Interferon For Chronic Hepatitis Research Articles

Meta‐analysis of interferon randomized trials in the treatment of viral hepatitis C in naive patients: 1999 Update

The aim of this study was to update our previous meta‐analysis of interferon (IFN) in the treatment of hepatitis C and to analyse new factors, namely, HCV RNA end‐point, patients with cirrhosis and patients with normal ALT. We use the Der Simonian and Laird method, with heterogeneity and sensitivity analyses. Seventy‐six randomized control trials (RCTs) in naive patients were found but we focused our analysis on 59 RCTs with chronic hepatitis C (26 vs. controls and 33 comparing different regimens) and on seven RCTs in acute hepatitis. Interferon‐α (IFN‐α) at 3 MU thrice weekly (TIW) for 12 months exhibited 39% of virological end‐of‐treatment response (ETR) and 17% of virological sustained response (SR), respectively, vs. 1% and 3% in untreated controls (all P < 0.001). There was a significant dose effect (in favour of 6 vs. 3 MU TIW): the virological SR at 6 months were 35% in the 6 MU group (95% CI: 24–47) and 16% in the 3 MU group (95% CI: 8–27) and were at 12 months 43% in the 6 MU group (95%CI: 31–56) and 25% in the 3 MU group (95% CI: 16–37). There was a significant duration effect (12 vs. 6 months) upon the virological SR rate both at 3 and 6 MU: 3 MU provided 14% of virological SR (95% CI: 11–19) in the 12 months group vs. 7% (95% CI: 5–11) in the 6 months group and 6 MU provided 22% (95% CI: 17–29) and 16% (95% CI: 11–22) virological SR in the 12 and 6 months groups, respectively. Cirrhotic treated patients had 17% of virological SR (95 CI: 9–24%; P < 0.001) vs. 0% in controls and provided a 20% reduction rate (95 CI: −2% to −37%, P=0.03) in hepatocellular carcinoma incidence. In acute hepatitis C, a 3‐month treatment with IFN‐α showed significant efficacy vs. controls upon the virological SR rate (32% vs. 4%, P < 0.001). In conclusion, we confirm the dose and duration effect of IFN in chronic hepatitis C, and the efficacy of IFN‐α in the treatment of acute hepatitis and in cirrhotic patients.

Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C in naive patients: 1999 update.

The aim of this study was to update our previous meta-analysis of interferon (IFN) in the treatment of hepatitis C and to analyse new factors, namely, HCV RNA end-point, patients with cirrhosis and patients with normal ALT. We use the Der Simonian and Laird method, with heterogeneity and sensitivity analyses. Seventy-six randomized control trials (RCTs) in naive patients were found but we focused our analysis on 59 RCTs with chronic hepatitis C (26 vs. controls and 33 comparing different regimens) and on seven RCTs in acute hepatitis. Interferon-alpha (IFN-alpha) at 3 MU thrice weekly (TIW) for 12 months exhibited 39% of virological end-of-treatment response (ETR) and 17% of virological sustained response (SR), respectively, vs. 1% and 3% in untreated controls (all P < 0.001). There was a significant dose effect (in favour of 6 vs. 3 MU TIW): the virological SR at 6 months were 35% in the 6 MU group (95% CI: 24-47) and 16% in the 3 MU group (95% CI: 8-27) and were at 12 months 43% in the 6 MU group (95%CI: 31-56) and 25% in the 3 MU group (95% CI: 16-37). There was a significant duration effect (12 vs. 6 months) upon the virological SR rate both at 3 and 6 MU: 3 MU provided 14% of virological SR (95% CI: 11-19) in the 12 months group vs. 7% (95% CI: 5-11) in the 6 months group and 6 MU provided 22% (95% CI: 17-29) and 16% (95% CI: 11-22) virological SR in the 12 and 6 months groups, respectively. Cirrhotic treated patients had 17% of virological SR (95 CI: 9-24%; P < 0.001) vs. 0% in controls and provided a 20% reduction rate (95 CI: -2% to -37%, P=0.03) in hepatocellular carcinoma incidence. In acute hepatitis C, a 3-month treatment with IFN-alpha showed significant efficacy vs. controls upon the virological SR rate (32% vs. 4%, P < 0.001). In conclusion, we confirm the dose and duration effect of IFN in chronic hepatitis C, and the efficacy of IFN-alpha in the treatment of acute hepatitis and in cirrhotic patients.

