| |
|
Budget Impact Analysis of 2 Different Methods of
Evaluating Early Viral Response to Peginterferon Alfa-2b (Peg-Intron)
Plus Ribavirin Therapy in Genotype 1 Patients
Genotype 1
patients with chronic hepatitis C are the least responsive to
peginterferon and ribavirin therapy and therefore monitoring
early virologic response (EVR)
is an important tool for identifying non-responders quickly,
permitting therapy discontinuation and avoiding side effects and
costs.
The objective of the current study was to analyze the financial
impact of two different measurement techniques for evaluating the
EVR during
peginterferon alfa-2b (Peg-Intron) plus
ribavirin therapy and to compare the results with
the full 48 week course of therapy in
genotype 1 naive patients
with chronic hepatitis C.
A financial impact
model was developed to compare two different strategies of
determining EVR and the resultant impact on treatment costs compared
with standard 48 weeks course of therapy.
Strategy 1:
peginterferon alfa-2b plus ribavirin for 12 weeks. Patients with a
decline in HCV-RNA >2 logs continue therapy to complete 48 weeks.
Strategy 2:
peginterferon alfa-2b plus ribavirin for 12 weeks. Patients with
HCV Core Ag negative
continue therapy to complete 48 weeks.
| |
EVR |
PPV (EVR and
SVR) |
|
Strategy 1 |
74% |
86% |
|
Strategy 2 |
82% |
84% |
EVR was defined at week 12 as either a decline of >2 logs in HCV RNA
levels tested with a quantitative HCV RNA assay (total 2 tests:
baseline / week12) or undetectable HCV Core Ag at week 12 (1 HCV
Core Ag test).
Clinical data
was taken from multi-center trials [JP1] , while costs were taken
from published literature based on the perspective of the Spanish
Health Care System. The base-case scenario assumed that a potential
study population of 85,000 people with genotype 1 would be eligible
for treatment in Spain.
Results
For genotype 1
patients with chronic hepatitis C, testing EVR by HCV Core Ag was
the most effective strategy resulting in 58,548 patients reaching
SVR and an overall budget of US $1,338 million (US $22,858 per
successfully treated patients).
Conversely,
evaluating EVR by means of quantitative HCV-RNA resulted in 54,094
patients and an investment of US $1,276 million (US $23,589 per
successfully treated patient). The incremental cost per successfully
treated patient with strategy 2 versus strategy 1 therefore
represents US $13,988.
Conclusion
The authors
conclude, “Assessment of EVR, specifically by HCV Core Ag test, in
genotype 1 chronic hepatitis C patients treated with peginterferon
alfa-2b and ribavirin provides an accurate tool for identifying
patients with SVR resulting in a lower overall cost. This strategy
should be recommended in current clinical practice.”
12/03/04
Reference
M Buti and others. BUDGET IMPACT ANALYSIS OF TWO
DIFFERENT METHODS OF EVALUATING EVR TO PEGINTERFERON ALFA-2B (PEGINTRON®)
PLUS RIBAVIRIN (REBETOL) THERAPY IN GENOTYPE 1 NAIVE PATIENTS WITH
CHRONIC HEPATITIS C. Abstract 427 (poster). October 29-November 2,
2004. Boston, MA.
http://www.hivandhepatitis.com/2004icr/aasld/docs/hcv/120304_a.html |
|
|
| |
Hepatitis C Infection and the Increasing Incidence of
Hepatocellular Carcinoma
A significant increase
in the incidence of
hepatocellular carcinoma (HCC) has
been reported in the United States. The risk factors underlying this
increase remain unclear.
By using Surveillance, Epidemiology, and End-Results program
(SEER)-Medicare–linked data, we conducted a population-based study to
examine temporal changes in risk factors for patients 65 years and older
diagnosed with HCC between 1993 and 1999.
Only patients with continuous Medicare enrollment for 2 years before and up
to 2 years after HCC diagnosis were examined.
Univariate and
multiple logistic regression analyses were used to evaluate changes in risk
factors over time (January 1993–June 1996 and July 1996–December 1999).
Results
The age-adjusted
incidence of HCC among persons 65 years of age and older significantly
increased from 14.2 per 100,000 in 1993 to 18.1 per 100,000 in 1999. We
identified 2584 patients with continuous Medicare enrollment 2 years before
and up to 2 years after HCC diagnosis.
The proportion of
hepatitis C virus (HCV)-related HCC increased from 11% during January of
1993 to June of 1996 to 21% during July of 1996 to December of 1999, whereas
hepatitis B virus (HBV)-related HCC increased from 6% to 11% (P <
.0001).
