Hepatitis C: An Overview

Treatment

Who should be treated?

NIH Consensus Statement
- Treatment is recommended for patients with increased risk of developing cirrhosis.
  - Detectable HCV RNA
  - A liver biopsy with portal or bridging fibrosis
  - At least moderate inflammation and necrosis
  - (Majority also have persistently elevated ALTs.)
- In some patient populations, the risks and benefits of treatment are less clear and should be determined on an individual basis.
AASLD Practice Guidelines
- Provides guidance under the following three categories:
  - Characteristics of Persons for Whom Therapy is Widely Accepted
  - Characteristics of Persons for Whom Therapy Should be Individualized
  - Characteristics of Person for Whom Therapy is Currently Contraindicated
Psychiatric Illness
- Individuals with major, uncontrolled depressive illness
  - AASDL: Listed as a characteristic of persons for whom therapy is currently contraindicated.
- History of depression but condition is well controlled.
  - AASDL: Listed as a characteristic of persons for whom treatment is widely accepted.
Active Substance Abuse
- AASDL: Listed as characteristic of persons for whom therapy should be individualized
  - Current users of illicit drugs or alcohol but willing to participate in substance abuse program or alcohol support group
- 2002 NIH:
  - Treatment of active injection drug users should be considered on a case-by-case basis.
  - Continued alcohol use during therapy adversely affects treatment response, and abstinence is strongly recommended before and during HCV treatment.
Treatment Goal
- To prevent complications of infection; principally achieved by eradication of the virus.
- HCV is considered to be eradicated when there is a Sustained Viral Response (SVR).
- An SRV is defined as the absence of detectable HCV RNA (virus) six months after treatment ends.
- A qualitative viral detection test is used for this purpose.
Standard of Care
- Treatment with Peginterferon and Ribavirin
- Peginterferon is administered once a week by subcutaneous injection.
- Ribavirin is administered orally twice a day.
Genotype 1
- 48-week course of treatment
- Higher rates of SVR achievement are seen with longer therapy.
- Test for HCV RNA level at initiation or shortly before starting treatment
- Start therapy with peginterferon and ribavirin
- At 12 weeks retest for HCV RNA level.
- If HCV RNA is negative or there has been greater than a two log drop, it is considered an Early Viral Response (EVR)
- EVR is highly predictive of achievement of SVR.
- IF EVR is achieved, continue treatment for 48 weeks.
- Throughout treatment, monitor symptoms, blood counts, and ALT.
- Test for HCV RNA at end of treatment.
- An End-of-Treatment Response (ETR) is defined as a lack of detectable HCV RNA at the end of treatment.
- If test at end of treatment is negative, test for HCV RNA 24 weeks after completion of therapy.
- Sustained Viral Response (SVR) is a lack of detectable virus 6 months post treatment.
Genotype 2 and 3
- Start 24-week therapy with pegintron and ribavirin
- Throughout treatment, monitor symptoms, blood counts, and ALT.
- Test for HCV RNA at end of treatment to determine if ETR was achieved.
- IF ETR is achieved test for HCV RNA at 24 weeks to determine if SVR was achieved.
Rates of Viral Clearance
- Genotype 1
  - SVR – 40 to 45 percent
- Genotype 2/3
  - SVR – 70 to 80 percent
Note:
- Key studies were done in naive patients.
- Key studies excluded those with co-morbid conditions and decompensated cirrhosis.
Strongest Predictor of Response
- Genotype
Other Predictors of Response

Higher SVR rates seen in patients:
- With lower pre-treatment viral loads
- Of younger ages
- With lower body weights
- With minimal liver damage
- Who are women
Lower SVR rates seen in African Americans with genotype 1

Other Treatment Terminology
- Non-Responder – HCV RNA levels remain stable during treatment.
- Partial Responder – HCV RNA levels decline but never become undetectable.
- Relapser – HCV RNA levels undetectable during treatment but detected again after treatment ends.
Common Side Effects of Peginterferon
- Occurring in more than 10 percent of patients
  - Fatigue
  - Muscle aches
  - Headaches
  - Nausea and vomiting
  - Skin irritation on injection site
  - Low-grade fever
  - Weight loss
  - Depression
  - Mild bone marrow suppression
  - Hair loss
Common Side Effects of Ribavirin
- Occurring in more than 20 percent of patients
  - Anemia
  - Fatigue and irritability
  - Itching
  - Rash
  - Nasal stuffiness, sinusitis, and cough
  - Ribiviran can cause birth defects
  - Must use strict contraceptive methods during treatment and for six months after. (AASDL)
Uncommon Side Effects of Treatment
- Less than 2 percent of patients
  - Autoimmune disease (especially thyroid disease)
  - Severe bacterial infections
  - Marked thrombocytopenia (decreased platelets)
  - Marked neutropenia (decreased white blood cells)
  - Seizures
  - Depression and suicidal idea or attempts
  - Retinopathy (microhemorrhages)
  - Hearing loss and tinnitus
Rare Side Effects
- Acute congestive heart failure
- Renal failure
- Vision loss
- Pulmonary fibrosis
- Sepsis
Careful monitoring of all patients is needed for early identification and management of side effects.
In some cases, treatment may need to be discontinued.
General Management Issues (AASLD)
- Advise HCV infected people of measures that might reduce or prevent further fibrosis
  - Alcohol use
  - Obesity
  - Hepatitis A vaccination
  - Hepatitis B vaccination
HIV/HCV Co-Infection
- 25 percent with HIV have HCV
- 10 percent with HCV may have HIV
Testing (AASDL)

All HIV infected person should be tested for HCV
All HCV infected person with HIV risk factors should be tested for HIV

Treatment
- Urgency of treatment may be greater.
- Likelihood of achieving SRV is lower.
- There are no FDA approved drugs for the treatment of co-infection. (2004)
- Most existing studies have treated co-infected people for 48 weeks regardless of genotype.
- There may be additional safety concerns due to side effects and medication interactions.