PBCers MEETING THE
CHALLENGE
PBC
Conference 2003 "Progressing
Through Education, Research & Support" Sunday,
May 4 - Thursday, May 8, 2003 New Palace Hotel, ___________________ Note
from one of your Editors… I bet some of you are wondering how
important can the Conference be to me?
What will I get from attending a Conference? Well, let me tell you
that I have been to every single one of our Conferences and each
year I learned something new; made a new friendship; and continued the
fight against PBC. This year my
husband is going with me and I know the impact of listening to the speakers,
meeting PBCers and learning about some of the most recent research in the
medical fields fight against PBC will be awesome. Please join us – you will never regret
it! Linda
Lynch PBC
& AIH ___________________________________
The purpose of our medical conference is to give PBCers, other liver
disease patients, family members, friends and the medical community a
chance to learn more about PBC, other liver diseases, current research, new
treatments, share
experiences, and have some relaxing fun.
Form and mailing instructions are located on our website.
http://pbcers.org/MC2003.htm and
in this Newsletter. Please make sure
you include the conference fee form with your check or money order.
Please refer to Page 7 of this Newsletter for a Conference Form.
2nd Annual PBC Fund for the Cure 5K
Walk at the PBC Conference 2003- When: Wednesday, May 7, 2003 Get everyone you know to
sponsor you by contributing whatever amount they want, you may just win the
special prize for the most amount of money collected. Checks should be made
payable to ALF/PBC Fund for the Cure.
Where: Palace Hotel Lobby
Time: Check-in 9:30 a.m.
, Walk: 10 a.m.
HEPATOLOGY WATCH FOR THE STUDY OF LIVER DISEASES -
NOVEMBER 1-5, 2002 Low-accelerating-dose regimen (LADR) protocol for decompensated
liver disease. Existing studies have not examined treatment outcomes
in HCV patients with decompensated liver disease. Gregory Everson and
associates initiated interferon alfa-2b plus ribavirin therapy according to
the LADR protocol in 102 HCV patients with decompensated liver
disease. Preliminary data for 91 patients shows that the
end-of-treatment rate of virological clearance was 38% and the SVR rate was
22%. SVR was correlated with non-1 genotype and achievement of full
dose therapy. These findings indicate that LADR protocol therapy can
result in virological remission in HCV patients with decompensated liver
disease. (Abstract 536) Retreatment with peginterferon (PegIFN) and ribavirin (RVN).
Mitchell Shiffman and colleagues report that SVR is evaluable in 212 of 863
patients enrolled in the HALT-C Trial. In this study, HCV patients
who have failed to respond to treatment with either IFN or IFN plus RVN are
retreated with PegIFN plus RVN. Dose reductions of PegIFN and/or RVN
have been required in 60% of patients, but only 5% of patients have been
unable to complete 24 weeks of treatment. The end-of-treatment
response rate was 53%, but the SVR rate was only 20%. The SVR rate
was greater in patients who: 1) had failed prior IFN monotherapy compared
to IFN plus RVN (34% vs. 11%); 2) were non-African Americans (22% vs. 0%);
3) had non-1 genotype infection (60% vs. 15%); 4) were <50 years of age
(25% vs. 13%); or 5) had a 2 log decline in HCV RNA by week 12 (41% vs.
7%). PegIFN maintenance therapy is being evaluated. (Abstract 527) CHRONIC HEPATITIS B VIRUS (HBV) INFECTION -- Rising health burden of HBV in the Entecavir (ETV) treatment of lamivudine (LAM) failures. Ting-Tsung
Chang et al. conducted an international study in which 181 HBV patients who
had failed to respond to 24 weeks of LAM therapy or had evidence of YMDD
mutation were randomized to receive one of 3 doses of daily ETV (0.1, 0.5,
or 1.0 mg) or to continue LAM 100 mg daily. The mean decrease in HBV
DNA at 48 weeks for all 3 ETV treatment groups was superior to that for
patients treated with LAM (p0.01). No patient in the ETV 1.0 mg group
had breakthrough viremia within 48 weeks and no mutations conferring
resistance to ETV were identified in any ETV treatment group. These
data demonstrate that ETV is potentially effective therapy for
LAM-resistant HBV. (Abstract 550) PRIMARY BILIARY CIRRHOSIS -- Occurrence in monozygotic twins.