Onset of coeliac disease during treatment with interferon for chronic hepatitis C

Onset of coeliac disease during treatment with interferon for chronic hepatitis C

Psychiatric symptoms related to interferon therapy for chronic hepatitis C: clinical features and prognosis.

Psychiatric symptoms during interferon (IFN) therapy for viral hepatitis have been a crucial problem in consultation-liaison psychiatry. However, there have been few studies on psychiatric management for these symptoms and their prognosis. Among 943 patients who were treated with IFN for chronic hepatitis C between 1991 and 1995, 43 patients (4.6%) developed psychiatric symptoms during IFN treatment. Three patients (0.3%), with pre-existing psychiatric disorders showed aggravated symptoms and were excluded from the study. All three patients were able to finish the IFN therapy with psychiatric management. Forty patients (4.2%) manifested psychiatric symptoms induced by IFN. Thirteen patients (1.4%) were diagnosed as anxiety disorder and 21 patients (2.2%) revealed mood disorder with depressive features. There were other psychiatric disorders in six patients (0.6%), including psychotic disorder with delusions/hallucinations in four patients (0.4%), mood disorder with manic features in one patient (0.1%) and delirium in one patient (0.1%). Women developed psychiatric symptoms significantly more than men. Ten of 40 patients (25%) stopped IFN treatment because of manifesting psychiatric symptoms induced by IFN. Twelve patients (30%) required psychiatric treatment for more than 24weeks after ceasing IFN, and seven patients still had anxiety, insomnia and mild hypothymia at the end of the present study. Statistical analysis revealed that IFN-beta therapy and psychiatric manifestations including psychotic symptoms, delirium and manic symptoms were significantly related to long-term psychiatric problems. There are considerable numbers of patients who have required long-term psychiatric management even after cessation of IFN treatment.

Onset of coeliac disease during treatment with interferon for chronic hepatitis C

The immunomodulatory properties of interferon may concur to precipitate or worsen an underlying autoimmune disorders. We report the cases of two men who displayed the various features of coeliac disease during a treatment with 4-interferon (in one case associated with ribavirin) for chronic hepatitis C. The patients stopped the interferon treatment and the symptoms and histological disorders improved after a gluten-free diet. Alpha-interferon is available worldwide for treatment of chronic viral hepatitis. Before treatment with this drug, the patients would have to be monitored for coeliac disease.

Early addition of ribavirin to interferon in chronic hepatitis C not responsive to interferon monotherapy

Background/Aim: Persistence of HCV-RNA in serum early in treatment is a strong predictor of failure of α-interferon therapy for chronic hepatitis C. Therefore, we compared the efficacy of ribavirin addition to α-interferon with a doubling of the dosage of α-interferon in case of lack of early virological response to α-interferon therapy. Methods: Sixty patients were administered interferon α2b at the dosage of 3 million units 3 times a week. After the first 4 weeks of therapy, serum HCV-RNA was evaluated. The patients with negative HCV-RNA test received the same treatment for a further 11 months, while those with detectable HCV-RNA were randomized to receive either the same dosage of α-interferon plus ribavirin (1000 mg/day) or double dosage of α-interferon (6 million units tiw) for 11 months. We considered sustained response to be the maintenance of normal alanine aminotransferase and negativity at HCV-RNA testing until the end of a 6-month post-treatment follow-up. Results: After the first 4 weeks of treatment, 12 (20%) patients showed virological response and 48 patients (80%) remained positive on HCV-RNA testing. Sustained response was observed in 5/12 (42%) patients with early virological response, in 10/24 (42%) patients without early virological response who were administered ribavirin and α-interferon, and in only 1/24 (4%) patients who were administered the double dosage of α-interferon ( p=0.006). Conclusions: This study shows the efficacy of the addition of ribavirin to α-interferon and the lack of efficacy of doubling the dosage of α-interferon in patients without clearance of hepatitis C virus early on in treatment.

Treatment of interferon in chronic hepatitis C patients with normal ALT: Results of a controlled study

Treatment of interferon in chronic hepatitis C patients with normal ALT: Results of a controlled study

Does low socioeconomic status influence response to interferon in chronic hepatitis C?

Does low socioeconomic status influence response to interferon in chronic hepatitis C?

