Prevalence of hepatitis C virus antibody in patients on chronic hemodialysis

Hepatitis C virus antibody (anti-HCV) was studied in 267 patients undergoing maintenance hemodialysis using an anti-HCV enzyme-linked immunosorbent assay. Furthermore, both hepatitis B virus core antibody (anti-HBc) and human T cell leukemia virus type 1 antibody (anti-HTLV-1) were determined in these patients to compare their prevalence rates. Seventy one patients (27%) had positive anti-HCV, 134 patients (50%) positive anti-HBc and 40 patients (15%) positive anti-HTVL-1. Among the 183 patients who had received blood transfusion, the prevalence of these antibodies was 34% for anti-HCV, 56% for anti-HBc and 17% for anti-HTLV-1, respectively. A significance between those with and without blood transfusion was recognized for anti-HCV (p < 0.001) and anti-HBc (p < 0.01). Of 56 patients who had received hemodialysis for over 15 years, the positive antibody was found in 63% for anti-HCV (p < 0.001), 73% for anti-HBc (p < 0.001) and 25% for anti-HTLV-1 (p < 0.05), which was significantly higher than that of patients receiving a less than 15 years hemodialysis. The prevalence rates of anti-HCV and anti-HTLV-1 did not increase with age, while that of anti-HBc increased. These findings suggest that blood transfusions during hemodialysis play a very important role in the infection of hepatitis C virus.     

Detectable levels of IgM antibodies to hepatitis C virus core protein predict breakthrough in patients with chronic hepatitis C treated with interferon-alpha

The predictive value of IgM antibodies to hepatitis C virus core antigen (HCcAb) is controversial. We studied 79 patients undergoing interferon-alpha (IFN-alpha) treatment and we found that detectable levels of IgM HCcAb could predict breakthrough on treatment.     

Immunoglobulin M antibody response to hepatitis C virus core protein in patients with chronic hepatitis C

We retrospectively assessed the frequency and clinicopathologic and virologic significance of production of immunoglobulin M (IgM) antibody to hepatitis C virus (HCV) core protein in patients with chronic hepatitis C. Sera from 60 patients with chronic hepatitis C were tested for IgM anti-HCVcore (anti-HCc). Twenty of these patients received ribavirin plus interferon-alpha for 24 weeks, and were classified as sustained, transient, or nonresponders on the basis of alanine aminotransferase levels and the presence of HCV RNA at the end of treatment and 24 weeks later. IgM anti-HCc was detected in 21 patients. There was no correlation between the presence of IgM anti-HCc and clinical features such as sex, age, mode of transmission, serum levels of alanine aminotransferase, HCV genotype, serum HCV titer, or histologic findings. Among the patients who received ribavirin plus interferon-alpha, the mean IgM anti-HCc level before therapy was comparable between sustained (n = 10), transient (n = 8), and nonresponders (n = 2). A statistically significant decrease in IgM anti-HCc response during antiviral therapy was observed in the 18 responders who became negative for serum HCV RNA at the end of therapy. These data suggest that IgM anti-HCc is of limited clinical usefulness as a marker of chronic HCV infection. Serial testing for IgM anti-HCc may provide a marker of antiviral response.     

Prevalence of cryoglobulinemia in chronic hepatitis C virus infection and response to treatment with interferon-alpha

A recombinant Schistosoma mansoni protein has been identified as a useful antigen for the detection of S. mansoni and Schistosoma haematobium antibodies. The purified recombinant protein, Sm22.3, was assayed using an enzyme-linked immunosorbent assay format against a battery of 491 well defined sera, including S. mansoni, S. haematobium, and Schistosoma japonicum infection sera, normal human sera, sera from 9 other parasitic infections, and sera from 2 additional infections. The sensitivity for detecting S. mansoni and S. haematobium infections with this single recombinant protein is 80.1%. The specificity is 94.8%. However, 15 of the 16 cross-reactive sera are malaria infection sera, and we have data suggesting that these malaria sera are actually recognizing an epitope on the vector-derived 6Xhistidine tag of recombinant Sm22.3. If this is the case, then, the actual specificity of the assay is 99.6%.     

