丙肝治疗指南2006（英文）

American Gastroenterological Association Medical Position
Statement on the Management of Hepatitis C
Hepatitis C accounts for a sizable proportion of
cases of chronic liver disease, liver disease
deaths, and cases of hepatocellular carcinoma and represents
the most common indication for liver transplantation.宁波大学医学院附属医院消化内科丁勇
Projections based on the current prevalence
of infection and anticipated rates of progression
suggest that the morbidity and mortality, as well as
the medical care costs attributable to hepatitis C virus
(HCV) infection, will escalate alarmingly during the
next 2 decades.
The substantial clinical and economic impact of
hepatitis C focuses attention on the critical need to
prevent and control HCV infection. Public health
measures, changes in behavior to avoid blood-borne
infections, and screening of donated blood and organs
for HCV have reduced dramatically the frequency of
new infections, and substantial progress has been
achieved in antiviral therapy for hepatitis C. Applied
effectively, contemporary antiviral therapy can prevent
chronic infection in almost all persons with acute
hepatitis C and can cure chronic liver disease associated
with HCV infection in as many as half of patients
with compensated, HCV-associated liver disease. In
short, hepatitis C is an important public health problem
whose consequences can be reduced by appropriate
application of antiviral therapy. Because the demand
for management of chronic hepatitis C has
increased so considerably over the past decade, the
American Gastroenterological Association developed a
technical review1 and this medical position statement.
This medical position statement, which contains
practice guidelines intended for physicians, nurse
practitioners, physician assistants, and other health
care workers who participate in the care of patients
with hepatitis C, includes suggestions for preferable
approaches to the management of persons with hepatitis
C. These guidelines, which are recommendations
intended to assist physicians and other health care
workers in arriving at reasoned patient care decisions,2
are designed to be flexible rather than rigidly inflexible
universally applied “standards of care.” Although
these recommendations should be followed in most
cases, management decisions are left to the individual
physician and health care worker based on the circumstances
of the individual patient. As in previous guidelines
issued by the American Gastroenterological Association,
specific recommendations are based on
relevant published information.
Screening
Routine screening of all asymptomatic adults,
who have a low prior probability of HCV infection, is
not recommended. Among high-risk groups (eg, injection
drug users, persons who received a transfusion
before 1992 [when donor screening for antibody to
HCV was introduced], persons with hemophilia who
received clotting factors before 1987, persons with
frequent percutaneous exposures, immigrants from
countries with a high prevalence of HCV infection,
and persons with clinical or biochemical evidence for
chronic liver disease, even among asymptomatic persons),
diagnostic testing for HCV infection has been
recommended by the US Public Health Service, expert
panels, and professional medical specialty societies.
Spouses of persons with chronic hepatitis C are also
candidates for HCV serologic testing. Persons in
whom the diagnosis of hepatitis C is established are
candidates for hepatitis A and hepatitis B vaccines.
Pretreatment Diagnostic Evaluation
of Patients With Chronic
Hepatitis C
Persons with a reactive enzyme immunoassay
for antibody to HCV, the presence of HCV RNA, and
compensated liver disease are potential candidates for
antiviral therapy. Currently, antiviral therapy is not
recommended routinely for patients with hepatic decompensation;
patients with a history of severe, uncontrolled
psychiatric disorder; and/or patients with
severe hematologic cytopenias.
Elevation of alanine aminotransferase (ALT) and
aspartate aminotransferase levels is not a requirement
for therapy. All candidates for antiviral therapy should
be tested for HCV RNA with a quantitative amplification
assay and should be tested for HCV genotype.
Patients in whom antiviral therapy is being considered
are candidates for liver biopsy, the gold standard for
© 2006 by the American Gastroenterological Association
0016-5085/06/$32.00
doi:10.1053/j.gastro.2005.11.011
GASTROENTEROLOGY 2006;130:225–230

determining histologic grade and stage, unless the potential
for complications is unacceptably high. For patients
with moderate to severe fibrosis (Ishak stage
3,
METAVIR stage
F2; please see technical review1 for
histologic scoring systems), antiviral therapy is recommended
uniformly. For patients with milder histologic
disease, progression may be sufficiently slow to justify
monitoring without imminent therapeutic intervention
in a proportion of these patients (see Treatment Recommendations).
