THE CIRRHOTIC PATIENT ON HCV THERAPY

Dr. David PearsonGastroenterology, Victoria

Disclosures

None relevant to this presentation

Why is Fibrosis/Cirrhosis Important?

Progressive fibrosis may lead to debility and death from liver failure or cancer

Advanced fibrosis (F3-4) means reduced response to Hepatitis C therapies

Successful treatment of Hepatitis C infection will halt the progression of liver disease in these patients at high risk of symptomatic decompensation

When to treat?

Before the onset of advanced fibrosis Better response in early disease: F0-2 Treatment better tolerated if patient is

healthier Fatigue and other symptoms Anemia No risk of decompensation from loss of

functioning liver mass Best response to therapy:

Younger age Less fibrosis Elevated ALT Female

What is cirrhosis?

What is cirrhosis?

Architectural description of the liver after long term injury and regeneration with replacement of functioning liver tissue by fibrosis.

Is partially reversible if the noxious agent is removed and the liver is able to regenerate.

Eventually leads to functional liver impairment.

How do we know the patient is cirrhotic?

History Alcohol excess Male sex Longer duration of infection (>20 years) Steatosis

Physical exam Liver contour (enlarged left lobe, rounded,

firm) Splenomegally, ascites, caput: portal HTN Spider angiomas, gynecomastia: estrogenic Jaundice Asterixis

How do we know the patient is cirrhotic?

Imaging Nodular contour, altered shape Enlarged spleen, abdominal varices Ascites

Lab Thrombocytopenia, anemia, leukopenia INR, albumin, bilirubin AST/ALT ratio (often normal ALT) Biopsy

Fibroscan: Transient elastography Fibrotest/FibroSure

Pretreatment evaluation of the cirrhotic patient

Education and preparation are important Vaccinations (CDC)

HBV, HAV, Strep pneumonia (Pneumovax) Influenza, varicella, MMR, tetanus, diptheria

Screening Gastroscopy Abdominal U/S

Portal Hypertension Portal vein thrombosis Hepatocellular carcinoma

Pretreatment evaluation of the cirrhotic patient

Contraindications to treatment Pregnancy/contraception advice Auto-immune hepatitis Renal insufficiency Severe cardiopulmonary disease Uncontrolled affective disorder/psychosis Hepatocellular carcinoma

Is there a history of liver decompensation?

Potential drug interactions

Pretreatment evaluation of the cirrhotic patient

Is there an opportunity for improvement? Alcohol/smoking cessation Other comorbidities to optimize?

Diabetes, cardiac, pulmonary Relative contraindications to treatment

Decompensated cirrhosis Ascites, encephalopathy, jaundice

Albumin <35 Bilirubin >25 Platelets <75, 000 Anemia: Hg <130 male; <120 female

Pretreatment evaluation of the cirrhotic patient

What about non medical factors? Housing Disability coverage/income replacement Drug coverage Preparing patient expectations for the

experience on therapy

Cirrhosis: Implications for treatment

48 wks therapy for G1; 24 wks for G2/3 More likely to need medications tapered,

more frequent measurement of hematology recommended.

Less able to tolerate therapy: need closer follow up and reassessment

Higher rate of drop out due to adverse effects, esp G1’s

Cirrhosis: Implications for treatment

Recent French report treating cirrhotics with triple therapy: 35-45%signficant adverse events (anemia, infection, renal failure, decompensation) 1% death from infection, bleeding 50% significant anemia and EPO use 5% significant neutropenia and

thrombocytopenia Esp age>65, female, low initial Hg

A practical approach

Anticipate trouble! Identify the fragile cirrhotic: Thorough work up

before treatment should identify those most at risk

4 week lead in may be illuminating…. How bad is a patient’s liver disease

Compensated Previously decompensated: “Recompensated” Currently decompensated Abnormal liver functions: bilirubin, albumin,

INR Abnormal hematology at baseline predicts

cytopenias on therapy

How do you know you’re in trouble?

Symptomatic decompensation Variceal bleeding, ascites, encephalopathy Treatment of symptoms Is there an identifiable precipitant?

Alcohol, new medication, infection Does therapy need to be stopped?

Infection Low threshold for antibiotic use with bacterial

infection; patient are immune compromised Respiratory, urinary, skin

How do you know you’re in trouble?

Treatment related issues Cytopenias: dose reductions; growth factors Symptoms: Fatigue, mucositis Other organ systems: cardiac, skin rash,

diarrhea

What to do when you’re in trouble

Limited options Anemia: taper Riba/IFN; NOT DAA’s

?role of EPO Platelets/WBC: taper IFN Diarrhea Rash

When to stop

Futility rules Decompensation Medication intolerance

Fatigue, Rash, Diarrhea Low doses, regression to single agent IFN

The case

54 yr old man; G1a, start Pegasys Sept 2010

Cirrhosis: ex-IVDU/Alcohol; compensated 2007 Thoracic aortic aneurysm repair 2009 Aortic valve endocarditis Baseline: WBC 3.8/Hg121/plt 68

INR 1.1, ALT 94, alb 40, bili 25 IFN 1000 mg/ IFN 180 mcg

Week 5 Hg 95, plt 30 Hold riba a week, restart at 600

The case

Week 12 Hg 80-95, plt 30-40; fatigue – off work Riba 400-600, IFN 2/3 – PCR 2 log drop

Week 26 Riba stopped, had been interrupted and dose

reduced IFN 2/3 dose Week 24 PCR negative

Week 30 ascites, increased fatigue, 25 lb wt loss then 12 lb gain Stop all Rx

The case

PCR negative at wk 30 = end treatment PCR relapsed 12 weeks later Ascites slow to resolve; issues with

congestive failure and required urgent aortic valve replacement May 2011

Now wants to be retreated!

Role of the Hepatitis Nurse

Educator Advisor Coach Confidant

ThePlan

An Individual Effort

Inspiration

Encouragement

Motivation

Thank you for your attention

Questions?