Elana S. Rosenthal, MD

The United States is experiencing an epidemic of nonmedical opioid use. A concerted effort to better address pain increased the provision of prescription narcotics in the late 1990s and early 2000s.¹ Since then, there has been significant growth of opioid use and acorresponding increase in overdose-related deaths.^1-3 Public health officials have responded with initiatives to secure the opioid supply and improve outpatient treatment resources. However, the role of hospitalists in addressing opioid use disorder (OUD) is not well established. The inpatient needs for these individuals are complex and require a collaborative approach with input from outpatient clinicians, inpatient clinicians, addiction specialists, social workers, and case managers. Hospitals are often under-resourced to provide such comprehensive services. This frequently results in the hospitalist bearing significant responsibility for inpatient addiction management despite often insufficient addiction education or experience.^4,5

Therefore, there is a need for hospitalists to become leaders in the inpatient management of OUD. In this review, we will discuss the hospitalist’s role in the inpatient management of individuals with OUD.

INPATIENT MANAGEMENT OF OPIOID USE DISORDER

Opioid use disorder is a medical illness resulting from neurobiological changes that cause drug tolerance, dependence, and cravings.⁶ It should be considered a treatable chronic medical condition, comparable to hypertension or diabetes,⁷ which requires a multifaceted treatment approach, including psychosocial, educational, and medical interventions.

Psychosocial Interventions

Individuals with OUD often have complicated social issues including stigmatization, involvement in the criminal justice system, unemployment, and homelessness,^5,8-10 in addition to frequent comorbid mental health issues.^11,12 Failure to address social or mental health barriers may lead to a lack of engagement in the treatment of OUD. The long-term management of OUD should involve outpatient psychotherapy and may include individual or group therapy, behavioral therapy, family counseling, or support groups.¹³ In the inpatient setting, hospitalists should use a collaborative approach to address psychosocial barriers. The authors recommend social work and case management consultations and consideration of psychiatric consultation when appropriate.

Management of Opioid Withdrawal

The prompt recognition and management of withdrawal is essential in hospitalized patients with OUD. The signs and symptoms of withdrawal can be evaluated by using the Clinical Opiate Withdrawal Scale or the Clinical Institute Narcotics Assessment, and may include lacrimation, rhinorrhea, diaphoresis, yawning, restlessness, insomnia, piloerection, myalgia, arthralgia, abdominal pain, nausea, vomiting, and diarrhea.⁴ Individuals using short-acting opioids, such as oxycodone or heroin, may develop withdrawal symptoms 8 to 12 hours after cessation of the opioid. Symptoms often peak on days 1 to 3 and can last for up to 10 days.¹⁴ Individuals taking long-acting opioids, such as methadone, may experience withdrawal symptoms for up to 21 days.¹⁴

While the goal of withdrawal treatment is to reduce the uncomfortable symptoms of withdrawal, there may be additional benefits. Around 16% of people who inject drugs will misuse drugs during their hospitalization, and 25% to 30% will be discharged against medical advice.^15,16 In hospitalizations when patients are administered methadone for management of withdrawal, there is a significant reduction in discharges against medical advice.¹⁶ This may suggest that treatment of withdrawal has the added benefit of preventing discharges against medical advice, and the authors postulate that treatment may decrease surreptitious drug use during hospitalizations, although this has not been studied.

There are 2 approaches to treating opioid withdrawal—opioid substitution treatment and alpha₂-adrenergic agonist treatment (Table 1).^4,17-20 Of note, opioid substitution treatment, especially when using buprenorphine, should be started only when a patient has at least mild withdrawal symptoms.²⁰

An important exception to the treatment approach listed in Table 1 occurs when a patient is already taking methadone or buprenorphine maintenance therapy. In this circumstance, the outpatient dose should be continued after confirmation of dose and timing of last administration with outpatient clinicians. It is important that clear communication with the patient’s addiction clinician occurs at admission and discharge to prevent an inadvertently duplicated, or missed, dose.

Factors to consider when selecting a withdrawal treatment regimen include comorbidities, anticipated length of stay, anticipated discharge setting, medications, interest in long-term addiction treatment, and other patient-specific factors. In general, treatment with methadone or buprenorphine is preferred, because they are better tolerated and may be more effective than clonidine.^21-24 The selection of methadone or buprenorphine is often based on physician or patient preference, presence of contraindications, or formulary restrictions, as they have similar efficacy in the treatment of opioid withdrawal.²³ In cases where opioid replacement therapy is contraindicated, such as in an individual who has received naltrexone, clonidine should be used.²⁴

Methadone and buprenorphine are controlled substances that can be prescribed only in outpatients by certified clinicians. Therefore, hospitalists are prohibited from prescribing these medications at discharge for the treatment of OUD. However, inpatient clinicians are exempt from these regulations and may provide both medications for maintenance and withdrawal treatment in the inpatient setting.

As such, while a 10 to 14-day taper may be optimal in preventing relapse and minimizing withdrawal, patients are often medically ready to leave the hospital before their taper is completed. In these cases, a rapid taper over 3 to 5 days can be considered. The disadvantage of a rapid taper is the potential for recrudescence of withdrawal symptoms after discharge. Individuals who do not tolerate a rapid taper should be treated with a slower taper, or transitioned to a clonidine taper.

Many hospitals have protocols to help guide the inpatient management of withdrawal, and in many cases, subspecialist consultation is not necessary. However, the authors recommend involvement of an addiction specialist for patients in whom management of withdrawal may be complicated. Further, we strongly encourage hospitalists to be involved in creation and maintenance of withdrawal treatment protocols.

 

Medication-Assisted Treatment

It is important to recognize that treatment of withdrawal is not adequate to prevent long-term opioid misuse.²⁵ The optimal long-term management of OUD includes the use of medication-assisted treatment (MAT). The initiation and titration of MAT should always be done in conjunction with an addiction specialist or buprenorphine-waivered physician who will ensure continuation of MAT as an outpatient. This means that, while hospitalists may be critical in facilitating linkage to MAT, in general, they will not have a significant role in the long-term management of OUD. However, hospitalists should be knowledgeable about MAT because it is relatively common and can complicate hospitalizations.

There are two types of MAT: opioid-agonist treatment (OAT) and opioid-antagonist treatment. Opioid-agonist treatment involves the use of methadone, a long-acting opioid agonist, or buprenorphine, a long-acting partial opioid agonist. These medications decrease the amount and severity of cravings and limit the euphoric effects of subsequent opioid use.¹⁷ Compared to abstinence-based treatment, OAT has been associated with increased retention in addiction treatment and employment, and reductions in incarceration, human immunodeficiency virus transmission, illicit drug use, opioid-overdose events, and mortality.^26-32An alternative to OAT is naltrexone, an opioid antagonist. Naltrexone for OUD is administered as a monthly depot injection that prevents the user from experiencing opioid intoxication or dependence, and is associated with sustained abstinence.^17,33,34 The authors strongly recommend that hospitalists discuss the benefits of MAT with hospitalized individuals with OUD. In addition, when appropriate, patients should receive consultation with, or referral to, an addiction specialist.

Adverse Effects of Methadone, Buprenorphine, and Naltrexone

The benefits of MAT are substantial, but there are adverse effects, potential drug-to-drug interactions, and patient-specific characteristics that may impact the inpatient management of individuals on MAT. Selected adverse effects of OAT are listed in Table 1. The adverse effects of naltrexone include nausea, vomiting, and transaminitis. It should also be noted that the initiation of buprenorphine and naltrexone may induce opioid withdrawal when administered to an opioid-dependent patient with recent opioid use. To avoid precipitating withdrawal, buprenorphine should be used only in individuals who have at least mild withdrawal symptoms or have completed detoxification,²⁰ and naltrexone should be used only in patients who have abstained from opioids for at least 7 to 10 days.³⁵

Opioid-agonist treatments are primarily metabolized by the cytochrome P450 3A4 isoenzyme system. Medications that inhibit cytochrome P450 3A4 metabolism such as fluconazole can result in OAT toxicity, while medications that induce cytochrome P450 3A4 metabolism such as dexamethasone can lead to withdrawal symptoms.¹⁸ If these interactions are unavoidable, the dose of methadone or buprenorphine should be adjusted to prevent toxicity or withdrawal symptoms. The major drug interaction with naltrexone is ineffective analgesia from opioids.

Another major concern with MAT is the risk of overdose-related deaths. As an opioid agonist, large doses of methadone can result in respiratory depression, while buprenorphine alone, due to its partial agonist effect, is unlikely to result in respiratory depression. When methadone or buprenorphine are taken with other substances that cause respiratory depression, such as benzodiazepines or alcohol, the risk of respiratory depression and overdose is significantly increased.^36,37 Overdose-related death with naltrexone usually occurs after the medication has metabolized and results from a loss of opioid tolerance.³⁸

Special Populations

Medication-assisted treatment in individuals with acute pain. Maintenance treatment with OAT does not provide sufficient analgesia to treat episodes of acute pain.³⁹ In patients on methadone maintenance, the maintenance dose should be continued and adjunctive analgesia should be provided with nonopioid analgesics or short-acting opioids.³⁹ The management of acute pain in individuals on buprenorphine maintenance is more complicated since buprenorphine is a partial opioid agonist with high affinity to the opioid receptor, which limits the impact of adjunctive opioids. The options for analgesia in buprenorphine maintenance treatment include 1) continuing daily dosing of buprenorphine and providing nonopioid or opioid analgesics, 2) dividing buprenorphine dosing into a 3 or 4 times a day medication, 3) discontinuing buprenorphine and treating with opioid analgesics, 4) discontinuing buprenorphine and starting methadone with nonopioid or opioid analgesics.³⁹ In cases where buprenorphine is discontinued, it should be restarted before discharge upon resolution of the acute pain episode. An individual with acute pain on naltrexone may require nonopioid analgesia or regional blocks. In these patients, adequate pain control may be challenging and require the consultation of an acute pain specialist.

Pregnant or breastfeeding individuals. Opioid misuse puts the individual and fetus at risk of complications, and abrupt discontinuation can cause preterm labor, fetal distress, or fetal demise.⁴⁰ The current standard is to initiate methadone in consultation with an addiction specialist.⁴⁰ There is evidence that buprenorphine can be used during pregnancy; however, buprenorphine-naloxone is discouraged.^18,40 Of note, use of OAT in pregnancy can result in neonatal abstinence syndrome, an expected complication that can be managed by a pediatrician.⁴⁰

Methadone and buprenorphine can be found in low concentrations in breast milk.⁴¹ However, according to the Academy of Breastfeeding Medicine’s clinical guidelines, women on stable doses of methadone and buprenorphine should be encouraged to breastfeed.⁴¹ Naltrexone enters breast milk and has potential adverse effects for the newborn. Either the mother should discontinue naltrexone or should not breastfeed.³⁵

Treatment of polysubstance misuse. Individuals with OUD may also misuse other substances. The concomitant use of opioids and other central nervous system depressants, such as alcohol and benzodiazepines, is especially worrisome as they can potentiate respiratory depression. The presence of polysubstance misuse does not preclude the use of MAT for the treatment of OUD. In those with comorbid alcohol use disorder, the use of naltrexone may be appealing as it can treat both alcohol use disorder and OUD. Given the complexities of managing polysubstance misuse, addiction specialists should be involved in the care of these patients.⁴² In addition, patients should be educated on the risks of polysubstance misuse, especially when it involves 2 central nervous system depressants.