Carlo Selmi et al., through an international effort, have identified 8 sets
of identical twins within 1,400 families in which a member had PBC.
The identical twins were all female and 6 of the sets of twins were
concordant for PBC. The high concordance for PBC suggests that genetic
factors play a major role and highlight the need for genetic studies in PBC
patients. (Abstract 897) Possible role of xenobiotics for induction of antimitochondrial
antibodies (AMA). Patrick Leung and coworkers performed detailed
experiments in which rabbits were immunized with BSA-conjugated halogenated
hydrocarbons. Within 4 weeks after immunization, the rabbits
developed antibodies to PDC-E2, BCOADC-E2, and OGDC-E2. Furthermore,
these antibodies were found to recognize rabbit mitochondrial proteins by
immunoblotting. These experiments provide the first evidence that AMA
may be induced by exposure to a chemical xenobiotic, leading to the
postulate that PBC may occur from chemical exposure. (Abstract 528) Ondansetron ameliorates fatigue. Fatigue is commonly associated with
PBC and may be related to altered serotonergic neurotransmission.
Jeremy Theal and colleagues conducted a multicenter, double-blind,
placebo-controlled study in which 56 patients
HIGHLIGHTS OF THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION
CHRONIC HEPATITIS C VIRUS (HCV) INFECTION
-- BILN 2061. BILN 2061
is a potent and specific inhibitor of HCV serine protease. Holger
Hinrichsen and associates treated 31 patients with HCV genotype 1 and
minimal hepatic fibrosis in a sequential group comparison with 2 days of
oral BILN 2061 25, 200, or 500 mg b.i.d. In each group, patients were
randomized to placebo in a 2:8 ratio. Viral load was decreased by 1
LOG10 unit in 7 of 9, 8 of 8, and 8 of 8 patients treated with 25, 200, and
500 mg of BILN 2061, respectively, while no responses were seen in
placebo-treated patients. In a second study, Yves Benhamou et al.
randomized 10 patients with HCV genotype 1 and advanced hepatic fibrosis to
receive 200 mg b.i.d. of BILN 2061 or placebo for 2 days. All 8
patients randomized to oral BILN 2061 achieved a decrease in virus load of
1 LOG10 unit. BILN 2061 was well tolerated in both studies. These
preliminary studies demonstrate that BILN 2061 is active against HCV.
(Abstracts 866 and 563)
Impact of psychiatric illness, drug use, and alcohol use in recovering
injection drug users. Diane Sylvestre and Barry Clements administered
standard interferon/ribavirin therapy to 66 recovering heroin users
(stabilized on methadone maintenance) with active HCV infection.
Neither psychiatric illness, occasional drug use, nor alcohol use was found
to adversely affect the sustained virological response (SVR) rate.
However, none of 7 patients who used drugs regularly and none of 4 patients
with psychiatric illness who also used drugs and/or alcohol had a
virological response. Multiple logistic regression analysis revealed
only psychiatric illness to be an independent predictor of poor
outcome. These data suggest that reasonably successful outcomes can
be expected with anti-HCV treatments in a recovering injection-drug-use
population. (Abstract 225)
Continued from Page 4
were
randomized to receive either ondansetron (a selective HT5-HT3 receptor
antagonist) 4 mg t.i.d. or placebo for 4 weeks and then crossed over for another 4 weeks of
treatment. Fatigue was assessed by the Fisk Fatigue Severity Score (FFSS).
The ondansetron-treated patients had a greater reduction of fatigue compared to
patients in the placebo group (P <0.03). No serious adverse events
were reported, and the most common side effects were headaches and
constipation. These findings suggest ondansetron may effectively treat
PBC-related fatigue. (Abstract 533)
NONALCOHOLIC STEATOHEPATITIS
(NASH) -- Leptin
is a marker of liver fibrosis. High levels of leptin have been reported
in obese and diabetic subjects and in patients with alcoholic or hepatitis C
cirrhosis. Laura Alba and colleagues assessed fasting serum levels of
leptin, glucose, insulin, and c-peptide in 88 patients with NAFLD.
