Generally Accepted Indicators for Treatment: The AASLD/IDSA guidance provides a hepatitis C priority ranking for treatment based on both clinical and public health factors: highest priority for treatment based on increased risk of liver-related complications and severe extrahepatic HCV-related complications (Figure 1), high priority for treatment based on moderate fibrosis or other concomitant complications (Figure 2), and a priority category based on elevated risk of HCV transmission to others (Figure 3). Measures used to identify patients with F3 or F4 fibrosis include liver biopsy, an Aspartate aminotransferase-to-Platelet Ratio Index (APRI) score above 2, or a fibrosis-4 index (FIB-4) above 3.25. The APRI threshold of 2 and the FIB-4 threshold of 3.25 have good specificity for correlating with advanced fibrosis, but scores below these values do not have adequate sensitivity to rule out advanced fibrosis.
- Module 4 Overview
- 0%Lesson 1
Goals for Treatment and Predicting ResponseActivity
- 1A.Core Concepts
- 1B.Goals for Treatment and Predicting Response
- 1C.ACG Treatment Resources
- Lesson 1 Quiz/CME/CNE
- 0%Lesson 2
Making a Decision on When to Initiate HCV TherapyActivity
- 2A.Core Concepts
- 2B.Making a Decision on Whether to Initiate Treatment
- 2C.Impact of Successful Treatment of Hepatitis C
- Lesson 2 Quiz/CME/CNE
- 0%Lesson 3
Cost and Access to Direct-Acting Antiviral AgentsActivity
- 3A.Core Concepts
- Lesson 3 Quiz/CME/CNE
- 0%Lesson 4
Evaluating Persons with Substance or Alcohol Use for Treatment of Hepatitis CActivity
- 4A.Core Concepts
- 4B.Addressing Substance and Alcohol Use Prior to HCV Treatment
- 4C.Harm Reduction Coalition and Hepatitis C
- Lesson 4 Quiz/CME/CNE
- 0%Lesson 5
Addressing Anticipated Adherence Problems Prior to TreatmentActivity
- 5A.Core Concepts
- 5B.Addressing Anticipated Adherence Problems Prior to HCV Treatment
- 5C.MedCoach Medication Reminder
- Lesson 5 Quiz/CME/CNE
- Module 4 Self Assessment
Core Concepts. Making a Decision on When to Initiate HCV Therapy
- Reflect on the indications, contraindications, and patient readiness when considering initiating hepatitis C therapy.
- Integrate knowledge of new medications when considering the timing of initiating hepatitis C therapy.
Continuing EducationThis lesson qualifies for 1 CME credit and 1 CNE contact hour. CE Notice.
InstructionsTo complete this lesson you must work through all Lesson 2 Activities (listed below and on the left-hand navigation bar). After finishing the lesson activities, take the Lesson 2 Quiz. You can choose to obtain Continuing Medical Education (CME) or Continuing Nursing Education (CNE) credit at that point, but you must answer at least 80% of the questions correctly. After finishing the Lesson 2 Quiz, proceed to the next Lesson. After finishing all Module 4 lessons, you will be ready to take the Module 4 Self-Assessment.Last Updated: October 26th, 2015Authors:John D. Scott, MD,John D. Scott, MD
Assistant Director Hepatitis and Liver Clinic
Harborview Medical Center
Associate Professor of Medicine
Division of Infectious Diseases
University of WashingtonDisclosures: Grant/Research Support: Genentech, Merk, Roche, and Vertex
Consulting and Speakers Bureau: Genentech, Gilead, and Roche
Advisor Committes or Review Panel: VertexSophie L. Woolston, MDSophie L. Woolston, MD
Infectious Diseases Fellow
University of WashingtonDisclosures: NoneTable of Contents
Indications for TreatmentBackground: Multiple studies have shown that successful antiviral therapy of chronic hepatitis C infection dramatically reduces both liver-related morbidity (including rates of end-stage liver disease and hepatocellular carcinoma) and mortality, as well as all-cause mortality. The new state-of-the-art treatment for hepatitis C in 2015 is much safer, better tolerated, and more effective than treatments used in the interferon era. Accordingly, from a medical standpoint, the decision of when to initiate therapy has become much easier. The cooperative guidance issued from the American Association for the Study of Liver Disease (AASLD) and Infectious Diseases Society of America (IDSA) notes that evidence clearly supports treatment of nearly all HCV-infected persons. The hepatitis C guidance provides priority criteria for treatment, outlining when therapy is most likely to provide the most immediate and impactful benefit. Decisions regarding initiating therapy must also take into account the patient willingness to undertake treatment and the ability to have the medication regimen paid for.