Comorbid medical disease. In general, medical comorbidities do not significantly affect the treatment of OUD; however, dysfunction of certain organ systems may necessitate a dose reduction or discontinuation of MAT. Severe liver disease may result in decreased hepatic metabolism of OAT.^35,42 Prolonged QTc, or history of arrhythmia, may preclude the use of methadone.^17,35,42 In addition, chronic hypercapnic respiratory failure or severe asthma may be contraindications for the use of methadone in an unmonitored setting.³⁵ Kidney failure is not known to be a contraindication to MAT, and there is no consensus on the need for dose reduction of MAT with decreasing glomerular filtration rate; however, some authors recommend a 25% to 50% dose reduction of methadone when the glomerular filtration rate is less than 10 milliliters per minute.⁴³ There is no such recommendation with buprenorphine, although it has not been adequately studied in individuals with renal failure. Close monitoring for evidence of toxicity is prudent in individuals on MAT with acute or chronic renal failure.³⁵

Rural or resource-limited areas. There is a significant shortage of addiction treatment options in many regions of the United States. As of 2012, there were an estimated 2.3 million individuals with OUD; however, more than 1 million of these individuals do not have access to treatment.⁴⁴ As a result, many addiction treatment programs have wait lists that can last months or even years.⁴⁵ These shortages are especially apparent in rural areas, where individuals with OUD are particularly reliant upon buprenorphine treatment because of prohibitive travel times to urban-based programs.⁴⁶ To address this problem, new models of care delivery are being developed, including models incorporating telemedicine to support rural primary care management of OUD.⁴⁷

 

The Future of Medication-Assisted Treatment

Currently, MAT is initiated and managed by outpatient addiction specialists. However, evidence supports initiation of MAT as an inpatient.⁴⁸ A recent study compared inpatient buprenorphine detoxification to inpatient buprenorphine induction, dose stabilization, and postdischarge linkage-of-care to outpatient opioid treatment clinics. Patients who received inpatient buprenorphine initiation and linkage-of-care had improved buprenorphine treatment retention and reported less illicit opioid use.⁴⁸ The development of partnerships between hospitals, inpatient clinicians, and outpatient addiction specialists is essential and could lead to significant advances in treating hospitalized patients with OUD.

The initiation of MAT in hospitalized patients with immediate linkage-of-care shows great promise; however, at this point, the initiation of MAT should be done only in conjunction with addiction specialists in patients with confirmed outpatient follow-up. In cases where inpatient MAT initiation is pursued, education of staff including nurses and pharmacists is essential.

Harm Reduction Interventions

Ideally, management of OUD results in abstinence from opioid misuse; however, some individuals are not ready for treatment or, despite MAT, have relapses of opioid misuse. Given this, a secondary goal in the management of OUD is the reduction of harm that can result from opioid misuse.

Many individuals inject opioids, which is associated with increased rates of viral and bacterial infections secondary to nonsterile injection practices.⁴⁹ Educating patients on sterile injection methods (Table 2),⁵⁰ including the importance of sterile-injecting equipment and water, and cleaning the skin prior to injection, may mitigate the risk of infections and should be provided for all hospitalized people who inject drugs.

Syringe-exchange programs provide sterile-injecting equipment in exchange for used needles, with a goal of increasing access to sterile supplies and removing contaminated syringes from circulation.⁵¹ While controversial, these programs may reduce the incidence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus.⁵¹

In addition, syringe-exchange programs often provide addiction treatment referrals, counseling, testing, and prevention education for human immunodeficiency virus, hepatitis C virus, and sexually transmitted infections.⁴⁹ In the United States, there are 226 programs in 33 states (see https://nasen.org/directory for a list of programs and locations. Inpatient clinicians should provide a list of local resources including syringe-exchange programs at the time of discharge for any people who inject drugs. In addition, individuals with OUD are at increased risk for overdose, especially in the postdischarge setting due to decreased opioid tolerance.⁵² In 2014, there were 28,647 opioid overdose-related deaths in the United States.² To address this troubling epidemic, opioid overdose education and naloxone distribution has been championed to educate patients at risk of opioid overdose and potential first responders on how to counteract an overdose by using naloxone, an opioid antagonist (see Table 2 for more information on opioid overdose education). The use of opioid overdose education and naloxone distribution has been observed to reduce opioid overdose-related death rates.⁵³

Hospitalists should provide opioid overdose education and naloxone to all individuals at risk of opioid overdose (including those with OUD), as well as potential first responders where the law allows (more information including individual state laws can be found at http://prescribetoprevent.org).²⁰

Considerations at Discharge

There are a number of considerations for the hospitalist at discharge (see Table 3 for a recommended discharge checklist). In addition, it is important to appreciate, and minimize, the ways that hospitalists contribute to the opioid epidemic. For instance, prescribing opioids at discharge in opioid-naïve patients increases the risk of chronic opioid use.⁵⁴ It is also essential to recognize that increased doses of opioids are associated with increased rates of opioid overdose-related deaths.⁵⁵ As such, hospitalists should maximize the use of nonopioid analgesics, prescribe opioids only when necessary, use the smallest effective dose of opioids, limit the number of opioid pills distributed to patients, and check prescription-monitoring programs for evidence of misuse.

CONCLUSION

Hospitalization serves as an important opportunity to address addiction in individuals with OUD. In addressing addiction, hospitalists should identify and intervene on psychosocial and mental health barriers, treat opioid withdrawal, and propagate harm reduction strategies. In addition, there is a growing role for hospitalists to be involved in the initiation of MAT and linkage-of-care to outpatient addiction treatment. If hospitalists become leaders in the inpatient management of OUD, they will significantly improve the care provided to this vulnerable patient population.

Disclosure

The authors report no financial conflicts of interest.

 

The United States is experiencing an epidemic of nonmedical opioid use. A concerted effort to better address pain increased the provision of prescription narcotics in the late 1990s and early 2000s.¹ Since then, there has been significant growth of opioid use and acorresponding increase in overdose-related deaths.^1-3 Public health officials have responded with initiatives to secure the opioid supply and improve outpatient treatment resources. However, the role of hospitalists in addressing opioid use disorder (OUD) is not well established. The inpatient needs for these individuals are complex and require a collaborative approach with input from outpatient clinicians, inpatient clinicians, addiction specialists, social workers, and case managers. Hospitals are often under-resourced to provide such comprehensive services. This frequently results in the hospitalist bearing significant responsibility for inpatient addiction management despite often insufficient addiction education or experience.^4,5

Therefore, there is a need for hospitalists to become leaders in the inpatient management of OUD. In this review, we will discuss the hospitalist’s role in the inpatient management of individuals with OUD.

INPATIENT MANAGEMENT OF OPIOID USE DISORDER

Opioid use disorder is a medical illness resulting from neurobiological changes that cause drug tolerance, dependence, and cravings.⁶ It should be considered a treatable chronic medical condition, comparable to hypertension or diabetes,⁷ which requires a multifaceted treatment approach, including psychosocial, educational, and medical interventions.

Psychosocial Interventions

Individuals with OUD often have complicated social issues including stigmatization, involvement in the criminal justice system, unemployment, and homelessness,^5,8-10 in addition to frequent comorbid mental health issues.^11,12 Failure to address social or mental health barriers may lead to a lack of engagement in the treatment of OUD. The long-term management of OUD should involve outpatient psychotherapy and may include individual or group therapy, behavioral therapy, family counseling, or support groups.¹³ In the inpatient setting, hospitalists should use a collaborative approach to address psychosocial barriers. The authors recommend social work and case management consultations and consideration of psychiatric consultation when appropriate.

Management of Opioid Withdrawal

The prompt recognition and management of withdrawal is essential in hospitalized patients with OUD. The signs and symptoms of withdrawal can be evaluated by using the Clinical Opiate Withdrawal Scale or the Clinical Institute Narcotics Assessment, and may include lacrimation, rhinorrhea, diaphoresis, yawning, restlessness, insomnia, piloerection, myalgia, arthralgia, abdominal pain, nausea, vomiting, and diarrhea.⁴ Individuals using short-acting opioids, such as oxycodone or heroin, may develop withdrawal symptoms 8 to 12 hours after cessation of the opioid. Symptoms often peak on days 1 to 3 and can last for up to 10 days.¹⁴ Individuals taking long-acting opioids, such as methadone, may experience withdrawal symptoms for up to 21 days.¹⁴

While the goal of withdrawal treatment is to reduce the uncomfortable symptoms of withdrawal, there may be additional benefits. Around 16% of people who inject drugs will misuse drugs during their hospitalization, and 25% to 30% will be discharged against medical advice.^15,16 In hospitalizations when patients are administered methadone for management of withdrawal, there is a significant reduction in discharges against medical advice.¹⁶ This may suggest that treatment of withdrawal has the added benefit of preventing discharges against medical advice, and the authors postulate that treatment may decrease surreptitious drug use during hospitalizations, although this has not been studied.

There are 2 approaches to treating opioid withdrawal—opioid substitution treatment and alpha₂-adrenergic agonist treatment (Table 1).^4,17-20 Of note, opioid substitution treatment, especially when using buprenorphine, should be started only when a patient has at least mild withdrawal symptoms.²⁰

An important exception to the treatment approach listed in Table 1 occurs when a patient is already taking methadone or buprenorphine maintenance therapy. In this circumstance, the outpatient dose should be continued after confirmation of dose and timing of last administration with outpatient clinicians. It is important that clear communication with the patient’s addiction clinician occurs at admission and discharge to prevent an inadvertently duplicated, or missed, dose.

Factors to consider when selecting a withdrawal treatment regimen include comorbidities, anticipated length of stay, anticipated discharge setting, medications, interest in long-term addiction treatment, and other patient-specific factors. In general, treatment with methadone or buprenorphine is preferred, because they are better tolerated and may be more effective than clonidine.^21-24 The selection of methadone or buprenorphine is often based on physician or patient preference, presence of contraindications, or formulary restrictions, as they have similar efficacy in the treatment of opioid withdrawal.²³ In cases where opioid replacement therapy is contraindicated, such as in an individual who has received naltrexone, clonidine should be used.²⁴

Methadone and buprenorphine are controlled substances that can be prescribed only in outpatients by certified clinicians. Therefore, hospitalists are prohibited from prescribing these medications at discharge for the treatment of OUD. However, inpatient clinicians are exempt from these regulations and may provide both medications for maintenance and withdrawal treatment in the inpatient setting.

