Ribavirin in chronic hepatitis

Niro GA, Rosina F, Rizzetto M (2005b) Treatment of hepatitis D. J Viral Hepat 12 2-9 Niro GA, Ciancio A, Gaeta GB, SmedUe A, Marrone A, OUvero A, Stanzione M, David E, Bran-caccio G, Fontana R, Perri F, AndriuUi A, Rizzetto M (2006) Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology 44 713-720... 

Bajaj, J.S., Molina, E., Regev, A., Schiff, E.R., Jeffers, L.J. Pretreatment laparoscopic appearance of the liver can predict response to combination therapy with interferon alpha 2b and ribavirin in chronic hepatitis C. Gastrointest. Endosc. 2003 58 380- 383... 

Pegylated protein of rDNA origin containing 165 residues. Used either alone or in combination with antiviral agent ribavirin in chronic hepatitis C. 

Glue P, Rouzier-Panis R, Raffanel C, Sabo R, Giq)ta SK, Salfi iVf Jacobs S, Clement RP. A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. The Hepatitis C Intervention Therapy Group. Hepatology (2000) 32, 647-53. 

Thus, ribavirin is ineffective in chronic hepatitis D, whether given alone or in combination with IFN-a. 

Gunsar E, Akarca US, Ersoz G, Kobak AC, Karasu Z, Yuce G, liter T, Batur Y (2005) Two-year interferon therapy with or without ribavirin in chronic delta hepatitis. Antivir Ther 10 721-726 Habersetzer E, Boyer N, MarceUin P, Badly F, Ahmed SN, Alam J, Benhamou JP, Trepo C (2000) A pdot study of recombinant interferon beta-la for the treatment of chronic hepatitis C. Liver 20 437 41... 

Jen J, Laughlin M, Chung C, Heft S, Affrime MB, Gupta SK, Glue P, Hajian G (2002) Ribavirin dosing in chronic hepatitis C application of population pharmacokinetic-pharmacodynamic models, Clin Pharmacol Ther 72 349-361... 

Vidigal, P. G., Germer, J. J., and Zein, N. N., Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-betal genes in chronic hepatitis C patients treated with interferon and ribavirin, J. Hepatol., 36, 271, 2002. 

A severe acute flare of porphyria cutanea tarda has been reported in a 61-year-old man after 4 months of treatment with interferon alfa-2b plus ribavirin for chronic hepatitis C (553). No further relapse was observed after chloroquine treatment, despite continuation of the antiviral drugs. 

Antiviral Efficacy and Clinical Use. Ribavirin (Vira-zole) is active against several RNA and DNA viruses, including respiratory syncytial virus (RSV).106 Clinically, this drug is used to treat severe RSV pneumonia in infants and young children,106 and RSV in certain adult populations, including the elderly, people with cardiopulmonary problems, and people with a compromised immune system.29 Ribavirin may also be useful as a secondary agent in the treatment of influenza A and B in young adults. The combination of ribavirin and interferons (see section on Interferons, later) is often the treatment of choice in chronic hepatitis C infection.30 72... 

As regular psychiatric assessment is not always possible, the identification of easily detectable predictive factors of severe psychiatric disorders may help select which patients should undergo close psychiatric assessment. In 71 patients treated with interferon alfa alone or combined with ribavirin for chronic hepatitis C, female sex, scores on the MADRS at 4 months of treatment, sleep disorders, and prior antidepressant use were independent risk factors of suicidal behavior or depression (349). This study also suggested that prolonged follow-up is required, as 8% of patients still had suicidal behavior 6 months after the end of treatment. 

Itoh, Y., Okanoue, T. Ribavirin-induced hemolytic anemia in chronic hepatitis C patients (editorial). J. Gastroenterol. 2004 39 704—705... 

Thnlnvath, P.J., Pande, H., Maygers, J. Combination therapy with interferon-alpha (2b), ribavirin, and amantadine in chronic hepatitis C nonresponders to interferon and ribavirin. Dig. Dis. Sci. 2003 48 594- 597... 

Ribavirin This guanosine analogue was first used experimentally by o. Reichard et al. (1991) and in chronic hepatitis C by J. Andersson et al. (1991). It is rapidly absorbed and distributed in the body, but is excreted slowly (half-life 79 hours). The bioavailability is 45-65%. As a monotherapy, it only leads to a decrease in transaminases and a slight improvement in histological activity. Ribavirin may not exhibit a direct antiviral effect, but can trigger a favourable response to interferon. When combined with IFN, ribavirin proved far more efficacious in chronic hepatitis C (immunomo-dulation ) without any increase in the typical side effects of IFN. (49, 51, 53) (s. p. 707)... 

In a 61-year-old man, who was taking long-term warfarin after a heart valve replacement, the dose of warfarin had to be increased by 40% after the introduction of ribavirin for chronic hepatitis C the inhibition of the effect of warfarin was reproduced on rechallenge (272). 

