Chronic hepatitis C long-term responders to human leukocyte interferon-alpha therapy: persistence of a sustained biochemical and virological response during 5 years of surveillance.

OBJECTIVES: To define the biochemical and virological course and IgM response to HCV-core protein in long-term responders (LTRs) during a long surveillance (5 years). DESIGN: From 1989 to 1991, 98 patients (pts) with biopsy-proven chronic hepatitis C were enrolled into this study. These pts underwent human leukocyte interferon-alpha (LE-IFN alpha) therapy at the prolonged schedule (3 MU thrice weekly for 1 year). METHODS: Serum alanine-aminotransferases (ALTs) were assessed monthly during and until 1 year after treatment, then every 3 months during the observation period. Qualitative and quantitative HCV RNA and HCV IgM were measured in all pts on baseline samples and in LTRs also after treatment and every following year. RESULTS: Based on serum ALT course, the pts were defined as: LTRs (14 pts), if their serum ALT levels returned to the normal range during therapy and remained so for at least 1 year afterwards; responders with relapse (RRs, 20 pts), if their serum ALT levels returned to the normal range during therapy but increased after ending treatment; and non-responders (NRs, 64 pts), if their serum ALT levels remained abnormal throughout therapy. No significant differences were seen regarding IgM anti-HCV positivity and serum ALT levels among the three groups. LTRs (12 HCV-RNA negative and two HCV-RNA positive at the end of treatment) maintained their virological status and not one of them experienced an elevation of serum ALT levels throughout the surveillance. CONCLUSION: Patients affected by chronic hepatitis C and treated with interferon, but who did not experience a biochemical or virological relapse within the first year of follow-up would not relapse later on; thus, we are able to conclude that these subjects made a complete recovery.

Subjects positive for hepatitis C virus RNA with normal aminotransferase levels, a "trompe l'oeil" clinical picture?

BACKGROUND: Quite often subjects affected by chronic hepatitis C virus infection have no clinical signs of liver disease and serum aminotransferase values never go beyond the upper limit of normal. Yet these subjects, defined "asymptomatic HCV carriers", often have active viral replication and various degrees of histological damage. AIMS: To verify, in a population of antibody to hepatitis C virus carriers, if normal serum aminotransferase values in hepatitis C virus-RNA positive differed considerably from those in hepatitis C virus-RNA negative subjects. SUBJECTS/METHODS: We followed 24 anti-hepatitis C virus-positive subjects (15 hepatitis C virus-RNA positive and 9 negative) by measuring alanine and aspartate aminotransferase levels at 3-month intervals for a median of 40 months (range 6-77). RESULTS: Determinations resulted repeatedly and rigorously within the normal range in all participants. Alanine aminotransferase values were higher in hepatitis C virus-RNA positives than in negatives (mean +/- SD: 0.609+/-0.172 vs 0.434+/-0.153 times the upper limit of normal; p

Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C.

BACKGROUND: A high incidence of thyroid autoantibodies and/or disorders was observed in subjects with hepatitis C virus-related chronic hepatitis during interferon-alpha therapy. AIM: To evaluate whether thyroid autoimmunity and dysfunction, induced by interferon-alpha therapy, could be viewed as predictors for treatment response and as valid prognostic markers of liver disease progression. PATIENTS: A total of 136 subjects (96 males/40 females; median age 48 years; range 23-64) affected by biopsy-proven chronic hepatitis C (33.1% with compensated liver cirrhosis). METHODS: All subjects were treated with interferon-alpha therapy at 6 MU 3 times weekly for 12 months and then followed up for an average period of 60 months (range 12-108). Routine laboratory tests, virological assessment, liver ultrasound, thyroid function tests (serum free-triiodothyronine, free-thyroxine, serum thyrotropin), and autoimmunity were performed for all subjects. RESULTS: Percentage of thyroid autoimmunity and thyroid dysfunction in long-term responders was not significantly different compared to that in non-responders (47.0% and 11.8% vs 35.3% and 5.9%, respectively; non significant). The multivariate model demonstrated that the absence of cirrhosis was the only factor significantly related to successful response to therapy (odds ratio: 14.9; 95% confidence interval: 1.9-115.0 for chronic hepatitis C vs presence of cirrhosis). Moreover, the occurrence of thyroid autoimmunity during interferon therapy was similar both in patients with or without worsening of liver disease (33.3% and 39.8%, respectively; p = not significant). No subject with on-going liver disease developed thyroid dysfunction during treatment, as opposed to the 10/118 (8.4%) with a better course of liver disease; however, this difference was not statistically significant. The multivariate model showed that age was the only covariate significantly associated with unfavourable outcome of liver disease (odds ratio: 18.6; 95% confidence interval: 2.3-151.9, for those over 48 years vs younger patients). CONCLUSIONS: There is no evidence that the immune mechanism involved in the pathogenesis of thyroid autoimmune phenomena is the same as that regulating the therapeutic clearance of HCV or modulating the unfavourable course of HCV-related chronic hepatitis. However, our study confirmed that liver disease seems to progress more slowly in younger subjects.

Clinical outcome of chronic hepatitis C in patients treated with interferon: comparison between responders and non-responders.

AIM: To evaluate the prognosis of chronic hepatitis C in relation to interferon therapy response and the persistence of therapeutic benefits. PATIENTS/METHODS: We studied the clinical outcome of 191 patients with chronic infection (152 chronic hepatitis C and 39 cirrhosis) treated with recombinant alpha-interferon (3-6 MU on alternate days for 1 year) during a mean period of 47 months (range 22.5-73.8). Control tests were done at 6-month intervals. HCV RNA was determined pre- and post-treatment in all participants, but continued yearly in long-term responders. The appearance of cirrhosis was estimated using a non-invasive method that utilizes a model based on clinical, instrumental and biochemical variables. Ascites, encephalopathy, haemorrhage, hepatocellular carcinoma, and death were considered liver-disease-related events. RESULTS: A total of 39 patients were long-term responders, 36 relapsers, and 116 non-responders; 92% of long-term responders cleared HCV RNA and remained negative throughout the study period. The 3 HCV-RNA-positive long-term responders continued being so. No biochemical relapse was observed in long-term responders regardless of virological status. New cirrhosis was observed in 3/30 relapsers, in 9/85 non-responders, and in no long-term responders. Overall, 9 episodes of severe events occurred in 20% of cirrhotics and in 0.6% of chronic hepatitis, all non-responders. CONCLUSIONS: Long-term response interrupts the progression to cirrhosis and reduces the incidence of severe complications. Multivariate analysis revealed that "baseline diagnosis of cirrhosis" was the only independent factor predictive of an unfavourable outcome of chronic HCV-related liver disease.