The role of coronary calcium score in the risk assessment of liver transplant candidates.

BACKGROUND: Coronary artery disease (CAD) is a common cause of morbidity and mortality in liver transplant (LT) recipients. To date there is no consensus on the preferred screening tests to detect CAD in the pre-LT population. Therefore the aim of this study was to: 1) evaluate the utility of a noninvasive tool (cardiac computerized tomography [CT] scan); and 2) determine the prevalence of CAD in low-risk LT candidates. METHODS: Using our transplant database we identified all LT candidates classified as low risk for CAD. All low-risk candidates underwent cardiac CT scan for coronary calcium score (CCS) estimation. Those with CCS >100 underwent coronary angiogram, and those with <100 underwent stress test and if stress test was positive then coronary angiography was performed. The Agatston calcium score was classified as: normal (0), mild (1-100), moderate (101-400), severe (401-1,000), or extensive (>1,000). RESULTS: Eighty-five LT candidates were classified as low risk and underwent cardiac CT scan. The mean calcium score was 325 (range, 0-3,707). In our study cohort, 21% had normal CCS score, 43% mild, 13% moderate, 11% severe, and 12% extensive. A calcium score >400 was significantly associated with CAD on angiography (P = .02). Although male sex was significantly associated with the presence of CAD (P = .006), there was no correlation with age, ethnicity, liver diagnosis, or Model for End-Stage Liver Disease score. CONCLUSIONS: Prevalence of asymptomatic CAD in this low-risk population is relatively high. Cardiac CT is well tolerated and is a useful noninvasive screening tool in LT candidates. Future studies to determine its utility as a prognostic tool after LT will be invaluable.

Health-related quality of life in subjects with HCV/HIV coinfection: results from ACTG 5178 study.

Although health-related quality of life (HRQOL) is diminished in HCV/HIV, the relationship between virologic response and maintenance therapy with HRQOL in this population is unknown. ACTG 5178 was a phase 2, randomized trial, with three steps - Step 1: all subjects received pegylated interferon (PEG-IFN)/ribavirin (P/R) for 12 weeks. Step 2: subjects who failed to achieve early viral response (EVR) were randomized to PEG-IFN or observational control for an additional 72 weeks. Step 3: subjects with EVR from step 1 continued on P/R for a total of 72 weeks with 24 weeks follow-up off-therapy. HRQOL, symptom distress and depression levels were measured at multiple time points. In step 1 (n = 329), there was a significant decline in HRQOL in all dimensions. In step 3 (n = 169), the overall HRQOL and three of its eight dimensions (general health, role function and pain score) were increased, and achievement of sustained virologic response was associated with increased general health and cognitive function. In step 2 (n = 85), there was no significant change in HRQOL and no significant difference between groups (PEG-IFN vs observational control). There was a significant decline in HRQOL during the initial 12 weeks of therapy. Thereafter, the HRQOL profile differed for subjects with EVR vs without EVR. Maintenance therapy with PEG-IFN had no impact on the HRQOL.

Social determinants of orthotopic liver transplantation candidacy: role of patient-related factors.

INTRODUCTION: Eligibility for orthotopic liver transplantation (OLT) requires careful selection of the best possible candidate. The aim of this study was to identify factors associated with transplantation ineligibility. METHOD: This was a retrospective cohort study of all patients evaluated for OLT at our center (2004-2006) and deemed not eligible. We identified all patients who were evaluated using information from our transplantation database. We extracted demographic data, insurance status, laboratory data, and clinical information including psychosocial evaluations. RESULTS: During the study period 242 evaluated candidates were not listed for transplantation. The most common reason for ineligibility for transplantation listing was early referral (n=59; 24.4%), followed by psychosocial (18.6%), medical contraindications (17.3%), death during evaluation (n=32; 13.2%), malignancy (n=22; 9.1%), declined evaluation or transfer to other transplantation center (n=21; 8.7%), and other reasons (8.7%). In contrast to whites, psychosocial factors were the most common reason among African American candidates. CONCLUSION: This study provides insight into factors contributing to OLT ineligibility among candidates of various ethnic backgrounds.