In one study in 119 patients treated with interferon alfa and ribavirin for chronic hepatitis C, in whom neutropenia was not considered as a cause for exclusion or dosage modification, the neutrophil count fell by an average of 34% (31-74%) (226). During the course of treatment, 32 patients had at least one neutrophil count below 1 X 10 /1, 11 had a neutrophil count below 0.75 x 10 /1, and 2 had a neutrophil count below 0.5 x 10 /1 however, none of these patients required dosage modification because of neutropenia. None of the 22 patients who developed documented or suspected bacterial infections... 

A spectrum of cutaneous lesions has been described distant from sites of interferon alfa injection. The clinical and histological characteristics of inflammatory skin lesions that occurred away from injection sites have been investigated in 20 patients treated with interferon alfa-2a or 2b plus ribavirin for chronic hepatitis C (299). Cutaneous lesions developed between 2 weeks and 4 months and consisted of pruritic papular erythematous eruptions with occasional vesicles. These eczema-like skin lesions predominated on the distal limbs, the head, and the neck. Photosensitivity was also noted in four patients and mucous lesions in two. Skin biopsy mostly showed non-specific mononuclear infiltrates. The skin lesions were promptly reversible in 10 patients who required treatment withdrawal, while others improved after symptomatic treatment. Two of the three patients who again received the same or another type of interferon alfa had recurrence of their lesions. Skin tests performed in six patients were negative, including the two patients who relapsed after rechallenge with interferon alfa, and were therefore considered unhelpful. 

Kumar AS, Russo MW, Esposito S, Borezuk A, Jacobson I, Brown M, Brown RS. Severe pulmonary toxicity of interferon and ribavirin therapy in chronic hepatitis C. Am J Gastroenterol 2001 96(Suppl) 127. 

Jain K, Lam WC, Waheeb S, Thai Q, Heathcote J. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin. Br J Ophthalmol 2001 85(10) 1171-3. 

Torriani EJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia J, et al, APRICOT Study Group. Pegin-terferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004 351 438-50. 

The availability of pegylated versions of interferon has allowed for less frequent dosing and better therapeutic response in chronic hepatitis C. However, therapeutic response of patients with chronic hepatitis C to combination pegylated interferon-a and ribavirin therapy is expected in less than half of treated patients with genotype 1. 

Khakoo S, Glue P, Grellier L, Wells B, Bell A, Dash C, Murray-Lyon I, Lypnyj D, Flaimery B, Walters K, Dusheiko GM. Ribavirin and interferon alfa-2b in chronic hepatitis C assessment of possible pharmacokinetic and pharmacod3fnamic interactions. BrJ Clin Pharmacol (1998) 46, 563-70. 

In a systematic review of case reports of pneumonitis in patients receiving peginter-feron and ribavirin for chronic hepatitis C infection, 58 cases were traced [37 ]. Pneumonitis presented with any of the combination of fever, dyspnea, and cough and was fatal in 7% of cases, exclusively with pegin-terferon alfa-2b. 

Type I diabetes mellitus and thyroid disease reportedly develop in 0.08-2.6% and 10-15% of patients treated with combined interferon alfa- -ribavirin for chronic hepatitis C but rarely coexist however, both conditions have been reported in a 33-year-old woman [50 ]. In another case, a 55-year-old woman developed type 1 diabetes and had a recurrence of Graves disease during treatment with peginterferon alfa -I- ribavirin for chronic hepatitis C [51 ]. There were serum anti-glutamic acid decarboxylase antibodies and the authors suggested that she had autoimmune polyglandular syndrome type III. 

Shakoor A, Shafqat F, Te Mehmud, Akram M, Riaz S, Iqbal Z, Khan AA. Frequency of depression and somatic symptoms in patients on interferon alpha/ ribavirin for chronic hepatitis C. J Ayub Med Coll Abbottabad 2010 22(4) 6-9. 

Shin MK, Kim TH, Ju K, Ha CY, Min HJ, Jung WT, Lee OJ. A case of sudden-onset hearing loss in a patient treated with peginterferon alpha-2b and ribavirin for chronic hepatitis C. Korean J Hepatol 2009 15(3) 370. ... 

Pawelczyk T, Pawelczyk A, Strzelecki D, Rabe-Jablonska J. Pegylated interferon alpha and ribavirin therapy may induce working memory disturbances in chronic hepatitis C patients. Gen Hosp Psychiatry 2008 30(6) 501-8. 

Cardiovascular IFN-induced cardiotoxicity which occurs rarely was recently reported in the form of so-called sick sinus syndrome, a malfunction of the sinus node producing arrhythmias. A 45-year-old woman suffered sinus node dysfunction after receiving pegylated IFNa-ribavirin for chronic hepatitis C. Withdrawal of the therapy did not reverse the dysfunction and the patient required the implantation of a permanent pacemaker [31 ]. 

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