Introduction
Up to 56% of people with
chronic hepatitis C treated with interferon-based therapy have
sustained clearance of the hepatitis C
(HCV) from their bodies.1 Sustained
clearance or sustained response means the virus
can no longer be detected in your blood even after treatment has stopped.
Studies show that the lowest rates of sustained response are seen when
interferon is given alone for a
short period of time. Only 5-15% of people clear virus with six months of
interferon monotherapy.2 The highest sustained
response rates occur in people treated with a combination of
pegylated interferon plus
ribavirin for 12 months. The
reported sustained response rate is 54-56% for this treatment protocol.1, 3
The impressive increases in response rates have provided considerable hope
to those seeking treatment for hepatitis C and those of us who treat them.
However, it is still true that about half of people treated with the
maximum amount of our best current therapy still do not clear HCV.
This chapter covers several topics that are relevant if your initial
treatment with interferon-based therapy failed to clear HCV. These topics
include:
 What are the goals of retreatment?
Who should consider
retreatment?
Who should be retreated
with pegylated interferon plus ribavirin?
What is the evidence
that retreatment clears HCV?
What is the evidence
that treatment slows disease progression?
What is the evidence
that treatment reduces the risk of liver
cancer?
Who should be screened
for liver cancer?
What tests should be
done?
What are the Goals of
Retreatment?
There are three main reasons to consider retreatment:
to clear the virus from your body
if the virus cannot be
eliminated, to slow disease progression
if the virus cannot be
eliminated, to reduce the risk of liver cancer (also known as
hepatoma, hepatocellular carcinoma, and HCC)
The goals of retreatment vary from person
to person. Table 1 summarizes the issues doctors take into account when
recommending retreatment to people with hepatitis C. Each of these issues
is important. We must determine which therapy gives a particular patient
the best chance to clear the virus. We must also determine if there are
supportive care measures needed to slow the rate of liver injury. These
measures could include reducing the amount of iron in the body,
antioxidant therapy, and/or
long-term treatment with low-dose, pegylated interferon.
Table
1: Management Issues in Retreatment of Non-Responders to Previous
Interferon Based Therapy
Clearing the Virus
Viral clearance is the elimination
of HCV from the blood and the liver. The most common test used to measure
viral load is the polymerase chain
reaction (PCR) assay. Sustained viral clearance means HCV is
undetectable in the blood for six months or more after completing a course
of antiviral therapy. Clearance of
HCV from the blood is usually accompanied by clearance of virus from the
liver. This is known as a virologic cure. A virologic cure is assumed to
occur when a person maintains a sustained response for at least six months
following completion of therapy. A small percentage of people (less than
5%) who have a sustained response may relapse,
meaning the virus becomes detectable again. This usually occurs within a
year of completion of therapy.4
Certain characteristics predict the likelihood of clearing HCV with
retreatment using pegylated interferon plus ribavirin.
Relative effectiveness of prior
treatment: Patients who received the least effective initial therapy are
most likely to respond to maximally effective therapy.
Features of the infected
person: Young individuals, women, and people without cirrhosis are more
likely to respond than others are.
Viral status: Patients
with non-1 genotype and relatively low levels
of virus are more likely to respond than others are.
Slowing Disease Progression
If viral clearance cannot be achieved, the secondary goals of treatment
are to reduce the extent of liver damage, slow disease progression, and
reduce the risk of complications.
A non-responder is at risk for disease
progression and should be monitored for signs of liver
failure. If you are a non-responder, any clinical sign of liver
function deterioration should prompt your health care provider to refer
you to a treatment center experienced in liver transplantation for
evaluation.
Clinical information, laboratory tests, and/or liver biopsy results define
the progression of liver disease. See
Chapter 4, Signs and Symptoms That May Be Associated with Hepatitis C
and Chapter 5, Laboratory Tests and Procedures
for further explanation of the following criteria that point toward
disease progression.
