Transmission of HCV in the United States (CDC estimate)

Transmission of HCV in the United States (CDC estimate)

Past and Future US Incidence and Prevalence of HCV Infection Decline among IDUs Overall incidence Overall prevalence Infected 20+ years 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

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 is positive. 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 resolvedspontaneously or due to prior successful treatment. either 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 liver Does 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 liver structure-this stage is called cirrhosis

Options for Liver Fibrosis Assessment Liver biopsy: gold standard Elastography: approved in United States Liver Biopsy Serum markers of fibrosis Serum Biomar kers Axial CT/MRI, US can demonstrate cirrhotic morphology, portal hypertension

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 antiviral 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 antivirals 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 +/- ribavirin For 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%