Incidence of cardiovascular and cerebrovascular events associated with sirolimus use after liver transplantation.

BACKGROUND: Sirolimus (SRL) is an immunosuppressant often used in liver transplantation (LT) to mitigate renal insufficiency associated with calcineurin inhibitors. Sirolimus can cause hyperlipidemia, but its association with coronary artery disease (CAD) and cerebrovascular accidents (CVAs) is unclear. The purpose of this study was to assess the risk of CAD and CVAs with the use of SRL in LT recipients. METHODS: We retrospectively reviewed all of our LT recipients from 2000 to 2011. Patients with multiorgan transplant, multiple liver transplants, everolimus therapy, or survival <3 months were excluded. The 803 remaining patients were divided into 3 groups: 1) 134 patients who received and tolerated SRL; 2) 604 patients who never received SRL; and 3) 65 patients who started but discontinued SRL. The primary outcome was the development of CAD or CVA beyond 4 months after transplantation with the use of time-dependent Kaplan-Meier analysis. RESULTS: In group 1, there were 6 CAD and 2 CVA events; in group 2, 27 CAD and 16 CVA events; and in group 3, 10 CAD and 2 CVA events. The event-free survival for CAD/CVA at 1, 3, and 5 years was 100%, 98.1%, and 97.2% respectively for group 1; 99.7%, 98.4%, and 96.1% for group 2; and 92.3%, 92.3%, and 85.6% for group 3. On an unadjusted basis, compared with group 2, there was no difference in CAD/CVA rates in group 1 (hazard ratio [HR] 0.92; not significant), but there was an increase in group 3 (HR 2.94; P = .0019). However, on multivariate analysis, only age at transplantation (HR 1.06; P = .001) and diabetes before transplantation (P = .011) were associated with increased CAD/CVA risk. CONCLUSIONS: Our analysis showed that patients receiving SRL after LT had no increased risk of CAD/CVA events compared with patients maintained on a calcineurin inhibitor. The risk of CAD/CVA should not be a factor in avoiding SRL.

Frequency and predictors of venous thromboembolism in orthotopic liver transplant recipients: a single-center retrospective review.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of major abdominal operations. Liver transplantation is carried out as a treatment for end-stage liver disease (ESLD). It is not well studied whether this population is at increased or decreased risk of a VTE event after a liver transplantation. This study was to determine the frequency of VTE in this population and identify possible predictors. METHODS: Retrospective review of 917 patients over 15 years at a single tertiary center was conducted. Liver transplant recipients with symptomatic VTE occurring up to 1 year after liver transplantation were included. Upper and lower extremities deep vein thrombosis (DVT) was identified. The diagnosis of DVT and pulmonary embolism (PE) was made by appropriate diagnostic imaging. Data regarding known risk factors of VTE such as thrombophilia, recent hospitalization, malignancy, and other comorbid conditions were collected. RESULTS: Among 917 patients, a total of 45 events occurred in 42 (4.58%) patients. Twelve had PE and 33 had DVT events. On Cox regression analysis the absence of an alcoholism diagnosis (Hazard Ratio [HR], -0.33; 95% confidence interval [CI], 0.13-0.83), the presence of diabetes (HR, -3.36; 95% CI, 1.76-6.42), a history of VTE (HR, -8.06; 95% CI, 3.37-19.3), and the presence of end-stage renal disease (ESRD; HR, 3.68; 95% CI, 1.34-10.01) were significant predictors of a VTE outcome. No particular diagnosis, history of malignancy, or presence of thrombophilia were associated with increased risk of VTE. CONCLUSION: The 4.58 % incidence of VTE is comparable with the reported incidence after major abdominal procedures (5%-10%). This data also shows that there is increased risk of VTE in transplant recipients with comorbid conditions of diabetes, previous VTE, and ESRD. This study suggests that a more aggressive strategy for prophylaxis of VTE should be used in liver transplant recipients as with other major abdominal procedures.

