For Professionals

For Your Clinical Practice

• How can you implement HCV testing in your practice?
  • Set an alert/reminder as you would for any other routine preventive care test such as colorectal cancer screening. For example, modify the electronic medical record to flag any patients born between 1945 and 1965 who have not been previously tested for HCV. Ensure that the flag no longer activates when testing has been completed.
  • Alternatively, nurses or medical assistants can place order for HCV testing (as part of standing delegation order set) for all patients born between 1945 and 1965, as is often done with vaccinations.
  • Offer educational materials to baby boomer patients about HCV risk and treatment. You can give patients information about HCV with materials in the office. Offer opt-out testing, as this is associated with higher uptake than opt-in testing
    • Materials for patients
    • Posters in the waiting room can also help mass educate patients CDC Baby Boomer Posters

Diagnosis: Evaluation

• What hepatitis C tests should you order?
  

  1. Hepatitis C Antibody Testing: Presence of antibodies indicates the patient has been infected by HCV in the past but does not confirm current infection (see Figure on HCV testing. This is a screening test.

     ICD-10 Code	Indication for Screening
     Z11.59	Encounter for screening for other viral diseases (preferred for baby boomers)
     Z22.52	Carrier (includes suspect carrier) of viral hepatitis
     B18.9	Suspected carrier of viral hepatitis
     Z20.5	Contact with and (suspected) exposure to viral hepatitis

     CPT Code	Screening Test
     86803	HCV antibody alone
     86804	The Optimal screening method is a reflex test*that automatically follows up a positive HCV antibody result with a quantitative test for HCV RNA from the same blood sample
     G0472	HCV antibody screen, for individual at high risk and other covered indication

     *Reflex testing permits the diagnosis of chronic HCV from one blood specimen (see below for description of need for HCV RNA). This can also minimize patient travel and blood draw costs.
  2. HCV RNA – is a confirmatory test to determine whether a patient has virus present indicating chronic HCV infection. The use of a confirmatory testing is similar to testing for HIV that requires follow-up with a Western Blot for HIV. 20 to 30 % of patients who have a positive HCV antibody will be negative for HCV RNA, suggesting that they spontaneously cleared the infection or were successfully treated. The quantitative test for HCV RNA is preferred because it provides a viral load number whereas a qualitative test does not.

     CPT Codes	HCV RNA tests
     87522	HCV RNA quantification (preferred)
     87520	HCV RNA, direct probe technique (qualitative
     87521	HCV RNA, amplified probe technique (qualitative):

  3. HCV genotype test: CPT 87902 The genotype is a classification of the type hepatitis C virus based on sequence analysis. Hepatitis C is divided into six distinct genotypes that are located throughout the world and may have several subtypes. Management differs based on genotype.

  Printable Version of this Section

• Chronic HCV Evaluation

  Chronic Hepatitis C infection (ICD-10 code B18.2) requires evaluation of disease severity and a management plan

  Fibrosis of the liver is an accumulation of scar tissue from ongoing inflammation that can occur with any chronic liver disease. Fibrosis occurs when scar tissue builds up faster than it is broken down and removed from the liver. As scar tissue accumulates, it can lead to cirrhosis, where the liver is severely scarred, its blood flow is restricted, and its ability to function is impaired.

  Several scales can be used to stage fibrosis; however, many physicians use a scale from 0 to 4 where:

  • Stage 0 indicates no fibrosis
  • Stage 1 indicates minimal fibrosis
  • Stage 2 indicates mild fibrosis
  • Stage 3 indicates moderate fibrosis
  • Stage 4 indicates severe fibrosis, i.e. cirrhosis
  • Liver Biopsy Liver biopsy is traditionally considered the gold standard method for assessing fibrosis; however the procedure is invasive and has a risk of complications (1 in 100-1000). In addition, liver biopsy is limited by sampling error as only a small portion of the liver is assessed. 
  • Non-invasive methods Non-invasive markers of fibrosis are increasingly used to assess severity of liver disease
    1. Serum measures using routine laboratory tests
    • AST to platelet ratio index (APRI) APRI Calculator
      • Based on patient AST level and platelet count
      • Large meta-analysis found APRI cut-off of 0.7 had a sensitivity of 0.77 and specificity of 0.72 for predicting significant fibrosis. Estimated positive predictive value and negative predictive value are approximately 70% and 79%, respectively. Test may be less accurate in patients co-infected with HIV 
    2. FIB-4 – Give reference and sensitivity and specificity Fib-4 Calculator
       • Based on patient age, AST, ALT, and platelet count
         • A FIB-4 index > 3.25 has a positive predictive value to confirm existence of significant fibrosis (F3-F4) of 82%, a specificity of 0.98 and sensitivity of 0.38. Using a cut-off of < 1.45 for exclusion of significant fibrosis (F3-F4), sensitivity and specificity were 0.82 and 0.69, respectively . Serum markers using specialized laboratory tests
           • Fibrosure Fibrosure is calculated combining six serum markers with patient age and gender: alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glytamyl transpeptidase, total bilirubin, and ALT.
    3. Hepascore is calculated combining four serum markers with patient age and gender: hyaluronic acid, alpha-2-macroglobulin, gamma-glytamyl transpeptidase, and total bilirubin.
    4. Imaging measures of fibrosis include:
       • Liver ultrasound – Ultrasound can assist in evaluating for liver fibrosis or cirrhosis (nodular liver); however, fibrosis can be difficult to distinguish from steatosis. The positive predictive value of liver surface nodularity alone is poor (~50%), although liver nodularity with signs of portal HTN is specific for cirrhosis. 
       • Transient elastography, i.e. FibroScan-Transient elastography can assess liver stiffness to differentiate stiff fibrotic hepatic parenchyma from normal liver tissue. Transient elastography has a sensitivity and specificity of 0.79 and 0.78, respectively, for diagnosis of significant fibrosis (F2-F4 ).  However, its performance is worse in overweight/obese patients and those with ascites. Further, it may have limited availability in some areas.
       • MR elastography- MR elastography can also assess fibrosis by evaluating liver stiffness. Initial data suggest it is more accurate than transient elastography; however, its routine use is limited by availability and cost.

