hep c screening recs; underscreening teens

The USPSTF just came out with new recommendations to screen adults aged 18-79-yo for hepatitis C infection (see hep c uspstf recs screen all jama2020 in dropbox, or doi:10.1001/jama.2020.1123; or see https://jamanetwork.com/journals/jama/fullarticle/2762185?resultClick=24 for the full systematic review leading to these new guidelines)

Details:

-- recommendation: screen adults aged 18-79 for hepatitis C virus (HCV) infection, grade B recommendation

-- the recommendation:

    -- all asymptomatic adults in that age group without known liver disease have a one-time screen

    -- those at high risk, in particular with past or current injection drug use (highest risk factor), should be screened periodically (though no clear evidence on what that screening interval should be)

-- this is an expansion of the prior recommendation of screening all born between 1945 and 1965, as well as others at high risk (not defined in the current recommendations, but per https://www.hcvguidelines.org/evaluate/testing-and-linkage) also includes intranasal drug use, MSM, longterm hemodialysis, tatoos and other percutaneous exposures in unregulated setting, needlesticks in healthcare workers/public safety workers, children born to HCV-positive women, blood transfusion before 1987, persons who were ever incarcerated, HIV-infected, sexually-active people about to start PrEP, elevated LFTs (though, i would add that about 1/2 the people with HCV infection have normal LFTs) or other chronic hepatitis (though not specific, i would add the remarkably common NAFLD to the list, given the suggestion of increased liver disease progression with NAFLD and HCV (eg see https://www.ncbi.nlm.nih.gov/pubmed/16557185 ).

Commentary:

-- HCV is the most common chronic blood-borne pathogen in the US, and is associated with more deaths than the top 60 other reportable infectious diseases combined, including HIV

-- the most important risk factor is people who inject drugs (PWID), past or current (see fuller list above)

    -- estimates are that there are 4.1 million people inthe US having evidence of HCV infection by the HCV antibody test, and 2.4 million have current infection based on positive HCV RNA viral loads, with a prevalence of about 1%

-- 44,700 new HCV infections were estimated to have occurred in 2017, a 3.8-fold increase from 2010- 2017, attributed to increasing injection drug use and improved surveillance.

    -- Approximately one third of PWID aged 18-30  are infected with HCV, as well as 70-90% of older PWID

-- The most rapid increases in HCV have been in those aged 20-39 who inject drugs, with increases in both sexes but moreso in men. Rates of increase have been particularly high in American Indian/Alaska native and non-Hispanic white populations

-- clinicians “may want to consider screening in adolescents younger than 18 years and in adults older than 79 years who are at high risk”

-- pregnant women should be screened: HCV has doubled in women aged 15-44 from 2006 to 2014

-- about 1700 infected infants are born annually to 29,000 HCV infected mothers

    -- 5 observational studies showed no clear association between mode of delivery and  risk of vertical transmission of HCV infection; one good-quality study found increased risk in those having prolonged rupture of membranes; one found that internal fetal monitoring was associated with increased vertical transmission; no studies have found increased risk of vertical transmission through breast-feeding

-- screening consists of checking for anti-HCV antibodies followed by PCR testing for HCV RNA viral load

-- the obvious purpose of screening is that there is remarkably effective treatment and it does dramatically prevent the long-term complications of HCV, especially in the vast majority who achieve sustained virologic response (SVR), including decreases in cirrhosis, liver failure, all-cause mortality and hepatocellular carcinoma

-- the reason for the grade B recommendation (moderate certainty of substantial net benefit) is that there is no real direct evidence that screening asymptomatic adults is effective, despite the evident benefit of therapy

    -- there are harms of screening: inducing anxiety, patient labeling, stigmatization; and potential adverse effects of the medications for treatment (serious adverse effects noted in 1.9%, with treatment interruption in 0.4%; however there is much, much more than adequate evidence that the benefits far outweigh the risks)

-- adolescents: limited data, though 7 trials with 300 people found that 97-100% had sustained virologic response to medications; limited data on long-term outcomes

-- mathematical modeling data suggest that screening all persons 18 years and older would identify an estimated 256,000 additional HCV cases and lead to 280,000 additional individuals who achieve SVR and an estimated 4400 fewer cases of hepatocellular carcinoma over a lifetime

