Hepatitis C Update

September 2015Amy C. Smith, FNP

Hepatitis C

• Identified 1989• Testing available 1992• Non-A, Non-B• Blood-borne infection• No vaccine available• Leading cause of liver transplant

Hepatitis C

• According to CDC– New infections: 21,870/ year– Chronic infections: 2.7 – 3.9 M • Does not include prisoners, homeless, institutionalized

– Annual deaths: 15,000• In 2007, HCV deaths > HIV deaths

• Prevalence– US: 3-5 M– Worldwide: 170 M

Epidemiology

• VERY high rate with IV illicit drug use– 60% all new infections– Single largest risk category

• High rate in correctional institutions– 31% + (2000)

• Incarceration + IV drug use EXTREMELY high– Up to 91% in one state facility tested– General assumption is ~ 80%

Epidemiology• Other risks:– Blood products and transplants before 1992– Multiple sexual partners (? 4+)– Intranasal drug use– “Unclean” body piercing or tattoos– Occupational exposure– Dialysis– Tattooing/piercings– Low socioeconomic level– ETOH– ??? Many unknown source

Epidemiology

• VERY low risk:– Mother to fetus– Non-sexual household contact• Razors, toothbrushes, clippers

– Sexual transmission in monogamous relationship

Epidemiology

• NOT SPREAD BY:– Sneezing– Coughing– Food/water – Sharing utensils or drink– Handshake or holding hands– Hugging– Kissing– Playing – Donating blood

Overview

• HCV– Acute• Self-limited• Rare hepatic failure• Typically leads to chronic infection

– 20% clear spontaneously: + HVC Ab, - HCV RNA (PCR)

– Chronic• Progressive course over many years• Can result in cirrhosis and HCC• Can result in need for transplant

Overview

Overview• Fibrosis seems to be more rapid with:

– Duration of infection– Older age at exposure– Male– Co-infection with Hep B or HIV– Heavy ETOH use– Ongoing drug use– Obesity– Cigarette and marijuana smoking

• Fibrosis --> Cirrhosis– Compensated: extensive scarring but liver still works fairly well– Decompensated: very extensive scarring and liver function is

compromised• Portal HTN, Ascites, Varices, Encephalopathy, Coagulopathy

Overview

• Cirrhosis:– 3% to 5% will develop Hepatocellular Carcinoma

(HCC)– Incidence of HCV decreasing, but number of

cirrhotics and ESLD increasing– Expected to peak 2020 - 2030– Many will need transplant• Cost of transplant: $577,100• Cost of annual anti-rejection meds: $30,000

Symptoms

• Many have NO symptoms• Non-specific, mild, intermittent– Fatigue– Headache– Insomnia– Dark Urine– Joint pain– Pruritus– Jaundice

Evaluation

• Who to test:– USPSTF: everyone born 1945 – 1965– Received blood products or organ before 1992– IV drug use (even ONCE)– Chronic liver disease– HIV– Abnormal LFTs– Exposure to known HCV + blood– Hemodialysis– Mother with HCV

Diagnosis• Check HCV Ab

– If positive, confirm with HCV RNA (PCR)• Genotype:

– 7 different genotypes– In US, 70% are genotype 1

• 29% genotype 2 or 3• Subtypes• Immigrants

• Liver biopsy– Gold standard for assessing fibrosis– >Stage 3, easier to get treatment– Risks– Options of noninvasive “biopsy”

• Fibroscan, Fibrosure, Fibrospect, Hepascore• Limitations

Diagnosis• CBC• CMP• TSH• Hep A and B panel

– Acute panel does not tell immunity status– HAV IgM Ab, HBV sAg, HBV core IgM, HCV Ab– Must add HAV IgG, HBV sAb, HBV core Ab total

• HIV• AFP• PT/INR• Iron, ferritin• US

Diagnosis

• Once confirmed, then check HCV RNA Quantitative and Genotype– Gives specific genotype and viral load to direct

treatment

Management

• AASLD and IDSA joint guidelines (2014)• www.hcvguidelines.org• Treatment:– Direct Antiviral therapy (cornerstone)– Psychological counseling– Symptom management– Dose adjustment of medications– Assessment of fibrosis– Screening for cirrhosis/complications

Management• If no antibodies for Hep A and B, should get

vaccinated• Screening for depression at diagnosis and

subsequent visits• Support group• Fatigue– Cause uncertain– ? From liver disease vs depression/other – Improves with SVR– ?? Zofran

Management

• Counseling – Routes of HCV transmission– Risk of infecting household contacts– Lifestyle factors that promote hepatic fibrosis

Management

• Dose Adjustment of Medications– Try to avoid NSAIDs in advanced liver disease– Do not need to avoid acetaminophen, but do not

exceed 2g/24 hours– Available data FAILS to show an increased risk of

adverse effects with compensated chronic liver disease and statins• Safe in stable HCV• Associated reduction in portal pressure with cirrhotics

Management

• Screening – Cirrhotic:• Esophageal varices

– EGD

• Hepatocellular Carcinoma– U/S, AFP tumor marker

Goal of Antiviral Therpay• Eradicate HCV RNA (SVR)• SVR = cure of the HCV infection• Decrease:

– All-cause mortality– Liver-related death– Need for liver transplant– HCC rates– Liver-related complications

• Including those with advanced liver fibrosis– Reduce transmission

• ULTIMATE GOAL: achieve undetectalbe HCV RNA level– SVR at 12 or 24 weeks post-treatment completeion– Longterm clearance 99%– SVR: virologic cure

Antiviral Therapy• Direct acting antivirals has changed the face of

treatment and who we should treat– Vast majority of patients are candidates– Special consideration:

• Chronic kidney disease• Liver transplant• HCC

• Highly effective (98-100% SVR)• All-oral regimens– Interferon-free– Also Ribavirin-free in some cases

Antiviral Therapy

• $$$$• Media attention in the US• $95,000 (8 weeks) to $145,000 (12 weeks) • Even at high introductory cost, they are cost-

effective• Superior efficacy: 98-100%• Does limit access for some

Antiviral Therapy

• Treatment selection based on GENOTYPE– Genotype 1– Genotype 2 and 3– Genotype 4, 5, 6, 7

Antiviral Therapy

• Two main new drugs for Genotype 1– Harvoni (Sofosbuvir/Ledipasvir)– Viekira Pak (Ombitasvir/paritaprevir/ritonavir +

dasabuvir)• In combination with Ribavirin

Harvoni

• Adverse Events– > 10%: headache, fatigue– > 5%: nausea, diarrhea, insomnia

• Drug Interactions– Contraindication: Rifampin, St. John’s Wort– PPI, H2-blockers, antacids: can alter absorption

(dose separately)

Harvoni

• Treatment-naïve, no cirrhosis, viral load < 6M: 8 weeks (97% clearance)

• Treatment-naïve, with or without cirhosis, viral load > 6 M: 12 weeks (99% clearance)

• Treatment-experienced, without cirrhosis: 12 weeks (99% clearance)

• Treatment-experienced, with cirrhosis: 24 weeks (100% clearance)

Harvoni

• Price– 8 weeks: $63,000– 12 weeks: $94,500

• Highlights:– One pill once daily– With or without food– No Indication for ESRD– ? Genotype 4

Viekira Pak

• Competition for Harvoni• As effective as Harvoni• A little cheaper: 12 weeks for $88,000• 3 pills in AM, 1 pill in PM PLUS weight-based

Ribavirin (usually 2 pills twice daily)• Must be taken with food• Ribavirin has increased drug interactions and

must monitor labs closely (every 2-4 weeks)– CBC, CMP, TSH, INR

Viekira Pak

• Genotype 1a:– Without cirrhosis: 12 weeks– With cirrhosis: 24 weeks

• Genotype 1b:– Without cirrhosis: (NO RIBA) 12 weeks– With cirrhosis: 24 weeks

Who Should Be Treated?

• My theory: almost everyone– Exceptions: ESRD, ongoing drug and/or ETOH abuse

• Insurance company’s theory: almost noone– Want stage F3-F4 fibrosis (cirrhosis) before approval– Exclusion clauses– Numerous appeals and denials

• AASLD highest priority:– Advanced fibrosis, compensated cirrhosis, pre- and

post-transplant, Severe extra-hepatic complications

Who Should Be Treated?

• If 2 appeal failures with insurance, Gilead (Harvoni) will pay for treatment

• Similar program for Viekira• GREAT options for uninsured through the

pharm companies

Resources

• AASLD Guidelines• Hcvguidelines.org• UptoDate• CDC