May 16, 2005
Abstract ID: M965
R. Planas, I. Cirera,
I. Ojanguren, M. Giménez,
M. Rivera, M. Gimeno, C. Barranco, C. Tural, R. Solà
Introduction
Few studies have
examined the degree of fibrosis progression in patients with CHC non-responders
to IFN.
Aims
To assess the rate of fibrosis progression in CHC
patient’s non-responders to IFN and to identify associated variables.
Patients and methods
84 patients (50.5±1.3 years) with CHC non-responders
to IFN, and without cirrhosis in their initial biopsy, followed for 8.1±0.2
years. In 67 of them a second liver biopsy was performed after 8.6±1.7 years.
In the remaining 17 cases the second biopsy was not performed because the
diagnosis of cirrhosis was established after hepatic decompensation (10) or
hepatocellular carcinoma (7). Liver biopsy samples were re-examined blindly by
a pathologist who was unaware of the clinical and biochemical data of the
patients or the order of the biopsies. Studies on the liver biopsies included
assessment of fibrosis (METAVIR), and of steatosis.
Results
In the basal biopsy, fibrosis was F0 in 19 patients,
F1 in 19, F2 in 10 and F3 in 36. Steatosis was absent in 40 cases, but was
grade I in 36 and grade II in 8 cases. The overall rate of fibrosis progression
was 0.104 units per year. Fibrosis progression was found in 52 patients (62%)
(13/19 patients with F0 in the basal biopsy, 11/19 F1, 6/10 F2, and 22/36 F3).
Variables associated with fibrosis progression were age, HCV-RNA, GGTP, AP,
AST/ALT, platelets, cholesterol and steatosis in the initial biopsy. The
independent predictors for fibrosis progression were platelet count (OR 0.09;
95%IC: 0.01-0.67) and steatosis (OR 4.96; 5%IC: 1.11-25.5). 27 patients (32%)
developed cirrhosis (1 with F0 in the basal biopsy, 3 F1, 1 F2, and 22 F3), and
11 patients (13%) developed hepatocellular carcinoma.
Conclusions
1. The results
of this longitudinal study have shown progression of liver fibrosis, cirrhosis
and hepatocellular carcinoma development in approximately one half, one third
and one tenth, respectively, of CHC patients non-responders to IFN in a median
follow-up of 8 years.
2. The
variables independently associated with fibrosis progression were
thrombocytopenia and steatosis in the initial biopsy.
3. Re-treatment
is highly indicated in this subgroup of patients with high risk of fibrosis
progression.
Abstract ID:
M1031
Authors: J.P. Gisbert, L.
Garcia-Buey, J. Pajares, R.
Moreno-Otero
Aim
To systematically review the experience of therapeutic
studies where alfa-interferon (IFN) with or without ribavirin (RBV) was
administered to patients with lymphoproliferative
disorders, in order to evaluate whether eradication of hepatitis C virus (HCV)
may induce regression of lymphoproliferative
disorders.
Methods
Bibliographical searches were performed in several
electronic databases and in the Cochrane Controlled Trials Register, looking
for several key words related with “Hepatitis C” and “Lymphoma”. Articles
published in any language were included. Patients with only mixed
cryoglobulinemia but with no other associated lymphoproliferative
disorders were not included.
Results
Sixteen therapeutic studies where antiviral regimen
(with IFN with or without RBV) was administered to HCV-infected patients with lymphoproliferative disorders (mainly low-grade, but also intermediate/high
grade non-Hodgkin’s lymphomas) have been performed, including a total of 65
patients. Complete remission of the lymphoproliferative
disorder was achieved in 75% (95% confidence interval, 64-84%) of the cases. In
contrast with infected patients, HCV-negative subjects did not respond to IFN
therapy, indicating that the response observed in the HCV-infected patients is
not merely due to the antiproliferative effect of
IFN. Remission of lymphoproliferative disorders after
HCV eradication with IFN was maintained, provided that HCV infection did not
reappear; however, viral relapse was usually followed by recurrence of
lymphoma. Several studies demonstrated a similar response to chemotherapy in
non-Hodgkin’s lymphoma patients infected and non-infected with HCV. It was
reported that in HCV-infected patients with non-Hodgkin’s lymphoma treated with
corticoids and chemotherapy liver function tests deterioration did not occur,
thus indicating that immunosuppressive therapy does not, apparently, increase
HCV replication. Some studies suggest that the addition of IFN to standard CHOP
may decrease hepatic side effects of chemotherapy.