Clinical Criteria
ankle
edema
ascites
encephalopathy
gastrointestinal
bleeding from varices
skin manifestations
(spider telangiectasia, palmar erythema)
varices
Blood Tests
increased
bilirubin
increased
prothrombin time
reduced
albumin
reduced
platelet and/or
neutrophil count
Liver Biopsy Findings
increased fibrosis
development of cirrhosis
Despite increased awareness of the potentially serious consequences of
hepatitis C, many people ignore early warning signs and only see their
health care provider when they already have late stage disease.
Unfortunately, it is more difficult to treat people with late stage
disease using interferon-based therapy. Many of these patients progress to
liver failure and may ultimately need a liver transplant.
Reducing the Risk of Liver Cancer
The third goal of retreatment is to reduce or eliminate the risk of
developing liver cancer. Among people with chronic hepatitis C, the risk
of liver cancer is mainly limited to those with cirrhosis.5 Screening tests for
liver cancer often include twice yearly blood tests for alpha-fetoprotein
and ultrasound imaging of the liver. Despite aggressive screening efforts,
at least one-third of liver cancers are not detected in the early stages
of the disease. Later stage tumors may not be curable with surgery and
cannot be cured with liver transplantation.
Current studies suggest but have not proven that interferon may reduce the
risk of developing liver cancer.6 It has also been
suggested that interferon may slow the growth of liver cancer. This would
allow more time to find the cancer at a potentially curable stage.
Detection of slow growing cancers at an early stage of disease can allow
effective and possibly curative therapies such as liver transplant. The
new procedure living donor liver transplantation
may be of particular benefit for people with liver cancer since it can be
performed relatively quickly once the cancer has been diagnosed.7
Who Should Consider
Retreatment?
You may want to consider retreatment with interferon-based therapy if:
the initial therapy you received failed
to clear the virus (non-response)
the initial therapy
cleared the virus, but the virus recurred after treatment was stopped
(relapse)
If your prior therapy was one of the pegylated interferon plus
ribavirin combinations and your goal is to clear HCV from your body,
retreatment with the same or another pegylated interferon plus ribavirin
combination is unlikely to achieve this goal.
Non-Response
Non-response is the inability of a treatment to clear HCV both during and
after a course of antiviral therapy.
There are five main reasons for non-responsive treatment failures.
The type of hepatitis
C infection was resistant to interferon-based treatment.
The therapy used was
inferior to the best current therapy.
The person did not
comply with the prescribed treatment regimen.
Treatment doses had to
be reduced because of low levels of white cells, red cells, and/or
platelets.
The length of treatment
was reduced due to side effects and/or poor quality of life.
Relapse
Relapse is not the same as non-response. In people who relapse, the virus
is undetectable during treatment, but becomes detectable again after
treatment ends. Relapse is a common occurrence with interferon
monotherapy (interferon used as
single agent therapy). It is less common with the combination of
interferon plus ribavirin, especially when pegylated interferon is used.
Who Should be
Retreated with Pegylated Interferon Plus Ribavirin?
You and your doctor have several retreatment options if your prior
treatment was interferon monotherapy. These include:
interferon alfa-2b
plus ribavirin combination therapy
pegylated interferon
monotherapy
pegylated interferon
plus ribavirin combination therapy
There are fewer retreatment options if your initial treatment was
combination therapy using interferon alfa-2b plus ribavirin. The only
western treatment options for retreatment would be the combination of
pegylated interferon plus ribavirin or enrollment in a
clinical trial involving a new,
novel treatment.
The retreatment regimen with the greatest chance of clearing HCV is the
combination of pegylated interferon plus ribavirin. The chance of response
to retreatment can be estimated based on clinical trial findings of
treatment-naive patients.8
The estimated chances for virologic cure in non-responders after
retreatment with pegylated interferon plus ribavirin are 52% for people
previously treated with six months of interferon monotherapy, and 18-27%
for people previously treated with 12 months of combination therapy using
interferon alfa-2b plus ribavirin (see Table 2).
