hepatitis c screen all, and treatment changes
Geoff A. Modest, M.D.
Mon 10/7/2019 7:51 AM
The US Preventive Services Task Force issued a draft recommendation to screen all adults aged 18-79 for hepatitis C (see https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/hepatitis-c-screening1 ), as a Grade B recommendation (high certainty that net benefit is moderate, or moderate certainty that net benefit is moderate to substantial.)
-- risk assessment: all adults 18-79 should be screened, though consider screening if younger or older than that if risk factors
--there have been recent increases in hepatitis C virus (HCV) infection, mostly in young people who inject drugs (PWID); 1/3 of PWID aged 18-30 are infected with HCV and 70-90% of older PWID are infected
--all pregnant women should be tested: HCV prevalence in women 14-44 yo has doubled from 2006 to 2014. clinicians should consider testing those <18yo
--from 2011-14, 0.73% of pregnant women had HCV infection, a 68% increase in the proportion of infants born to HCV-positive mothers
--approx 1700 infected infants are born annually to HCV-infected mothers
-- screening intervals: once, unless there is continued risk for HCV infection (but limited data to support this)
--the CDC estimates that 2.7-3.9 million people in the US have chronic hepatitis C virus (HCV) infection, and children born to mothers with HCV are at risk for infection, with estimates of 23,000 to 46,000 children in the US having HCV infection
--in fact, a new CDC study (https://www.cdc.gov/mmwr/volumes/68/wr/mm6839a1.htm?s_cid=mm6839a1_w ) found:
--the US rate of HCV infection overall at hospital delivery increased form 0.8 per 1000 live births in 2000 to 4.1 in 2015 (>400% increase!!!)
--for women with opioid use disorder (OUD), the increase was from 87.4 to 216.9 (148% increase)
--review of their graph: major increase from 2000-2004 (15.7% increase), then level, then major increase from 2012-2015 (7.9% from 2010 to 2015)
--for women without OUD, the increase was from 0.7 to 2.6 (271% increase)
--review of their graph: gradual increase over the 15 years, with gradual upsurge from 2012-2015
--68% of pregnant women with HCV have OUD
--the largest group (by far) with HCV infection only, OUD only, and the combo in 2015 was in women 25-34 yo
--by region: the South was highest (3760 women with HCV only, 5600 with OUD only, 1665 with combo); Northeast was next (1110 women with HCV only, 3390 with OUD only, 1190 with combo); then Midwest (1375 women with HCV only, 3300 with OUD only, 895 with combo); and West (1250 women with HCV only, 2585 with OUD only, 370 with combo)
--of note, this study likely underestimated actual cases, since universal testing was not in place in many areas
--so, reasons that the recommendations were changed from the prior ones (which were: screen high-risk and those born between 1945-65):
--treatments are better and of shorter duration, with greater benefits and fewer harms (see next part, below)
--HCV infection rates have increased in younger people
--the risk in those born from 1945-65 is still high, and those people are getting older: but there now are more studies documenting the benefit in treatment in those into their 80s
--benefits of early detection and treatment: treatment by DAAs (direct-acting antivirals), in pooling 49 studies, was associated with sustained viral responses at 12-weeks post-therapy (SVR-12) of 95.5 to 98.9%, across genotypes
--treatment by DAAs is associated with:
--short-term improvements in quality of life
--SVR-12, after adjustment for potential confounders, is associated long-term with:
--60% decrease in all-cause mortality, HR 0.40 (0.28 to 0.56)
--89% decrease in liver mortality, HR 0.11 [0.04 to 0.27)
--64% decrease in cirrhosis, HR, 0.36 ( 0.33 to 0.40)
--71% decrease in hepatocellular carcinoma, HR 0.29 (0.23 to 0.38)
--pregnancy risks:
--no clear association between risks of vertical transmission and mode of delivery
--prolonged rupture of membranes (>6 hours) is associated with more HCV transmission: odds ratio, OR 9.3 (1.5-180)
--internal fetal monioriting is associated with increased risk of vertical transmission, OR 6.7 (1.1-35.9)
--no evidence of association between breast feeding and vertical transmission
--adolescents: limited evidence, though 7 trials with 300 people found similar SVR of 97-100% with DAAs
--mathematical modeling: expanded screening of all people 18-79, with conservative assumptions, would identify 256,000 more HCV cases, 280,000 additional cures, and 4,400 fewer cases of hepatocellular carcinoma over a lifetime
--harms of screening: DAAs do have lots of adverse events (73.3%, most commonly fatigue, headache, nausea and diarrhea), but serious ones were in 1.9% and withdrawal from an adverse event is 0.4%
bottom line: though this was a draft recommendation by the USPSTF (comment period is over now, final recommendations pending, but hard to believe they will be different), the data and rationale seem to be quite persuasive, and are reflected throughout the US: we should be doing routine HCV screening and early treatment when appropriate!!!
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New FDA recommendations that shorter courses of glecaprevir/pibrentasvir (Mavyret) for patients with HCV and compensated cirrhosis (see https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-adults-and-children-all-genotypes-hepatitis-c-and-compensated-cirrhosis )
-- treatment recommendation: Mavyret (glecaprevir and pibrentasvir) is now approved as an 8-week course for adults and children ages 12 years and older or weighing at least 99 pounds who have chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection and compensated cirrhosis and have not been previously treated for HCV (treatment-naïve)
--Mavyret is the first eight-week treatment approved for all treatment-naïve adult and certain pediatric patients with HCV genotypes 1-6 both without cirrhosis and with compensated cirrhosis. Standard treatment length for patients with compensated cirrhosis was previously 12 weeks or more.
--studies have shown sustained viral responses (SVR-12) ranging from 91-100%, including patients with HIV co-infection, kidney or liver transplant recipients, and those with advanced kidney disease including those on hemodialysis
--Mavyret is contraindicated in in those with moderate or severe liver impairment (Child-Pugh B or C) or in those with any history of liver decompensation
so, these 2 articles reinforce and extend the dramatic changes we have seen with hepatitis C (quite extraordinary, to those of us practicing for many years, and analogous to what happened with the HIV epidmeic): going from a disease with no treatment but high morbidity and mortality; to one with a pretty awful long-term injections (interferon) with terrible adverse effects and limited efficacy; to a really pretty easy, short-term (and getting shorter for some), simple and tolerable pill regimen with shockingly high pan-genotypic efficacy. And, it is abundantly clear that we should be identifying and treating patients as early as possible to avoid long-term complications of HCV infection and the intensive monitoring required for those with more advanced liver disease, instead of having to beg insurers and file lots of paperwork to get treatment approved, as we had to do in the past (some insurers previously limited treatment to those with more advanced liver disease!!!). so, as appropriate, we should now test everyone, pick up more cases at an earlier stage of disease, and be able to treat most with a 2-month course of therapy!!! I should add that DAAs are not approved during pregnancy, so at this point testing should be used to identify women for postpartum treatment and infants for futher evaluation
geoff
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