Mechanisms of action of interferon and ribavirin in chronic hepatitis C: Summary of a workshop

Chung, Raymond T.; Gale, Michael; Polyak, Stephen J.; Lemon, Stanley M.; Liang, T. Jake; Hoofnagle, Jay H.

doi:10.1002/hep.22070

Cited by 82 publications

(62 citation statements)

References 71 publications

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“…74 Proposed mechanisms explaining the efficacy of ribavirin have included its role in driving mutational frequencies, decreasing viral synthesis, or as an immunologic enhancer. [90][91][92][93] The importance of ribavirin in delaying the emergence of drug resistance has also been well illustrated. In PROVE 2, viral breakthrough (defined as Ͼ1 log above HCV RNA nadir or increase to Ͼ100 IU/mL in patients with previous viral suppression) was much higher in the "no ribavirin" arm compared to the SOC and triple therapy arms (24% compared to 1% and 2%, respectively).…”

Section: Role Of Ribavirin With Stat-cmentioning

confidence: 99%

Avoiding therapeutic pitfalls: The rational use of specifically targeted agents against hepatitis C infection

2008

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The development of specifically targeted antiviral agents against hepatitis C is a major therapeutic advance that promises to markedly improve treatment response rates in patients with chronic infection. However, rapid emergence of drug resistance has already been described, the consequences of which are not yet understood. Although there are important differences between hepatitis C (HCV) and human immunodeficiency virus (HIV) infection, the judicious use of candidate agents against HCV should be guided by principles that have been established in the HIV therapeutic arena. In this review, we attempt to draw useful parallels between the development of antiretroviral therapy for HIV and preliminary data on antiviral agents for hepatitis C virus infection. Applying concepts learned in HIV therapeutics will hopefully lead to a prudent and cautious path in HCV treatment paradigms, particularly with respect to drug resistance. (HEPATOLOGY 2008;48:1700-1712

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Section: Role Of Ribavirin With Stat-cmentioning

confidence: 99%

Avoiding therapeutic pitfalls: The rational use of specifically targeted agents against hepatitis C infection

2008

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“…In the present case, new onset of type 1 diabetes and recurrence of Graves' disease were observed following PEG-IFN-alpha plus ribavirin treatment for chronic hepatitis C. It is well known that autoimmune disorders develop following IFN treatment (5)(6)(7)(8). IFN has been reported to exert antitumor activity, cytostatic activity and immunoregulatory effects, and antiviral activity (3).…”

Section: Discussionmentioning

confidence: 81%

“…In addition, animals administered ribavirin show enhancement of autoimmune reaction (4). Thus, the combination of IFN and ribavirin may induce autoimmune-related disorders, type 1 diabetes, autoimmune thyroid disease, systemic lupus erythematosus (SLE), and rheumatoid arthritis (5)(6)(7)(8). Graves' disease and type 1 diabetes are considered in relation to organ-specific autoimmune disease.…”

Section: Introductionmentioning

confidence: 99%

A Case of Type 1 Diabetes Onset and Recurrence of Graves' Disease During Pegylated Interferon-Alpha Plus Ribavirin Treatment for Chronic Hepatitis C

Fujioka¹,

Honda²,

Yoshizaki³

et al. 2010

Intern. Med.

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We report a case of type 1 diabetes onset and recurrence of Graves' disease during pegylated interferon (PEG-IFN)-alpha plus ribavirin treatment for chronic hepatitis C. The patient was a 55-year-old woman diagnosed with chronic hepatitis at age 46 years. She was treated for Graves' disease at 50 years of age. Because Graves' disease remitted, PEG-IFN-alpha plus ribavirin treatment was started for chronic hepatitis C. She was examined because of complaints of general fatigue, weight loss, and palpitations after 24 weeks of the treatment. She was diagnosed with a recurrence of Graves' disease, and methimazole treatment was started. However, she complained of malaise, thirst, polyuria, and loss of body weight. Her fasting blood glucose level was 292 mg/dL and HbA1c was 9.3%. Serum anti-GAD (glutamic acid decarboxylase) antibodies were 2.2 U/mL. She was diagnosed with type 1 diabetes with ketosis, and insulin treatment was started. Serum anti-GAD antibodies gradually increased to 15.1 U/mL. Graves' disease and type 1 diabetes are often complicated, and the coincidental occurrence of these 2 diseases is known as autoimmune polyglandular syndrome type III. However, only a few cases have shown that these diseases occur after IFN treatment.

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“…This activation is not virus-specific, and genetic variants (both host and pathogen) allow for resistance and varied responses to treatment. Consensus opinion has suggested that the innate and adaptive immune responses, host genetic variables, genetic diversity of the virus, and clinical comorbidities (diabetes) may all account for the ineffectiveness of IFN/RBV in the treatment of HCV [23].…”

Section: Discussionmentioning

confidence: 99%

HCV Triple Therapy is Equally effective in African-Americans and Non-African-Americans

Wysocki

Newby

Balart

et al. 2014

J. Racial and Ethnic Health Disparities

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Real-world experience with HCV medications differs from original the index studies. AfricanAmericans (AA) are commonly underrepresented in clinical trials. Therefore, we hypothesized that postmarketing experience with the first generation HCV protease inhibitors (PI) (telaprevir and boceprevir) differs from premarket reports in clinically meaningful ways regarding patient race. We conducted a single-center, retrospective, observational analysis to evaluate the efficacy of HCV triple therapy in a nontrial setting. Clinical response and quantitative laboratory values were compared between AA and non-AA patients throughout the duration of treatment. Patients were included if they started triple therapy treatment after July 2011 and are not a part of any other clinical/pharmaceutical trials. Thirty-five patients with HCV genotype 1 were included in this study-22 non-AA and 13 AAs. AAs had a higher BMI compared to non-AA (33.6 vs 28.8, p=0.046). "High" baseline HCV RNA values (above 800,000 copies) were more prevalent in AA (69.2 %) vs non-AA (63.6 %). AA had less favorable IL28B genotypes; only 7.7 % had type CC compared to 40.9 % of non-AA. SVR12 was achieved 82 % of the time with each PI but there was no significance in type of PI used (p=1.00). Patients with cirrhosis were less likely to achieve SVR12 (40 %) compared to those without cirrhosis (88 %, p = 0.013). Thirty-three percent of the patients who received blood transfusions did not achieve SVR12 while every patient who did not require transfusion achieved SVR12 (p=0.001). All patients with IL28B genotype CC achieved SVR12 (p=0.007). SVR12 did not differ among AA (77 %) and non-AA (86.4 %) (p=0.528).

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Mechanisms of action of interferon and ribavirin in chronic hepatitis C: Summary of a workshop

Cited by 82 publications

References 71 publications

Avoiding therapeutic pitfalls: The rational use of specifically targeted agents against hepatitis C infection

Avoiding therapeutic pitfalls: The rational use of specifically targeted agents against hepatitis C infection

A Case of Type 1 Diabetes Onset and Recurrence of Graves' Disease During Pegylated Interferon-Alpha Plus Ribavirin Treatment for Chronic Hepatitis C

HCV Triple Therapy is Equally effective in African-Americans and Non-African-Americans

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