HEPATOLOGY WATCH®
SPECIAL
ISSUE: NAVIGATING THE CLINICAL AND MEDICAL/LEGAL LANDSCAPE
AASLD
SATELLITE SYMPOSIUM, NOVEMBER, 2002
The purpose of this symposium,
chaired by Dr. Luis Balart, was to review medical/legal and risk/benefit issues
associated with the considerable variation in the use of antiviral therapy for
the management of chronic hepatitis C virus (HCV) infection.
Peginterferon (PEG-INF) in the management of HCV infection. Dr. Donald
Jensen reviewed the sustained virological response (SVR) rates from the initial
studies of PEG-IFN monotherapy vs. standard IFN: PEG-IFN alfa-2b 1 µg/kg and
1.5 µg/kg weekly (25% and 23% vs. 12%), and PEG-IFN alfa-2a 180 µg weekly (39%
vs.19%). In a study of chronic hepatitis C and cirrhosis, 30% achieved an SVR
with PEG-IFN alfa-2a. In combination trials, the maximum SVR using PEG-IFN
alfa-2b plus ribavirin (RBV) was achieved using PEG-IFN alfa-2b at 1.5 µg
weekly plus RBV 800 mg/d, i.e., 54%. When results were analyzed by genotype,
the SVR for patients with genotype 1 was 42% vs. 82% for those with genotypes 2
and 3. Of patients with genotype 1, those with a high viral load (HVL) of >2
x 106 copies/mL had an SVR of 30%, vs. 68% in those with a low viral
load (LVL) of ≤ 2 x 106 copies/mL. In combination treatment
trials using PEG-IFN alfa-2a 180 µg weekly plus RBV 1,000-1,200 mg/d, the
overall SVR was 56%. When analyzed by genotype, 46% of patients with genotype 1
vs. 76% with genotypes 2 or 3 had a SVR.
When patients with genotype 1 were further analyzed, 41% with a HVL vs.
56% with a LVL had a SVR. Both of these trials were conducted over 48 wk. A
recent study, in which patients were randomized to PEG-IFN alfa-2a 180 µg
weekly plus RBV for either 24 or 48 wk, and with either 800 mg/d or 1,000-1,200
mg/d, showed that genotype 1 patients required 48 wk and the higher dose of RBV
for a maximum SVR, while genotypes 2 or 3 patients achieved maximal SVR with 24
wk of therapy and 800 mg/d of RBV.
Medical-legal considerations in gastroenterology. Dr. Brian
Boyle confirmed that most malpractice lawsuits are based on an allegation of
negligence, i.e., the physician failed to meet the standard of care, and as a
result, the patient suffered an injury. Claims involving drug-related adverse
events typically involves allegations that: 1) the drug was unsafe; 2) the drug
was prescribed in an unsafe or negligent manner; or 3) there was failure to
obtain appropriate informed consent. Physicians prescribing a drug for
off-label use, based on unique circumstances or new data, should be more
cautious regarding knowledge of the indications, contraindications, warnings,
precautions and proper dosing of the drug; informed consent; monitoring; and
proper documentation. Another potential source of liability for practitioners
prescribing drugs is based upon failure to properly monitor the patient after a
course of therapy has been initiated. Practitioners should be aware that what
is contained in the PDR will almost always be presented to a jury.
Benefit/risk assessment of HCV treatment practices. Dr. Mitchell Shiffman stated that in patients
with mild chronic hepatitis C (stage 0-1 fibrosis and minimal inflammation),
the side effects of antiviral therapy far outweigh the need to obtain an SVR. However,
in patients with advanced disease, the goal is to achieve an SVR; thus, the
risk/benefit ratio shifts toward tolerating and managing side effects. The
early virological response (EVR), defined as either negative or 2-log drop in
HCV RNA during the first 12 weeks of therapy, is a useful predictor of SVR. In
the PEG-IFN alfa-2a plus RBV pivotal trial, there was a high negative
predictive value for the EVR - 97% without an EVR did not achieve a SVR.
Another important factor from retrospective analyses of pivotal trials is the
importance of adherence to therapy. Using the definition of taking 80% of RBV
and 80% of PEG-IFN for 80% of the time, an SVR was achieved in 62% of patients
receiving PEG-IFN alfa-2b 1.5 µg/wk and RBV 800 mg/d who were adherent over 48
wk vs. 51% adherent for >12 wk and 34% adherent < 12 wk. Patients were
generally not adherent to therapy because of fatigue and poor quality of life
or dose reduction secondary to anemia, neutropenia or thrombocytopenia. There
are no randomized trials supporting efficacy of GCSF for neutropenia or epoetin
for anemia. In addition, there are no reports of severe infections secondary to
neutropenia in major trials, and a white blood cell count down to 500 cells and
platelet counts of >25,000 are well tolerated.
Billing and coding issues for gastroenterology. Cecile
Katzoff, MGA addressed the standard evaluation and management services and use
of CPT codes, including required documentation, for new and established
outpatients, inpatients and outpatient consultations, inpatient hospital
visits, and counseling and coordination of care and consultation.
2002 NIH Consensus Conference guidelines. Dr.
Adrian DiBisceglie stated that liver biopsy remains the standard of care to
determine the stage of fibrosis and grade of inflammation, but may not be
necessary in all patients, such as those with genotypes 2 and 3 with a
favorable SVR. Patients with mildly elevated ALT levels and minimal or no
fibrosis have a favorable prognosis and may defer therapy. In patients with
persistently normal ALT, experts differ whether to biopsy and treat these
individuals, although there is agreement that SVR rates are not different. SVR
is the best indicator of effective therapy, and the highest response rates
occur with PEG-IFN plus RBV. For patients with genotypes 2 and 3, 24 wk of
therapy and RBV at 800 mg/d is sufficient, while patients with genotype 1 need
48 wk of treatment and standard doses of RBV. EVR is predictive of SVR and
should be used routinely for patients with genotype 1; treatment need not be
extended beyond 12 wk in patients who fail to achieve an EVR. Patients with
decompensated cirrhosis should only be treated with antiviral therapy in
clinical trials, and there were no recommendations for post-transplant
management of recurrent hepatitis C. The most effective retreatment strategy
remains unknown, since only 15-20% of nonresponders will have an SVR. Side
effects should be managed by patient education and the possible use of SSRIs;
hematopoetic growth factors may be useful to prevent dose decrease or
discontinuation, but have not been proven beneficial.
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