Table 2: Estimated Sustained Response Rates after
Retreatment with Pegylated Interferon plus Ribavirin
|
|
Predicted Sustained Response (%)
After Retreatment with Pegylated interferon plus Ribavirin |
|
Prior Antiviral
Therapy |
All Patients |
Genotype I
Patients |
|
Interferon, thrice
weekly, 6 months |
52% |
41% |
|
Interferon, thrice
weekly, 12 months |
48% |
38% |
| |
|
Rebetron®,
6 months |
35% |
31% |
|
Rebetron®,
12 months |
18 to 27% |
8 to 19% |
| |
|
Pegasys®
monotherapy, 12 months |
27 to 36% |
19 to 34% |
|
Peg-Intron®
monotherapy, 12 months |
40% |
33% |
| |
From
Living with Hepatitis C: A Survivor's Guide. 3rd Edition. Everson
GT, Weinberg H. Hatherleigh Press, Inc., NY, NY. Copyright 20018
This table depicts the expected rates of response to retreatment of
non-responders with 48 weeks of pegylated interferon plus ribavirin.
The spectrum of non-responders includes those who failed to clear HCV
after short term or long term treatment with either interferon
monotherapy or Rebetron, or those who failed 12 months of monotherapy
with pegylated interferon. The derivation of the data in this table is
described in Chapter 9 of reference 8.
Please note that the sustained response rates reported in this table
were derived from existing literature describing the treatment of
naïve patients. The response rates for non-responders listed in the
table have not yet been verified by controlled, clinical trials.
Actual sustained virologic responses from
clinical trials may not be as optimistic as the projections provided in
Table 2. The results of the lead-in phase of the National Institutes of
Health (NIH) sponsored trial known as HALT C have recently become
available and are shown in Table 3.9
All HALT C participants had prior treatment failure with interferon-based
therapy and biopsy proven liver fibrosis. The study incorporated a lead-in
phase where all patients, previously treated with either interferon
monotherapy or a combination of non-pegylated interferon plus ribavirin,
were retreated with pegylated interferon alfa-2a plus ribavirin.
Responders who were HCV RNA negative after 20 weeks of treatment continued
treatment for a total of 48 weeks. Virologic cure (sustained viral
response or SVR) was achieved in 28% of patients whose prior therapy was
interferon monotherapy and in 12% of patients whose prior therapy was
non-pegylated interferon plus ribavirin. SVR was 14%, 65%, and 54% for
genotypes 1, 2, and 3, respectively. SVR was more likely in Caucasians
(20%) and Hispanics (18%) compared to African Americans (6%). SVR was 23%
among people without cirrhosis and 11% in people with cirrhosis. Ribavirin
dose reductions during the first 24 weeks from greater than 80% of the
prescribed dose to less than 60% of prescribed dose reduced SVR from 21%
to 11%. Viral clearance or a two log10 reduction in HCV viral
load by week 12 (early viral response or EVR) correlated strongly with
treatment response (34% for those with EVR versus 1% for those without
EVR). These results will help doctors group people into high and low
responder categories for selection of retreatment.
Table
3: Actual Sustained Response Rates after Retreatment
with Pegylated Interferon plus Ribavirin in the HALT C Trial
|
Independent Variable |
Sustained Response (%)
After Retreatment with Peginterferon alfa-2a* plus Ribavirin** |
| Interferon Monotherapy
vs. Combination |
28% |
12% |
| Genotype 1 vs.
Genotypes 2 & 3 |
14% |
65%, 54% |
| Caucasians & Hispanics
vs. African Americans |
20%, 18% |
6% |
| Adherence vs. Dose
Reductions |
21% |
11% |
| No Cirrhosis vs.
Cirrhosis |
23% |
11% |
| EVR vs. No EVR |
34% |
1% |
*Peginterferon
alfa-2a is marketed as Pegasus®.
**The ribavirin used in this trial
was Copegus®.