Orthotopic liver transplantation in a multiethnic population: role of spatial accessibility.

INTRODUCTION: Access to orthotopic liver transplantation (OLT) varies among different ethnic groups. The aim of this study was to determine if distance from transplantation center (DT) impedes referral pattern and accessibility to OLT among ethnic groups. METHOD: This is a retrospective cohort study of all patients evaluated for OLT at our center (2002-2007). The ZipCode Basic software was used to compute distance between the candidate's residence and transplantation center. RESULTS: Five hundred one patients were evaluated during the study period and there were 439 (87.6%) whites 43 (8.6%) African Americans (AA), and others (3.8%). The median DT was 36.8 miles (range, 0.5-231), and there was no significant correlation with the Model for End-Stage Liver Disease (MELD) at presentation (P=.87). Although AA had a higher likelihood of residing closer to a transplantation center they were more likely to have a higher MELD at presentation (20 vs 15.4; P<.001) and less likely to be referred early to initiate OLT evaluation (11.6% vs 26.4%; P=.04). Additionally, type of insurance correlated with higher MELD at presentation. CONCLUSION: DT was not a contributory factor to the observed access disparity in our patient population, rather the insurance type and disease severity as determined using MELD differed significantly among ethnic groups.

Recipient-based approach to tailoring immunosuppression in liver transplantation.

Improvements in the field of transplant immunosuppression (IS) have led to significant advances in long-term survival of liver transplant recipients. Despite this progress, survival rates vary depending on recipient, donor and/or perioperative factors. Tailoring IS based on recipient factors is of growing interest among health care providers involved in the care of organ transplant recipients. To date there is no consensus document addressing individualized IS therapy for liver transplant recipients. This review will discuss the information available on the effect of the various IS drugs on recipient-based factors such as age, ethnicity, and liver disease etiology.

Acquired platelet dysfunction with spontaneous intramuscular hematoma and compartment syndrome in cirrhosis.

Cirrhosis patients are at high risk for bleeding as a result of decreased platelet counts and impaired function, defective production of coagulation factors and abnormalities in clot lysis. The authors report the case of a 58 year-old man with cryptogenic cirrhosis who presented initially with intramuscular hematoma in the thigh which progressed to compartment syndrome. The patient developed disseminated progressive intramuscular hematomas in the muscles of chest, abdomen and finally retroperitoneal hemorrhage secondary to probable accelerated intravascular coagulation and fibrinolysis (AICF) culminating in death. This case highlights many of the common coagulation abnormalities seen in cirrhosis. The authors speculate the sequence of events in our patient at every level of the coagulation cascade which could have lead to this fatal outcome.

Alpha-1-antitrypsin deficiency: outcomes after liver transplantation.

Alpha-1-antitrypsin deficiency (AAT) is the most common inherited metabolic disease leading to liver transplantation (LT) in children and adults. The aim of the study was to determine transplantation trends and survival of LT recipients with AAT. Using the UNOS (United Network for Organ Sharing) database, we identified 567 patients who underwent LT and 3 who received lung and LT from 1995 to 2004. AAT accounted for 1.06% of all adult LTs and 3.51% for pediatric LT. The 1-, 3-, and 5-year patient survival was 89%, 85%, and 83%, respectively, for adults versus 92%, 90%, and 90% for pediatric patients (P = .04), and graft survival was 83%, 79%, and 77% for adults versus 84%, 81%, and 78% for pediatric patients (P = .51). By regression analysis, age was the only predictor for patient survival (P = .04). In conclusion, adult and pediatric LT recipients with AAT are predominantly of Caucasian ethnicity and have an excellent post-LT survival.

