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ARTICLE

Another Adverse Effect of the Opioid Epidemic: Hepatitis C Infections

JUN 19, 2018 | JENNIFER ANDRES, PHARMD, BCPS
Amid the ongoing opioid epidemic, hepatitis C virus (HCV) infection should be at the forefront of health care providers’ minds. Although HCV has been widely viewed as predominantly affecting baby boomers—those born between 1945 and 1965—a younger generation is experiencing increased incidence of infection.

From 2010 to 2015, the number of newly reported HCV diagnoses almost tripled, with the highest rate among people in their 20s.1 These new cases are likely a result of injection drug use in younger patients.2 These patients may be referred to as persons who inject drugs (PWIDs) or intravenous drug users. Because HCV is a blood-borne pathogen, intravenous (IV) drug use is a major risk factor for acquisition. In fact, a recent analysis suggested that in the United States, approximately 50% of PWIDs are infected with HCV.3

The use of new syringes is a viable way to avoid HCV infection; however, the virus also can be found and transmitted via preparation equipment including containers, filters, and rinse water. Practicing “back-loading”—injecting drugs from 1 syringe to the back of another open syringe—also can lead to HCV transmission. Furthermore, the development of antibodies against HCV is not protective, leading to a risk of reinfection in treated patients who later have another exposure.4

Seven HCV genotypes exist.4 Although genotype 1 infection is most common in the United States, genotype 3 infection has been increasingly linked with PWIDs.4,5 Genotype 3 is linked to faster cirrhosis development than other genotypes, and so it is urgent to treat patients infected with this genotype.

Results of studies have shown that, compared with the other types, genotype 3 is more easily treated with interferon regimens, with response rates of approximately 60% compared with 30% for genotype 1 infection. However, with the advent and use of direct acting antivirals (DAAs), genotype 3 became harder to treat relative to other types, with lower sustained viral response (SVR) rates at 12 weeks (SVR12) than genotype 1.4,5 SVR12 rates are >97% for all preferred regimens in treatment-naïve individuals with genotype 1 infection without cirrhosis. There are fewer available DAA regimens for genotype 3 infection compared with genotype 1; however, all preferred available regimens are equally effective. Current treatment recommendations from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America are listed in the Table.6 Since the approval of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, ribavirin is not needed for most treatment-naïve individuals. SVR12 rates have improved, from 90% with sofosbuvir/ribavirin in those without cirrhosis to 95% and 98% with glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, respectively.7,8


Glecaprevir/pibrentasvir can be used for an 8-week duration in most treatment-naïve patients. Notably, the presence of compensated cirrhosis in an individual lowers the likelihood of SVR12 attainment. Baseline resistance testing for the Y93H and A30K mutations should be considered for patients with cirrhosis, either compensated or decompensated, and patients who have failed previous treatment, also referred to as treatment-experienced patients.6 Presence of these mutations could signify a lower chance of treatment success. 

Patients being treated for opioid use disorders are frequently on maintenance medications, or opiate substitution therapy, to prevent withdrawal and aid recovery. Commonly used medications include buprenorphine/naloxone, buprenorphine alone, and methadone. No drug–drug interactions exist with opioid substitution therapy that would reduce efficacy or cause toxicity of DAAs; however, additional characteristics relevant to the PWID population, including the age of the infected patient, could have an impact on choice of treatment. Because these cases may involve younger patients, childbearing potential should be evaluated. Female patients of childbearing age will need contraception. No DAA regimens have been studied in pregnancy; all regimens should be avoided in patients who are pregnant or breastfeeding. HCV can be transmitted from mother to fetus, so children born to infected women should be screened for HCV. If ribavirin will be a part of an HCV regimen, female patients must avoid pregnancy during treatment and for 6 months following its completion.

HCV TREATMENT CONCERNS IN IV DRUG USERS

From both public health and ethical perspectives, concerns exist regarding the treatment of HCV in PWIDs. Many current PWIDs are excluded from clinical trials, leading to fear that DAAs may be ineffective in this population; however, a recent real-world study in the United States found similar SVR12 rates in groups that continued to use IV drugs and in those who did not use IV drugs.9

Fear that current or past PWIDs will not adhere to their medication regimen may be a barrier to treatment. Strategies for adherence include the use of patient navigators, group therapy, and directly observed treatment. With patient support, including access to substance abuse treatment, HCV treatment in these populations is possible. A recent study in New York evaluated 3 models of HCV treatment, comparing 150 patients on opiate agonist treatment with directly observed treatment, group treatment, and treatment as usual, in which patients took their own medication. Overall, 94% of patients achieved SVR12. More patients did so in the directly observed and group treatment arms than in the treatment as usual arm, but this was not statistically significant.10

Of note is that private or public health insurance plans may deny patients treatment based on current IV drug use. Furthermore, some insurance plans may require 6 or more months of abstinence prior to approval. Current AASLD/IDSA guidelines do not list being a current or former PWID as a contraindication to treatment and should not be used to limit treatment access.6