Abbreviations and
Definitions:
HALT C
- Hepatitis C Antiviral Long-Term Treatment to Prevent Cirrhosis Trial
EVR - early virologic response
defined by greater than a 2 log10 drop in HCV RNA after 20
weeks of treatment
Adherence was defined as taking
80% or more of the prescribed dose of both peginterferon alfa-2a and
ribavirin.
Dose reduction was defined as
taking 60% or less of the prescribed dose of either medication.
Your doctor may not recommend pegylated
interferon plus ribavirin for clinical reasons. In this situation, options
include retreatment with either interferon alfa-2b plus ribavirin or
pegylated interferon monotherapy. The chance for a virologic cure with
these regimens is less than that for pegylated interferon plus ribavirin.
Pegylated interferon monotherapy might be preferred over interferon plus
ribavirin for patients with renal failure, cardiac
conditions, anemia, or for women of childbearing
age.
What Is The Evidence That
Retreatment Can Clear HCV?
The probability that retreatment will clear HCV is affected by the type of
prior treatment, your personal characteristics, and viral characteristics.
For example, there is a good chance retreatment will provide virologic
cure in a person without cirrhosis who did not respond to six months of
interferon monotherapy, and who has less than a million copies of genotype
2b HCV per milliliter of blood. This is true whether the person is
retreated with a combination of interferon alfa-2b plus ribavirin or
pegylated interferon plus ribavirin.
In contrast, retreatment is unlikely to clear virus in people with
cirrhosis whose initial treatment was interferon alfa-2b plus ribavirin
and who have high levels of genotype 1b HCV. Virus levels greater that 2
million copies of virus per milliliter of blood are considered high. The
treatment goals for a person in this situation are to slow disease
progression and reduce the risk of liver cancer.
Researchers have examined multiple studies from many parts of the world in
which non-responders to interferon monotherapy were retreated with six
months of interferon plus ribavirin combination therapy.10 Their analysis found
that 13.2% of non-responders who received this shortened course of
treatment cleared HCV. Rates of viral clearance varied considerably among
the studies ranging from 0-40%. In one large study from a single center,
30.6% of patients who received 6-12 months of retreatment with combination
therapy achieved viral clearance.11
My own experience retreating people who
did not respond to monotherapy has been encouraging. At our center, we
recruited 96 patients into a prospective study involving 48 weeks of
retreatment with interferon alfa-2b plus ribavirin. The study involved 67
men and 29 women. They ranged in age from 30 to 64. Forty-three percent
had contracted HCV through IV drug use. Sixty-eight percent had HCV
genotype 1, one of the most difficult genotypes to treat. Sixteen percent
of the patients in this study had already developed cirrhosis. About 30%
of those enrolled in the study had sustained viral clearance.12
What Is The Evidence
That Treatment Slows Disease Progression?
Patients treated with interferon monotherapy may potentially gain clinical
benefits even if the treatment fails to provide sustained virologic
clearance. Potential benefits include reducing liver
inflammation and the rate of
fibrosis, slowing the rate of progression to cirrhosis, and reducing the
rate of liver decompensation.
Data from existing clinical trials suggest that interferon therapy reduces
liver damage. Eighty percent of people who clear virus show significant
improvement on post-treatment liver biopsy. The major improvement is
reduced liver injury and inflammation, but the amount of fibrosis may also
decrease. Importantly, 40% of those who do not clear virus also
show improved liver histology after treatment. Once
again, the biggest improvement is reduced inflammation. Because
inflammation stimulates fibrosis, it has been suggested that long term
interferon therapy may slow fibrosis and progression to cirrhosis.
One published trial evaluated the effectiveness of long-term interferon
therapy in preventing progressive fibrosis in patients who had not
responded to therapy.13
Patients had a pre-treatment liver biopsy and a second biopsy following a
six-month course of interferon therapy. Those patients whose liver
biopsies showed improvement were randomly assigned to stop interferon
therapy or to continue on interferon treatment for a two-year follow-up
period. Those who continued interferon therapy had a reduction in liver
inflammation and a decline in liver fibrosis. Those who did not continue
therapy had increases in liver inflammation and fibrosis.