The influence of alcohol abuse history on the differential, longitudinal patterns of mental and physical quality of life following liver transplantation.

This prospective, longitudinal study investigated change in physical and mental health quality of life (QoL) in a sample of 65 end-stage liver disease patients before and after liver transplantation. Physical and mental health QoL were assessed using the SF-36 Physical Health Summary and Mental Health Summary, respectively. Baseline data were collected prior to transplant and follow-up data were collected at 1 and 6 months after transplantation. Repeated-measures analysis of variance results indicate that physical QoL did not improve significantly between baseline and 1-month follow-up (F = .031, P = .860) but did between 1- and 6-month follow-up (F = 20.873, P < .001). Significant between-subject effects suggested attenuated improvement for patients with alcohol abuse histories (F = 6.213, P = .017). Physical QoL did not improve between 1- and 6-month follow-up for patients with alcohol abuse history (t((13)) = -1.074, P = .112). By contrast, mental health QoL improved significantly between baseline and 1-month follow-up (F = 13.840, P < .001), but not between 1- and 6-month follow-up (F = .750, P = .391). No significant differences were found on the Mental Health Summary index based on alcohol abuse history for either time period. Post hoc multivariate analysis of variance results suggested worse functioning (F = 2.674, P = .013) for individuals with alcohol abuse history on SF-36 Physical Functioning (F = 5.55, P = .021), Body Pain (F = 13.578, P < .001), Vitality (F = 4.337, P = .040), and Social Functioning (F = 10.50, P = .002) subscales. For liver transplant patients, improvements in psychosocial functioning and QoL precede improvements in physical QoL. Attenuated physical QoL improvements for patients with alcohol abuse histories are related to greater pain and physical deficits.

Survival after liver transplantation in patients who develop renal insufficiency.

BACKGROUND: Renal insufficiency (RI) after liver transplantation (OLT) is associated with worse outcomes but the actual survival after RI ensues is not well described. We examined the survival of OLT recipients who developed moderate or severe RI or end-stage renal disease (ESRD), seeking to identify variables associated with these outcomes. METHODS: Between 1993 and 2007, 731 patients underwent OLT. After excluding patients undergoing retransplantation, combined kidney-liver grafts, and those who died within 1 year, we had a cohort of 527 subjects whose basic demographic data were obtained. Glomerular filtration rate (GFR) calculated (by MDRD4-Modification of Diet in Renal Disease 4-formula) at 3-month intervals in the first year and then at 6-month intervals. Moderate RI was defined as a GFR < 60 mL/min/1.73 m(2); severe RI, GFR < 30; and ESRD by need for dialysis or renal transplantation. We determined survival from the point of developing RI. An analysis determined factors associated with survival. RESULTS: Among 527 patients, 251 developed moderate (47.6%) and 40 (7.6%) severe RI as well as 40 (7.6%) with ESRD. Once RI ensued, the 5-year survivals for patients with moderate RI, severe RI or ESRD were 84.0%, 67.7%, and 48.5%, respectively. Five-year survival, for patients receiving a renal transplant was 100%. On multivariate Cox regression analysis, the only variables associated with time to death for patients with any RI were higher age at transplant (hazard ratio [HR] = 1.04, P = .02), higher creatinine at transplant (HR = 1.25, P = .01), pretransplant diabetes (HR = 2.34, P = .008), and transplantation in the Model for End-stage Liver Disease (MELD) era (HR = 0.15, P = .002). CONCLUSION: Development of severe RI or ESRD correlated with diminished survival. For patients with RI, age and creatinine at transplant, pretransplant diabetes, and transplantation in the pre-MELD era were associated with lower survival rates. Five-year survival for dialysis patients was somewhat higher than that previously reported but worse than that of subjects treated by renal transplantation.

The impact of donor race on recurrent hepatitis C after liver transplantation.

