HCV: From Screening to Management
SUMMARY:
Hepatitis C virus (HCV) is the most common blood-borne pathogen in the USA. It is generally asymptomatic in its acute phase, often going unrecognized until chronic infection leads to cirrhosis and significant morbidity and mortality. With the advent of direct-acting antiviral (DAA) therapies, effective treatment options are now available that can cure patients of a disease that was once considered a chronic, life-threatening illness. Universal screening has become a cornerstone in the management of HCV, as patients can be diagnosed while asymptomatic and receive treatment before any lasting damage is done. The IDSA (Infectious Disease Society of America) and AASLD (American Association for the Study of Liver Disease) have released updated guidance on the screening, management and treatment of HCV.
Screening
- IDSA/AASLD recommend universal screening at least once in all adults (age ≥ 18)
- Screening should be a one time, routine, opt out HCV-antibody testing with reflex HCV RNA polymerase chain reaction (PCR)
- HCV RNA testing should be considered in patients who are immunosuppressed (e.g., patients who may not develop HCV antibodies if infected)
- More frequent screening should occur in special patient populations: Injection drug users | HIV-uninfected MSM presenting for HIV pre-exposure prophylaxis (PrEP) | HIV infected patients | Persons in correctional settings | Pregnant persons (during each pregnancy)
- Additional high-risk activities, exposures, and conditions warrant periodic screening
- Long term hemodialysis
- Glass crack pipe use
- Intranasal illicit drug use
- Persons who were ever incarcerated
- HBV infection
- Solid organ donors and recipients
- Patients with chronic liver diseases or chronic hepatitis
- Men who have sex with men
- Persons with exposure to percutaneous or parenteral blood (i.e. healthcare workers following needlestick injuries)
- Recipients of prior blood transfusion or organ donations
Diagnosis
- Positive HCV Ab AND positive HCV RNA PCR testing indicates active infection
- Positive HCV Ab AND negative HCV RNA PCR indicates prior infection that has been cleared (e.g., Patient cleared the virus following previous exposure or patient previously treated for HCV and cured)
- Patients found to have evidence of prior infection should be told that they are NOT protected from reinfection
- Quantitative HCV-RNA testing is recommended prior to initiation of antiviral therapy to document the baseline level of viremia
- HCV genotype should also be obtained in patients in whom it may alter treatment (e.g., prior treatment failure)
Management
- Patients found to have active HCV infection should receive counseling on reducing transmission and decreasing liver disease progression
- Encourage abstinence from alcohol
- Check patients for HIV and HBV coinfection
- Evaluate patients for other conditions that may contribute to liver disease
- Evaluation for advanced hepatic fibrosis using noninvasive testing (see below)
- Vaccination for HAV and HBV, as well pneumococcal vaccine in patients with cirrhosis
- Counseling on how to decrease spread via blood transmission, especially for patients with IV drug use (e.g., use new sterile syringes and filters, clean injection sites with alcohol, dispose of needles in a safe place)
- Routine testing to determine liver disease severity includes
- ALT | AST | Albumin | Bilirubin |INR | CBC with platelet count
- Serum fibrosis marker panels (e.g., FibroSure, Enhanced Liver Fibrosis Test)
- Transient elastography
- Liver US or CT
- Calculate a Fibrosis-4 (FIB-4) Score (see “Learn More”)
- A FIB-4 score is >3.25 is consistent with cirrhosis
Treatment
- Prior to beginning treatment assess patient for evidence of cirrhosis (see above)
- US of the liver must be done prior to initiating treatment in patients with cirrhosis to exclude HCC or subclinical ascites
- Complete a medication reconciliation, including review of supplements and over the counter drugs
- Check for potential drug-drug interactions, such as with the Liverpool drug interaction checker (see “Learn More”)
- IDSA/AASLD recommend a simplified HCV treatment pathway for qualifying patients
- Patients must be: Treatment naïve | No special circumstances (see below) | No current or former decompensation of their cirrhosis
- Compensated cirrhosis refers to patients with Child-Pugh A cirrhosis
Treatment of Naïve Patients without Cirrhosis
- Glecaprevir (300 mg) / Pibrentasvir (120 mg) (Mavyret)
- Once daily with food for 8 weeks
- Sofosbuvir (400 mg) / Velpatasvir (100 mg) (Epclusa)
- Once daily for 12 weeks
- While on treatment:
- Patients on diabetes medications should be counseled and monitored for symptomatic hypoglycemia
- Patients on Warfarin should have special monitoring of their INR to monitor for possible subtherapeutic levels
- No other laboratory monitoring is necessary
- Follow up:
- Repeat HCV RNA and LFTs should be done 12 weeks following completion of therapy to confirm virologic cure and AST/ALT normalization
- Patient who do not achieve sustained virologic remission (SVR) should be referred to a specialist (see below – Special Circumstances)
Treatment of Naïve Patients with Compensated Cirrhosis
- The following regimens are not recommended for patients with cirrhosis AND eGFR <30 mL/min/m2
- Glecaprevir (300 mg) / Pibrentasvir (120 mg) (Mavyret)
- Once daily with food for 8 weeks
- Sofosbuvir (400 mg) / Velpatasvir (100 mg) (Epclusa)
- Once daily for 12 weeks
- If wishing to use Sofosbuvir/Velpatasvir (Epclusa), genotype testing must first be obtained in patients with cirrhosis
- Patients with genotype 3 require baseline NS5A resistance-associated substitution (RAS) testing; if negative they may proceed with Sofosbuvir/Velpatasvir (Epclusa) treatment
- While on treatment:
- Patients on diabetes medications should be counseled and monitored for symptomatic hypoglycemia
- Patients on Warfarin should have special monitoring of their INR to monitor for possible subtherapeutic levels
- Consider monitoring LFTs as hepatic decompensation can rarely occur in patients with cirrhosis on DAA therapy
- Follow up:
- Repeat HCV RNA and LFTs should be done 12 weeks following completion of therapy to confirm virologic cure and AST/ALT normalization
- Patient who do not achieve sustained virologic remission should be referred to a specialist (see below – Special Circumstances)
- Patients will need to continue their regular cirrhosis follow ups (e.g., Liver US every 6 months to evaluate for HCC) following HCV treatment, as sustained virologic remission (SVR) does not reverse cirrhosis
Special Circumstances
- Certain patients will require care from an infectious disease specialist or hepatologist and may not be eligible for the simplified HCV treatment pathway
- Retreatment and treatment failures
- HIV/HCV co infection
- HCV and pregnancy
- Acute HCV infection
- Decompensated cirrhosis
- HBsAg positive
- Known or suspected HCC
- Prior liver transplant
KEY POINTS:
- Universal one time opt out screening for HCV infection should be done in all adults
- Certain at-risk patient populations should be screened periodically due to increased risk of HCV transmission
- Cure rates are ≥95% with direct-acting antiviral (DAA) therapies for 8 to 12 weeks, and the drugs are generally well tolerated with few adverse effects
- Simplified treatment pathways exist for uncomplicated, low risk patients to assist primary care doctors in their management of HCV
Learn More – Primary Sources:
CDC: Testing Recommendations for Hepatitis C Virus Infection
AASLD and IDSA: Recommendations for testing, managing, and treating Hep C
Liverpool Drug Interaction Checker
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