The primary goal of the NIH-sponsored
HALT C trial is to determine if maintenance therapy with pegylated
interferon alfa-2a blocks disease progression in people with chronic
hepatitis C. See
Appendix
III: Western (Allopathic) Medicine for
additional information on the HALT C trial.
What Is The
Evidence That Treatment Reduces The Risk Of Liver Cancer?
Several studies suggest that prior treatment with interferon reduces the
risk of developing liver cancer. Data indicate that interferon therapy has
anti-inflammatory, anti-fibrotic, and
anti-proliferative effects.14 These effects may
slow disease progression and prevent liver cancer. The HALT C trial will
examine the ability of maintenance therapy with low dose pegylated
interferon alfa-2a to prevent liver cancer.
A study involving patients with cirrhosis showed that only 4% of those
previously treated with interferon developed liver cancer, while 38% of
those not treated with interferon went on to develop liver cancer.15 The patients in this
study were followed for an average of 4.4 years after treatment. There
were two surprising aspects of this study. The first was that the
reduction in cancer risk was achieved with a limited, six-month course of
interferon therapy. The second was that the beneficial effect occurred in
both those who cleared the virus and in those who did not.
A review article reported the results of three studies addressing the
effect of interferon therapy on the development of liver cancer in
hepatitis C patients with cirrhosis.6 The studies involved
a total of 272 patients who received no treatment, 371 patients who
received but did not respond to interferon treatment, and 60 patients who
had a sustained response to interferon treatment. The incidence of liver
cancer was 15% among those who received no treatment, 4% among those who
did not respond to treatment, and 0% among those who had a sustained
response. The greatest reduction in the incidence of liver cancer was
among those who had sustained viral clearance. However, even those who did
not respond to interferon therapy had a reduced risk of liver cancer.
The studies cited above appear to support the use of interferon therapy to
prevent liver cancer in cirrhotic patients. However, analysis of these and
other data suggest that clinical differences in the patients at the time
of their entry into the trials and not interferon therapy may have
been the reason for the reduced incidence of liver cancer. Additional
analyses suggest that progression from cirrhosis to liver cancer may be
related to such factors as HCV genotype 1b, male gender, and age greater
than 60 years. This supports the unproven theory that the characteristics
of the person (the host) infected with the virus and variations in the
virus itself may be more important in the development of liver cancer than
treatment with antiviral therapy. This conclusion was also reached in a
study that reviewed the cases of 163 hepatitis C patients with cirrhosis.
In these patients, the apparent reduction in the incidence of liver cancer
was associated with less advanced disease among the participants.16
It is important to conduct properly controlled trials to determine if
antiviral therapy can slow the progression of fibrosis to cirrhosis, and
reduce the risk of cancer. These trials must involve large populations of
hepatitis C patients who have significant fibrosis or cirrhosis, and are
willing to be treated with antiviral therapy for an extended period of
time. We hope the HALT C trial will allow us to determine the role of
antiviral therapy in preventing liver cancer and slowing disease
progression.
Who Should Be
Screened For Liver Cancer? What Tests Should Be Done?
Because chronic hepatitis C increases your risk for liver cancer,
screening is recommended for people with advanced fibrosis or cirrhosis.
However, there are no screening guidelines with which everyone agrees.
Liver cancer can be effectively treated if detected early. For this
reason, I recommend that people with bridging fibrosis or cirrhosis have
an ultrasonography of the liver and
an alpha-fetoprotein blood test every six months. A persistent,
progressive rise in alpha-fetoprotein levels or the development of a new
liver mass indicates the need for additional tests. These tests might
include special radiologic studies of the tumor or a biopsy of the mass.
If liver cancer is diagnosed, it can be treated with surgery, liver
transplantation, and/or other non-surgical approaches.