As such, while a 10 to 14-day taper may be optimal in preventing relapse and minimizing withdrawal, patients are often medically ready to leave the hospital before their taper is completed. In these cases, a rapid taper over 3 to 5 days can be considered. The disadvantage of a rapid taper is the potential for recrudescence of withdrawal symptoms after discharge. Individuals who do not tolerate a rapid taper should be treated with a slower taper, or transitioned to a clonidine taper.

Many hospitals have protocols to help guide the inpatient management of withdrawal, and in many cases, subspecialist consultation is not necessary. However, the authors recommend involvement of an addiction specialist for patients in whom management of withdrawal may be complicated. Further, we strongly encourage hospitalists to be involved in creation and maintenance of withdrawal treatment protocols.

 

Medication-Assisted Treatment

It is important to recognize that treatment of withdrawal is not adequate to prevent long-term opioid misuse.²⁵ The optimal long-term management of OUD includes the use of medication-assisted treatment (MAT). The initiation and titration of MAT should always be done in conjunction with an addiction specialist or buprenorphine-waivered physician who will ensure continuation of MAT as an outpatient. This means that, while hospitalists may be critical in facilitating linkage to MAT, in general, they will not have a significant role in the long-term management of OUD. However, hospitalists should be knowledgeable about MAT because it is relatively common and can complicate hospitalizations.

There are two types of MAT: opioid-agonist treatment (OAT) and opioid-antagonist treatment. Opioid-agonist treatment involves the use of methadone, a long-acting opioid agonist, or buprenorphine, a long-acting partial opioid agonist. These medications decrease the amount and severity of cravings and limit the euphoric effects of subsequent opioid use.¹⁷ Compared to abstinence-based treatment, OAT has been associated with increased retention in addiction treatment and employment, and reductions in incarceration, human immunodeficiency virus transmission, illicit drug use, opioid-overdose events, and mortality.^26-32An alternative to OAT is naltrexone, an opioid antagonist. Naltrexone for OUD is administered as a monthly depot injection that prevents the user from experiencing opioid intoxication or dependence, and is associated with sustained abstinence.^17,33,34 The authors strongly recommend that hospitalists discuss the benefits of MAT with hospitalized individuals with OUD. In addition, when appropriate, patients should receive consultation with, or referral to, an addiction specialist.

Adverse Effects of Methadone, Buprenorphine, and Naltrexone

The benefits of MAT are substantial, but there are adverse effects, potential drug-to-drug interactions, and patient-specific characteristics that may impact the inpatient management of individuals on MAT. Selected adverse effects of OAT are listed in Table 1. The adverse effects of naltrexone include nausea, vomiting, and transaminitis. It should also be noted that the initiation of buprenorphine and naltrexone may induce opioid withdrawal when administered to an opioid-dependent patient with recent opioid use. To avoid precipitating withdrawal, buprenorphine should be used only in individuals who have at least mild withdrawal symptoms or have completed detoxification,²⁰ and naltrexone should be used only in patients who have abstained from opioids for at least 7 to 10 days.³⁵

Opioid-agonist treatments are primarily metabolized by the cytochrome P450 3A4 isoenzyme system. Medications that inhibit cytochrome P450 3A4 metabolism such as fluconazole can result in OAT toxicity, while medications that induce cytochrome P450 3A4 metabolism such as dexamethasone can lead to withdrawal symptoms.¹⁸ If these interactions are unavoidable, the dose of methadone or buprenorphine should be adjusted to prevent toxicity or withdrawal symptoms. The major drug interaction with naltrexone is ineffective analgesia from opioids.

Another major concern with MAT is the risk of overdose-related deaths. As an opioid agonist, large doses of methadone can result in respiratory depression, while buprenorphine alone, due to its partial agonist effect, is unlikely to result in respiratory depression. When methadone or buprenorphine are taken with other substances that cause respiratory depression, such as benzodiazepines or alcohol, the risk of respiratory depression and overdose is significantly increased.^36,37 Overdose-related death with naltrexone usually occurs after the medication has metabolized and results from a loss of opioid tolerance.³⁸

Special Populations

Medication-assisted treatment in individuals with acute pain. Maintenance treatment with OAT does not provide sufficient analgesia to treat episodes of acute pain.³⁹ In patients on methadone maintenance, the maintenance dose should be continued and adjunctive analgesia should be provided with nonopioid analgesics or short-acting opioids.³⁹ The management of acute pain in individuals on buprenorphine maintenance is more complicated since buprenorphine is a partial opioid agonist with high affinity to the opioid receptor, which limits the impact of adjunctive opioids. The options for analgesia in buprenorphine maintenance treatment include 1) continuing daily dosing of buprenorphine and providing nonopioid or opioid analgesics, 2) dividing buprenorphine dosing into a 3 or 4 times a day medication, 3) discontinuing buprenorphine and treating with opioid analgesics, 4) discontinuing buprenorphine and starting methadone with nonopioid or opioid analgesics.³⁹ In cases where buprenorphine is discontinued, it should be restarted before discharge upon resolution of the acute pain episode. An individual with acute pain on naltrexone may require nonopioid analgesia or regional blocks. In these patients, adequate pain control may be challenging and require the consultation of an acute pain specialist.

Pregnant or breastfeeding individuals. Opioid misuse puts the individual and fetus at risk of complications, and abrupt discontinuation can cause preterm labor, fetal distress, or fetal demise.⁴⁰ The current standard is to initiate methadone in consultation with an addiction specialist.⁴⁰ There is evidence that buprenorphine can be used during pregnancy; however, buprenorphine-naloxone is discouraged.^18,40 Of note, use of OAT in pregnancy can result in neonatal abstinence syndrome, an expected complication that can be managed by a pediatrician.⁴⁰

Methadone and buprenorphine can be found in low concentrations in breast milk.⁴¹ However, according to the Academy of Breastfeeding Medicine’s clinical guidelines, women on stable doses of methadone and buprenorphine should be encouraged to breastfeed.⁴¹ Naltrexone enters breast milk and has potential adverse effects for the newborn. Either the mother should discontinue naltrexone or should not breastfeed.³⁵

Treatment of polysubstance misuse. Individuals with OUD may also misuse other substances. The concomitant use of opioids and other central nervous system depressants, such as alcohol and benzodiazepines, is especially worrisome as they can potentiate respiratory depression. The presence of polysubstance misuse does not preclude the use of MAT for the treatment of OUD. In those with comorbid alcohol use disorder, the use of naltrexone may be appealing as it can treat both alcohol use disorder and OUD. Given the complexities of managing polysubstance misuse, addiction specialists should be involved in the care of these patients.⁴² In addition, patients should be educated on the risks of polysubstance misuse, especially when it involves 2 central nervous system depressants.

Comorbid medical disease. In general, medical comorbidities do not significantly affect the treatment of OUD; however, dysfunction of certain organ systems may necessitate a dose reduction or discontinuation of MAT. Severe liver disease may result in decreased hepatic metabolism of OAT.^35,42 Prolonged QTc, or history of arrhythmia, may preclude the use of methadone.^17,35,42 In addition, chronic hypercapnic respiratory failure or severe asthma may be contraindications for the use of methadone in an unmonitored setting.³⁵ Kidney failure is not known to be a contraindication to MAT, and there is no consensus on the need for dose reduction of MAT with decreasing glomerular filtration rate; however, some authors recommend a 25% to 50% dose reduction of methadone when the glomerular filtration rate is less than 10 milliliters per minute.⁴³ There is no such recommendation with buprenorphine, although it has not been adequately studied in individuals with renal failure. Close monitoring for evidence of toxicity is prudent in individuals on MAT with acute or chronic renal failure.³⁵

Rural or resource-limited areas. There is a significant shortage of addiction treatment options in many regions of the United States. As of 2012, there were an estimated 2.3 million individuals with OUD; however, more than 1 million of these individuals do not have access to treatment.⁴⁴ As a result, many addiction treatment programs have wait lists that can last months or even years.⁴⁵ These shortages are especially apparent in rural areas, where individuals with OUD are particularly reliant upon buprenorphine treatment because of prohibitive travel times to urban-based programs.⁴⁶ To address this problem, new models of care delivery are being developed, including models incorporating telemedicine to support rural primary care management of OUD.⁴⁷

 

The Future of Medication-Assisted Treatment

Currently, MAT is initiated and managed by outpatient addiction specialists. However, evidence supports initiation of MAT as an inpatient.⁴⁸ A recent study compared inpatient buprenorphine detoxification to inpatient buprenorphine induction, dose stabilization, and postdischarge linkage-of-care to outpatient opioid treatment clinics. Patients who received inpatient buprenorphine initiation and linkage-of-care had improved buprenorphine treatment retention and reported less illicit opioid use.⁴⁸ The development of partnerships between hospitals, inpatient clinicians, and outpatient addiction specialists is essential and could lead to significant advances in treating hospitalized patients with OUD.

The initiation of MAT in hospitalized patients with immediate linkage-of-care shows great promise; however, at this point, the initiation of MAT should be done only in conjunction with addiction specialists in patients with confirmed outpatient follow-up. In cases where inpatient MAT initiation is pursued, education of staff including nurses and pharmacists is essential.

Harm Reduction Interventions

Ideally, management of OUD results in abstinence from opioid misuse; however, some individuals are not ready for treatment or, despite MAT, have relapses of opioid misuse. Given this, a secondary goal in the management of OUD is the reduction of harm that can result from opioid misuse.

Many individuals inject opioids, which is associated with increased rates of viral and bacterial infections secondary to nonsterile injection practices.⁴⁹ Educating patients on sterile injection methods (Table 2),⁵⁰ including the importance of sterile-injecting equipment and water, and cleaning the skin prior to injection, may mitigate the risk of infections and should be provided for all hospitalized people who inject drugs.

