| |
Future Therapies
Given the frequency, morbidity, and mortality associated with
recurrent bleeding, novel drugs and interventions have been studied.
Argon Plasma Coagulation
Cipolletta and colleagues[87] compared argon plasma
coagulation (APC) with observation alone in 30 patients (median
follow-up of 16 months) after variceal eradication with ligation.
Variceal recurrence was significantly lower in the APC group and
recurrent bleeding occurred in 1 patient in the control group (no
recurrent bleeding occurred in the APC group). Recent studies suggest
that patients with large paraesophageal varices on endosonography (after
endoscopic ligation) have a higher risk of developing recurrent varices
and rebleeding.[45] Caution must be exercised during
application of APC given the potential of thermal damage to the
muscularis propria with higher-power settings.[88]
Endothelin Receptor Antagonists
Recent evidence indicates that hepatic stellate cells, which are
resident perisinusoidal mesenchymal cells with a microanatomical
position in the sinusoids analogous to vasoregulatory pericytes, may
regulate sinusoidal blood flow. This fact is most evident in the context
of liver injury, when these cells transform into myofibroblasts
(activated stellate cells), but may apply also to the normal liver.
Endothelins (ETs) and nitric oxide (NO) play important roles in
modulating this cell contractility, and their interplay is a determinant
factor of local sinusoidal blood flow, especially in injured liver.[89,90]
ET levels are increased in injury, and activated hepatic stellate
cells have the ability to respond to ETs via the expression of ETA
and ETB receptors. Exposure of stellate cells to ET-1 results
in dramatic cellular spreading, proliferation, and the acquisition of a
myofibroblast-like appearance typical of the activated phenotype.
Induction of smooth muscle alfa-actin, a marker of activation, is
prominent and is dose-dependent after exposure to ETs. Because ET is
overproduced in liver injury, enhanced stellate cell contractility in
this setting may lead to a perisinusoidal constriction and increased
intrahepatic resistance. A mixed ETA/ETB receptor
antagonist (bosentan) was administered to isolated perfused cirrhotic
livers; a high concentration of bosentan was found to reduce portal
pressure by 15% to 20%.[91] Similar compounds are currently
undergoing phase 1 clinical trials, opening new perspectives for the
treatment of portal hypertension.
Nitric Oxide
Vasodilatory molecules, NO being one of intense interest,
counterbalance the contractile effects of vasoconstrictors in the liver
and other organs. NO blockade in normal rat livers has been shown to
increase portal pressure and enhance the vasoconstriction induced by
norepinephrine.[92]
Vascular beds with defective NO synthesis demonstrate an abnormally
increased vascular resistance. A recent experimental study demonstrated
that in the cirrhotic rat liver, there is a deficit in the production of
NO that is associated with an impairment in the intrahepatic
vasodilatory response to an endothelial agonist such as acetylcholine.[93]
Elevation of hepatic NO is another approach that holds promise as a
means to compensate for the NO deficit and reduce activated hepatic
stellate cell contractility. Orally administered nitrates may serve this
purpose, but thus far, because of their effect in the systemic
circulation, they have only been shown to be beneficial in combination
with beta-blockers. Aiming to increase the intrahepatic production of
NO, portal injection of adenovirus coupled with the gene encoding
endothelial NO synthase has been reported. This approach enhances the
expression of NO synthase in liver cells and, although still
experimental and far from being clinically applicable, significantly
reduced portal pressure for a short period.[94]
Antifibrotic Agents
Currently there are no data on antifibrotic agents and reduction of
portal pressure, but it is intuitive that this link should exist.
Alcoholic cirrhotics who abstain, and therefore have stable or improved
liver histology, have a reduced portal pressure and less rebleeding.[28]
Moreover, sustained response to antiviral therapy for chronic hepatitis
C results in a significant decrease in HVPG.[95]
The vasoactive compounds (angiotensin II [ANG-II], ETs, NO) play a
major role in the injured liver -- not only by regulation of the
intrahepatic blood flow, but also by direct modulation of extracellular
matrix production and fibrogenesis.
The role of ANG-II and its antagonism in portal hemodynamics will be
discussed later in this article. Recent studies, however, have suggested
a putative role for this agent in hepatic fibrogenesis. ANG-II, as
reported by Bataller and colleagues,[96] elicits a marked
dose-dependent cell contraction and proliferation in activated human
hepatic stellate cells. These effects were totally blocked by losartan
and reduced by NO donors or prostaglandin E2. It is important to note
that the effects of ANG-II were barely detectable on quiescent cells.[96]
However, although systemic infusion of ANG-II induced fibrosis in other
organs (heart, kidney), no significant fibrotic response was detected in
the liver.[97] Nevertheless, when captopril was administered
in bile duct-ligated rats, it significantly attenuated the progression
of hepatic fibrosis.[98] Additional research is required on
the pathogenetic role of ANG-II in hepatic fibrogenesis and the possible
role of ANG-II receptor antagonists or angiotensin-converting enzyme
(ACE) inhibitors as antifibrotic agents.
