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From: B. Harris)
Subject: Re: HELP FOR CIRRHOSIS (Hepatitis C)
Date: 30 Sep 1996

On Wed, 25 Sep 1996 21:52:38, (John Pearson) wrote:

>>A close friend of mine was recently diagnosed with hepatitis and
>>cirrhosis of the liver, and only has about 20% usage of his liver.
>>His doctor says he is too far gone to do a liver transplant, but will
>>give him interferon.  He does not drink.

There is no such thing as a person "too far gone" for a liver
transplant.  That's ridiculous.  People have been saved by liver
transplants when they are so far gone in hepatic coma that some of
their doctors thought they were brain dead (in one famous case, a
"brain-dead" man presented as a potential heart donor, ended up being a
liver *recipient*, and did well).

If your friend is getting interferon, he's probably got hepatitis C.
A couple of antivirals also seem to work for hepatitis C, though
neither is used routinely in the US.  One is ribavirin (Virazole),
which is used with interferon in England, and has a number of studies
behind it. Another is amantidine, which is used in the US against
influenza A, but also has activity against hep C.  In a preliminary
study done by Jill P. Smith at Hershey medical center in Pennsylvania
was presented in May at the Digestive Disease Week Conferences in San
Francisco, amantidine seems to be worth looking into.  In this study, 8
out of 20 patients who completed the study had a partial response to 6
months of amantidine, and another 6 had complete response (liver
enzymes normalized).  This is as good as the results of interferon, and
at about 4% of the price.

Neither amantidine or ribivirin is very toxic at the doses used for hep
C (1.2 grams/d for ribivirin, and 200 mg/d for amantidine).  Ribivirin
can be bought as the drug "Vilona" in Mexico and brought across the
border quite legally.  Amantidine is a standard pharmaceutical
available anywhere in the US on prescription.  If I had hep C and was a
layman, I'd be looking for a doctor willing to follow my liver enzymes
with me as I experimented with both medications, singly and in
combination, PLUS interferon alfa-2b.  Viral load tests for hep C are
also now available, and can probably help customize treatment with
antivirals, in much the same way they are doing for AIDS/HIV patients.
Specialist help is needed for this, and also because interferon has
side effects which can be managed with other drugs.  FIND A DOCTOR
These exist.

Good luck.  Your friend may also want to try the American Liver
Foundation Hotline at 1-800-223-0179.  They keep track of the latest

From: B. Harris)
Subject: Re: Is Hepatitits C contagious?
Date: 12 Apr 1997

In <> robinhood2@juno.comREMOVE
(Mick) writes:

>How can you catch it?

   Just as with hepatitis B:  A transfusion in a country where blood is
not sufficiently screened, or a transfusion before blood was screened
in the US (about 1991 for hep C).  Any activity in which blood from one
person gets into another:  sharing toothbrushes, needles, tattoo and
manicure equipment, etc.  Blood splashes on raw skin or open wounds
will probably do it.  Hep C is also transmitted sexually, but much less
easily than B.  And probably, there are mechanisms of transmission for
C which haven't been discovered yet, since there are people who have it
without a good explanation.  Still, current theory is that casual
polite public contact (handshakes, kisses, etc) will NOT do it.  In
this respect, Hep C can be thought of as much like the AIDS agent HIV:
transmissable, but not in the usual sense contageous.

                                        Steve Harris, M.D.

From: B. Harris)
Subject: Re: HepC MediScam & Unethical Pharmaco Goonsquads
Date: 7 Dec 1998 22:02:16 GMT

In <> (fred)

>The drug company scam moves on to Hepatitis C ... their
>doctor-minions are the key to yet another Drugs-Into-Bodies
>Scam: they target healthy people among the "undersirable"
>social classes (blacks, drug users, gays, etc) who are
>obviously too dumb to realize how sick they are and how
>badly they need drugs to combat a disease that wouldn't likely
>cause a problem until the immune system weakens
>(for most, old age).