Managing chronic hepatitis C in relapsers and non-responders.

Chronic hepatitis C virus (HCV) infection poses a challenge for a growing number of infected patients who exhibit disease complications, including cirrhosis, hepatocellular carcinoma, and liver failure. Treatment with pegylated interferon (peg-IFN) plus ribavirin improves hepatic markers and eradicates the virus in about 50% of patients; however, a significant number of patients do not respond to therapy or relapse following treatment discontinuation. Several viral, hepatic, and patient-related factors influence response to IFN therapy; many of these factors cannot be modified to improve long-term outcomes. Identifying risk factors and measuring viral load early in the treatment can help to predict response to IFN therapy and determine the need to modify or discontinue treatment. Treatment options for complicated cases of chronic HCV infection are limited. Retreatment with peg-IFN has been successful in some patients who exhibit an inadequate response to conventional IFN treatment, particularly those who have relapsed. Consensus IFN, another option in treatment-resistant patients, has demonstrated efficacy in the retreatment of non-responders and relapsers. Although optimal duration of retreatment and benefits and safety of maintenance therapy have not been determined, an extended duration is likely needed. Anti protease inhibitor drugs, the new frontier of HCV treatment, are now searched as the future answer in the treatment of difficult patients. Unfortunately the results are still confined in a preliminary phase. This article reviews risk factors for HCV treatment resistance and discusses assessment and management of difficult-to-treat patients such as non responders or relapsers to previous treatment.

Outcomes in adult and pediatric liver transplantation among various ethnic groups.

BACKGROUND: The reported patient and graft survivals among adults post-orthotopic liver transplantation (OLT) are variable, with an apparent discrepancy between ethnic groups. The aim of this study was to evaluate the impact of ethnicity on patient and graft survivals among adult and pediatric patients. METHODS: A retrospective analysis from the UNOS/OPTN databank between January 1995 and December 2006 was performed on adult and pediatric liver transplant recipients. Patients were divided into 4 groups based on ethnicity: African Americans, Hispanic, Caucasians, and other. Kaplan-Meier (KM) analysis was used to calculate patient and graft survival. Log-rank tests were used to compare survival rates between groups. RESULTS: In our study 42,710 OLT patients were included in the analysis, 90% of whom were adults. Of the 38,639 adult recipients, 29,432 (76.1%) were Caucasian, 4369 (11.3%) were Hispanic, 2963 (7.7%) were African American, and the remaining 1875 (4.9%) were of other ethnicities. KM estimates and Cox regression analyses demonstrated that there was a significant ethnic difference in both patient and graft survivals at 1, 3, 5, and 10 years. African Americans showed a lower rate (P<.001). Of the 4341 pediatric recipients, 2461 (56.7%) were Caucasian, 797 (18.4%) were Hispanic, 824 (18.9%) were African American, and the remaining 259 (5.9%) were of other ethnicities. Unlike the adults, there were no significant differences among ethnic groups in terms of patient (P=.31) and graft (P=.33) survival at 1, 3, 5, and 10 years after OLT. CONCLUSION: These results showed that adult African American OLT patients have a reduced transplantation rate and a worse survival rate when compared with other ethnicities in the adult but not in the pediatric population. This information suggests that further studies are indicated to identify the causes of racial differences in transplant access and outcomes in the adult patient population.

Intestinal schistosomiasis following orthotopic liver transplantation: a case report.

Recent World Health Organization (WHO) reports estimate that 500-600 million people worldwide are at risk of schistosomiasis. In areas of high prevalence of hepatitis C (HCV) and schistosomiasis there is an increased risk for end-stage liver disease. Liver transplant is a viable option for those with HCV or other liver pathology and schistosomiasis. Posttransplant recurrence of schistosomiasis has rarely been described. We report a case of posttransplant recurrence of schistosomiasis.

Long-term analysis of primary nonfunction in liver transplant recipients.