Syringe-exchange programs provide sterile-injecting equipment in exchange for used needles, with a goal of increasing access to sterile supplies and removing contaminated syringes from circulation.⁵¹ While controversial, these programs may reduce the incidence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus.⁵¹

In addition, syringe-exchange programs often provide addiction treatment referrals, counseling, testing, and prevention education for human immunodeficiency virus, hepatitis C virus, and sexually transmitted infections.⁴⁹ In the United States, there are 226 programs in 33 states (see https://nasen.org/directory for a list of programs and locations. Inpatient clinicians should provide a list of local resources including syringe-exchange programs at the time of discharge for any people who inject drugs. In addition, individuals with OUD are at increased risk for overdose, especially in the postdischarge setting due to decreased opioid tolerance.⁵² In 2014, there were 28,647 opioid overdose-related deaths in the United States.² To address this troubling epidemic, opioid overdose education and naloxone distribution has been championed to educate patients at risk of opioid overdose and potential first responders on how to counteract an overdose by using naloxone, an opioid antagonist (see Table 2 for more information on opioid overdose education). The use of opioid overdose education and naloxone distribution has been observed to reduce opioid overdose-related death rates.⁵³

Hospitalists should provide opioid overdose education and naloxone to all individuals at risk of opioid overdose (including those with OUD), as well as potential first responders where the law allows (more information including individual state laws can be found at http://prescribetoprevent.org).²⁰

Considerations at Discharge

There are a number of considerations for the hospitalist at discharge (see Table 3 for a recommended discharge checklist). In addition, it is important to appreciate, and minimize, the ways that hospitalists contribute to the opioid epidemic. For instance, prescribing opioids at discharge in opioid-naïve patients increases the risk of chronic opioid use.⁵⁴ It is also essential to recognize that increased doses of opioids are associated with increased rates of opioid overdose-related deaths.⁵⁵ As such, hospitalists should maximize the use of nonopioid analgesics, prescribe opioids only when necessary, use the smallest effective dose of opioids, limit the number of opioid pills distributed to patients, and check prescription-monitoring programs for evidence of misuse.

CONCLUSION

Hospitalization serves as an important opportunity to address addiction in individuals with OUD. In addressing addiction, hospitalists should identify and intervene on psychosocial and mental health barriers, treat opioid withdrawal, and propagate harm reduction strategies. In addition, there is a growing role for hospitalists to be involved in the initiation of MAT and linkage-of-care to outpatient addiction treatment. If hospitalists become leaders in the inpatient management of OUD, they will significantly improve the care provided to this vulnerable patient population.

Disclosure

The authors report no financial conflicts of interest.

 

The United States is experiencing an epidemic of nonmedical opioid use. A concerted effort to better address pain increased the provision of prescription narcotics in the late 1990s and early 2000s.¹ Since then, there has been significant growth of opioid use and acorresponding increase in overdose-related deaths.^1-3 Public health officials have responded with initiatives to secure the opioid supply and improve outpatient treatment resources. However, the role of hospitalists in addressing opioid use disorder (OUD) is not well established. The inpatient needs for these individuals are complex and require a collaborative approach with input from outpatient clinicians, inpatient clinicians, addiction specialists, social workers, and case managers. Hospitals are often under-resourced to provide such comprehensive services. This frequently results in the hospitalist bearing significant responsibility for inpatient addiction management despite often insufficient addiction education or experience.^4,5

Therefore, there is a need for hospitalists to become leaders in the inpatient management of OUD. In this review, we will discuss the hospitalist’s role in the inpatient management of individuals with OUD.

INPATIENT MANAGEMENT OF OPIOID USE DISORDER

Opioid use disorder is a medical illness resulting from neurobiological changes that cause drug tolerance, dependence, and cravings.⁶ It should be considered a treatable chronic medical condition, comparable to hypertension or diabetes,⁷ which requires a multifaceted treatment approach, including psychosocial, educational, and medical interventions.

Psychosocial Interventions

Individuals with OUD often have complicated social issues including stigmatization, involvement in the criminal justice system, unemployment, and homelessness,^5,8-10 in addition to frequent comorbid mental health issues.^11,12 Failure to address social or mental health barriers may lead to a lack of engagement in the treatment of OUD. The long-term management of OUD should involve outpatient psychotherapy and may include individual or group therapy, behavioral therapy, family counseling, or support groups.¹³ In the inpatient setting, hospitalists should use a collaborative approach to address psychosocial barriers. The authors recommend social work and case management consultations and consideration of psychiatric consultation when appropriate.

Management of Opioid Withdrawal

The prompt recognition and management of withdrawal is essential in hospitalized patients with OUD. The signs and symptoms of withdrawal can be evaluated by using the Clinical Opiate Withdrawal Scale or the Clinical Institute Narcotics Assessment, and may include lacrimation, rhinorrhea, diaphoresis, yawning, restlessness, insomnia, piloerection, myalgia, arthralgia, abdominal pain, nausea, vomiting, and diarrhea.⁴ Individuals using short-acting opioids, such as oxycodone or heroin, may develop withdrawal symptoms 8 to 12 hours after cessation of the opioid. Symptoms often peak on days 1 to 3 and can last for up to 10 days.¹⁴ Individuals taking long-acting opioids, such as methadone, may experience withdrawal symptoms for up to 21 days.¹⁴

While the goal of withdrawal treatment is to reduce the uncomfortable symptoms of withdrawal, there may be additional benefits. Around 16% of people who inject drugs will misuse drugs during their hospitalization, and 25% to 30% will be discharged against medical advice.^15,16 In hospitalizations when patients are administered methadone for management of withdrawal, there is a significant reduction in discharges against medical advice.¹⁶ This may suggest that treatment of withdrawal has the added benefit of preventing discharges against medical advice, and the authors postulate that treatment may decrease surreptitious drug use during hospitalizations, although this has not been studied.

There are 2 approaches to treating opioid withdrawal—opioid substitution treatment and alpha₂-adrenergic agonist treatment (Table 1).^4,17-20 Of note, opioid substitution treatment, especially when using buprenorphine, should be started only when a patient has at least mild withdrawal symptoms.²⁰

An important exception to the treatment approach listed in Table 1 occurs when a patient is already taking methadone or buprenorphine maintenance therapy. In this circumstance, the outpatient dose should be continued after confirmation of dose and timing of last administration with outpatient clinicians. It is important that clear communication with the patient’s addiction clinician occurs at admission and discharge to prevent an inadvertently duplicated, or missed, dose.

Factors to consider when selecting a withdrawal treatment regimen include comorbidities, anticipated length of stay, anticipated discharge setting, medications, interest in long-term addiction treatment, and other patient-specific factors. In general, treatment with methadone or buprenorphine is preferred, because they are better tolerated and may be more effective than clonidine.^21-24 The selection of methadone or buprenorphine is often based on physician or patient preference, presence of contraindications, or formulary restrictions, as they have similar efficacy in the treatment of opioid withdrawal.²³ In cases where opioid replacement therapy is contraindicated, such as in an individual who has received naltrexone, clonidine should be used.²⁴

Methadone and buprenorphine are controlled substances that can be prescribed only in outpatients by certified clinicians. Therefore, hospitalists are prohibited from prescribing these medications at discharge for the treatment of OUD. However, inpatient clinicians are exempt from these regulations and may provide both medications for maintenance and withdrawal treatment in the inpatient setting.

As such, while a 10 to 14-day taper may be optimal in preventing relapse and minimizing withdrawal, patients are often medically ready to leave the hospital before their taper is completed. In these cases, a rapid taper over 3 to 5 days can be considered. The disadvantage of a rapid taper is the potential for recrudescence of withdrawal symptoms after discharge. Individuals who do not tolerate a rapid taper should be treated with a slower taper, or transitioned to a clonidine taper.

Many hospitals have protocols to help guide the inpatient management of withdrawal, and in many cases, subspecialist consultation is not necessary. However, the authors recommend involvement of an addiction specialist for patients in whom management of withdrawal may be complicated. Further, we strongly encourage hospitalists to be involved in creation and maintenance of withdrawal treatment protocols.

 

Medication-Assisted Treatment

It is important to recognize that treatment of withdrawal is not adequate to prevent long-term opioid misuse.²⁵ The optimal long-term management of OUD includes the use of medication-assisted treatment (MAT). The initiation and titration of MAT should always be done in conjunction with an addiction specialist or buprenorphine-waivered physician who will ensure continuation of MAT as an outpatient. This means that, while hospitalists may be critical in facilitating linkage to MAT, in general, they will not have a significant role in the long-term management of OUD. However, hospitalists should be knowledgeable about MAT because it is relatively common and can complicate hospitalizations.

There are two types of MAT: opioid-agonist treatment (OAT) and opioid-antagonist treatment. Opioid-agonist treatment involves the use of methadone, a long-acting opioid agonist, or buprenorphine, a long-acting partial opioid agonist. These medications decrease the amount and severity of cravings and limit the euphoric effects of subsequent opioid use.¹⁷ Compared to abstinence-based treatment, OAT has been associated with increased retention in addiction treatment and employment, and reductions in incarceration, human immunodeficiency virus transmission, illicit drug use, opioid-overdose events, and mortality.^26-32An alternative to OAT is naltrexone, an opioid antagonist. Naltrexone for OUD is administered as a monthly depot injection that prevents the user from experiencing opioid intoxication or dependence, and is associated with sustained abstinence.^17,33,34 The authors strongly recommend that hospitalists discuss the benefits of MAT with hospitalized individuals with OUD. In addition, when appropriate, patients should receive consultation with, or referral to, an addiction specialist.

Adverse Effects of Methadone, Buprenorphine, and Naltrexone

The benefits of MAT are substantial, but there are adverse effects, potential drug-to-drug interactions, and patient-specific characteristics that may impact the inpatient management of individuals on MAT. Selected adverse effects of OAT are listed in Table 1. The adverse effects of naltrexone include nausea, vomiting, and transaminitis. It should also be noted that the initiation of buprenorphine and naltrexone may induce opioid withdrawal when administered to an opioid-dependent patient with recent opioid use. To avoid precipitating withdrawal, buprenorphine should be used only in individuals who have at least mild withdrawal symptoms or have completed detoxification,²⁰ and naltrexone should be used only in patients who have abstained from opioids for at least 7 to 10 days.³⁵

Opioid-agonist treatments are primarily metabolized by the cytochrome P450 3A4 isoenzyme system. Medications that inhibit cytochrome P450 3A4 metabolism such as fluconazole can result in OAT toxicity, while medications that induce cytochrome P450 3A4 metabolism such as dexamethasone can lead to withdrawal symptoms.¹⁸ If these interactions are unavoidable, the dose of methadone or buprenorphine should be adjusted to prevent toxicity or withdrawal symptoms. The major drug interaction with naltrexone is ineffective analgesia from opioids.