   Hepatitis C infection becomes chronic in 80% of people who are
infected.  In these, 20% will progress to cirrhosis within 20 years.
That percentage goes up a bit with even further time, but 20 years is
the average time between hepatitis C infection and cirrhosis for those
who do get cirrhosis (obviously, some of these will get it at 10 years,
after infection, and some at 30).  Once a person has viral cirrhosis,
mortality rates become high, in part because risk of hepatoma (liver
cancer) is about 5% a year, and is nearly always fatal.  Mean time
between infection and hepatoma, for those who die of hepatoma, is
estimated to be 30 years.  Cirrhosis also leads directly to liver
failure, which is not always fatal, but only because of extreme
technical intervention.  Hepatitis C cirrhosis is the leading cause of
liver transplant in this country.

   Contrary to Fred's (as usual) misinformation, most people do not
acquire hepatitis C infection in middle age, and therefore the average
20 year period between infection and cirrhosis, and the average 30 year
period between infection and hepatoma, do not represent "problems"
mainly in old age.  In fact, the largest prospective study of hepatitis
C patients to date has found mortality increases mainly in those who
have reached cirrhosis before the age of 50.

   Until recently treatment for hepatitis C has been interferon alfa, a
treatment which suppresses viral replication and blood viral load while
given, but only rarely cures persons of the virus.  Interferon
treatment is epidemiologically associated with decreased mortality from
hepatitis C, but there are no prospective randomized studies to prove
definitively that this is not a selection bias effect. Evidence that it
is not, however, comes from the fact that interferon does NOT
statistically improve chances of dying of hepatitis C associated
hepatoma, but only of dying of other hepatitis C liver complications.
If selection bias factors were opperating, which caused healthier
people to be more likely to take the medication, one would expect that
all causes of hepatitis C mortality would have been affected.

   Current best treatment for hepatitis C involves treatment with a
limited duration course of interferon and the antiviral ribivirin (a
nucleoside analog like AZT, but not one which is incorporated into
DNA).  This combined treatment has a 40-50% chance of clearing the
virus from the system.  In that case, unlike the case when either of
these drugs is given alone, there is no recurrance of chronic hepatitis
(viral load, liver enzyme elevation) after all medication is stopped
(followups have been up to a year on this, so far).  Thus, unlike the
case with HIV, this combined treatment represents a reasonable chance
of complete viral eradication from the system.  Apparently the greedy
drug companies have shot themselves in the foot on this one, and were
too stupid to have stayed with chronic interferon, instead of
developing a cure which needs no further treatment.

   Interferon and ribivirin are too new to have any definitive followup
studies, which would take 20-30 years.  Not surprisingly, many of those
people with chronic hepatitis C liver infection have elected not to
wait that long.

                                      Steve Harris, M.D.

From: B. Harris)
Subject: Re: ? Giardiasis
Date: 3 Jan 2000 09:36:27 GMT

In <> fran&tom <> writes:

>Thanks for answering so quickly...I *do* have an ulcer (huge duodenal,
>asymptomatic, discovered on routine scope for varices, which are
>nonexistent), am taking Prilosec, but have always been HP
>SO, however, hasn't been tested...hmmm...guess that might be the next
>step. He also is HCV+ but his LFTs are okay and he has no symptoms
>(probably from a blood transfusion about 25 years ago at the VA).
>But...have *you* ever heard of these sort of sulfuric-smelling burps that
>come and go maybe once a month? Gets pretty disgusting, I tell you!

   Nope, other than the fact that foul burping are sometimes the result
of incomplete gastric emptying-- which can happen with ulcers or
diabetes, etc.  And gas production is influenced by the fact that the
stomach also gets colonized by different bacteria when you suppress
acid.  But I wouldn't recommend in your case going off prilosec.  If
you have GI bleeding, you'll really bleed.

   To get sulfur up, you have to eat sulfer, so watch for associations
with sulfur in your diet (eggs, mostly, but also cruciferous veggies).
And some supplements, of course (NAC).

>And what else might cause it, any more ideas? Will talk to my GI or
>hepatologist next time I see one of them, but my malabsorption is really
>worrying me; my liver is apparently so bad that, as I said before, I'm
>waiting for transplant (AB+ thankfully) and actually *feel* extremely
>well except for usually being unable to stay awake! so I have to find
>*some*thing to worry about, it seems! (Haven't had a liver bx, as my
>platelets are only about 25K and clotting time is 15+ minutes, so don't
>actually know the real state of my liver itself and my spleen is so huge
>I look six months pregnant -- every woman's a half pound of
>brie and lose 5 lb!)...also live out in the boonies, about 40 minutes
>from the nearest hospital, (we're thinking about moving but really love
>our little hippie town of 1202 people) so gimme something to worry about,
>and I'll worry!