Case Histories Of
Retreatment
Non-Responder to Monotherapy
The following is a case study of a man who came to me after his initial
treatment with interferon monotherapy failed to clear the virus.
After interferon monotherapy (three
times per week for six months) failed to clear HCV, this 35-year-old man
consulted me for retreatment. At week 24 of his prior therapy, his
ALT was 88 IU/L and his viral load
was 88,000 vEq/mL (vEq = viral equivalents). Six months after treatment,
his ALT was 145 IU/L and his viral load was 1,180,000 vEq/mL. His only
complaints were fatigue and poor concentrating
ability. He had no symptoms of severe liver disease such as
gastrointestinal bleeding, fluid retention, or altered mental state. His
physical exam was unremarkable.
His laboratory results when he first came to see me were platelet count
155,000, ALT 196 IU/L, viral load 1,800,000 copies/mL, and HCV genotype
2b. His most recent liver biopsy showed grade II
inflammation and stage II fibrosis.
This individual's clinical course is typical of a non-responder to
monotherapy. He was treated for six months with a standard dose of
interferon monotherapy but remained HCV positive. His ALT was abnormal
both during and after initial treatment. When he came to me for
consultation, he had minor symptoms, an elevated ALT level, and a
positive HCV RNA. His liver biopsy revealed mild-to-moderate
inflammation and some increase in fibrosis, but no cirrhosis. Because he
had genotype 2b HCV, he had more than a 50% chance of responding to
combination antiviral treatment.
I retreated this patient with
combination therapy. His response to treatment is shown in Figure 1. His
retreatment cleared HCV, and he remains free of the virus two years
following retreatment.
Figure 1:
Response to Interferon Alfa-2b, 5 MU three times per week
plus Ribavirin, 1.2 g/day
RNA = HCV RNA
Viral Load Test Results
Non-Responder to Combination
Therapy
The following is a case study of a woman who sought consultation with me
after her initial treatment with combination therapy failed. Retreatment
also failed to clear the virus.
This 45-year-old woman with chronic HCV failed to respond to
combination therapy. At week 48 of her initial therapy, her ALT was 68
IU/L and her viral load was 182,000,000 vEq/mL. Six months after
initial treatment, her ALT was 115 IU/L and her viral load was
5,180,000 vEq/mL. She complained only of fatigue and poor
concentrating ability.
Her laboratory results at the time of her initial visit with me were
platelet count 115,000, ALT 226 IU/L, viral load 4,800,000 copies/mL,
and HCV genotype 1b. A liver biopsy revealed grade II inflammation and
stage IV fibrosis (cirrhosis).
She complained of only minor symptoms, however examination showed
evidence of early liver decompensation: spider telangiectasia, an
enlarged spleen, low platelets, and low albumin. Because she had
genotype 1b with a viral load of almost 5 million vEq/mL, retreatment
was not likely to clear the virus. Many doctors would not recommend
retreatment. Because viral clearance was unlikely, the goals of
therapy for this person were shifted to limiting the rate of disease
progression and reducing the risk of liver cancer.
She was enrolled in the HALT C trial. Her viral load did not decrease
with pegylated interferon alfa-2a, but her ALT levels declined. The
patient is currently on long-term maintenance with pegylated
interferon alfa-2a in the HALT C trial to try to slow disease
progression and reduce the risk of liver cancer.
Options For People
Who Are Not Candidates For Retreatment Or Who Choose Not To Be Retreated
Despite many advances in antiviral treatment for HCV, some people decide
against retreatment with currently available combination therapies. They
may choose different therapies, or decide not to have any therapy.
Alternatives to interferon-based treatment protocols include:
western clinical trials
 protease, helicase,
or polymerase inhibitors (none
currently in progress as of the writing of the 3rd edition of
Choices)
interferon plus ribavirin-like drugs or
IMPDH inhibitors such as mycophenolate mofetil
complementary and alternative therapies
(CAM)
no treatment
Factors such as religious
beliefs, lifestyle, lack of financial resources or insurance coverage,
and/or health conditions that might make undergoing existing
interferon-based treatment difficult can affect the decision each person
makes.