In multiple logistic
regression analyses that adjusted for
age, sex, race, and geographic
region, the risk for HCV-related HCC and HBV-related HCC increased by 226%
and 67%, respectively.
Idiopathic HCC decreased from 43% to 39%. This decrease did not fully
account for the significant increases observed for HCV and HBV.
No significant
changes over time were observed for
alcohol-induced liver disease,
nonspecific
cirrhosis, or nonspecific hepatitis.
Conclusion
The authors conclude,
“There has been a significant recent increase in HCV- and HBV-related HCC.
Increasing rates of HCV-related HCC can explain a substantial proportion of
the reported increase in HCC incidence during recent years.”
12/03/04
Reference
J A Davilla and others. Hepatitis C infection and the increasing incidence
of hepatocellular carcinoma: A population-based study. Gastroenterology
127(5): 1372-1380. November 2004.
http://www.hivandhepatitis.com/hep_c/news/2004/aa/120104_f.html
|
| |
Epoetin Alfa Improves Quality of Life in Anemic HCV Patients
Receiving Combination Therapy
Anemia and
decreased health-related
quality of life (HRQL)
are common
in patients receiving combination therapy of interferon alfa (IFN) and
ribavirin (RBV) for
chronic hepatitis C virus (HCV) infection.
In a
randomized, prospective study evaluating the effectiveness of
epoetin alfa
in maintaining RBV dose, alleviating
anemia,
and improving HRQL in anemic (Hb -12 g/dL) HCV-infected patients receiving
combination therapy, patients receiving epoetin alfa had significant
improvements in HRQL compared with placebo.
In this
study, 185 patients were randomized to 40,000 units of epoetin alfa
subcutaneously weekly or placebo for an 8-week double-blind phase (DBP),
followed by an 8-week open-label phase during which all patients received
epoetin alfa. To further assess the impact of epoetin alfa on HRQL, post
hoc analyses were conducted in the same patient population to compare
the HRQL of these patients at randomization with norms of other populations,
and to determine the critical relationship between hemoglobin (Hb) levels
and HRQL.
Mean HRQL
scores of anemic HCV-infected patients receiving combination therapy at
randomization were significantly lower than those of both the general
population and patients who had other chronic conditions.
Patients
receiving epoetin alfa who had the greatest Hb increases from randomization
to the end of the DBP also had the largest improvements in HRQL. Hb
improvement was an independent predictor of HRQL improvement in these
patients.
The
authors conclude, “Epoetin alfa provided clinically significant HRQL
improvement in HCV-infected patients receiving IFN/RBV therapy.”
12/03/04
Reference
P J
Pockros and others. Epoetin alfa improves quality of life in anemic HCV-infected
patients receiving combination therapy. Hepatology 40(6): 1450-1458.
Epub November 24, 2004.
http://www.hivandhepatitis.com/hep_c/news/2004/aa/120104_d.html
|
| |
Peginterferon Alfa-2a (Pegasys) and Ribavirin in Patients
with Chronic HCV and Normal ALT Levels
Patients with chronic
hepatitis C and persistently
normal alanine aminotransferase (ALT)
levels have been routinely excluded from large randomized treatment trials;
consequently, the efficacy and safety of antiviral therapy in this
population are unknown.
Patients with at least 3
normal ALT values over an 18-month period were randomized (3:3:1) to
treatment with
peginterferon alfa-2a (Pegasys) 180 ěg/wk plus
ribavirin 800 mg/day for 24 weeks (212 patients), the same
combination for 48 weeks (210 patients), or no treatment (69 patients) in a
multinational study.
All patients were
monitored for 72 weeks. The primary measure of efficacy was
sustained virologic response (SVR),
defined as undetectable
serum hepatitis C virus (HCV) RNA by
qualitative polymerase chain reaction
at the end of 24 weeks of untreated follow-up.
Results
No patient cleared HCV RNA in the untreated control group. SVR rates of 30%
and 52% were obtained in the 24- and 48-week treatment groups, respectively.
In patients infected with
HCV genotype 1, SVR rates of 13% and
40% were obtained with 24 and 48 weeks of treatment, respectively (P
< .0001).
In patients infected with
genotypes 2 or 3, SVR rates were 72% and 78% with 24 and 48 weeks of
treatment, respectively (P = .452).
