Effects of long-term course of alpha-interferon in patients with chronic hepatitis C associated to mixed cryoglobulinaemia

Eur J Gastroenterol Hepatol. 1997 Nov;9(11):1067-72. doi: 10.1097/00042737-199711000-00008.


Objective: To evaluate the efficacy of a long-term course of alpha-interferon (alpha-IFN) in the treatment of HCV-related mixed cryoglobulinaemia and to determine the impact of cryoglobulinaemia on therapeutic response to IFN in chronic hepatitis C (CHC) patients.

Design: Prospective controlled study.

Setting: University Medical Centre.

Participants: Ninety consecutive CHC patients, 50 with cryoglobulinaemia (25 symptomatic and 25 asymptomatic; median cryocrit, 8%; chronic persistent hepatitis (CPH) 7, chronic active hepatitis (CAH) 27, cirrhosis 16) and 40 without cryoglobulinaemia (CPH 6, CAH 20, cirrhosis 14). HCV genotypes in the cryoglobulinaemic and non-cryoglobulinaemic groups were: 1b 40% and 45%; 2a 40% and 30%; others 20% and 25%, respectively.

Interventions: Twelve-month course of alpha-IFN 2a, 3 MU, three times weekly.

Main outcome measures: Disappearance of cryoglobulinaemia and related syndrome, clearance of serum HCV RNA and normalization serum transaminase levels at the end of treatment (response) and after 12 months follow-up (sustained response).

Results: Overall, cryoglobulinaemic patients showed a similar response to IFN to those without cryoglobulinaemia (44% vs. 42.5%, respectively). In the cryoglobulinaemic group, symptomatic patients showed a lower response rate than asymptomatic patients (28% vs. 60%, respectively; P<0.05). HCV genotype 2a/c, absence of cirrhosis and a low cryocrit (<9%) were predictive factors of high response rate to IFN. Sustained response in non-cryoglobulinaemic patients (22.5%) tended to be higher than in patients with symptomatic cryoglobulinaemia (4%), as well as among patients carrying genotype 2a/c (67% vs. 10%, respectively; P<0.02). IFN was effective in controlling purpura (80%) but was moderately effective on severe haematuria/proteinuria, renal insufficiency and neuropathy.

Conclusions: A 12-month course of alpha-IFN is effective treatment for HCV-related cryoglobulinaemia. However, patients with CHC associated to symptomatic cryoglobulinaemia have a lower response rate to IFN.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cryoglobulinemia / diagnosis
  • Cryoglobulinemia / drug therapy*
  • Female
  • Follow-Up Studies
  • Genotype
  • Hepatitis C / diagnosis
  • Hepatitis C / genetics
  • Hepatitis C / therapy*
  • Hepatitis, Chronic / diagnosis
  • Hepatitis, Chronic / drug therapy*
  • Hepatitis, Chronic / genetics
  • Humans
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • RNA, Viral / blood
  • Treatment Outcome


  • Interferon-alpha
  • RNA, Viral