Treatment and Management

• Overview of HCV Treatment
  

  HCV treatment has dramatically changed in the last few years (See Figure above). This figure shows that patients were previously treated with injectable interferon that only achieved a cure (sustained viral response) in a minority of patients. However, with the advent of new direct acting, anti-HCV drugs that can be taken orally, the cure rate has increased dramatically – over 90%.

  Learn about treatment options in Texas for liver cancer

  • Dallas area
  • South Texas area
    • These centers often have open clinical trials for HCC patients
• Developing a management plan

  HCV treatment is now composed solely of oral drugs, which are highly effective with short courses (< 6 months) and well tolerated. Although Interferon-based therapy was the main treatment for hepatitis C, for several years, oral directly acting antivirals became available in 2014 and are now standard of care. This means there are NO longer any injections. The new hepatitis C treatments have a higher efficacy (>90%) than interferon based therapy, which was effective in a minority of patients. The new HCV therapies are also better tolerated, with little to no side effects in most patients. Finally, the treatments are shorter in duration, lasting 8-24 weeks depending on your HCV genotype, degree of fibrosis and prior HCV treatment history.

  Drug	Dosing regimen	Typical duration	Effective for Genotypes	Efficacy
  Sofosuvir/ledipasvir (Harvoni)	1 pill once a day	12 weeks	1, 4, 5, 6	94-99%
  Sofosbuvr, ribavirin (Sovaldi, Copegus)	Once pill + 3 pills twice a day	12-24 weeks	2, 3	95% (genotype 2); 93% (genotype 3 treated 24 weeks if no cirrhosis)
  Ombitasvir/paritepravir/ritonavir and dasabuvir (Viekira Pak)	2 tabs once a day+ 1 tab twice a day+- Ribavirin twice a day	12-24 weeks	1, 4	90-99%
  Daclatasvir, sofosbuvir (Daklinza, Sovaldi)	Two pills once a day	12 weeks	1, 3	91-98% (genotype 1), 65-96%  Lower response if cirrhosis genotype 3
  Elbasvir/grazoprevir (Zepatier)	One pill once a day	12-16 weeks	1, 4	90-95%
  Sofosbuvir/Velpatasvir (Epclusa)	One pill once a day	12 weeks	1, 2, 3, 4, 5, 6	>95%

  • New drugs being rapidly developed and FDA approved. Excellent resource for information on HCV Treatment is AASLD/IDSA HCV guidance
  • Patient Assistance Programs. Patients meeting certain income criteria can receive drug at no cost from pharmaceutical companies. Extensive documentation can be required
  • HCV treatment slides
• Monitoring for cirrhosis

  Cirrhosis monitoring for HCC

  • Patients with cirrhosis are at high risk for HCC, with an annual incidence of 2-6% per year
  • Patients with HCC who are found at an early stage are eligible for curative therapies (median survival > 5 years), whereas those found at late stages are only amenable to palliative therapies (median survival 1-2 years), highlighting the importance of early tumor detection
  • Screening should be done in all patients with cirrhosis every 6 months. HCC screening is strongly associated with early tumor detection, curative treatment receipt, and improved survival in several (> 30) cohort studies and is considered one of the primary quality metrics for cirrhosis care.
  • Screening should be using ultrasound with or without the serum biomarker, alpha fetoprotein
  • Although CT and MRI may be used for HCC screening, there is a dearth of data showing how well they work and their routine use is limited by high costs and harms (radiation and contrast exposure).
  • All patients with a mass > 1 cm on ultrasound or elevated AFP (most common cut-off in clinical practice is 20 ng/mL) should have diagnostic evaluation with 4-phase CT or dynamic contrast-enhanced MRI
  • To see current treatment guidelines please click on the link and create a free account.(link below)
    • https://www.nccn.org/professionals/physician_gls/f_guidelines.asp

The AAHIVM Institute for Hepatitis C has partnered with the American College of Physician (ACP) to release the brand new Guide to Hepatitis C testing! The Guide to Hepatitis C testing is designed for primary care clinicians to help screen patient for hepatitis C (HCV). It is a summary of the latest testing recommendations, along with diagnostic, billing, and laboratory codes for testing. Please click on the button to access the guide!

Guide to Hepatitis C Testing