Another major concern with MAT is the risk of overdose-related deaths. As an opioid agonist, large doses of methadone can result in respiratory depression, while buprenorphine alone, due to its partial agonist effect, is unlikely to result in respiratory depression. When methadone or buprenorphine are taken with other substances that cause respiratory depression, such as benzodiazepines or alcohol, the risk of respiratory depression and overdose is significantly increased.^36,37 Overdose-related death with naltrexone usually occurs after the medication has metabolized and results from a loss of opioid tolerance.³⁸

Special Populations

Medication-assisted treatment in individuals with acute pain. Maintenance treatment with OAT does not provide sufficient analgesia to treat episodes of acute pain.³⁹ In patients on methadone maintenance, the maintenance dose should be continued and adjunctive analgesia should be provided with nonopioid analgesics or short-acting opioids.³⁹ The management of acute pain in individuals on buprenorphine maintenance is more complicated since buprenorphine is a partial opioid agonist with high affinity to the opioid receptor, which limits the impact of adjunctive opioids. The options for analgesia in buprenorphine maintenance treatment include 1) continuing daily dosing of buprenorphine and providing nonopioid or opioid analgesics, 2) dividing buprenorphine dosing into a 3 or 4 times a day medication, 3) discontinuing buprenorphine and treating with opioid analgesics, 4) discontinuing buprenorphine and starting methadone with nonopioid or opioid analgesics.³⁹ In cases where buprenorphine is discontinued, it should be restarted before discharge upon resolution of the acute pain episode. An individual with acute pain on naltrexone may require nonopioid analgesia or regional blocks. In these patients, adequate pain control may be challenging and require the consultation of an acute pain specialist.

Pregnant or breastfeeding individuals. Opioid misuse puts the individual and fetus at risk of complications, and abrupt discontinuation can cause preterm labor, fetal distress, or fetal demise.⁴⁰ The current standard is to initiate methadone in consultation with an addiction specialist.⁴⁰ There is evidence that buprenorphine can be used during pregnancy; however, buprenorphine-naloxone is discouraged.^18,40 Of note, use of OAT in pregnancy can result in neonatal abstinence syndrome, an expected complication that can be managed by a pediatrician.⁴⁰

Methadone and buprenorphine can be found in low concentrations in breast milk.⁴¹ However, according to the Academy of Breastfeeding Medicine’s clinical guidelines, women on stable doses of methadone and buprenorphine should be encouraged to breastfeed.⁴¹ Naltrexone enters breast milk and has potential adverse effects for the newborn. Either the mother should discontinue naltrexone or should not breastfeed.³⁵

Treatment of polysubstance misuse. Individuals with OUD may also misuse other substances. The concomitant use of opioids and other central nervous system depressants, such as alcohol and benzodiazepines, is especially worrisome as they can potentiate respiratory depression. The presence of polysubstance misuse does not preclude the use of MAT for the treatment of OUD. In those with comorbid alcohol use disorder, the use of naltrexone may be appealing as it can treat both alcohol use disorder and OUD. Given the complexities of managing polysubstance misuse, addiction specialists should be involved in the care of these patients.⁴² In addition, patients should be educated on the risks of polysubstance misuse, especially when it involves 2 central nervous system depressants.

Comorbid medical disease. In general, medical comorbidities do not significantly affect the treatment of OUD; however, dysfunction of certain organ systems may necessitate a dose reduction or discontinuation of MAT. Severe liver disease may result in decreased hepatic metabolism of OAT.^35,42 Prolonged QTc, or history of arrhythmia, may preclude the use of methadone.^17,35,42 In addition, chronic hypercapnic respiratory failure or severe asthma may be contraindications for the use of methadone in an unmonitored setting.³⁵ Kidney failure is not known to be a contraindication to MAT, and there is no consensus on the need for dose reduction of MAT with decreasing glomerular filtration rate; however, some authors recommend a 25% to 50% dose reduction of methadone when the glomerular filtration rate is less than 10 milliliters per minute.⁴³ There is no such recommendation with buprenorphine, although it has not been adequately studied in individuals with renal failure. Close monitoring for evidence of toxicity is prudent in individuals on MAT with acute or chronic renal failure.³⁵

Rural or resource-limited areas. There is a significant shortage of addiction treatment options in many regions of the United States. As of 2012, there were an estimated 2.3 million individuals with OUD; however, more than 1 million of these individuals do not have access to treatment.⁴⁴ As a result, many addiction treatment programs have wait lists that can last months or even years.⁴⁵ These shortages are especially apparent in rural areas, where individuals with OUD are particularly reliant upon buprenorphine treatment because of prohibitive travel times to urban-based programs.⁴⁶ To address this problem, new models of care delivery are being developed, including models incorporating telemedicine to support rural primary care management of OUD.⁴⁷

 

The Future of Medication-Assisted Treatment

Currently, MAT is initiated and managed by outpatient addiction specialists. However, evidence supports initiation of MAT as an inpatient.⁴⁸ A recent study compared inpatient buprenorphine detoxification to inpatient buprenorphine induction, dose stabilization, and postdischarge linkage-of-care to outpatient opioid treatment clinics. Patients who received inpatient buprenorphine initiation and linkage-of-care had improved buprenorphine treatment retention and reported less illicit opioid use.⁴⁸ The development of partnerships between hospitals, inpatient clinicians, and outpatient addiction specialists is essential and could lead to significant advances in treating hospitalized patients with OUD.

The initiation of MAT in hospitalized patients with immediate linkage-of-care shows great promise; however, at this point, the initiation of MAT should be done only in conjunction with addiction specialists in patients with confirmed outpatient follow-up. In cases where inpatient MAT initiation is pursued, education of staff including nurses and pharmacists is essential.

Harm Reduction Interventions

Ideally, management of OUD results in abstinence from opioid misuse; however, some individuals are not ready for treatment or, despite MAT, have relapses of opioid misuse. Given this, a secondary goal in the management of OUD is the reduction of harm that can result from opioid misuse.

Many individuals inject opioids, which is associated with increased rates of viral and bacterial infections secondary to nonsterile injection practices.⁴⁹ Educating patients on sterile injection methods (Table 2),⁵⁰ including the importance of sterile-injecting equipment and water, and cleaning the skin prior to injection, may mitigate the risk of infections and should be provided for all hospitalized people who inject drugs.

Syringe-exchange programs provide sterile-injecting equipment in exchange for used needles, with a goal of increasing access to sterile supplies and removing contaminated syringes from circulation.⁵¹ While controversial, these programs may reduce the incidence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus.⁵¹

In addition, syringe-exchange programs often provide addiction treatment referrals, counseling, testing, and prevention education for human immunodeficiency virus, hepatitis C virus, and sexually transmitted infections.⁴⁹ In the United States, there are 226 programs in 33 states (see https://nasen.org/directory for a list of programs and locations. Inpatient clinicians should provide a list of local resources including syringe-exchange programs at the time of discharge for any people who inject drugs. In addition, individuals with OUD are at increased risk for overdose, especially in the postdischarge setting due to decreased opioid tolerance.⁵² In 2014, there were 28,647 opioid overdose-related deaths in the United States.² To address this troubling epidemic, opioid overdose education and naloxone distribution has been championed to educate patients at risk of opioid overdose and potential first responders on how to counteract an overdose by using naloxone, an opioid antagonist (see Table 2 for more information on opioid overdose education). The use of opioid overdose education and naloxone distribution has been observed to reduce opioid overdose-related death rates.⁵³

Hospitalists should provide opioid overdose education and naloxone to all individuals at risk of opioid overdose (including those with OUD), as well as potential first responders where the law allows (more information including individual state laws can be found at http://prescribetoprevent.org).²⁰

Considerations at Discharge

There are a number of considerations for the hospitalist at discharge (see Table 3 for a recommended discharge checklist). In addition, it is important to appreciate, and minimize, the ways that hospitalists contribute to the opioid epidemic. For instance, prescribing opioids at discharge in opioid-naïve patients increases the risk of chronic opioid use.⁵⁴ It is also essential to recognize that increased doses of opioids are associated with increased rates of opioid overdose-related deaths.⁵⁵ As such, hospitalists should maximize the use of nonopioid analgesics, prescribe opioids only when necessary, use the smallest effective dose of opioids, limit the number of opioid pills distributed to patients, and check prescription-monitoring programs for evidence of misuse.

CONCLUSION

Hospitalization serves as an important opportunity to address addiction in individuals with OUD. In addressing addiction, hospitalists should identify and intervene on psychosocial and mental health barriers, treat opioid withdrawal, and propagate harm reduction strategies. In addition, there is a growing role for hospitalists to be involved in the initiation of MAT and linkage-of-care to outpatient addiction treatment. If hospitalists become leaders in the inpatient management of OUD, they will significantly improve the care provided to this vulnerable patient population.

Disclosure

The authors report no financial conflicts of interest.

 

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Case

A 65-year-old male with a history of a motor vehicle accident that required emergency surgery in 1982 is hospitalized for acute renal failure. He reports a distant history of IV heroin use and a brief incarceration. He does not currently use illicit drugs. He has no signs or symptoms of liver disease. Should this patient be screened for chronic hepatitis C virus (HCV) infection?

Brief Overview

HCV is a major public health concern in the United States and worldwide. It is estimated that more than 4.1 million people in the U.S. (1.6% prevalence) and more than 180 million worldwide (2.8% prevalence) are HCV antibody-positive.^1,2 The acute infection is most often asymptomatic, and 80% to 100% of patients will remain HCV RNA-positive, 60% to 80% will have persistently elevated liver enzymes, and 16% will develop evidence of cirrhosis at 20 years after initial infection.³

A number of organizations in the United States have released HCV screening guidelines, including the CDC, the American Association for the Study of Liver Disease (AASLD), and the U.S. Preventive Services Task Force (USPSTF); however, despite these established recommendations, an estimated 50% of individuals with chronic HCV infection are unscreened and unaware of their infection status.⁴ Furthermore, in a recent study of one managed care network, even when one or more risk factors were present, only 29% of individuals underwent screening for HCV antibodies detection.⁵ The importance of detecting chronic HCV infection will have greater significance as newer and better-tolerated treatment options become available.⁶

Multiple organizations recommend screening for chronic HCV infection. This screening is recommended for patients with known risk factors and those in populations with a high prevalence of HCV infection.

