TREATMENT OF PUTATIVE NON-A, NON-B, NON-C HEPATITIS WITH ALPHA INTERFERON: A PRELIMINARY TRIAL.

Van Thiel DH; Gavaler JS; Baddour N; Friedlander L; Wright HI; Oklahoma Transplantation Institute, Baptist Medical Center of Oklahoma, Oklahoma City 73112. J Okla State Med Assoc, 1994 Aug, 87:8, 364-8

Chronic hepatitis due to putative non-A, non-B, non-C hepatitis occurring in an individual who is negative for HBV and HCV markers has been identifiable only recently. Little or nothing is known about its natural history or response to interferon therapy. In the present study, 13 subjects with chronic non-A, non-B, non-C hepatitis were treated with interferon for 6 months (5 million units, three times per week). Prior to and after 6 months of therapy and again 6 weeks after discontinuing interferon therapy, each subject underwent a liver biopsy. These tissues were used to define the histopathology, the character of the cellular infiltrate within the liver, and the changes in histopathology and inflammatory infiltrate achieved in response to interferon therapy and withdrawal. No differences for age, gender, initial AST, bilirubin, histopathology, or Knodell score were evident between responders (n = 7) and non-responders (n = 6). Only the number of NK cells was altered significantly as a result of IFN treatment and distinguished responders from non-responders. These data demonstrate that: (1) chronic non-A, non-B, non-C hepatitis can be treated with interferon; (2) interferon activates NK cells and enhances hepatocyte expression of Class II MHC antigens; and (3) interferon also increases the number of CD3, CD4, and CD8 cells found within the liver but these changes do not distinguish between responders and non-responders.

HISTOLOGICAL OUTCOME IN INTERFERON ALPHA-2B TREATED PATIENTS WITH CHRONIC POSTTRANSFUSION NON-A, NON-B HEPATITIS.

Schvarcz R; Glaumann H; Weiland O; Norkrans G; Wejstål R; Frydén A; Department of Infectious Diseases, Karolinska Institute, Roslagstull Hospital, Stockholm, Sweden. Liver, 1991 Feb, 11:1, 30-8

The histological outcome in liver biopsies following 9 months of interferon alpha-2b treatment was assessed in detail in 19 patients with chronic posttransfusion non-A, non-B hepatitis (PTH-NANB) and compared with 12 untreated PTH-NANB patients. Fourteen (74%) treated and 7 (58%) control patients were reactive for antibodies against hepatitis C virus (anti-HCV). Liver biopsies taken before and after the 9-month period were scored numerically for portal inflammation, piecemeal necrosis (PMN) and fibrosis, without knowledge of whether the specimens came from control or treated patients. There were no score differences in the initial biopsies between the treated and control group. In the follow-up biopsies the treated group showed significantly less portal inflammation, PMN and fibrosis than the control group (p less than 0.05-0.01). When paired samples from the treated group were compared, significantly regressed portal inflammation, PMN and fibrosis were noted in the follow-up biopsies (p less than 0.05-0.001). The presence or not of anti-HCV antibodies in serum had no impact on the histological response to interferon treatment. We conclude that a 9-month course of interferon alpha-2b treatment significantly diminishes not only inflammation but also fibrosis in the liver of patients with PTH-NANB whether they are anti-HCV reactive or not.

INTERFERON-ALPHA FOR CHRONIC HEPATITIS C: AN ANALYSIS OF PRETREATMENT CLINICAL PREDICTORS OF RESPONSE.

Pagliaro L; Craxí A; Cammaá C; Tiné F; Di Marco V; Lo Iacono O; Almasio P; Instituto di Medicina Generale e Pneumologia, University of Palermo, Italy. Hepatology, 1994 Apr, 19:4, 820-8

To identify predictors of short-term and sustained ALT normalization after interferon treatment in adult patients with chronic hepatitis C, we performed a meta-analysis of individual patients’ data, with construction and cross-validation of a prediction rule, in 361 patients from two randomized trials. In one trial, 116 subjects with transfusion-related chronic hepatitis C were treated with lymphoblastoid interferon (5 MU/m2 three times a week for 2 mo, then 3 MU/m2 three times a week for 4 or 10 mo). In the other study, 245 patients with community-acquired chronic hepatitis C received recombinant interferon-alpha 2b (10 MU three times a week for 2 mo, then 5 MU three times a week for 4 mo; then random allocation of subjects with normal aminotransferase levels to stop or continue interferon for a further 6 mo). Overall, 164 subjects (45%; 95% confidence interval, 40% to 50%) had short-term responses; 61 (18%; 95% confidence interval, 14% to 22%) maintained sustained responses. Sixty patients (17%; 95% confidence interval, 13% to 21%) withdrew from treatment because of side effects or subjective intolerance. Logistic regression analysis showed that short-term and sustained response were independently predicted by lobular structure on pretreatment liver biopsy (p < 0.0001) and by short disease duration, defined as the time elapsed since transfusion in posttransfusion cases or since the first observation of abnormal aminotransferase levels in cryptogenic disease (p < 0.01).

