Interferon-alpha For Chronic Hepatitis Research Articles

SAT-164 - Hepatitis B surface antigen loss rate and safety and discontinuations with pegylated interferon alpha in chronic hepatitis B virus infection, a systematic review

SAT-164 - Hepatitis B surface antigen loss rate and safety and discontinuations with pegylated interferon alpha in chronic hepatitis B virus infection, a systematic review

Interferon-alpha-associated presumed ocular sarcoidosis

Interferon alpha, used in the treatment of different viral, autoimmune and malignant diseases, is known to induce a variety of side effects. Recently, induction of sarcoidosis during interferon therapy has been reported. We analyzed patients for uveitis, possibly induced by interferon alpha. We report on three patients who had developed typical signs of ocular sarcoidosis under treatment with interferon alpha for chronic hepatitis C virus infection. In two patients, conventional interferon alpha was used and in another one, pegylated interferon alpha-2b. All patients additionally received ribavirin. In all three cases, panuveitis was diagnosed. The mean duration of interferon treatment before development of uveitis was 10 months. Clinically, all patients demonstrated granulomatous panuveitis with choroidal granulomas of various sizes. In one case, the uveitis developed together with renal failure, fever and malaise. In this patient, an elevated ACE level was detected. In another patient, the diagnosis of sarcoid induced uveitis was confirmed by positive chest CT scan. The intraocular inflammation was managed with a reduction of the interferon dosage. The therapy with ribavirin was not changed. All patients received topical steroids. Systemic steroids were applied only in the case with systemic disease manifestations. Uveitis can be a sign of sarcoidosis induced by interferon alpha. Further studies are required to support the observation that with early diagnosis the prognosis of uveitis seems to be good.

Response to Interferon-Alpha in Chronic Hepatitis B Patients with and without Precore Mutant Strain and Effects on HBsAg Titers

Background: Chronic hepatitis B (CHB) affects 400 million people worldwide and is a major cause of morbidity and mortality. It is known that HBV DNA sequences were detected after the clearance of serum hepatitis B surface antigen (HBsAg) often in serum, liver and peripheral blood mononuclear cells. The objectives of our study were to evaluate the previous measurements of HBsAg titers versus. quantitative hepatitis B virus (HBV) DNA and ALT measurements in order to predict the nonresponse and response in interferon-alpha (IFN-α)-treated HBeAg-positive and HBeAg-negative chronic HBV patients. Methods: We investigate whether the presence of precore mutant affects the response to IFN-α therapy and on the titer of HBsAg or not. Twenty-one HBeAg-positive (group1), 38 HBeAg-negative (group 2), and 47 healthy inactive carriers (group 3) made up this study. Liver biopsy showed chronic hepatitis, there was no cirrhosis and none of the patients had IFN-α therapy before. Results: The decrease in HBsAg titers was found as statistically not significant in groups 1 (p = 0.192) and 3 (p = 0.236) and statistically significant in group 2 (p = 0.0001) within a 6-month interval. Conclusion: HBsAg titer may be a factor to predict the primary responders and nonresponders specially in HBeAg-negative patients.

Exacerbation of Graves Ophthalmopathy With Interferon-α Therapy.

Thyroid dysfunction, particularly hypothyroidism, following interferon-α therapy is not uncommon. To our knowledge, this is the first case report of exacerbation of Graves ophthalmopathy during treatment with interferon-α for chronic hepatitis C virus.

Systemic sarcoidosis presenting in a tattooed man undergoing treatment for hepatitis C

A heavily tattooed man presented with nodular, ulcerated sarcoidal lesions distributed throughout all the colours of his tattoos. The lesions developed within the confines of his tattoos 4 months into therapy with ribavirin and interferon-alpha for chronic hepatitis C. This appears to be the first case of sarcoidosis in association with numerous pigment colours as well as dual therapy for hepatitis C.

Assessing Clinical Utility of Hepatitis C Virus Quantitative RT-PCR Data: Implications for Identification of Responders Among alpha-Interferon-treated Patients.

Background: Detection of hepatitis C virus (HCV) RNA in serum or plasma is currently the best means of identifying active HCV infection. In this study, we assessed the clinical utility of the HCV Amplicor Monitor (Roche Molecular Diagnostics, Branchburg, NJ) quantitative assay for monitoring viral burden and its implications for identifying responders among alpha-interferon-treated patients with chronic hepatitis C. Methods and Results: Precision and linearity were determined on aliquots of a pooled control serum. Error of the mean was normally distributed. The coefficient of variation of log10-transformed titers was 2%-6% over a range of 1.5 x 10(4)-1.5 x 10(5) copies/mL. Linearity over this range was high (R=.98-.99). Accuracy, as evaluated by comparison of split samples, showed that the Amplicor assay provided an unbiased estimate of the values from a reference laboratory. In a sample of 36 patients treated with alpha-interferon for chronic hepatitis C disease, mean viral titer declined with improvement of disease. The assay demonstrated heterogeneity among clinical responders with regard to their ability to actually clear their viral burden. Conclusions: Decreased viral burden as measured by the HCV Amplicor assay is potentially useful for monitoring individuals with HCV infection.

