Phytoestrogens and liver disease.

Phytoestrogens are plant substances that are similar to 17-beta-estradiol and produce estrogenic effects. A protective role in the development of breast and prostate cancer has been hypothesized. Estrogen receptors and their variant forms play a significant role in the pathogenesis of hepatocellular carcinoma (HCC); therefore weak estrogenic substances in the diet may play a role in its development. To investigate the role of phytoestrogens in HCC an investigation of dietary intake of these substances has been performed. Cases, patients at first diagnosis of cirrhosis or HCC were chosen. Questionnaire was built up using indications from previously published papers, extending the registration of details of the diet to reconstruct intake of nutrients for the last year. Interviews were always performed by the same dietician. Quantities determined with the help of photos of servings. Data were analyzed with Winfood database completed with data regarding content in phytoestrogens of food, beverages and seasonings. So far 92 cirrhotic patients and 32 HCCs have been interviewed. No significant difference was registered among the two groups regarding total caloric intake or single nutrients (lipids, carbohydrates, proteins). A significant lower intake of genistein was evidenced in patients at first diagnosis of HCC in comparison with cirrhotics; no significant difference was found in daidzein intake. Lignans intake was strictly related with wine intake; intake was significantly lower in cases only when wine was taken into account otherwise it was similar. Results can be summarized as follows: (1) there are no clear-cut differences (both qualitative or quantitative) between cirrhotics and HCC patients in the overall daily caloric intake while; (2) definite differences exist in the intake of some of the phytoestrogens (genistein, SEC, MAT); (3) differences between cases and controls in SEC and MAT are mainly attributable to lower alcohol intake in cases while; (4) significantly lower genistein intake in HCC only seems due to personal preferences of patients. In conclusion, these differences that we have evidenced in the diet in regard to estrogen-like substances may be relevant in modulating the risk of developing HCC in cirrhotic patients.

Pretransplantation pre-S2 and S protein heterogeneity predisposes to hepatitis B virus recurrence after liver transplantation.

Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection often is complicated by recurrence of infection despite immunoglobulin treatment. To evaluate whether variability in HBV genomic sequences and the target of antibody to hepatitis B surface antigen action in pre-LT samples may be associated with a high recurrence rate, HBV pre-S/S regions of 14 HBV-positive candidates for LT (in 9 of these patients, HBV infection subsequently recurred) were amplified and sequenced. Two hundred ninety-one mutations in 1,167 sequenced nucleotides (24.9%) were found. Of these, 120 mutations (10.2%) led to an amino-acid change. The only significant difference between patients with and without recurrent disease was in the number of mutations in the pre-S2 region (total mutations, P =.042; missense mutations, P =.012) of pre-LT HBV DNA. In addition, a difference in amino-acid level was present in the pre-S2 region (P =.030). The delay in HBV infection recurrence was proportional to the number of pre-LT HBV mutations in the pre-S2 and S genes: the higher the number, the longer the interval between LT and recurrence of infection (pre-S2, P =.0124; S, P =.0060; total number of mutations in S protein, P =.0421). In conclusion, pre-LT determination of pre-S/S gene sequence variability showed that heterogeneity of the pre-S2 and, to a lesser extent, S genes was associated with a greater chance for HBV recurrence. Modification of B-cell epitopes of S, but especially of pre-S2, protein leading to conformational changes and alterations in the viral encapsidation and secretion process may facilitate HBV recurrence and contribute to the failure of immune globulin therapy.