Arthritis in patients with chronic hepatitis C virus infection

OBJECTIVE: To describe the clinical picture of arthritis in patients with chronic infection by hepatitis C virus (HCV). METHODS: Two patient populations were studied. Patients with arthritis and evidence of serum elevation of alanine aminotransferase (ALT) at the consultation were checked for HCV infection. A second group of 303 consecutive patients with rheumatoid arthritis (RA) were also checked for the presence of HCV antibodies. All patients attended the outpatient rheumatology unit of a tertiary care teaching hospital. Chronic HCV infection was determined by the presence of viral RNA in serum. A group of 315 first-time blood donors served as controls. RESULTS: Twenty-eight patients with arthritis and chronic HCV infection were identified. Seven fulfilled criteria for RA, psoriatic arthritis was found in one patient, systemic lupus erythematosus in one, gout in 2, chondrocalcinosis in 2, osteoarthritis in 7, and tenosynovitis in one. In 7 patients with a clinical picture of intermittent arthritis, a definitive diagnosis could not be made. In these patients, mixed cryoglobulinemia was present in 6/7 (86%), whereas mixed cryoglobulinemia was found in 6/21 (28%) of the other patients. Among patients with RA, 23 (7.6%) had HCV antibodies, and active infection by HCV was found in 7 (2.3%) patients. The prevalence of HCV antibodies in a blood donor population was 0.95%, significantly different (p<0.001; 95% CI 0.03, 0.10) compared to patients with RA. The distribution of antibodies determined by recombinant immunoblot analysis was similar (p = NS) between RA patients and blood donors with HCV antibodies. CONCLUSION: There is not a single clinical picture of arthritis in patients with chronic HCV infection. There is a well defined picture of arthritis associated with the presence of mixed cryoglobulinemia that consists of an intermittent, mono or oligoarticular, nondestructive arthritis affecting large and medium size joints. Although a high prevalence of HCV antibodies is suspected in patients with RA, its occurrence may be coincidental and its interpretation is difficult to determine from the data in this study.     

Effects of interferon-alpha on serum hepatitis C virus in patients with chronic hepatitis C

Interferon is beneficial in some patients with chronic hepatitis C. To assess the efficacy of interferon, we used the polymerase chain reaction (PCR) to measure HCV RNA in serial serum samples from 13 chronic hepatitis C patients who were treated with interferon-alpha. Serum alanine aminotransferase (ALT) values normalized in association with the disappearance of serum HCV RNA in nine cases during the therapy. Serum HCV remained negative after the therapy in the three patients who had no relapse, while serum HCV RNA reappeared in the six patients with elevation of ALT values. The persistence of normal ALT levels appears to be correlated with the clearance of the serum HCV. There were two patients whose ALT became normal immediately after the cessation of interferon. Serum HCV was detectable at the end of treatment when serum ALT was elevated, and thereafter serum HCV disappeared. This result suggests an immunomodulatory effect of interferon in the clearance of HCV in some cases. Furthermore, the semiquantitative PCR assay showed that all five patients in whom ALT values were normal at the end of follow-up without detectable serum HCV genome had lower HCV titers in the pretreatment sera than the other eight patients. The detection of HCV RNA by the PCR assay is useful in determining the efficacy of interferon and its mechanisms.     

Responsiveness to interferon alpha treatment in patients with chronic hepatitis C coinfected with hepatitis G virus

BACKGROUND/AIMS: Patients with chronic hepatitis C are often coinfected with the new identified Flaviviridae-like agent, termed hepatitis G virus (HGV). The aim of the study was to investigate the responsiveness of hepatitis G virus to interferon alpha and to evaluate whether a hepatitis G virus coinfection negatively influences the outcome of treatment in chronic hepatitis C. METHODS: One hundred and fifteen patients with histologically proven chronic hepatitis C were treated with interferon alpha and investigated for the presence of hepatitis G virus coinfection by nested polymerase chain reaction with primers from the helicase region of hepatitis G virus. All patients received at least 3 MU (range 3-6) interferon alpha thrice weekly for at least 6 months (mean 8, range 6-12). Polymerase chain reaction products of seven pre- and post-treatment hepatitis G virus positive patients were directly sequenced for identification of sequence variability during the follow-up. RESULTS: Eighteen (16%) patients were coinfected with hepatitis G virus. Although nine (50%) of these patients became HGV RNA negative during interferon alpha therapy, only three patients (17%) remained HGV RNA negative at the end of follow-up (mean 24 months). The rate of sustained response of chronic hepatitis C was not significantly different between patients with hepatitis C virus infection and HCV/HGV coinfection (19% vs 28%). Severity of liver disease as determined by alanine aminotransferase levels, histology and hepatitis C virus viremia was not significantly different in patients with hepatitis C virus or HCV/HGV coinfection. Sequence analysis of the helicase region revealed that our isolates all belonged to the hepatitis G virus and not to the GBV-C like genotype. No amino acid exchanges during the observation period of up to 48 months were observed, indicating that this region is highly conserved. CONCLUSIONS: The responsiveness of hepatitis G virus to interferon alpha in chronic HCV/HGV coinfected patients is similar to that observed in chronic hepatitis C. Hepatitis G virus coinfection seems not to interfere with the efficacy of interferon alpha treatment in patients with chronic hepatitis C.     

