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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.

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 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.

Background/aims: Hepatic iron may act as an important co-morbid factor in non-hemochromatotic liver diseases, but whether it may favour fibrogenesis after liver transplantation is not known. To verify whether the hepatic iron concentration of the graft might play a role in the rapid fibrotic progression frequently observed after liver transplantation for chronic hepatitis C., Methods: The hepatic iron concentration, measured at the time of the donor operation, was retrospectively related to the histological follow-up data of 68 recipients (49 males, 19 females), of whom 38 were hepatitis C virus positive., Results: The hepatic iron concentration in donor liver biopsies ranged from 25 to 7,100 microg/gdw. After a median follow-up of 19 months, nine patients (five HCV positive) had a staging score >3. There was a significant association between a higher frequency of increasing staging and donor age >50 years. In female HCV-positive recipients, a graft hepatic iron concentration >1,200 microg/gdw was associated with fibrosis progression >0.15 fibrosis units per month (4/4 vs. 1/7, p<0.01)., Conclusions: The graft hepatic iron concentration may be one of the factors involved in early fibrosis progression due to recurrent hepatitis C in female recipients.

Adefovir-dipivoxil has been shown to be effective against lamivudine-resistant mutants in immunocompetent patients and in a small number of liver transplant recipients with recurrent hepatitis B virus (HBV) infection. The therapeutic role of adefovir-dipivoxil in acute de novo HBV infection after transplantation is uncertain. We describe a case of acute de novo HBV infection that occurred after liver transplantation and that was treated with lamivudine followed (when viral escape mutants emerged) by adefovir-dipivoxil rescue. Treatment outcome was excellent, with complete viral clearance and development of a protective titer of antibodies to anti-hepatitis B surface antigen. Because the donor was vaccinated against HBV, it is conceivable that clearance of HBV infection in the recipient might have been favored by adoptive transfer of immunity to HBV. The immune status of the donor might be a factor to consider when determining the treatment options for de novo hepatitis B.

Recent years have witnessed tremendous advances in the fields of pathophysiology, diagnosis and management of hereditary hemochromatosis (HH) and other iron overload syndromes, the dreadful consequences of which are fully preventable by early diagnosis and treatment. Missense mutations in HFE, a newly discovered gene encoding for a major histocompatibility class-I like molecule, have been found to be strictly associated with most cases of HH. The mechanisms by which a dysfunctional HFE molecule determines increased absorption of iron in HH are on the way to be fully clarified, due to the availability of a knockout mouse model. Epidemiologic studies have shown that HH is one of the most common human hereditary disorders. The possibility to identify HFE heterozygotes by means of a simple genetic test have prompted studies on the association between HFE mutations and iron overload syndromes different from HH. In the era of the historic completion of the human genome projects, genetic testing for HH may soon qualify for being adopted in universal population screening policies. In the present paper, the recent advances in the fields of genetics and pathophysiology of HH and other iron overload syndromes will be summarized. Furthermore, its clinical features, pathology and treatment will be reviewed, and the emerging issues of cost-effective diagnosis and of possible population screening strategies will be succintly discussed.