Hepatic stellate cells are also a major target of ETs via type A and
type B receptors. Recently, Cho and associates[99] showed
that selective ETA receptor blockade dramatically reduced
collagen accumulation in rat secondary biliary fibrosis, a model
refractory to most potential antifibrotic agents.[99] Dual
receptor antagonism also prevents chronic fibrogenesis, as reported by
Rockey and colleagues.[100] Poo and coworkers[101]
studied the ET system in cirrhotic rats and concluded that the ETs do
not play a major role in the pathogenesis of portal hypertension, but do
participate in an autocrine loop that counteracts the development in
liver fibrogenesis. It is interesting to note that modification of the
microcirculation may well have a secondary effect on fibrogenesis and,
therefore, the interaction of vasoactive drugs/receptor
antagonists-hepatic stellate cells-microcirculation-fibrogenesis becomes
much more complex.[102]
A recent study evaluated the possible direct antifibrogenic effects
of canrenone, the active metabolite of spironolactone, in activated
human hepatic stellate cells -- it reduced in a dose-dependant manner
hepatic stellate cell proliferation and motility, de novo synthesis of
procollagen I/IV, and the hepatic stellate cell contraction.[103]
ACE Inhibitors and ANG-II Receptor Antagonists
ANG-II is considered to be a potential mediator of intrahepatic
portal hypertension because its plasma levels are increased in cirrhosis
and its administration induces a rise in portal pressure. The
enhancement of the adrenergic vasoconstrictor influence on the portal
system, direct contractile influence on stellate cells (and, therefore,
the increase in hepatic sinusoidal resistance) and, finally, sodium and
fluid retention induced by stimulation of aldosterone secretion may all
be mechanisms that contribute to the portal hypertensive effect of ANG-II.
Hence, the use of ACE inhibitors and ANG-II receptor antagonists should
improve portal hypertension by inhibiting the actions of ANG-II.
Captopril, an ACE inhibitor, has been evaluated in patients with
cirrhosis. No significant change in the HVPG was detected when this
agent was administered either as a single oral dose or for 3 weeks.[104,105]
In addition, there was a small but significant decrease in mean arterial
pressure, glomerular filtration rate, and urinary sodium excretion in
patients with cirrhosis with or without ascites.[104-106]
When enalapril -- likely more effective than captopril as an ACE
inhibitor[107] -- was tested, a significant reduction in HVPG
was observed, although there was a poor response in patients with severe
liver dysfunction.[108,109] Although mean arterial pressure
decreased, renal function did not change significantly. In another
study,[110] 5 different ACE inhibitors decreased portal flow
volume and total portal circulation resistance index, presumably
decreasing portal pressure.
ANG-II receptor antagonists were first studied in 1981 when
intravenous infusion of saralasin significantly reduced WHVP -- and also
mean arterial pressure.[111] Losartan produced a dramatic
reduction -- 46.8%+/- 15.5% -- in HVPG in all patients with severe and
moderate portal hypertension (the majority were alcoholic) without a
clinically important decrease in arterial blood pressure. Renal function
did not deteriorate.[112] Unfortunately, results of a recent
randomized controlled trial failed to confirm the above exciting data;
long-term losartan administration did not significantly reduce HVPG and
resulted in hypotension and a reduced glomerular filtration rate in
patients with moderate liver failure.[113] Irbesartan, an ANG-II
antagonist that does not require hepatic metabolism to an active
metabolite, has been reported to reduce HVPG by 42%.[114]
However, in a recent study, irbesartan only modestly reduced portal
pressure and induced marked arterial hypotension and renal impairment in
patients with advanced cirrhosis.[115] The pronounced effects
of reducing arterial pressure with marginal reduction in portal pressure
were once again emphasized in a pilot study with 25 patients with
cirrhosis.[116]
We recently reviewed the therapeutic effects of ACE and ANG-II
inhibitors in the management of chronic liver disease. These drugs may
prove to be useful in patients with early cirrhosis because of their
antifibrotic potential and the apparent absence of any deleterious renal
or systemic effects in this setting. Conversely, in cirrhotics with
established cirrhosis or end-stage liver disease, the
renin-angiotensin-aldosterone system is markedly activated, and
therefore any potentially beneficial effect of ANG-II inhibitors would
be countered by their unfavorable effect on systemic and renal
hemodynamics.[117]
Alpha-adrenoceptor Antagonists
Prazosin, an alpha-1-adrenergic blocker, is another vasodilator that
reduces portal pressure in patients with cirrhosis; it may have
synergism with propranolol. An initial study comparing prazosin with
propranolol showed reduction in the HVPG by 18% and 25%, respectively.[118]
Larger reductions in HVPG were reported in later studies: acute
reduction of HVPG (25.7%) and chronic reduction of HVPG (25.7%).
However, a significant fall in mean arterial pressure as well as a
decrease in sodium excretion (and, therefore, ascites) were observed.[119]
These findings were confirmed in a subsequent investigation that
compared propranolol plus prazosin with propranolol plus ISMN.[120]
The study authors reported that the combination of propranolol and
prazosin led to a greater reduction in HVPG (P < .01), but side
effects occurred more frequently in this group (46% vs 25%). These side
effects may preclude its use. At present, no clinical trials using
prazosin in primary or secondary prophylaxis of variceal hemorrhage are
available.
Carvedilol
Carvedilol is a novel vasodilating nonselective beta-blocker with
weak intrinsic anti-alpha-1-adrenergic and calcium channel antagonism.[121]
It has a rapid onset of action, with 2-4 times greater beta-blocking
action than propranolol.
The hemodynamic effects of acute and chronic treatment with
carvedilol in patients with cirrhosis have been assessed in 5 studies.[122-126]
In a randomized controlled trial,[123] carvedilol given as a
single dose decreased HVPG to > 20% from baseline and to < 12 mmHg (the
threshold for esophageal variceal bleed) in more than 50% of patients.
