Early detection of interstitial pneumonia by monitoring KL-6 in a chronic hepatitis C patient undergoing pegylated interferon and ribavirin therapy
Department of Medicine, Division of Gastroenterology and Hepatology Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan.Hepatology Research (Impact Factor: 2.74). 09/2011; 41(9):904-9. DOI: 10.1111/j.1872-034X.2011.00837.x
A 58-year-old woman with chronic hepatitis C developed interstitial pneumonia (IP) while undergoing pegylated interferon (PEG IFN)-α-2a and ribavirin (RBV) therapy. Serum levels of sialylated carbohydrate antigen KL-6 (KL-6), a known marker of disease activity in fibrosing lung disorders, had been regularly measured once a month for early detection of IP, and had begun rising noticeably from 12 weeks to 540 U/mL at 33 weeks of treatment. On examination, remarkable fine crackles were detected by dorsal auscultation and bilateral ground-glass opacities and reticular shadows were depicted by computed tomography. The patient successfully recovered from her early-stage pneumonia by immediate discontinuation of therapy, which indicates that regular monitoring of serum KL-6 may be effective for avoidance of IP progression induced by PEG IFN and RBV therapy.
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ABSTRACT: A 61-year-old Japanese woman suffered from a small, painful, subcutaneous nodule on the sole of her foot that was 10 mm across in diameter during pegylated interferon (PEG IFN) and ribavirin (RBV) combination therapy for chronic hepatitis C. Skin biopsy revealed multiple non-caseating granulomas composed of epithelioid histiocytes with multinucleate giant cells, which was consistent with sarcoidosis. Ophthalmologic examination revealed uveitis. Thoracic computed tomography (CT) showed multiple bilateral hilar lymphadenopathies and a diffuse micronodular interstitial pattern of the lungs. Genetic analysis indicated a probable homozygous haplotype of A*02:01-C*15:02-B*51:01-DRB1*16:02-DQB1*05:02 in human leukocyte antigen regions. The patient was observed carefully without any additional medication because no significant systemic symptoms were noted. Combination therapy was continued for 2 months afterwards. She was asymptomatic for over 3 years of follow up, and repeated hematological and biological investigations and chest CT showed improvement. In conclusion, clinicians should bear sarcoidosis in mind as a complication during PEG IFN and RBV combination therapy. They should also be aware of the usually good prognosis of PEG IFN-induced cutaneous sarcoidosis in order not to prematurely discontinue a treatment necessary for liver disease; maintenance of PEG IFN treatment may be advised with careful follow up.
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ABSTRACT: Background and AimsAlbinterferon is a fusion of albumin and interferon alfa-2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-α for the treatment of chronic hepatitis infections.Methods This open-label, randomized, active-controlled, multicenter study investigated the safety and efficacy of albinterferon in patients with chronic hepatitis B virus (HBV) infection who were e antigen (HBeAg) positive. 141 patients received one of four albinterferon doses/regimens or pegylated-interferon-α2a. Primary efficacy outcomes were changes in serum HBeAg and antibody, HBV DNA, and alanine aminotransferase. Principal safety outcomes were changes in laboratory values, pulmonary function, and adverse events.ResultsThe study was prematurely terminated as Phase III trials in hepatitis C infection indicated non-inferior efficacy but inferior safety compared to pegylated-interferon-α2a. Here, all treatment groups had a significant reduction in HBV DNA from baseline. Reductions in HBV DNA were not significantly different, except the 1200 μg q4w albinterferon dose which was inferior compared to pegylated-interferon-α2a. The serum alanine aminotransferase levels decreased in all arms. The per-patient incidence of adverse events was not significantly different for albinterferon (96.4-100%) and pegylated-interferon-α2a (93.1%). Total adverse events, however, were higher for albinterferon and correlated to dose. Decreased lung function was found in all arms (∼93% of patients), and was more common in some albinterferon groups.Conclusions Albinterferon doses with similar anti-HBV efficacy to pegylated-interferon-α2a had higher rates of certain adverse events, particularly changes in lung diffusion capacity (www.clinicaltrials.gov number NCT00964665).
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