Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon alfa-2a resembles other recombinant alpha interferons in structure and pharmacology. Studies delineating its efficacy suggest that after 6 to 12 months of therapy, sustained biochemical responses occur in 4% to 49% of patients, providing adequate doses (> or = 3 million units three times weekly) are used. Overall, a dose-response curve is evident in regard to biochemical responses, decrease in histological scores for inflammation, and virological responses (percent negative serum hepatitis C virus [HCV] RNA) after treatment. Differences in response rates between studies probably reflect patient selection and particularly the percent of patients with established cirrhosis, because these patients respond less well than those with earlier histological stages of disease. A variety of regimens of interferon alfa-2a have been used, including use of higher doses, longer periods of treatment, induction using higher doses initially, and intermittent pulse therapy. Both longer periods of therapy and induction dosing show strong but not significant trends toward improvement in response rates, which reach significance when the two strategies are combined. Outcome is not significantly improved by escalating doses during therapy when inadequate responses are seen, or by pulse therapy. The side effect profile of interferon alfa-2a is similar to that of other interferons. Long-term follow-up studies have demonstrated that 90% of patients with a sustained biochemical response at 6 months after therapy maintain the response, and 95% remain negative for HCV RNA in serum. Challenges for the future include better delineation of the advantages of induction dosing, the optimal duration of therapy, and further understanding of the frequent discordance between HCV RNA data and aminotransferase levels. This latter finding suggests that use of both parameters is necessary to evaluate fully responses to therapy.
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PMID:Therapy of hepatitis C: interferon alfa-2a trials. 930 71

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare yet severe adverse drug-induced reaction with up to 10% mortality rate. Recent clinical trials reported an association between DRESS and telaprevir (TVR), an NS3/4A protease inhibitor of chronic hepatitis C (CHC) virus genotype 1. Its diagnosis is challenging given the variable pattern of cutaneous eruption and the myriad internal organ involvement. We present two patients who are middle-aged, obese, and white with CHC cirrhosis. They both developed a progressive diffuse, painful pruritic maculopapular rash at weeks 8 and 10 of CHC therapy with TVR, Peg-Interferon alfa-2a, and Ribavirin. They had no exposures to other medications that can cause this syndrome. Physical exam and labs and skin biopsy supported a "Definite" clinical diagnosis of DRESS, per RegiSCAR criteria. Thus Telaprevir-based triple therapy was discontinued and both patients experienced rapid resolution of the systemic symptoms with gradual improvement of eosinophilia and the skin eruption. These two cases illustrate the paramount importance of having a high index of suspicion for TVR-induced DRESS, critical for early diagnosis. Immediate discontinuation of TVR is essential in prevention of a potentially life-threatening complication. Risk factors for development of DRESS in patients receiving TVR remain to be elucidated.
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PMID:Chronic Hepatitis C Therapy in Liver Cirrhosis Complicated by Telaprevir-Induced DRESS. 2521 47