{"id":6045,"date":"2015-01-18T10:02:19","date_gmt":"2015-01-18T15:02:19","guid":{"rendered":"http:\/\/blogs.nejm.org\/hiv-id-observations\/?p=5750"},"modified":"2015-01-18T10:02:19","modified_gmt":"2015-01-18T15:02:19","slug":"opposition-to-hcv-screening-raises-a-few-interesting-points-but-has-some-really-wacky-facts","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/opposition-to-hcv-screening-raises-a-few-interesting-points-but-has-some-really-wacky-facts\/2015\/01\/18\/","title":{"rendered":"Opposition to HCV Screening Raises a Few Interesting Points \u2014 But Has Some Really Wacky “Facts”"},"content":{"rendered":"

\"creepy<\/a>Over in the British Medical Journal<\/i>, there\u2019s a\u00a0provocative editorial<\/a>\u00a0entitled, \u201cIs widespread screening for hepatitis C justified?\u201d<\/p>\n

Based on the title alone, you can guess the authors\u2019 answer to that question \u2014 a resounding \u201cNo!\u201d<\/p>\n

By taking this position, of course, they are opposing some very data-driven and well-respected arbiters of policy and clinical practice. These include not only the Centers for Disease Control \u2014 which started\u00a0recommending universal screening in 2012<\/a>\u00a0to people born between 1945–1965 (the years of peak incidence) \u2014 as well as the\u00a0World Health Organization<\/a>, and, for good measure,\u00a0those staggeringly data-driven folks from the\u00a0U.S. Preventive Services Task Force (USPSTF).<\/a><\/p>\n

Remember, these USPSTF guys are a scrupulous bunch, opposing many forms of screening for insufficient evidence.\u00a0Just the very fact that they endorse HCV screening is\u00a0almost<\/em>\u00a0reason enough to accept it as worthwhile. Indeed, they reversed their\u00a0earlier opposition<\/a>\u00a0to HCV screening with their\u00a0latest review — and did so even before interferon-free therapies became standard of care!<\/p>\n

(Why is it so hard to say and write that combination of letters? \u2014 “USPSTF” reminds me of the confirmation codes that the airlines use for flights.)<\/p>\n

The key points of the of\u00a0the\u00a0BMJ<\/em>\u00a0opinion piece go like this, roughly in order:<\/p>\n

    \n
  1. The natural history of hepatitis C suggests it\u00a0is generally benign.<\/li>\n
  2. Achieving a\u00a0“sustained virology response,” or SVR, is only a surrogate marker for the important clinical endpoint of liver disease. Proof: \u00a0Some people who achieve SVR still go on to have decompensated disease\u00a0and hepatocellular carcinoma.<\/li>\n
  3. SVR\u00a0does not mean HCV is cured anyway.<\/li>\n
  4. Screening will\u00a0be dangerous because the treatment could be more harmful than the disease; we also need\u00a0long-term safety data on the newer drugs.<\/li>\n
  5. Before we adopt widespread HCV screening, a large randomized\u00a0trial should be done comparing broad to risk-based screening, with clinical outcomes as the primary endpoint.<\/li>\n<\/ol>\n

    There’s always\u00a0room for some dialogue in any policy statement, and the editorial does raise some important points.<\/p>\n

    But let’s take these above positions one at a time:<\/p>\n

      \n
    1. Most people with HCV will never develop clinically significant liver disease.<\/strong>\u00a0<\/em>Yes, this is true, but HCV is still the leading single cause of end-stage liver disease leading to liver transplantation<\/a> <\/strong>in the USA; HCV\u00a0can furthermore cause numerous\u00a0non-hepatic complications; and a chronic infection with high rates of ongoing replication is\u00a0probably bad for general health, which almost certainly\u00a0accounts for the higher rates of fatigue, nausea, pain, and decreased quality of life in those with HCV versus those without.<\/li>\n
    2. SVR is only a surrogate marker.<\/strong>\u00a0<\/em>If you’re a real skeptic, you’d argue\u00a0that\u00a0the better clinical outcomes observed in patients\u00a0who achieve SVR versus those that don’t might be confounded by their better health at baseline. On the other hand, many believe that the benefits of SVR have\u00a0been convincingly shown through\u00a0clinical cohorts, adjustment of baseline characteristics, and improvement in liver histology among those who achieve SVR<\/a><\/strong>.\u00a0And what about those patients with SVR who still get liver-related illness? Most had advanced liver disease before they were treated — one could argue that if they’d been diagnosed decades earlier and cured, their liver disease\u00a0never would have happened.<\/li>\n
    3. “Sustained virological response is not a cure,<\/em>“<\/strong>\u00a0writes the paper confidently. This is certainly a minority view, and seems to be based on the existence of\u00a0case reports of late relapses, with a\u00a0frequency of no greater than 3%<\/a><\/strong>\u00a0(and probably lower). Isn’t the very existence of these papers good evidence that most of the time SVR\u00a0is<\/em>\u00a0a cure? Why would any of them be published unless they were exceedingly rare events?<\/li>\n
    4. Treatment is harmful — in most patients, more harmful than the disease.<\/strong>\u00a0For\u00a0currently relevant treatments,\u00a0they cite\u00a0this paper<\/a><\/strong>, where “3% of participants taking sofosbuvir experienced serious adverse events compared with 1% in the peginterferon plus ribavirin arm.”\u00a0But these data are for\u00a0any<\/em>\u00a0serious adverse event, not just those that are drug-related. Bad things can happen to patients who are in clinical trials, especially trials that include patients with chronic diseases — it doesn’t mean the drugs caused them. In trials of newer HCV drugs, especially those that don’t include interferon or ribavirin, serious adverse events that are conclusively drug-related are extraordinarily rare. And one last thing:\u00a0No review of HCV therapy today should list side effects of\u00a0telaprevir or boceprevir as a reason for avoiding\u00a0treatment (both are cited).\u00a0These drugs are no longer recommended — and the former isn’t even available. Even interferon is rarely indicated today.<\/li>\n
    5. We need to do a large randomized strategy trial of broad versus targeted HCV screening with clinical outcomes.<\/strong>\u00a0It’s true\u00a0we do not definitively know that broad screening will prevent liver disease or death beyond a risk-based approach.\u00a0But unfortunately, patients can be infected with HCV (and unaware of that fact) for decades before showing up with advanced liver disease.\u00a0Seems that a cheap, reliable blood test is highly justified when we now have such safe and effective treatments.<\/li>\n<\/ol>\n

      I agree with the authors that\u00a0longer-term\u00a0follow-up data of treated patients are needed, especially using our currently available drugs.<\/p>\n

      The good news is that with\u00a0thousands taking of advantage of HCV therapy — including many patients who\u00a0could never be treated in the interferon era — and with over 90% of these patients cured (there, I said it), we shouldn’t have to wait long.<\/p>\n

       <\/p>\n","protected":false},"excerpt":{"rendered":"

      Over in the British Medical Journal, there\u2019s a\u00a0provocative editorial\u00a0entitled, \u201cIs widespread screening for hepatitis C justified?\u201d Based on the title alone, you can guess the authors\u2019 answer to that question \u2014 a resounding \u201cNo!\u201d By taking this position, of course, they are opposing some very data-driven and well-respected arbiters of policy and clinical practice. These […]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,5,8],"tags":[408,1023],"class_list":["post-6045","post","type-post","status-publish","format-standard","hentry","category-health-care","category-infectious-diseases","category-patient-care","tag-hcv","tag-hcv-screening"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/6045","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/comments?post=6045"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/6045\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=6045"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=6045"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=6045"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}