Chronic Hepatitis C Virus (Chronic HCV)

Transcription

1 Chronic Hepatitis C Virus (Chronic HCV) Amie Baumgartner PA-C Fall 2015 Purpose of Lecture! Educate Gastroenterology nurses about Hepatitis C and its treatment in order to improve their knowledge and confidence in caring for patients with Hepatitis C. Objectives! Discuss epidemiology of HCV (Hepatitis C Virus).! Discuss symptoms of HCV.! Discuss testing related to HCV.! Discuss treatments for HCV.! Discuss obstacles to treatment.

2 Hepatitis Viruses! Hepatitis A and E Fecal-oral transmission! Hepatitis B and D Blood and some body fluid transmission! Hepatitis C Blood transmission Chronic Hepatis C! 1.6% of population has HCV 5x increased risk if born (CDC rec screen)! Most common cause of chronic liver disease (40% of chronic liver disease)! Most common cause of liver transplant in the U.S.! Hepatitis C Virus (HCV) is 10 times more common in the alcoholic population than in the general population Genotypes! Type 1 through 6! Type 1, 2, and 3 most common in U.S.! Type 1 most common (about 70% of patients)

3 Transmission of HCV! Blood to blood! Rarely by mucosal tissue exposed to body fluids Not transmitted in breast milk! NOT transmitted by causal contact, kissing, drinking from same glass, etc! Should not share razors or tooth brushes Risk Factors for HCV! IVDU! Intranasal drug users! Blood or blood component transfusion or organ transplant prior to 1992! If received clotting factor concentrate (eg for Hemophilia) prior to 1987! Hemodialysis! Children of HCV mothers! Sexual transmission (rare if monogamous); increase with anal or oral intercourse! Exposure to blood as health care worker! Tattoos, piercings! Also test if elevated liver enzymes without known cause or if infected with HIV or HBV. Symptoms! Fatigue & Malaise! RUQ pain! Arthralgias! Rash (Cutanea Porphyria Tarda)! Cryoglobulinemia! Often no symptoms

4 Extrahepatic Manifestations! Skin lesions / rash! Arthralgias / Myalgias! Neuropathy! Hypertension! Diabetes! Ocular disease (dry eyes, uveitis)! Autoimmune disease! Cardiac disease (myocarditis, cardiomyopathy)! Hematologic disorders Cryoglobulinemia, lymphoma, Diagnosis! Hepatitis C antibody! HCV quantitative RNA levels! Genotyping! Check for concomitant Hepatitis B infection and HIV Determining degree of fibrosis! Lab tests Eg, APRI score, FibroTest, FibroSure, ActiTest, Hepascore, FibroSpect II, SHASTA, European Liver Fibrosis Panel! Imaging tests US elastography (eg, Fibroscan) MR elastography Acoustic radiation force impulse Imaging Real-time shear wave elastography (SWE)! Liver biopsy (eg, METAVIR score) F0: No fibrosis F1: Portal fibrosis without septa F2: Few septa F3: Numerous septa without cirrhosis F4: Cirrhosis

5 HCV Progression! 20-30% will develop cirrhosis over 20 years! Alcohol causes more severe and more rapidly progressive disease! HIV or HBV co-infection increases risk of cirrhosis and HCC! Once have cirrhosis, risk for HCC is 2-4% per year. Thus screen with every 6 month RUQ US. Used to also screen with AFP every 6 months. Now not considered cost effective. Risk factors for progression to cirrhosis! Alcohol use! Longer duration of HCV! Steatosis! Other co-infections (HBV, HIV)! Male gender! Extent of current histologic damage! Genotype 3 Treatment! Treatment medication selection, dosing, and duration depends on several variables: Genotype Viral load Treatment experienced vs naïve Presence of cirrhosis Degree of cirrhosis Renal function Co-infection with Hepatitis B Virus Co-infection with HIV.