Conclusion
Although it is evident that larger therapeutical
trials of antiviral therapy are needed to determine the role of this strategy
in HCV-infected patients with lymphoproliferative
disorders, encouraging data emerge from recent studies showing that IFN (plus
RBV) is an attractive therapeutic option for some HCV-related low-grade
lymphomas. Multicenter controlled studies with
pegylated IFN plus RBV are eagerly awaited.
Abstract ID: M1236
Authors: J.K. Lim, J.S. Ng, D.D. Proctor
BACKGROUND/AIMS
Primary care physicians may be inadequately prepared
to evaluate and manage patients with chronic HCV infection. Identification of specific areas of knowledge
deficit among internal medicine residents may provide targets for educational
intervention.
METHODS
We administered a structured 1-page survey assessing
knowledge and practices regarding HCV infection to 251 internal medicine
residents at 8 ACGME-accredited U.S. training programs.
RESULTS
Residents were equally distributed among three
post-graduate years. 89.6% were U.S. medical graduates, most were enrolled in
traditional (64.9%) or primary care (22.7%) programs, and nearly all (98.0%)
had seen patients with HCV within the past year, 60.6% of whom had seen >10
patients. Although most screen for HCV in patients with abnormal LFT’s (85.3%), prior needlestick
exposure (82.1%), prior IVDU (80.9%), or HIV co-infection (77.7%), few
performed screening in other at-risk populations, including individuals with a
history of transfusion (59.8%), snorting cocaine (26.7%), or incarceration
(21.5%). Only 45.5% and 36.7%, respectively, use the diagnostic tests HCV PCR
and genotype appropriately. Only a fraction vaccinate HCV (+) patients for
protection against HAV (33.1%) or HBV (61.4%), and few were familiar with
recommended vaccination schedules, 19.5% and 64.5%, respectively. Some report
they vaccinate HCV (-) individuals with HCV vaccine (20.3%) although it does
not exist. Only 25.5% and 22.3%, respectively, correctly identified genotype 1
as the most common in the U.S., and least responsive to antiviral therapy. Only 30.7% named HCV as the #1 indication for
liver transplantation. Although most correctly cited EtOH
(80.5%), HIV (75.3%), and HBV (64.1%) as risk factors for disease progression,
only 10.0% and 14.7%, respectively, correctly estimated the rate of chronic viremia following exposure, and risk for developing
cirrhosis at 20 yrs of infection. Only 35.5% identified IFN/RV or PEG-IFN/RV as
1st line antiviral therapy – 30.7% incorrectly named lamivudine. Few
residents feel adequately trained in HCV management (23.9%).
CONCLUSIONS
Many internal medicine residents receive inadequate
training in the management of chronic HCV infection. Most lack basic knowledge
regarding the epidemiology, natural history, diagnosis, clinical course, and
treatment of HCV. Targeted educational interventions are needed to address
knowledge deficits among future primary care physicians.
Abstract ID:
M1239
Authors: N.B. Shukla, C. Tenner, A. Aytaman, G.
Villanueva, E.J. Bini
BACKGROUND
Knowledge of risk factors for acquiring HCV infection
is crucial to reduce transmission. The aim of our study was to assess patient
knowledge of modes of HCV infection and long-term health problems.
METHODS
403 patients with chronic HCV infection and 556 HCV
negative controls completed a survey at the time of their outpatient clinic
visit at 3 study sites. Data collected included patient demographics, knowledge
of HCV risk factors, and HCV-associated health problems. Each patient completed anonymous
questionnaire of 14 questions. Limited knowledge of participants was defined as
less than 25% of correct answers.