UNLABELLED: Long-term allograft and patient survival following liver transplantation continues to improve with the development of new surgical techniques and immunosuppressive agents. Complications such as primary nonfunction (PNF) have not been well characterized in terms of long-term allograft and patient survival. The aim of this study was to determine the incidence of PNF in liver transplant recipients and patient and graft survival, in addition to identifying temporal trends in these parameters. METHOD: Data were obtained from the United Network for Organ Sharing/Organ Procurement and Transplant Network for all adults (>18 years old) who received a deceased donor liver transplant between January 1990 and December 2004. RESULTS: Of the 58,576 liver transplant recipients, 2061 had PNF, an overall incidence of 3.5%. There was a 30% annual increase in the incidence of PNF between 1990 and 2000; the incidence of PNF peaked at 7%, and then decreased by 20% annually thereafter. No differences in donor and perioperative variables were identified to account for this variation. One-, 3-, and 5-year patient and graft survival for patients with PNF who underwent retransplant were significantly lower than those with primary liver transplant. In conclusion, there has been decreased incidence of PNF among liver transplant recipients in the last decade.

Analysis of hospitalizations comparing rifaximin versus lactulose in the management of hepatic encephalopathy.

INTRODUCTION: Patients with end-stage liver disease often develop hepatic encephalopathy. The loss in cognitive abilities results in marked economic loss to the patient and health care community. We report hospital admission rates and economic impact of patients with end-stage liver disease suffering from hepatic encephalopathy. METHODS: The medical records were reviewed involving liver transplant patients started on lactulose or rifaximin therapy after presenting with stage 2 hepatic encephalopathy from January 2004 to November 2005. Information collected included demographics, hospitalizations required for hepatic encephalopathy, economic data, and Model for End-stage Liver Disease (MELD) score. RESULTS: Thirty-nine patients met study criteria: 24 patients treated with lactulose (group one) and 15 with rifaximin (group two). Group one included 18 men and six women of mean age 48 (range 39 to 58), average MELD 14 (range 10 to 19). Group two included 10 men and five women of mean age 47 (range 42 to 58), average MELD 15 (range 10 to 19). Group one patients required 19 hospitalizations overall: three patients with three hospitalizations, four patients with two hospitalizations, and two patients required one hospitalization. Total drug cost per month was 50 dollars(group one) and 620 dollars(group two). The average annual cost of hospitalization, emergency room visit, and drug per patient treated was 13,284.96 dollars for a total of 318,839 dollars (range 5005 dollars to 26,255 dollars, including drug cost and hospital care). Group two required three hospitalizations, all three with one visit. The average annual cost of hospitalization, emergency room visit, and drug per patient treated was 7958.13 dollars for a total of 119,372 dollars (range 6005 dollars to 19,255 dollars, including drug cost and hospital care). The total cost of therapy per patient per year was 13,285 dollars (group one) versus 7958 dollars (group two). The average length of stay was shorter in group two [3.5 days (range 3 to 4)] versus group 1 [5.0 days (range 3 to 10); P < .0001]. CONCLUSION: These pilot data demonstrate the marked difference in economic costs for the treatment of hepatic encephalopathy. The results also show that in comparative groups, the economic gains are quickly lost when using lactulose.

Hepatitis A.

Hepatitis A remains an important cause of community-acquired hepatitis in the United States and in the world. In recent years, improvements in personal hygiene and environmental sanitation have led to declines in overall hepatitis A infection rates in developed countries, although sporadic outbreaks still occur with similar rates of hospitalization and loss of work. Therapy remains supportive and prevention holds the key to elimination of widespread infection. Acute infection can be prevented or attenuated with IG or with inactivated, highly immunogenic vaccines. Elderly persons and those with advanced liver disease are at higher risk of the consequences of acute HAV, and they represent target populations for immediate vaccination. Challenges for the future include strategies for broad-based population vaccination, including cost-effective approaches.