High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study

BackgroundInterferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues.MethodsWe performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001.ResultsThere was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5–5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25–9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test).ConclusionWe confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis.

Responsiveness to interferon alpha in chronic hepatitis B by presumed vertical transmission

This study was to evaluate responsiveness to IFN-α and investigate the benefits of sustained response (SR) in patients who were presumed as being vertically transmitted in Korea. A total of 46 patients of presumed vertical transmission with biopsy-proven HBeAg-positive chronic HBV infection were treated with IFN-α and followed. We tried to find the factors associated with SR and compared the cumulative rate of HCC and survival between SR group and non-sustained/non-responder (NSR) group. HBeAg loss was acquired in 35% (16/46) within a year but SR was observed in 22% (10/46). Age <35 years and ALT levels >7×ULN were significant favorable factors for SR (OR 0.56, 0.49, 95%CI 0.38–0.82, 0.29–0.81, respectively) (both P<0.05). There were no significant differences of cumulative HCC-free survival (100 vs. 68% at 12 years, P=0.36) and survival (100 vs. 73% at 12 years, P=0.3) between SR group and NSR group. In conclusion, age below 35 years old and serum ALT levels above 7×ULN may predict IFN-α therapy-induced SR among them, although we cannot affirm the effects on HCC prevention or survival.

Weight-based dosing of pegylated interferon-alpha in chronic hepatitis C: just a marketing 'gag'?

Today medical-scientific data are diluted by the marketing strategies of the biomedical industry making it difficult for practising physicians to decide what is correct or wrong. One typical example is the use of pegylated interferons for treatment of chronic hepatititis C. In this report the arguments pro and contra weight-based dosing are critically discussed. The factors contributing to success or failure to eradicate the virus are manifold, and include the sensitivity of the virus to interferon, viral genotype, age, gender stage of fibrosis, presence or absense of steatosis. Weight by itself plays just a minor role. The impact of weight-based dosing in general is overestimated and certainly not needed when 40 kD branched PEG-IFNalpha2a with a restricted volume of distribution is used. Whether weight-based dosing of 12 kD linear PEG-IFNalpha2b provides any benefit over a flat dose of the drug remains to be studied.

971 Long term follow up of sustained responders to interferon alpha in chronic hepatitis C: a meta-analysis assessing true clinical endpoints

971 Long term follow up of sustained responders to interferon alpha in chronic hepatitis C: a meta-analysis assessing true clinical endpoints

WITHDRAWN: Ribavirin with or without alpha interferon for chronic hepatitis C.

Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy is not established. To assess the efficacy and safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders with chronic hepatitis C. Eligible trials were identified through searches on electronic databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted. We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo, or alpha interferon for chronic hepatitis C. The primary outcome measures were the 'sustained' (six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the 'end of treatment' and 'sustained' biochemical response, the 'end of treatment' virologic response, histology, quality of life, and adverse events. We included eight trials in which 271 patients were randomised to ribavirin versus placebo or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI) 0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy, combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84) or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events. Combination therapy increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological response, but also the occurrence of adverse events.

Ribavirin with or without alpha interferon for chronic hepatitis C.

Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy is not established. To assess the efficacy and safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders with chronic hepatitis C. Eligible trials were identified through searches on electronic databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted. We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo, or alpha interferon for chronic hepatitis C. The primary outcome measures were the 'sustained' (six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the 'end of treatment' and 'sustained' biochemical response, the 'end of treatment' virologic response, histology, quality of life, and adverse events. We included eight trials in which 271 patients were randomised to ribavirin versus placebo or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI) 0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy, combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84) or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events. Combination therapy increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological response, but also the occurrence of adverse events.

Impact of smoker's polycythemia on clinical and laboratory features and on the response rate to interferon-alpha in chronic hepatitis C (CHC) patients

Impact of smoker's polycythemia on clinical and laboratory features and on the response rate to interferon-alpha in chronic hepatitis C (CHC) patients

Human leucocyte interferon-alpha in the treatment of chronic hepatitis C.

To assess the efficacy of different schedules of human leucocyte interferon alpha in chronic hepatitis C. A total of 213 naive patients with chronic hepatitis C were treated with 4 different schedules of human leucocyte interferon alpha. Sustained response was defined as persistently normal alanine amino transferase values with negative serum hepatitis C virus-RNA up to 12 months after therapy withdrawal. Rates of sustained response were 16% with 3 MU tiw for 6 months, 33% with 6 MU tiw for 5 months after a priming dose of 9 MU tiw for a month, 32% with 3 MU tiw for 12 months and 20% with 3 MU daily for 6 months. The major factors affecting the response rate were age and the hepatitis C virus genotype, as a sustained response was significantly higher in patients under 45 years and infected by hepatitis C virus types other than hepatitis C virus-1. Treatment was well tolerated and side-effects and drop-out events were similar to those described with other types of alpha-interferons. Human leucocyte interferon alpha appears to be equivalent to recombinant interferon-alpha in the treatment of chronic hepatitis C.

