Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C

Marcellin, Patrick; Pouteau, M.; Martinot‐Peignoux, Michèle; Degos, Françoise; Duchatelle, V.; Boyer, Nathalie; Lemonnier, Catherine; Degott, Claude; Erlinger, S; Benhamou, Jean Pierre

doi:10.1016/0016-5085(95)90281-3

Cited by 93 publications

(41 citation statements)

References 27 publications

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“…chemical and histological response (37%). Serum HCV RNA became negative in 84% of these patients (virological re-These included higher doses [17][18][19] and longer duration of interferon therapy, 6,7,20,21 phlebotomy to reduce hepatic iron consponse). Biochemical response without histological response was observed in 11 of 84 patients (13%).…”

Section: Discussionmentioning

confidence: 99%

Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C

et al. 1997

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The response to interferon treatment for patients with The present study was conducted to evaluate the relationship between biochemical, virological, and histological re-chronic hepatitis C was originally defined biochemically as a decline in the value of an elevated serum alanine aminosponse during the course of interferon therapy. Ninety consecutive patients with well-documented chronic hepatitis C virus transferase (ALT) concentration into the normal range at the completion of therapy. According to this definition, 33%-(HCV) were treated with 5 MU of interferon alfa-2b three times weekly for 6 months. Liver biopsy was performed, and 50% of patients achieve biochemical response during treatment. [1][2][3][4][5][6][7] More recently, it has been shown that 80%-90% of serum HCV RNA titer was measured before and at the completion of interferon treatment. Normalization of serum alanine patients who achieve biochemical response also have virological response, i.e., disappearance of hepatitis C virus (HCV) transaminase (ALT) concentration (biochemical response) was observed in 50% of patients. In these patients, Knodell RNA from serum as assessed by a polymerase chain reaction (PCR) assay. [5][6][7][8] Unfortunately, approximately half of all pascore declined significantly from 9.6 { 0.5 to 5.0 { 0.5 (P õ .01), and 75% became HCV RNA negative. The re-tients treated with interferon continue to be classified as nonresponders; serum ALT concentration remains elevated maining patients (50%) were biochemical nonresponders; mean Knodell score declined from 9.6 { 0.5 to 7.7 { 0.5 and HCV RNA remains detectable in serum throughout the duration of therapy. (P õ .01), and 11% became HCV RNA negative. For both biochemical responders and nonresponders, the decline in Biochemical and virological response to interferon therapy is associated with a significant improvement in hepatic histolKnodell score was confined to the components of hepatic inflammation (piecemeal necrosis / lobular / portal inflam-ogy. 1-7 However, a consistent finding in many prior studies was that the mean hepatic histological index of interferon mation); no change in fibrosis was observed. Hepatic inflammation declined by 5 points or more in 69% of biochemical nonresponders also improved. We have therefore hypothesized that a subset of patients who do not respond to interresponders and 48% of biochemical nonresponders, and by at least 50% from pretreatment values in 74% and 38% of feron, according to the classic definitions, may in fact have significant improvement in hepatic histology and thereby biochemical responders and biochemical nonresponders, respectively. For all patients (both biochemical responders and also benefit from interferon treatment.The present study was performed to assess the relationship nonresponders) who remained viremic at the conclusion of interferon therapy, the reduction in hepatic inflammation was between biochemical, virological, and histological responses to interferon therapy in patients with chronic hepatitis C. a linear func...

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Section: Discussionmentioning

confidence: 99%

Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C

et al. 1997

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“…Our study was limited to the short-term effects of inter-RNA are at risk for a biochemical relapse after further followup, 11,106,110,111 and the absence of detectable RNA suggests feron treatment and to overall histological changes. Partial improvement or improvements in different components of that the virus may have been successfully eradicated from the body.…”

Section: Discussionmentioning

confidence: 99%

“…In three studies, 57,60,107 however, only a to the biochemical responses. 2,11,25,31,32, In three stud-minority of subjects underwent a second liver biopsy, and ies, [103][104][105] both interferon alfa and beta were used, and subjects the reasons for dropouts were unclear. Sensitivity analyses could not be separated.…”