Risk Factors and High-Prevalence Populations

IV or intranasal drug use. IV drug use is the main identifiable source of HCV infection in the U.S. It is estimated that 60% of new HCV infections occur in people who have injected drugs in the past six months.⁷ The prevalence of HCV antibodies in current IV drug users is between 72% and 96%.8 Intranasal cocaine use is also associated with a higher prevalence of HCV antibodies than the general population.⁸

Blood transfusion prior to July 1992. Testing of donor blood was not routinely done until 1990, and more sensitive testing was not implemented until July 1992.⁸ The prevalence of HCV antibodies in people who received blood transfusions prior to 1990 is 6%.8 Prior to 1990, the risk for transfusion-associated HCV infection was one in 526 units transfused.⁹ Since implementation of highly sensitive screening techniques, the risk of infection has dropped to less than one in 1.9 million units transfused.¹⁰

Clotting factors prior to 1987 or transplanted tissue prior to 1992. Individuals who have received clotting factors, other blood product transfusions, or transplanted tissue prior to 1987 are at an increased risk for developing HCV infection. For instance, individuals with hemophilia treated with clotting factors prior to 1987 had chronic HCV infection rates of up to 90%.⁸ In 1987, widespread use of protocols to inactivate HCV in clotting factors and other blood products was adopted.⁸ In addition, widespread screening of potential tissue donors and the use of HCV antibody-negative donors became routine.⁸

 

Alanine aminotransferase elevation. This can be considered screening or part of the diagnostic work-up of transaminitis. Regardless of the classification, this is a cohort of people with a high prevalence of HCV antibody. For individuals with one isolated alanine aminotransferase elevation, the prevalence is 3.2%.⁴ With two or more elevated aminotransferase results, the prevalence rises to 8.2%.⁴

Hemodialysis. Two major studies have estimated the prevalence of HCV antibody-positive in end-stage renal disease individuals on hemodialysis to be 7.8% and 10.4%.^11,12 This prevalence can reach 64% at some dialysis centers.¹¹ The risk of HCV infection has been associated with blood transfusions, longer duration of hemodialysis, and higher rates of HCV infection in the dialysis unit.¹³ With implementation of infection control practices in dialysis units, the incidence and prevalence of HCV infection are declining.¹³

Born in the U.S. between 1945 and 1965. The CDC and USPSTF recommend a one-time screening for HCV infection for people born in the U.S. between 1945 and 1965, regardless of the presence or absence of risk factors.^6,14 This age group has an increased prevalence of HCV antibodies, at 3.25%.⁶

Human immunodeficiency virus (HIV). HCV has a prevalence of 30% in people infected with HIV.¹⁵ The rate of co-infection is likely secondary to shared routes of transmission. For example, 72.7% of HIV-infected individuals who used IV drugs had HCV antibodies, but only 3.5% of “low-risk” HIV-infected individuals had HCV antibodies.¹⁶

Born in a high prevalence country. In the U.S., a significant number of immigrants are from areas with a high endemic rate of HCV infection. High prevalence areas (greater than 3.5%) include Central Asia and East Asia, North Africa, and the Middle East.⁷ Of note, Egypt is thought to have the highest prevalence of chronic HCV infection in the world, with well over 10% of the population being antibody-positive.¹⁷ Although major guidelines do not currently recommend it, the high prevalence of chronic HCV infection in this population may warrant screening.

Other high-risk or high-prevalence populations. The prevalence of HCV infection in people who have had over 10 lifetime sexual partners (3% to 9%), those with a history of sexually transmitted disease (6%), men who have had sex with men (5%), and children born to HCV-infected mothers (5%) is increased compared with the general population.⁸ Incarcerated people in the U.S. have an HCV antibody prevalence of 16% to 41%.¹⁸ In addition, people who have sustained needle-stick injury or mucosal exposure, or those with potential exposures in unregulated tattoo or piercing salons, may also benefit from HCV antibody screening.¹⁴

Table 1 reviews HCV screening recommendations for the CDC, AASLD, and USPSTF.^1,6,8,14

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Screening Method

The most common initial screening test for the diagnosis of chronic HCV infection is the HCV antibody test. A positive antibody test should be followed by an HCV RNA test. In an individual with recent exposure, it takes between four and 10 weeks for the antibody to be detectable. HCV RNA testing can be positive as soon as two to three weeks after infection.⁸

 

Hospitalist Role in HCV Screening

None of the U.S.-based guidelines make recommendations on the preferred setting for HCV screening. According to the CDC, 60.4% of HCV screening was done in a physician office and 5.9% was done as a hospital inpatient.¹⁹ Traditionally, the PCP is responsible for screening for chronic diseases, including HCV infection; however, the current screening rate is insufficient, as 50% of people with chronic HCV infection remain unscreened.⁴

Given the insufficient rate of HCV screening at present, hospital medicine (HM) physicians have an opportunity to help improve this rate. Currently, there is no established standard of care for HCV screening in hospitalized patients. HM physicians could use the following strategies:

• Continue the current system and defer screening to outpatient providers;
• Offer screening to selected inpatients at high risk for chronic HCV infection; or
• Offer screening to all inpatients who meet screening criteria based on current guidelines.

Given the shortcomings of the current screening strategies, these authors would recommend widespread screening for chronic HCV infection in hospitalized people who meet screening criteria per current guidelines.

If HM physicians are to take an increased role in HCV screening, there are a number of important considerations. Because hospitalized patients have a limited length of stay, it would be unreasonable to expect HM physicians to test for HCV RNA viral load or genotype for all patients with a positive antibody test, because the duration of the inpatient stay may be shorter than the time it takes for these test results to return. These tests are often indicated after a positive HCV antibody test, however. Thus, communication of HCV antibody results to PCPs or other responsible providers is essential. If no follow-up is available or there are no responsible outpatient providers, HM physicians should continue with a limited screening strategy.

Back to the Case

This individual has multiple indications for chronic HCV infection screening. His risk factors include date of birth between 1945 and 1965, a history of IV drug use, and a history of incarceration. He also notes a history of emergency surgery, for which he may have received blood products prior to 1987. These factors significantly raise the likelihood of chronic HCV infection when compared with the general population. He was screened and found to be HCV antibody-positive. A follow-up HCV RNA viral load was also positive. He did not have any evidence of liver disease but did have a mild transaminitis. He has followed up as an outpatient with plans to start therapy.

Bottom Line

The current screening strategies for individuals with high prevalence of chronic HCV infection are insufficient. HM physicians have an opportunity to improve the rates of screening in this population.

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Dr. Theisen-Toupal is an internist, Dr. Rosenthal is a clinical fellow in medicine, and Dr. Carbo is an assistant professor of medicine, all at Beth Israel Deaconess Medical Center in Boston. Dr. Li is an internist and associate professor of medicine at Harvard Medical School and director of the hospital medicine division at Beth Israel Deaconess Medical Center.

References

1. Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-1374.
2. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57(4):1333-1342.
3. Chopra S. Clinical manifestations and natural history of chronic hepatitis C virus infection. UpToDate. Available at: http://www.uptodate.com/contents/clinical-manifestations-and-natural-history-of-chronic-hepatitis-c-virus-infection. Accessed March 5, 2014.
4. Spradling PR, Rupp L, Moorman AC, et al. Hepatitis B and C virus infection among 1.2 million people with access to care: factors associated with testing and infection prevalence. Clin Infect Dis. 2012;55(8):1047-1055.
5. Roblin DW, Smith BD, Weinbaum CM, Sabin ME. HCV screening practices and prevalence in an MCO, 2000-2007. Am J Manag Care. 2011;17(8):548-555.
6. Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among people born during 1945-1965. MMWR. August 17, 2012. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6104a1.htm. Accessed March 5, 2014.
7. Chopra S. Epidemiology and transmission of hepatitis C virus infection. UpToDate. Available at: http://www.uptodate.com/contents/epidemiology-and-transmission-of-hepatitis-c-virus-infection?source=search_result&search=%22Epidemiology+and+transmission+of+hepatitis+C+virus+infection%22&selectedTitle=1~150. Accessed March 5, 2014.
8. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR. October 16, 1998. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/00055154.htm. Accessed March 5, 2014.
9. Donahue JG, Muñoz A, Ness PM, et al. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med. 1992;327(6):369-373.
10. Pomper GJ, Wu Y, Snyder EL. Risks of transfusion-transmitted infections: 2003. Curr Opin Hematol. 2003;10(6):412-418.
11. Tokars JI, Miller ER, Alter MJ, Arduino MJ. National surveillance of dialysis associated diseases in the United States, 1995. ASAIO J. 1998;44(1):98-107.
12. Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005;18(1):52-61.
13. Natov S, Pereira BJG. Hepatitis C virus infection in patients on maintenance dialysis. UpToDate. Available at: http://www.uptodate.com/contents/hepatitis-c-virus-infection-in-patients-on-maintenance-dialysis?source=search_result&search=Hepatitis+C+virus+infection+in+patients+on+maintenance+dialysis.&selectedTitle=1~150. Accessed March 5, 2014.
14. Moyer VA, U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(5):349-357.
15. Staples CT II, Rimland D, Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival. Clin Infect Dis. 1999;29(1):150-154.
16. Sherman KE, Rouster SD, Chung RT, Rajicic N. Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the U.S. adult AIDS clinical trials group. Clin Infect Dis. 2002;34(6):831-837.
17. Averhoff FM, Glass N, Holtzman D. Global burden of hepatitis C: considerations for healthcare providers in the United States. Clin Infect Dis. 2012;55 Suppl 1:S10-15.
18. Centers for Disease Control and Prevention. Prevention and control of infections with hepatitis viruses in correctional settings. MMWR. January 24, 2003. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5201a1.htm. Accessed March 5, 2014.
19. Centers for Disease Control and Prevention. Locations and reasons for initial testing for hepatitis C infection—chronic hepatitis cohort study, United States, 2006-2010. MMWR. August 16, 2013. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6232a3.htm?s_cid=mm6232a3_w. Accessed March 5, 2014.

 

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Case

A 65-year-old male with a history of a motor vehicle accident that required emergency surgery in 1982 is hospitalized for acute renal failure. He reports a distant history of IV heroin use and a brief incarceration. He does not currently use illicit drugs. He has no signs or symptoms of liver disease. Should this patient be screened for chronic hepatitis C virus (HCV) infection?

Brief Overview

HCV is a major public health concern in the United States and worldwide. It is estimated that more than 4.1 million people in the U.S. (1.6% prevalence) and more than 180 million worldwide (2.8% prevalence) are HCV antibody-positive.^1,2 The acute infection is most often asymptomatic, and 80% to 100% of patients will remain HCV RNA-positive, 60% to 80% will have persistently elevated liver enzymes, and 16% will develop evidence of cirrhosis at 20 years after initial infection.³

A number of organizations in the United States have released HCV screening guidelines, including the CDC, the American Association for the Study of Liver Disease (AASLD), and the U.S. Preventive Services Task Force (USPSTF); however, despite these established recommendations, an estimated 50% of individuals with chronic HCV infection are unscreened and unaware of their infection status.⁴ Furthermore, in a recent study of one managed care network, even when one or more risk factors were present, only 29% of individuals underwent screening for HCV antibodies detection.⁵ The importance of detecting chronic HCV infection will have greater significance as newer and better-tolerated treatment options become available.⁶

Multiple organizations recommend screening for chronic HCV infection. This screening is recommended for patients with known risk factors and those in populations with a high prevalence of HCV infection.

