1. Managing Hepatitis C in Vermont
Module 3:
The Post-Screening Process

2. Welcome to the Post-Screening Process module
Please take this brief pre-module quiz
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3. This module works a lot better in “presentation” mode
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4. Outline What to do with a positive HCV test
Screening for co-infections
Screening for liver fibrosis and cirrhosis
Risk-reduction for persons living with HCV

5. Outline What to do with a positive HCV test
Screening for co-infections
Screening for liver fibrosis and cirrhosis
Risk-reduction for persons living with HCV

6. Proceed to chronic HCV management
Test serum hepatitis C (HCV) antibody (Ab) in the following groups:
Birth year
Abnormal biochemical liver tests, present or past
History of intranasal or injection drug use
History of incarceration
Hemodialysis
Infection with hepatitis B or HIV
HCV Ab negative
HCV Ab positive indicates HCV exposure
Indicates no HCV exposure Repeat HCV Ab in future if ongoing risk
HCV infection > 6 months?
HCV RNA detected
Check serum HCV RNA
HCV RNA not detected no HCV infection Repeat HCV RNA in future if ongoing risk
No Repeat HCV RNA after 6 months
HCV no longer detected Repeat HCV RNA in future if ongoing risk
Yes
Proceed to chronic HCV management
HCV RNA still detected
Screen for co-infection
Initial tests
HCV genotype
ALT, AST, bilirubin, alkaline phosphatase
Albumin
Creatinine
Complete blood count
Prothrombin time
Assess extent of hepatic fibrosis with FIB-4 score

7. Screening for co-infection
Screening for co-infection serves two goals
1) Identify infections that need to be concurrently managed
2) Identify lack of immunity to hepato-pathologic infections for which there are effective vaccines

8. Screening for co-infection: Identify infections that need to be concurrently managed
Hepatitis B and HIV are the two main co-infections to look for when a patient is diagnosed with HCV
HBV/HCV Co-Infection
About 7% of patients with HCV also have HBV1
Increased rate of cirrhosis
Increased risk of hepatocellular carcinoma
HCV treatment can cause acute worsening of HBV and fulminant hepatitis, so both need-be managed concurrently
HIV/HCV Co-Infection
About 6% of patients with HCV also have HIV2
Increased rate of cirrhosis
About 15% of patients with HIV in the USA have not yet been diagnosed2
Life-saving to identify HIV in this population before it progresses to AIDS
1Konstantinou, Annals of Gastroenterology, 2015; 2CDC website, section on HIV/AIDS and Viral Hepatitis, 2018

9. Screening for co-infection: Identify what vaccines are indicated
Make sure patients with HCV infection are immune to Hepatitis A and B viruses, as infection with either could lead to rapid decompensation
Hepatitis A Virus (HAV)
Check HAV IgG serology
If negative, vaccinate against HAV
Repeat serology in 6 months to ensure vaccine response
Hepatitis B Virus (HBV)
Check HBV surface antigen, surface antibody, and core antibody
If HBV surface antigen positive, refer to ID or GI
If HBV surface antigen and antibody negative, vaccinate against HBV
Pneumococcal Vaccination
Patients with cirrhosis should also receive vaccination against pneumococcus

10. Proceed to chronic HCV management
Test serum hepatitis C (HCV) antibody (Ab) in the following groups:
Birth year
Abnormal biochemical liver tests, present or past
History of intranasal or injection drug use
History of incarceration
Hemodialysis
Infection with hepatitis B or HIV
HCV Ab negative
HCV Ab positive indicates HCV exposure
Indicates no HCV exposure Repeat HCV Ab in future if ongoing risk
HCV RNA detected within prior 6 months?
HCV RNA detected
Check serum HCV RNA
HCV RNA not detected no HCV infection Repeat HCV RNA in future if ongoing risk
No Repeat HCV RNA after 6 months
HCV no longer detected Repeat HCV RNA in future if ongoing risk
Yes
Proceed to chronic HCV management
HCV RNA still detected
Screen for co-infection
Go-to tests
HCV genotype
ALT, AST, bilirubin, alkaline phosphatase
Albumin
Creatinine
Complete blood count
Prothrombin time
Assess extent of hepatic fibrosis with FIB-4 score
HIV
HIV serology. Refer to ID if positive
Hepatitis B (HBV)
HBc Ab
HBs antigen
Neither positive:
get HBs Ab
Refer to GI or ID if either positive
Also get hepatitis A (HAV) Ab, total not IgM
Vaccinate against HAV and/or HBV if HAV Ab and/or HBs Ab negative

11. Fibrosis and Cirrhosis Assessment

12. Hepatocellular Carcinoma
Chronic HCV infection leads to increased hepatic fibrosis and eventual cirrhosis and liver cancer
Fibrosis
Cirrhosis
Hepatocellular Carcinoma
Fibrous scar tissue within the liver
HCC3
Cancer of the liver can develop after years of chronic HCV infection
Fibrosis can progress, causing severe scarring of the liver, restricted blood flow, impaired liver function, and eventually liver failure
Chronic liver disease includes fibrosis, cirrhosis, and hepatic decompensation; HCC=hepatocellular carcinoma. 1. Highleyman L. Hepatitis C Support Project. Accessed August 18, 2011; 2. Bataller R et al. J Clin Invest. 2005;115: ; 3. Medline Plus. Accessed August 28, 2012; 4. Centers for Disease Control and Prevention. Accessed May 8, 2012.

13. Scoring Hepatic Fibrosis
The most common fibrosis staging system is the METAVIR score
F0: no fibrosis
F1: mild fibrosis
F2: significant fibrosis
F3: advanced fibrosis but no cirrhosis
F4: cirrhosis

14. Scoring Hepatic Fibrosis
There are numerous ways to obtain a fibrosis score without doing a liver biopsy
Serum tests
Many available, none perfect. Sensitivity for advanced fibrosis (F3 or greater) ranges % and specificity is ~70-90%)
At the UVMMC Viral Hepatitis Center we use the FIB-4 Score for ease of testing and low cost.
FIB-4 score requires only ALT, AST, and platelet count
FIB-4 calculators are available online:
Imaging tests
Liver Ultrasound
Fibroscan (transient elastography)
MR Elastography

15. Scoring Hepatic Fibrosis
Imaging to assess hepatic fibrosis
Liver Ultrasound: readily detects advanced cirrhosis / nodular liver, but will not pick up advanced fibrosis and thus an inferior test for finding fibrosis or early cirrhosis
Patients with cirrhosis should receive liver US every 6 months to screen for hepatocellular cancer
Fibroscan (transient elastography): current test-of-choice, provides the most accurate fibrosis assessment.
May not be feasible with significant obesity or limited right shoulder mobility
Magnetic Resonance Elastography: most expensive, limited utility unless Fibroscan is unavailable or technically unfeasible

16. FibroScan - Transient Elastography
Ultrasound determines liver stiffness in kilopascal (kPa), which is then correlated with a METAVIR “F” score
Entire process requires 15 to 20 minutes, provides immediate results
RARELY is liver biopsy needed
Bonder, Curr Gastro Rep 2014; 16:372
ALV

17. Continuum of Fibrosis/Cirrhosis in HCV
Bonder, Curr Gastro Rep 2014; 16:372

18. Who needs what for hepatic fibrosis scoring?
Start with the FIB-4 score. Patients with:
Values < 1.45 are unlikely to have advanced fibrosis (NPV 94.7%1)
For most young patients with recently acquired HCV, FIB-4 score < 1.45 allows confident assessment that advanced fibrosis is unlikely
Further imaging usually not needed
Values of suggest advanced fibrosis is possible.
Get a Fibroscan
Values > 3.25 are concerning for cirrhosis (PPV 82%)
Get a liver US to see if advanced cirrhosis or hepatocellular carcinoma is present. If negative, get a Fibroscan
1 Valley-Pichard A, Mallet V, Nalpas B et al. FIB‐4: An inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology. June 2007.