Superoxide dismutase in patients with chronic hepatitis C virus infection

It has been reported that hepatitis C virus (HCV) may cause oxidative stress in infected cells. Patients with chronic hepatitis C exhibit an increased production of tumor necrosis factor-alpha (TNF alpha), a cytokine that can produce oxidative stress by stimulating the generation of reactive oxygen species (ROS). Cell defense against ROS includes overexpression of Mn-superoxide dismutase (SOD), an inducible mitochondrial enzyme. To investigate cell defense against oxidative stress in HCV infection, we analyzed Mn-SOD mRNA in liver and in peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis C. Mn-SOD expression in PBMC was significantly increased in patients with HCV infection. Patients with sustained virological and biochemical response after therapy showed significantly lower Mn-SOD than patients with positive viremia. By contrast, Mn-SOD expression was not enhanced in the liver of patients with chronic hepatitis C. The values of Mn-SOD mRNA did not correlate with TNF alpha mRNA expression, viral load, or liver disease activity. Our results indicate that in HCV infection an induction of Mn-SOD was present in PBMC but absent in the liver, suggesting that this organ could be less protected against oxidative damage. Oxidative stress could participate in the pathogenesis of HCV infection.     

Cellular immunity to hepatitis C virus core protein and the response to interferon in patients with chronic hepatitis C

To investigate the involvement of T-cell response against hepatitis C virus (HCV) antigens in viral clearance after interferon therapy, we measured interleukin-2 (IL-2) production by peripheral mononuclear cells in response to HCV core in patients with chronic hepatitis C. In a cohort of 43 patients, we investigated the frequency of circulating core-specific T-helper (Th) cell precursors by the limiting-dilution assay, and in a second cohort of 60 patients, we analyzed the response to specific core epitopes using 52 synthetic 15-mer overlapping peptides. We observed that the frequency of core-specific Th cell precursors was significantly higher in patients with sustained biochemical and virological response (SR) after interferon (IFN) therapy (median, 1/55,736) than in untreated patients (1/274,023) or that in patients who remained viremic after completion of the treatment-nonresponders (NR) plus transient responders (TR) (1/1,909,972). Patients who failed to respond to IFN (NR) and those who relapsed after IFN discontinuation (TR) had a similarly low number of precursors. The number of core peptides recognized by SR, TR, NR, UT, and healthy controls was 8.2 +/- 1.5, 6.5 +/- 1.2, 2.0 +/- 0.5, 2.7 +/- 0.9, and 0.3 +/- 0.2, respectively. In SR, the intensity of the proliferative response to core peptides as estimated by the summation of stimulation indexes (sigmaSI) was significantly higher than in NR and than in UT, but not different from that of TR. Our results indicate that both expansion of HCV-specific Th cell precursors and Th cell recognition of multiple core epitopes seem to be important in the elimination of HCV after IFN therapy.     

High frequency of antibodies to Hantaan virus and hepatitis C virus in chronic haemodialysis patients. Coincidence or cross-reaction?

Forty-eight patients with proven hyperparathyroidism underwent parathyroidectomy. All patients were post-operatively normocalcaemic and free of symptoms due to their pre-operative hypercalcaemic state. However, 20 (42%) post-operative patients still had increased serum PTH and low serum phosphate levels.     

Prevalence of antibodies against hepatitis C virus in a sample of homosexual males

BACKGROUND: The finding of an important proportion of cases of hepatitis C without previous contact with blood or hemoderivates has led to suspect that there may be other routes of transmission among which sexual transmission may be found. METHODS: The presence of antibodies against the hepatitis C virus (anti-HCV) and the association of this infection with certain epidemiologic parameters and sexual practice was determined in 184 homosexual males with no other risk factors for virasis of intravenous transmission. Moreover, the prevalence of anti-HCV was evaluated in 210 voluntary blood donors. Every homosexual was surveyed on sexual practice and the first serum sample available of each of these patients was analyzed for anti-HVC and anti-HIV-1. RESULTS: Twenty-two homosexual (12%) were anti-HCV positive while only one (0.5%) of the control was positive for this marker (p < 0.0001). Thirty-six cases (19%) were anti-HIV positive (none of the controls). No statistical association was found between both serologic markers or between the presence of anti-HCV and the epidemiologic parameters evaluated. CONCLUSIONS: Homosexuals constitute a risk group for hepatitis C virus infection although the sexual route is probably not effective for transmission of this entity.     