   Can't think of anything in particular.  Stay away from aspirin and
Tylenol, of course, and antiinflammatories unless administered by your
hepatologist. For other reasons, if you're malabsorbing fat, you should
probably take vitamin supplements.  Everything but iron and vitamin A
(take beta carotene instead).  Certainly a vitamin K supplement.  And
have your blood vitamin D levels (25-hydroxy-D) checked.  People worry
about vitamin E and bleeding, but my patients on coumadin tolerate E
well.  Standard dose is 400 IU.  Take it at a different time than the
vitamin K, talk it over with the hepatatologist *first,* (he she might
object violently, or might not), and get the PT tested sometime (a week
or two) after you start.

   Sleepiness: get your blood ammonia done if you haven't already.
Your GI guy can show you how.  If it's up, you can always try the old
neomycin plus lactulose routine.  This may even help your GI bacterial

   As you've no doubt been told, with cirrhosis of this magnitude from
a virus, you're past the point that there's much to be done
therapeutically except transplant-- nobody can replace lost liver
archetecture.  However, AFTER the transplant, you'll need to carefully
check if your new liver is under attack by your old hep C.  If it is,
(and this often happens), the ribavirin/interferon combo is worth
doing.  Not for your husband, I agree, if his LFTs and viral load stay

From: B. Harris)
Subject: Re: Hepatitis C
Date: 8 Jan 2000 14:38:45 GMT

In <> fran&tom <> writes:

>I was diagnosed with hepatitis-C in October of 1998; although I have been
>one who has *never* been seriously ill in my life (haven't even had a
>cold/flu for at least 20 years; only diagnosed with "idiopathic"
>thrombocytopenia in 1992) I have apparently had the hep for something
>like 30 years now. Too late for any sort of chemo, so I am now waiting
>for a liver transplant. I am actually feeling pretty good except for
>extreme fatigue and very slight hepatic encephalopathy.
>I have recently started having extreme rigors, such that I shake so much
>I can't even talk or walk; only once have these been associated with
>(overt, at least) temp of 104 which was associated with an apparent bug
>bite or something that turned into a wound infection and left me with a
>skin/muscle defect about 1.5 inches deep and 3/4 inches in diameter; none
>of the other times have been associated with a temp. Now, getting info
>out of my hepatologist is like pulling teeth, and I only see him every
>two months, in any case, and can *not* contact him at any other time.
>Does anyone have any ideas with regard to this? The main problem I seem
>to find on the net associated with rigors is TB; obviously I've had a TB
>test recently. I'd appreciate any input or ideas anyone may have.

   See an infections disease guy.  The liver is part of your immune
system, and Kupfer cells and the like there keep you from getting
systemically infected from guy bacteria coming back from your portal
system. Yours liver archetecture is a mess.  You could be getting
showers of endotoxin into your blood as a result, or even bacteria.
Spontaneous peritonitis is the bane of cirrhotics.  Use the
thermometer, and get some good antibiotics on hand.  Every time you
have rigors annd run over 100 F you should get to the ER and have a
complete CBC with hand-differential done.  Get your pneumonia and
Neiseria menigitis vaccines up to date (and hep B and A, too, of

From: B. Harris)
Subject: Re: Hepatitis C
Date: 9 Jan 2000 14:28:05 GMT

In <> fran&tom <> writes:

>To steven and dlnevins:
>Thanks for the advice. I've been pushing and pushing this "rigor" thang
>with my hepatologist (it is scaring the hell out of me!) for months now
>and he basically just shrugs his shoulders. We're talking about a
>prestigious med center in SF, not some fly-by-night bunch of quacks,
>Thanks for the advice about seeing and ID guy. Don't think I mentioned
>that my spleen makes me look like I'm 7 months pregnant, with a platelet
>count of about 25-27K and my bleeding time is 15 minutes. Can you maybe
>come up with two or three questions for my hep guy, in any case?

   Is my blood ammonia high?

   Could I be getting endotoxin from my gut, as papilli necrose

    Would a course of neomycin and lactulose be worth trying, to see if
symptoms are affected?

   Can I have some antibiotics on hand (amoxicillin, metronidazole) in
case my temp goes over 101F in the middle of the weekend?

From: B. Harris)
Subject: Re: Hepatitis C
Date: 11 Jan 2000 07:38:48 GMT

In <85a9a8$1n7g$> "Beachhouse"
<> writes:

>Steven B. Harris <> wrote in message
>>    Is my blood ammonia high?
>Blood ammonia levels correlate poorly

Correlate poorly with what?

>and are not used as a measure of
>synthetic function

Didn't suggest they should be.

>(nor should they be used to exclude/diagnose hepatic

Didn't suggest they should, as no test is 100% specific or sensitive.
Exclude/diagnose is a black/white thing.  Blood ammonia levels
correlate with hepatic encephalopathy better than any other known LAB
test.  Want to argue the point?

>>    Can I have some antibiotics on hand (amoxicillin, metronidazole) in
>> case my temp goes over 101F in the middle of the weekend?
>Bad idea for obvious reasons.  Better advice: "Who can I reach immediately
>if I have problems over a weekend?"

   And if the answer is: "Nobody who can do anything for me without
sending the paramedics to see if I'm sick enough to be hospitalized,"
then what?  She dials 911 whenever she doesn't feel good?

From: B. Harris)
Subject: Re: Hepatitis C
Date: 12 Jan 2000 08:58:04 GMT

In <85guef$26mo$> "Beachhouse"
<> writes:

>Serum ammonia levels are USELESS for medical decision-making. They
>shouldn't even be ordered. I'd use a combination of coags, albumin,
>presence of ascites, a mental status exam, and physical findings like
>asterixis (i.e. clinical criteria) to diagnose hepatic encephalopathy --
>lots of folks with normal ammonia levels are encephalopathic and vice

  Lots of people with normal abnormal coags have no encephelopahy, and
vice verse.  Ascites?  That a mechanical obstruction and tells about
your liver archtecture, not how well it's doing its job.   Asterixis--
sure.  But were were talking about lab tests.  Asterixis is reasonably
specific, but it's not very sensitive.  I've seen more patients looney
as toons with no palm flap at all, than I have the classical picture.

> So what if the serum ammonia level is elevated?  You're out of date

>> Didn't suggest they should, as no test is 100% specific or s
>>ensitive.  Exclude/diagnose is a black/white thing.  Blood ammonia
>>levels  correlate with hepatic encephalopathy better than any other
>>known LAB test.  Want to argue the point?


Okay, chew on these to start.  I've left out a lot of animal data which
merely proves that the association is not spurious, and that ammonia,
introduced as the only variable, is indeed singly toxic to the brain,
and in the way the produces the changes associated with encephalopathy.

J Neurochem 1996 Oct;67(4):1584-94

Severity of hyperammonemic encephalopathy correlates with brain ammonia
level and saturation of glutamine synthetase in vivo.

Kanamori K, Ross BD, Chung JC, Kuo EL
Magnetic Resonance Spectroscopy Laboratory, Huntington Medical Research
Institutes, Pasadena, California 91105, USA.

Correlation among in vivo glutamine synthetase (GS) activity, brain
ammonia and glutamine concentrations, and severity of encephalopathy
was examined in hyperammonemic rats to obtain quantitative information
on the capacity of GS to control these metabolites implicated in the
etiology of hepatic encephalopathy. Awake rats were observed for
neurobehavioral impairments after ammonium acetate infusion to attain a
steady-state blood ammonia  concentration of 0.9 (group A) or 1.3
mumol/g (group B). As encephalopathy progressed from grade III to IV,
brain ammonia concentration increased from 1.9 to 3.3 mumol/g and then
decreased to 1.3 mumol/g on recovery to
grade III. In contrast, brain glutamine concentration was 26, 23, and
21 mumol/g, respectively. NH(4+)-infused rats pretreated with
L-methionine DL-sulfoximine reached grade IV when brain ammonia and
glutamine concentrat ions were 3.0 and 5.5 mumol/g, respectively;
severity of encephalopathy correlates with brain ammonia, but not
glutamine. In vivo GS activity, measured by NMR, was 6.8 +/- 0.7
mumol/h/g for group A and 6.2 +/- 0.6 mumol/h/g for group B. Hence, the
in vivo activity, shown previously to increase with blood ammonia over
a range of 0.4-0.64 mumol/g, approaches saturation at blood ammonia >
0.9 mumol/g. This is likely to be the major cause of the observed
accumulation of brain ammonia and the onset of grade IV encephalopathy.

