Characteristics of chronic hepatitis C in patients infected by human immunodeficiency virus

BACKGROUND: After recently published own investigations on subjective and objective cyclorotatory changes following inferior oblique recession for inferior oblique overaction, it was our aim to determine and to compare subjective and objective cyclorotatory changes following a modified Harada-Ito procedure for acquired trochlear palsy. PATIENTS AND METHODS: Eight patients suffering from acquired uni-(n = 3) or bilateral (n = 5) trochlear palsy were investigated before surgery and 1 day, 3 days and 4 months after surgery. Subjective cyclodeviation was assessed by Harms' tangent scale. Objective cycloposition was measured by means of fundus cyclometry using an infrared Scanning Laser Ophthalmoscope. RESULTS: The immediate postoperative incyclorotatory effect was 12 degrees in the unilateral group and 18 degrees in the bilateral group. Subjective and objective changes were nearly equal in both groups, with a subjective over-effect of 1 degree. After two days of binocular stimulation a marked regression of the surgical effect was found which still increased after four months. The long term incyclorotatory effect was subjectively and objectively nearly equal in the unilateral group which showed a relaps of subjective excyclodeviation of 5 degrees: in the bilateral group, the subjective effect was more pronounced than the objective effect, the immediate postoperative over-effect being disappeared. CONCLUSIONS: In contrast to our results concerning inferior oblique muscle recession for strabismus sursoadductorius, subjective and objective cyclorotatory changes did not differ grossly following a modified Harada-Ito procedure. Subjective and objective short and long term regression was confirmed which objectively exceeded the amount of over-correction. As the underlying cause mechanical and sensory mechanisms are discussed.     

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.     

Interferon treatment of chronic hepatitis C in human immunodeficiency virus infected patients]

There are no reports to date of entire gene sequences coding for chitinolytic enzymes from entomopathogenic fungi, even though these enzymes act synergistically with proteolytic enzymes to solubilize insect cuticle during the key step of host penetration, having considerable importance in the biological control of some insect pests. This paper reports the complete nucleotide sequence and analysis of the chromosomal and full-length cDNA copies of the regulated gene (chit1) coding one of the chitinases produced by the biocontrol agent Metarhizium anisopliae. Degenerated primers, encompassing conserved regions of other fungal chitinases, were used to amplify a 650-bp DNA fragment, which was used to isolate genomic and cDNA clones from M. anisopliae. Albeit at least two different chitinases are characterized in this fungus, only one chit gene was isolated. The chit1 gene is interrupted by three short typical fungal introns and has a 1,521-bp ORF, which encodes a protein of 423 amino acids with a stretch of 35 amino acid residues displaying characteristics of signal peptide. The deduced sequence of the mature protein predicts a 42-kDa protein with pI of 5.8. Southern analysis of genomic DNA indicates a single copy of chit1 in the M. anisopliae genome.     

Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users

To assess the effect of human immunodeficiency virus (HIV) immunosuppression on ongoing hepatitis C virus (HCV) infection, CD4 lymphocyte counts and serum concentrations of HCV RNA, HIV RNA, and alanine aminotransferase (ALT) were evaluated among members of a cohort of injecting drug users (IDUs). With 100 participants randomly selected at various stages of HIV-related immunosuppression, serum HCV RNA concentrations increased with age (P = .007) and were higher in HIV-positive IDUs with 201-500 (P = .026) and 51-200 (P = .004) CD4 cells/mL than in HIV-negative participants. Among 27 HCV-infected IDUs who acquired HIV infection, serum HCV RNA concentrations varied between semiannual visits by a mean of 0.45 logs, increasing by 0.60 logs after HIV seroconversion (P < .0001), by 0.12 logs each subsequent year (P = .006), and by 0.36 logs per log increase in CD4 cells (P = .01). Serum ALT levels were similar between HIV-positive (40.1 IU/mL) and HIV-negative (45.4 IU/mL) patients (P > .10). While HIV infection and possibly HIV progression are associated with increased HCV RNA levels, other factors appear to affect biochemical and virologic markers of HCV infection in some dually infected persons.     

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.     