Prevalence of serological markers of autoimmunity in hemodialysis patients with hepatitis C virus

Pulmonary arteriovenous malformation can occur in up to 25% of patients after a classic Glenn shunt. Although unproven, exclusion of hepatic venous blood from the lungs has been proposed as a possible cause. We present a patient born with anomalous hepatic venous drainage into the left atrium with an intact atrial septum in whom pulmonary arteriovenous malformation developed in childhood. This was reversed after diversion of the hepatic venous drainage to the right atrium, supporting exclusion of hepatic venous flow as the cause of pulmonary arteriovenous malformation. The association with the hepatopulmonary syndrome is discussed.     

Liver histology in chronic hemodialysis patients infected with hepatitis C virus

To investigate the influence of genetic and/or environmental factors in the development and shaping of the human peripheral T cell repertoire the authors studied the T-cell receptor (TCR) V beta usage in 10 adult monozygous (Mz) and nine dizygous (Dz) twin pairs living in a Plasmodium falciparum endemic area in West Africa. The TCR repertoire was determined using a small panel of anti-V beta specific monoclonal antibodies (MoAbs) using conventional immunofluorescence assays. The results revealed that the V beta repertoire was similar to that recently described for a Caucasian population using a similar panel of antibodies. The frequencies of particular V beta genes tested were influenced neither by anti-malarial antibody titres nor by parasite densities, indicating that the P. falciparum parasite is not a dominating factor in determining the peripheral T cell repertoire. All donors were human leucocyte antigen (HLA) class I and II typed; no association was found between the expression of any V beta genes and MHC haplotype. The V beta usage was more concordant within the Mz than within the Dz pairs. For a group comprising four HLA class II identical individuals, the average within-pair difference was significantly greater than for the whole Mz group, but similar to that seen for the total Dz group. Thus, the data suggest that genetic, rather than environmental, factors have a profound effect on the shaping of the human circulating T cell repertoire and that the major genetic factors are encoded by non-HLA class II genes.     

Prevalence of hepatitis B and C virus infections among haemodialysis patients in Pune (western India)

Vascular injuries may occur as complications of elbow dislocation and usually involve the brachial artery. A case report is presented in which only the radial artery was compromised as a result of the dislocation.     

Effect of immunosuppression on composition of quasispecies population of hepatitis C virus in patients with chronic hepatitis C coinfected with human immunodeficiency virus

BACKGROUND/AIMS: To study the effects of the immunosuppression caused by the reduction of CD4 activity on the composition of hepatitis C virus (HCV) populations, we analyzed the number of HCV quasispecies clones and the nucleotide diversity of the hypervariable region 1 (HVR1) of HCV in 37 patients with hemophilia with persistent HCV infection, with or without human immunodeficiency virus (HIV). METHODS: The numbers of HCV quasispecies clones were measured by fluorescence single-strand conformation polymorphism analysis. Direct sequencing was used to analyze the degree of diversity of HVR1. We compared these values according to coinfection with HIV, and CD4 counts of patients. RESULTS: There were no differences in either the number of HCV clones or the diversity between patients with and without HIV coinfection. In HIV coinfected patients the diversity decreased in association with the decrease in CD4 count while the number of HCV clones did not. The diversity of HVR1 was 3.64 +/- 5.03% in patients with a CD4 count < 50/microliters and 14.92 +/- 6.03% in patients with a CD4 count > or = 50/microliters; it was significantly lower in the former (p = 0.0002). CONCLUSIONS: A severe reduction in the CD4 count, which is considered to cause a decline in the activity of helper T-lymphocytes, induced changes in the composition of HCV populations; one or a few quasispecies clones are predominant in the HCV population in the serum of individual patients.     

Negative strand of hepatitis C virus RNA in the liver of patients with chronic hepatitis C after interferon treatment

In patients receiving interferon therapy for chronic hepatitis C, serum hepatitis C virus (HCV) RNA often reverts from an undetectable to a detectable form after completion of treatment. Detection of the negative strand of HCV-RNA in liver tissue is regarded as an index of viral proliferation. Therefore, we investigated changes in the hepatic negative-strand HCV-RNA following interferon therapy to determine whether this parameter could predict the long-term response to treatment. The subjects of this study were 27 patients with chronic active hepatitis C. Serum positive-strand and hepatic tissue negative-strand HCV-RNA were detected using polymerase chain reaction. At the completion of interferon treatment, serum HCV-RNA was not detected in 21 patients. One year following treatment it remained undetectable in 14 of these patients but it had reverted to a detectable form in seven. The 14 patients in whom hepatic negative-strand RNA was not detected between 2 weeks and 12 months after treatment, had not relapsed after another year. In the 13 remaining patients, negative-strand RNA was found in liver tissue and serum RNA either reverted to a detectable form or remained detectable throughout. From these findings, we conclude that the detection of negative-strand HCV-RNA in liver tissue 2 weeks after the completion of interferon therapy is useful for predicting the long-term effect of therapy.