Why this Clinic now ? Increasing public awareness of this disease and the availability of new drugs

that can cure almost everyone. Patients will be asking about HCV.

Increasing emphasis on screening

Chance to cure a potentially deadly disease- how often do you get to do that?

Much easier regimens soon available that require minimum monitoring. No more interferon or ribavirin !

Landmark NEJM study from New Mexico ECHO HCV program showed primary care physicians can achieve equivalent cure rates to fancy treatment centers

Some insurance carriers approve HCV therapy done only by GI, ID or physicians supervised by an ECHO program

We can help walk you through evaluation and treatment with your first patients

Outline of today’s discussion

What is Hepatitis C

How is it transmitted

What are the potential complications of HCV infection

Why treat HCV

Who has HCV in the United States

Role of Screening

What tests do you need to order

Who should you treat

Next Clinic- Treatment regimens are changing on October 10!

Hepatitis C Basics

RNA Virus infection of the liver that is transmitted by blood exposure-transfusions before 1992, needle sharing, snorting cocaine

Not transmitted within a family by casual exposure- sharing food, drink, kissing

Almost never sexually transmitted in monogamous heterosexual couples, even after 30 years of marriage. Very different than HBV and HIV.

Can increase risk of heart disease, diabetes and some cancers, particularly lymphoma- a systemic disease, premature death

There is no vaccination (only for Hepatitis A and B)

Transmission of HCV in the United States (CDC estimate)

What are the potential complications of Hepatitis C infection?

There is a wide spectrum of outcomes, ranging from asymptomatic

benign infection for decades to rapidly progressive cirrhosis or liver

cancer in 20 to 30 years.

Alcohol, NASH, diabetes, HIV, hemochromatosis can also adversely

effect the liver and speed the destruction of the liver in the HCV

patient

Hepatitis C to Hepatocellular CA Pyramid

HCV Infection

Chronic Hepatitis

Cirrhosis

HCC

1%

(1%–3%/y)

100%

25 years

90%

(60%–95%/y)

15% (10%–30%/y)

Graphic courtesy of Dr. H.B. El-Serag.

Past and Future US Incidence and Prevalence of HCV Infection

Infected 20+ years

Overall prevalence

Decline among IDUs

Overall incidence

Armstrong GL, et al. Hepatology. 2000;31:777-782. Graphic courtesy of the CDC.

Often a Silent Disease until its too late

Over the last 20 to 30 years, liver disease in many undiagnosed or untreated hepatitis C patients has silently progressed:

-In the 1990s, the most common finding on liver biopsy was stage 0 (no liver damage). -Now 20 years later the most common finding will soon be Stage 4 (cirrhosis).

1990s 2015

Potential Complications of Hepatitis C:

I. Hepatocellular Carcinoma (HCC)-fastest growing cancer in the United States

II. Decompensated liver disease-jaundice, ascites, wasting, encephalopathy, variceal bleeding

Vertex Pharmaceuticals Incorporated, March 2010

Does curing Hepatitis C alter the patient’s prognosis? YES!!!

Curing HCV has many benefits:

I. Actual regression (improvement) of the liver scars

II. Decreased incidence of liver failure

III. Decreased incidence of liver cancer

IV. Reduced all-cause mortality

V. Improved life expectancy

VI. Prevent viral transmission to others

How to work up your patient with Hepatitis C

You screen your patient, and the HCV antibody test is positive. What do you do next?

The antibody test only means they have been exposed to HCV. About 20 % of patients will spontaneously clear the infection, but their antibody test will remain positive. They do not need treatment!

To confirm active disease obtain:

Virus (HCV), Quantitative, PCR (QuantaSURE®)

If HCV RNA is detectable- they have active disease

If HCV RNA is not-detectable- the disease has resolved-either spontaneously or due to prior successful treatment

Blood work

1. HCV Genotype – over time, HCV has evolved into different strains, referred to as genotypes 1 thru 6. Some HCV drugs may only block viral replication in a specific genotype, while other drugs may work against all genotypes. Genotype 1, the most common genotype in the United States is broken down further into genotype 1a and 1b.

It is critical to determine the genotype before prescribing therapy.

In the United States:

Genotype 1a – 55% genotype 3- 14%

genotype 1b- 15% genotype 4- 1%

genotype 2 15 %

Other blood tests:

Chemistry panel and Protime – evaluates liver function – albumin, t.bili and ProTime; and inflammation-AST and ALT

CBC- thrombocytopenia is a good predictor of cirrhosis

Iron panel and ferritin- increased levels could mean hemochromatosis or cirrhosis

AFP- elevated levels seen in cirrhosis and liver cancer

Hepatitis A antibody, total and Hepatitis B Surface ag and Surface ab- if not immune, good to vaccinate these patients against HAV and/or HBV

HIV screen

Other tests:

Liver /spleen Ultrasound- don’t order an abdominal ultrasound, L/S ultra is cheaper and it is all you need: write “evaluate Hepatitis C” – this way the radiologist knows to look for signs of cirrhosis and hepatoma

Hepatitis C FibroSURE© – LabCorp only. An indirect blood test that takes a number of lab values and correlates them with stage of liver disease.

Stage of Disease-how much damage has occurred to the liver Does your patient have cirrhosis?

Need to know if the patient has cirrhosis, since this is when the risk of liver cancer or decompensation increases big time

Liver biopsies have fallen out of favor because the new treatments are so effective and well tolerated, so mostly determined by lab tests and physical exam

Amount of Liver Damage is described by Stage, and reflects the amount of scarring to the liver

Stage of liver disease Stage 0- no damage

Stage 1 – mild scarring

Stage 2- moderate scarring

Stage 3- advanced disease

Stage 4- severe scarring with distortion of the liver structure- can be either compensated- liver still

functions well, or decompensated- ascites, jaundice, encephalopathy etc

Results suggesting cirrhosis

Physical exam- palmer erythema, spider angiomata, irregular liver edge

Labs- ultrasound shows nodular liver or big spleen, low platelet count <140,000. Low albumin, increased ProTime, increased bilirubin

FibroSURE® - good for identifying early and advanced disease, not so much for middle stages

APRI (AST to Platelet Index) score- uses AST and platelet count to estimate likelihood of cirrhosis- equation available online

62 year old business executive has elevated transaminases on routine chemistry panel. Despite stop drinking for 2 months, repeat panel again shows AlT- 57, AST- 45, t.bili 1.1mg/dl. HCV antibody test is positive

What test do you order now to confirm dx?

PE-

WBC 3.2, Hbg 14.1 ,platelets 128,000.

Fe/TIBC % sat- 62%

Albumin 3.3, PT- 12.8. AFP- 12 (nl to 8)

Ultrasound- coarse liver, no masses, spleen slightly enlarged

Hepatitis A Total – positive, Hepatitis B S Ag -/ S ab-, HIV –neg

HCV genotype 1a, viral load- 2.3 million copies/ml