However, carvedilol, compared with propranolol, was associated with a
greater reduction in mean arterial pressure. The same group of
investigators expressed concern about this reduction in mean arterial
pressure in a recently published abstract that reported on chronic
administration of carvedilol at 31 mg/day.[124] Four weeks of
therapy with 25 mg/day of carvedilol had similar portal hypotensive
effects and no significant effects on mean arterial pressure, hepatic
blood flow, or renal function; however, a high dropout rate was
observed, mostly due to systemic hypotension.[125] When
recently tested in 10 patients with cirrhosis for a period of 4 weeks,
low-dose (12.5 mg/day) carvedilol produced a significant reduction in
portal pressure, with minimal effects on systemic hemodynamics.[126]
Carvedilol has unpredictable bioavailability among the population of
patients with cirrhosis; therefore, it should be used with caution due
to the potential for systemic hypotension. A low starting dose of 3.125
mg given twice daily (as in patients with heart failure) is strongly
recommended. To date, there are no clinical studies examining the effect
of carvedilol in preventing variceal bleeding.
Clonidine
Clonidine is a central alpha-2-adrenoreceptor agonist that induces a
sustained decrease in sympathetic nervous activity and portal pressure,
without adverse effects on hepatic blood flow or liver function.[127]
Short- and long-term clonidine administration did not modify renal
hemodynamics or induce natriuretic responses in patients with ascites
despite the marked decrease in arterial pressure and the reduction in
cardiac output.[128] Clonidine administration was associated
with a greater decrease in portal pressure compared with propranolol in
patients with alcoholic cirrhosis.[127] In a more recent
study,[129] only when combined with propranolol was clonidine
associated with a reduction in portal blood flow. There are no data
regarding the use of clonidine in the prophylaxis of variceal bleeding.
However, the hypotensive effect of this agent may limit its clinical
use.
Diuretics
Most patients with portal hypertension have an expanded plasma
volume, associated with a peripheral vasodilation. The use of
antialdosteronic drugs aims at decreasing portal pressure through a
reduction in blood volume. The administration of loop diuretics is
associated with acute depletion of plasma volume, with a reduction in
the portohepatic gradient -- but this depletion is promptly followed by
an increase in sodium retention.[130,131] Chronic
administration of spironolactone in patients with cirrhosis without
ascites leads to a significant reduction in the HVPG.[132,133]
Moreover, results of a recent study demonstrated the efficacy of
spironolactone in reducing esophageal varix pressure, both as a single
agent and in combination with propranolol in patients who did not
respond to beta-blockers.[134] However, Sugano and colleagues[135]
showed that spironolactone given as an adjunct to low-dose transdermal
nitroglycerin did not demonstrate a therapeutic portal-pressure
reduction in cirrhotic patients.
The use of antialdosteronic agents, which are already widely used in
patients with cirrhosis for the treatment of ascites, may be useful as
adjunctive therapy in the treatment of portal hypertension.
5-hydroxytryptamine (5-HT) Receptor Antagonists
A serotoninergic mechanism has been reported to contribute to the
hyperdynamic circulation of portal hypertension. Several studies
conducted in portal hypertensive rats demonstrated that serotonin
antagonists decreased portal pressure, mainly due to a decrease in
portal vein inflow. These findings led to human studies, which showed
significant reduction in the HVPG (from 23% to 14.6%) as well as in mean
arterial pressure after single[136] dose or chronic[137]
administration of ketanserin. Additionally, reversible portosystemic
encephalopathy was observed in 50% of patients in one study.[138]
Combination treatment with 5-HT3 antagonists and propranolol
has also been studied and was found to be associated with a reduction in
the HVPG in patients who did not initially respond to propranolol.[139]
An initial reduction in the portal pressure was not sustained during
follow-up.[138]
Antibiotics
The strong association between bacterial infections and
gastrointestinal bleeding has led to the use of antibiotic prophylaxis
in the setting of acute gastrointestinal bleeding. The obvious
hypothesis that could explain this connection is that gastrointestinal
hemorrhage may predispose bleeding cirrhotic patients to bacteremia.
However, this proposal has been challenged by data that support a
different sequence of events. In our unit, we have postulated that
bacterial infection may be the critical factor that triggers
gastrointestinal hemorrhage, particularly variceal bleeding.[140]
In patients with varices, the high levels of endotoxin introduced into
systemic circulation during episodes of bacterial infection[141,142]
result in a further increase in portal pressure through the synthesis of
ETs and contraction of hepatic stellate cells[143]; induction
of cyclooxygenase products may also contribute to this process.[144]
Furthermore, endotoxin-induced NO, along with prostacyclin induced by
both ET and endotoxin, could inhibit platelet aggregation.[145]
The increase in portal -- and subsequently variceal -- pressure, coupled
with impairment in primary hemostasis, could lead to the onset of
variceal bleeding. Based on these data, antibiotic treatment in
combination with oral NSBBs or other drugs may have a role in the
prevention of variceal bleeding, and thus requires serious consideration
and investigation.
