Low fibrosis progression of recurrent hepatitis C in apolipoprotein E epsilon4 carriers: relationship with the blood lipid profile.

BACKGROUND: The histological outcome of chronic hepatitis C is better among carriers of the apolipoprotein E (ApoE) epsilon4 allele, for reasons unknown. The orthotopic liver transplantation (OLT) setting allows to separate the role played by liver-derived ApoE (graft) from ApoE of different origin (recipient). PATIENTS AND METHODS: Forty-six OLT recipients with recurrent hepatitis C were studied. Grafts and recipients were genotyped for ApoE. In a follow-up extending up to 4 years, the serum triglycerides-to-cholesterol ratio (T/C ratio) was measured 1 year after OLT, whereas fibrosis progression was assessed yearly and expressed as fibrosis units/month (FU/mo). RESULTS: A T/C ratio < or =0.75 was observed in 13/15 cases in which both donor and recipient were epsilon4 carriers, 10/19 cases in which epsilon4 alleles were of exclusive recipient's origin and 5/12 cases in which epsilon4 alleles were of exclusive donor's origin or absent (P<0.02). One year after OLT, a fibrosis progression < or =0.100 FU/mo was associated with a low T/C ratio (24/34 vs. 4/12, P<0.05). An Ishak staging score >2 was reached later by male recipients who were epsilon4 carriers (P<0.002). CONCLUSIONS: Recipient's carriage of ApoE epsilon4 affects fibrosis progression of recurrent hepatitis C through gender-specific mechanisms, associated with a peculiar, ApoE-associated, lipid profile.

Weight gain after liver transplantation and the insertion/deletion polymorphism of the angiotensin-converting enzyme gene.

BACKGROUND: Subjects who carry the D allele of the angiotensin-converting enzyme (ACE) gene have higher plasma and tissue angiotensin II levels, possibly concurrent with the development of obesity. In transplant recipients, treatment with calcineurin antagonists would magnify these effects. The present study verifies whether the allelic variants of ACE are a factor involved in excess weight gain after liver transplantation. METHODS: A consecutive series of 108 liver transplant recipients (73 males) were studied. Recipient ACE genotypes, determined by a polymerase chain reaction-based method, were related to body mass changes 1 year after transplant. RESULTS: Body mass index (BMI) increased from the pretransplant value of 25.1+/-3.3 kg/m2 to 25.9+/-3.5 kg/m2 (P<0.005). The difference was mainly attributable to recipients carrying 1 D allele or more (N=88) in whom the BMI increased from 25.3+/-3.1 kg/m2 to 26.3+/-3.3 kg/m2 (P<0.005). A BMI of 25 kg/m or greater was measured in 30 of 45 deletion/deletion homozygotes and 25 of 43 insertion/deletion heterozygotes; in contrast, 14 of 20 insertion/insertion homozygotes had a normal body mass (P<0.01). Among patients with normal body mass pretransplant (N=56), none of 13 insertion/insertion homozygotes reached a BMI value 25 kg/m or greater posttransplant (P<0.005). At multivariate analysis, pretransplant body mass and carriage of 1 D allele or more were independent predictors of body mass gain greater than 2 kg/m. CONCLUSIONS: Carriage of the D allele of the ACE gene is a strong, independent risk factor for excess weight gain after liver transplantation.

Pegylated versus standard interferon-alpha in antiviral regimens for post-transplant recurrent hepatitis C: Comparison of tolerability and efficacy.

BACKGROUND: In the treatment of hepatitis C virus (HCV) infection, regimens including pegylated interferon-alpha are superior to those including standard interferon; the present retrospective study was performed to verify whether the same is applicable to biopsy-proven recurrent hepatitis C (genotype 1b) after liver transplantation (OLT). METHODS: Twenty-four patients (16 male) were studied. Twelve had received interferon-alpha(2b) (IFN), 9 MU weekly and 12 received pegylated interferon-alpha(2b) (PEG-IFN), 0.5 microg/kg weekly. All had received oral ribavirin 600-800 mg/day. Treatment duration was intended for 12 months. A repeat liver biopsy, with evaluation of the Ishak grading and staging scores, was obtained at 1 year. RESULTS: Only 12/24 patients (50%) completed a full year of therapy; 17 (71%) experienced side-effects requiring a 50% dosage reduction or discontinuation of the IFN, PEG-IFN and/or ribavirin. This was observed in 6/12 patients (50%) treated with IFN in comparison to 11/12 patients (92%) treated with PEG-IFN (P < 0.05). The difference was mainly accounted for by anemia and leukopenia that were reported in 4/12 IFN patients (33%) versus 9/12 PEG-IFN patients (75%; P < 0.05), respectively. End-of-treatment viral response (ETVR) and histological response were always associated and occurred in 4/24 patients (17%), two in each treatment arm. Patients with ETVR were younger, had always completed 1 year of therapy, had had recurrent hepatitis later after transplantation and presented a higher baseline grading score. CONCLUSIONS: In the OLT setting, the potential benefits of antiviral treatments including PEG-IFN may be limited by the poor tolerability of the adopted drugs.

Carriage of the apolipoprotein E-epsilon4 allele and histologic outcome of recurrent hepatitis C after antiviral treatment.

Carriage of the epsilon4 allelic variant of the apolipoprotein E (ApoE) gene might affect the outcome of hepatitis C virus (HCV) infection. The liver transplantation setting offers the opportunity to verify the role of the donor's vs recipient's ApoE polymorphism. Twenty-four patients (16 men) with recurrent hepatitis C, all infected by HCV-1b and treated with interferon and ribavirin, were genotyped for ApoE variants. Liver biopsies were done at baseline and 12 months later After treatment, staging scores improved in 10 of 24 patients. Staging improvement was associated with recipient sex, completion of the full antiviral schedule, and recipient's epsilon4 carriage. The beneficial effect of epsilon4 carriage toward the progression of fibrosis was due entirely to the contribution given by male patients and was independent of the viral response. Recipients', but not donors', carriage of at least 1 epsilon4 allele might be associated with a better histologic outcome in recurrent HCV infection.