6 Treatment! Medications must be taken religiously. No missed doses!! It must be a priority for the patients. They need to do whatever it takes to remember (setting alarms, having other people help them remember, etc.).! Each medicine is unique and has its own side effect profile, drug interactions, etc. Treatment! Pegylated Interferon alpha-2a and alpha-2b! Ribavirin (Copegus, Moderiba, Rebetol, Ribasphere, Ribasphere RibaPak, Virazole))! Direct Acting Antivirals Daklinza (Daclatasvir) Sovaldi (Sofosbuvir) Olysio (Simepravir) Harvoni (Sofosbuvir/Ledipasvir) Viekira Pak (Ombitasvir, Paritaprevir with Ritonavir, Dasabuvir) Treatment Options Genotype 1a! Alphabetical Order! Harvoni weeks! Daklinza plus Sovaldi +/- Ribavirin x weeks! Olysio plus Sovaldi x weeks! Viekira Pak plus Ribavirin x weeks

7 Treatment Options Genotype 1b! Alphabetical Order! Harvoni weeks! Daklinza plus Sovaldi +/- Ribavirin x weeks! Olysio plus Sovaldi x weeks! Viekira Pak +/- Ribavirin x weeks Treatment Options Genotype 2! Alphabetical Order! Daklinza plus Sovaldi +/- Ribavirin x weeks! Solvaldi plus Ribavirin x weeks Treatment Options Genotype 3! Alphabetical Order! Daklinza plus Sovaldi +/_ Ribavirin x weeks.! Sovaldi plus Ribavirin plus Interferon x 12 weeks

8 Pegylated Interferon alpha-2a/2b! Mechanism of Action: Inhibits viral replication! Dose: injection once weekly! Contraindications: Dose adjustments based upon renal function.! Side effects: MULTITUDE!!! Terrible fatigue, bone marrow suppression, elevated liver tests (including liver failure), hypersensitivity reactions, depression (including suicidal ideation), Headaches, Rash (including potentially life-threatening), pulmonary disease, thyroid disease, ophthalmic disease. Pegylated Interferon alpha-2a/2b! Lab monitoring: Every 2 weeks to start with then every 4.! Drug Interactions: MULTITUDE!!! Cost Estimate for 4 week supply: $4,560 Ribavirin! Mechanism of Action: Inhibits viral replication.! Dose: 1000 mg daily if < 75 kg (400 mg am, 600 mg pm) OR 1200 mg daily if >=75 kg (600 mg BID). Administer with food.! Drug Interactions: Several. See package insert.! Cost Estimate per 4 week supply: $3,927

9 Ribavirin! Potential side effects Teratogenic must absolutely not become pregnant during tx and for 6 mo afterward. Anemia usually hgb decreases by 2-3 grams. Neutropenia, thrombocytopenia Fatigue and malaise Depression / mood changes GI symptoms Rash Blurred vision Itching Insomnia Ribavirin! Contraindications / Cautions:! Contraindicated in women who are pregnant and in the male partners of women who are pregnant; FDA Pregnancy Category X.! Male patients: Condoms every time and female partners also on a reliable method of birth control for duration of treatment AND for 6 months after completion of treatment.! Female patients: Two forms of birth control and male partners also must use condoms, for duration of treatment AND for 6 months after completion of treatment.! Renal dose adjustments Ribavirin! Monitor:! AST, ALT, alk phos, bili, CBC, lytes, creatinine, uric acid (weeks 0, 2, 4, 6, 8, 12, 16, 20, 24)! HCV quantitative level (weeks 0, 4, 12, 24)! TSH (weeks 0, 12, 24)! Pregnancy test (weeks 0, 4, 8, 12, 16, 20, 24)

10 Sovaldi (Sofosbuvir)! Mechanism of Action: Directly kills the Hepatitis C virus. It can be used for genotypes 1, 2, 3, and 4.! Dose: one tablet daily with or without food. Must be combined with other medications. Cannot be used as mono-therapy.! Contraindications: Cannot be used in severe renal impairment (GFR < 30) or ESRD (end-stage renal disease) Avoid use if pregnant or breast feeding Sovaldi (Sofosbuvir)! Common side effects: headache, fatigue, nausea, insomnia, diarrhea. Severity is usually mild.! Can cause elevations of Total Bilirubin, Lipase, CPK usually transient and asymptomatic.! Some Drug Interactions: Amiodarone, St John s Wort! Cost Estimate per 4 week supply: $33,600 Harvoni (Ledipasvir / Sofosbuvir)! Mechanism of Action: Directly kills the Hepatitis C virus.! Dose: one tablet daily with or without food. It can be used for genotypes 1 and potentially 4.! Contraindications: Cannot be used in severe renal impairment (GFR < 30) or ESRD (end-stage renal disease) Avoid use if pregnant or breast feeding

