. Survival of 14 recipients of antiHBVc+ allografts and 180 recipients of antiHBVc-negative grafts was equal (minimum follow up of five yr). Liver biopsies at four yr showed grade 0/1 and stage 0/1 in >70%; only two patients showed bridging fibrosis. A literature review of dual hepatitis virus infection revealed an overall milder course of hepatitis post-LT. CONCLUSION: The outcome of HCV patients receiving anti-HBc+ grafts is good and may be associated with a milder course of recurrent HCV.

Whipple's procedure in a renal transplant recipient with polycystic liver disease.

CONTEXT: Polycystic disease is a rare disorder, which most commonly manifests in the kidney and liver. Recently an increased risk for pancreatic malignancies in subsets of patients with polycystic disease has been reported. CASE REPORT: We report a patient with polycystic liver and kidney disease who successfully underwent a Whipple's procedure for pancreatic adenocarcinoma. CONCLUSION: Although technical difficulty may increase, pancreaticoduodenectomy can be safely performed in patients with polycystic liver disease.

Patient selection for liver transplant: 1-year experience with 555 patients at a single center.

Liver transplant (LT) has revolutionized the management of end-stage liver disease in the past 2 decades. The institution of the Model for End-Stage Liver Disease scoring system for organ allocation has de-emphasized recipient waiting time, but its effect on patients' referral to liver transplant centers is unclear. The aim of this retrospective study was to analyze the outcome of patients referred for liver transplant in a 12-month period (January 1, 2005, through December 31, 2005) after the institution of the new scoring system. During the study period, 555 patients were presented 605 times to the Liver Transplant Selection Committee. Of the 295 patients initially denied LT, 150 patients (51%) were denied because they were considered too early, 29 (10%) because their tumor did not meet institutional criteria, 72 (24%) because of concomitant psychosocial issues, and 44 (15%) because of comorbid conditions. Patients considered too early and those with psychosocial reasons for denial were often re-presented and listed for LT. Our findings suggest that patients could benefit from early referral to an LT center, even if they are initially denied listing, because management of end-stage renal disease could be initiated and psychosocial issues could be addressed. Referring physicians and transplant centers need to develop a strategy to ensure optimal timing of referrals for LT.