Nucleotide sequence analysis of the NS5B region was performed to identify genotypes of 8,479 hepatitis C virus (HCV) RNA-positive patient samples collected in the Canadian province of Quebec. Genotypes could be determined for 97.3% of patients. Genotypes 1 to 6 were found in 59.4, 9.0, 25.7, 3.6, 0.6, and 1.8% of patients, respectively. Two isolates did not classify within the six genotypes. The subtype 1 distribution was 76.7% 1a, 22.6% 1b, and 0.7% others, while the subtype 2 distribution was 31.8% 2a, 47.6% 2b, 10.9% 2c, 4.1% 2i, and 5.6% others. Subtype 3a accounted for 99.1% of genotype 3 strains, while all genotype 5 samples were of subtype 5a. The subtype 4 distribution was 39.2% 4a, 15.4% 4k, 11.6% 4d, 10.2% 4r, and 23.6% others. The subtype 6 distribution was 40.4% 6e, 20.5% 6a, and 39.1% others. The 5 untranslated region (5UTR) sequences of subtype 6e were indistinguishable from those of genotype 1. All samples that did not classify within the established subtypes were also sequenced in C/E1 and 5UTR. C/E1 phylogenetic reconstructions were analogous to those of NS5B. The sequences identified in this study allowed the provisional assignments of subtypes 1j, 1k, 2m, 2r, 3i, 4q, 6q, 6r, and 6s. Sixty-four (0.8%) isolates classifying within genotypes 1 to 6 could not be assigned to one of the recognized subtypes. Our results show that genotyping of HCV by nucleotide sequence analysis of NS5B is efficient, allows the accurate discrimination of subtypes, and is an effective tool for studying the molecular epidemiology of HCV.Hepatitis C virus (HCV) was first identified in the late 1980s and is a major cause of liver disease throughout the world (40). It is a single-stranded, positive-polarity RNA virus classified in the genus Hepacivirus of the family Flaviviridae. The HCV genome encodes a single long polyprotein with the following gene order:

Chylous ascites refers to the accumulation of lipid-rich lymph in the peritoneal cavity due to disruption of the lymphatic system secondary to traumatic injury or obstruction. Worldwide, abdominal malignancy, cirrhosis, and tuberculosis are the commonest causes of CA in adults, the latter being most prevalent in developing countries, whereas congenital abnormalities of the lymphatic system and trauma are commonest in children. The presence of a milky, creamy appearing ascitic fluid with triglyceride content above 200 mg/dL is diagnostic, and, in the majority of cases, unless there is a strong suspicion of malignancy, further investigations are not required in patients with cirrhosis. If an underlying cause is identified, targeted therapy is possible, but most cases will be treated conservatively, with dietary support including high-protein and low-fat diets supplemented with medium-chain triglycerides, therapeutic paracentesis, total parenteral nutrition, and somatostatins. Rarely, resistant cases have been treated by transjugular intrahepatic portosystemic shunt, surgical exploration, or peritoneovenous shunt.

The in situ inflammatory response developing in the human lung during a localized bacterial infection was studied in 15 patients with unilateral community-acquired pneumonia (CAP). The local response in the involved lung was compared with that in the contralateral, noninvolved lung as well as with the systemic blood response. Eight healthy volunteers served as control subjects. Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured by ELISA in bronchoalveolar lavage (BAL) fluids (n = 15), serum (n = 15), and alveolar macrophage and monocyte culture supernatants (n = 8). The concentrations of TNF-alpha, IL-beta and IL-6 in BAL fluid were significantly higher in the involved lung than in the paired noninvolved lung (p < or = 0.01) or in healthy subjects (p < or = 0.02, p < or = 0.01, and p < or = 0.001, respectively). Serum IL-6 concentrations were higher in patients than in control subjects, whereas IL-1 beta and TNF-alpha concentrations did not differ in the two groups. Alveolar macrophages from the involved lung spontaneously released higher concentrations of IL-1 beta, IL-6, and TNF-alpha (p < or = 0.05) than did macrophages from the noninvolved lung, which served as controls. However, macrophages were hyporesponsive in terms of cytokine production to further stimulation by lipopolysaccharide (LPS) in the noninvolved and involved lung compared with controls, whereas peripheral blood monocytes were not.(ABSTRACT TRUNCATED AT 250 WORDS)

The hypothesis was investigated that hepatitis C virus (HCV) infection behaves like an opportunistic infection in which progressive liver disease (PLD) is the principal manifestation. PLD in 81 hemophiliacs coinfected with HCV and human immunodeficiency virus (HIV) was compared with 53 HIV-seronegative HCV-infected hemophiliacs. Progression to AIDS and death in 22 HCV/HIV-coinfected hemophiliacs with PLD was also compared with 59 coinfected hemophiliacs who did not develop PLD. The risk of PLD occurrence associated with an HIV-positive status was 7.4 (95% confidence interval [CI], 2.2-25.5; Cox model). In the coinfected group, the risk of PLD occurrence was higher in subjects with severe AIDS-defining immunodeficiency than in those without (odds ratio, 3. 6; 95% CI, 1.3-10). Persons with PLD also had a faster progression to AIDS (P=.03, log rank test) than those without PLD. Thus, as with other chronic resident human viruses, HCV should be considered another opportunistic pathogen in HIV disease.