Treatment-related flares
in ALT activity were not observed
Conclusions
In conclusion, the authors
write, “The efficacy and safety of peginterferon alfa-2a and ribavirin
combination therapy in patients with
chronic hepatitis C and persistently
normal ALT levels are similar to that in patients with elevated ALT levels.”
“The indication for
treatment of hepatitis C can be evaluated independently from baseline ALT
activity.”
12/03/04
Reference
S Zeuzem and others. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in
patients with chronic hepatitis C and normal. aminotransferase levels.
Gastroenterology 127(6): 1724-1732. December 2004.
http://www.hivandhepatitis.com/hep_c/news/2004/aa/120104_a.html
|
| |
Only One Therapy Option Is FDA-approved for Treatment of
Hepatitis C Infection in Children
Multiple factors support treatment of hepatitis C virus (HCV) infection in
children. These factors include the anticipated long duration of infection
after early acquisition, relatively good tolerance of antiviral medications,
and avoidance of social stigmatization.
Nevertheless, careful
selection of appropriate candidates for therapy is important. If a
contraindication to current therapeutic agents is present, treatment should
be withheld until this has resolved or until new agents are available.
Children without
contraindications to the medications used for HCV should undergo
liver biopsy to determine the presence and
degree of
fibrosis. In the absence of
fibrosis, treatment may be deferred.
If any degree of hepatic
fibrosis is present, antiviral therapy for HCV should be considered.
At present, in the United
States, the only therapy approved for children by the Food and Drug
Administration (FDA) is a
combination of interferon (IFN) alfa-2b (Intron A) and
ribavirin.
No safe therapies have
been established for children younger than 3 years of age.
Pegylated interferon in combination with ribavirin
may be considered in adolescents older than 16 years of age who are
post-pubertal, or in younger children in the context of clinical trials.
Multicenter trials are
currently underway to determine the safety and effectiveness of other forms
of therapy for HCV infection in children.
Pediatric
Gastroenterology and Nutrition, Children's Hospital of Boston, Harvard
Medical School, Boston, MA, USA.
12/06/04
Reference
A Delgado-Borrego and M M
Jonas. Treatment Options for Hepatitis C Infection in Children.
Current Treatment Options
in Gastroenterology
7(5): 373-379. October 2004.
http://www.hivandhepatitis.com/hep_c/news/2004/aa/120704_d.html
|
| |
Early Viral Kinetics and Treatment Outcome in Combination
of High-dose Interferon Induction vs. Pegylated Interferon Plus Ribavirin
for Treatment-naive HCV Patients with Genotype 1b and High Viral Load
An investigation was
carried out to determine whether early viral monitoring could predict
efficiently the virological response to combination therapy of two different
regimens in treatment-naive chronic hepatitis C patients infected with
genotype 1b with high baseline viral
load.
Patients were
randomly assigned to receive
interferon (IFN) alfa-2b (Peg-Intron) induction (6 MU
daily for 2 weeks) followed by 6 MU thrice weekly for 46
weeks (IFN/R group; n = 20), or
pegylated IFN alfa-2b (1.5 mug/kg) weekly for 48 weeks
(PEG/R group; n = 28),
in combination with ribavirin (600-1,000 mg
daily).
Serum HCV RNA was
quantitated at 0, 6, 12, 24, and 48 hr post-dose, weekly during the first 4
weeks. Thereafter viral kinetics were assessed every 4 weeks.
Results
The sustained virological response (SVR)
rates in the IFN/R and PEG/R groups were 40% (8/20) and 43% (12/28),
respectively. The non-virological response rates were 40% (8/20) and 39%
(11/28), respectively. The cumulative virological response rates were
similar in both groups.
Multivariate analyses
identified no independent baseline variables linked to sustained virological
or non-virological response.
Early log viral load
changes from baseline in both groups were significantly greater at all
time-points after 24 hr in virological response patients than in non-virological
response patients (P < 0.001 for all).
On the receiver
operating characteristics curves for prediction of non-virological response,
the area under the curves (0.951-1.000), sensitivity (90%-100%), and
negative predictive value (96%- 100%) were similar at any time-points after
24 hr.
For prediction of
sustained virological response, sensitivity of 80% with 86% negative
predictive value was observed for negative HCV RNA at week 12, with the
highest area under the curves value of 0.919.
In conclusion, the
authors write, “The results suggest that early monitoring of viral kinetics
is a useful measure to predict virological response, and might facilitate
development of rational and effective therapeutic strategies.”
Department of Gastroenterology, Toranomon Hospital, Minato-ku, Tokyo,
Japan.