Section: Database Of Studiesmentioning

confidence: 99%

Correlation of biochemical response to interferon alfa with histological improvement in hepatitis C: A meta-analysis of diagnostic test characteristics

et al. 1997

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44%-65%) and 75% (95% CI, 67%-81%), respectively. As The current goal of interferon treatment for chronic hepatimany as 51% (95% CI, 38%-64%) may have improved, despite tis C is to normalize alanine aminotransferase (ALT) and to failure to normalize ALT. A substantial number of patients eradicate detectable viral RNA. Many patients do not achieve may improve histologically after interferon therapy. The sigthis objective during treatment, and most do not sustain these nificance of histological changes observed after interferon outcomes after interferon is discontinued. However, biochemtherapy must be weighed against the limitations of liver biical or virological responses to interferon may not reflect accuopsy and the uncertain natural history of hepatitis C. Neverrately the histological consequences of therapy. The aim of theless, the ALT does not always reflect liver histology accuthis study was to determine the extent to which the biochemirately after interferon alfa treatment and may underestical measures reflect the histological outcomes in the treatment mate histological improvement. (HEPATOLOGY 1997;26:1035-of hepatitis C with interferon alfa using a meta-analysis of 1044.) diagnostic test characteristics. The data sources were English and non-English language studies retrieved from Medline (from 1966 to December 1995). The sudy selection includedInterferon alfa is widely used in the treatment of hepatitis studies in which interferon alfa was used for treatment of C. Clinically, alanine aminotransferase (ALT) and more rechronic hepatitis C with liver biopsies performed before and cently RNA determinations are used to measure the response after therapy. Data on histological and biochemical outcomes to treatment. However, not all patients normalize their ALT were extracted independently by two reviewers. Two separate during treatment, and only a fraction of responders will suscriteria were used for defining histological response. When tain a normal ALT after interferon is discontinued.1-13 To strict definitions of histological improvement were consid-further complicate matters, the long and variable natural hisered, histology improved in 28% (95% confidence interval tory of the disease 14-16 makes it difficult to establish the true [95% CI], 17%-43%) of patients after interferon treatment. clinical benefit of such biochemical responses. The sensitivity and specificity of the ALT for determiningLiver histology may offer additional insight into disease histological change were 70% (95% CI, 56%-81%) and 66% activity. An improvement in hepatic histology may be seen (95% CI, 56%-75%), respectively. As many as 17% (95% CI, as a favorable response to therapy. Neither ALT nor RNA 9%-30%) of subjects with an abnormal ALT at the end of measures reflect liver histology accurately before interferon therapy may have improved histologically after interferon treatment.17 However, it is currently unclear as to what extent therapy. When less stringent definitions of histological im-biochemical responses after treatment refle...

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“…Another approach has been the use of escalating doses and in one study (Marcellin et al, 1995), 50 patients were prescribed 3 MU three times weekly of interferon α for 8 weeks which was increased to 5 MU three times weekly for 8 weeks if the transaminase values remained abnormal and further increased to 10 MU three times weekly for 8 weeks if transaminases remained elevated. This group was compared with 25 patients who received a constant dosage of 3 MU three times weekly for 24 weeks.…”

Section: Interferon-αmentioning

confidence: 99%

Treatment of Chronic Viral Hepatitis

Main

McCarron

1998

Antivir Chem Chemother

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Interferon-α therapy has proved effective for up to 40% of patients with adult-acquired chronic hepatitis B virus (HBV) infection and for 20-25% of those with chronic hepatitis C virus (HCV) infection. Nucleoside analogues, such as lamivudine and famciclovir, are showing promise as antiviral agents for chronic HBV and the combination of interferon-α and ribavirin is proving to be successful therapy for 40-50% of patients with chronic HCV. In this article we review current therapy and discuss future strategies of the therapy of chronic viral hepatitis.

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Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C

Cited by 93 publications

References 27 publications

Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C

Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C

Correlation of biochemical response to interferon alfa with histological improvement in hepatitis C: A meta-analysis of diagnostic test characteristics

Treatment of Chronic Viral Hepatitis

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