Reacquisition of HCV infection following successful treatment is a valid concern. All current and past PWIDs should receive risk-reduction education, including information about injection techniques that minimize risk.11 Additionally, although HCV can be reacquired, some small studies show that the reacquisition rate, estimated at 2.9 per 100 person-years, is lower than the new acquisition rate, estimated at 6.1 to 27.2 per 100 person-years. Even in those who continue to use IV drugs, the reinfection rate is 6.44 per 100 person-years.12-14 This rate is similar to the late relapse rate, according to a recent meta-analysis, indicating that most patients—even those at high risk—will not become reinfected.15 This will need to be followed in the future because most of these analyses included patients on pegylated interferon and ribavirin rather than DAAs. Treating the large cohort of infected HCV individuals could also reduce incidence and prevalence in the PWID population, which may help mitigate the reinfection rate.16

Because of these concerns, the AASLD/IDSA guidelines have been updated to include patients with current or past injection drug use as a unique population. Routine HCV screening should be performed annually, if not more frequently, based on risk. The need for harm reduction services, such as patient counseling, needle syringe exchange, and substance use disorder treatment, to minimize the risk of infection and transmission are also highlighted in the new guidelines.6

CONCLUSION

IV drug use is the largest risk factor for hepatitis C transmission, and IV opioid use has increased in the United States, augmenting the likelihood of acquiring HCV infection, especially of genotype 3. Treatment of HCV in current or past PWIDs should be considered to prevent transmission of HCV, as no drug–drug interactions exist between opioid substitution therapy and DAAs. In addition, risk-reduction education should focus on this population to prevent HCV infection from occurring in the first place.    
 
Dr. Andres is a clinical assistant professor at Temple University School of Pharmacy in Philadelphia, Pennsylvania who practices in a hepatology clinic. She received a PharmD from Temple and completed PGY-1 pharmacy practice residency at the Martinsburg Veterans Affairs Medical Center in West Virginia. She is an active member of SIDP.

References:
  1. New hepatitis C infections nearly tripled over five years [press release]. Atlanta, GA: Centers for Disease Control and Prevention; May 11, 2017. cdc.gov/media/releases/2017/p-hepatitis-c-infections-tripled.html. Accessed April 8, 2018.
  2. Zibbell JE, Iqbal K, Patel RC, et al; Centers for Disease Control and Prevention (CDC). Increases in hepatitis C virus infection related to injection drug use among persons aged ≤30 Years - Kentucky, Tennessee, Virginia, and West Virginia, 2006–2012. MMWR Morb Mortal Wkly Rep. 2015;64(17):453-458.
  3. Degenhardt L, Peacock A, Colledge S, et al. Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review. Lancet Glob Health. 2017;5(12):e1192-e1207. doi: 10.1016/S2214-109X(17)30375-3.
  4. Hepatitis C FAQs for health practitioners. CDC website. cdc.gov/hepatitis/hcv/hcvfaq.htm. Published January 27, 2017. Updated April 30, 2018. Accessed April 8, 2018.
  5. Salemovic D, Pesic-Pavlovic I, Jevtovic D, et al. Intravenous drug use – an independent predictor for HCV genotypes 3 and 4 infection among HIV/HCV co-infected patients. Arch Med Sci. 2017;13(3): 652–658. doi: 10.5114/aoms.2017.66022.
  6. HCV guidance: recommendations for testing, managing, and treating hepatitis C. hcvguidelines.org. HVCGuidelines.org website. Accessed May 29, 2018.
  7. Foster GR, Gane E, Asatryan A, et al. ENDURANCE-3: safety and efficacy of glecaprevir/pibrentasvir compared to sofosbuvir plus daclatasvir in treatment-naïve HCV genotype 3-infected patients without cirrhosis. J Hepatol. 2017;66(1):S33. doi: 10.1016/S0168-8278(17)30326-4.
  8. Foster GR, Afdhal N, Roberts SK, et al; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015;373(27):2608-2617. doi: 10.1056/NEJMoa1512612.
  9. Norton, BL, Fleming, J, Bachhuber, MA, et al. High HCV cure rates for people who use drugs treated with direct-acting antiviral therapy at an urban primary care clinic. International Journal of Drug Policy, 47, 196–201.
  10. Litwin AH, Agyemang L, Akiyama M, et al. The PREVAIL Study: intensive models of HCV care for people who inject drugs. Journal of Hepatology 2017; 66. S72. S0168-8278(17)30406-3.
  11. Hagan H, Pouget ER, Des Jarlais DC. A systematic review and meta-analysis of interventions to prevent hepatitis C virus infection in people who inject drugs. J Infect Dis. 2011;204(1):74-83
  12. Aspinall EJ, Corson S, Doyle JS, et al. Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clin Infect Dis. 2013;57(Suppl 2):S80-S89.
  13. Grady BP, Schinkel J, Thomas XV, Dalgard O. Hepatitis C virus reinfection following treatment among people who use drugs. Clin Infect Dis. 2013;57(Suppl 2):S105-S110.
  14. Grebely J, Prins M,  Hellard M, et al. Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine. Lancet Infect Dis 2012 vol.12 (pg. 408-14)
  15. Simmons B, Saleem J, Hill A, Riley RD, Cooke GS. Risk of late relapse or reinfection with hepatitis c virus after achieving a sustained virological response: a systematic review and meta-analysis. Clin Infect Dis. 2016;62:683-94.
  16. Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, Vickerman P. Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin Infect Dis. 2013;57 Suppl 2:S39-45.


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