Hepatitis C infection

Hepatitis C infection has an unpredictable natural history with significant potential for causing severe liver disease and variable response to current therapy based on pretreatment factors. Therefore, HCV is an excellent model to describe the... 

Zeuzem S, Buti M, Ferenci P, Sped J, Horsmans Y, Cianciara J, Ibranyi E, Weiland O, NovieUo S, Brass C, Albrecht J (2006) Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J Hepatol 44(1) 97-103... 

HCV NS5B polymerase is an RNA-dependent RNA polymerase that is essential for viral replication. Thus, the inhibition of this enzyme offers a potential treatment for hepatitis C infection. Beaulieu et al. [51] report on the parallel optimization of enzyme inhibition potency and physical properties. In the first stage of hit characteri-... 

Interferon-a causes hypothyroidism in up to 39% of patients being treated for hepatitis C infection. Patients may develop a transient thyroiditis with hyperthyroidism prior to becoming hypothyroid. The hypothyroidism may be transient as well. Asians and patients with preexisting anti-TPOAbs are more likely to develop interferon-induced hypothyroidism. The mechanism of interferon-induced hypothyroidism is not known. If LT4 replacement is initiated, it should be stopped after 6 months to re-evaluate the need for replacement therapy. 

Yee LJ, Tang J, Gibson AW, Kimberly R, Van Leeuwen DJ, Kaslow RA. Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection. Hepatology 2001 33[3] 708—712. 

Rebetron Combination Therapy (kit containing interferon alfa-2b inj plus ribavirin capsules) more effective than interferon alfa-2b monotherapyfor chronic hepatitis C infection... 

Drug interactions It is not known if PEG-Intron causes clinically significant drug-drug interactions with drugs metabolized by the liver in patients with chronic hepatitis C infection. 

Dolan KA, Shearer J, White B, Zhou J, Kaldor J Wodak AD (2005). Four-year follow-up of imprisoned male heroin users and methadone treatment mortality, re-incarceration and hepatitis C infection. Addiction, 100, 820-8... 

Rodger A, Roberts S, Lanigan A et al. (2000). Assessment of long-term outcomes of community-acquired hepatitis C infection in a cohort with sera stored from 1971 to 1975. Hepatology, 32, 582-7... 

Pharmacokinetics, safety, and antiviral effects of hypericin were studied in patients with chronic hepatitis C infection (Fig. 4) (71). The patients received an eight-weeks course of 0.05 and 0.10 mg/kg hypericin orally once a day. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 hours, respectively, for the doses of 0.05 and 0.10 mg/ kg) and mean AUC determinations of 1.5 and 3.1 pg/mL/hr, respectively. Because relatively high doses of 0.05 and O.lOmg/kg/day were given, which will probably be not reached after oral intake of recommended doses of SJW extract preparations, it is not surprising that hypericin caused a considerable phototoxicity in this study. 

In addition to oral administration for hepatitis C infection in combination with interferon alfa, aerosolized ribavirin is administered by nebulizer (20 mg/mL for 12-18 hours per day) to children and infants with severe respiratory syncytial virus (RSV) bronchiolitis or pneumonia to reduce the severity and duration of illness. Aerosolized ribavirin has also been used to treat influenza A and infections but has not gained widespread use. Systemic absorption is low (< 1%). Aerosolized ribavirin is generally well tolerated but may cause conjunctival or bronchial irritation. Health care workers should be protected against extended inhalation exposure. The aerosolized drug may precipitate on contact lenses. 

Tasi TN, Hsieh CH. Development of reversible diabetes mellitus after cessation of interferon-alpha therapy for chronic hepatitis C infection. NZ Med J 2004 117 U1230. 

Amantadine and rimantadine are administered to individuals already infected with influenza A to lessen the extent of the illness associated with the virus. These drugs are also given prophylactically to individuals who may have been exposed to influenza A and to high-risk patients such as the elderly or those with cardiopulmonary and other diseases. Amantadine may also be somewhat effective in treating certain cases of hepatitis C infection.103 These drugs are typically administered orally, either in capsule form or in a syrup preparation. 

