Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
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Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
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PMID:Treatment of chronic hepatitis B infection using interferon. 1610 70

For the treatment of HBV/HIV-co-infection, study data on interferon-based therapy are very limited and insufficient to draw any specific conclusions. In contrast, data on HBV-polymerase inhibitors (lamivudine, adefovir, tenofovir) are available from controlled trials. Lamivudine is well tolerated and safe, however, development of HBV-resistance is frequent. Adefovir has a nephrotoxic potential and may at least theoretically induce antiretroviral resistance in HBV/HIV-patients treated with adefovir. Tenofovir has gastrointestinal side effects, is associated with hypophospatemia, which has not induced serious osteopenia so far and may have a nephrotoxic potential. For HCV/HIV-co-infection pegylated interferon alpha plus ribavirin is standard of care. Flu-like symptoms, fatigue and depressive mood changes are frequent. In patients with a history of neurotic or minor depression initiation of treatment with antidepressants before the start of interferon-based therapy should be considered. Weight loss may be pronounced in individual cases. A marked decrease in absolute, but not relative CD4 +/- cells is the rule, but no relevant increase in opportunistic infection was observed, and anaemia (<10 g/dl) is reported in up to 30% of patients. Neutropenia (< 1,000 cells/microl) is observed in up to 50% of the patients. Adverse events specific to the HCV/HIV-patient population as compared to HCV-mono-infected patients are the occurrence of hyperlactataemia/lactic acidosis and hepatic decompensation.
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PMID:Treatment of viral hepatitis in HIV-coinfected patients-adverse events and their management. 1635 79

Persistent eosinophilia was diagnosed in a 19-year-old woman with general malaise, dyspnoea attacks, coughing and episodes of angioedema and associated swallowing problems, and in a 21-year-old man with visual problems, dyspnoea, fatigue, reduced appetite, weight loss and gastrointestinal problems. Both had hypereosinophilic syndrome (a rare disease) with organ damage. In both patients, fluorescence-in-situ-hybridisation (FISH) was negative for the fusion gene FIP1L1-PDGFRA (FIPI-like-1-platelet-derived growth factor receptor alpha). The female patient's disease did not respond to either oral corticosteroids or imatinib, but did respond to hydroxycarbamide. The male patient successively received prednisone, interferon alpha and hydroxycarbamide. His eosinophilia progressed nonetheless, but responded partially to imatinib. In addition, the patient underwent an allogenic non-myeloblative stem cell transplantation from his HLA-identical sister. In patients with persistent eosinophilia accompanied by organ damage or organ dysfunction, hypereosinophilic syndrome can be diagnosed providing all secondary causes of the eosinophilia have been ruled out. Complementary investigations should include cytogenetic and clonal analysis to rule out haemopoietic malignancy. Prednisone, hydroxycarbamide, interferon alpha and the promising imatinib are all treatment options.
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PMID:[Two patients with hypereosinophilic syndrome]. 1676 84

Interferon-induced sarcoidosis is well documented. We report a case of sarcoidosis in a patient with hepatitis C virus infection treated with pegylated interferon alpha and ribavirin. The patient developed cutaneous sarcoidosis about 6 months after beginning of the combination therapy. Spontaneous regression of the lesions was noted after discontinuation of the treatment. Interferon-alpha is known to stimulate T helper cells with a TH-1 profile immune response, which is the key immunologic event of a sarcoid granuloma formation. In addition to its antiviral action, ribavirin also enhanced the TH-1 response. Incidence of drug induced sarcoidosis may be underreported, because many symptoms of sarcoidosis mimic the side-effects of interferon as fever, myalgias, arthralgias, fatigue and symptoms of pulmonary diseases.
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PMID:[Cutaneous sarcoidosis during pegylated interferon alpha and ribavirin treatment of chronic hepatitis C--a case report]. 1737 Apr 74

The treatment of chronic hepatitis C, now well codified with the association of a pegylated interferon alpha and ribavirine, allows to obtain a prolonged virological response in more than half of the cases. The results are even better and reach about 70% of success when the treatment is optimized. In spite of these therapeutic advances, a substantial percentage are non responders or relapsers, mainly because of adverse effects of the treatment which lead to dose reductions or premature discontinuation. The main side effects involved in treatment modification are fatigue, muscular and articular pains, disturbance the humor, insomnia, depression, anaemia and leucopenia. These adverse effects can modify the quality of life of the patients considerably. Thus it is important to take care of them quickly after their appearance or even to try to anticipate them. It is also essential to provide a well adapted therapeutic education to get an optimal compliance to the treatment and thereby a better chance of success.
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PMID:[Chronic hepatitis C: management of side effects of treatment]. 1796 31

Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 degrees C. Clinically cryoglobulinemia is manifested in a variety of symptoms on different organs. The most important clinical symptoms are fatigue, peripheral neuropathy and vasculitis associated skin lesions. Pathophysiologically cryoglobulinemia is based on a disturbed immunocascade with an elevated B-cell-activity. Often a cryoglobulinemia progresses smoothly to a Non-Hodgkin-Lymphoma. The main activator of a cryoglobulinemia is a Hepatitis C virus infection. Other causes for developing a cryoglobulinemia are rheumatological and haematological diseases. In the past cryoglubulinemia has predominantly been treated with plasmapheresis and immunosuppression, nowadays antiviral strategies are becoming more important. Cases of rapid worsening under therapy with interferon alpha have also been reported. A promising new option is the use of rituximab.
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PMID:[Hepatitis associated cryoglobulinemia]. 1832 17