Daily use of consensus interferon for chronic hepatitis C among patients who had relapsed or not responded to previous treatment with alpha interferon 2b: One year treatment results

Daily use of consensus interferon for chronic hepatitis C among patients who had relapsed or not responded to previous treatment with alpha interferon 2b: One year treatment results

Steatosis of the liver and response to interferon (IFN) in chronichepatitis C

STEATOSIS OF THE LIVER AND RESPONSE TO INTERFERON (IFN) IN CHRONIC HEPATITIS C I. Ketiko,,lou, S. Karatapanis, G. Kafiri, I. Elefsiniotis, M. Dimopoulou, I. Lafiatis, T.H. Christoforatos, G. Karvountzis Liver Clinic and State Department of Internal Medicine, Ippokration General Hospital, Athens, Greece. Several factors have been identified that predict a high likelihood of response after IFN therapy in patients with chronic hepatitis C (CHC). The aim o f the present study was to evaluate if the presence of steatosis in patients with CHC has any predicting value regarding the response to interferon. 68 patients (40M/28F, mean age 49) with biopsy proven chronic hepatitis C (HCV-RNA+) were included in our study.Steatosis in the liver was graded as mild if 2/3 of the liver was affected. All pts received a six month course with interferon-a 3MU thrice weekly. HCVRNA was retested 6 and 12 months after start o f treatment. Virological (clearance o f viremin) and biochemical (normalization o f t r a n s ~ s ) responses were recorded after the end of treatment. Absence o f steatosis observed in 36 pts, mild in 17, and moderate in 19. No response was found in 9/36 (25%) pts without steatosis, 3/17(17%) in pts with mild and 9/19(47%) pts with moderate steatosis (p<0,05).The virological responses were 16/36(44%), 9/17(52%) and 7/19(37%) respeeively. Our results indicate that presence of steatosis may be a negative prognostic factor regarding to response to IFN in patients with chronic hepatitis C. ] C06/063 I

Treatment of interferon in chronic hepatitis C patients with normal ALT: Results of a controlled study

Treatment of interferon in chronic hepatitis C patients with normal ALT: Results of a controlled study

Perihepatic lymphadenopathy and the response to alpha interferon inchronic hepatitis C

Perihepatic lymphadenopathy and the response to alpha interferon inchronic hepatitis C

Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL.

We assessed the genetic polymorphism of mannose-binding lectin (MBL) in 93 patients with chronic hepatitis C (45 responders and 48 nonresponders to interferon) and 218 healthy controls. Mutant allele was identified only at codon 54 (Gly-->Asp), leading to three genotypes (54 m/m, 54 W/m, and 54 W/W). Frequency of 54 m/m was significantly lower in interferon-responders (2.2%), compared to those in nonresponders (14.6%) and controls (10.6%): p < 0.05. Our results suggest that homozygous carriage of the variant allele of codon 54 of MBL may predict poor response to interferon in chronic hepatitis C patients.

Mutations in the hemochromatosis gene and response to interferon in chronic hepatitis C

Mutations in the hemochromatosis gene and response to interferon in chronic hepatitis C

The cost-effectiveness of prolonged alfa interferon for chronic hepatitis C in Spain

The cost-effectiveness of prolonged alfa interferon for chronic hepatitis C in Spain

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

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.

Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient data from European centers.

This study aimed to obtain a more precise estimation of the efficacy and tolerability of interferon-ribavirin combination therapy for chronic hepatitis C. A meta-analysis was carried out of individual patient data comprising about 90% of the published experience with combination therapy. The study was set in four European university-affiliated liver referral centers. A total of 186 individuals with chronic hepatitis C who had participated in three randomized controlled trials and one open study were selected for the study. Fifty-one had received ribavirin monotherapy (1000-1200 mg/day), 37 interferon monotherapy (3 MU 3x/week) and 78 interferon-ribavirin combination therapy (dosage as for monotherapy) for 6 months. Twenty patients served as controls. Follow-up after therapy was 6 months. Data analysis was by the multivariate logistical regression method. The primary outcome measure for efficacy was the percentage with a sustained response (ALT normalization and HCV RNA negativity 6 months after therapy). The sustained response rate was significantly higher for interferon-ribavirin combination therapy than for interferon or ribavirin monotherapy (odds ratio IFN-Riba vs IFN = 9.8, 95% CI 1.9-50). The estimated probability of sustained response following interferon-ribavirin combination therapy was 51% for patients without previous IFN therapy, 52% for patients with previous IFN therapy and response-relapse, and 16% for previous IFN non-responders. No serious adverse events were observed and less than 10% withdrew. The efficacy of interferon-ribavirin therapy appears to be enhanced two- to threefold over interferon monotherapy in all major subgroups of chronic hepatitis C patients tested. In view of its acceptable toxicity profile, interferon-ribavirin combination therapy is a candidate for the new standard therapy for chronic hepatitis C.