12/06/04
Reference
A Tsubota and others. Early viral kinetics and treatment outcome in
combination of high-dose interferon induction vs. pegylated interferon plus
ribavirin for naive patients infected with hepatitis C virus of genotype 1b
and high viral load. Journal of Medical Virology 75(1): 27-34.
January 2005.
http://www.hivandhepatitis.com/hep_c/news/2004/aa/120704_b.html
|
| |
Pegylated interferon-alfa-2b
+ ribavirin therapy for recurrent hep C virus
|
| Combination pegylated interferon with ribavirin is effective
therapy in hepatitis C Virus recurrence and in hepatitis C virus
nonresponsive to interferon and ribavirin, reports the most recent issue
of Transplantation. |
| |
| The management issues of transplant patients with hepatitis
C virus (HCV) are complex, and interferon therapy is often ineffective.
Dr Slapak-Green and colleagues from Miami, America undertook a
retrospective review of liver-transplant recipients suffering from HCV
recurrence that were treated with pegylated alpha-2b interferon and
ribavirin.
Participants received combination pegylated alpha-2b interferon (1.5
mcg/kg/wk) and ribavirin (400-600 mg/day) and therapy intended for at
least 48 weeks.
The researchers then recorded complications, including neutropenia
(<750 cells), anemia (hemoglobin <8 g) with and without treatment
consisting of blood transfusions, erythropoietin, or dose reduction of
ribavirin, and depression.
The research team determined a diagnosis of hepatitis C virus
recurrence by an increase in liver chemistries, histopathologic findings
with inflammation along with viral recurrence using the COBAS AMPLICOR
HCV test.
 |
| 28% of patients who were naďve to therapy and 21% of
nonresponders were HCV nondetectable at the end of 48 weeks of
therapy |
| Transplantation |
The researchers included a total of 57 liver-transplant recipients in
the study.
The participants were separated into Group 1 , 29 participants naive
to therapy and Group 2, 28 nonresponders.
The research team administered at least 6 months of interferon and
ribavirin therapy.
The researchers observed that 8 (28) patients in group 1 and six
(21%) patients in group 2 were HCV nondetectable at the end of 48 weeks
of therapy.
In addition, the research team noted that ribavirin therapy was
decreased in 13 of 29 (45%) for group 1 and 11 of 28 (39%) in group 2.
Therapeutic interventions were 4 of 57 (7%) blood transfusions, 23 of
57 (40%) erythropoietin, and 17 of 57 (30%) filgrastim.
Dr Slapak-Green concluded, "Combination pegylated interferon with
ribavirin appears to be effective therapy in HCV recurrence and in HCV
nonresponsive to interferon and ribavirin."
She added, "This data reveals the difficulty and caution that must be
taken when treating HCV-R liver-transplant recipients with combination
pegylated alpha-2b interferon and ribavirin therapy."
|
|
|
|
|
Transplantation; 2004: 78(9):1303-1307
02 December 2004 |
|
| |
Controlling pain in
liver biopsy, or "we will probably need to repeat the biopsy
in a year or two to assess the response"
|
| |
| |
American Journal of Gastroenterology
Volume 96 Issue 5 Page 1327 - May 2001
Stephen H. Caldwell, M.D.
Division of Gastroenterology and Hepatology, Box 10013,
University of Virginia Health System, Charlottesville, VA
22906-0013
Liver biopsy is a fundamentally important procedure in the
evaluation of chronic and acute liver diseases. Although
specific figures are not available, the epidemic of
hepatitis C, the growing number of therapeutic options in
various liver diseases, and, more recently, the recognition
of the potential severity of fatty liver have increased the
number of biopsies in most centers over the past 10 yr.
Based on the experience at our center, where approximately
five biopsies are performed per week, it can be
conservatively estimated that over 30,000 liver biopsies are
performed annually in the US (assuming an average of three
similar centers per state). Surrogate markers for measuring
the degree of liver injury continue to attract attention but
are unlikely to supplant histological examination in the
foreseeable future (1). Because of the central role of liver
biopsy in diagnosis, staging, and assessing treatment
response, it is important to examine ways to make the
procedure more acceptable to patients. Castéra et al. have
addressed this problem in an article in this issue (2)
reporting on a placebo-controlled trial of self-administered
nitrous oxide in patients undergoing percutaneous liver
biopsy.