Agents That Increase the Lower Esophageal Sphincter Pressure
Agents that constrict the physiologic lower esophageal sphincter --
that is, domperidone and metoclopramide -- have been suggested as
therapy for the management of variceal bleeding. These agents reduce
variceal blood flow by constricting the "palisade zone," where the
collaterals feed the varices. Results of previous studies have shown
that these drugs decrease azygos blood flow and variceal pressure.[146,147]
However, the role of these compounds in arresting variceal bleeding is
uncertain.[148]
Antianginal Agents
While organic nitrates reduce portohepatic pressure, they lower
arterial pressure and induce tolerance. Molsidomine, an antianginal
agent which is known to have little effect on arterial pressure in
normal patients and does not produce pharmacologic tolerance, has been
studied in a population of patients with cirrhosis. In this setting,
molsidomine was found to be associated with significant and sustained
reduction in WHVP (11%), HVPG (15%), and mean arterial pressure (13.5%).[149]
When the combination of propranolol and molsidomine was studied in a
randomized controlled trial of 34 patients, results showed that it did
not achieve greater reduction in HVPG than propranolol given alone.[150]
However, Combis and colleagues[151] supported the use of
combination molsidomine and propranolol therapy based on a 21% reduction
in HVPG that was reported in a study of 15 patients. Similarly,
favorable results with this regimen were reported in animal studies[152];
an antifibrotic effect of molsidomine was also observed.[153]
Medscape General Medicine 5(2),2003
Doctors are advocating an alternative treatment approach
for minimal hepatic encephalopathy (MHE), a liver condition that can also
cause brain dysfunction in some patients. MHE can cause changes in
behavior, intelligence, consciousness and neuromuscular function, experts
say. Minimal hepatic encephalopathy is a more subtle version of the overt
form, causing only minimal dysfunction. Since ammonia has been shown to
play a key part in the development of overt hepatic encephalopathy,
treatment options for MHE have also focused on reducing ammonia levels.
Synbiotics: An Alternative for MHE?
In a study in the May 2004 issue of the medical journal Hepatology,1
researchers in China, Britain and Australia considered the effects
of treatment with synbiotics or fermentable fiber that alters the flora in
the intestinal tract of
cirrhosis patients. This also lowers pH
levels, as well as blood levels of ammonia, doctors contend.
Flora is the medical term for the various microorganisms
that exist in the body.
When MHE occurs, the liver cannot properly detoxify and
metabolize toxic substances in the body. As a result, these toxic
substances, like ammonia, build up in the bloodstream. This ammonia can
also be created by intestinal bacteria.2
What Are Synbiotics?
Synbiotics is an umbrella term used to define both probiotics and
prebiotics. A probiotic is a viable microbial dietary supplement that
beneficially affects the host through certain effects in the intestinal
tract. These are widely used to prepare fermented dairy products like
yogurt and freeze-dried cultures.3 A prebiotic is a
nondigestable food ingredient that beneficially affects the host by
selectively stimulating growth and/or the activity of one or more numbers
of bacteria in the colon.3
To evaluate the effects of synbiotics and fermentable
fiber on microorganisms living in the intestinal tract, as well as MHE,
the scientists conducted a pilot study of 55 patients with the disease.
Twenty of them were treated for a month with a daily synbiotic
preparation, another 20 took fermentable fibers for 30 days, and the
remaining 15 received a placebo for a month.
At the 1-month mark, all patients were re-screened for
MHE, and the researchers also evaluated the levels of intestinal flora in
three separate fecal samples. Those were compared with the findings of
intestinal flora of 20 healthy volunteers.
Comparing Notes
At the end of the study period, half of the patients who were treated with
either the synbiotic preparation or fermentable fiber showed a reversal of
MHE, compared to a 13% reversal rate in the placebo group. Further,
patients in both treatment groups had a lower fecal pH level at day 30,
along with significantly reduced levels of ammonia in their bloodstream,
and significantly reduced endotoxin levels.
There were benefits for cirrhotic patients in the study,
as well. Both treatments appeared to have significantly altered the
intestinal flora of patients with cirrhosis, said the study investigators.
At the start of the study, the cirrhotic patients with MHE were found to
have significant fecal overgrowths of E. coli and Staphylococcus.
Treatment with the synbiotic preparation reduced these levels to those of
the healthy individuals. Treatment with placebo did not change the counts
of any of the intestinal flora, the investigators found.
"Our study is the first to examine the impact of
synbiotics and fermentable fiber on MHE and other aspects of hepatic
function in patients with cirrhosis," the study authors reported. "We
conclude that treatment with synbiotics or fermentable fiber alone is an
alternative to use of non-absorbable disaccharides, such as lactulose, for
the management of MHE in patients with cirrhosis. Significant reductions
in viable counts of potentially pathogenic [disease-causing] gut flora
occur with both treatments."
Lactulose is a laxative that is used to prevent bacteria
in the intestines from making toxic ammonia.2
'Impressive and Exciting'
In an editorial about the study, Steven F. Solga, M.D., and Anna Mae
Diehl, M.D., of Johns Hopkins University discuss the "impressive and
exciting improvements in hepatic encephalopathy with both synbiotic
therapy and fiber alone." They note that it is even more exciting that
altering intestinal flora may improve not only hepatic encephalopathy, but
also
liver disease.
"We expect this research to stimulate further interest
in the study of gut flora therapy, and the 'gut-liver' axis, because the
liver does, indeed, care about the gut," they wrote.
1. Liu Q, Duan ZP, Ha da K et al. Synbiotic modulation
of gut flora: Effect on minimal hepatic encephalopathy in patients with
cirrhosis. Hepatology 2004 May;39(5):1441-9.
2. Duke University Medical Center.
3. Roberfroid MB. Prebiotics and probiotics: Are they functional foods?
Am J Clin Nutr 2000 Jun;71(6):1682S-1687s.
