Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventional interferons including interferon-alpha (IFN-alpha) are cytokines used for years in the treatment of solid tumors and hematological malignancies. Their half-life is short. Pegylated forms of IFN-alpha present an improved pharmacokinetic profile that rendered them the preferred IFNs in hepatitis therapy. In the last decade, pegylated interferons (PegIFNs) have been investigated in melanoma patients. We review the scientific published literature on biology, pharmacokinetics, side effects and clinical applications of PegIFN-alpha in the treatment of stage III and IV melanoma. In the adjuvant setting, PegIFNalpha-2b has significant prolonged distant metastases free survival in patients with microscopic nodal involvement (stage TxN1aM0) and therefore is a promising treatment option in this patient population. In the palliative setting, monotherapy with PegIFNalpha-2alpha can induce complete remissions in a minority of stage IV melanoma patients. The combination of monochemotherapy is feasible and may result in lasting complete remissions. Ongoing research must focus on the identification of patients who mostly benefit, so that unnecessary toxicity would be avoided. Combining PegIFNs and chemotherapy or targeted agents deserves further exploration.
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PMID:Long-term pegylated interferon-alpha and its potential in the treatment of melanoma. 1970 6

Metastatic cutaneous melanoma has poor prognosis with 2-year survival rate of 10-20%. Melanoma cells express various antigens including gp100, melanoma antigen recognized by T cells 1 (MART-1), and tyrosinase, which can induce immune-mediated anticancer response via T cell activation. Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is an immune check point molecule that negatively regulates T cell activation and proliferation. Accordingly, recent phase III clinical trials demonstrated significant survival benefit with ipilimumab, a human monoclonal antibody (IgG1) that blocks the interaction of CTLA-4 with its ligands. Since the efficacy of ipilimumab depends on T cell activation, it is associated with substantial risk of immune mediated adverse reactions such as colitis, hepatitis, thyroiditis, and hypophysitis. We report the first case of late onset pericarditis and cardiac tamponade associated with ipilimumab treatment in patient with metastatic cutaneous melanoma.
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PMID:Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication. 2591 58

After 4 weeks of the last dose of nivolumab, a 59-year-old man with stage IV melanoma was subject to treatment with ipilimumab. After 5 weeks, the patient developed severe hepatitis, showing markedly elevated levels of both aspartate aminotransferase and alanine aminotransferase (>2000 U/l). Using pulse steroid therapy with 1000 mg/d of methylprednisolone, liver function initially improved, but then deteriorated upon dosage reduction. Subsequently, mycophenolate mofetil (MMF) was administered at a dose of 2 g/d in addition to the corticosteroid, which resulted in aspartate aminotransferase and alanine aminotransferase levels gradually improving to grade 1, and the corticosteroid dose was successfully reduced to 0.5 mg/kg/d of oral prednisolone. Liver function then remained stable when MMF was tapered. In conclusion, the use of MMF improved liver function in this patient with steroid-refractory hepatitis induced by immune checkpoint inhibitor administration.
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PMID:Severe hepatitis arising from ipilimumab administration, following melanoma treatment with nivolumab. 2817 41

Nivolumab is widely used to treat several late-stage malignancies such as melanoma and non-small-cell lung cancer by inhibiting the interaction between the programmed cell death protein-1 and its ligand. By stimulating an antitumor immune response, it also leads to immune adverse events. Here. we report two cases of subacute cutaneous lupus erythematosus (SCLE) induced by nivolumab. Case 1: a 72-year-old woman with a stage IV melanoma. Two months after nivolumab discontinuation because of autoimmune hepatitis, the patient was in complete remission and pruritic nummular erythematous plaques appeared on the back and arms. Case 2: a 43-year-old man put under nivolumab for a metastatic non-small-cell lung cancer. After two cycles, an annular erythematous eruption appeared on the hands, arms, and chest. The hypothesis of SCLE was confirmed by biopsies showing lymphoid perivascular inflammatory infiltrates, with scarce C3 deposits along the basal layer of the epidermis in patient 2. Both patients tested positive for antinuclear antibodies and anti-SSA antibodies. Lesions were regressive under topical corticosteroids and hydroxychloroquine for the first patient and oral prednisone for the second patient. No systemic involvement was observed. The occurrence of SCLE 2 months after nivolumab discontinuation is evidence that the drug effect is prolonged because of the maintenance of programmed cell death protein-1 reception saturation for months. A causal relationship between SCLE and nivolumab is suggested by (i) the occurrence of SCLE after at least two cycles, (ii) the regression of lesions following treatment with corticosteroids and hydroxychloroquine, and (iii) the fact that it appeared after remission in our first patient.
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PMID:Subacute cutaneous lupus erythematosus induced by nivolumab: two case reports and a literature review. 3048 84

Nivolumab is an anti-programmed death-1 inhibitor used in the treatment of cancer. Nivolumab has recently been approved as an adjuvant treatment for patients with stage IIIB, IIIC, and completely resected stage IV melanoma in the Netherlands. Despite the promising results of nivolumab, there is a wide variation in toxic side effects. A nivolumab-induced bilateral vocal cord paralysis (BVCP) was not reported. In this case, we present a nivolumab-induced BVCP. A 75-year-old man received nivolumab as adjuvant therapy for stage III melanoma. After the first cycle of nivolumab, this patient developed immune-related hepatitis and colitis. During admission, the patient became respiratory insufficient as a result of a BVCP. This case report describes immune-related hepatitis, colitis, and BVCP after the first cycle of nivolumab in the treatment of stage IIIb melanoma. Follow-up has not yet shown improvement in the mobility of the vocal cords.
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PMID:Bilateral Vocal Cord Paralysis Due to an Immune-related Adverse Event of Nivolumab: A Case Report. 3201 18