GB virus C infection in patients with type II mixed cryoglobulinemia.

BACKGROUND: Hepatitis C virus (HCV) infection is present in most but not all patients with type II mixed cryoglobulinemia. OBJECTIVE: To investigate the role of GB virus C (GBV-C) in type II mixed cryoglobulinemia. DESIGN: Retrospective study of serum and cryoprecipitate samples. SETTING: Tertiary care hospital in Bergamo, Italy. PATIENTS: 58 cryoglobulinemic patients, 35 of whom were treated with interferon-alpha. MEASUREMENTS: GB virus C RNA was determined by a reverse-transcription polymerase chain reaction assay done by using primers derived from the conserved GBV-C helicase region. RESULTS: GB virus C RNA was detected in serum specimens from 23 of 58 cryoglobulinemic patients (40% [95% CI, 27% to 53%]) and 1 of 145 healthy blood donors (0.7%) (P < 0.001). Twenty of the 23 patients with GBV-C RNA were simultaneously infected with HCV. Unlike antibodies to HCV and HCV RNA, GBV-C RNA did not concentrate in cryoprecipitate in patients co-infected with GBV-C and HCV. Furthermore, the therapeutic effectiveness of interferon-alpha in patients with coinfection was related to the disappearance of HCV RNA but not GBV-C RNA from serum. None of 3 patients with GBV-C infection alone had detectable GBV-C RNA in cryoprecipitate. CONCLUSIONS: Infection with GBV-C, usually associated with HCV, is common in patients with type II mixed cryoglobulinemia but is unlikely to have a primary role in this disease.

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.

Fluctuations in viremia, aminotransferases and IgM antibody to hepatitis B core antigen in chronic hepatitis B patients with disease exacerbations.

We studied the relationships between the serum levels of viremia, aminotransferases and IgM anti-HBc, measured by monthly quantitative assays, in 52 untreated chronic hepatitis B patients (41 anti-HBe+, 11 HBeAg+) followed up for 12-20 months. Forty hepatitis exacerbations were observed in 17/41 anti-HBe+ (41.5%) and in 6/11 HBeAg+ patients (54.5%) (p = NS); all but one were clinically asymptomatic. We analyzed the fluctuations in the serum levels of the three parameters before, during and after the hepatitis exacerbations and found this chronological sequence of events in 96.2% of them: HBV-DNA increase-->ALT flare-->IgM anti-HBc increase. These results suggest that both antiviral immune reactions and ALT flares were triggered by quantitative variations in viremia. HBV-DNA baseline levels before flares were lower in anti-HBe+ (3.9 +/- 1.2 pg/ml) than in HBeAg+ patients (35.3 +/- 5.4 pg/ml) (p < 0.0001) and there was an inverse correlation between basal values and viremia level increases at the time of disease exacerbations (p < 0.001). This suggests that for a hepatitis exacerbation to occur, low basal viremia needed to increase markedly, while moderate increases in HBV-DNA serum levels were sufficient to trigger ALT flares in patients with elevated basal viremia. In conclusion, asymptomatic hepatitis B exacerbations are frequent in the natural history of chronic HBV infection, and monthly monitoring of HBV-DNA, ALT and IgM anti-HBc appears to be a suitable method to evaluate their frequencies and entities. This method can be a helpful guide for clinical and therapeutic decision-making in the single patient with chronic hepatitis B.

Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus.

