Treatment of Chronic Non-A, Non-B Hepatitis with Recombinant Human Alpha Interferon

Jh, Hoofnagle; Kd, Mullen; Db, Jones; Rustgi,; A, Di Bisceglie; Peters, Marion G.; Jg, Waggoner; Y, Park; Ea, Jones

doi:10.1056/nejm198612183152503

Cited by 901 publications

(312 citation statements)

References 12 publications

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“…Bone marrow suppression is a common side effect of interferon alfa. 32 Furthermore, patients with end-stage liver disease frequently have thrombocytopenia and/or leukopenia secondary to hypersplenism. Hypothyroidism and nausea and vomiting also are frequent side effects of this treatment in patients with noncirrhotic disease.…”

Section: Discussionmentioning

confidence: 99%

A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus–infected patients awaiting liver transplantation

Crippin

McCashland

Terrault

et al. 2002

Liver Transplantation

321

191

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Decompensated liver disease associated with chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation. It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival. The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known. We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b, with or without ribavirin. HCV RNApositive patients at or near the top of their respective waiting lists were randomly assigned to one of three treatment regimens until the time of liver transplantation: (1) group A, interferon alfa-2b, 1 ؋ 10 6 U/d; (2) group B, interferon alfa-2b, 3 ؋ 10 6 U three times weekly; or (3) group C, interferon alfa-2b, 1 ؋ 10 6 U/d, plus ribavirin, 400 mg twice daily. Less than half the patients screened met entry criteria, with thrombocytopenia and leukopenia the most common reasons for exclusion. Fifteen patients were administered antiviral therapy; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients, whereas 55% had a decrease in viral titers on therapy. Twenty-three adverse events occurred, including 20 serious adverse events. Thrombocytopenia was the most common adverse event. Two infectious complications occurred; one of these had a fatal outcome. We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria, adverse events associated with therapy are frequent and often severe in patients with Child's class B and C cirrhosis. C hronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States. 1 Although patients undergoing liver transplantation for HCV have been reported to have similar overall patient and graft survival to most other indications, 2-6 recurrence of HCV is a substantial source of morbidity, mortality, and graft loss. 2,4,7-10 To date, meaningful data regarding posttransplantation follow-up in HCV-infected recipients are only available for a mean of 3 to 5 years. [2][3][4][5][6] In the nontransplantation setting, it is estimated that the mean time from infection to the development of cirrhosis is 20 years. 11,12 In liver transplant recipients, the course of HCV-induced liver injury is accelerated, with HCV recurrence apparent histologically in approximately 50% of HCVinfected transplant recipients and HCV-associated allograft failure leading to death or graft loss in approximately 10% of transplant recipients by the fifth postoperative year. 2,3,7,10,[13][14][15][16][17] Greater pretransplantation levels of viremia have been associated with attenuated patient and allograft survival among HCV-infected liver transplant recipients. 7 The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplant Database report...

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Section: Discussionmentioning

confidence: 99%

A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus–infected patients awaiting liver transplantation

Crippin

McCashland

Terrault

et al. 2002

Liver Transplantation

321

191

View full text Add to dashboard Cite

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“…1 As a main player in innate immunity against viruses, the interferon (IFN) system has a key role in curtailing pathogens by putting infected and neighboring cells into an antiviral state. 2 Also, HCV has been known for a long time to be highly sensitive to treatment with type I IFNs, 3 and still today IFN-␣ is the major component of HCV therapy. The fact that HCV is sensitive to IFN yet it manages to establish persistent infections suggested that the virus may have evolved mechanisms to circumvent detection by the innate antiviral defense system.…”

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confidence: 99%

Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy

et al. 2007

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“…The potent antiviral and antitumor activity of IFNs has been used therapeutically in humans [8], and tried in cattle [12], horses [16], and pigs [13]. Recombinant feline interferon-ω (rFeIFN-ω), produced in silkworm larvae using a baculovirus vector [27,33], has shown antiviral activity against infection with feline calicivirus, herpesvirus and enteropathogenic virus [19,35].…”

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confidence: 99%

Clinical Effects of the Recombinant Feline Interferon-.OMEGA. on Experimental Parvovirus Infection in Beagle Dogs.

1998

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ABSTRACT. The clinical effects of recombinant feline interferon-ω (rFeIFN-ω), produced in silkworm by recombinant baculovirus, were examined in 3-4 month-old beagle dogs given an experimental canine parvovirus type-2 (CPV-2) infection. Clinical symptoms, such as pyrexia, vomiting, anorexia and diarrhea, were observed on day 4 after oral inoculation of 10 7 TCID 50 of CPV-2 (cc 238 strain) in almost all the inoculated dogs. From day 4, rFeIFN-ω (1 mega units/kg/day) or physiological saline was administered intravenously to infected dogs for 3 consecutive days. Seven out of 17 dogs treated with physiological saline showed hemorrhagic diarrhea and continuously expressed severe clinical enteritis; one dog died with a large amount of hemorrhagic rice-water stool on day 6 after viral exposure. In contrast, 4 out of 12 dogs treated with rFeIFN-ω showed severe clinical enteritis associated with intermittent diarrhea. Scoring of fecal condition revealed that treatment with rFeIFN-ω significantly shifted the enteritis from a severe to mild form. Furthermore, rFeIFN-ω administered in the morning decreased the number of dogs expressing clinical enteritis in the evening suggesting a rapid effect. Vomiting and anorexia were also improved by treatment with rFeIFN-ω. These results suggest that rFeIFN-ω can reduce severe enteritis caused by CPV-2 infection in dogs. -KEY WORDS: beagle dog, canine parvovirus, enteritis, experimental infection, recombinant feline interferon-ω.J.

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Treatment of Chronic Non-A, Non-B Hepatitis with Recombinant Human Alpha Interferon

Cited by 901 publications

References 12 publications

A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus–infected patients awaiting liver transplantation

A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus–infected patients awaiting liver transplantation

Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy

Clinical Effects of the Recombinant Feline Interferon-.OMEGA. on Experimental Parvovirus Infection in Beagle Dogs.

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