Risk Factors and High-Prevalence Populations

IV or intranasal drug use. IV drug use is the main identifiable source of HCV infection in the U.S. It is estimated that 60% of new HCV infections occur in people who have injected drugs in the past six months.⁷ The prevalence of HCV antibodies in current IV drug users is between 72% and 96%.8 Intranasal cocaine use is also associated with a higher prevalence of HCV antibodies than the general population.⁸

Blood transfusion prior to July 1992. Testing of donor blood was not routinely done until 1990, and more sensitive testing was not implemented until July 1992.⁸ The prevalence of HCV antibodies in people who received blood transfusions prior to 1990 is 6%.8 Prior to 1990, the risk for transfusion-associated HCV infection was one in 526 units transfused.⁹ Since implementation of highly sensitive screening techniques, the risk of infection has dropped to less than one in 1.9 million units transfused.¹⁰

Clotting factors prior to 1987 or transplanted tissue prior to 1992. Individuals who have received clotting factors, other blood product transfusions, or transplanted tissue prior to 1987 are at an increased risk for developing HCV infection. For instance, individuals with hemophilia treated with clotting factors prior to 1987 had chronic HCV infection rates of up to 90%.⁸ In 1987, widespread use of protocols to inactivate HCV in clotting factors and other blood products was adopted.⁸ In addition, widespread screening of potential tissue donors and the use of HCV antibody-negative donors became routine.⁸

 

Alanine aminotransferase elevation. This can be considered screening or part of the diagnostic work-up of transaminitis. Regardless of the classification, this is a cohort of people with a high prevalence of HCV antibody. For individuals with one isolated alanine aminotransferase elevation, the prevalence is 3.2%.⁴ With two or more elevated aminotransferase results, the prevalence rises to 8.2%.⁴

Hemodialysis. Two major studies have estimated the prevalence of HCV antibody-positive in end-stage renal disease individuals on hemodialysis to be 7.8% and 10.4%.^11,12 This prevalence can reach 64% at some dialysis centers.¹¹ The risk of HCV infection has been associated with blood transfusions, longer duration of hemodialysis, and higher rates of HCV infection in the dialysis unit.¹³ With implementation of infection control practices in dialysis units, the incidence and prevalence of HCV infection are declining.¹³

Born in the U.S. between 1945 and 1965. The CDC and USPSTF recommend a one-time screening for HCV infection for people born in the U.S. between 1945 and 1965, regardless of the presence or absence of risk factors.^6,14 This age group has an increased prevalence of HCV antibodies, at 3.25%.⁶

Human immunodeficiency virus (HIV). HCV has a prevalence of 30% in people infected with HIV.¹⁵ The rate of co-infection is likely secondary to shared routes of transmission. For example, 72.7% of HIV-infected individuals who used IV drugs had HCV antibodies, but only 3.5% of “low-risk” HIV-infected individuals had HCV antibodies.¹⁶

Born in a high prevalence country. In the U.S., a significant number of immigrants are from areas with a high endemic rate of HCV infection. High prevalence areas (greater than 3.5%) include Central Asia and East Asia, North Africa, and the Middle East.⁷ Of note, Egypt is thought to have the highest prevalence of chronic HCV infection in the world, with well over 10% of the population being antibody-positive.¹⁷ Although major guidelines do not currently recommend it, the high prevalence of chronic HCV infection in this population may warrant screening.

Other high-risk or high-prevalence populations. The prevalence of HCV infection in people who have had over 10 lifetime sexual partners (3% to 9%), those with a history of sexually transmitted disease (6%), men who have had sex with men (5%), and children born to HCV-infected mothers (5%) is increased compared with the general population.⁸ Incarcerated people in the U.S. have an HCV antibody prevalence of 16% to 41%.¹⁸ In addition, people who have sustained needle-stick injury or mucosal exposure, or those with potential exposures in unregulated tattoo or piercing salons, may also benefit from HCV antibody screening.¹⁴

Table 1 reviews HCV screening recommendations for the CDC, AASLD, and USPSTF.^1,6,8,14

click for large version

Screening Method

The most common initial screening test for the diagnosis of chronic HCV infection is the HCV antibody test. A positive antibody test should be followed by an HCV RNA test. In an individual with recent exposure, it takes between four and 10 weeks for the antibody to be detectable. HCV RNA testing can be positive as soon as two to three weeks after infection.⁸

 

Hospitalist Role in HCV Screening

None of the U.S.-based guidelines make recommendations on the preferred setting for HCV screening. According to the CDC, 60.4% of HCV screening was done in a physician office and 5.9% was done as a hospital inpatient.¹⁹ Traditionally, the PCP is responsible for screening for chronic diseases, including HCV infection; however, the current screening rate is insufficient, as 50% of people with chronic HCV infection remain unscreened.⁴

Given the insufficient rate of HCV screening at present, hospital medicine (HM) physicians have an opportunity to help improve this rate. Currently, there is no established standard of care for HCV screening in hospitalized patients. HM physicians could use the following strategies:

• Continue the current system and defer screening to outpatient providers;
• Offer screening to selected inpatients at high risk for chronic HCV infection; or
• Offer screening to all inpatients who meet screening criteria based on current guidelines.

Given the shortcomings of the current screening strategies, these authors would recommend widespread screening for chronic HCV infection in hospitalized people who meet screening criteria per current guidelines.

If HM physicians are to take an increased role in HCV screening, there are a number of important considerations. Because hospitalized patients have a limited length of stay, it would be unreasonable to expect HM physicians to test for HCV RNA viral load or genotype for all patients with a positive antibody test, because the duration of the inpatient stay may be shorter than the time it takes for these test results to return. These tests are often indicated after a positive HCV antibody test, however. Thus, communication of HCV antibody results to PCPs or other responsible providers is essential. If no follow-up is available or there are no responsible outpatient providers, HM physicians should continue with a limited screening strategy.

Back to the Case

This individual has multiple indications for chronic HCV infection screening. His risk factors include date of birth between 1945 and 1965, a history of IV drug use, and a history of incarceration. He also notes a history of emergency surgery, for which he may have received blood products prior to 1987. These factors significantly raise the likelihood of chronic HCV infection when compared with the general population. He was screened and found to be HCV antibody-positive. A follow-up HCV RNA viral load was also positive. He did not have any evidence of liver disease but did have a mild transaminitis. He has followed up as an outpatient with plans to start therapy.

Bottom Line

The current screening strategies for individuals with high prevalence of chronic HCV infection are insufficient. HM physicians have an opportunity to improve the rates of screening in this population.

---

Dr. Theisen-Toupal is an internist, Dr. Rosenthal is a clinical fellow in medicine, and Dr. Carbo is an assistant professor of medicine, all at Beth Israel Deaconess Medical Center in Boston. Dr. Li is an internist and associate professor of medicine at Harvard Medical School and director of the hospital medicine division at Beth Israel Deaconess Medical Center.

References

1. Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-1374.
2. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57(4):1333-1342.
3. Chopra S. Clinical manifestations and natural history of chronic hepatitis C virus infection. UpToDate. Available at: http://www.uptodate.com/contents/clinical-manifestations-and-natural-history-of-chronic-hepatitis-c-virus-infection. Accessed March 5, 2014.
4. Spradling PR, Rupp L, Moorman AC, et al. Hepatitis B and C virus infection among 1.2 million people with access to care: factors associated with testing and infection prevalence. Clin Infect Dis. 2012;55(8):1047-1055.
5. Roblin DW, Smith BD, Weinbaum CM, Sabin ME. HCV screening practices and prevalence in an MCO, 2000-2007. Am J Manag Care. 2011;17(8):548-555.
6. Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among people born during 1945-1965. MMWR. August 17, 2012. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6104a1.htm. Accessed March 5, 2014.
7. Chopra S. Epidemiology and transmission of hepatitis C virus infection. UpToDate. Available at: http://www.uptodate.com/contents/epidemiology-and-transmission-of-hepatitis-c-virus-infection?source=search_result&search=%22Epidemiology+and+transmission+of+hepatitis+C+virus+infection%22&selectedTitle=1~150. Accessed March 5, 2014.
8. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR. October 16, 1998. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/00055154.htm. Accessed March 5, 2014.
9. Donahue JG, Muñoz A, Ness PM, et al. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med. 1992;327(6):369-373.
10. Pomper GJ, Wu Y, Snyder EL. Risks of transfusion-transmitted infections: 2003. Curr Opin Hematol. 2003;10(6):412-418.
11. Tokars JI, Miller ER, Alter MJ, Arduino MJ. National surveillance of dialysis associated diseases in the United States, 1995. ASAIO J. 1998;44(1):98-107.
12. Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005;18(1):52-61.
13. Natov S, Pereira BJG. Hepatitis C virus infection in patients on maintenance dialysis. UpToDate. Available at: http://www.uptodate.com/contents/hepatitis-c-virus-infection-in-patients-on-maintenance-dialysis?source=search_result&search=Hepatitis+C+virus+infection+in+patients+on+maintenance+dialysis.&selectedTitle=1~150. Accessed March 5, 2014.
14. Moyer VA, U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(5):349-357.
15. Staples CT II, Rimland D, Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival. Clin Infect Dis. 1999;29(1):150-154.
16. Sherman KE, Rouster SD, Chung RT, Rajicic N. Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the U.S. adult AIDS clinical trials group. Clin Infect Dis. 2002;34(6):831-837.
17. Averhoff FM, Glass N, Holtzman D. Global burden of hepatitis C: considerations for healthcare providers in the United States. Clin Infect Dis. 2012;55 Suppl 1:S10-15.
18. Centers for Disease Control and Prevention. Prevention and control of infections with hepatitis viruses in correctional settings. MMWR. January 24, 2003. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5201a1.htm. Accessed March 5, 2014.
19. Centers for Disease Control and Prevention. Locations and reasons for initial testing for hepatitis C infection—chronic hepatitis cohort study, United States, 2006-2010. MMWR. August 16, 2013. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6232a3.htm?s_cid=mm6232a3_w. Accessed March 5, 2014.

 

click for large version

Case

A 65-year-old male with a history of a motor vehicle accident that required emergency surgery in 1982 is hospitalized for acute renal failure. He reports a distant history of IV heroin use and a brief incarceration. He does not currently use illicit drugs. He has no signs or symptoms of liver disease. Should this patient be screened for chronic hepatitis C virus (HCV) infection?