John Martin is a long-time health journalist and an
editor for Priority Healthcare. His credits include coverage of health
news for the website of Fox Television's The Health Network, and articles
for the New York Post and other consumer and trade publications.
|
The Benefit of Natural
Therapies
B Vitamins and Metabolic Functioning
The Synergistic Effects of Vitamins C and E
Essential Trace Minerals
Protecting and Improving Liver Function
Improving Cellular Metabolism
Amino Acids that Support Liver Health
Herbal Extracts
Due to the small number of conventional drug therapies presently used
to treat cirrhosis, alternative therapies must be considered. Note that
the vast majority of natural or alternative treatments act by having an
antioxidant or anti-inflammatory effect. As with almost all disease
processes, research has demonstrated that good antioxidant levels are
necessary for optimum health and to protect us from the physical
assaults of trauma and disease. Some of the therapies listed in this
section also act by having an effect on the immune system (an immune
modulating effect).
Because the liver can often continue to perform essential functions
in spite of serious damage, it is important to eat foods and take proper
nutrients to retain its regeneration and detoxification abilities.
B Vitamins and Metabolic Functioning
Vitamin B Complex
Folic Acid
Choline
Vitamin B Complex
Vitamin B complex is a group of vitamins (B1, thiamine; B2, riboflavin;
B3, niacin; B5, pantothenic acid; B6, pyridoxine; folic acid; betaine;
inositol; and B12, cyanocobalamin) that differ from each other in
structure and the effect they have on the human body. The B vitamins
(thiamine, riboflavin, niacin, pantothenic acid, pyridoxine) play a
vital role in numerous metabolic functions including enzyme activities.
These enzyme activities have many roles and are involved in the
metabolism of carbohydrates and fats, functioning of the nervous and
digestive systems, production of red blood cells, and having a
synergistic effect with each other (Clayman 1989). The B vitamins are
found in large quantities in the human liver. Dietary sources of vitamin
B are wheat germ, bran, whole grain cereals and bread, brown rice,
pasta, fish, lean meats, beans, nuts, bananas, green leafy vegetables,
and eggs (Clayman 1989). Heat and overcooking destroys the B vitamins (Glanze
1996).
Folic Acid
Folic acid (vitamin B4) is an important member of the B complex family,
known for reducing harmful levels of homocysteine (a sulfur-containing
amino acid) known to be a major culprit in heart disease. At normal
levels, homocysteine plays a vital role in the biosynthesis of cysteine,
which assists glutathione in the liver to detoxify carcinogens and other
toxins, but without adequate methylation, which is provided by folic
acid and other B vitamins, biochemical reactions generated from
beneficial byproducts of homocysteine cannot occur.
Decreases in folate (folic acid) are also associated with increased
levels of lipoperoxidases, that is, an indicator of increased oxidative
stress. Therefore, folic acid is potentially beneficial in the early
stages of cirrhosis or for the ongoing oxidative damage seen in the
cirrhotic process. In humans with viral hepatitis, treatment with folic
acid improved liver chemistry measurements in the recovery period
following the illness. This improvement was thought to be due to an
effect on nucleotide (genetic building block) synthesis (Zviarynski et
al. 1999). In an experiment using rats, the occurrence of decreased
folate and elevated homocysteine documented the strong association of
decreased folate with increased oxidative stress and liver peroxidation
(Huang et al. 2001).
Dietary sources of folic acid are green, leafy vegetables such as
broccoli and spinach; mushrooms; liver; nuts; dried beans and peas; egg
yolk; and whole-wheat breads and cereals (Clayman 1989; Glanze 1996). A
varied diet that includes fruits and vegetables will usually provide
sufficient folic acid, but mild to moderate deficiencies are not
uncommon. More severe deficiencies result from certain blood disorders,
malabsorption disorders, alcohol dependence, and certain drugs (oral
contraceptives, anticonvulsants, antimalarials, analgesics,
corticosteroids, and sulfonamides) (Clayman 1989).
Choline
Choline is another of the B complex vitamins, essential for the use of
fats in the body. It is a precursor to acetylcholine, a nerve signal
carrier in the brain. Choline also stops fats from being deposited in
the liver and help move fats into the cells. Deficiency of choline can
lead to cirrhosis with associated conditions such as bleeding; kidney
damage hypertension (high blood pressure); cholesterolemia (high blood
levels of cholesterol); and atherosclerosis (occulsive deposits in blood
vessels) (Glanze 1996). Sources of dietary choline are liver, wheat
germ, legumes, brewer's yeast, and egg yolk.
The Synergistic Effects of Vitamins C and E
Vitamins C and E
Vitamins C and E used in combination have been demonstrated to improve
liver function in chronic liver disease patients. Both vitamins C and E
act as antioxidants. Vitamin C is a potent antioxidant that is found
naturally in many fruits and vegetables. Researchers have found
inadequate levels of vitamin C in patients with degenerative diseases.
According to Garg et al. (2000), vitamin C has protective effects
against liver oxidative damage, particularly when used in combination
with vitamin E. Garg et al. (2000) found that supplementation in rats
lowered plasma and liver lipid peroxidation, normalized plasma vitamin C
levels, and raised vitamin E above normal levels, suggesting that the
improved levels of lipid peroxidation products in the plasma and liver
with vitamin C and E supplementation and the activities of antioxidant
enzymes in the liver indicated that vitamins C and E reduced lipid
peroxidation by quenching free radicals.
Sources of dietary vitamin C are fresh fruits and vegetables.
Particularly good sources are citrus fruits, tomatoes, green leafy
vegetables, potatoes, green peppers, strawberries, and cantaloupe.