RESULTS
·
The median patient age was 57 years (HCV + pts, 56.3 ±
9.7; HCV - pts, 56.4 ± 11.1), 87.8% were male,
·
The majority were of low socioeconomic status.
·
The demographic characteristics of the HCV+ and HCV-
patients were similar.
·
Ethnic/Racial characteristics:
o Non-Hispanic
White- HCV + = 29.3%, HCV – = 45.7%
o Non-Hispanic
Black – HCV + = 40.7%, HCV - = 31.7%
o Hispanics –
HCV + = 24.6%, HCV - = 17.1
o Other - HCV + = 5.5%, HCV – 5.6%
·
Alcohol use:
o None – HCV +
= 68.5%, HCV - = 54.9%
o 1-6
drinks/day – HCV + = 22.1%, HCV - = 35.4%
o 7 or more
drinks/day – HCV + = 9.4%, HCV - = 9.7%
·
HCV+ and HCV- subjects, respectively, agreed/strongly
agreed:
o HCV can be
transmitted by one-time injection drug use (74.4% vs. 61.9%, P <0.001),
o Blood
transfusion (72.7% vs 51.3%, P <0.001),
o Sexual
intercourse (65.0% vs 58.8%, P = 0.52),
o Tattoos (72.7%
vs 51.3%, P <0.001),
o Body
piercing (69.0% vs 48.6%, P <0.001),
o Sharing
razors (72.5% vs 51.4%, P <0.001)
o Toothbrushes
(58.3% vs 46.4%, P <0.001),
o Holding
hands (4.7% vs 9.9%, P <0.003),
o Coughing
(59.2% vs 25.2%, P <0.001),
o Eating
contaminated food (17.9% vs 31.3%, P <0.001).
o Mother to
child (53.3% vs. 56.8%, P=2.8)
HCV+ patients were less likely to think that IV drug
use is the only way to get HCV (25.1% vs. 31.7%, P = 0.002) and more likely to
know that condoms protect against HCV infection (63.8% vs. 40.5%, P <0.001).
Among HCV+ patients, whites were more likely than blacks, Hispanics, or other
races to know that one-time injection drug use (94.1% vs
74.6% vs 78.3% vs 71.4%, P
= 0.003) and blood transfusions (94.8% vs 74.4%, vs 78.1%, vs 78.6%, P = 0.004)
were risk factors for HCV infection and that condoms can prevent HCV
transmission (84.4% vs 57.9% vs
56.2% vs 50.0%, P <0.001).
CONCLUSIONS
1. Patient
knowledge of risk factors for HCV infection and transmission is limited,
especially among those who are not infected.
2. Limited
knowledge of risk factors for HCV infection was more common among older patients,
those of low socioeconomic status, and racial ethnic minorities.
3. Public health programs to educate patients
about HCV risk factors are needed to reduce HCV transmission.
Abstract ID:
M1238
Authors: F. Serejo, A. Costa, M.C. Moura, M.J.
Lacerda
BACKGROUND
The mechanisms of fibrogenesis in chronic hepatitis C
are not well understood. Human liver stellate cells
(LSC) express the á-isotype of actine,
specific to smooth muscle cell differenciation. Aims:
to evaluate the expression of á-smooth muscle actin (á-SMA) in liver stellate cells of chronic hepatitis C patients, to
correlate with Histological Activity Index (HAI), with fibrogenic
markers (PIIIP and TGF â1) and whether such expression can be modified by
anti-viral therapy.
Methods
30 chronic hepatitis C patients (pts) were treated
with á-interferon 3MU s.c.,
tiw, 6 to 12 months + ribavirin (1000-1200 mg/day),
22 male and 8 female, mean age 37.5 ± 12.8 years. HAI before and after therapy,
was graded according Knodell / Peter Scheuer
(Hepatology 1992;15). Using immunohistochemistry and
the semi-quantitative method of Shmith-Graff (Am J Pathol 1991; 138) we evaluated á-SMA
expression in liver stellate cells before and after
anti-viral therapy (Liver stellate cell index –LSCI
in 6 controls= 0.4 ± 0.2). Serum aminoterminal propeptide of procollagen type
III (PIIIP) was quantified by RIA (Riagnost PIIIP c.t. Biodesign, 20 controls= 0.4 ± 0.2 U/L). Transforming growth
factor â1 (TGFâ1) was quantified by Tsushima method (J Hepatol 1999; 30) (6
controls: plasma= 4.4 ± 0.7 ng/ml; tissue= 3.4 ± 0.6 ng/g protein).
