Hepatitis C Virus Type 1b (II) Infection in France and Italy

Nousbaum, Jean-Baptiste; Pol, Stanislas; Nalpas, Bertrand; Landais, Paul; Berthelot, Pièrre; Bréchot, Christian

doi:10.7326/0003-4819-122-3-199502010-00001

Cited by 462 publications

(254 citation statements)

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“…Patients with HCV genotype non-1 had better responses compared with patients with HCV genotype 1, across all treatment arms, as has been observed in other trials of IFN-based therapy. 1,2,6,[9][10][11] This study demonstrated that PEG(40kd) IFN ␣-2a is superior to IFN ␣-2a in the treatment of patients with CHC. The 180-g PEG(40kd) IFN ␣-2a dose was associated with the highest sustained virological and biochemical responses (36% and 38%, respectively).…”

Section: Discussionmentioning

confidence: 97%

Efficacy and Safety of Pegylated (40–Kd) Interferon α–2A Compared With Interferon α–2A in Noncirrhotic Patients With Chronic Hepatitis C

et al. 2001

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Administration of interferon (IFN) 3 times weekly in patientsInterferon ␣ (IFN) is an essential component of therapy for patients with chronic hepatitis C (CHC) virus infection; however, 3 MIU IFN ␣-2b administered 3 times weekly for 48 weeks produces low sustained virological responses (13%-19%). 1,2 Previously, attempts at improving responses to IFN ␣-n3 monotherapy through daily administration met with limited success, because a trend for improved response was only observed in patients with hepatitis C virus (HCV) genotype non-1 infections. 3 More recently, the addition of ribavirin to the standard IFN regimen has resulted in improved sustained virologic responses (38%-43%), but at the cost of additional toxicity. 1,2 IFN has a half-life of approximately 8 hours, and, consequently, a 3-times-weekly dosing schedule may be insufficient to maintain adequate serum concentrations. 4 Pegylated interferon ␣-2a (PEG[40kd] IFN ␣-2a) was developed in an attempt to improve the pharmacological profile of IFN ␣-2a. Covalent attachment of a branched 40-kd polyethylene glycol moiety to IFN ␣-2a results in more sustained absorption (time to peak plasma concentration increased Ͼ7-fold), reduced clearance (10-fold), and a smaller volume of distribution (4-fold), thereby permitting once-weekly dosing. 5,6 This study evaluated the safety and efficacy of 4 doses of once-weekly PEG(40kd) IFN ␣-2a administered for 48 weeks compared with 3 MIU IFN ␣-2a 3 times weekly in the treatment of patients with CHC. The primary intention of the study was to establish the most appropriate dose of PEG(40kd) IFN ␣-2a for subsequent, larger trials. MATERIALS AND METHODSPatient Selection. The target population comprised patients with CHC but without associated bridging fibrosis or cirrhosis (fibrosis score 3 and 4) 7 on pretreatment liver biopsies, who had not previously been treated with IFN therapy. The definition of CHC required documentation of persistently abnormal serum alanine aminotransferase (ALT) activity (2 occasions Ն14 days apart), a positive anti-HCV antibody (anti-HCV-EIA version 2), a pretreatment liver biopsy obtained within 12 months before study treatment consistent with chronic hepatitis (as determined by a central pathologist), and detectable pretreatment HCV RNA by a polymerase chain reaction assay (AMPLICOR HCV MONITOR™ version 1.0, Roche Diagnostics, Branchburg, NJ; lower limit of quantitation of 2,000 copies/mL) within 35 days before the first dose of study medication.Patients were excluded during screening for any of the following reasons: liver disease from causes other than CHC; white blood cell count Ͻ1,500/mm 3 ; platelet count Ͻ90,000/mm 3 ; serum creatinine Abbreviations: IFN, interferon alfa; CHC, chronic hepatitis C; PEG(40kd) IFN ␣-2a, 40-kd pegylated interferon ␣-2a; MIU, million international units; ALT, alanine aminotransferase; HCV, hepatitis C virus; SRB, Safety Review Board; HAI, histological activity index.From the

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Section: Discussionmentioning

confidence: 97%

Efficacy and Safety of Pegylated (40–Kd) Interferon α–2A Compared With Interferon α–2A in Noncirrhotic Patients With Chronic Hepatitis C

et al. 2001

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“…[25][26][27][28] In Italy, type 1b is the most common, accounting for more than 60% of infected cases. [29][30][31] In our control population (healthy blood donors and patients with chronic liver disease, CLD), genotype 1b was present in 64% of cases, with each of the other genotypes being present in less than 10% of cases. The clinicopathologic correlation of specific genoptypes is currently the subject of active investigation.…”