Multivariate analysis identified serum leptin levels >19.7 ng/mL, serum
glucose levels >13.5 uU/mL, age >45 years, diabetes mellitus, and AST/ALT
ratio >1 to be independent predictors of advanced fibrosis (stage
3-4). (Abstract 531)
Rosiglitazone therapy. Brent Neuschwander-Tetri and associates treated 30
NASH patients with rosiglitazone (a PPARg agonist that improves insulin
sensitivity) 4 mg b.i.d. for 48 weeks. Insulin sensitivity was increased
with rosiglitazone therapy and serial liver biopsies revealed improvements in
the grade and stage of NASH. Furthermore, hepatic steatosis was improved as
measured by CT imaging. These preliminary results warrant further
investigations of rosiglitazone treatment for NASH. (Abstract 863)
ALCOHOL-INDUCED LIVER INJURY
-- Effect of
polyenylphosphatidylcholine (PPC). PPC is a 95% pure mixture of polyunsaturated
phosphatidylcholine extracted from soybeans that has been shown to prevent the
progression of alcohol-induced liver fibrosis in non-human primates.
Charles Lieber and colleagues in the VA Cooperative Studies Program randomized
789 patients with alcoholic liver disease in a multicenter study to receive
either daily PPC (1.5 gm) or placebo for 4-6 years. Counseling
successfully caused most patients to markedly reduce their alcohol intake,
resulting in a slowing of the progression of liver fibrosis. PPC had
little effect in this population; however, in the subgroup of patients that
continued to consume 6 drinks/day, there was a trend in favor PPC therapy in
terms of progression of fibrosis as assessed by the semi-quantitative scoring
system, change from baseline for ALT, AST, and bilirubin (p<0.05), and the
occurrence of ascites. This study demonstrates that a sustained marked
decrease of alcohol intake slows the progression of liver fibrosis and that PPC
may alleviate some manifestations of liver disease. (Abstract 874)
LIVER FAILURE -- Molecular adsorbents recirculating system (MARS) therapy.
Christian Steiner and Steffen Mitzner (University of Rostock) reported the
results of a retrospective analysis of extracorporeal liver support using MARS
therapy for 202 patients with liver failure (acute-on-chronic liver failure
[AoCLF]; acute liver failure [ALF]; primary graft dysfunction [PGD]; liver
failure post liver surgery; and misc.). AoCLF patients were observed to
have a decrease of hepatic encephalopathy grade, an increase in mean arterial
pressure, and improved biochemical parameters. The hospital survival of
ALF patients was 61%, and 56% of PGD patients recovered without
retransplantation. These findings indicate that MARS therapy is effective
treatment for patients with liver failure. (Abstract 16)
Prognostic
factors for progression to deep hepatic encephalopathy (HE). An analysis
of 170 ALF patients with grade 1,2 HE at baseline by Javier Vaquero and
colleagues of the ALF Study Group showed that survival was poorer for patients
who progressed to grade 3,4 HE (69.7% vs. 26.8%). Multivariate analysis
determined that baseline AST in the non-acetaminophen group and early infection
in the acetaminophen group were the most important variables to predict
progression of HE. (Abstract 221)
Meet the
PBCers – Fonda
by Jori Just one year ago, Fonda was
diagnosed with PBC and is now learning to cope with her illness. As a recent member of the PBCers
Organization, she is finding the support and friendship she has needed to
help her deal with her situation. Fonda said, “At first I was terrified,
but the PBCers did so much to help calm me down and get me focused on
surviving. I will be eternally grateful to this group!” One of the biggest issues for
Fonda right now is a lack of family support. Fonda explained, “My family doesn't take
it as a serious problem yet. They don't want to talk about it, think
about it, or make any long-term plans for dealing with it. They are
all incurable optimists and to them it isn't an issue until it IS an
issue. I wish I could think about it the same way, but at this point
I still can't. My mother and sister have refused to be tested much to
my dismay. If they have it, they don't want to know.” Right now Fonda says she has no symptoms
of PBC, except occasional mild pain in her right side. “Since I have no symptoms, the diagnosis
isn't real to them”, she said. After growing up in