Body composition changes in patients with human immunodeficiency virus infection

Malnutrition characterized by weight loss and often extreme wasting generally develops when patients progress from infection with human immunodeficiency virus (HIV) to AIDS. There is evidence that before the development of AIDS, HIV-infected patients without weight loss show early signs of malnutrition, defined as an increase in the ratio of extracellular mass (ECM) to body cell mass (BCM). As part of a dietary intervention study, body composition measurement were obtained at baseline and after 6 wk in 18 patients with HIV infection and CD4 counts between 140 and 740 cells/mm3. Only one patient had a prior weight loss (3.7 kg); patients gained 2 pounds after 3 wk of dietary supplementation of 500 kcal daily. Bioelectrical impedance was used to measured body compartments. The average ECM/BCM ratio (0.77 +/- 0.13) was within the normal range (0.83 +/- 0.16) indicating the absence of malnutrition by this criterion. Most measurements of BCM (kg) approximated normal values, while several for BCM (kg) exceeded normal. BCM (kg) correlated poorly with the ECM/BCM ratio (r2 = 0.08; P = 0.11) in contrast to ECM (kg), which was well correlated (r2 = 0.82; P = 0.00). In addition, there was a significant correlation of body mass index (BMI) with the ECM/BCM ratio (r2 = 0.38; P = 0.00) and with ECM (r2 = 0.244; P = 0.003) indicating that overweight patients may be more likely to be considered malnourished than normal weight patients using this ratio. Without use of bioelectrical impedance, these subtle changes might be missed. Once significant weight loss has occurred coupled with decreases in BCM (kg), the ECM/BCM ratio may be more reflective of malnutrition. These conjectures will require prospective evaluation, but for now it seems reasonable to include bioelectrical impedance as a potentially useful tool in the evaluation of malnutrition in this population.     

Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis

Four patients with chronic hepatitis B infection and chronic active hepatitis were treated with human leukocyte interferon. Three of them had consistently elevated levels of circulating Dane-particle markers, including Dane-particle-associated DNA polymerase activity, hepatitis B core antigen and Dane-particle-associated DNA. Parenteral interferon administration at a dosage between 6.0 X 10(3) and 17 X 10(4) U per kilogram per day was associated with a rapid and reproducible fall in all Dane-particle markers in the three patients. The suppressive effect was transient when the interferon was given for 10 days or less but appeared to be more permanent when administration was prolonged for a month or more. In addition, long-term interferon therapy was associated with a marked fall in hepatitis B surface antigen in two of three patients and a disappearance of e antigen in two of two patients. Interferon may be useful in limiting carrier infectivity or eradicating chronic infection.     

Interactions between the human immunodeficiency virus and hepatitis C virus

INTRODUCTION: Prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected subjects is around 9%, varying according to the mode of contamination. Reciprocal interactions between the two viruses have to be evaluated. CURRENT KNOWLEDGE AND KEY POINTS: HCV infection is usually associated with chronic hepatitis and detectable viremia in HIV-infected patients. HIV infection enhances HCV replication, leading to more severe liver lesions and to a more rapid occurrence of cirrhosis. This underlines the need for both early diagnosis and therapy in order to avoid severe evolution of the liver disease. FUTURE PROSPECTS AND PROJECTS: Even though the rate of long-term responses to interferon alpha is low, improvement may be expected from combined therapies, especially with combination including ribavirin. The impact of both antiretroviral triple therapy and accompanying immune restoration on natural history and treatment of HCV infection has to be assessed, as the above mentioned consensual conclusions may be modified in a near future.     

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.     

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.     

Should patients with human immunodeficiency virus infection or chronic hepatitis donate blood for autologous use?

