A summary of the abstracts for the just concluded AASLD conference in
Boston is available at
http://www.hcvadvocate.org/news/reports/AASLD_2004/TOC_AASLD_2004_HCV2.htm

Lots of interesting info, just picking a few highlights:

====
QUANTITATIVE LIVER FUNCTION TESTS PREDICT SUSTAINED VIROLOGIC RESPONSE
TO RETREATMENT WITH PEGINTERFERON ALFA-2A PLUS RIBAVIRIN

Shows that decreased liver function also decreases your chance of SVR in
treatment. A good argument for not waiting until things get worse...
====
THE IMPACT OF PEGINTERFERON (PEGIFN) AND RIBAVIRIN (RBV) DOSING ON
SUSTAINED VIROLOGIC RESPONSE (SVR) ...

Better numbers on the effects of interrupting treatment or reducing the
dose. The worst: "Discontinuing the dose of RBV during the initial 20
weeks of treatment had a dramatic effect on SVR with no patient
receiving an SVR"
====
HISTOLOGIC BENEFIT OF PEGINTERFERON ALFA-2A (40KD) (PEGASYS®)
MONOTHERAPY IN PATIENTS WITH ADVANCED FIBROSIS OR CIRRHOSIS

"Patients with advanced fibrosis and cirrhosis, experience sustained
histologic benefit after treatment with IFN. Although the greatest
benefit was seen in patients with SVR, relapsers and nonresponders still
obtained a moderate histologic benefit. In light of these results
suggesting that potential to delay liver decompensation and avoid liver
transplantation, the 12 week stopping rule may be reconsidered."
====
BONE MINERAL DENSITY IS IMPROVED AFTER 48 WEEKS COMBINATION THERAPY WITH
INTERFERON-a AND RIBAVIRIN

A previous study found "patients with chronic hepatitis C had low bone
mineral density (BMD) and a high prevalence of osteopenia". The new
study finds that treatment significantly improves mineral densities and
reduces bone turnover.
====
EFFICACY OF IRON DEPLETION AND ANTIVIRAL THERAPY IN PATIENTS WITH
PORPHYRIA CUTANEA TARDA (PCT) AND ... (HCV) CHRONIC INFECTION

Sorry, Doe: "iron depletion does not affect significantly the rate of
viral replication. 3) The rate of sustained response to antiviral
teraphy is low in patients with PCT and HCV chronic hepatitis 4) Iron
depletion doesn’t seem to improve the rate of response in these
patients."
====
INFORMATION PROCESSING DEFICITS IN PATIENTS WITH CHRONIC HEPATITIS C

This explains a lot... ;-)

"Patients with chronic HCV hepatitis have significant impairment in all
stages of information processing. [...] These functions have major
importance in everyday activity, quality of life and driving skills. The
correlation between severity of disease and degree of cognitive
impairment may necessitate further investigation. [...]
In addition, the authors concluded that cognitive task (probably with
evaluation of field abilities) is mandatory in patients with HCV in
professions that demand such everyday skills:  driving, military
exercising, surgery, etc.  Otherwise patients with chronic HCV should
not drive or operate machinery."

and related: IMPROVEMENT IN COGNITIVE FUNCTIONS IN PATIENTS WITH CHRONIC
HEPATITIS C UNDER TREATMENT WITH PEG. INTERFERON+RIBAVIRIN

"Patients with chronic HCV hepatitis have significant impairment in all
stages of information processing. Deficits in performance on tests of
selective attention, working memory and learning ability suggests an
impairment in fronto-subcortical circuits, especially in anterior
cingulated girus.
However some of these function tend to show significant improvement
after 3-6 months of treatment."
====
Three long-term followup studies on SVR:

1) 194 patients with SVR were followed for up to 6 years, no case of
relapse was found.

2) "After a mean follow-up of 119 weeks (range 24-537 weeks) post
sustained virologic response, there was no evidence of virologic relapse
in 146/147 patients (99%). One patient experienced a virologic relapse
at some time between 24- 94 weeks after an end of treatment response.
[...] Virologic relapse after a sustained virologic response in
hepatitis C virus infection is rare. We have shown that, irrespective of
genotype and treatment(s) received, the response is maintained up to 10
years with virtually no late relapse."