11 Harvoni (Ledipasvir / Sofosbuvir)! Common side effects: headache, fatigue, nausea, insomnia, diarrhea. Severity is usually mild.! Can cause elevations of Total Bilirubin, Lipase, CPK usually transient and asymptomatic.! Some Drug Interactions: Antacids such Maalox or Rolaids can be taken between 4 hours after and 4 hours before Harvoni, H2-blocker or a PPI (low dose only) must be given on an empty stomach, at the same time as the Harvoni. St John s Wort, Amiodarone Harvoni (Ledipasvir / Sofosbuvir! Estimate of cost for 4 week supply: $37,800 Viekira Pak (Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir)! Mechanism of Action: Directly kills the Hepatitis C virus.! Dose: Three tablets am, and one tablet pm. It can be used for genotypes 1 and potentially 4. It usually, but not always, requires the use of Ribavirin as well.! Contraindications: Cannot be used in ESRD (end-stage renal disease) on hemodialysis. Avoid use if pregnant or breast feeding

12 Viekira Pak (Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir)! Common side effects: nausea, pruritus, insomnia. Severity is usually mild. Can cause elevations of AST, ALT and Total Bilirubin. These are usually asymptomatic.! Some Drug Interactions: It cannot be used if the patient is taking certain birth control pills. Note that if Ribavirin is used, 2 non-hormonal birth control methods must be used. Amiodarone, some narcotics, St John s Wort Many drug interactions, not all of them significant! Cost Estimate per 4 week supply: $33,328 Olysio (Simeprevir)! Mechanism of Action: Directly kills the Hepatitis C virus.! Dose: one 150 mg tablet daily with food. Must be combined with other medications. Cannot be used as monotherapy.! Contraindications / Cautions: Cannot be used in pregnancy or breast feeding. Pregnancy class C. The patient must use birth control throughout duration of treatment and for 6 months after treatment. Patients with East Asia ancestry have an increased risk of side effects. Use with caution. If genotype 1a, check for the NS3Q80K polymorphism. If present, the sustained viral response with the use of Simeprevir is markedly reduced. Contains a sulfa moiety. Use with caution in patients with a sulfa allergy. Olysio (Simeprevir)! Common side effects: photo (sun) sensitivity, rash, fatigue, headache, dizziness, insomnia, nausea, diarrhea, elevated bilirubin, myalgia, dyspnea, elevated alk phos.! Monitor: bili, alk phos, AST, ALT, UA, HCV at weeks 4, 12, 24! Some drug interactions: St John s Wort, statins! Estimated cost of 4 week supply: $28,544

13 Daklinza (Daclatasvir)! Mechanism of Action: Directly kills the virus. Pangenotypic.! Dose: one tablet daily. Not to be used as monotherapy. Dose may be changed based upon drug interactions.! Contraindications / Cautions No issues with renal function! Common side effects Fatigue, headache, nausea, diarrhea, elevated lipase Daklinza (Daclatasvir)! Estimated cost of 4 week supply: $25,200! Some drug interactions St John s Wort, Amiodarone, statins Many drugs change dosing on Daklinza Cure Rates Overall! Type 3: about 84-88%! Type 2: about 93%! Type 1: about 95%! Treatment duration is weeks! (Note: This does not cover decompensated cirrhosis (Child-Pugh class B or C))

14 Child-Pugh Class! Scoring system based upon T bili, albumin, INR, ascites, encephalopathy! Class A: Compensated cirrhosis! Class B: Decompensated cirrhosis! Class C: Severely decompensated cirrhosis (End Stage Liver Disease (ESLD)) Barriers to Treatment! Cost is very expensive! Limitations by some insurers Must meet certain criteria (eg, degree of fibrosis)! Limitations by pharmaceutical companies Some will not provide free drug if treatment not covered by insurance. Do offer co-pay assistance for commercial insurers What if you are exposed?! Get baseline HCV antibody test! 4 weeks after exposure get HCV antibody test and a quantitative HCV RNA test

15 References! AASLD, IDSA, IAS-USA Recommendations for Testing, Managing, and Treating Hepatitis C. 12/ Mayo Clinic Gastroenterology & Hepatology Board Review, 4 th Edition.! Up-To-Date! GI / Liver Secrets Plus, 4 th Edition. Peter R McNally. Questions? Thank You!!