The prevalence of HCV genotypes in French and Italian patients has been changing; the prevalence of HCV type 1b (II) infection has progressively decreased, although it still accounts for most HCV-related cirrhosis and hepatocellular carcinoma. High HCV viremia levels and HCV genotype type 1b (II) are independent predictors for poor response to interferon-alpha therapy and should be considered in the management of patients with HCV infection.

Recent studies have shown that the diagnosis of spontaneous bacterial peritonitis (SBP) can be rapidly obtained using leukocyte esterase reagent strips. However, published studies were restricted to one or two centers, and the number of patients with SBP was thus limited. The aims of the current prospective multicenter study were: (1) to assess the diagnostic accuracy of the Multistix 8SG urine test for the diagnosis of SBP; and (2) to assess the prevalence of SBP. From January to May 2004, 2 reactive strips were tested independently in inpatients with cirrhosis and in outpatients undergoing paracentesis. Cultures of ascitic fluid were performed at the bedside using aerobic and anaerobic blood culture bottles. Two thousand one hundred twenty-three paracenteses were performed in 1,041 patients from 70 centers. One hundred seventeen samples, obtained from 91 patients, had ascites polymorphonuclear cell (PMN) counts >250/ l (range, 250-34,000), among which 56 were associated with positive ascitic fluid cultures. The prevalence of SBP was 5.5% in the whole population, 9% in inpatients, and 1.3% in outpatients (P < 0.0001). The prevalence of SBP was 0.57% in asymptomatic outpatients versus 2.4% in symptomatic outpatients (P ‫؍‬ 0.04). Using a threshold of 2؉ for positivity of the reagent strip, sensitivity was 45.3% for the diagnosis of SBP, specificity was 99.2%, positive predictive value was 77.9%, and negative predictive value was 96.9%. Conclusion: This study confirms the low prevalence of SBP in asymptomatic outpatients according to a priori defined criteria, and indicates an absence of diagnostic efficacy for this specific strip test. (HEPATOLOGY 2007;45:1275-1281

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein has been controversially implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy in clinical studies. In this study, the relationship between NS5A mutations and selection pressures before and during antiviral therapy and virologic response to therapy were investigated. Full-length NS5A clones were sequenced from 20 HCV genotype 1-infected patients in a prospective, randomized clinical trial of IFN induction (daily) therapy and IFN plus ribavirin combination therapy. Pretreatment NS5A nucleotide and amino acid phylogenies did not correlate with clinical IFN responses and domains involved in NS5A functions in vitro were all well conserved before and during treatment. A consensus IFN sensitivity-determining region (ISDR 237-276 ) sequence associated with IFN resistance was not found, although the presence of Ala 245 within the ISDR was associated with nonresponse to treatment in genotype 1a-infected patients (P < 0.01). There were more mutations in the 26 amino acids downstream of the ISDR required for PKR binding in pretreatment isolates from responders versus nonresponders in both HCV-1a-and HCV-1b-infected patients (P < 0.05). In HCV-1a patients, more amino acid changes were observed in isolates from IFN-sensitive patients (P < 0.001), and the mutations appeared to be concentrated in two variable regions in the C terminus of NS5A, that corresponded to the previously described V3 region and a new variable region, 310 to 330. Selection of pretreatment minor V3 quasispecies was observed within the first 2 to 6 weeks of therapy in responders but not nonresponders, whereas the ISDR and PKR binding domains did not change in either patient response group. These data suggest that host-mediated selective pressures act primarily on the C terminus of NS5A and that NS5A can perturb or evade the IFN-induced antiviral response using sequences outside of the putative ISDR. Mechanistic studies are needed to address the role of the C terminus of NS5A in HCV replication and antiviral resistance.Hepatitis C virus (HCV) is a major cause of chronic liver disease leading to cirrhosis worldwide and is now recognized as a leading indication for orthotopic liver transplantation in the United States. The HCV genome has a high degree of genetic variability. Interindividual HCV sequence variability has led to the classification of at least six genotypes, while intraindividual variability is referred to as a quasispecies, which usually consists of a predominant viral variant and a variable mixture of highly genetically related yet distinct variants (23, 36).Interferon (IFN) monotherapy leads to sustained virological responses in less than 20% of chronic hepatitis C cases (47). The recent introduction of IFN plus ribavirin combination therapy has significantly improved response rates (8, 38). In multivariate analyses, HCV genotype and high viral load are two important virologic factors that independently predict the likelihood of treatment failure (37, 39)...

The aim of this prospective double-blind study was to evaluate the value of long-term antibiotic prophylaxis using ciprofloxacin for the prevention of spontaneous bacterial peritonitis (SBP) in 60 cirrhotic patients with low ascitic fluid protein levels (<15 gL). The patients were assigned to two groups: group I (n = 28) ciprofloxacin 750 mg per 0s once a week for 6 months, group 11 (n = 32) placebo. The two groups were similar for clinical and laboratory characteristics. Twelve patients developed an intercurrent disorder, and 10 patients died during the trial. There were no adverse effects in the treated group. There was a significant decrease in the incidence of SBP (3.6 vs. 22%) (P < .05) and duration of hospitalization (9.3 i 4.5 vs. 17.6 ? 6.2 days) (P < .