Vitamin E is found in vegetable oils, nuts, meats, green leafy
vegetables, whole grain cereals, wheat germ, and egg yolk (Clayman
1989).
Essential Trace Minerals
Selenium
Zinc
CoQ10
Selenium
Selenium is a trace element that acts by several mechanisms, including
detoxifying liver enzymes, exerting anti-inflammatory effects, and
providing antioxidant defense. Selenium is found in minute amounts in
foods (Glanze 1996), with the richest sources being from meats, fish,
whole grains, and dairy products. The selenium content of vegetables is
dependent on the soil in which they are grown (Clayman 1989). Using
selenium-deficient rats, experiments have shown that selenium deficiency
causes oxidative stress (Ueda et al. 2000). The presence of selenium
helps induce and maintain the glutathione antioxidant system.
Epidemiological studies in China have also shown that selenium
provides protection against both hepatitis B and C and liver cancer. In
a 4-year trial on 130,471 Chinese individuals, those who were given
selenium-spiked table salt showed a 35.1% reduction in primary liver
cancer, compared with the group given salt without selenium added. A
clinical study of 226 hepatitis B-positive people showed that one
200-mcg tablet daily of selenium reduced the incidence of primary liver
cancer to zero. Upon cessation of selenium supplementation, primary
liver cancer incidences began to rise, indicating that viral hepatitis
patients should take selenium on a continuous basis (Yu et al. 1997).
Zinc
Zinc is used in numerous drugs and preparations that are protective:
zinc oxide in skin ointments; zinc stearate in acne and eczema
preparations; and zinc permanganate to treat bladder inflammation. Zinc
deficiency features weakness, decreased taste and appetite, lengthy
wound healing, and risk of infection. Zinc levels that are low have also
been related to the progression of cirrhosis to hepatic encephalopathy
(Romero-Gomez et al. 2001). An earlier study in rats (Okegbile et al.
1998) demonstrated that the amount of dietary zinc dramatically affected
the ability of the rats' livers to synthesize cellular components
(nucleic acid building blocks) and maintain normal alkaline phosphatase
(indicated by a blood test of liver function, which is related to
cholestasis or accumulation of bile acids). Cholestasis has been shown
to play a role in facilitating the development of cirrhosis.) Dietary
sources of zinc are meats, eggs, liver, seafood, vegetables with pods,
nuts, peanut butter, and whole-grain cereals (Glanze 1996). Zinc
supplementation can vary from 25-90 mg daily.
Multifaceted Effects of CoQ10
Coenzyme Q10 (CoQ10) is an excellent antioxidant that is protective for
a liver that has been damaged by ischemia (reduced blood flow). CoQ10 is
also an important component of healthy metabolism. It protects the
mitochondria and cell membrane from oxidative damage and helps generate
ATP, the energy source for cells. CoQ10 is absorbed by the lymphatic
system and distributed throughout the body. Japanese researchers studied
the effects of the toxic drug hydrazine on liver cells. They
administered hydrazine to rats to study the effect of free radicals on
liver cells (hepatocytes). One group of rats was given hydrazine only; a
second group of rats was given CoQ10 in addition to the hydrazine.
Hepatocyte cell mitochondria from the hydrazine-only group were found to
be extremely enlarged, a state often preceding cell death from oxidative
stress. The mitochondria of rats given CoQ10 along with hydrazine were
nearly normal, showing only slight enlargement.
-
Note: Cachexia is a condition
of general poor health and dietary state associated with wasting
diseases. Hydrazine sulfate is an anticachexia drug. Hydrazine sulfate
is also used to reverse the metabolic processes of debilitation and
weight loss in some cancer patients (NCI 2001). Other researchers have
reported that hydrazine sulfate also acts to stabilize or cause some
types of tumors to regress in some patients, but this benefit has been
contested (Green 1997). Therefore, drugs containing hydrazine may be
required in a treatment plan even when the liver is weakened or at
risk.
In other studies in rats, liver ischemia (poor blood supply) was
induced surgically to investigate the effects of CoQ10 on oxidative
stress (Yamamura et al. 1980; Genova et al. 1999). In the study by
Genova et al. (1999), lipid peroxidation occurred as a result of
ischemia. However, when the rats were pretreated with CoQ10 for 14 days,
the liver peroxidation parameters were normalized. The CoQ10-treated
rats were also more resistant than nontreated rats to oxidative stress
by free radicals. According to Genova et al. (1999), their preliminary
study suggests that pretreatment with CoQ10 can have a beneficial effect
against oxidative damage during surgical liver transplantation. Ito et
al. (1999) induced hepatic ischemia by clamping the liver artery, portal
vein, and bile duct. After 15 minutes, the levels of glutathione rapidly
decreased. When reperfusion was started, the glutathione levels promptly
increased for about an hour before they began to decline. When Ito et
al. administered CoQ10 to the rats prior to ischemia, the reduction of
glutathione levels induced by ischemia/reperfusion was protected.
Our bodies can produce some of the CoQ10 that we need. The rest is
synthesized from our diet. The best dietary sources of CoQ10 are fresh
sardines and mackerel; heart and liver of beef, pork, and lamb; meat
from beef and pork; and eggs. Vegetable sources of CoQ10 are spinach,
broccoli, peanuts, wheat germ, and whole grains. Meat sources of CoQ10
are higher than vegetable and grain sources. It is important to remember
that foods must be fresh and unprocessed (no milling, canning, freezing,
preserving, etc.) and grown in unpolluted areas to be considered as
viable sources (Bliznakov 1987). |
|
|
Protecting and Improving Liver
Function N-Acetyl-Cysteine
S-Adenosyl Methionine
Polyenylphosphatidylcholine
Alpha-Lipoic Acid
N-Acetyl-Cysteine (NAC)
N-acetyl-cysteine (NAC) is a substance that acts as an antioxidant or
free-radical scavenger. Most scientific articles related to liver
protection with NAC emphasize this effect. NAC is frequently used in
medical settings to treat liver toxicity associated with ingesting
Tylenol (also poisonous mushrooms). In this situation, NAC is given
orally or intravenously. In liver transplantation, NAC reduces liver
injury associated with reperfusion (resumption of blood flow after
transplant) (Taut et al. 2001; Weinbroum et al. 2001). NAC also has been
found to improve liver blood flow and liver function in patients who
have extremely critical infections such as septic shock (Rank et al
2000).
In ingestion of methanol (a very toxic form of alcohol different from
the ethanol in alcoholic drinks), NAC partially prevented liver damage
from methanol (Dobrzynska et al. 2000). Another study also showed that
NAC slowed liver damage caused by methanol (Dobrzynska et al. 2000). In
another experiment that used cocaine as a pro-oxidant, NAC was found to
exert a protective effect by acting as a precursor for glutathione, a
vitally important antioxidant and free-radical scavenger (Zaragoza et
al. 2000). The best dietary sources of NAC are meat, fish, poultry,
eggs, and dairy products (Young et al. 1994).
S-Adenosyl Methionine (SAMe)
SAMe is a methylation agent (a methyl group donor) and is necessary for
the synthesis of glutathione, necessary for liver health. Medical
studies have shown that SAMe has beneficial antioxidant effects on the
liver and other tissues, particularly in protecting and restoring liver
cell function destroyed by the hepatitis C virus. When mice were given
paracetamol (a hepatotoxic substance), SAMe was found to be as effective
as N-acetyl-cysteine (NAC) in preventing liver damage. Additionally,
SAMe has a positive effect on the fluidity of the cell membrane, as
demonstrated in red blood cells from patients with cirrhosis (Turchetti
et al. 2000). However, in a major review that was limited to alcoholic
liver disease and cirrhosis (Rambaldi et al. 2001), researchers
concluded that there were no significant effects of SAMe on mortality,
liver-related mortality, liver transplantation, or liver complications
in patients with alcoholic liver disease. This review concluded that
SAMe should not be used routinely in alcoholic liver disease.
In critical care medicine, it is occasionally necessary to provide
total nutrition via special IV solutions to patients who are unable to
eat for a prolonged period of time (i.e., several months). This process
is called total parenteral nutrition (TPN). Various complications are
associated with the parenteral method of providing calories and
nutrients, including liver cholestasis (interruption or blockage of the
bile ducts). When studying extremely ill pediatric surgical patients,
Amii et al. (1999) stated, "SAMe is the most promising treatment of
total parenteral nutrition-associated cholestasis." In another study on
hepatic cholestasis and oxidative stress in rats, Lopez et al. (2000)
concluded, "the results confirmed the function of SAMe as an antioxidant
and hepatoprotector."
SAMe is found naturally in every cell of the body. It is synthesized
from a combination of the amino acid L-methionine, folic acid, vitamin
B12, and trimethylglycine, provided all these ingredients are present
and performing (Anon. 2002).
Polyenylphosphatidylcholine (PC)
PC is one of the most important substances for liver protection and
health and is a primary constituent of the cell membrane. As such, PC is
necessary for integrity of liver cells. In studies in rats, PC has
prolonged the survival of rat liver cells in culture by stabilizing the
cell membrane (Miyazak et al. 1991). Liver cells that have been damaged
by alcohol or cirrhosis are unable to meet the ongoing demands of the
liver for phospholipid synthesis. Adding phospholipids such as PC via
oral intake played an important role in regeneration of damaged liver
cells (Horejsova et al. 1994). In an early study, Neuberger (1983)
stated: "It has been shown that orally administered polyunsaturated PC
can be incorporated into the liver cell membrane."
Other studies have shown the antifibrotic effect of PC. Not only does
PC inhibit the development of hepatic fibrosis, it actually accelerates
the regression of existing fibrosis (Ma et al. 1996). Part of this
effect is probably due to PC promoting the breakdown of collagen (Lieber
1999), but it may also be due to an inhibitory effect on the stellate
cell (Poniachik et al. 1999). In experimental studies, PC was also found
to protect against alcoholic cirrhosis in baboons and against carbon
tetrachloride-induced cirrhosis in rats (Aleynik et al. 1997). In
another study (Navder et al. 1997), PC was shown to prevent earlier
changes induced in the alcoholic liver before cirrhosis even develops.
When liver cells are damaged, apoptosis (programmed cell death) is
activated. If apoptosis can be decreased, more liver cells (hepatocytes)
can be preserved and actually still function. PC decreases apoptosis,
but alcohol consumption increases the rate of apoptosis in liver cells
(Mi et al. 2000). The positive effect of PC on hepatocyte apoptosis is
probably via an antioxidant mechanism. As a result, the antioxidative
hepatoprotective mechanism of PC is one of the most studied mechanisms.
Numerous medical articles have noted the antioxidant properties of PC
and other related phospholipid compounds and how toxic metabolites
associated with liver injury are decreased when they are used (Navder et
al. 1999).