CHRONIC HEPATITIS C AND INTERFERON ALFA THERAPY: PREDICTORS OF LONG TERM RESPONSE

Jenkins PJ; Cromie SL; Bowden DS; Finch CF; Dudley FJ; Gastroenterology Department, Alfred Hospital, Melbourne, VIC, Australia. Med J Aust, 1996 Feb 5, 164:3, 150-2

OBJECTIVE: To identify independent patient, disease and viral characteristics that predict a sustained biochemical or viral response to interferon alfa therapy in patients with chronic hepatitis C. Design: Comparison of interferon responders and non-responders by univariate and multivariate analysis. SETTING: The hepatitis clinic of the Alfred Hospital, Melbourne (a tertiary referral hospital), between July 1989 and June 1994. SUBJECTS: All patients with chronic hepatitis C who were treated with interferon alfa (IFN-alpha; 3 million IU, three times a week or more) for at least 12 weeks. OUTCOME MEASURES: Patient demographic and epidemiologic characteristics, pretreatment serum alanine aminotransferase (ALT) and 2-gamma-glutamyl transpeptidase (GGT) levels, histological grading of hepatic steatosis, necroinflammatory activity and fibrosis, serum hepatitis C virus (HCV) RNA titres and genotype and post-treatment serum ALT levels and presence of HCV RNA. Results: Of 58 patients, 13 (22%) had a sustained (six months or longer) biochemical response to IFN-alpha therapy, including 12 (21%) with a sustained viral response. Univariate analysis showed that young patients with a normal serum GGT level, grade 0-1 steatosis and fibrosis, low viral titre and infection with genotypes 3a and 2a were more likely to have a sustained response. Infection with genotypes other than 1a and 1b was the only independent variable associated with both a sustained biochemical and viral response. After adjusting for genotype, a hepatic fibrosis grade of 0-1 was also independently associated with viral response. This logistic regression model accurately predicted the virological response in 80% of cases. Conclusion: In Australian patients with chronic hepatitis C, a sustained viral response to IFN-alpha therapy is most likely in those infected with a genotype other than 1a or 1b and with minimal hepatic fibrosis.

A COMPARISON BETWEEN TWO INDUCTION REGIMES FOR THE INTERFERON TREATMENT OF CHRONIC HEPATITIS C: RESPONSE RELATED FACTORS.

Pérez R; Pravia R; Artímez ML; Linares A; Lombrana JL; Pérez-López R; Rodrigo L; San Miguel G; Pons F; Suárez F; Caro-Patón; A; Digestive Service, Hospital Marqués de Valdecilla, Santander. Rev Esp Enferm Dig, 1997 Mar, 89:3, 159-73

Treatment of chronic hepatitis C with alfa interferon for 6 months achieves sustained responses in 15-25% of the patients. The initial induction with higher doses and the prolongation of treatment can improve the results. A randomized, prospective study was carried out to compare the efficacy of a short term induction schedule of interferon alfa-2b (group A) versus a long term one (group B). 106 patients with chronic hepatitis C were included: 54 received 5 megaunits tiw for 8 weeks and 52 for 16 weeks; afterwards, interferon was reduced to 3 megaunits up to 9 months. The percentage of sustained responses, transient responses and non responses were 18.5%, 24% and 57.4% in group A and 23.1%, 28.8% and 48.1% in group B (NS). The following factors were related to a poor response in the univariate analysis: an increase of serum iron levels, ferritin, Gamma-GT and bilirubin, anti-nuclear antibody positivity, presumed non-parenteral infection, an AST/ALT ratio greater than 0.75, a higher Knodell's index and a greater necrosis and fibrosis score. The multivariate analysis revealed that elevated serum iron and ferritin and anti-nuclear antibody positivity had an independent predictive value related to a non response. Our results appear to suggest that an induction with higher doses and the treatment over nine months are more efficient than the classic schedule. The prolongation of the induction period does not provide additional advantages.

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