Contraindications for TreatmentAbsolute Contraindications: Many fewer contraindications exist in the modern hepatitis C treatment era, as therapy has evolved to predominantly interferon-free regimens. Even patients with decompensated cirrhosis or renal failure can undergo treatment if managed by a provider expert in the management of hepatitis C. The AASLD/IDSA hepatitis C treatment guidance recommends against treating persons with short life expectancies. Available data from animal studies indicate that ribavirin has significant teratogenic and embryocidal adverse effects. Accordingly, use of ribavirin is contraindicated in women who are pregnant, women who may become pregnant, or men whose female partners are pregnant. Patients with chronic hepatitis C who are of reproductive age and are to receive a regimen that includes ribavirin should be advised to use two forms of contraception during treatment and for at least 6 months following the end of treatment.
Relative Contraindications: In addition to some absolute contraindications, there are several situations in which the clinician should exert careful consideration before starting hepatitis C treatment: active severe substance abuse, psychiatric issues not optimally controlled, and social issues that may negatively impact a patient’s ability to adhere with therapy, make visits for blood draws to monitor for treatment safety, or to show up for scheduled office visits.
Assessing Readiness: A patient’s readiness to start therapy can be difficult to assess, but a checklist can be used as a general guide (Figure 4). Note that many current regimens no longer use ribavirin or peginterferon and checklist items related to these medications pertain only to those patients who will receive them. It is important to have a frank discussion with each patient about the chance of cure, the side effects of therapy, and the cost of treatment, and, if using interferon-based therapy, the impact of treatment on their quality of life during the treatment course.
Pre-Treatment Counseling: In addition, the pre-treatment discussion should cover counseling on adherence, drug-drug interactions, potential side effects, contact numbers for after-hour questions or issues, and specific information on follow-up visits. Given the extremely high cost of new direct-acting antivirals and the potential for drug resistance, it is very important that patients fully understand the importance of remaining 100% adherent with the treatment regimen.
Timing of Initiation of TreatmentNew Antiviral Agents: The availability of new direct acting antivirals has provided tremendous opportunities for highly effective, convenient, well-tolerated therapy. The very high cost of these medications has created difficulty in payment and reimbursement for current recommended therapy. In general, nearly all patients with chronic hepatitis C have an indication to receive HCV therapy, but cost issues have forced an approach whereby those likely to receive the most immediate benefit, such as those with advanced fibrosis, are prioritized to receive therapy first. It is anticipated that more direct acting agents will receive FDA approval in the next several years, including several agents that have pan-genotypic activity and may require only 6 or 8 weeks of therapy.
Advanced Age and Comorbid Conditions: Many North American patients with hepatitis C are older than age 50. With availability of new highly effective, safe, well-tolerated regimens, it is likely that more interest and experience will accumulate in treating patients with advanced age. Notably, some clinical trials with newer direct acting antivirals have enrolled patients older than 70, but overall relatively little experience exists with treatment of HCV in patients older than 70. In some circumstances, patients may have advanced age and minimal HCV-related fibrosis and thus HCV may not be expected to play a major role in shortening their lifespan. In addition, some patients may have limited life expectancy due to other co-morbid conditions, and as such, hepatitis C treatment would not be expected to alter their quality of life or life expectancy. Thus, in some situations involving patients with advanced age or expected short lifespan (less than 12 months), it may be sensible to withhold therapy.
Obtaining Authorization and Payment for Medications: If a patient has been deemed to be an appropriate candidate for antiviral therapy and is in need of therapy, the medical provider should begin investigating payment for the treatment. Because these antiviral agents are quite costly, they typically need to be pre-approved. The authorization process may last several months, with the exact time dependent on the insurance coverage and state of residence.
Monitoring and Follow-Up if Not Treated
General Recommendations for Monitoring and Follow-Up: Although the AASLD/IDSA hepatitis C guidance recommends that all patients should be considered for antiviral therapy, a substantial proportion of these individuals do not start therapy, primarily because they are not able to access highly effective directly acting antivirals for hepatitis C. The reasons for denial usually fall into two broad categories: 1) insurance denial based on early stage fibrosis; or 2) an unstable psychosocial situation. In both situations, at least annual follow-up is recommended to assess liver functioning and to readdress the barrier. During these annual follow-up visits, patients should have counseling regarding behaviors that will optimize liver health. This includes avoiding a diet high in saturated fat, achieving an optimal body weight, limiting intake of hepatoxic medications and abstaining from or limiting alcohol intake. Medical providers should have awareness of indicators associated with accelerated hepatic fibrosis progression, such as older age at the time of HCV infection, male sex, alcohol consumption, non-alcoholic steatohepatitis (NASH), genotype 3 HCV, and coinfection with hepatitis B or HIV (Figure 5). Patients receive information and education on the warning signs and symptoms of liver dysfunction, including jaundice, melena, clay-colored stools, confusion, abdominal distention and lower extremity edema.