3) "To date >99% of patients have remained HCV RNA negative during
long-term follow-up. 7 patients (<1%) have become HCV RNA positive,
although whether these cases represent re-infection or true ‘relapse’ is
at present unknown."
====
SUSTAINED VIRAL RESPONSE (SVR) WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN
IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) WHO WERE NON RESPONDERS (NR)
TO PEGINTERFERON ALFA-2B AND RIBAVIRIN

SVR of 32% in mostly genotype 1 patients re-treated with Peg-Intron
combo after failed Pegasys combo. An interesting result for those whose
tx has failed with either form - it's likely the reverse might work as
well.
====
ELEVATED ALT AND AST DUE TO PEGYLATED INTERFERON –a INDUCED POLYMYOSITIS
IN TREATED PATIENTS WITH UNDETECTABLE HEPATITIS C VIRAL LOAD

Interesting in light of recent questions about elevated LFTs during tx:

"Polymyositis is recognized side effect of pegylated interferon-a 2a and
–a 2b therapies for HCV. It should be suspected in patients with
elevation in AST/ALT during interferon therapy with a negative viral
load or if patients develop skeletal muscle weakness. Diagnosis can be
confirmed by measurement of CPK, EMG and muscle biopsy when indicated.
Most patients can continue treatment under close scrutiny with favorable
virological outcomes."
====
PREVALENT MANIC SYMPTOMS IN PEGINTERFERON-INDUCED MOOD DISORDERS IN
PATIENTS WITH CHRONIC HEPATITIS C: THERAPEUTIC IMPLICATIONS

This seems important for those on tx:

"Our findings, showing that IFN-induced mood disorders consist of a
mixture of manic/hypomanic and depressive symptoms, differ substantially
from those of studies published so far identifying depression as a
hallmark of IFN-induced mood disorders. They may have important
therapeutic implications : when manic symptoms are prevalent,
antidepressant may exacerbate these symptoms. Antipsychotic such as
amisulpride should rather be used, allowing the continuation of
antiviral therapy in the majority of patients."
====
CAUSAL RELATIONSHIP BETWEEN HEPATITIS C VIRUS INFECTION AND THE
DEVELOPMENT OF TYPE 2 DIABETES MELLITUS

"We report here for the first time community-based evidence for an
association between HCV infection and insulin resistance, and a causal
relationship between HCV infection and the development of type 2 DM"
====
EVALUATION OF AMANTADINE IN CHRONIC HEPATITIS C

"Combination therapy with amantadine is of no benefit in naive patients
or relapsers. In high-difficult to treat patients (non-repsonders),
triple therapy with amantadine improved the sustained response."
====
HOW NORMAL ARE NORMAL ALANINE AMINOTRANSFERASE (ALT) LEVELS IN PATIENTS
WITH CHRONIC HEPATITIS C (CHC)?

"This suggests that the baseline ALT activity exceeds the patients’ true
‘healthy’ ALT activity, and that virological responses are accompanied
by further decreases in ALT activity because of reduced hepatic
inflammation. According to these findings, an update of the definition
of healthy serum ALT activity is warranted."
====
STUDY COMPARING 16 VS. 24 WEEKS OF COMBINATION THERAPY IN PATIENTS
CHRONICALLY INFECTED WITH HCV GENOTYPE 2 OR 3

"At week 4 of treatment with peginterferon alfa-2a plus ribavirin an
early virologic response was observed in more than 90% of patients
chronically infected with HCV genotype 2 or 3. Combination therapy for
16 or 24 weeks achieved similar sustained virologic response rates in
these early virologic responders. In contrast, the lower sustained
virologic response rate in patients without an early virologic response
at week 4 (group C) implies that a treatment duration longer than 24
weeks may be necessary in this small subset of patients."
====
REDUCTION OF THE RELATIVE RELAPSE RATE BY PROLONGATION OF THE DURATION
OF A THERAPY WITH PEGINTERFERON ALFA-2A PLUS RIBAVIRIN IN PATIENTS WITH
GENOTYPE 1 INFECTION UP TO 72 WEEKS

"In patients with a late virological response (HCV RNA positive at week
12 and negative at week 24) a significant reduction of the relapse rate
may be achieved by prolonging the duration of therapy up to 72 weeks."
====

On the new treatment front, some indication that VX-950 and BILN-2061
are still being investigated. Some promising phase I results for NM283
(a polymerase inhibitor). Hints that a therapeutic vaccine, IC41, may
increase T-cell responses. But nothing earth-shaking. Consensus
Interferon has shown some good results, but similar to the other
interferons.

So much info, so little time... There's a lot more, especially about
transplant and HIV coinfection that I've completely left out. Check the
link above.

Thomas