PMID: 8858943, UI: 97012127


Proc Soc Exp Biol Med 1994 Sep;206(4):329-44
Current theories on the pathogenesis of hepatic encephalopathy.

Mousseau DD, Butterworth RF
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal),
Quebec, Canada.

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication
of both acute and chronic liver disease. Several hypotheses have
emerged following the development of appropriate animal models of HE
and following studies using postmortem brain tissue from HE patients.
It was originally suggested that primary energy failure was responsible
for HE; however, there is now mounting evidence that the pathogenetic
defect involves neurotransmission failure. Specific neurotransmitter
systems implicated in the pathogenesis of portal-systemic
encephalopathy (PSE) include the excitatory amino acid glutamate as
well as neuroactive and/or neurotoxic biogenic amine metabolites.
Although it has been proposed that alterations in the
gamma-aminobutyric acid (GABA) system may play a pathogenic role in HE
associated with both chronic and acute liver failure, there is now
overwhelming evidence to the contrary. On the other hand, there is
evidence to suggest that a subgroup of patients with HE have increased
blood and CSF concentrations of substances that bind to GABA-related
benzodiazepine receptors in brain. ***Alterations of both the
glutamatergic and serotoninergic neurotransmitter systems in PSE likely
result from the metabolic consequences of chronic exposure of brain to
toxic levels of ammonia.** In addition to its effects on glutamatergic
and serotoninergic systems during chronic liver disease, ammonia has
been intimately associated  with the brain edema invariably observed in
acute liver failure. It is evident that, regardless of the type of
liver failure, effective reductions of ammonia levels remains the
strategy of choice in the prevention of encephalopathy. The further
elucidation of neurotransmitter alterations in HE could result in novel
 "downstream" neuropharmacologic approaches to its prevention and


J Inherit Metab Dis 1998;21 Suppl 1:6-20

Effects of hyperammonaemia on brain function.

Butterworth RF
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal),
Quebec, Canada.

Neuropsychiatric symptoms of hyperammonaemia include alterations of
mood and personality, cognitive impairment, ataxia, convulsions and
coma. The nature and severity of CNS dysfunction depend upon the
aetiology and degree of hyperammonaemia, its acuteness of onset and the
age of the patient. Neuropathological studies reveal Alzheimer type II
astrocytosis in the adult hyperammonaemic patient, whereas
hyperammonaemia in the infant resulting from congenital urea cycle
disorders or Reye syndrome is accompanied by cerebral atrophy, neuronal
loss and cerebral oedema. Several electrophysiological and biochemical
mechanisms have been proposed to explain the de
leterious effects of ammonia on CNS function. Such mechanisms include
direct effects of the ammonium ion on excitatory and inhibitory
neurotransmission and a deficit in cerebral energy metabolism due to
ammonia-induced inhibition of alpha-ketoglutarate dehydrogenase. In
addition, ammonia has been shown to interfere with normal processes of
uptake, storage and release of various neurotransmitters. Ammonia
disrupts monoamine storage, inhibits the high-affinity uptake of
glutamate by both astrocytic and neuronal elements and activates
'peripheral-type' benzodiazepine receptors leading to the potential
synthesis of neuroactive steroids in brain. On the bas
is of these actions, it has been proposed that ammonia disrupts
neuron-astrocyte trafficking of amino acids and monoamines in brain.
The increased formation of brain glutamine in hyperammonaemic syndromes
could be responsible for the phenomenon of brain oedema in these
disorders. Therapies aimed at either decreasing ammonia production in
the gastrointestinal tract or increasing ammonia removal by liver or
skeletal muscle are the mainstay in the prevention and treatment of the
CNS consequences of hyperammonaemia. New therapeutic approaches aimed
at correction of the neurotransmitter and cerebral energy deficits in
these syndromes could hold promise for he future.


Proc Soc Exp Biol Med 1999 Nov;222(2):99-112
Hepatic encephalopathy: An update of pathophysiologic mechanisms.

Hazell AS, Butterworth RF
Neuroscience Research Unit, Center Hospitalier de l'Universite de
Montreal, Quebec, Canada.

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs
in both acute and chronic liver failure. Although the precise
pathophysiologic mechanisms responsible for HE are not completely
understood, a deficitin neurotransmission rather than a primary deficit
in cerebral energy metabolism appears to be involved. The neural cell
most vulnerable to liver failure is the astrocyte. In acute liver
failure, the astrocyte undergoes swelling resulting in increased
intracranial pressure; in chronic liver failure, the astrocyte
undergoes characteristic changes known as Alzheimer type II
astrocytosis. In portal-systemic encephalopathy resulting from c
hronic liver failure, astrocytes manifest altered expression of several
key proteins and enzymes including monoamine oxidase B, glutamine
synthetase, and the so-called peripheral-type benzodiazepine receptors.
In addition, expression of some neuronal proteins such as monoamine
oxidase A and neuronal nitric oxide synthase are modified. In acute
liver failure, expression of the astrocytic glutamate transporter GLT-1
is reduced, leading to increased extracellular concentrations of
glutamate. Many of these changes have been attributed to a toxic effect
of ammonia and/or manganese, two substances that are normally removed
by the hepatobiliary route and that  in liver failure accumulate in the
brain. Manganese deposition in the globus pallidus in chronic liver
failure results in signal hyperintensity on T1-weighted Magnetic
Resonance Imaging and may be responsible for the ex
trapyramidal symptoms characteristic of portal-systemic encephalopathy.
Other neurotransmitter systems implicated in the pathogenesis of
hepatic encephalopathy include the serotonin system, where a synaptic
deficit has been suggested, as well as the catecholaminergic and opioid
systems. Further elucidation of the precise nature of these alterations
could result in the design of novel pharmacotherapies for the
prevention and treatment of hepatic encephalopathy.

Next topic:

>> >>    Can I have some antibiotics on hand (amoxicillin,metronidazole) in
>> >> case my temp goes over 101F in the middle of the weekend?
>> >
>> >Bad idea for obvious reasons. Better advice: "Who can I reach
>> >immediately if I have problems over a weekend?"
>>    And if the answer is: "Nobody who can do anything for me without
>> sending the paramedics to see if I'm sick enough to be hospitalized,"
>> then what? She dials 911 whenever she doesn't feel good?
>Oh come on, Steve.   You'd rather someone pop antibiotics empirically
>without having them evaluated?  Geezus.

   It's not a question of "rather."  It's a question of antiotics and
not get evaluated, or just not get evaluated at all.   Or at ruinous

From: B. Harris)
Subject: Re: Hepatitis C
Date: 12 Jan 2000 17:42:02 GMT

In <85hsef$20hu$> "Beachhouse"
<> writes:

>I've put my money where my mouth is... see below.
>Please note... I am *not* disputing the potential role of Ammonia
>toxicity (among other metabolic derangements) in contributing to the
>signs/syxs of hepatic encephalopathy... what I *AM* disputing
>wholeheartedly is the notion that serum/plasma levels of Ammonia (in
>*humans not animals*) are *clinically* helpful in monitoring these
>patients or in establishing the diagnosis... My reading of the literature
>and my clinical experience has taught me that this is unreliable.
>Basically, people can have hepatic encephalopathy with NORMAL serum
>ammonia levels -- the problem appears to be one of abnormal permeability
>at the blood/brain barrier level.