Postbiopsy pain is the most common complication of liver
biopsy, although the incidence varies depending on the
assessment of severity (3). Moderate to severe pain, often
requiring hospitalization, is seen in 1-5% of patients in
past series (4, 5). Aside from trauma to adjacent organs,
the pain in this situation is more often associated with the
need for blood transfusions and hence is likely related to
frank bleeding, although most recover with only supportive
measures. The higher range is seen with cutting needles (6)
(such as Tru-Cut [Travenol, Deerfield, IL]) as opposed to
aspiration needles [such as Menghini style (7) needles],
although this is disputed (5). Similarly, the amount of
moderate to severe pain experienced by the patient varies
with the experience of the practitioner (8), although there
is also disagreement on this point (5).
The incidence of less severe pain has been reported in
several studies. Pain requiring postprocedure analgesia is
seen in approximately 50% of patients undergoing biopsy with
an automated cutting needle, but this figure is reduced to
approximately 30% when ultrasound is used to guide the
cutting needle (9). In contrast, in a series of 101
consecutive patients undergoing non -ultrasound guided
biopsy with an aspiration needle (1.6 mm, Jamshidi,
Allegiance, McGaw Park, IL), 34% of the patients experienced
pain requiring analgesics (10). In this issue's Castéra et
al. study, which also used an aspiration needle (1.8 mm,
Hepafix, Braun, Melsungen, Germany), 39% of patients in the
placebo group reported postprocedure pain. Thus, the overall
frequency of pain requiring analgesics appears to be around
30-50% in patients not receiving prebiopsy medications. It
is worth noting that moderate pain was reported in about
30-40% of patients using the non-ultrasound guided
aspiration needles (Menghini style, such as Jamshidi or
Hepafix) in two studies. A similar figure for the cutting
needle was obtained only with ultrasound guidance. It is
speculative, but this difference may relate to the loss of
tactile guidance with the automated cutting needles relative
to the aspiration needles and perhaps the longer dwell-time
of the latter needle style (11).
Outside of frank trauma to adjacent organs or severe
bleeding, the mechanism of postbiopsy pain is uncertain.
Small hematoma formation has been implicated in one study
that reported that 20% of liver biopsy patients had
postbiopsy hematomas (12). However, these findings were
disputed in a number of letters written in response to that
report (13-15). On the other hand, surface bleeding at the
biopsy site is almost universal, as any laparoscopist will
attest. Oozing typically commences immediately when the
needle is withdrawn and sometimes begins with a slight gush.
Liver bleeding time-the time until the oozing spontaneously
stops-is typically 3-5 min (16). The amount of blood is
usually only 30-50 ml as estimated by gross inspection.
However, it seems likely that this hemodynamically
inconsequential amount of blood is the source of most
postbiopsy pain because of irritation of the capsule and
peritoneum. This relationship is supported by the low
frequency of pain (10%) reported in a study of percutaneous
biopsy site plugging (17) and the significantly decreased
liver bleeding time noted laparoscopically when plugging
agents are used (18).
Castéra and colleagues report a novel, convenient,
inexpensive means of controlling pain in patients undergoing
standard percutaneous liver biopsy. One hundred average risk
patients undergoing percutaneous biopsy with an aspiration
style needle (1.8 mm, Hepafix) with local xylocaine were
randomized to either a mixture of equal parts N2O/oxygen or
an oxygen placebo. The study was blinded and pain was
measured by a previously reported visual analog pain score
in which the patient made a mark on a 10-mm line to indicate
no pain (at the far left of the line) or maximal pain (at
the far right). The gas was delivered via face mask by a
self-activated device that required triggering by the
patient to activate. When drowsiness developed, the patient
relaxed the grip on the mask and thus turned off gas flow.
Using this device, the authors noted a significant decrease
in the mean reported pain scores and a complete absence of
pain in 19 patients (38%) in the treatment group versus only
two (4%) in the placebo group. One patient (2%) in the
treatment group experienced severe pain, compared to nine
(18%) in the placebo group. A nurse, trained in use of the
dispenser, supervised the administration of the nitrous
oxide, which cost an estimated $4/patient. Their results
offer potential benefit in pain relief, as compared with
results using either an aspiration or a cutting needle in
nonpremedicated patients.
In the US, the performance of percutaneous liver biopsy has
undergone remarkable changes recently. Although biopsy
remains a staple in most academic GI/hepatology units, the
procedure appears to be performed less commonly by
gastroenterologists in private practice. We recently polled
16 of our past fellows who are now in private practice. Only
one-half continued to perform liver biopsy on a routine
basis, and one-half did not perform the procedure at all.