MMF is effective and well tolerated by patients with autoimmune hepatitis who do not respond to, or are intolerant of, conventional immunosuppressive agents.

Recipients who develop EAD have longer ICU and hospital stays and greater mortality than those without. Donor, graft, and recipient risk factors all contribute to the development of EAD. Results of these analyses identify factors that, if modified, may alter the risk of EAD.

Background & AimsNon-invasive diagnostic methods for liver fibrosis predict clinical outcomes in viral hepatitis and nonalcoholic fatty liver disease (NAFLD). We specifically evaluated prognostic value of non-invasive fibrosis methods in nonalcoholic steatohepatitis (NASH) against hepatic venous pressure gradient (HVPG) and liver histology.MethodsThis was a retrospective cohort study of 148 consecutive patients who met the following criteria: transjugular liver biopsy with HVPG measurement; biopsy-proven NASH; absence of decompensation; AST-to-Platelets Ratio Index (APRI), fibrosis-4 (FIB-4), NAFLD fibrosis score, ultrasound, hepatic steatosis index and Xenon-133 scan available within 6 months from biopsy; a minimum follow-up of 1 year. Outcomes were defined by death, liver transplantation, cirrhosis complications. Kaplan–Meier and Cox regression analyses were employed to estimate incidence and predictors of outcomes, respectively. Prognostic value was expressed as area under the curve (AUC).ResultsDuring a median follow-up of 5 years (interquartile range 3-8), 16.2% developed outcomes, including 7.4% who died or underwent liver transplantation. After adjustment for age, sex, diabetes, the following fibrosis tools predicted outcomes: HVPG >10mmHg (HR=9.60; 95% confidence interval [CI] 3.07-30.12), histologic fibrosis F3-F4 (HR=3.14; 1.41-6.95), APRI >1.5 (HR=5.02; 1.6-15.7), FIB-4 >3.25 (HR=6.33; 1.98-20.2), NAFLD fibrosis score >0.676 (HR=11.9; 3.79-37.4). Prognostic value was as follows: histologic fibrosis stage, AUC=0.85 (95% CI 0.76-0.93); HVPG, AUC=0.81 (0.70-0.91); APRI, AUC=0.89 (0.82-0.96); FIB-4, AUC=0.89 (0.83-0.95); NAFLD fibrosis score, AUC=0.79 (0.69-0.91). Neither histologic steatosis nor non-invasive steatosis methods predicted outcomes (AUC<0.50).ConclusionsNon-invasive methods for liver fibrosis predict outcomes of patients with NASH. They could be used for serial monitoring, risk stratification and targeted interventions.

Background:The management of patients with chronic hepatitis C who have relapsed or failed to respond to interferon based therapies is an important issue facing hepatologists. Aims: We evaluated the efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in this population by conducting a multicentre open label study. Patients: Data from adults with detectable serum hepatitis C virus (HCV) RNA who had not responded or had relapsed after previous conventional interferon or conventional interferon/ribavirin combination therapy were analysed. Methods: Patients were retreated with peginterferon alfa-2a (40KD) 180 mg/week plus ribavirin 800 mg/day for 24 or 48 weeks at the investigators' discretion. The study was conceived before the optimal dose of ribavirin (1000/1200 mg/day) for patients with genotype 1 was known. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA (,50 IU/ml) after 24 weeks of follow up. The analysis was conducted by intention to treat. Results: A total of 312 patients (212 non-responders, 100 relapsers) were included. Of these, 28 patients were treated for 24 weeks and 284 for 48 weeks. Baseline characteristics between non-responders and relapsers were similar although more non-responders had genotype 1 infection (87% v 69%). Overall SVR rates were 23% (48/212) for non-responders and 41% (41/100) for relapsers. When data were analysed by genotype, SVR rates were 24% (61/253) in genotype 1 and 47% (28/59) in genotype 2/3. Conclusions: These results in a large patient cohort demonstrate that it is possible to cure a proportion of previous non-responders and relapsers by retreating with peginterferon alfa-2a (40KD) plus ribavirin.