Reassessing Hepatic Fibrosis: For patients with mild to moderate fibrosis (F0 to F2), fibrosis progression can occur, so it is recommended that at least a liver function panel that includes an aspartate aminotransferase (AST) and complete blood cell count with platelet count be performed annually; from these basic laboratory tests, an AST to Platelet Ratio Index (APRI) can be calculated. In addition, additional noninvasive testing to estimate hepatic fibrosis (with a Fibrosure or Fibrotest) is also recommended every 1 to 2 years. If a liver biopsy is performed, one should obtain a non-invasive blood test at the time of biopsy to assess correlation with liver biopsy. With more antivirals to receive FDA approved, it is expected that competition will increase and hoped that the costs of antivirals will decline. Consequently, in the future, the fibrosis threshold that many payers use may also drop to earlier stages of fibrosis.
Monitoring and Assistance with Unstable Psychosocial Situation: For patients with an unstable psychosocial situation, that issue should be addressed and patients referred to the necessary resource, such as a mental health professional, substance abuse counseling. Ongoing alcohol abuse is perhaps the most worrisome behavior, because it can accelerate fibrosis and patients should be counseled strongly to abstain completely. Special effort should be made to address psychosocial issues in patients with advanced fibrosis (F3 or F4); in addition, these patients with advanced fibrosis need hepatocellular carcinoma surveillance with a hepatic ultrasound every 6 months.
- Availability of highly effective, convenient, safe, well-tolerated therapy has changed the landscape for the treatment of hepatitis C.
- Nearly all patients with hepatitis C may benefit from therapy. Those patients with a severely limited lifespan (less than 12 months) are the exception.
- Patients with "highest priority" for treatment have increased risk of liver-related complications and severe extrahepatic HCV-related complications; those considered "high priority" have moderate fibrosis or other concomitant complications. In addition, priority is given for the treatment of patients who have elevated risk of transmitting HCV transmission to others.
- The decision and timing for starting HCV therapy needs to be individualized.
- Reviewing a checklist before starting hepatitis C therapy may be beneficial to assure the patient is ready for treatment.
- In situations when treatment is deferred (for whatever reason), the patient should periodically undergo reevaluation for disease progression and reconsideration of treatment, with the frequency of reevaluation individualized based on the patient's current fibrosis stage, likely fibrosis progression rate, and other factors that may influence treatment readiness.
- AASLD/IDSA. Recommendations for testing, management, and treating hepatitis C. When and in whom to initiate HCV therapy.
- Asselah T, Marcellin P. Interferon free therapy with direct acting antivirals for HCV. Liver Int. 2013;33 Suppl 1:93-104.
- Bini EJ, Bräu N, Currie S, et al. Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. veterans with chronic hepatitis C virus infection. Am J Gastroenterol. 2005;100:1772-9.
- Butt AA, Wagener M, Shakil AO, Ahmad J. Reasons for non-treatment of hepatitis C in veterans in care. J Viral Hepat. 2005;12:81-5.
- Durier N, Nguyen C, White LJ. Treatment of hepatitis C as prevention: a modeling case study in Vietnam. PLoS One. 2012;7:e34548.
- European Association for Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60:392-420.
- 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;49:1335-74.
- Henderson DK, Dembry L, Fishman NO, et al. SHEA guideline for management of healthcare workers who are infected with hepatitis B virus, hepatitis C virus, and/or human immunodeficiency virus. Infect Control Hosp Epidemiol. 2010;31:203-32.
- Jacobson IM, Gordon SC, Kowdley KV, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368:1867-77.
- Poordad F, Lawitz E, Kowdley KV, et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med. 2013 Jan 3;368:45-53.
- Talal AH, LaFleur J, Hoop R, et al. Absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C: results from a US database of over 45 000 HCV-infected, evaluated patients. Aliment Pharmacol Ther. 2013;37:473-81.
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- HCV Medications
- Daclatasvir (Daklinza)
- Elbasvir-Grazoprevir (Zepatier)
- Ledipasvir-Sofosbuvir (Harvoni)
- Ombitasvir-Paritaprevir-Ritonavir (Technivie)
- Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir (Viekira Pak)
- Peginterferon alfa-2a (Pegasys)
- Peginterferon alfa-2b (PegIntron)
- Ribavirin (Copegus, Rebetol, Ribasphere)
- Simeprevir (Olysio)
- Sofosbuvir (Sovaldi)
- Sofosbuvir-Velpatasvir (Epclusa)
- Boceprevir (Victrelis)
- Telaprevir (Incivek)
- Course Modules
- Screening and Diagnosis of Hepatitis C Infection
- Evaluation, Staging, and Monitoring of Chronic Hepatitis C
- Management of Cirrhosis-Related Complications
- Evaluation and Preparation for Hepatitis C Treatment
- Treatment of Chronic Hepatitis C Infection
- Treatment of Special Populations and Special Situations
- Special Topics
- Slide LecturesCore ConceptsMaster Bibliography
ContributorsSite OverviewContent Bundles
- Clinical Calculators
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