Long-term follow-up of the hepatitis C HENCORE cohort: response to therapy and occurrence of liver-related complications.

The aims of the study were to verify the long-term effect of time on viral clearance in hepatitis C virus (HCV) patients and to find out factors possibly associated with disease progression. A total of 1641 patients recruited from eight European centres in 1996-1997 were re-analysed 5-7 years after inclusion. The occurrence of decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation was analysed in relation to different host and viral factors. Ninety-three per cent of the HCV patients who had cleared the virus (spontaneously or after antiviral therapy) remained HCV-RNA-negative during follow up and may be considered as 'cured'. Among patients who were sustained responders at inclusion, 2.3% developed liver complications during follow up, and 31% of non-responders did. Advanced age at infection and presence of the human leucocyte antigen (HLA) DRB1*1201-3 allele were possibly associated with a higher rate of progression to decompensated cirrhosis or HCC. Decompensated cirrhosis might be further associated with male gender, non-response to previous therapy, and lack of HLA DRB1*1301 allele, whereas HCC seems to be associated with the presence of the HLA DQ02 allele. Long-term follow up of HCV patients indicates that virological response persists over time and is associated with a very low incidence of liver complications. Advanced age at inclusion, advanced age at infection, viral genotype 1, non-response to previous therapy and possibly some specific HLA alleles are factors independently associated with a faster rate of progression towards liver complications. The large proportion of patients lost to follow up stresses the need for a strengthened and optimized management of HCV patients.

Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.

Virological, biochemical and histological effects of human lymphoblastoid interferon in Swedish patients with chronic hepatitis C.

Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.

Superoxide production of peritoneal macrophages in experimental gram-negative sepsis; influence of in vitro and in vivo supplements of zinc.

Although zinc is essential for the optimum function of the immune system, there is some controversy regarding treatment with zinc during acute infections where low serum zinc levels are often recorded. The aim of the present study was to investigate the influence of in vitro and in vivo zinc supplementation on the potentially toxic metabolic activity of peritoneal macrophages during infection. Rats were made septic by implanting a gelatin capsule containing known amounts of E. coli, and Bacteroides fragilis into the abdomen. Peritoneal macrophages were harvested by peritoneal lavage 72 hours after the induction of sepsis. Superoxide release was measured after stimulation with phorbol myristate acetate (PMA) or serum treated zymosan (STZ). Macrophages from septic rats released significantly higher amounts of superoxide compared with macrophages from sham operated controls after stimulation with both PMA and STZ. Following in vitro supplementation, zinc inhibited the superoxide production of macrophages harvested from septic rats after stimulation with both PMA and STZ. In vivo supplementation with zinc resulted in increased superoxide production from septic macrophages when stimulated with STZ, whereas stimulation with PMA produced no significant changes. Thus, in vitro incubation inhibited the superoxide production of peritoneal macrophages in intraabdominal sepsis, whilst in vivo administration of zinc produced no such effect, and the effect seemed to vary depending on the stimuli used to initiate the respiratory burst.

Cerebral cysticercosis successfully treated with praziquantel.

A 28-year-old woman presented with signs of relapsing meningeal inflammation 5 months after immigration from Chile. Cerebral cysticercosis was diagnosed with computed tomography (CT) scan, showing signs of intracranial hypertension and cystic lesions, and was confirmed by serological investigation. After treatment with praziquantel all clinical symptoms disappeared. A CT scan obtained 6 months after treatment showed almost complete resolution of the cystic changes in the brain.

Fulminant course of infectious mononucleosis with virus-associated hemophagocytic syndrome.

A fatal case of infectious mononucleosis due to serologically verified Epstein-Barr virus infection in a previously healthy 30-year-old man is presented. The clinical course was characterized by severe prostration, persistently high spiking fever, and continuous development of enlarged lymph nodes. Hematologic examination revealed peripheral leukopenia and thrombocytopenia, and in the bone marrow an increased number of benign histiocytes showed marked hemophagocytosis. At autopsy abnormal lymphoid infiltrates were present in several tissues. The pathogenesis of this infection-associated hemophagocytic syndrome is discussed in terms of the possibility of an impaired immune response to infectious agents.

Opsonic and antibody responses to pneumococcal polysaccharide types 6A, 19F and 23F after vaccination of immunocompromised patients.

Opsonic and antibody responses to pneumococcal polysaccharide types 6A, 19F and 23F were evaluated before and after vaccination with a 14-valent pneumococcal vaccine in 25 patients splenectomized due to trauma, non-malignant or malignant disease and in 8 non-splenectomized patients with malignant disease. In approximately 50% of the tests, a 2-fold or greater increase in antibody concentrations and a significantly enhanced opsonization of pneumococci was found. A close correlation between antibody increase an enhancement of opsonization was demonstrated. 93% of paired samples with postimmunization antibody increase above 150 ELISA units showed significantly enhanced opsonization. Increased postvaccination opsonic activity and antibody levels were infrequently accompanied by increased granulocyte chemotactic activity of the serum. No significant difference in antibody and opsonic response to vaccination was found between the groups of patients, except for patients with Hodgkin's disease receiving chemotherapy, who had a reduced immunization response. Prevaccination antibody concentration, type of antigen or age of the patients did not influence the outcome of vaccination.

Evaluation of phagocytic and bactericidal activities of neutrophil granulocytes. Determination of viable extracellular bacteria by their incorporation of 14C-leucine and 3H-thymidine.

A method for evaluation of human neutrophil granulocyte function based on the combined determination of total and extracellular bacteria is described. The total number of surviving bacteria is assessed by the determination of colony forming units (CFU) after hypotonic lysis of granulocytes. Extracellular viable bacteria can be determined by the incorporation of 14C-leucine or 3H-thymidine into bacterial macromolecules since there is a linear relationship between macromolecular synthesis and bacterial number and insignificant amounts of both 14C-leucine and 3H-thymidine is taken up by intracellular viable organisms. This method might be suitable for the differentiation of defects in phagocytosis and intracellular killing of various bacteria.