Relatively poor reimbursement in proportion to liability for
a high risk procedure was cited as a major reason for not
performing biopsy. Although abundant historical and more
recent literature support the use of traditional
percussion-guided biopsy (19, 20), heightened worry over
liability using this method as opposed to ultrasound-guided
biopsy has added to a shift toward performance of biopsy in
the radiology suite. This carries with it a move toward more
frequent use of automated cutting needles and a rate of
postprocedure pain similar to that seen with
percussion-guided aspiration needles (around 30% requiring
postprocedure analgesia).
Although the risk of a serious problem is low, the
possibility of a severe adverse event and the uncertainty of
interpreting postprocedure pain can cause a great deal of
angst. In comparison to the utility of the procedure in
liver disease and the seriousness with which one must
approach liver biopsy, the typical reimbursement seems
remarkably casual. The relative value unit for standard
liver biopsy was 3.43 last year (Current Procedural
Terminology code 47000). In our area, this translates to a
Medicare allowable reimbursement of $106 for the
professional fee. For a procedure with potentially severe
complications, this amounts to an inadequate reimbursement
for many practitioners facing tight schedules and decreased
reimbursements in other areas. Some gastroenterologists have
adapted to this climate by incorporating ultrasound guidance
into their own practice, although the Medicare allowable for
guidance is a modest $34 in our region, whereas Blue Shield
allows $45. In comparison, the Medicare allowable for a skin
biopsy is $41.40 and that for percutaneous kidney biopsy is
$160 in our region (not calculated with ultrasound
guidance).
Is use of nitrous oxide likely to be adopted in endoscopy or
radiology units performing liver biopsy? Castéra et al. have
demonstrated the efficacy of their nitrous oxide system in
controlling pain after routine percutaneous biopsy in this
randomized, placebo-controlled trial (2). However, adoption
of the system poses several problems. First, as pointed out
by the authors, the system costs about $700 to set up
(including the delivery apparatus with valves and mask). In
addition, there are concerns about possible exposure to
personnel administering the agent. Moreover, nurse training
would be required to safely use this form of analgesia.
Nursing supervision of conscious sedation is standard in
most endoscopy units but requires additional arrangements in
many radiology suites where sedation and analgesic use has
not been standard practice. Adoption of this technique is
furthermore unlikely to avoid the need for an i.v. line
placed as a safety measure in case of a complication. In
addition, many practitioners have already adopted routine
use of premedications before the biopsy.
Thus, there are a number of obstacles that make widespread
adoption of this system unlikely in the US. On the other
hand, the authors have highlighted the need for attention to
patient comfort in this increasingly common procedure, and
they have provided evidence supporting a valid means of
substantially achieving this goal. Their findings should be
borne in mind the next time one finds oneself discussing
liver biopsy with a patient and the potential need for
repeating the biopsy at some point in the future. It is
unclear whether or not similar results in pain control could
be obtained with more routine use of prebiopsy i.v. sedation
or small doses of i.v. analgesics. However, use of a
self-activated nitrous oxide analgesic system would likely
be welcome by most patients and appears to offer effective
analgesia at a low price per patient and with a quick
recovery.
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Gastroenterology 1978;74:103-106.
6 . Piccinino F., Sagnelli E., Pasquale G., Giusti G..
Complication following percutaneous liver biopsy. A
multicenter retrospective study on 68,276 biopsies. J
Hepatol 1986;2:165-173.
7 . Menghini G.. One-second needle biopsy of the liver.
Gastroenterology 1958;35:190-199.
8 . Froehlich F., Lamy O., Fried M., Gonvers J.J.. Practice
and complications of liver biopsy-results of a nationwide
survey in Switzerland. Dig Dis Sci 1993;38:1480-1484.
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percutaneous liver biopsy. Hepatology 1996;23:1079-1083.
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and analgesic use following percutaneous liver biopsy.
Hepatology 1998;28:768A.
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randomized to 6 or 24 hours of bed rest after percutaneous
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Y.M.. Hematomas after percutaneous liver biopsy.
Gastroenterology 1988;94:249(letter).
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1988;95:575(letter).
16 . Ewe K.. Bleeding after liver biopsy does not correlate
with indices of peripheral coagulation. Dig Dis Sci
1981;26:388-393.
17 . Tobin M.V., Gilmore I.T.. Plugged liver biopsy in
patients with impaired coagulation. Dig Dis Sci
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18 . Falstrom J.K., Goodman N.C., Moore M.M., et al. Use of
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