BACKGROUND: Several studies have demonstrated mixed results regarding the influence of donor race on patient and graft survival in patients infected with hepatitis C virus (HCV) after liver transplant. However, few studies have looked at the impact of donor race on recurrent HCV. This study is a retrospective analysis of the influence of patient and donor race on the severity of recurrent HCV at a single center. METHODS: Of patients transplanted at our center between 2000 and 2006, 222 were infected with HCV. Of these, 165 were eligible to be evaluated for recurrent HCV after transplant. We excluded those with patient and graft loss within 1 year that was not related to recurrent HCV, patients with advanced fibrosis from other causes, those who did not undergo posttransplant liver biopsy, and those lost to follow-up. Patients were given a recurrent HCV score of 1, 2, or 3. A score of 1 was assigned if the patient had no more than mild portal fibrosis at 1 year and no bridging fibrosis at any point. A score of 2 was defined as moderate portal fibrosis or focal bridging fibrosis at 1 year or bridging fibrosis or cirrhosis after 3 years. A score of 3 was defined as bridging fibrosis, cirrhosis, or graft loss from HCV within 3 years. Baseline characteristics including donor and recipient age, race, sex, body mass index, ischemia time, hypertension, and diabetes were recorded. Analysis was performed with ordinal multivariate logistic regression modeling. RESULTS: Of the 165 patients with a recurrent HCV score, 105 (64%) had a score of 1, 29 patients (17%) had a score of 2, and 31 patients (19%) had a score of 3. In all, 132 recipients (80%) had white donors, and 26 (16%) had African American donors, 115 patients (70%) were white and 40 (24%) were African American. The mean recurrent HCV scores for the patient donor and recipient race combinations are as follows: white donor and white recipient, 1.54; white donor and African American recipient, 1.89; African American donor and white recipient, 1.18; and African American donor and African American recipient, 1.23. Having a white donor also significantly associated with a higher recurrent HCV score regardless of recipient race (odds ratio 2.93, P = .044) in African American patients, having a white donor had an odds ratio of 4.62 (P = .046). After adjusting for donor age and sex and patient age and sex, having a white donor was still found to be associated with a higher recurrent HCV score (4.48, P = .0275) on multivariate analysis. For all 222 patients, donor race was not associated with overall patient and graft survival. CONCLUSION: Patients receiving white donor grafts had significantly worse recurrent HCV than those receiving grafts from African American donors regardless of recipient race. This difference was especially marked in African American recipients and persisted on multivariate analysis. These data suggest a graft from a white donor is potentially one more important variable in identifying patients at risk for more aggressive recurrent HCV after orthotopic liver transplant.

Biliary complications after orthotopic liver transplantation from donors after cardiac death: broad spectrum of disease.

BACKGROUND: Donation-after-death liver transplantation (DCD-LT) carries higher complication rates compared with donation-after-brain death liver transplantation (DBD-LT). In this report we describe our experience with biliary complications in DCD-LT with emphasis on anatomical patterns and outcomes. MATERIALS AND METHODS: We performed retrospective review of patients' medical records from August 2004 to December 2008, during which time total of 26 DCD-LTs were performed. Mean follow-up was 29 months (range 3 to 51 months). RESULTS: Biliary complications occurred in 12 patients (46%), of whom 9 were related to DCD (35%). Four patients had more than 1 biliary complication, and 4 had concomitant arterial problems (stricture/thrombosis). Treatment of complications included: ERCP (n = 5, 3 resolved), conversion to roux (n = 5, 2 resolved), revision of roux (n = 1), percutaneous transhepatic cholangiography (n = 1), artery revision (n = 3). Three patients with casts had operative extraction of casts depicting a mummified biliary tree; histology showed casts and fibrosis and anastomotic suture material. Six patients underwent retransplantation (23%). Among retransplanted patients, 2 deaths occurred (7.7%). CONCLUSION: Our experience with DCD-LT reveals a high prevalence of biliary complications with a new and wide spectrum of clinicopathologic findings. Better strategies for prevention of these unique biliary complications are needed to better justify the added risks and costs for performance of DCD-LT.