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... 

Ribavirin capsules in combination with subcutaneous interferon alfa-2b are effective for the treatment of chronic hepatitis C infection in patients with compensated liver disease (see Anti-Hepatitis Agents, above). Monotherapy with ribavirin alone is not effective. 

In addition to oral administration for hepatitis C infection in combination with interferon alfa (see above), aerosolized ribavirin is administered by nebulizer (20 mg/mL for 12-18 hours per day for... 

ISIS 14803 HepC Hepatitis C infection Intravenous Isis... 

Epidemiological studies have identified a number of factors that contribute to the risk of developing cirrhosis. Regular (moderate) alcohol consumption, age older than 50 years, and male gender are examples that increase cirrhosis risk in chronic hepatitis C infection, and older age, obesity, insulin resistance or type 2 diabetes, hypertension and hyperlipidaemia in non-alcoholic steatohepatitis. 

The relation between interferon alfa-induced depressive disorders and the viral response to treatment has been examined in 39 patients with hepatitis C infection and no history of active psychiatric disease (359). After treatment with interferon alfa-2b and ribavirin for 6-12 months, 13 developed major depressive disorders requiring treatment with citalopram. The end-of-treatment response rates and sustained viral response rates were significantly greater in patients who developed a major depressive disorder than in those who did not (62% versus 27% and 39% versus 12% respectively). Despite the small sample, these results suggest that interferon alfa-induced depression occurs at doses or concentrations that... 

Ribavirin (Tribavirin) is a synthetic nucleoside which may be administered by inhalation via a special ventilator for RSV bronchiolitis in infants and children. Efficacy for this indication is controversial, and it is usually reserved for the most severe cases, and those with co-existing illnesses, such as immunosuppression. Systemic absorption by the inhalational route is negligible. It is effective by mouth 45 h) in treating Lassa fever and, when combined with interferon alfa-2b, for chronic hepatitis C infection (see below). Systemic ribavirin is an important teratogen, and it may cause cardiac, haematological, gastrointestinal and neurological side effects. 

Most individuals infected with the hepatitis C virus become long-term carriers. Chronic infection with hepatitis C virus affects an estimated 170 million individuals worldwide. Up to one-third of these will progress to cirrhosis with its attendant complications including hepatocellular carcinoma, over a period of 30-40 years. In the western world hepatitis C infection arises mainly from intravenous drug abuse. 

Dietrich, C.R, Stryjek-Kaminska, D., Teuber, G., Lee, J.H., Caspary, W.R, Zeuzem, S. Perihepatic lymph nodes as a marker of antiviral response in patients with chronic hepatitis C infection. Amer. J. Roentgenol. 2000 174 699-704... 

Goetz, A.M., Ndimbie, O.K., Wagener, M.M., Muder, R.R. Prevalence of hepatitis C infection in health care workers affiliated with a liver transplant center. Transplantation 1995 59 990-994... 

Gordon, F.D., Anastoponlos, H., Khettry, U., Loda, M., Jenkins, R.L., Lewis, W.D., Trey, C. Hepatitis C infection a rare cause of fulminant hepatic failure. Amer. X Gastroenterol. 1995 90 117-120... 

Kenny-Walsh, E. Clinical outcome after hepatitis C infection from contaminated anti-D immune globulin. New Engl. X Med. 1999 340 1228-1233... 

Loustaud-Ratti, V., Liozon, E., Karaaslan, H., Alain, S., le Meur, Y., Denis, F., Vidal, E. Interferon alpha and ribavirin for membranoproli-ferative glomerulonephritis and hepatitis C infection. Amer. J. Med. 2002 113 516-519... 

R., Jnca, N., Mizokami, M., McFarlane, I.G. Chronic hepatitis C infection influence of the viral load, genotypes, and GBV-C/HGV coinfection on the severity of the disease in a Brazilian population. X Med. Virol. 2002 67 27-32... 

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