Section: Discussionmentioning

confidence: 99%

The genotype of the hepatitis C virus in patients with HCV-related B cell non-Hodgkin’s lymphoma

et al. 1997

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Increasing evidence suggests that the hepatitis C virus (HCV) might be involved in the pathogenesis of B cell non-Hodgkin's lymphomas (NHL). Since several HCV genotypes are currently identifiable and might be involved in the pathogenesis of different diseases (with different severity and responsiveness to therapy), the aim of our study was to assess the prevalence of viral genotypes in a group of patients with HCV-related NHL. Among 470 consecutive patients, 42 HCV Ab-positive cases were identified. HCV RNA could be detected by reverse transcriptase-polymerase chain reaction and genotyping performed in 31 of these cases. As compared to our control group (211 healthy blood donors and patients with chronic liver disease), a striking high prevalence of genotype 2ac was detected among B cell NHL (48.4 vs 9.0%), with a relative risk of infection of 5.37 (P Ͻ 0.0001). No major differences were observed in the distribution of NHL histotypes and in the clinical features among patients with genotype 1b (the other most frequent genotype) or 2ac, a part from a trend towards a higher percentage of liver disease and a lower likelihood of response to interferon for patients with genotype 1b. The same high prevalence of genotype 2ac has been recently reported in patients with mixed cryoglobulinemia (MC), monoclonal gammopathies, B cell NHL complicating MC and autoimmune hepatitis. All these data taken together suggest that genotype 2ac might be involved in the pathogenesis of lymphoproliferative and autoimmune disorders.

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“…It remains to be seen whether or not such clinically important features of genotype II/lb are shared by other genotypes in genetic group 1. Some groups of investigators report differences in the response to interferon between patients infected with HCV genotype I/la and those infected with II/lb (Qu et al, 1994;Nousbaum et al, 1995), while others do not (Mahaney et al, 1994). Additional clinical and therapeutic trials are required to settle this.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus variants from Jakarta, Indonesia classifiable into novel genotypes in the second (2e and 2f), tenth (10a) and eleventh (11a) genetic groups

Tokita

Okamoto

Iizuka

et al. 1996

Journal of General Virology

142

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Hepatitis C virus (HCV) isolates from 126 hepatitis patients in Jakarta, Indonesia were genotyped by PCR with genotype-specific primers deduced from the HCV core gene. Fifty-five isolates (44%) were classified as genotype II/lb, 15 (12 %) as lc, 33 (26 %) as III/2a, and 1 (1%) as V/3a, while the remaining 22 (17 %) were not classifiable into any of the five common genotypes (I/la, II/lb, III/2a, IV/2b and V/3a) or lc. Sequences of a part of the NSSb region [1093 bp (nucleotides 8279-9371)] of the 22 isolates of unclassifiable genotype were subjected to pair-wise comparison and phylogenetic analysis along with those of 62 isolates of 25 genotypes in nine genetic groups. Seven of the isolates were classified into 2e and two into 2f, representing novel genotypes in genetic group 2, while ten and three were classified into two new genetic groups, l0 and 11, respectively, and their genotypes were provisionally designated 10a and l la. The isolates of genotype 10a (JK049) and 1 la (JK046) were sequenced in full. Comparison of 24 HCV genomes including those of JK049 and JK046, over the entire genome and subgenomic regions, supported the classification of HCV into 11 genetic groups.

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Hepatitis C Virus Type 1b (II) Infection in France and Italy

Cited by 462 publications

References 0 publications

Efficacy and Safety of Pegylated (40–Kd) Interferon α–2A Compared With Interferon α–2A in Noncirrhotic Patients With Chronic Hepatitis C

Efficacy and Safety of Pegylated (40–Kd) Interferon α–2A Compared With Interferon α–2A in Noncirrhotic Patients With Chronic Hepatitis C

The genotype of the hepatitis C virus in patients with HCV-related B cell non-Hodgkin’s lymphoma

Hepatitis C virus variants from Jakarta, Indonesia classifiable into novel genotypes in the second (2e and 2f), tenth (10a) and eleventh (11a) genetic groups

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