The influence of induction therapy on graft and patient survival in patients with and without hepatitis C after liver transplantation.

We used the United Network for Organ Sharing Database to determine the influence of antibody-based induction therapy on patient and graft survival in orthotopic liver transplant (OLT) recipients with and without hepatitis C (HCV). We identified all initial OLT patients with HCV serology. Patients were divided into four groups: HCV positive without induction (17 362), HCV positive with induction (3479), HCV negative without induction (20 417) and HCV negative with induction (4357). Both HCV positive and negative patients who received induction did better than those who did not. For HCV positive patients, 5-year patient survival was 70.8% versus 68.7% (p = 0.004) and graft survival was 65.2% versus 62.1% (p < 0.001). For HCV negative patients, 5-year patient survival was 78.8% versus 76.7% (p < 0.001) and graft survival was 74.0% versus 70.8% (p < 0.001). On multivariate analysis, induction was associated with improved patient (HR = 0.91: p = 0.024) and graft (HR = 0.88: p < 0.001) survival in HCV positive patients and improved patient (HR = 0.87: p = 0.003) and graft survival (HR = 0.87: p < 0.001) in HCV negative patients. The benefit of induction occurred early and largely dissipated when patients with death within a year were censored. The benefit of induction therapy appeared most pronounced in patients with renal insufficiency or on organ-perfusion support at transplant.

Long-term management of the liver transplant patient: recommendations for the primary care doctor.

No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient.

Incidental hepatocellular carcinoma after liver transplantation: population characteristics and outcomes.

We combined data from two liver transplant centers to determine the tumor characteristics and outcomes of 51 patients transplanted with incidental hepatocellular carcinoma (iHCC) compared with 143 patients transplanted for previously known HCC (pkHCC). There were no differences in age, gender, or frequency of hepatitis C infection. Patients with iHCC were more likely to be African-American (22% vs 10%; P = .016), more likely to be screened by ultrasound (38% vs 9%; P < .001), had a lower alpha-fetoprotein (83.9 +/- 258.1 vs 572.4 +/- 2376.4 ng/mL; P = .005), and had a higher model for end-stage liver disease (MELD) score (14.3 +/- 4.1 vs 11.8 +/- 4.7; P < .001). The liver explants of patients with iHCC had smaller total tumor burden than patients with pkHCC (3.1 +/- 3.5 vs 4.1 +/- 2.6 cm; P < .001), but a similar percentage of single lesions (66% vs 65%) and tumors that met Milan criteria (76% vs 65%). Patients with iHCC had 1-, 3-, and 5-year survivals of 78%, 67%, and 58%, and 1-, 3-, and 5-year recurrence-free survivals of 90%, 87%, and 87% compared with the 1-, 3-, and 5-year survivals of 90%, 82%, and 70%, and the 1-, 3-, and 5-year tumor-free survivals of 91%, 84%, and 78% in patients with pkHCC. We concluded that patients with iHCC were more likely to be African-American, to be screened by ultrasound, to have a lower alpha-fetoprotein, and a higher MELD score. Ultrasound is not a sensitive modality for screening patients for HCC. Patients with iHCC do not have an advantage in survival over those with pkHCC.

Impact of model for end-stage liver disease on patient survival and disease-free survival in patients receiving liver transplantation for hepatocellular carcinoma.

We combined data from two transplant centers to determine the impact of the model for end-stage liver disease (MELD) allocation system on outcomes in patients undergoing liver transplantation for hepatocellular carcinoma (HCC). We compared 55 patients listed before MELD to 117 patients in the MELD era. Patients before MELD were less likely to receive a transplant (67% vs 91%) and waited a median of 127 days vs 20 days (P < .001). On an intention to treat (ITT) basis, the 1-, 3-, and 5-year survivals for patients before MELD were 79%, 60%, and 48%, and in the MELD era were 84%, 73%, and 73% (P = .055). On an ITT basis, the 1-, 3-, and 5-year tumor-free survivals before MELD were 58%, 58%, and 55% vs 83%, 74%, and 70% in the MELD era (P = .018). In patients who received a transplant, however, there were no differences in overall or tumor-free survival. In these patients, the 1-, 3-, and 5-year patient survivals were 92%, 84%, and 67% before MELD, and 90%, 81%, and 81% in the MELD era (P = .57). In transplanted patients, the 1-, 3-, and 5-year tumor-free survivals before MELD were 88%, 88%, and 83% vs 92%, 83%, and 78% in the MELD era (P = .403). On explant, patients listed before MELD had lower grade tumors (P = .046). We concluded that patients with HCC listed in the MELD era had higher and more rapid rates of transplantation with improvements in survival. However, the more efficacious rates of transplantation did not result in lower rates of tumor recurrence.

Influence of hepatitis C on renal function after liver transplantation.

Liver transplantation (OLT) is often complicated by renal failure. Hepatitis C (HCV) is said to be a risk factor for renal failure after OLT, but few studies have analyzed this directly. We evaluated all patients who received a liver transplant from 1995 through 2003. There were 147 patients infected with HCV and 202 not infected. Patients with HCV were further divided into 114 patients with benign HCV and 33 patients with severe HCV defined by bridging fibrosis or cirrhosis. The groups were evaluated for the development of renal insufficiency defined as a creatinine above 1.8 mg/dL on three consecutive occasions or renal failure as defined by the need for dialysis or renal transplant. The incidence of renal failure in patients with HCV was 10.2% and in patients without HCV was 3.5% (P = .004). Patients with severe HCV had an incidence of 12.1% vs 9.7% for patients with mild HCV. The linear trend in renal failure from non-HCV to mild HCV to severe HCV was significant (P = .012). The incidence of renal insufficiency was 23.4% in patients with HCV and 14.9% in patients without HCV (P = .080). The incidence was 32.3% in patients with severe HCV and 20.6% in patients with mild HCV. The trend in renal insufficiency across the three groups was mildly significant (P = .042). On multivariate analysis, HCV was a risk factor for renal failure with a relative risk of 2.58 (P = .045). The study suggests that HCV and the severity of recurrent HCV are risk factors for renal dysfunction after liver transplantation.

Renal disease burden following liver transplantation.

UNLABELLED: Significant chronic kidney disease (CKD) occurs following orthotopic liver transplant (OLT). Since CKD is associated with increased cardiovascular events, mortality, and hepatic allograft dysfunction, early recognition of CKD and implementation of changes may improve the long-term outcome. The purpose of this study was to determine the burden of renal disease following OLT. PATIENTS AND METHODS: We retrospectively reviewed our OLT recipients from 1997 until 2004. We calculated glomerular filtration rates (GFR) using the Modification of Diet in Renal Disease study (MDRD) method. The GFRs were further subdivided into pre-MELD and post-MELD eras. RESULTS: During the study period, we performed 407 OLTs. We censored data from living donor liver transplants (n = 14), combined liver-kidney transplants (n = 12), and from patients whom we did not have complete data for 6 months after transplant (n = 40). Mean MELD score at the time of transplant was 18 +/- 7 (mean +/- standard deviation). The mean GFR at 6 months following OLT was 63.7 +/- 30.2 mL/min per 1.73 m(2). Only 14% (n = 47) of our patients had normal renal function at 6 months, while 78% (n = 266) of our patients had mild to moderate risk for renal failure. Eight percent (n = 28) had stage 4 or 5 CKD. There were no differences between the pre-MELD and post-MELD GFRs. CONCLUSIONS: The burden of renal disease is significant in our patient population at 6 months posttransplantation. It may be important to introduce CKD management as early as 6 months after transplant to impact the outcomes of OLT recipients.

Transjugular intrahepatic portosystemic shunts for refractory ascites after liver transplantation.

PURPOSE: To study the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in the management of refractory ascites after liver transplantation. PATIENTS AND METHODS: Between January 1995 and December 2003, 309 primary adult liver transplants were performed. Refractory ascites was defined as active interventions (salt restriction, diuretic use, repeated paracentesis) needed beyond 30 days after transplantation. These patients were managed with TIPS placement. RESULTS: Eight TIPS were placed in 8 patients at a mean of 11.5 months after transplantation (range, 2-36 months). There were 5 males and 3 females, age 54 +/- 8.2 years. Hepatitis C was the primary diagnosis in 7 patients and primary biliary cirrhosis in 1. Indications for TIPS included refractory ascites (8), associated variceal bleeding (2), and various degrees of hepatic vein outflow stenosis (3). Seven patients had resolution of ascites and associated findings of portal hypertension, and 1 patient with persistent ascites had severe hepatic vein outflow stenosis and associated hepatitis C in the allograft. Two patients required retransplantation for recurrent hepatitis C. There were 3 deaths: liver failure (1), organ failure after retransplantation (1), and lung cancer 5 months after TIPS (1). Currently, 5 patients are alive without clinical evidence of ascites 9, 13, 15, 24, and 70 months after TIPS. CONCLUSIONS: The TIPS device can be used safely and effectively to control refractory ascites after liver transplantation. In the setting of organ dysfunction, these patients should be considered sooner for retransplantation.

A pilot trial of recombinant interleukin-12 in patients with chronic hepatitis C who previously failed treatment with interferon-alpha.

OBJECTIVE: Interleukin-12 is a cytokine with a multitude of immunomodulatory actions. Currently, interferon-alpha (IFN-alpha) monotherapy and combination treatment with IFN and ribavirin are the only therapies with proven efficacy against chronic hepatitis C infection. The purpose of this study was to assess the safety and antiviral activity of recombinant interleukin-12 (rhIL-12) in adults with chronic hepatitis C who did not achieve a sustained response to previous IFN-alpha therapy. METHODS: This was a randomized, placebo-controlled, double-blind trial. We randomized 24 patients to one of three dose groups: 30 ng/kg, 100 ng/kg, and 300 ng/kg. Within each group, six patients received rhIL-12, and two patients received placebo administered s.c. twice a week for 12 wk. RESULTS: Three of six patients treated with rhIL-12 at a dose of 300 ng/kg had loss of detectable hepatitis C RNA by reverse transcription-polymerase chain reaction compared with the placebo group (p = 0.05). All patients relapsed at the end of the 3-month treatment period. No other dose group demonstrated a loss of detectable hepatitis C RNA. CONCLUSIONS: RhIL-12 at 300 ng/kg can suppress hepatitis C RNA to undetectable levels by reverse transcription-polymerase chain reaction, although relapse occurred when treatment was stopped. RhIL-12 was well tolerated with the most common side effects being flu-like symptoms and headaches.

The use of hepatitis C viral RNA levels in liver tissue to distinguish rejection from recurrent hepatitis C.