Results
Before therapy, a significantly
great numbers of á-SMA reactive LSC were present
throughout all acinar zones comparing with controls
(LSCI =2.5 ± 1.7 vs 0.4 ± 0.2, p <0.005). A
significant reduction in á-SMA reactivity of LSC was
noticed in liver biopsies performed 6 months after stop anti-viral therapy
(LSCI before= 2.5 ± 1.7; after= 1.5 ± 0.7), p <0.005. A significant
correlation was seen between portal á-SMA reactive
LSC and fibrosis staging (r= 0.42 p <0.03) but not with grading. Sinusoidal á-SMA reactive LSC correlates with PIIIP (r= 0.39 p =0.04)
and TGFâ1 (plasma r= 0.50 p =0.04; tissue r=0.56 p=0.02) but not with the HAI
scores. Comparing the different types of response, the drop in the number of á-SMA reactive LSC was only significant in the 10 sustained
responders (LSCI before= 1.2 ± 0.6; after= 0.4 ± 0.8, p <0.03) and was
associated with a significant improvement of HAI.
Conclusions
The mechanisms of fibrogenesis in chronic hepatitis C
may have different pathways involving the activaction
of stellate cells, suggesting an anti-fibrotic effect
of á-interferon especially on sustained responders.
Abstract ID:
M1241
Authors: M. Takase, K. Abe, E. Murashima, K. Ueda, K. Maruta, T. Katagami, M. Yamada, S. Sugiki, M. Miyaoka
Introduction
In chronic hepatitis C
(CH-C), it is said that the intrahepatic iron volume influences the effects of
IFN therapy and liver function stability.
Aims
We examined the
significance of measuring blood ferritin levels by
measuring dynamics of blood ferritin levels before,
during (after 2, 4, and12 weeks), directly after, and more than 6 months after
administration of interferon and ribavirin (IFN+Rib)
in chronic hepatitis C, and comparing the results of the therapeutic effect,
and further by examining the relationships with liver function(ALT), blood
platelets (PLT), and host immunocytokines (Th1:IL-18,
Th2:IL-10) before and after administration. Subjects were 64 patients
(M/F35/29; Mean age: 52.5) who underwent IFN+Rib
administration. Those who remained negative for blood HCV-RNA 6 months after
the treatment and maintained normal ALT level for at least 6 months were
defined as complete response (CR) cases, and all other cases were defined as
non-response (NR) cases.
Results
Compared to before IFN +
Rib administration, blood ferritin levels
significantly increased to a peak after 2 weeks of administration (total:
p<0.0001,CR: p=0.0009,NR: p=0.0016), and it was significantly high also
after 4 weeks (total: p<0.0001, CR: p<0.0001, NR: p=0.0002) and after 12
weeks (total: p=0.0034,CR: p=0.0283, NR: p=0.0283), but there were no
significant differences immediately after the completion of administration.
However, after the completion of administration, the level significantly
decreased from the pre-administration level in CR cases (p=0.0015). Blood ferritin levels after 4 weeks of administration (p=0.0016)
and after the completion of administration (p=0.0011) was shown to
significantly decrease more in CR cases than in NR cases. Examination of the
correlation with blood ferritin levels before and
after administration revealed that before administration, there was a
correlation with ALT (r=0.513; p<0.0001) and after administration, there was
a correlation with ALT (r=0.488; p=0.0001) and IL-18(r=0.597; p<0.0001).
Conclusions
1. Blood ferritin levels correlated with liver function before and
after administration.
2. Blood ferritin levels after 4 weeks of IFN + Rib therapy might
act as a predictor of therapy effectiveness.