   Yes, they can have, but your own citations show that this is true
for only 1 out of 10.   That's better than the correlation between
people who die of primary lung cancer and people who smoke, for heavens

  So my question for you: why would a test with 90% sensitivity not be
clinically helpful?   Have you got any other single clinical or lab
test you can name which is that useful in helping to rule out a
diagnosis?  I'd be happy to have a 90% sensity test for every
mulifactorial disease I see.  Wherever did I ever claim that an
arterial ammonia level was a substitute for a full exam and lab workup
by a hepatologist?  I'm merely arguing against your idea that blood
ammonia levels are "worthless" (your words), and idea which your own
citations don't support.  Indeed, since you note that there is evidence
that actively lowering ammonia levels post hoc in humans ammeliorates
symptoms of hepatic encephalopathy, that pretty much destroys the idea
that ammonia might be purely a confounder, and not in any way primarily
causal (an idea you seem to be suggesting from the animal models).
Well, the animal models for hepatic toxicity have been a lot more
successful the animal models for cigarette induced lung cancer.  I'm
not saying the blood brain barier doesn't contribute, but if the blood
brain barier was the whole problem, we would expect no correlation
between arterial ammonia and encephalopathy *at all*, except as ammonia
happened to a marker for liver disease, like high creatinine for renal
disease.  But there's a way to check that, and that's to do
intervention studies.  As for your complaining that the animal ammonia
models are artificial I'm reminded of nothing so much as the critics
who complained and complained that cholesterol and heart disease in
humans were merely correlational, that blood cholesterol was a
cofounder, and (here's the part with the chutzpah) that the experiments
giving animals heart disease with cholesterol were "artificial."  Which
is beggining to stretch coincidences pretty far.  Except that in that
case most of said critics really did have the sense to quit and shut up
when 4S, WOSCOPS and TexCAPS randomized prospective intervention
HMG-CoA RI ("-statin") studies hit.  You're a hard case.

>Additionally, what exactly should the cut-off level be for serum ammonia?
>Haven't seen this specified in the literature -- nor have I seen specific
>data on PPV/NPV. Note that the literature cites *arterial* measurements
>of ammonia -- not venous specimens.

    Sure enough.  Where did I suggest otherwise?  As for the limits,
see your local lab.  If you're merely arguing that the technique is
valid in theory, but difficult in practice due to quality control,
that's a bit different.  I've not found it so, if your lab is
experienced, and you take and treat your specimens like blood gases.
But if you've quit using the test and don't believe in it, how are you
ever going to be convinced otherwise?  You can't see with eyes
squinched shut.

From: David Rind <>
Subject: Re: Hepatitis C
Date: Thu, 13 Jan 2000 09:24:19 -0500

I have to say that I mainly agree with Beachhouse in this
thread.  Measuring serum ammonia levels rarely seems to provide
clinically useful information.  "Never" would be overly strong.
There are occasional patients who have multiple possible etiologies
for encephalopathy, and who also have a long individual history
correlating ammonia levels in them with hepatic encephalopathy,
where measurements do sometimes seem to help sort things out.  But
in most people with hepatic encephalopathy, following serum
ammonia levels doesn't add much information to the clinical picture.

As Beachhouse suggests, when the ammonia level doesn't agree with
the clinical exam, you just tend to ignore the ammonia level. When
it does agree with the exam, not much information has been added.

David Rind

From: Steve Harris <>
Subject: Re: Treatment of Chronic Hepatitis C Virus Infection via Antioxidants
Date: 9 Aug 2005 14:38:33 -0700
Message-ID: <> wrote:
> J Clin Gastroenterol. 2005 Sep;39(8):737-742. Related Articles, Links
> Treatment of Chronic Hepatitis C Virus Infection via Antioxidants:
> Results of a Phase I Clinical Trial.
> Melhem A, Stern M, Shibolet O, Israeli E, Ackerman Z, Pappo O, Hemed N,
> Rowe M, Ohana H, Zabrecky G, Cohen R, Ilan Y.
> >From the *Liver Unit, Department of Medicine, and daggerDepartment of
> Pathology, Hebrew University, Hadassah Medical Center, Jerusalem,
> Israel; and double daggerMarcus Foundation, Atlanta, GA.
> These
> data suggest that multi antioxidative treatment in chronic HCV patients
> is well tolerated and may have a beneficial effect on
> necro-inflammatory variables.


Hep C does change over time, and viral load levels do drop
spontaneously in some patients. It has a lot more spontaneous
remissions than cancer, that's for sure.

Thus, a treatment study such as the above BADLY needs a control group
of some kind. It's not there. None of the results seen are so far out
of the ordinary that it's impossible to believe they are not the result
of the treatments proferred. In the abstract, they don't even attempt
to use case controls or a *historical* control group. Lousy science.


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