Persistence of hepatitis C virus (HCV) after orthotopic liver transplantation is almost universal in HCV-infected patients. Histological examination of liver biopsy specimens can be variable in distinguishing between recurrent hepatitis C and acute cellular rejection. The purpose of this study is to determine whether hepatic HCV RNA levels can be used to distinguish rejection from recurrent HCV by determining whether hepatic HCV RNA levels correlate with histological characteristics and clinical course. Seventy-two biopsy specimens were evaluated from 36 liver transplant recipients with HCV and elevated liver-related enzyme levels. Based on histological findings and clinical response to therapy, patients were defined as belonging to 1 of 5 groups: (1) definite rejection, (2) probable rejection, (3) indeterminate findings, (4) probable HCV, and (5) definite HCV. Hepatic HCV RNA was quantified using the Amplicor Monitor assay (Roche Diagnostic Systems Inc, Branchburg, NJ). There was a difference across groups in HCV RNA levels (P =.046). The median HCV RNA level was 10,695 copies/mg of tissue DNA in the definite-HCV group compared with 1,024 copies/mg of tissue DNA in the definite-rejection group. Using pairwise comparisons, significant differences were found between definite HCV and definite rejection, probable HCV and definite rejection, probable HCV and probable rejection, and probable HCV and indeterminate. Our findings support the following conclusions. (1) In liver transplant recipients, hepatic HCV RNA levels are statistically greater in patients with recurrent HCV than rejection, although there is considerable overlap between groups. (2) Patients with low HCV RNA levels were unlikely to have recurrent HCV. (3) Patients with minimal and indeterminate findings on biopsy (group 3) had low HCV RNA levels.

High levels of hepatitis C virus RNA in native livers correlate with the development of cholestatic hepatitis in liver allografts and a poor outcome.

A subset of hepatitis C virus (HCV)-positive liver transplant recipients develop cholestatic hepatitis (CH). We investigated the role of pretransplantation disease activity (estimated by Knodell score and HCV RNA quantitation) in the native liver explant on the development of CH and graft and patient outcome. Eight patients with CH were identified among HCV-positive liver transplants and were compared with 20 consecutive patients with recurrent HCV hepatitis of noncholestatic type in liver transplants. We evaluated all 28 explanted native livers histologically using the Knodell scoring system. HCV viral load was measured in the native explant and 5 allograft explants from the CH group using Amplicor HCV RNA Monitor test. Six of 8 patients with CH had HCV RNA levels of 5,000 copies/microg of DNA or greater in the native liver explant, whereas only 1 of the control group had viral loads greater than this level. Greater HCV RNA levels correlated with worse graft and patient survival (P <.001). The 3-year survival rate in the CH group was 18% compared with 77% in the control group (P <.001). There was no difference in the primary immunosuppressive regimens used in the 2 groups. We conclude that (1) CH has a uniformly poor prognosis, (2) type of immunosuppressive therapy appears to have little influence on the development of CH, (3) high pretransplantation HCV RNA levels in the native explant may predict the development of CH, and (4) patients with high HCV RNA levels in the explanted native liver may be appropriate candidates for antiviral therapy to prevent the development of CH.

Liver transplantation.

Continued discussion over organ allocation and distribution remained a focal point in the field of liver transplantation in the year 2000. Despite the ongoing debate, no significant changes were implemented in the current allocation system. By far, the most widely discussed topic in liver transplantation this year was live donor adult-to-adult liver transplantation. Several authors reported on their initial experience, with both recipient and donor outcomes appearing excellent. As the number of transplant centers performing this procedure increases we look forward to further studies regarding the safety and long-term outcome of this innovative procedure. Studies on viral hepatitis after liver transplantation again focused on the problem of recurrent hepatitis B and hepatitis C. Several small studies found benefit in patients with hepatitis B treated with intramuscular hepatitis B immunoglobulin and lamivudine after transplantation. Although breakthrough replication remains a problem in some patients, these studies offer hope that combination therapy for hepatitis B may provide improved long-term graft survival in these patients. In patients with hepatitis C, several studies focused on identifying risk factors to predict graft recurrence of the virus after liver transplantation. Both cellular rejection and level of viral replication may be important predictors of recurrent hepatitis C virus in the graft. Early treatment reports using interferon and ribavirin suggest that some patients may have a viral response during therapy; however, it is short lived, and tolerance of medication is difficult. Certainly, we look forward to further studies looking at means of prevention and treatment of viral hepatitis in patients undergoing liver transplantation.