Pulmonale Sarkoidose: eine seltene Nebenwirkung einer Interferon-α-Therapie bei chronischer Hepatitis-C-Infektion

This is a case report of a 44-year-old woman who received a 1-year-treatment with interferon-alpha for chronic hepatitis C virus infection. 3 months after cessation of the therapy she relapsed and was successfully retreated 12 months with a combination of interferon-alpha and ribavirin thereafter. During the treatment the patient developed a typical flue-like syndrome, dry cough with exertional dyspnea that was initially interpreted as a typical side effect of interferon-alpha treatment. Due to the persisting cough, further radiologic and histologic work up was done and results were significant for interstitial sarcoidosis. After interferon-treatment was stopped the pulmonary symptoms resolved completely while pathologic changes in radiographic imaging persisted. Interferon-alpha may have contributed to the development and progression of sarcoidosis by activation of cellular immunity. Although there are only few reports about pulmonary sarcoidosis associated with interferon-alpha treatment, this entity should be included in the differential diagnosis of putative side effects of interferon-alpha therapy.

Effects of interferon treatment on the glucose metabolism of patients with chronic hepatitis C

Background: The authors report on changes in carbohydrate metabolism observed in 32 patients undergoing therapy with interferon-alpha for chronic hepatitis C. Methods: Diabetes had been diagnosed in three patients and impaired glucose tolerance ascertained in one patient before interferon therapy was started. The remaining 28 patients were non-diabetic. Interferon-alpha was administered in 3-MU doses three times per week. Results: Glucose tolerance deteriorated in two of the three diabetics, and eventually these patients had to be switched from oral hypoglycemic agents to insulin. The patient with impaired glucose tolerance at baseline progressed gradually to overt diabetes. Nine of the 28 previously non-diabetic patients developed impaired glucose tolerance during interferon therapy. Conclusion: The deleterious effects of interferon-alpha on carbohydrate metabolism proved to be reversible. Regular monitoring of the glucose level of patients during and after interferon therapy is mandatory.

Perihepatic lymphadenopathy and the response to alpha interferon inchronic hepatitis C

Perihepatic lymphadenopathy and the response to alpha interferon inchronic hepatitis C

Health profile preferences of hepatitis C patients.

The side effects of interferon-alpha for chronic hepatitis C are well-known. Patients may differ with respect to their tolerance of these side effects and also with respect to their individual preferences. We administered a brief questionnaire to 67 outpatients with hepatitis C virus infection. Patients were asked to make hypothetical choices between six-month profiles of health. The results were as follows: (1) patients preferred to expedite rather than postpone intervals of poor health; (2) preferences of patients with low quality-of-life were quite similar to preferences of healthier patients; (3) patients' choices satisfied transitivity; (4) patients' choices satisfied preferential independence; and (5) patients gave a variety of reasons for their choices. These results corroborate other investigations of health preferences, and serve to introduce the field of preference elicitation to gastroenterologists.

Treatment with interferon-α in patients with chronic hepatitis and mood or anxiety disorders

We prospectively studied 50 patients treated with interferon-alpha for chronic hepatitis and found no evidence that patients with a pre-existing mood or anxiety disorder were more likely than other patients to interrupt the interferon-alpha therapy.

Interferon-alpha in chronic hepatitis C infection in dialysis patients.

This study assesses the efficacy and adverse effects of interferon-alpha (IFN-alpha) administered at a dosage of 3 million units three times weekly for 1 year in 17 hemodialysis patients with hepatitic C virus (HCV)-associated chronic hepatitis (biopsy proven). The patients were prospectively followed up for a period of 18 months. Liver biopsy was repeated after 6 months of treatment in 13 patients. Patients were classified according to the histological activity index. Biochemical and virological responses were evaluated at the end (end-of-treatment response) and 6 months after completion of therapy (sustained response). HCV RNA became negative in 76% of the patients after 12 weeks of treatment, in 88% after 12 months of treatment, and in 71% of the patients 6 months after completion of therapy. HCV genotype 4 was found in 60% of our population. Alanine aminotransferase (ALT) levels were initially increased in only 6 patients and normalized in 4 of these patients after 12 weeks of therapy, with end-of-treatment and sustained biochemical responses of 83% and 67%, respectively. Of 13 patients who underwent liver biopsies after 6 months of therapy, 11 patients (85%) showed histological improvement. One patient could not tolerate therapy because of marked lethargy and myalgia; the other patients had minor side effects that did not require discontinuation of treatment. Two patients received a cadaveric renal transplant after 1 year of IFN treatment, and they continued to maintain biochemical and virological responses after a follow-up of 17 and 28 months, respectively.