Clinical Trials
If you are being treated at a major teaching hospital and/or by a
hepatitis C specialist, you may have access to any of a number of clinical
trials. Some of these trials will study new formulations of standard
interferon and other antiviral agents. Others will be looking at
completely new drugs or approaches to the treatment of hepatitis C. Talk
with your doctor about which of these trials might be available and
appropriate for you. The Internet is a good source of information about
clinical trials. Check the Resource Directory at the back of
this book for Internet addresses.
Many new drugs are under development and preliminary evaluation of them
may have a therapeutic role in the management of those who do not respond
to conventional, interferon-based therapy. These options may include
thymosin alpha-1, histamine analogues, oligonucleotides,
amantadine and its
analogues, inhibitors of IMPDH, and
protease inhibitors. To date, none
of these agents has been completely evaluated, nor have they been shown to
slow disease progression or reduce the risk of liver cancer.
Complementary and Alternative Medicine
If your treatment with western medicine failed to clear HCV and there is
little hope that retreatment will be successful, you may choose a CAM
treatment approach. Treatment strategies for most CAM approaches are
generally focused on reducing the amount and rate of liver damage caused
by the virus and slowing the progression of liver fibrosis.
CAM approaches to chronic hepatitis C include antioxidant therapy, Chinese
herbal remedies, Ayurvedic practices, and others. The rationale, goals,
and objectives of these treatment approaches are described in other
chapters of this book.
People exploring CAM options should be advised that these therapies have
not been fully evaluated for proof of effectiveness in controlled clinical
trials. Specifically, you must understand there is no evidence that CAM
clears HCV, slows disease progression, or reduces the risk of liver
cancer.
No Treatment
You may decide against retreatment with any of the options discussed. This
is a personal decision, but it must be made after you have carefully
weighed the information concerning the natural progression of hepatitis C
and your treatment options. The reasons people choose not to be treated
vary. Often, these decisions are related to cost, inconvenience, and the
severity of side effects of treatment.
There are major health
issues that are important for you to understand even if you elect not to
be retreated. You need to understand the natural history of hepatitis C
and the long-term consequences of infection. You need to know how the
virus affects other parts of the body in addition to the liver. This is
particularly crucial if you have advanced fibrosis or cirrhosis. If you
have advanced fibrosis or cirrhosis, you are at risk for liver
deterioration, liver failure, and the development of liver cancer. You may
eventually need a liver transplant. Your doctor or health care provider
must examine you regularly for signs of clinical deterioration. He or she
may order tests to screen for the development of liver cancer.
Summary
This chapter addresses several important clinical issues for an
increasingly large population of patients with chronic hepatitis C: those
in whom treatment failed to clear HCV. You have been provided with
information to help you determine if you should consider retreatment with
pegylated interferon plus ribavirin. You have also learned about some of
the issues surrounding maintenance interferon.
The goals of retreatment are to clear virus, slow disease progression, and
reduce the risk of liver cancer. This chapter identifies criteria for
selection of patients for retreatment and provides definitions for
response. Studies are summarized that provide information on expected
response rates should you elect to undergo retreatment with
interferon-based therapy.
Results from past and current clinical trials suggest retreatment clears
virus in a subset of non-responders. They also show that viral clearance
is especially dependent upon viral genotype. Even if the virus is not
cleared, evidence suggests you may still benefit from retreatment by
slowing disease progression and reducing your risk of liver cancer.
Definitive clinical trials such as HALT C are currently underway to
attempt to prove whether these impressions from smaller trials are
accurate. Regardless of whether you decide on retreatment, if you have
advanced fibrosis or cirrhosis, you must have regular clinical follow-up
to monitor for liver decompensation, liver failure, and the development of
liver cancer.
|
