A. C. Stieber

Can patients awaiting liver transplantation elicit an immune response to the hepatitis A vaccine

HEPATITIS A remains one of the most frequently reported vaccine-preventable diseases in the USA, despite the availability of the hepatitis A vaccine in 1995. Approximately one third of the population of the USA has serologic evidence of prior hepatitis A infection. In addition, hepatitis A case fatality rates in persons with chronic liver disease have increased 23to 58-fold. This led the Advisory Committee on Immunization Practices (ACIP) to suggest in its 1996 recommendations that persons with chronic liver disease should receive the hepatitis A vaccination. Studies involving healthy adults and children have demonstrated high immune responses to the hepatitis A vaccine. In combined clinical studies used for obtaining FDA approval for the VAQTA hepatitis A vaccine, 1178 of 1214 (97%) healthy children and adolescents 2 to 17 years of age seroconverted within 4 weeks after a single dose. Immune memory was demonstrated by antibody response in those who received a booster dose after transplantation. Although more studies of patients with chronic liver disease are available, relatively little data are available regarding hepatitis A antibody production in end-stage liver disease patients (ESLD) awaiting liver transplantation. The purpose of this investigation is to determine if patients awaiting liver transplantation with ESLD seroconvert following hepatitis A vaccination.

Nonresponders of interferon/ribavirin treatment for recurrent hepatitis C following liver transplantation

BACKGROUND Treatment of recurrent hepatitis C (HCV) following liver transplant currently includes alpha-interferon with ribavirin. OBJECTIVE The aim of this study is to evaluate nonresponder protocols for patients failing current treatment for recurrent hepatitis C following liver transplantation. METHODS From February 1998 through November 2002, 67 patients, all serum RNA-positive for hepatitis C with histological evidence of recurrent hepatitis C, underwent treatment with alpha-interferon and ribavirin. For patients who failed initial treatment, patients were begun on either amantadine along with interferon/ribavirin or peginterferon with ribavirin. RESULTS Of the initial 67 patients, there was a complete viral clearance in only 14.9% (10/67). Of the 57 remaining patients not clearing the virus, 30 (52.6%) were taken off treatment due to adverse events associated with bone marrow or hemoglobin suppression. In the amantadine group (n = 12), three (25%) had to discontinue due to CNS side effects of slurred speech, dizziness, and increased depression. In the amantadine group, no patients cleared the virus but there was a one log drop in viral load (1.6 x 10(6) vs 0.9 x 10(6); P =.4). In the peginterferon group, there were three (20%) patients with complete viral clearance during treatment with similar drops to amantadine. There was also seen a biochemical response by month 3 with peginterferon, which was not seen with amantadine. CONCLUSIONS Peginterferon with ribavirin appears to be superior to amantadine with interferon/ribavirin when used in nonresponders for hepatitis C viral clearance.

Adult and pediatric liver transplantation for autoimmune hepatitis.

BACKGROUND Due to the early age that pediatric patients with autoimmune hepatitis (AIH) are transplanted, it is theorized that older AIH patients may have different outcomes than pediatric patients following liver transplantation. METHODS This is a retrospective review of both the adult and pediatric liver transplant programs consisting of 56 patients. Rejection and recurrence of AIH were determined by biopsy. RESULTS The autoimmune patient having rejection episodes had a 1.76-fold increase in relative risk to develop autoimmune recurrence when compared to patients without rejection [RR = 1.76; 95% CIRR (1.08, 2.86)]. The pediatric group had a 6.62-fold increase in relative risk to develop colitis following liver transplantation [RR = 6.62; 95% C.I.R.R. (1.36, 32.13); P =.02]. Mean days to recurrence of AIH were similar in both groups (1364 +/- 1074 vs 936; P = NS). There were more hospitalized days in the pediatric group compared to the adults (20.5 +/- 13.3 days vs 51.7 +/- 22.2 days, P =.039). OKT-3 was rarely used (n = 5) in either group (9.3% vs 7.7%, P = NS) and was not correlated with which patients would be weaned from steroids or recurrence. CONCLUSIONS Based on this review, pediatric patients were more likely to develop ulcerative colitis following liver transplantation and they incurred longer hospital stays than adults. The adult group was more likely to be weaned from steroids, with AIH recurrence unrelated to weaning.

Renal sparing effects of mycophenolate when used in long-term liver transplant receipients

LONG-TERM, chronic use of calcineurin inhibitors (tacrolimus and cyclosporine) is known to lead to nephrotoxicity and renal failure. Mycophenolate mofetil (MMF) is metabolized to mycophenolic acid, which acts as an immunosuppressive agent by blocking de novo purine synthesis in both Tand B-cell lymphocytes. Infectious complications with the use of MMF have been questioned due to the perceived implication of increased immunosuppression. A multivariate analysis of risk of infection in liver transplant recipients receiving MMF was preformed to determine the incidence of bacterial, viral, and fungal infections. The cohort consisted of more than 150 consecutive liver transplant recipients, and an increase in risk of developing infection after liver transplantation was not demonstrated. Mycophenolate has been used in multiple roles in transplantation. One role for which MMF had been evaluated is steroid-free immunosuppression. For patients with renal impairment, MMF has been useful in limiting calcineurin dosing to help increase or maintain renal function. Creatinine clearance has been shown to increase from 38.16 ( 5.60) to 47.01 ( 6.76) mL/min (P .005). Monotherapy with MMF has also been reported for limiting calcineurin-induced nephrotoxicity. The aim of this review was to determine if a mycophenolate-based immunosuppressive regimen that limits calcineurin inhibitors can prevent further renal dysfunction in the long-term, stable liver transplant recipient.