Brief Overview

HCV is a major public health concern in the United States and worldwide. It is estimated that more than 4.1 million people in the U.S. (1.6% prevalence) and more than 180 million worldwide (2.8% prevalence) are HCV antibody-positive.^1,2 The acute infection is most often asymptomatic, and 80% to 100% of patients will remain HCV RNA-positive, 60% to 80% will have persistently elevated liver enzymes, and 16% will develop evidence of cirrhosis at 20 years after initial infection.³

A number of organizations in the United States have released HCV screening guidelines, including the CDC, the American Association for the Study of Liver Disease (AASLD), and the U.S. Preventive Services Task Force (USPSTF); however, despite these established recommendations, an estimated 50% of individuals with chronic HCV infection are unscreened and unaware of their infection status.⁴ Furthermore, in a recent study of one managed care network, even when one or more risk factors were present, only 29% of individuals underwent screening for HCV antibodies detection.⁵ The importance of detecting chronic HCV infection will have greater significance as newer and better-tolerated treatment options become available.⁶

Multiple organizations recommend screening for chronic HCV infection. This screening is recommended for patients with known risk factors and those in populations with a high prevalence of HCV infection.

Risk Factors and High-Prevalence Populations

IV or intranasal drug use. IV drug use is the main identifiable source of HCV infection in the U.S. It is estimated that 60% of new HCV infections occur in people who have injected drugs in the past six months.⁷ The prevalence of HCV antibodies in current IV drug users is between 72% and 96%.8 Intranasal cocaine use is also associated with a higher prevalence of HCV antibodies than the general population.⁸

Blood transfusion prior to July 1992. Testing of donor blood was not routinely done until 1990, and more sensitive testing was not implemented until July 1992.⁸ The prevalence of HCV antibodies in people who received blood transfusions prior to 1990 is 6%.8 Prior to 1990, the risk for transfusion-associated HCV infection was one in 526 units transfused.⁹ Since implementation of highly sensitive screening techniques, the risk of infection has dropped to less than one in 1.9 million units transfused.¹⁰

Clotting factors prior to 1987 or transplanted tissue prior to 1992. Individuals who have received clotting factors, other blood product transfusions, or transplanted tissue prior to 1987 are at an increased risk for developing HCV infection. For instance, individuals with hemophilia treated with clotting factors prior to 1987 had chronic HCV infection rates of up to 90%.⁸ In 1987, widespread use of protocols to inactivate HCV in clotting factors and other blood products was adopted.⁸ In addition, widespread screening of potential tissue donors and the use of HCV antibody-negative donors became routine.⁸

 

Alanine aminotransferase elevation. This can be considered screening or part of the diagnostic work-up of transaminitis. Regardless of the classification, this is a cohort of people with a high prevalence of HCV antibody. For individuals with one isolated alanine aminotransferase elevation, the prevalence is 3.2%.⁴ With two or more elevated aminotransferase results, the prevalence rises to 8.2%.⁴

Hemodialysis. Two major studies have estimated the prevalence of HCV antibody-positive in end-stage renal disease individuals on hemodialysis to be 7.8% and 10.4%.^11,12 This prevalence can reach 64% at some dialysis centers.¹¹ The risk of HCV infection has been associated with blood transfusions, longer duration of hemodialysis, and higher rates of HCV infection in the dialysis unit.¹³ With implementation of infection control practices in dialysis units, the incidence and prevalence of HCV infection are declining.¹³

Born in the U.S. between 1945 and 1965. The CDC and USPSTF recommend a one-time screening for HCV infection for people born in the U.S. between 1945 and 1965, regardless of the presence or absence of risk factors.^6,14 This age group has an increased prevalence of HCV antibodies, at 3.25%.⁶

Human immunodeficiency virus (HIV). HCV has a prevalence of 30% in people infected with HIV.¹⁵ The rate of co-infection is likely secondary to shared routes of transmission. For example, 72.7% of HIV-infected individuals who used IV drugs had HCV antibodies, but only 3.5% of “low-risk” HIV-infected individuals had HCV antibodies.¹⁶

Born in a high prevalence country. In the U.S., a significant number of immigrants are from areas with a high endemic rate of HCV infection. High prevalence areas (greater than 3.5%) include Central Asia and East Asia, North Africa, and the Middle East.⁷ Of note, Egypt is thought to have the highest prevalence of chronic HCV infection in the world, with well over 10% of the population being antibody-positive.¹⁷ Although major guidelines do not currently recommend it, the high prevalence of chronic HCV infection in this population may warrant screening.

Other high-risk or high-prevalence populations. The prevalence of HCV infection in people who have had over 10 lifetime sexual partners (3% to 9%), those with a history of sexually transmitted disease (6%), men who have had sex with men (5%), and children born to HCV-infected mothers (5%) is increased compared with the general population.⁸ Incarcerated people in the U.S. have an HCV antibody prevalence of 16% to 41%.¹⁸ In addition, people who have sustained needle-stick injury or mucosal exposure, or those with potential exposures in unregulated tattoo or piercing salons, may also benefit from HCV antibody screening.¹⁴

Table 1 reviews HCV screening recommendations for the CDC, AASLD, and USPSTF.^1,6,8,14

click for large version

Screening Method

The most common initial screening test for the diagnosis of chronic HCV infection is the HCV antibody test. A positive antibody test should be followed by an HCV RNA test. In an individual with recent exposure, it takes between four and 10 weeks for the antibody to be detectable. HCV RNA testing can be positive as soon as two to three weeks after infection.⁸

 

Hospitalist Role in HCV Screening

None of the U.S.-based guidelines make recommendations on the preferred setting for HCV screening. According to the CDC, 60.4% of HCV screening was done in a physician office and 5.9% was done as a hospital inpatient.¹⁹ Traditionally, the PCP is responsible for screening for chronic diseases, including HCV infection; however, the current screening rate is insufficient, as 50% of people with chronic HCV infection remain unscreened.⁴

Given the insufficient rate of HCV screening at present, hospital medicine (HM) physicians have an opportunity to help improve this rate. Currently, there is no established standard of care for HCV screening in hospitalized patients. HM physicians could use the following strategies:

• Continue the current system and defer screening to outpatient providers;
• Offer screening to selected inpatients at high risk for chronic HCV infection; or
• Offer screening to all inpatients who meet screening criteria based on current guidelines.

Given the shortcomings of the current screening strategies, these authors would recommend widespread screening for chronic HCV infection in hospitalized people who meet screening criteria per current guidelines.

If HM physicians are to take an increased role in HCV screening, there are a number of important considerations. Because hospitalized patients have a limited length of stay, it would be unreasonable to expect HM physicians to test for HCV RNA viral load or genotype for all patients with a positive antibody test, because the duration of the inpatient stay may be shorter than the time it takes for these test results to return. These tests are often indicated after a positive HCV antibody test, however. Thus, communication of HCV antibody results to PCPs or other responsible providers is essential. If no follow-up is available or there are no responsible outpatient providers, HM physicians should continue with a limited screening strategy.

Back to the Case

This individual has multiple indications for chronic HCV infection screening. His risk factors include date of birth between 1945 and 1965, a history of IV drug use, and a history of incarceration. He also notes a history of emergency surgery, for which he may have received blood products prior to 1987. These factors significantly raise the likelihood of chronic HCV infection when compared with the general population. He was screened and found to be HCV antibody-positive. A follow-up HCV RNA viral load was also positive. He did not have any evidence of liver disease but did have a mild transaminitis. He has followed up as an outpatient with plans to start therapy.

Bottom Line

The current screening strategies for individuals with high prevalence of chronic HCV infection are insufficient. HM physicians have an opportunity to improve the rates of screening in this population.

---

Dr. Theisen-Toupal is an internist, Dr. Rosenthal is a clinical fellow in medicine, and Dr. Carbo is an assistant professor of medicine, all at Beth Israel Deaconess Medical Center in Boston. Dr. Li is an internist and associate professor of medicine at Harvard Medical School and director of the hospital medicine division at Beth Israel Deaconess Medical Center.

References

1. Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-1374.
2. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57(4):1333-1342.
3. Chopra S. Clinical manifestations and natural history of chronic hepatitis C virus infection. UpToDate. Available at: http://www.uptodate.com/contents/clinical-manifestations-and-natural-history-of-chronic-hepatitis-c-virus-infection. Accessed March 5, 2014.
4. Spradling PR, Rupp L, Moorman AC, et al. Hepatitis B and C virus infection among 1.2 million people with access to care: factors associated with testing and infection prevalence. Clin Infect Dis. 2012;55(8):1047-1055.
5. Roblin DW, Smith BD, Weinbaum CM, Sabin ME. HCV screening practices and prevalence in an MCO, 2000-2007. Am J Manag Care. 2011;17(8):548-555.
6. Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among people born during 1945-1965. MMWR. August 17, 2012. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6104a1.htm. Accessed March 5, 2014.
7. Chopra S. Epidemiology and transmission of hepatitis C virus infection. UpToDate. Available at: http://www.uptodate.com/contents/epidemiology-and-transmission-of-hepatitis-c-virus-infection?source=search_result&search=%22Epidemiology+and+transmission+of+hepatitis+C+virus+infection%22&selectedTitle=1~150. Accessed March 5, 2014.
8. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR. October 16, 1998. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/00055154.htm. Accessed March 5, 2014.
9. Donahue JG, Muñoz A, Ness PM, et al. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med. 1992;327(6):369-373.
10. Pomper GJ, Wu Y, Snyder EL. Risks of transfusion-transmitted infections: 2003. Curr Opin Hematol. 2003;10(6):412-418.
11. Tokars JI, Miller ER, Alter MJ, Arduino MJ. National surveillance of dialysis associated diseases in the United States, 1995. ASAIO J. 1998;44(1):98-107.
12. Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005;18(1):52-61.
13. Natov S, Pereira BJG. Hepatitis C virus infection in patients on maintenance dialysis. UpToDate. Available at: http://www.uptodate.com/contents/hepatitis-c-virus-infection-in-patients-on-maintenance-dialysis?source=search_result&search=Hepatitis+C+virus+infection+in+patients+on+maintenance+dialysis.&selectedTitle=1~150. Accessed March 5, 2014.
14. Moyer VA, U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(5):349-357.
15. Staples CT II, Rimland D, Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival. Clin Infect Dis. 1999;29(1):150-154.
16. Sherman KE, Rouster SD, Chung RT, Rajicic N. Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the U.S. adult AIDS clinical trials group. Clin Infect Dis. 2002;34(6):831-837.
17. Averhoff FM, Glass N, Holtzman D. Global burden of hepatitis C: considerations for healthcare providers in the United States. Clin Infect Dis. 2012;55 Suppl 1:S10-15.
18. Centers for Disease Control and Prevention. Prevention and control of infections with hepatitis viruses in correctional settings. MMWR. January 24, 2003. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5201a1.htm. Accessed March 5, 2014.
19. Centers for Disease Control and Prevention. Locations and reasons for initial testing for hepatitis C infection—chronic hepatitis cohort study, United States, 2006-2010. MMWR. August 16, 2013. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6232a3.htm?s_cid=mm6232a3_w. Accessed March 5, 2014.