Severe endobronchial papillomatosis is associated with recurrent respiratory infections and airway obstruction. Current management includes treatment with antiviral and cytotoxic agents to slow papilloma growth and endobronchial therapies to excise the lesions. We report 2 cases of severe tracheobronchial papillomatosis which were managed with endobronchial laser and airway stenting. A 32-year-old man and a 55-year-old woman with known history of tracheobronchial papillomatosis were admitted with hemoptysis and dyspnea, respectively. They presented increasing frequencies of respiratory infections in the preceding year despite therapy with interferon alpha-2A, acyclovir, methotrexate and endobronchial treatment. Moreover, the 2nd patient presented 6 months previously to another institution with central airway obstruction which was treated with a covered metallic stent. Both patients underwent rigid bronchoscopy which revealed airway obstruction by papillomatous lesions. In the 2nd case, the metallic stent was broken due to fatigue and was infiltrated by a giant papilloma. Both patients received laser treatment and airway silicone stenting. After stenting, respiratory infection rate was greatly reduced and no further complications related to the papillomas occurred. This paper highlights the serious complications which may arise if endobronchial management of the disease includes insertion of metallic stents. In contrast, airway stenting with a silicone prosthesis may be useful in refractory endobronchial papillomatosis and may offer permanent control of symptoms.
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PMID:Airway stenting for severe endobronchial papillomatosis. 1848 74

Metastatic renal cell carcinoma is notoriously resistant to chemotherapy and radiotherapy. Immunotherapy with interferon alpha is widely used for the disease, but its treatment effects are poor. A 69-year-old Japanese women presented with gross hematuria. Imaging studies revealed a left renal tumor, 12 cm in diameter, and multiple pulmonary and hepatic lesions. No abnormal laboratory data were observed other than anemia with Hb 9.2 g/dl. Performance status was 0. She underwent radial left nepherectomy. Pathological examination showed clear cell renal cell carcinoma with moderate histological differentiation (grade 2) and microscopic vessel invasion; pT3aN0M1 (Pul, Hep). Memorial Sloon-Kettering Cancer Center classification was an intermediate risk due to anemia. She received interferon alpha, 5 million IU three times per week, postoperatively. In three months, hepatic lesions rapidly progressed although there was no interval change of pulmonary lesions. Then, the patient received interferon alpha at the same dose as described above and half-dose sorafenib, 400 mg per day. Grade 2 hypertension was under control by calcium channel blocker and the hand-foot syndrome was not obvious. No other grade 3/4 drug-related adverse events were observed. In one month after combination therapy, not only pulmonary lesions but also hepatic lesions were smaller. She has received this combination therapy with stable disease for six months. Performance status was 1 with grade 1 fatigue. The doses of this regimen may be tolerable, and might be an available treatment option for interferon alpha-resistant advanced renal cancer.
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PMID:[Interferon alpha and half-dose sorafenib is an effective treatment modality for interferon alpha-resistant metastatic renal cell carcinoma: a case report]. 1958 63

The objectives of this study were to (a) pilot test instruments measuring fatigue and quality of life (QOL); (b) pilot test an exercise intervention; and (c) estimate the effect size of this intervention relative to completion of combination therapy, fatigue, QOL, and walking distance in 20 patients with chronic hepatitis C about to begin interferon alpha and ribavirin treatment. Alpha reliabilities for both the Schwartz Cancer Fatigue Scale and Hepatitis Quality of Life Questionnaire were moderately high. Power analyses of all outcome measures indicated a small effect size and sample size estimate of 30-40 per group to achieve power of >.80.
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PMID:An intervention to prevent symptoms associated with hepatitis C: a pilot study. 2042 Oct

We report on a 19-year-old male patient with chronic HBeAg-positive hepatitis B-infection and agranulocytosis as a severe side effect of pegylated interferon alpha therapy. Within the first six months of therapy the hepatitis B virus DNA became undetectable in parallel with a significant decrease of the HBsAg serum concentration. After a six-month course of therapy the patient was admitted to our emergency unit. He appeared significantly ill and reported that he had fever for two days, painful oral mucosa, throat pain and general fatigue and discomfort. A complete blood cell count was performed and revealed a complete agranulocytosis with no detectable neutrophilic granulocytes in the blood smear. Antiviral therapy was immediately stopped and he was admitted to our clinic where a supportive therapy and an empirical course of broadband antibiotics were initiated. A few days later an additional treatment with intravenous prednisolone was started. Within the next week the agranulocytosis resolved and the neutrophil count was completely restored. In parallel, the clinical status improved quickly. This case demonstrates the need for our awareness of agranulocytosis as a rare but severe and potentially life-threatening side effect of interferon alpha therapy.
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PMID:Severe agranulocytosis as a rare side effect of pegylated interferon therapy for chronic hepatitis B. 2155 70


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