Resident Editor: Michael Incze, MD, MSEd

Faculty Editor: Bryn Boslett, MD

Background

• Hepatitis C virus (HCV) is the most common chronic blood-borne infection, with 180 million people infected globally and nearly 4 million people infected in the US. 45-85% unaware of their status.
• Accounts for 40% of chronic liver disease and is the most common indication for liver transplantation in the US. 
• HCV is transmitted primarily via exposure to infected blood; vertical and sexual transmission occur but less commonly. 
• HCV natural history:
  • 15-20% spontaneously clear (usually young patients, women)
  • 55-85% become chronically infected, of which 15-30% eventually progress to cirrhosis and end-stage liver disease
  • Risk factors for rapid progression: heavy EtOH use (>40 grams/day), male, obesity, older age at time of infection (> 40 years old), immunocompromised, co-infection with HIV or HBV

Evaluation

** CDC (2012) & USPSTF (2013) recommendation:  Screen at least once for all persons born between 1945 and 1965 (USPSTF Grade B). 

• Patients in this birth cohort account for ~70% of all HCV infections.

   

  15-30% of HCV+ patients report no known risk factors!

• Specific groups to screen:
  • ANY history of IV drug use
  • Intranasal illicit drug use
  • Patients with HIV or HBV
  • Hemodialysis
  • Healthcare professionals with needlestick injury
  • Recipient of blood transfusion or organ transplant before July 1992
  • Recipient of clotting factor concentrates before 1987
  • History of incarceration, tattoos
  • Abnormal transaminases or LFTs
  • Annual screening recommended for people who inject drugs and HIV+ men who have unprotected sex with men
• Diagnosis:
  • Screen with HCV antibody serum assay (anti-HCV) – often ELISA and expressed as “positive” or “negative,” highly sensitive and specific (~99%). 
• Positive anti-HCV can indicate current infection, past resolved infection, or false positive. Send HCV RNA to assess for viremia.
• Anti-HCV can be falsely negative if exposure occurred within past 6 months, or immunocompromised. The window period of seroconversion is approximately 8-12 weeks.
  • HCV RNA– Order quantitative HCV RNA if anti-HCV is newly positive, or if considering antiviral treatment.
    • If HCV RNA by PCR is negative, then the patient is not viremic and does not have active or current HCV infection. 
    • No need to trend HCV RNA, does not correlate with disease activity.
  • HCV genotype – Six types (1-6). Type 1a and 1b are most common in the US (~70% of infections), followed by types 2 and 3. Only do this test if the patient is viremic and a possible treatment candidate. Genotype 1 has been historically more difficult to treat, especially in African American patients. With novel direct-acting antivirals (DAAs) as treatment options, Genotype 3 now most difficult to cure.  
• Workup:
  • Baseline labs – LFTs, CBC, PT/INR, HAV IgG, HBsAg, HBsAb, HBcAb, HIV Ab/Ag. 
  • Fibrosis Assessment – at diagnosis, evaluate for disease activity, fibrosis, and risk of progression to cirrhosis. Non-invasive serum biomarkers such as FIB4, APRI and FibroSURE can be calculated using basline labs and are the preferred initial tests to assess level of fibrosis, which can then help determine need for transient elasatography (e.g., Fibroscan) or liver biopsy. Normal liver ultrasound does NOT exclude signficant fibrosis or cirrhosis. 
  • HCC screening – in HCV positive patients with cirrhosis, AASLD recommends screening with ultrasound every 6 months; however other major international guidelines include serum alpha-fetoprotein (AFP). While AFP has low sensitivity and specificity, in clinical practice, it is commonly checked in combination with ultrasound.  

Treatment

A. Antiviral treatment

• Objective – prevent transmission and complications of infection (cirrhosis, HCC). Eradication of infection is defined as sustained virologic response (SVR), which is the absence of HCV RNA in serum at the end of treatment and at 3 months after treatment completion (i.e, SVR12). 
• Availability of medications via insurance coverage is based on severity of disease, potential for side effects, likelihood of treatment response, presence of comorbidities, and patient readiness. 
• Familiarize yourself with Medi-Cal’s treatment priority criteria to improve access to treatment for those with minimal fibrosis.  These include active IVDU, HIV infection, Type 2 Diabetes, Fatigue, Woman of Childbearing Age, and more
• Treatment guidelines are changing rapidly with the advent of novel direct-acting antiviral (DAA) medications.  
  • Currently, regimens are primarily comprised of combination DAAs (e.g. sofosbuvir + velpatasvir, glecapravir + pibrentasvir, etc.).  Medication and duration of therapy are dependent on factors such as genotype, presence of cirrhosis, comorbidities and prior response to treatment. 
  • Excellent SVR rates with current regimens (>95%).
• Updates with most recent joint recommendations from AASLD and IDSA are available at www.hcvguidelines.org. These guidelines are updated regularly and are the definitive source of treatment recommendations for all genotypes. 

B. General care 

• All HCV positive patients should be counseled to abstain from alcohol. They should review medications (including OTCs and supplements) to avoid potential hepatotoxicity.
• Be aware that different DAA have specific drug-drug interactions (i.e., statins with glecapravir + pibrentasvir).  http://www.hep-druginteractions.org is a good resource to learn more about these. 
• Immunizations – All HCV positive patients who are not immune to HAV and HBV should be vaccinated.
• Patients should be generally counseled on avoiding transmission, including avoidance of IVDU or use of needle exchanges, avoidance of blood / tissue / semen donation, and no sharing of toothbrushes or razors. If patients are in a monogamous sexual relationship, their partner should consider being tested. Sexual transmission increasingly seen in certain higher-risk populations, such as HIV+ men who have unprotected sex with men. 
• Monitor for symptoms of cryoglobulinemia, which can cause vasculitis and small vessel thromboses. This includes purpura, livedo reticularis, arthralgias, or glomerulonephritis. Development of these complications is an indication for treatment.

When to Refer

• Refer to hepatology clinic for treatment if cirrhosis, HBV co-infection, prior treatment failure, post-transplant, or ESRD.  Patients with HIV co-infection may be referred to hepatology or HIV clinic. 
• Refer for radiologic abnormality suspicious for hepatocellular carcinoma.

References 

AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;(62):932-954

Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58(1):1-10.

AASLD-IDSA . Recommendations for testing, managing, and treating hepatitis C [Internet]. 2017. http://hcvguidelines.org/

Rosen HR. Clinical Practice: Chronic Hepatitis C Infection. N Engl J Med 364; 25. June 23, 2011.

Moyer VA, US Preventive Services Task Force: Screening for Hepatitis C Virus Infection in Adults. Annals of Internal Medicine, 2013 Sep 3;159(5):349-57.