3. It might be
possible to assess the effectiveness of treatment by blood ferritin
levels after the completion of administration.
4. Blood ferritin levels were related to the Th1 system immune
response caused by IFN + Rib therapy.
Abstract ID:
M1233
Authors: J. Uribe, T. Matheus, M. Dejongh, V. Araya, S.
Muñoz
BACKGROUND
Emerging data indicates that chronic hepatitis C virus
infection (HCV) has a differential impact in Caucasian and African American
patients in terms of response to antiviral therapy and possibly natural
history. Little is known on the features of HCV infection in Hispanic patients,
in spite of the fact that the last population census revealed that Hispanics
are one of the largest ethnic groups (12.5 % of U.S. population). It is projected by the year 2010 that
Hispanics will comprise 15% of the U.S. population, which will make it the
largest minority group in the United States.
AIM
We evaluated the care of HCV in a large cohort of
Hispanic patients.
METHODS
Medical records of 150 consecutive Hispanic patients
attending an urban academic gastroenterology and hepatology
practice in the Mid Atlantic U.S. were carefully reviewed to determine demographics,
status of initial evaluation, extent of follow up, viral load, genotype,
frequency of liver biopsy and antiviral therapy. As controls, the same variables were also
studied in a cohort of 100 randomly selected Caucasian patients.
RESULTS
The proportion of females and the frequency of obesity
were similar between Hispanics and controls although the former were somewhat
younger (44.7 vs. 47.68 years; p<
0.01). A significantly smaller proportion of Hispanics completed the initial
evaluation of HCV compared to controls (56.7% vs. 74%; p< 0.01), but the
groups were not different in terms of follow up compliance. Distribution of HCV genotypes were similar in
both groups but a significantly greater number of Hispanic patients had low
viral loads (< 600,000 U/ml, 70.8% vs. 59.4%; p< 0.01). The proportions
of Hispanic patients who had a diagnostic liver biopsy or underwent antiviral
therapy with interferon (49.3% and 31.8%, respectively) were significantly
lower than the proportions observed in
Caucasian controls (81% and 48%, respectively; p< 0.01). This may be
due to genetic variation, dietary factors or lifestyle factors.
CONCLUSIONS
Hispanic patients with chronic HCV complete their
initial evaluation, undergo liver biopsy and receive interferon treatment less
often than Caucasians. However, Hispanics have similar genotype distribution,
follow up visits, and are more likely to have low viral levels, a favorable
predictor of response to antiviral therapy. Additional studies are necessary to
determine the reasons for the lower frequency of completion of evaluation,
liver biopsy and therapy in this ethnic group
Abstract ID:
M1229
H. Uto,
K. Hayashi, K. Kusumoto, S.
Kanmura, H. Abe, M. Numata, S. Hasuike, k. Nagata, A. Ido, S.O. Stuver, H. Tsubouchi
Background
It is important to clarify whether hepatitis C virus (HCV)
carriers with persistently normal serum alanine aminotransferase (ALT) levels
progress to liver disease, in order to assess the necessity of interferon
therapy. We conducted a cohort study in
a hyperendemic area of HCV infection in Japan and
examined the clinical features and natural course of HCV carriers with
persistently normal ALT levels.
Methods and Results
Twenty-one percent of residents were seropositive for
anti-HCV antibodies. In 1995, 591 of 836
anti-HCV seropositive residents were positive for HCV core antigen (HCVcAg) (by fluorescence enzyme immunoassay) and/or HCV RNA
(by reverse transcription polymerase chain reaction). Of these HCV carriers, 449 had at least four
available ALT measurements taken annually between 1993 and 2000 and did not
report receiving interferon therapy. One
hundred sixty-two residents had persistently normal ALT levels (<35 IU/L)
(group N), and 287 had abnormal levels (group A). Although there was no difference in HCVcAg levels between the two groups in 1995, the frequency
of infection in females and serologically-defined (serotype) II infections was
significantly higher in group N (75.9 and 40.3%, respectively) than in group A
(56.4 and 29.3%, respectively) (P<0.001 and P=0.03, respectively). Furthermore, spontaneous elimination of serum
HCV RNA was observed in three residents in group N and two in group A between
1996 and 2002. Although there was a
significant relationship between the loss of HCV RNA and low levels of HCVcAg (<20 pg/ml) (P=0.03), this elimination was not
related to ALT status, gender, or serotype.
Hepatocellular carcinoma (HCC) was observed in seven residents in group
A subjects, but none in group N, between January 2001 and September 2004.
Conclusions
HCV-infected residents with persistently normal ALT
are not rare in this community-based population and are more likely to be
female or to have serotype II infections.
Furthermore, the spontaneous elimination of HCV RNA is highly unusual
and unrelated to ALT status, while occurrence of HCC may be associated with ALT
status. Based on the findings of our
study, treatment of HCV carriers with stable, normal ALT levels may not be
necessary.
Abstract ID:
M1219
B. Danesh, J. Kim, D.A. Labowitz, A. Davatgarzadeh, P. Suwandhi, A. Walfish, I.M. Grosman, D. Clain, H.C. Bodenheimer, Jr., A.D. Min
Introduction
The aspartate aminotransferase-to-platelet
ratio index (APRI) has been developed as a simple, non-invasive, inexpensive
predictor of significant fibrosis and cirrhosis in patients with chronic
hepatitis C (CHC). Since patients infected with the human immunodeficiency
virus (HIV) often have aspartate aminotransferase (AST) and platelet (PLT)
abnormalities, this index may not be as accurate in patients co-infected with
HIV. We sought to determine the accuracy of the APRI in patients with CHC and
HIV co-infection.
Methods
56 CHC patients
co-infected with HIV who had undergone liver biopsies were identified, and
compared with 56 age- and gender-matched non-HIV CHC patients with available
liver histology. Hepatitis C viral load, AST value and its upper limit of
normal (ULN), PLT count, and modified Ishak fibrosis stage (FS) were obtained.
4 HIV patients and 3 non-HIV patients were excluded because of missing lab
values. All lab data were within 6 months of the liver biopsy date. The APRI was calculated using the formula:
(AST / ULN) / PLT count) x 100. The
sensitivity, specificity, positive predictive value (PPV), and negative
predictive value (NPV) of the APRI in predicting significant fibrosis (FS³2) and cirrhosis (FS=4) were then
calculated.
Results
The mean age of the 52
patients with HIV (46.4 ± 6.7) was similar to that of the 53 patients without
HIV (48.5 ± 8.4). The mean FS (2.4 ± 1
vs. 2.1 ± 1.1) and the gender of the
patients were also similar (82% vs. 82.5% male). The data on accuracy of the
APRI in predicting significant fibrosis or cirrhosis are presented in the table
1.
Table 1.
|
|
APRI |
Sensitivity (%) |
Specificity (%) |
PPV (%) |
NPV (%) |
||||
|
HIV+ |
HIV- |
HIV+ |
HIV- |
HIV+ |
HIV- |
HIV+ |
HIV- |
||
|
Prediction of significant fibrosis |
> 0.50 |
86 |
69 |
56 |
43 |
90 |
77 |
45 |
33 |
|
> 1.50 |
33 |
10 |
100 |
100 |
100 |
100 |
24 |
29 |
|
|
Prediction of cirrhosis |
> 1.00 |
60 |
100 |
53 |
81 |
12 |
36 |
92 |
100 |
|
> 2.00 |
40 |
40 |
83 |
98 |
20 |
67 |
93 |
94 |
|
Accuracy of APCI in predicting significant fibrosis
and cirrhosis in HCV mono-infected patients presented by Berg et al and Wai et. al
|
|
APRI |
Sensitivity (%) |
Specificity (%) |
PPV (%) |
NPV (%) |
||||
|
Berg |
Wai |
Berg |
Wai |
Berg |
Wai |
Berg |
Wai |
||
|
Prediction of significant fibrosis |
> 0.50 |
89 |
91 |
53 |
47 |
66 |
61 |
73 |
86 |
|
> 1.50 |
37 |
41 |
|||||||