For patients with genotypes 2 and 3, the
likelihood of response is so high that the benefits of
treatment may outweigh the importance of histologic
considerations; therefore, some authorities forego a baseline
liver biopsy in patients with genotypes 2 and 3. Data
to support routine ultrasonography for localization of the
liver before liver biopsy are insufficient to justify mandating
prebiopsy ultrasonography in all cases and for all
practitioners regardless of levels of skill and experience.
Treatment of Chronic Hepatitis C
The current standard of care for the treatment
of previously untreated patients with chronic hepatitis
C is combination pegylated interferon (PEG-IFN) alfa
by subcutaneous injection once a week and oral ribavirin
daily. For patients with contraindications to
ribavirin but who have indications for antiviral therapy,
PEG-IFN represents the best available treatment.
Two PEG-IFN alfa preparations are available: (1)
PEG-IFN alfa-2b, administered at a weight-based,
1.5-
g/kg dose, and (2) PEG IFN alfa-2a, administered
at a fixed, 180-
g dose. Randomized controlled
trials (RCTs) have shown that combination PEG-IFN
alfa and ribavirin therapy can achieve a sustained
virologic response (SVR) in 54%–56% of patients:
42%–52% of patients with genotype 1 and 76%–84%
of those with genotypes 2 and 3. Whether one of these
PEG-IFN/ribavirin regimens or weight-based modifications
of the 2 regimens will prove to be superior is
the subject of ongoing trials. Predictors of response to
therapy in these large RCTs are displayed in Table 1.
The results of a single, large RCT support a recommendation
that patients with genotype 1 require 48
weeks of therapy with higher daily doses of ribavirin
(1000 –1200 mg, depending on weight 75 or
75
kg) (some clinicians may wish to adhere to the Food
and Drug Administration–approved 800 mg daily
dose of ribavirin when used with PEG-IFN alfa-2b,
especially in patients who weigh 65 kg), while
patients with the more treatment-favorable genotypes
2 and 3 can be treated for only 24 weeks and with only
800 mg of ribavirin daily. Moreover, 12 weeks of
therapy suffices in patients with genotypes 2 and 3 in
whom HCV RNA levels are undetectable at week 4. In
the group of patients with genotypes 2 and 3, patients
with genotype 2 are more likely than those with
genotype 3 to achieve an SVR; for patients with
genotype 3 who have high levels of HCV RNA or
advanced fibrosis on liver biopsy, many authorities
recommend treatment for 48 weeks. Pending additional
data, in patients with genotypes 2 and 3, clinicians
may wish to consider higher doses of ribavirin
or a longer duration of therapy on an individual basis,
taking into account considerations such as high viral
level, cirrhosis, or delayed response to therapy. For
patients with genotype 4, 48 weeks of treatment with
PEG-IFN alfa plus full-dose (1000 –1200 mg) ribavirin
is recommended. The potential added benefit of a
broader range (800 –1400 mg) of ribavirin weightbased
dosing as part of combination therapy with
PEG-IFN is currently being studied.
Therapy is indicated for previously untreated patients
with chronic hepatitis C, circulating HCV
RNA, elevated aminotransferase levels, evidence on
liver biopsy of moderate to severe hepatitis grade and
stage (METAVIR stage
F2, Ishak stage
3, septal
or bridging fibrosis), and compensated liver disease.
Patients with milder histologic changes (METAVIR
stage F1, Ishak stage 3) (and normal serum
aminotransferase activity; see following text) appear to
respond as well as patients with more advanced histologic
changes; such patients can be counseled about
the reduced risk of disease progression but still can be
offered therapy. If a decision is made to defer therapy
in patients with mild disease, periodic laboratory and
histologic monitoring should be pursued; however,
data to support a recommendation on the frequency of
histologic monitoring are wanting.
Table 1. Predictors of Response to PEG-IFN Plus Ribavirin
Therapy in RCTs Conducted in Previously
Untreated, Immunocompetent Patients With
Compensated Chronic Hepatitis C
Non-genotype 1
Low HCV RNA levels
Absence of cirrhosis/bridging fibrosis
Duration of therapy (for genotype 1)
Age 40 years or younger
Lighter body weight
Nonblack ethnicity
Adherence
Absence of steatosis on liver biopsy
NOTE. Non-genotype 1 is the most influential predictor of response to
standard of care therapy with combination PEG-IFN plus ribavirin. The
relative weighting of variables analyzed in RCTs of PEG-IFN/ribavirin
combination therapy is presented in the technical review.1
226 AMERICAN GASTROENTEROLOGICAL ASSOCIATION GASTROENTEROLOGY Vol. 130, No. 1