BACKGROUND: The purpose of this project is to formally evaluate the benefits and the risks of allowing patients with human immunodeficiency virus (HIV) infection or hepatitis to donate blood for autologous use. STUDY DESIGN AND METHODS: With data on the incidence of transfusion-transmitted hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV; administrative error; and health-care worker exposure, decision analysis was used to quantitate the benefits and risks of autologous blood transfusions versus those of transfusions of blood from allogeneic donors. RESULTS: Assuming the highest documented probability of transfusion-related infection, the days of life saved by allowing the transfusion of autologous blood to a 30-year-old noninfected or HBV-, HCV-, or HIV-infected patient are 92.52, 70.60, 0.95, and 5.69, respectively. Assuming the lowest documented probability of transfusion-related infection, the days of life saved decrease to 2.96, 2.26, 0.15, and 0.18, respectively. Avoidance of HCV accounts for over 90 percent of the days gained. The days of life lost by other noninfected patients through administrative error average 0.11 in the case of HIV and those lost by health care workers average 0.04, 0.18, and 0.07 in the case of HBV, HCV, and HIV, respectively. CONCLUSION: The benefit of autologous transfusions in patients infected with HBV, HCV, and HIV is significantly less than that in noninfected patients. The risks of this infected blood to other noninfected patients are significant only in the case of HIV-infected blood transfusions; however, there is a measurable risk to health-care workers should all infected blood be allowed into the blood supply.     

Differential sensitivity of hepatitis C virus quasispecies to interferon-alpha therapy

The quasispecies nature of hepatitis C virus was investigated in a patient with chronic hepatitis C virus infection who underwent interferon-alpha therapy. The hepatitis C virus E2/NS1 region was amplified and cloned, and multiple clones were sequenced before and after interferon-alpha therapy. The hepatitis C virus quasispecies can be grouped into three groups by phylogenetic tree analysis. Quasispecies from all the groups were present before interferon-alpha therapy. However, only group 3 remained after interferon-alpha therapy. In addition, only group 3 hepatitis C virus quasispecies were present during the early biochemical relapse. These data indicate that various groups of hepatitis C virus quasispecies may have different sensitivity to interferon-alpha.     

Persistent hepatitis C virus RNA replication in haemophiliacs: role of co-infection with human immunodeficiency virus

In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57 = 75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.     

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 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.     

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 antibodies to hepatitis C virus among family members of patients with chronic hepatitis C

In this study, 108 family members of 40 chronically HCV-infected patients (19 post-transfusion and 21 sporadic), and 45 families of 16 anti-HCV-negative index cases (control group) were tested for anti-HCV antibodies. Anti-HCV antibodies were found in 16 (14.8%) families of anti-HCV-positive index cases (15% males and 14.6% females; p = NS), with no difference between families of index cases with post-transfusion and those with sporadic HCV infection. Out of the 16 anti-HCV positive family members, 12 (75%) had clinical and/or serological evidence of chronic liver damage. None of the control group subjects were anti-HCV-positive (p < 0.01). The rate of anti-HCV positivity was 34.4% among spouses, 14.3% among siblings, 16.7% among cohabitants and 2.3% among children; anti-HCV antibodies were not detected among parents. We found a positive correlation between the prevalence of anti-HCV antibodies among families and the severity of the HCV-related chronic liver damage of the index cases (p < 0.00005). In addition, to confirm that HCV infection and HCV-related chronic hepatitis may be transmitted intrafamiliarly, our findings also indicate that horizontal, especially sexual contact, is a more important route of HCV infection than vertical/perinatal transmission. Finally, the risk of acquiring HCV infection among families appears to be the highest when index cases are suffering from severe HCV-related chronic hepatitis.     

Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus

The effect of a therapeutic dose of fluconazole on the disposition of zidovudine was evaluated in 12 men infected with human immunodeficiency virus. The study was designed as a randomized, two-period, two-treatment, crossover trial. On two occasions, 21 days apart, patients received either zidovudine alone or zidovudine (each, 200 mg every 8 h) and fluconazole (400 mg daily) for 7 days. Fluconazole coadministration decreased (P < .001) the apparent oral serum clearance of zidovudine by 43% and the apparent oral formation clearance to zidovudine glucuronide (GZDV) by 48%, resulting in increases (P < .002) in the area under the serum concentration time curve (74%), the maximum serum concentration (84%), and the terminal half-life (128%) of zidovudine. The molar ratio of GZDV to zidovudine recovered in urine was reduced by 34% with fluconazole (P < .001). These pharmacokinetic changes suggest that 400 mg of fluconazole inhibited the conversion of zidovudine to GZDV. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions.