S. Baracetti

Interferon versus steroids in patients with hepatitis C virus-associated cryoglobulinaemic glomerulonephritis

BACKGROUND/AIMS The association between mixed cryoglobulinaemia, cryoglobulinaemic glomerulonephritis, and chronic hepatitis C virus infection has recently been described. The renal disease had usually been treated with immunosuppressive therapy, but, given the presence of viral infection, this therapy is no longer recommended. In this study, we compare steroid vs interferon therapy in a group of patients affected by hepatitis C virus-positive cryoglobulinaemic glomerulonephritis in the stationary phase. PATIENTS/METHODS The diagnosis of cryoglobulinaemic glomerulonephritis was made bearing in mind standard criteria. Patients were randomly assigned to 2 groups receiving oral prednisone 0.2 mg/kg/die for 6 months (6 patients, group A) or lymphoblastoid interferon 3 MU, three times a week for 6 months [7 patients, group B). Hepatitis C virus-RNA was determined by reverse transcription-polymerase chain reaction and hepatitis C virus genotype according to Okamoto. Hepatitis C virus-RNA quantitation was performed by competitive polymerase chain reaction. RESULTS; The 2 groups were comparable in terms of age and severity of kidney failure. All genotypes of hepatitis C virus were found with a prevalence of Type 1b. In group A, 4 patients showed a partial response; in group B, 1 patient achieved complete remission, 4 a partial response, 2 patients in both groups showed no response. At the end of the treatment, all patients in both groups relapsed. Only 1 patient in group B became hepatitis C virus-RNA negative, and recovered from cryoglobulinaemic glomerulonephritis. CONCLUSIONS Interferon seems to be an effective drug in the treatment of cryoglobulinaemic glomerulonephritis, but dosage and length of treatment still need to be addressed by large multicentre studies.

Hepatitis C virus risk: a hepatitis C virus related syndrome

Abstract. Mazzaro C, Panarello G, Tesio F, Santini G, Crovatto M, Mazzi G, Zorat F, Tulissi P, Pussini E, Baracetti S, Campanacci L, Pozzato G (Pordenone General Hospital, Pordenone; University of Trieste, School of Medicine, Trieste, Italy). Hepatitis C virus risk: a hepatitis C virus‐related syndrome. J Intern Med 2000 247: 535–545.

Ethnic difference in the prevalence of monoclonal B-cell proliferation in patients affected by hepatitis C virus chronic liver disease.

BACKGROUND/AIM In previous studies we demonstrated that all patients affected by HCV-positive type II mixed cryoglobulinaemia have a monoclonal B-cell population in peripheral blood mononuclear cells, and that a large fraction of HCV-infected patients develop a monoclonal B-cell expansion, even in the absence of dosable serum cryoglobulins. However, the prevalence of Type II mixed cryoglobulinaemia in HCV-infected individuals seems to be high in Italy, whereas it is very low in Japan. This study was performed to investigate whether there are ethnic differences in the prevalence of asymptomatic HCV-associated monoclonal B-cell expansions. METHODS Forty-four Japanese patients affected by HCV-positive chronic liver disease (two healthy carriers, 31 chronic hepatitis and 11 cirrhosis) were compared with a group of 60 Italian patients (one healthy carrier, 49 chronic hepatitis, and 10 cirrhosis) without dosable levels of cryoglobulins. The monoclonality of peripheral blood mononuclear cells was investigated by RT/PCR analysis of Immunoglobulin gene rearrangements. Liver function tests, rheumatoid factor, cryocrit level, anti-HCV antibodies, HCV-RNA, and HCV genotype were performed according to standard methodology. RESULTS A B-cell monoclonal population was found in 26% of Italian patients, whereas all Japanese patients were negative. No correlation was found between B-cell monoclonality and severity of liver disease, length or source of the infection, HCV genotype, sex, clinical and biochemical parameters. CONCLUSIONS This study indicates that a monoclonal B-cell proliferation in peripheral blood mononuclear cells is common in HCV infection, but only in Italy, whereas it is absent in Japan. This explains the very low prevalence of Type II mixed cryoglobulinaemia in HCV-positive Japanese subjects, and suggests that HCV is able to determine a B-cell expansion only in the presence of, presently undetermined, host factors.

Haemochromatosis gene mutations in a clustered Italian population: Evidence of high prevalence in people of Celtic ancestry

Hereditary haemochromatosis is an inherited disorder characterised by an excessive iron absorption from the diet and is associated with several HFE gene mutations. One hypothesis is that these genetic mutations originated in the Celtic populations. The aim of this study is to determine the frequency of HFE gene mutations in a clustered Italian population of Celtic ancestry (Cimbri, Asiago plateau). One hundred and forty-nine consecutive unrelated blood donors (31 females and 118 males) were enrolled in this study. A family investigation was performed in each case to identify the ethnic origin of the individuals. The analysis of HFE gene mutations was performed by PCR amplification followed by digestion with RsaI and DpnII restriction enzymes. At least one HFE gene mutation was identified in 49 individuals (32.9%) of the studied population. The allele frequencies of the C282Y and H63D were respectively 0.037 and 0.144. When we considered only the 103 individuals with relatives born in Asiago, the prevalence of the HFE mutations rose from 32.9 to 39.8%; the allele frequencies of the C282Y and H63D were respectively 0.048 and 0.174. The mean serum iron and ferritin levels were significantly higher in individuals with the HFE mutations than in normal cases. This study indicates that the prevalence of the HFE gene mutations is surprisingly high in Italians with Celtic ancestry. This could suggest the need to perform large mass studies in selected areas of the country to detect the affected patients and prevent the disease in homozygous individuals.

Effects of interferon therapy on fibrosis serum markers in HCV-positive chronic liver disease.

Objective To evaluate serum levels of prolyl-hydroxylase and helical domain of Type IV° collagen, markers of hepatic fibrogenesis, in patients with HCV-positive chronic liver disease and the effects of Interferon therapy on these markers. Design Prolyl-hydroxylase and Type IV collagen were determined before therapy and each month during the treatment and follow-up. Methods Fifty-seven HCV-positive patients were studied. All the subjects received α2a recombinant interferon, 6 MU subcutaneously three times a week for 4 weeks, followed by 3 MU thrice weekly for 5 months. After cessation of treatment, each patient was followed for 12 months. Prolyl-hydroxylase and helical domain of Type IV° collagen were measured by using immunoenzymatic methods. HCV-RNA and HCV genotype were determined according to the method of Okamoto. Results In the patients prolyl-hydroxylase (39.8 ± 8.9 ng/ml) was not different from controls (39.1 ± 5.9 ng/ml). On the contrary, the patients showed a mean Type IV collagen (133.6 ± 93.3 ng/ml) significantly (P< 0.01) higher than controls (100.2 ± 10.5 ng/ml). A good relationship between the degree of liver fibrosis and the Type IV° collagen serum level was found (r = 0.68; P < 0.005). In both responders and non-responders the Type IV collagen levels decreased during interferon therapy. During the follow-up, in responders the Type IV° collagen did not show modifications, while in non-responders/relapsers it returned rapidly to the pretreatment levels (139.1 ± 100.7 ng/ml). Conclusion In HCV-positive chronic liver disease, prolyl-hydroxylase is not a good marker of hepatic fibrosis, while Type IV collagen is a useful tool for evaluating fibrogenic activity. Interferon seems to be able to reduce the liver fibrosis even without the inhibition of viral replication and independently from liver necrosis.

GBV-C/HGV and HCV infection in mixed cryoglobulinaemia

Recently, a new, suspected hepatotropic virus has been identified. Named GBV‐C/HGV, this virus shares with the hepatitis C virus (HCV) routes of transmission and molecular organization. Indeed, a proportion of HCV‐infected patients (10–25%) are also carriers of GBV‐C/HGV. Since mixed cryoglobulinaemia (MC) is closely associated with HCV infection, the aim of this study was to determine the prevalence of GBV‐C/HGV infection in MC patients, and to investigate whether the double infection influenced the clinical and/or laboratory aspects of the disease.