19. Consider ID or GI referral. Treatment of HCV per HCVguidelines.org
Test serum hepatitis C (HCV) antibody (Ab) in the following groups:
Birth year
Abnormal biochemical liver tests, present or past
History of intranasal or injection drug use
History of incarceration
Hemodialysis
Infection with hepatitis B or HIV
HCV Ab negative
HCV Ab positive indicates HCV exposure
Indicates no HCV exposure Repeat HCV Ab in future if ongoing risk
HCV RNA detected within prior 6 months?
HCV RNA detected
Check serum HCV RNA
HCV RNA not detected no HCV infection Repeat HCV RNA in future if ongoing risk
No Repeat HCV RNA after 6 months
HCV no longer detected Repeat HCV RNA in future if ongoing risk
Yes
Proceed to chronic HCV management
HCV RNA still detected
Consider ID or GI referral.
Treatment of HCV per HCVguidelines.org
Screen for co-infection
Go-to tests
HCV genotype
ALT, AST, bilirubin, alkaline phosphatase
Albumin
Creatinine
Complete blood count
Prothrombin time
Assess extent of hepatic fibrosis with FIB-4 score
Stiffness ≤ F3
HIV
HIV serology. Refer to ID if positive
Hepatitis B (HBV)
HBc Ab
HBs antigen
FIB-4 < 1.45
Measure liver stiffness (transient elastography, MR elastography)
FIB
Neither positive:
get HBs Ab
FIB-4 > 3.25
No cirrhosis or hepatic lesion
Refer to GI or ID if either positive
Also get hepatitis A (HAV) Ab, total not IgM
Stiffness ≥ F4
RUQ abdominal ultrasound
Vaccinate against HAV and/or HBV if HAV Ab and/or HBs Ab negative
Refer to GI if cirrhosis or hepatic lesion detected
Schedule RUQ abdominal ultrasound and refer to GI

20. Outline What to do with a positive HCV test
Screening for co-infections
Screening for liver fibrosis and cirrhosis
Risk-reduction for persons living with HCV

21. Risk-reduction for patients living with HCV
1) Minimize risk of developing cirrhosis
There is no safe amount of alcohol to drink in patients with chronic HCV
Complete abstinence is recommended
Marijuana, obesity, and diabetes also increase the rate of progression to cirrhosis
Acetaminophen use should be no more than 2g per day
Daily coffee intake may help prevent progression to cirrhosis

22. Risk-reduction for patients living with HCV
2) Test for immunity to Hepatitis A and B viruses, and vaccinate if negative

23. Risk-reduction for patients living with HCV
3) Decrease transmission risk
Avoid: blood donation, sharing toothbrushes, nail clippers, or dental or shaving equipment, cover bleeding wounds to prevent others from coming into contact
HCV is rare as a sexually transmitted disease but can happen, particularly among men who have sex with men
Amongst patients who inject drugs:
Counseling to stop injection and enter substance abuse treatment
Avoid reusing or sharing needles, syringes, or any drug paraphernalia
Promote use of syringe-exchange programs. Those available in Vermont can be found here: service-programs
Dispose of all needles after one use in a safe, puncture-proof container

24. Risk-reduction for patients living with HCV
4) Get treated for HCV! Cure of HCV is possible for most patients in Vermont See Module IV for Linkage to Care and HCV Treatment Basics

25. The Post-Screening Process: Key Points
Ensure a positive HCV RNA viral load for a positive HCV antibody screen: ~25% of patients will have naturally cleared the HCV infection
For acute HCV infection, wait 6 months from time of infection to see if infection will clear naturally
For chronically positive HCV viral load:
Obtain basic lab testing and HCV genotype
Rule out co-infection from HBV and/or HIV
Vaccinate against HBV and HAV as needed
Assess extent of fibrosis and if cirrhosis is present or not
Combination of serum and imaging tests, depending on the situation
Connect to HCV treatment
Next Step: Module 4: Linkage to Care and HCV Treatment Basics

26. Congratulations! Click here for brief post-module quiz
Please take the post-module quiz here
Click here for brief post-module quiz
or use this web address: