{"id":514,"date":"2016-09-22T03:40:32","date_gmt":"2016-09-22T08:40:32","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=514"},"modified":"2016-09-22T03:40:32","modified_gmt":"2016-09-22T08:40:32","slug":"ursodeoxycholic-acid-exacerbates-peginterferon-induced-interstitial-pneumonia-in-a-patient-with-hepatitis-c","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/ursodeoxycholic-acid-exacerbates-peginterferon-induced-interstitial-pneumonia-in-a-patient-with-hepatitis-c\/","title":{"rendered":"Ursodeoxycholic acid exacerbates peginterferon-induced interstitial pneumonia in a patient with hepatitis C"},"content":{"rendered":"

Eradication of hepatitis C virus<\/a> (HCV) infection is extremely important to either cure hepatitis or prevent the\u00a0progression of hepatic fibrosis and the development of\u00a0hepatocellular carcinoma. Antiviral therapy using peginterferon<\/a> and ribavirin<\/a>\u00a0is effective for approximately 70% of\u00a0patients with hepatitis C. However, the sustained\u00a0virological response is lower in patients with a heavy viral\u00a0load and HCV genotype. In addition, this therapy\u00a0can cause various adverse effects. Among these, interstitial\u00a0pneumonia is potentially severe and life-threatening, limiting both the use and efficacy of interferon. After the\u00a0failure of first-line antiviral therapy, anti-inflammatory\u00a0agents such as ursodeoxycholic acid<\/a> (UDCA) and glycyrrhizin<\/a> are used as adjunctive therapy for cytoprotection.<\/p>\n

Administration of UDCA is thought to alleviate hepatitis\u00a0by suppressing the apoptosis of hepatocytes, which is\u00a0achieved by stabilization of cellular and microsomal\u00a0membranes and by inhibition of DNA fragmentation.\u00a0Furthermore, combining UDCA with interferon increases\u00a0the complete remission rate and reduces the relapse of\u00a0hepatitis C after interferon therapy. In Japan, UDCA is\u00a0used annually by 2.8 million patients without severe\u00a0adverse effects. This may lead physicians to be somewhat\u00a0careless when prescribing it. However, we recently experienced a hepatitis C patient in whom peginterferoninduced interstitial pneumonia was exacerbated by UDCA\u00a0administration.<\/p>\n

The patient was a man born in 1944. He was an occasional drinker and had a history of smoking 20 cigarettes\u00a0per day for 30 years. At the age of 19 years, he received\u00a0a blood transfusion during surgery for lumbar intervertebral disk herniation. After an annual medical check at\u00a0the age of 50 years, he was diagnosed as having hepatitis\u00a0C, for which he received treatment with UDCA and\u00a0glycyrrhizin. However, little effect of this therapy was\u00a0observed.<\/p>\n

After eight months of therapy, cough and exertional\u00a0dyspnea occurred, and the serum KL-6 level rose to\u00a0716 U\/mL. Chest X-ray films and CT scans revealed bilateral linear and reticular\u00a0pulmonary infiltration suggestive of interstitial pneumonia. PaO2<\/sub>\u00a0was 96% and fine crackles were audible\u00a0on auscultation. We discontinued both peginterferon and\u00a0ribavirin, after which his exertional dyspnea resolved and\u00a0KL-6 decreased to 488 U\/mL. On the other hand,\u00a0PCR showed that HCV-RNA increased to above\u00a050 IU\/mL and there was elevation of serum transaminases.<\/p>\n

Two months later, he commenced treatment with\u00a0Glycyron (ammonium glycyrrhizate) at a dose of 300 mg\u00a0per day, which was increased to 600 mg daily because\u00a0transaminase levels remained high. Because this drug alone\u00a0had little effect, UDCA was added at a dose of 300 mg per\u00a0day. His ALT level decreased to 49 IU\/L, but productive\u00a0cough and exertional dyspnea occurred along with an\u00a0increase of KL-6 to 580 U\/mL. Because these symptoms\u00a0had occurred soon after UDCA therapy was commenced,\u00a0UDCA was discontinued. His transaminases increased\u00a0further, so intravenous infusion of Stronger Neo-Minophagen C (SNMC), a\u00a0glycyrrhizin-containing preparation, at\u00a0100 mL once a week was started .\u00a0The KL-6 level remained high despite the cessation of\u00a0UDCA, suggesting that it was not responsible for his lung\u00a0abnormalities, so UDCA treatment at a dose of 300 mg\u00a0per day was restarted. Although ALT decreased to\u00a030 IU\/L, the KL-6 level increased to 1,340 U\/mL. Productive cough and dyspnea occurred, and fine crackles\u00a0became audible on auscultation. In addition, PaO2<\/sub>\u00a0<\/sub>decreased to 93%. Therefore, UDCA was discontinued\u00a0and prednisolone (15 mg\/day) was administered. His\u00a0symptoms subsided, and the dose of prednisolone was\u00a0tapered. Chest X-ray films and CT scan showed\u00a0evidence of interstitial pneumonia, with the changes being\u00a0similar to those detected in December 2005. In July 2007,\u00a0the patient was well and was continuing to receive weekly\u00a0SNMC infusions.<\/p>\n

