{"id":870,"date":"2015-10-29T15:32:38","date_gmt":"2015-10-29T15:32:38","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=870"},"modified":"2017-08-21T11:26:46","modified_gmt":"2017-08-21T11:26:46","slug":"primary-care-corner-with-geoffrey-modest-md-hep-c-treatment-and-hep-b-reactivation","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/10\/29\/primary-care-corner-with-geoffrey-modest-md-hep-c-treatment-and-hep-b-reactivation\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Hep C Treatment and Hep B Reactivation"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>Thanks to Dr. Jon Pincus for his suggestions on this blog.<\/p>\n<p>A brief report was just published with 2 cases of\u00a0hepatitis B virus\u00a0(HBV)\u00a0reactivation during successful treatment of hepatitis C \u00a0virus\u00a0(HCV) \u2013see Clin Infect Dis 2015;61:1304\u200b.<\/p>\n<p>Details of the Cases:<\/p>\n<ul>\n<li>55yo male with chronic HBV and genotype 1a HCV infections. The patient had failed 2 prior courses of interferon-based therapy and\u00a0had underlying\u00a0compensated cirrhosis. His HBV viral load prior to the new\u00a0treatment for HCV\u00a0was 2300 IU\/ml and had been consistently &lt;2000 before; ALT 62 and AST 59, bili 0.7,\u00a0normal INR. Hepatitis B e antigen was\u00a0negative and antibody positive. Given sofosbuvir and simeprevir for the HCV. The HCV VL (viral load) was undetectable by week 4 of treatment. By week 7 he developed symptoms of hepatitis and by week 8 had tender hepatomegaly and jaundice, with ALT 1495, AST 1792, bili 12.2 and INR 1.96. HCV VL was still undetectable, no evidence of drugs or acetaminophen to\u00a0cause the hepatitis, and his HBV VL increased to 22 million. They stopped the HCV treatment, and began tenofovir\/emtricitabine. By\u00a0week 14, symptoms had resolved, and LFTs were back to baseline. At week 28 (20 weeks after stopping HCV drugs), his HCV\u00a0and HBV VLs were both\u00a0undetectable<\/li>\n<li>57 yo male with chronic HCV genotype 1a, ALT of 54, and hepatitis B serologies of: positive hep b core antibody (HBcAb), negative hep b surface antigen (HBsAg)\u00a0and antibody (HBsAb), and undetectable HBV VL. He had received interferon-based therapy 5 years before. Begun on\u00a0sofosbuvir and simeprevir\u00a0for HCV with undetectable HCV VL at 2 weeks, though HBV VL increased to 353. At 4 weeks, HCV VL undetectable, but HBV VL increased to 11,255. Patient remained\u00a0asymptomatic and LFTs remained normal. Tenofovir was added and both HCV and HBV VLs were undetectable after 12 weeks of therapy.<\/li>\n<\/ul>\n<p>So, raises a few issues:<\/p>\n<ul>\n<li>Treatment of HCV infection can cause reactivation of HBV, so it is important to test for HBV infection in those with HCV.<\/li>\n<li>There can be significant HBV flares which are asymptomatic, as in the second patient. Also in this case, there can be HBV flares with no detectable serum HBV\u00a0VL beforehand.<\/li>\n<li>In general I usually\u00a0consider that anyone with\u00a0an isolated\u00a0HBcAb\u00a0(which I do see pretty commonly, and as in the second case above) and an undetectable HBV VL are likely to either have a false-positive\u00a0HBcAb\u00a0or an old infection with waning and undetectable HBsAb (or, rarely, be in the window of an acute infection with a clearing HBsAg and prior to the emergence of a detectable HBsAb, and actually have the IgM\u00a0HBcAb, if you check it).\u00a0This study raises the issue that even with hepatitis B serologies that appear to indicate no active\u00a0infection, there is still the possibility of a dormant HBV infection which may energize with HCV treatment (as sometimes happens in those getting transplants or biologicals\u00a0with the attendant\u00a0immunosuppression). This phenomenon is referred to as an &#8220;occult HBV infection&#8221;, found\u00a0in people who do not\u00a0have\u00a0detectable\u00a0HBsAg in the blood,\u00a0where there is HBV in the liver but sometimes\u00a0with no VL found\u00a0in the blood. The prevalence of this\u00a0varies in studies, perhaps due to differing definitions\/methodology, but seems to be more frequent in those with HCV infection (also in injection drug users and those\u00a0with\u00a0HIV or hepatocellular carcinoma) &#8212;\u00a0see\u00a0\u00a0doi:10.1128\/CMR.00018-11.\u200b Interestingly,\u00a0an older study from 1999 found\u00a020 people\u00a0without any of the serologic markers of HBV infection\u200b\u00a0had liver biopsies\u00a0finding\u00a0HBV\u00a0sequences, more commonly in those with concommitant HCV infection\u00a0(see\u00a0<a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJM199907013410104\">http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJM199907013410104<\/a>\u200b ), raising the importance to check for acute HBV in anyone with acute hepatitis, even if recently checked serologies are totally normal. And those with HCV and occult HBV together had more cirrhosis (and, those without HCV but only occult HBV\u00a0had more &#8220;cryptogentic liver disease&#8221;)<\/li>\n<li>The\u00a0editorialists (see\u00a0Clin Infect Dis 2015;61:1307) feel that the likely pathophysiology, with some experimental evidence in support, is that HCV creates a host immune state in the liver which suppresses HBV replication, and that the effective treatment of HCV disrupts this control. \u00a0for clinical management, they\u00a0suggest the following:\n<ul>\n<li>Always check the full array of hepatitis B serologies (HBsAg, HBsAb, HBcAb), and if negative, immunize.<\/li>\n<li>Check HBV VL prior to starting HCV therapy in those who are either HBsAg\u00a0or HBcAb positive.<\/li>\n<li>If the HBV VL is negative, repeat &#8220;at least every 4 weeks&#8221;, and initiate treatment if they reach the usual criteria to start HBV therapy.<\/li>\n<li>\u200bThose with evidence of immune recovery from prior HBV infection (with both HBsAb\u00a0and HBcAb\u00a0positive) should get one HBV VL at 4 weeks, even though their chances of reactivation are low. If the 4 week VL is negative, then no further testing is needed.<\/li>\n<li>The editorialists are less aggressive in treatment of those with asymptomatic HBV reactivation, noting that the optimal treatment is unknown (the second patient above had dramatically increasing HBV levels but was asymptomatic). I personally would\u00a0argue that, in the absence of clear studies, treatment to\u00a0prevent\u00a0acute clinical HBV infection seems reasonable, given the real morbidity and mortality of HBV and the relatively benign nature of current HBV treatment (i.e., so I would have treated the second patient above, though the editorialists were equivocal).<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Hep C Treatment and Hep B Reactivation  [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/10\/29\/primary-care-corner-with-geoffrey-modest-md-hep-c-treatment-and-hep-b-reactivation\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-870","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/870","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=870"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/870\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=870"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=870"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=870"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}