Elsevier

Journal of Hepatology

Volume 26, Issue 6, July 1997, Pages 1187-1199
Journal of Hepatology

The effect of interferon on the liver in chronic hepatitis C: a quantitative evaluation of histology by meta-analysis

https://doi.org/10.1016/S0168-8278(97)80451-5Get rights and content

Abstract

Background/Aims: Several randomized clinical trials of interferon in chronic hepatitis C have examined the histological changes in paired biopsy specimens. We have attempted a quantitative evaluation by meta-analysis.

Methods: Randomized Clinical Trials found by MEDLINE search were included if: a) they compared different IFN regimens with non-active treatment or with each other, b) they obtained biopsies before starting and at the time of stopping IFN in a sizable proportion of the treated and control patients, and c) they assessed the biopsy-specimens semi-quantitatively according to Scheuer's numerical scoring, system or Knodell's Histological Activity Index, with quantitation of fibrosis and Iobular, portal and periportal necroinflammation.

Results: Seventeen trials were identified, in which 1223 adult patients had been studied. All trials homogeneously pointed towards a favorable interferon effect. The pooled data show a statistically significant histological improvement in treated patients as compared with controls for each of the four Histological Activity Index components and for the total Histological Activity Index score (overall improvement was −0.82 in favor of interferon, p<0.0001, 95% Confidence Interval −1.25 to −0.40). In the ten trials reporting histological changes separately in biochemical responders (primary and sustained responders) and non-responders, histological improvement was confined to the subset of biochemical responders. No change or very little change occurred in non-responders.

Conclusions: Interferon treatment in chronic hepatitis C significantly improves liver histology. The effect of interferon is closely related to biochemical response. Studies assessing histological outcome 1 year or more after interferon treatment in long-term responders and comparatively in non-responders or relapsers would be important to confirm the regression of the necroinflammatory process in the former, as suggested by the normal serum alanine aminotransferase levels.

References (100)

  • L Cimino et al.

    Treatment of chronic hepatitis C with recombiannt interferon alfa

    Ital J Gastroenterol

    (1991)
  • S Nishiguchi et al.

    Randomized trial of effect of interferon-α on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis

    Lancet

    (1995)
  • R Pérez et al.

    Treatment of chronic hepatitis C with recombinant interferon alfa-2b for nine months

    Gut

    (1993)
  • T Poynard et al.

    A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis

    N Engl J Med

    (1995)
  • G Saracco et al.

    A randomized controlled trial of interferon alfa-2b as therapy for chronic non-A, non-B hepatitis

    J Hepatol

    (1990)
  • R Schvarcz et al.

    Interferon alpha-2b treatment of chronic post-transfusion non-A non-B/C hepatitis: long-term outcome and effect of increase interferon doses in non-responders

    Scand J Infect Dis

    (1991)
  • G Varagona et al.

    A phase II study of interferon alfa-2b treatment of anti-HCV positive and negative chronic NANB hepatitis: interim analysis

    J Hepatol

    (1990)
  • G Angelini et al.

    Alpha-interferon treatment of chronic hepatitis C: a controlled, multicentre, prospective study

    Digestion

    (1995)
  • P Bonetti et al.

    Treatment of cryptogenic chronic liver diseases with recombinant alpha-2a interferon. Preliminary results of a randomized controlled clinical trial

    Ann Ital Med Int

    (1990)
  • M Shindo et al.

    Decrease in serum hepatitis C viral RNA during alpha-interferon therapy for chronic hepatitis C

    Ann Intern Med

    (1991)
  • S Iino

    High dose interferon treatment in chronic hepatitis C

    Gut

    (1993)
  • M Makris et al.

    Interferon alfa for chronic hepatitis C in haemophiliacs

    Gut

    (1993)
  • AR Watson et al.

    High-dose interferon alfa-2A for the treatment of chronic hepatitis C

    Ann Pharmacother

    (1994)
  • M Angelico et al.

    Recombinant interferon-α and ursodeoxycholic acid versus interferon-α alone in the treatment of chronic hepatitis C: a randomized clinical trial with long-term follow-up

    Am J Gastroenterol

    (1995)
  • S Iino et al.