In this patient, interstitial pneumonia was induced by\u00a0peginterferon, but not by non-pegylated interferon. Interstitial pneumonia occurs in 0.1\u20130.2% of patients treated\u00a0with non-pegylated interferon, and the rate increases to\u00a00.3% when pegylated interferon is used. Pegylation\u00a0prolongs the serum half-life of interferon by about tenfold,\u00a0which may increase its toxicity. At present, however, it\u00a0is not clear whether the increased incidence of adverse\u00a0effects is merely because of the prolonged duration of\u00a0interferon activity or to some other specific toxicity of\u00a0peginterferon, which is a conjugate of interferon with a\u00a0polyethylene glycol moiety.<\/p>\n

In our patient, UDCA administration ameliorated hepatitis but led to exacerbation of interstitial pneumonia.\u00a0UDCA very rarely has adverse effects on the lungs. In fact,\u00a0only three Japanese cases of UDCA-induced interstitial\u00a0pneumonia have been reported. This indicates that the incidence of interstitial pneumonia in UDCA-treated Japanese patients is\u00a0less than 0.0001%, whereas the reported incidence of\u00a0idiopathic interstitial pneumonia ranges from 0.003 to\u00a00.005%. These data suggest that UDCA monotherapy does\u00a0not increase the incidence of interstitial pneumonia. In this\u00a0case, some interaction between UDCA and peginterferon\u00a0may have occurred. As far as we know, however, there\u00a0have been no reports of an additive or synergistic effect of\u00a0UDCA combined with peginterferon.<\/p>\n

This case demonstrates that UDCA therapy can exacerbate\u00a0peginterferon-induced interstitial pneumonia during treatment of hepatitis C, suggesting that UDCA should be used\u00a0cautiously after antiviral therapy with peginterferon.<\/p>\n

 <\/p>\n

Reference:<\/p>\n

Rena Kaneko,\u00a0Masazumi Ogawa,\u00a0Tomoyuki Iwata. Clin J Gastroenterol (2009) 2:296\u2013299<\/p>\n

Related\u00a0Products:<\/h4>\n
<\/div>
<\/th><\/th><\/th><\/th><\/th><\/tr><\/thead>
CAS Number <\/td>Product Name <\/td>Molecular Weight <\/td>Molecular Formula <\/td>Description <\/td><\/tr>
215647-85-1 <\/td>Peginterferon alfa-2b<\/a><\/td>Unspecified <\/td>Unspecified <\/td>Peginterferon alfa-2b can be used to treat hepatitis C virus. <\/td><\/tr>
36791-04-5 <\/td>Ribavirin<\/a><\/td>244.21 <\/td>C8H12N4O5 <\/td>Ribavirin is a guanosine (ribonucleic) analog used to stop viral RNA synthesis and viral mRNA capping, thus, it is a nucleoside inhibitor. <\/td><\/tr>
128-13-2 <\/td>Ursodeoxycholic acid<\/a><\/td>392.57 <\/td>C24H40O4 <\/td>Ursodeoxycholic acid (UDCA) is a cell protectant used extensively to mitigate hepatic and biliary diseases. Ursodeoxycholic acid may be used to study its specific activities that range from reduction of cholesterol absorpition, cholesterol gallstone dissolution to suppression of immune response <\/td><\/tr>
1405-86-3 <\/td>Glycyrrhizin<\/a><\/td>822.93 <\/td>C42H62O16 <\/td>Glycyrrhizin (Glycyrrhizic Acid) is a widely used anti-inflammatory agent isolated from the licorice root. <\/td><\/tr><\/tbody><\/table><\/div>\n","protected":false},"excerpt":{"rendered":"

Eradication of hepatitis C virus (HCV) infection is extremely important to either cure hepatitis or prevent the\u00a0progression of hepatic fibrosis and the development of\u00a0hepatocellular carcinoma. Antiviral therapy using peginterferon and […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[181],"tags":[311,310,313,314],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/514"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=514"}],"version-history":[{"count":2,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/514\/revisions"}],"predecessor-version":[{"id":516,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/514\/revisions\/516"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=514"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=514"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=514"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}