BACKGROUND: Essential mixed cryoglobulinemia is frequently associated with hepatitis C virus (HCV) infection. A beneficial effect of interferon alfa therapy has been reported, but we do not know whether the antiviral activity of the drug affects the clinical and biochemical manifestations of disease. METHODS: In a prospective randomized, controlled trial, we studied 53 patients with HCV-associated type II cryoglobulinemia. A group of 27 patients received recombinant interferon alfa-2a thrice weekly at a dose of 1.5 million units for a week and then 3 million units thrice weekly for the following 23 weeks. The 26 control patients did not receive anything apart from previously prescribed treatments. All patients were then followed for an additional 24 to 48 weeks. RESULTS: Interferon was usually well tolerated, but it was permanently discontinued in two patients because of atrial fibrillation and depression. Two of the 26 patients in the control group were lost to follow-up. After the treatment period, serum HCV RNA was undetectable in 15 of the remaining 25 patients who received interferon alfa-2a, but in none of the controls. In comparison with the control group, the 15 patients with undetectable levels of HCV RNA in serum had significant improvement in cutaneous vasculitis (P = 0.04) and significant decreases in serum levels of anti-HCV-antibody activity (P = 0.007), cryoglobulins (P = 0.002), IgM (P = 0.002), rheumatoid factor (P = 0.001), and creatinine (P = 0.006). After treatment with interferon alfa-2a was discontinued, viremia and cryoglobulinemia recurred in all 15 HCV RNA-negative patients. On resumption of treatment, three of four patients had a virologic, clinical, and biochemical response. CONCLUSIONS: The therapeutic efficacy of interferon alfa-2a in HCV-associated cryoglobulinemia is closely related to its antiviral activity, thus supporting the idea that HCV infection may be a cause of this disease.

Role of IgM antibody to hepatitis B core antigen in the diagnosis of hepatitis B exacerbations.

IgM anti-HBc levels were measured by the IMx Core-M Abbott assay in 939 serum samples in order to define a specific and sensitive cut-off value for diagnosis of chronic hepatitis B. The sera used were obtained from 52 chronic HBV patients and 10 HBV carriers with HCV or HDV co-infections and 155 asymptomatic subjects without evidence of liver disease. A Youden index value of 95.4% with 98% sensitivity and 97.4% specificity was obtained for an IMx Index value of 0.204 as cut-off. A one-year follow-up study with monthly tests has shown that quantitative analysis of IgM anti-HBc can serve as a noninvasive tool for monitoring HBV infection, and provides an accurate diagnosis of hepatitis B exacerbations. Significant elevations of IgM anti-HBc levels were associated with hepatitis B exacerbations in 96.2% of the cases but with none of the ALT flare-ups observed in HCV or HDV infected individuals. These results suggest that quantitative analysis of IgM anti-HBc provides the highest degree of confidence in definition of spontaneous and therapy-induced exacerbations or remissions of hepatitis B.

Peripheral T-cell subsets in patients with alopecia areata in different clinical phases.

An analysis of T-cell subpopulations was carried out in the peripheral blood of 21 subjects with alopecia areata (AA) of the scalp in various phases of its evolution and in 18 healthy control subjects by means of different monoclonal antibodies of OKT series (T3, T4, T8, T11). Patients with AA in active phase showed a significant reduction of OKT 8+ cells (p less than 0.002) and a significant increase of OKT 4+ cells (p less than 0.002) versus controls. On the contrary, patients with regrowing hair showed a significant increase of circulating OKT 8+ cells compared with controls (p less than 0.002). No abnormality in the distribution of T-cell subsets in patients with AA in stable phase has been observed.

Familial alopecia areata--genetic susceptibility or coincidence?

Three generations of a not consanguineous Italian family and 40 subjects suffering from alopecia areata (AA) and residing in Northern Italy were studied. There were 321 healthy control subjects of both sexes. Six family members from three generations were affected with alopecia universalis. The subjects were HLA-phenotyped using different HLA-A, B and C antigen specificities. No significant association was found between HLA-A, B and C antigens and AA patients at the population level. Segregation analysis showed that affected members shared a common haplotype, HLA-Aw32, B18,-.

[HBV serologic markers in the chronic alcoholism (author's transl)]. / I marcatori sierici dell'HBV nell'etilismo cronico.

The prevalence of serum markers, HBsAg, anti-HBsAg, HBcAg and anti-HBeAg in a group of subjects affected by chronic alcoholism with fatty liver or with cirrhotic stages is reported. An incidence of chronic HBsAg carriers, similar to that found in healthy subjects, was noticed, while an elevated incidence of other serological markers of previous contact with HBV were found. The Authors discuss the significance of this report, on the basis of a greater possibility of contact with HBV, for social-economic situations of those patients. The etiopathogenetic role of HBV in the cirrhotic evolution of alcoholic liver diseases was excluded.