    Treatment of chronic hepatitis C with hig-dose interferon a-2b: a multicenter study

    Dig Dis Sci

    (1193)
  • GEM Kleter et al.

    Detection of hepatitis C virus RNA in patients with chronic hepatitis C virus infections during and after therapy with alpha interferon

    Antimicrob Agents Chemother

    (1993)
  • A Matsumoto et al.

    Viral and host factors that contribute to efficacy of interferon-α2a therapy in patients with chronic hepatitis C

    Dig Dis Sci

    (1994)
  • T Saito et al.

    A randomized controlled trial of human lymphoblastoid interferon in patients with compensated type C cirrhosis

    Am J Gastroenterol

    (1994)
  • O Yokosuka et al.

    Efficacy of longterm interferon treatment in chronic liver disease evaluated by sensitive polymerase chain reaction assay for hepatitis C virus RNA

    Gut

    (1995)
  • RG Knodell et al.

    Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis

    Hepatology

    (1981)
  • PJ Scheuer et al.

    The hepatology of hepatitis C

    Hepatology

    (1992)
  • J Ludiwig

    The nomenclature of chronic active hepatitis: an obituary

    Gastroenterology

    (1993)
  • L Pagliaro et al.

    Interferon-α for chronic hepatitis C: an analysis of pretreatment clinical predictors of response

    Hepatology

    (1994)
  • O Ricahrd et al.

    Two-year biochemical, virological, and histological follow-up in patients with chronic hepatitis C responding in a sustained fashion to interferon alfa-2b treatment

    Hepatology

    (1995)
  • L Mattsson et al.

    Long-term follow-up of chronic post-transfusion non-A, non-B hepatitis: clinical and histological outcome

    Liver

    (1988)
  • AM Di Bisceglie et al.

    Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis

    Hepatology

    (1991)
  • R Wejstål et al.

    Long-term follow-up of chronic hepatitis non-A, non-B with special reference to hepatitis C

    Liver

    (1991)
  • LB Seeff et al.

    Long-term mortality after transfusion associated non-A, non-B hepatitis

    N Engl J Med

    (1992)
  • RL Koretz et al.

    Non-A, non-B post-transfusion hepatitis. Looking back in the second decade

    Ann Intern Med

    (1993)
  • L Mattsson et al.

    Chronic non-A, non-B hepatitis developed after transfusions, illicit self-injections or sporadically. Outcome during long-term follow-up — a comparison

    Liver

    (1989)
  • X Causse et al.

    Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis

    Gastroenterology

    (1991)
  • A Gallorini et al.

    Serum markers of hepatic fibrogenesis in chronic hepatitis type C treated with alfa-2a interferon

    Liver

    (1994)
  • M Gomez-Rubio et al.

    Prolonged treatment (18 months) of chronic hepatitis C with recombinant α-interferon in comparison with a control group

    J Hepatol

    (1990)
  • R Lin et al.

    Interferon alfa-2b for chronic hepatitis C: effects of dose increment and duration of treatment on response rates

    J Hepatol

    (1995)
  • G Mazzella et al.

    Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: gamma GT levels predictive for response

    Dig Dis Sci

    (1994)
  • M Omata et al.

    Randomized, double-blind, placebo-controlled trial of eight-week course of recombinant α-interferon for chronic non-A, non-B hepatitis

    Dig Dis Sci

    (1991)
  • J Richen et al.

    Low-dose interferon in chronic hepatitis non-A/non-B: effects on quantitative liver function and structure in a randomized, controlled multicenter trial

    Clin Invest

    (1993)
  • MG Rumi et al.

    Long-term titrated recombinant interferon-α2a in chronic hepatitis C: a randomized controlled trial

    J Viral Hep

    (1995)
  • F Saez-Royuela et al.

    High doses of recombinant α-interferon or gamma-interferon for chronic hepatitis C: a randomized, controlled trial

    Hepatology

    (1991)
  • JO Sieck et al.

    Histologically advanced chronic hepatitis C treated with recombinant alpha-interferon: a randomized placebo-controlled double-blind cross-over study

    J Hepatol

    (1993)
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