Transmission of HCV in the United States (CDC estimate)

Infected 20+ years

Overall prevalence

Past and Future US Incidenceand Prevalence of HCV Infection

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

Decline among IDUs

Overall incidence

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

Good news- Less new cases of Hepatitis C over the last 20 years

Bad news- many of the millions of people infected in the 1970’s and 1980’s are silently progressing to cirrhosis and liver failure

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 screened your patient, and now the HCV antibody test ispositive. What do you do next?

1.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 .

A positive HCV 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!

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 ultrasound is cheaper and it is all you need: write “evaluate Hepatitis C” – this way the radiologist knows to look for signs of cirrhosis, portal hypertension and hepatoma

Hepatitis C FibroSURE© – (A LabCorp test) A 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 liverDoes your patient have cirrhosis?

1. Need to know if the patient has cirrhosis, since this is when the risk of liver cancer or decompensation increases, and the course of therapy may need to be extended

2. Degree of liver damage is described by Stage, and reflects the amount of scarring to the liver

3. At this time- most insurances only cover therapy if patient has moderate to advanced liver disease

Stage of liver disease – based on Metavir Scale from 0 to 4- how much scarring (fibrosis) is present in the liver

Stage 0- no damage

Stage 1 – mild scarring

Stage 2- moderate scarring

Stage 3- advanced disease

Stage 4- severe scarring with distortion of the liverstructure-this stage is called cirrhosis

Options for Liver Fibrosis Assessment

Liver BiopsySerum

Biomarkers

Liver biopsy: gold standard

Axial CT/MRI, US can demonstrate cirrhotic morphology, portal hypertension

Serum markers of fibrosis

Elastography: approved in United States

HCV life cycle and how the new drugs work -Right now there are three important enzymes ( a protease, a polymerase and an enzyme involved in viral replication) which are the targets of the new anti-viral drugs. If you can block these enzymes effectively enough- then the virus has no where to hide and the infection resolves . Two or three potent anti-virals working together at different sites in the life cycle are enough to cure most patients

Treatment :For Genotype 1a or 1b:Two choices : Either a combination of two antiviral drugs Sofosbuvir and Ledipasvir (in one tablet called Harvoni®) Or three antivirals in a BID regimen called Viekira Pak® +/- ribavirinFor Genotype 2 or 3:Sofosbuvir (Sovaldi®) and ribavirin together 90 to 100% of all patients can be cured with these regimens!

Three Hepatitis C treatment terms to know:

1. SVR12- (Sustained Virologic Response, week 12)- this is

the accepted definition of cure. It means at 12 weeks after completion of therapy, the HCV remains non-detectable. Very rare to relapse after that time period.

2. Treatment naïve- patient has never been treated before

3. Treatment experienced- the patient has been treated with but

not cured previously with dual therapy (interferon and ribavirin) or triple therapy (interferon, ribavirin and a protease inhibitor). These patients may not respond as quickly to the new therapies as a treatment naïve patient, and may therefore require a longer course of medication to achieve SVR12.

Case #1- 65 year old vet with mild disease

Used drugs in the late 1960s in the service, hospitalized with hepatitis. None since

No alcohol for 27 years

Diagnosed at VA when established care in 2008

Liver biopsy showed Stage 1 fibrosis in 2008

Had some depression, decided against therapy with interferon and ribavirin then

Recently saw a TV ad about new HCV meds, decided to come to see if he was a candidate

HCV antibody test is positive

Case 1, cont

PMH- none

PE- sharp, palpable liver edge

NO palmer erythema or spider angiomata

Case 1-Lab results

Platelets- 280,000

AST/ALT- 45/73

Albumin – 4.2, T. bilirubin 0.9mg/dl

INR- nl

Fe/TIBC- 34%

AFP- 4.2

Genotype – 1a

HCV viral load- 695, 657 copies/ml

HIV- neg, HAV IgG +, HBV Sag-/Sab-

APRI score- (45/33)/280 x 100 = 1.1 (mild fibrosis)

Ultrasound- mildly enlarged liver, no masses or portal hypertension

Questions ?

In 2008, how did we confirm he has active Hepatitis C?

It is an active infection, so what is the utility now of each of the following tests in evaluating your patient?

1. CBC

2. Chemistry panel, PT/INR

3. Fe/TIBC

4. Genotype

5. Ultrasound and AFP

6. HIV, HAV IgG , HBV Sag and Sab

Started on Harvoni daily for 8 weeks, so far non-detectable week 4. Cure rate > 95%

Case #2- 65 year old alcoholic with cirrhosis

Used nasal cocaine in the 1970s and 1980s, none for 30 years. No combat, no tattoos, no transfusions

Retired, plays golf and has 3 to 4 hard drinks a few times a week with his buddies

Diagnosed in 2014 at the VA with HCV

No other major medical problems

Case #2, cont.

PE:

tremulous, has rosacea

enlarged liver, possible spleen tip

palmer erythema

distended veins on abdomen

Case 2-Lab results

Platelets- 94,000

AST/ALT- 48/51

Albumin – 3.5 mg, T. bilirubin 0.6mg/dl

INR- nl

Fe/TIBC- 34%

AFP- 9.6

Genotype – 1b

HCV viral load- 388,800 copies/ml

HIV- neg, HAV IgG -, HBV Sag-/Sab-

APRI score- (48/33)/94 x 100 = 1.6 (advanced fibrosis)

Ultrasound- mildly enlarged, nodular liver, no masses or portal hypertension, c/w cirrhosis (Stage 4)

Case #2, cont.

Patient told unless he completely stops drinking , will not be offered HCV therapy and likely to die in relatively near future of liver failure

Over next 6 months switches to Coors non-alcohol beer after golfing, loses 30 pounds. Appears motivated

To start Viekira Pak with ribavirin for 12 weeks this week – cure rate > 95%