Pegylated interferon alpha-2b plus ribavirin for naive patients with HCV-related cirrhosis

BACKGROUND: Data on the efficacy of antiviral therapy in patients with HCV-related compensated cirrhosis are generally drawn from analyzing subgroups in larger trials. AIMS: (1) To analyze the safety and efficacy of combination therapy in naive patients with HCV-related cirrhosis; (2) to evaluate the factors influencing the sustained virologic response (SVR) in cirrhotic patients by comparison with a group of noncirrhotic patients; (3) to analyze the outcome of cirrhotic patients either acquiring SVR and nonresponders to the antiviral therapy during the posttreatment follow-up. METHODS: We consecutively enrolled 365 patients with biopsy-proven HCV-related chronic hepatitis meeting the inclusion criteria for pegylated interferon a-2b plus Ribavirin: 87 patients had compensated liver cirrhosis and 278 had histologic stages between 1 and 4 according to Ishak's classification. RESULTS: The 2 groups were comparable for genotype, viral load, and alanine transferase at presentation. Cirrhotic patients were significantly older and had significantly higher body mass index, serum ferritin, and gamma-glutamyl transpeptidase. The rate of side effects was similar in the 2 groups, whereas the rate of SVR was significantly lower in cirrhotic (45.9%) than in noncirrhotic patients (65.8%). Logistic regression analysis showed that genotype 1 to 4 and high viral load were independent variables correlating with nonresponse in the sample as a whole. During follow-up, hepatocellular carcinoma developed in 5/38 (13.2%) cirrhotic patients not responding or relapsing after treatment. No cases of hepatocellular carcinoma were seen among cirrhotic or noncirrhotic patients with a SVR. CONCLUSIONS: Cirrhotic patients with compensated disease have a reasonably good chance of virologic response and should be offered treatment, carefully monitoring any side-effects

A 4-year treatment with clodronate plus calcium and vitamin D supplements does not improve bone mass in primary biliary cirrhosis.

INTRODUCTION: International guidelines for managing osteoporosis in cirrhosis or severe cholestasis indicate a <-2.5 t-score as a cut-off for medical treatment, while no treatment is recommended in the case of osteopenia (t-scores ranging from -1.0 to -2.5). AIM: We conducted a prospective study in primary biliary cirrhosis with a view to optimizing the rationale for the medical treatment of bone loss. METHODS: All na\uefve post-menopausal women with primary biliary cirrhosis were enrolled in the study. Bone metabolism was evaluated by measuring 25-hydroxy-vitamin D, parathyroid hormone, osteocalcin. Bone mineral density was assessed at the lumbar spine by dual-photon X-ray absorptiometry at the baseline and every 2 years for up to 4 years. Patients with either osteopenia or osteoporosis received the following treatment: oral calcium carbonate (1000 mg/day)+vitamin D3 (880 IU/day)+i.m. disodium clodronate 100mg every 10 days for 4 years. RESULTS: Ninety-six patients completed the study: 30 had a normal bone mineral density (group 1), 37 had osteopenia (group 2), 29 had osteoporosis (group 3). No significant differences in biochemical parameters of bone metabolism were observed between the three groups. A total of 288 bone mineral density measurements were taken. Linear regression analysis failed to reveal significant changes in t-score over the follow-up in all groups. CONCLUSIONS: A 4-year treatment with clodronate+calcium/vitamin D3 supplements does not significantly improve osteoporosis or osteopenia in primary biliary cirrhosis women in menopause, but prevents the natural bone loss in these patients. Extensive international trials are warranted to optimize the prevention and treatment of bone loss in primary biliary cirrhosis

A novel multidrug-resistance protein 2 gene mutation identifies a subgroup of patients with primary biliary cirrhosis and pruritus

Abstract: A single nucleotide polymorphism characterized by the substitution of valine for glutamate (V1188E) in exon 25 of the multidrug resistance protein 2 gene was found in a group of patients with primary biliary cirrhosis. This heterozygous mutation was significantly associated with the presence of pruritu

Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women whit intrahepatic cholestasis of pregnancy

12noIntrahepatic cholestasis of pregnancy is a multifactorial disorder of pregnancy associated with a genetic background.To evaluate the genetic contribution of ABCB4, MDR3 gene in the development of intrahepatic cholestasis of pregnancy in a large cohort of Italian subjects.This study represents an extension of a previous multicentre-prospective study including three Italian referral centres. In all, we enrolled 96 women at the 3rd trimester of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes by standard procedures. Polymerase chain reaction was used to amplify exon 14, 15 and 16 of MDR3 gene.We found 3 non-synonymous heterozygous mutations in exon 14 (E528D, R549H, G536A), 1 in exon 15 (R590Q) and 2 in exon 16 (R652G, T6671). MDR3 gene variants in exons 14, 15 and 16 occurred in 7/96 of pregnant mothers with intrahepatic cholestasis of pregnancy (7.2%), and in none of 96 pregnant controls matched for age and parity. All seven patients had normal gamma-glutamyl transpeptidase, normal bilirubin, but high levels of both alanine transferase and serum bile acids. One had cholesterol biliary lithiasis. The outcome of pregnancy was normal in four cases (with vaginal delivery), while there was one fetal distress.MDR3 mutations are responsible for the development of intrahepatic cholestasis of pregnancy in only a small percentage of Italian women. Further genetic studies are warranted, however, to clarify the role of different mutations in intrahepatic cholestasis of pregnancy.reservedmixedAZZAROLI F.; BRAGHIN C.; CARDERI L.; ESPOSITO W.; FLOREANI A.; MARCHESONI Diego; MAZZELLA G.; MONTAGNANI M.; PATERNOSTER D.; ROSA RIZZOTTO E.; SOARDO GIORGIO; VARIOLA A.Azzaroli, F.; Braghin, C.; Carderi, L.; Esposito, W.; Floreani, A.; Marchesoni, Diego; Mazzella, G.; Montagnani, M.; Paternoster, D.; ROSA RIZZOTTO, E.; Soardo, Giorgio; Variola, A

Maximal amenable subalgebras arising from maximal amenable subgroups

We provide a general criterion to deduce maximal amenability of von Neumann subalgebras LΛ ⊂ LΓ arising from amenable subgroups Λ of discrete countable groups Γ. The criterion is expressed in terms of Λ-invariant measures on some compact Γ-space. The strategy of proof is different from S. Popa's approach to maximal amenability via central sequences [Po83], and relies on elementary computations in a crossed-product C *-algebra