Virological and biochemical long-term follow-up of patients with chronic hepatitis c treated with interferon

Castillo, Inmaculada; Bartolomé, Javier; Navas, Sonia; Gonzalez, Sara Sierra; Herrero, María Trinidad; Carréño, Vicente

doi:10.1002/hep.1840190604

Cited by 66 publications

(19 citation statements)

References 17 publications

(11 reference statements)

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“…Clearance of serum or Pl viral RNA at the end of treatment is not a useful parameter to predict a sustained response, although detection of serum HCV RNA at the end of treatment in CRs usually portends relapse. [14][15][16] Assessment of HCV RNA in liver biopsy specimens at the end of treatment appears to more accurately predict sustained response [36][37][38] ; however, liver biopsy after therapy is not a realistic management option because of the additional patient risk and expense.…”

Section: Discussionmentioning

confidence: 99%

Effect of interferon therapy on hepatitis C virus RNA in whole blood, plasma, and peripheral blood mononuclear cells

Schmidt¹,

Wu²,

Brashear³

et al. 1998

Hepatology

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Fifty-two patients with chronic hepatitis C virus (HCV)infection were treated with standard doses of interferon alfa-2b. During treatment, HCV RNA detection was studied in samples of whole blood (WB), plasma (Pl), and peripheral blood mononuclear cells (PBMCs). Individuals were classified as sustained responders (SRs), complete responders with relapse (CRs), partial responders (PRs), or nonresponders (NRs) according to normalization of serum alanine transaminase (ALT) during treatment and follow-up. Before treatment, 100% of WB samples and more than 95% of Pl and PBMC samples were positive for HCV RNA. During treatment, there was progressive clearance of HCV RNA from Pl and PBMCs in SRs and CRs, but CRs had significantly more positive WB samples during and following treatment (P Ͻ.0001). At 6 months, only 10% of CR patients were positive by Pl assay, but 50% were positive by WB assay (P Ͻ.01). In the PR group, all WB samples remained positive throughout treatment, although 25% to 40% of PBMC and Pl samples became negative for HCV RNA during the first 2 months of therapy (WB Ͼ Pl or PBMC; P Ͻ .001). However, at later times during treatment most Pl and PBMC samples in the PR group were positive. Samples from the NR group showed no clearance of HCV RNA from WB, Pl, or PBMC fractions. These data document the increased sensitivity of WB assays for detecting HCV RNA in the peripheral blood of patients during interferon therapy. Furthermore, our findings suggest that WB analysis of HCV RNA may be a useful parameter to monitor in determining the end point of interferon therapy.(HEPATOL-OGY 1998;28:1110-1116.)Hepatitis C virus (HCV) is a small, enveloped RNA virus of approximately 9,500 nucleotides that is responsible for more than 90% of parenterally transmitted cases of non-A, non-B hepatitis. 1-3 Infection with HCV usually results in chronic active hepatitis, which may progress to cirrhosis. Currently, end-stage liver disease resulting from chronic HCV infection is a major reason for referral of patients for orthotopic liver transplantation in the United States. 4,5 Interferon therapy is the only approved treatment for chronic hepatitis C. Approximately 50% of patients who are treated respond with normalization of serum aminotransferase levels, although more than half of these responders will relapse after discontinuation of the drug. Thus, approximately 20% of treated patients have a durable, sustained response. 6,7 Although the reasons responsible for relapse are unclear, variables such as length of treatment, HCV genotype, and histological evidence of inflammation and fibrosis at the start of therapy appear to correlate with treatment outcomes. 3,[8][9][10][11] Reverse-transcription (RT) polymerase chain reaction (PCR) techniques to detect HCV RNA during interferon therapy have been widely employed and are considered to be important for optimum management. 12,13 A high level of HCV RNA in serum before treatment is a poor prognostic sign for sustained response; unfortunately, clearance of virus from serum or plasma ...

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Section: Discussionmentioning

confidence: 99%

Effect of interferon therapy on hepatitis C virus RNA in whole blood, plasma, and peripheral blood mononuclear cells

Schmidt¹,

Wu²,

Brashear³

et al. 1998

Hepatology

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“…Detection of serum HCV-RNA was carried out by nested PCR, using primers from the 5'-noncoding region, as previously described (13). Total RNA from liver biopsies was obtained by using the RNAgents kit (Promega Corp., Madison, WI), following supplier instructions, and the amount of isolated total RNA was measured by spectrophotometry at 260 nm.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis C Virus Genotypes in Serum and Liver of Children with Chronic Hepatitis C

et al. 1995

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Hepatitis C virus (HCV) la, lb, 2a, and 2b subtypes have been studied in 30 serum samples and in 20 paired liver biopsies from children with chronic hepatitis C. One serum sample was negative to the four HCV subtypes studied. HCV lb was detected alone in 53.3% (16130) of the serum samples; HCV la alone in 23.3% (7130) and a mixed infection in 20% (6130). In liver samples, HCV mixed infection was detected in a significantly higher proportion (50%: p < 0.05) than in serum, whereas HCV lb was detected alone in 35% (7120) and HCV l a alone in the remaining 15% (3120) Since identification of the HCV as the major causative agent of postransfusional non-A, non-B hepatitis (I), different HCV types and subtypes have been described (2). The development of PCR-based methods for HCV genotyping (3-5) has permitted the study of the prevalence of HCV types and subtypes in adult patients with chronic hepatitis C (3, 6). Most of these studies have shown that HCV type 1 is prevalent in European countries (7-9). The pathobiology of the different HCV types is, furthermore, currently under active investigation (10-12). However, all these studies have been based on the analysis of HCV types in serum, and, to our knowledge, there have been no reports concerning detection of HCV types in liver cells.In this study, we have determined the prevalence of HCV types 1 and 2 in serum and in liver samples from Spanish children with chronic hepatitis C. METHODSAll 30 children included in this study (mean age: 10.1 + 4.5 y; range 2-17) had increased ALT levels for at least 6 mo previous to study entry; all had a chronic hepatitis histologically proven (24 chronic persistent hepatitis, 6 chronic active hepatitis), and all had serum HCV-RNA. Of these 30 children,

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“…8 HCV-RNA was tested by PCR using primers from the 5Ј noncoding region. 9 Antinuclear, anti-DNA, anti-smooth muscle, anti-liver-kidney microsome type 1, antimitochondrial, antithyroglobulin, and antimicrosomal autoantibodies were analyzed by indirect immunofluorescence on cryostat sections (Bio System, Barcelona, Spain).…”

Section: Patientsmentioning

confidence: 99%

Clinical and histological outcome after hepatitis B e antigen to antibody seroconversion in children with chronic hepatitis B

et al. 1999

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Data regarding the outcome of children with chronic hepatitis B after seroconversion are scarce. We describe the long-term evolution of these patients. One hundred and three children with antibody against hepatitis B e antigen and normal alanine aminotransferase (ALT) levels were followed for 0.6 to 12.5 years (mean, 6.3 years). Paired liver biopsies (before and after seroconversion) were available in 83 cases. Final biopsies were obtained 0.5 to 12.5 years (mean, 4.5 years) after seroconversion. ALT levels remained normal in most of the children (79%) throughout the follow-up. All children, except five who lost hepatitis B surface antigen, had serum viral DNA detected by polymerase chain reaction. When comparing baseline and final liver biopsies, a significant improvement (P F .001) was found in the histological activity index and in the necrosis, cytolysis, inflammation, and fibrosis scores. The histological diagnosis improvement in the final biopsy was significantly related (P F .001) to the time from seroconversion to the biopsy performance. All children had viral DNA on their final liver biopsy. In summary, seroconversion and ALT normalization are quite stable findings in children, and no differences in the long-term outcome between treated and untreated children were found. In light of the histological outcome, it seems unnecessary to perform a follow-up liver biopsy in these cases.(HEPATOLOGY 1999;29:572-575.)Although the long-term outcome of patients with chronic hepatitis B (HBV) after hepatitis B e antigen to antibody (anti-HBe) seroconversion and normalization of serum alanine aminotransferase (ALT) levels has already been reported, 1-6 these reports include a relatively small number of liver biopsies. Thus, the information about the liver histological activity and hepatitis B virus DNA (HBV-DNA) status is scarce. In addition, the time when a liver biopsy should be taken after seroconversion to anti-HBe, to definitively establish the histological status, has not yet been defined. Furthermore, differences in the long-term outcome between hepatitis B surface antigen (HBsAg)-carriers who seroconvert to antiHBe spontaneously and those who do so because of interferon-␣ treatment have not been conclusively shown, especially in children with chronic HBV.We studied the long-term outcome of children with chronic HBV who had seroconverted to anti-HBe, either spontaneously or as a result of interferon-␣ treatment, by comparing the baseline and final liver biopsies obtained at different time periods after ALT normalization and by determining the liver HBV-DNA status. PATIENTS AND METHODS Patients.Patients with chronic HBV under 18 years of age who attended our pediatrics department between 1978 and 1996 were retrospectively eligible if the following inclusion criteria were fulfilled: (1) Strictly documented seroconversion to anti-HBe with serum HBV-DNA clearance (as detected by dot-blot hybridization) and normal ALT levels on two consecutive occasions, 6 months apart; (2) Histologic evidence of chronic hepatitis ...

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Virological and biochemical long-term follow-up of patients with chronic hepatitis c treated with interferon

Cited by 66 publications

References 17 publications

Effect of interferon therapy on hepatitis C virus RNA in whole blood, plasma, and peripheral blood mononuclear cells

Effect of interferon therapy on hepatitis C virus RNA in whole blood, plasma, and peripheral blood mononuclear cells

Hepatitis C Virus Genotypes in Serum and Liver of Children with Chronic Hepatitis C

Clinical and histological outcome after hepatitis B e antigen to antibody seroconversion in children with chronic hepatitis B

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