Hepatitis G virus infection in chronic hepatitis C: frequency, features and response to interferon therapy

Background/Aims: The pathogenic relevance of the hepatitis G virus (HGV) and its sensitivity to interferon are currently under investigation. This study aimed to investigate the prevalence of HGV infection in patients with chronic hepatitis C and to elucidate if HGV co-infection modifies the clinical course and the response to interferon therapy in this disease. Methods: HGV-RNA was investigated by reverse transcription-polymerase chain reaction in serum from 143 consecutive patients who received interferon α-2b (3 MU t.i.w.) for 24 weeks. Baseline features and response to therapy in HGV-infected and non-infected patients were compared. To assess the antiviral effect of interferon, serial quantitative measurement of HCV-RNA and HGV-RNA in serum was performed in patients co-infected with HCV and HGV. Results: Eight patients (5.6%) presented HGV-RNA sequences in serum. No significant differences were found between HGV-infected and non-infected patients in relation to age, sex, source of infection, liver function tests, liver histology and HCV genotype, nor in the biochemical response to interferon, which was sustained in 12% and 15%, transient in 37% and 30% and absent in 50% and 55% of HGV-infected and non-infected patients, respectively. HGV-RNA became negative in all treated patients, but sustained viral inhibition was observed only in those with low viral load. Conclusions: The prevalence of HGV infection in HCV-infected patients is relatively low in our geographical area. HGV co-infection does not appear to modify the clinical presentation nor the response to interferon in chronic hepatitis C. HGV is sensitive to interferon, particularly if pre-treatment viral load is low.

Quantification and genotyping of serum HCV-RNA in patients with chronic hepatitis C undergoing interferon treatment.

Quantification of serum HCV-RNA and HCV genotyping was studied in 27 patients with chronic hepatitis C undergoing interferon treatment. Pretreatment serum HCV-RNA levels were quantified using competitive RT-PCR and compared to a quantitative RT-PCR assay based on co-amplification of HCV-RNA with a synthetic RNA standard. HCV genotyping was performed using a line probe reversed hybridisation assay or direct solid-phase sequencing. This study shows the feasibility of performing HCV-RNA quantification. RT-PCR based on co-amplification HCV-RNA titer less than 6 x 10(4) genome equivalents/ml serum did correlate with a complete sustained response to alpha interferon in chronic hepatitis C. HCV genotype 1b was alpha predominantly associated with a high non-responder rate. Future prospective trials will be required to evaluate quantitative HCV-RNA levels and HCV genotyping as response predicting parameters for interferon-treatment.

Duration of chronic HCV infection and efficacy of interferon in chronic hepatitis C patients with a history of blood transfusion. The Study Group for Treatment of Hepatitis in the Kyushu Area.

To investigate correlations between the interval between blood transfusion and the start of IFN therapy, and IFN efficacy, we studied chronic hepatitis C patients with a history of blood transfusion. The subjects were 122 patients with chronic hepatitis C and a history of blood transfusion at 64 institutions. The patients were treated with high or low-dose IFN. High-dose therapy consisted of intramuscular injection of human lymphoblastoid interferon (HLBI), 6 x 10(6) IU daily for 2 weeks, then 3 times a week for 22 weeks, and low-dose interferon therapy of intramuscular injection of HLBI, 6 x 10(6) IU daily for 2 weeks, then 3 x 10(6) IU 3 times a week for 22 weeks. Normal serum ALT levels for 6 months or more after completing IFN (complete response) were found in 44/122 (36.2%) patients and HCV RNA was no longer detectable after completing IFN therapy in 19/68 (27.9%). Patients in whom the interval between blood transfusion and the start of IFN therapy was less than 20 years had significantly higher rates of HCV RNA-negative complete response than those in whom the interval was 20 years or more (p < 0.039). When chronic HCV infection is caused by blood transfusion, the efficacy of IFN depends on the duration of chronic HCV infection. Since the duration of HCV infection is a factor in predicting efficacy, early IFN therapy may be more effective.