Hep C articles: treatment in current drug users, HBV reactivation, and effects on psoriasis

​several articles came out recently on hepatitis C (HCV) treatment.

A small study found equal efficacy of pangenotypic hep c treatment in patients who are current injection drug users (see doi.org/10.1016/S2468-1253(17)30404-1).

Details:

--103 patients enrolled in an open-label, single-arm study (SIMPLIFY study) with hepatitis C and continuing injection drug use (IDU) within the past 6 months, from 19 sites in 7 countries (Australia, Canada, New Zealand, Norway, Switzerland, UK, USA). All patients were naive to prior therapy. HIV-positive patients were excluded

--median age 48, 28% female, 61% mild or no hepatic fibrosis (F0-1)/28% moderate to advanced fibrosis (F2-3)/9% had cirrhosis, genotype: 35% had 1/5% genotype 2/58% genotype 3/2% genotype 4, HCV viral load 6.1 log units, 59% on opioid substitution therapy (mostly methadone), 60% with some alcohol use in past 30 days/17% with "hazardous" alcohol use

--74% injected in past month/26% at least daily in past month. of those injecting in the past month, 75% used heroin/17% cocaine/41% methamphetamines/29% "other opioids"

--primary endpoint= SVR12 (non-measurable HCV viral load 12 weeks after completing therapy).

--All patients included in analysis if took at least one dose of meds

Results:

--self-reported drug use in current users continued at a stable rate throughout the study

--94% of the patients were at least 90% adherent to therapy

--97% completed treatment with oral sofosbuvir 400mg and velpatasvir 100mg daily for 12 weeks, given in 1-week electronic blister packs which recorded time and date of each dose.

--94% achieved SVR12 (97% of those who completed treatment)

--drug use either before or during treatment did not affect SVR

--47% had treatment-related adverse events (though only 1 grade 3 and no grade 4). mostly fatigue (22%), headache (18%), nausea (14%), and (all<10%) insomnia, arthralgia, dizziness, nasopharyngitis, back pain, diarrhea, vomiting.

    ​--of the 7 patients with serious adverse events, only one (rhabdomyolysis, which resolved) was felt to be "possibly related to the therapy"

--there were 4 deaths during the study period, all from drug overdoses

--1 case of reinfection with hep C: a man who injected morphine 3x/day, had SVR at end of treatment but virus present at 12 weeks, and sequencing showed it to be a reinfection

Commentary:

--globally 71 million people have chronic HCV infection, with 39% HCV prevalence globally in those who injected drugs in the past 12 months (6.1 million people)

--WHO has target of eliminating HCV as a major public health threat by 2030

--newer guidelines do not exclude patients who are current IDUs from getting hepatitis C treatment, though some US health insurers do not approve it and some clinicians may not feel comfortable prescribing this therapy:

    --US, European, and WHO all recommend treatment in those injecting drugs, and even prioritize them since that would more likely reduce subsequent hep C transmission

    ​--a study in 2016 of HCV practitioners found that only 15% were willing to use HCV meds in patients who are injecting drugs, mostly from concerns about reinfection, adherence, and medication costs

    --but, 23% of all new HCV infections globally are in people who are currently injecting drugs

--this was short-term study: there will be a 3 year follow-up to assess reinfection rates. also, these patients were recruited from drug treatment clinics, so they might be a more stable and more plugged into the medical system than some drug users. And, there was an incentive to return their weekly med blister-packs (the equivalent of $8 US) and filling out questionnaires every 4th week ($16 US), which may have increased medication taking. [though, personally, i think it makes sense to give incentives, since it helps many disenfranchised people to get care, which in this case not only benefits them personally but also serves an important public health imperative (and, in the long run, undoubtedly saves health care expenditures)]. Aldo, there was minimal participation of those with genotypes 2 and 4.

So,

--seems pretty clear that patients with current IDU should not be excluded from receiving hepatitis C therapy, and that we should be using the same inclusion/exclusion criteria for all, and specifically assessing their motivation to take these meds regularly and be monitored closely

--one potentially very positive collateral effect of HCV therapy in active drug users is that they become more involved in the health care system (in this study, patients were seen weekly for the 12 weeks). this gives multiple opportunities to support patients and work with them to transition into some long-term opioid substitution therapy, try to get them into needle exchange programs, make sure they have naloxone, etc.

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There have been several reports of hepatitis B reactivation in patients receiving direct-acting antiviral therapy for chronic hepatitis C. A systematic review/meta-analysis of 17 observational studies quantified this risk (see 10.1016/S2468-1253(18)30002-5) -- i could not get the full article for review, not available yet on PubMed:

--162 patients with chronic hepatitis B (HBV) and 1379 with resolved HBV (not sure how defined)

    --HBV reactivation rate of 24% in those with chronic HBV, 9% developed HBV-reactivation-related hepatitis

    --HBV reactivation rate of 1.4% in those with resolved HBV, none developed HBV-reactivation-related hepatitis

--relative rate of HBV-reactivation-related hepatitis​ was 83% lower in those without quantifiable HBV DNA, RR 0.17 (0.06-0.50), p=0.0011

--3 major clinical events from HBV-reactivation: 1 pt with liver decompensation, 2 with liver failure (1 getting transplant)

Prior reports of HBV reactivation have had mixed results. for example, a report from earlier this month (Yanny BT. J Clin Gastroenterol. jan 2018; DOI: 10.1097/MCG.0000000000000986​) did not find reactivation of HBV in 283 pateints with hep B (though they defined it as actively infected or with prior exposure: isolated hep B core antibody or surface antigen), though only 71% had an HBV viral load done and the numbers were pretty low (mean of <100 IU/mL). unfortunately, i do not have the HBV quantification from the study above in order to compare these results.

so, we should routinely check HBV surface antigen routinely in those with hepatitis C (as well as checking for immunity to hepatitis A/immunizing if nonimmune), and if hepatitis B positive, consider HBV prophylaxis with meds (tenofovir, entecavir, etc) especially in those with quantifiable viral loads. I would also think that we should check HBV viral load in those who are only hep b core antibody positive. These seem quite reasonable suggestions, with the caveat that they have not be rigorously tested.

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A case report of a patient who had improvement in his refractory psoriasis with hep c treatment (see doi:10.7326/L17-0613):

Details:

--80 yo man with 9 year history of refractory psoriasis, despite topical therapy with clobetasol and a vitamin D3 analog, and the addition of narrowband ultraviolet phototherapy

--he  had chronic HCV infection genotype 1b, and had partial hepatectomy for hepatocellular carcinoma the previous year

--HCV status:  basic hepatic labs were mildly abnormal, platelet count 60K, HCV RNA 6.5 log units

--he then got a 12-week course of ledipasvir-sofosbuvir, with undetectable HCV RNA at week 4 and thereafter

--psoriasis lesions began to resolve soon after beginning therapy, leading to reductions in topical meds and phototherapy

Commentary:

--HCV itself is associated with several skin problems including mixed cryoglobulinemia, lichen planus, and porphyria cutanea tarda, and (in some studies) psoriasis

--and there are a couple of case reports documenting one patient developing new-onset psoriasis and one with worsening psoriasis when starting direct-acting HCV meds​

--with the older biological agents, there were  more common exacerbations of psoriasis, presumably from distortions of the immune system by these agents.  ​

so, basically this case report counterweighs the prior cases of worsening psoriasis with hep c treatment. current guidelines encourage HCV treatment even in those with psoriasis (a pretty common problem), and this case helps quell fears in those with psoriasis, even when severe and refractory to treatments.

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