-- USPSTF notes that more research is needed: to identify the yield of single vs repeated screenings, preferred labor-management practices during delivery, and the epidemiology and effectiveness of treatment regimens in adolescents

-- these guidelines are very similar to those of the 2019 American Association for the Study of Liver Diseases and the Infectious Diseases Society of America, though these latter ones do not have an upper age limit and they recommend periodic testing of those with increased risk of HCV exposure and annual HCV testing for all PWID and for HIV-infected men who have unprotected sex with men (see https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.31060 )

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and, as a timely additional article, we are doing pretty terribly in screening/treating high-risk adolescents for HCV (see hep c testing low in adol jama2019 in dropbox, or Epstein RL. JAMA. 2019; 322 (22):2245).

Details:

--researchers accessed OCHIN, a national electronic health record affiliated with 57 US federally-qualified health centers (FQHCs) in 19 states

    --they accessed de-identified information about those 13-21yo who had at least one health center visit from 2012-2017, excluding those people with an HCV diagnosis

-- they considered documented use of opioids, amphetamines, or cocaine as a surrogate for high-risk for HCV, with prior studies finding that this has a sensitivity of 80% and specificity of 81% for injection drug use (the strongest HCV risk factor)

--HCV care was considered present if there was HCV antibody testing

    --they also assessed the full cascade of followup: viral load if HCV antibody positive, then genotype if that were positive, and then treatment

--269,124 youths met inclusion criteria

--55% female, 63% nonwhite,  opioid use 0.3%, alcohol 0.6%, amphetamines 0.6%, marijuana 7.5%, cocaine 0.3%; and overall, any potentially injectable substance 1%

Results:

--6812 (2.5%) were tested for HCV antibody, 122 (1.8% of them) were anti-HCV antibody positive

    --of these 122 patients, 92 had RNA confirmatory testing, 41 had RNA detected and 15 had a completed genotype

--mean age at first HCV test 18.5 years, first positive test 19.1 yrs

--of the 2573 (1%) with documented drug use, 761 (30%) were tested for HCV of whom:

    --HCV positive: 54, 7% of those tested

    --only 1 individual had documented therapy for HCV

Commmentary:

--most of the new HCV transmissions are in those <30yo who inject drugs, with the proportion of new HCV cases in 15-24yo rising from 3.8% in 2009 to 9.1% (13,292 new infections) in 2013-16 (per MMWR: https://www.cdc.gov/hepatitis/statistics/2016surveillance/commentary.htm ). also see blog reviewing drug use in teens: http://gmodestmedblogs.blogspot.com/2018/11/teen-drug-use-in-us-2016-survey.html

    --there was an estimated  41,200 new acute HCV infections in 2016; and a total of 148,932 newly reported cases of confirmed chronic hep c

--as pointed out in the article above, there may be under-reporting of drug use (patients weren't asked or results not documented/or were documented but in an unsearchable way) or over-reporting (noting use of opiates/amphetamines/cocaine is only 81% specific). so ??do these balance out??,  though, i would add: 

    --studies have been pretty consistent that noninjection use of cocaine still increases HCV risk

    --and, as above per the AASLD/IDSA guidelines, even intranasal drug use is a risk factor for HCV

    --and, i personally would recommend HCV testing to patients with above drug use for HCV anyway, even if i were reasonably convinced of no injection drug use

--it is not only pretty shocking that adolescents are not being screened much, and that those few who had been screened and found to have HCV antibodies did not get the absolutely routine further testing to see if they had a treatable on-going infection, but even those actually screened and found to be positive had almost no chance of being treated!! (ie, only 1 person!!)

--this (quite large) database may not be generalizable to non-FQHC patient populations (which are largely poorer inner-city or rural persons). though i would suggest that drug use is everywhere....

so, this study reinforces that we clinicians should be very aggressive in talking with adolescent patients about drug use, offering HCV testing if there is any question at all, and treating as appropriate. the goal here is decreasing the associated severe morbidity and mortality of the many preventable sequelae of HCV in the future. and the added benefit that detecting earlier is much more likely to decrease the need for further active hepatocellular carcinoma surveilance (ultrasounds etc) if treated prior to significant hepatic fibrosis.

geoff​

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