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

Welcome to the Post-Screening Process module Please take this brief pre-module quiz Click here for brief pre-module quiz or use this web address: https://forms.gle/gDF627Zh3AAWLvd36

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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

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

Proceed to chronic HCV management Test serum hepatitis C (HCV) antibody (Ab) in the following groups: Birth year 1945-1965 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

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

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

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

Proceed to chronic HCV management Test serum hepatitis C (HCV) antibody (Ab) in the following groups: Birth year 1945-1965 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

Fibrosis and Cirrhosis Assessment

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. http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Fibrosis.pdf. Accessed August 18, 2011; 2. Bataller R et al. J Clin Invest. 2005;115:209-218; 3. Medline Plus. http://www.nlm.nih.gov/medlineplus/enxy.article/000280.htm. Accessed August 28, 2012; 4. Centers for Disease Control and Prevention. http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm. Accessed May 8, 2012.

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

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 60-80% 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: https://www.hepatitisc.uw.edu/page/clinical-calculators/fib-4 https://www.mdcalc.com/fibrosis-4-fib-4-index-liver-fibrosis Imaging tests Liver Ultrasound Fibroscan (transient elastography) MR Elastography

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

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 10.7.13

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

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 1.45-3.25 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.

Consider ID or GI referral. Treatment of HCV per HCVguidelines.org Test serum hepatitis C (HCV) antibody (Ab) in the following groups: Birth year 1945-1965 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-4 1.45-3.25 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

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

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

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

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: www.healthvermont.gov/disease-control/hiv-std-hepatitis-community-resources/syringe- service-programs Dispose of all needles after one use in a safe, puncture-proof container

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

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

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