Hepatitis C

The major cause of chronic post-transfusion hepatitis, the hepatitis C virus (HCV), has been identified. HCV is a single-stranded linear RNA virus with characteristics similar to the flaviviruses. A different agent, the hepatitis E virus, is associated with epidemic (enterically-transmitted) non-A, non-B hepatitis. At present, infection with HCV is recognized by the finding of anti-HCV antibodies, positive in up to 90% of patients with chronic non-A, non-B post-transfusion hepatitis. Antibodies to HCV are detected in 1% of normal volunteer blood donors and in the majority of donors implicated in post-transfusion hepatitis. HCV antibodies are also found in patients with autoimmune liver disease and hepatocellular carcinoma. Moreover, HCV infection may contribute to the pathogenesis of liver disease in alcoholic patients. The role of HCV infection in fulminant non-A, non-B hepatitis and hepatitis-associated aplastic anemia has not been elucidated as yet. Therapy of chronic non-A, non-B hepatitis with recombinant human alpha-interferon has been shown to improve or normalize aminotransferase levels in approximately 50% of patients, most of whom have evidence of HCV infection. However, relapse after cessation of treatment is common. In the future, screening blood for evidence of HCV infection may prevent most cases of non-A, non-B post-transfusion hepatitis.     

Hepatitis C

In the latter half of the 20th century, HCV emerged as the most common cause of chronic liver disease, and will likely remain so. Since its initial discovery in 1989, rapid progress has been made in our understanding of the virology, epidemiology, natural history, diagnosis, and treatment of HCV. Over the next few decades, as further advancements are made, superior treatment options will become available.     

Hepatitis C

Hepatitis C virus commonly causes chronic liver disease. Chronicity as a result of the failure of T-cell-mediated immunity, liver damage caused by cytotoxic T lymphocytes, and the evolution of genetic diversity characterize hepatitis C infection. Progression, typically silent, is determined by sex, age, alcohol and immune status. Interferon and ribavirin are effective in the substantial minority of patients with less advanced fibrosis and lower hepatitis C viral loads.     

Hepatitis C

Opinion statement  

Cleavage of C2 by C1s into the antigenically distinct fragments C2a and C2b: demonstration of binding of C2b to C4b.

The activation of complement component C2 by C1s is a major reaction step leading to the assembly of two related macromolecular enzymes in the classical complement pathway C3 convertase and C5 convertase. The present studies clearly document the smaller fragment, C2b, that results when human C2 reacts with C1s. We have identified and characterized C2b (34,000 daltons) as a single protein on disc electrophoresis and immunoelectrophoresis. C2a (73,000 daltons), the larger fragment from this reaction, has a more acidic nature and C2b is more basic. These fragments can also be detected by their different antigenic determinants. When the C2-C4b complex is activated in the fluid phase by C1s and allowed to decay, it dissociates into C2a and the C2b-C4b complex. Furthermore, when C2 is bound to C4b-Sepharose and then reacted with C1s, only the C2a fragment is released from the solid phase C2-C4b-Sepharose into the fluid phase, and the C2b fragment remains noncovalently bound to C4b-Sepharose. These results suggest that the C2b portion of C2 contains a stable binding site for C4b and, after the decay release of C2a from this C3 convertase, the C2b fragment remains bound. Thus, the decay release of C2a may represent a temperature-dependent dissociation from C2b.     

Evaluation of C3c,C4 and C1-esterase inhibitor (C1-INH) during unstable angina

BACKGROUND: The complement system plays an important role in the physiopathology of acute myocardial infarction (AMI) taking part in myocardial damage and reperfusion injury. The aim of this study is to investigate the plasmatic levels of some complement components (C3c, C4 and C1-INH) during unstable angina (C1-INH) and their different concentrations in relation to the different myocardial areas affected by ischemia. METHODS: The plasmatic levels of C1-INH, C3c and c4 in 30 patients affected by unstable angina, and those of 22 clinically healthy subjects (control group) were evaluated (Nefelometer Behering). The patients were divided into four groups according to the different myocardial area affected by ischemia (anterior, antero-lateral, lateral or inferior ischemia), RESULTS: No statistically significant differences were found in plasmatic levels of C3c, C4 and C1-INH between the group of patients and the control group. There is a statistically significant difference between the C1-INH levels of the patients with inferior ischemia and the plasmatic concentrations of the whole patients' group (p<0,01), the control group (p<0,01) and the group of patients with lateral ischemia (p<0,02). CONCLUSIONS: There seems to be a different activation of the complement system during unstable angina, in relation to the different myocardial area affected by ischemia.     

Early Antihepatitis C Virus Response with Second—Generation C200/C22 ELISA

Detection of early antibody to hepatitis C virus (HCV) by a new second-generation C200/C22 anti-HCV enzyme-linked immunosorbent assay (ELISA) and a four-antigen recombinant immunoblot assay (4-RIBA) was compared with the first-generation anti-HCV C100 ELISA using sequential serum samples of 9 recipients who were infected with HCV, as detected by polymerase chain reaction after transfusion of blood products. Within 26 weeks after transfusion, 9/9 (100%) recipients seroconverted with C200/22 ELISA, and 6/9 (67%) seroconverted with C100 ELISA. Compared with C100 ELISA, C200/C22 ELISA seroconversion occurred simultaneously in 3 cases, 5-6 weeks earlier in 3 other cases, and 20 weeks earlier in 1 case. Seven of 9 (78%) recipients became positive, and 2/9 (22%) became indeterminate with 4-RIBA. In 8 cases with clinical posttransfusion hepatitis non-A, non-B (PTH-NANB), anti-HCV C200/C22 ELISA seroconversion occurred 2-17 (mean 6) weeks after the onset of hepatitis. In 6 cases of PTH-NANB, anti-HCV C100 ELISA seroconversion occurred 2-26 (mean 9) weeks after the onset of hepatitis. It is concluded that the second-generation C200/C22 ELISA is more sensitive than the C100 ELISA for the detection of antibody during early HCV infection. Indeterminate 4-RIBA results are found in the early phase of HCV infection.     

Physiologic anterior subluxation: case report of occurrence at C5 to C6 and C6 to C7 spinal levels

Physiologic anterior subluxation is a phenomenon that is common to the upper pediatric cervical spine and characterized by the normal forward displacement of one cervical vertebra relative to the subjacent one. Physiologic anterior subluxation can be seen in children in the setting of trauma, when it must be distinguished from pathologic subluxation. Physiologic anterior subluxation has not been reported at lower cervical spinal levels (C 5 to C 6 or C 6 to C 7 ). This is a report of physiologic anterior subluxation at C 5 to C 6 and C 6 to C 7 spinal levels distinguished from pathologic subluxation in a 9-year-old child evaluated in the acute setting after cervical spine injury.     

Hepatitis C virus genotypes in chronic hepatitis C of children

SUMMARY. Several hepatitis C virus (HCV) genotypes have been recently identified and genotype 1b has been correlated with severe liver disease and a poor response to interferon therapy. HCV infection in children is an interesting model for evaluation of the relationship between HCV genotypes and liver disease, because of its relatively short duration and the infrequent association with confounding cofactors. We have investigated HCV genotypes, using a dot-blot hybridization assay with genotype-specific probes, in 36 Italian children with chronic hepatitis C who were otherwise well and had no other underlying disease. Only four patients were symptomatic; liver histology, obtained in 3 3 patients, showed minimal hepatitis in 17 and mild chronic hepatitis in 16. Infection with HCV genotype Ib was found in 55.5% of patients, with a peak prevalence of 83% in children from southern Italy (P < 0.05 vs other regions). The remaining children were infected with HCV genotype la (16.6%), genotype 2 (11.1%). and mixed (10.9%) or undetermined (2.7%) genotypes. In one patient, HCV viraemia was never detected. There was no statistically significant correlation between genotype and age, sex, source of infection, alanine aminotransferase pattern and histological activity index. These results indicate that genotype 1b is widespread among Italian children with chronic hepatitis C, although with significant geographical variations. It is not associated with a more severe liver disease, therefore suggesting that the greater severity of liver disease recently reported in adults could reflect the cumulative effects of disease duration and of interfering cofactors.     

Chronic hepatitis C without anti-hepatitis C antibodies by second-generation assay

To study the clinicopathologic features of hepatitis C viremic patients negative for hepatitis C antibodies (anti-HCV) by current second-generation assay, we categorized 139 consecutive histologically verified patients with chronic non-A, non-B hepatitis into three groups: 121 (87%) were positive for second-generation anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and viremia (group C). Six (60%) of group B patients could be further detected by a new third-generation assay, but none of group C patients was third-generation anti-HCV-positive. The demographic features, mean peak serum alanine aminotransferase levels, HCV genotype distribution, and histologic changes were comparable among the three groups. The study indicates that most patients with chronic hepatitis C in Taiwan could be identified by current second-generation assay, and viremic but antibody seronegative patients were clinicopathologically similar to the seropositives. Most patients of the latter group could be diagnosed by a third-generation assay, indicating the usefulness of this assay.     

Protein C deficiency

Summary. Severe protein C deficiency (i.e. protein C activity <1 IU dL^?1) is a rare autosomal recessive disorder that usually presents in the neonatal period with purpura fulminans (PF) and severe disseminated intravascular coagulation (DIC), often with concomitant venous thromboembolism (VTE). Recurrent thrombotic episodes (PF, DIC, or VTE) are common. Homozygotes and compound heterozygotes often possess a similar phenotype of severe protein C deficiency. Mild (i.e. simple heterozygous) protein C deficiency, by contrast, is often asymptomatic but may involve recurrent VTE episodes, most often triggered by clinical risk factors. The coagulopathy in protein C deficiency is caused by impaired inactivation of factors Va and VIIIa by activated protein C after the propagation phase of coagulation activation. Mutational analysis of symptomatic patients shows a wide range of genetic mutations. Management of acute thrombotic events in severe protein C deficiency typically requires replacement with protein C concentrate while maintaining therapeutic anticoagulation; protein C replacement is also used for prevention of these complications around surgery. Long‐term management in severe protein C deficiency involves anticoagulation with or without a protein C replacement regimen. Although many patients with severe protein C deficiency are born with evidence of in utero thrombosis and experience multiple further events, intensive treatment and monitoring can enable these individuals to thrive. Further research is needed to better delineate optimal preventive and therapeutic strategies.