The best dietary sources of phosphatidylcholine are beef steak,
liver, organ meats, egg yolks, spinach, soybeans, cauliflower, germ,
peanuts, and brewer's yeast. Smaller amounts are found in oranges,
apples, potatoes, lettuce, and whole-wheat bread (Canty et al. 1994).
Alpha-Lipoic Acid (ALA)
Alpha-lipoic acid is an antioxidant that has been shown to decrease the
amount of hepatic fibrosis associated with liver injury. Both of these
mechanisms suggest it has promise for cirrhosis. Alpha-lipoic acid is
considered to be the universal antioxidant by Dr. Lester Packer, who has
studied the effects of ALA extensively (Constantinescu et al. 1994;
Packer 1994, 1997; Podda et al. 1994). Because alpha-lipoic acid is
fat-soluble, it can penetrate the cell membrane to exert therapeutic
action. It has been shown to effectively scavenge harmful free radicals,
chelate toxic heavy metals, and help to prevent mutated gene expression
(Biewenga et al. 1997). Another of its most beneficial functions is to
enhance the effects of other essential antioxidants including
glutathione, which is vital to the health of the liver (Lykkesfeld et
al. 1998; Khanna et al. 1999).
The effects of ALA have been studied in rats and mice. In studies in
rats, when the rat liver was insulted with a chemical agent, dietary
alpha-lipoic acid encouraged healing (Arend et al. 2000). Alpha-lipoic
acid also demonstrated promise in the treatment of sepsis (a
life-threatening systemic infection) (Liang et al. 2000) in septic mice.
In septic mice, alpha-lipoic acid improved carbohydrate metabolism in
liver cells by its effect on nitric oxide pathways.
The body can make some of its own lipoic acid, but most must be
obtained from dietary sources, either from food or supplements. Dietary
sources of alpha-lipoic acid include yeast, liver, and spinach,
potatoes, and carrots. Unfortunately, the best sources of dietary alpha-lipoic
acid are red meats, which also contain high levels of saturated fats,
and it would require huge amounts of spinach to consume the amount of
alpha-lipoic acid conveniently obtained from the supplementation of 1
capsule.
Improving Cellular Metabolism
Acetyl-L-Carnitine
Acetyl-L-carnitine has been shown to convert some hepatic parameters to
more youthful levels. Acetyl-L-carnitine is the biologically active form
of the amino acid L-carnitine that has been shown to protect cells
throughout the body from age-related degeneration. By facilitating the
youthful transport of fatty acids into the cell mitochondria, acetyl-L-carnitine
facilitates conversion of dietary fats to energy and muscle. Acetyl-L-carnitine
has also been shown to regenerate nerves (Fernandez et al. 1997);
provide protection against glutamate and ammonia-induced toxicity to the
brain (Rao et al. 1999); and to reverse the effects of heart aging in
animals (Paradies et al. 1999).
In an aging mouse model, two studies (Hagen et al. 1998a, b)
illustrated the ability of acetyl-L-carnitine to increase cellular
respiration. The first study at the University of California (Berkeley)
examined liver parenchymal cells in old mice after feeding them a 1.5%
solution of acetyl-L-carnitine for 1 month (Hagen et al. 1998a). The
results showed that acetyl-L-carnitine supplementation significantly
reversed the age-associated decline of mitochondrial membrane function.
In the second study, also at Berkeley, researchers again confirmed the
ability of acetyl-L-carnitine to reverse age-related mitochondrial decay
(Hagan et al. 1998b). In another study, also conducted with old rats,
acetyl-L-carnitine improved liver metabolism and slowed age-related
decline in metabolism and biosynthetic function (Mollica et al. 2001).
Primary dietary sources of L-carnitine are meats (especially beef and
lamb) and dairy products. The liver and kidneys can also synthesize L-carnitine
from the amino acids lysine and methionine (Plawecki 2001).
Amino Acids that Support Liver Health
Taurine
L-Arginine
L-Glutamine
Branched-Chain Amino Acids
Taurine
Taurine is a conditionally essential amino acid produced from cysteine
by the body. It is abundantly found in the body, particularly the
central nervous system where it is thought to have a regulating
influence. Taurine is a crystallized acid that comes from bile, which is
produced by the liver. Sources of dietary taurine are cow's milk, meats,
seafood, and poultry. Plants have virtually no taurine. Taurine can be
deficient in our daily diet and can also be insufficiently produced by
the body in certain disease states. Taurine exerts a protective effect
against liver cirrhosis, working by a mechanism that decreases oxidative
stress (Balkan et al. 2001).
L-Arginine
L-arginine is an essential amino acid. L-arginine is also a key building
block for repair of damaged tissue. Numerous studies have documented
enhanced wound healing in response to L-arginine supplements. Dietary
sources of L-arginine are high-protein foods (meats, eggs, nuts and nut
products), seeds, brown rice, whole-wheat grains, oatmeal, raisins, and
legumes. Persons with diabetes (or borderline diabetics), persons who do
not have complete bone growth (children and teenagers), pregnant women,
persons who have a latent herpes virus, or persons with psychoses should
consult their physician before taking L-arginine. Antioxidants should
always be taken with L-arginine.
L-Glutamine
L-glutamine is a nonessential amino acid that has benefits for the liver
and intestines, particularly for those who use NSAIDs (nonsteroidal
anti-inflammatory drugs). L-glutamine may also be useful in neutralizing
the effects of alcohol and strengthening the immune system. Sources of
dietary L-glutamine are plant (e.g., nuts and nut products, seeds, and
brown rice) and animal protein (e.g., meats and eggs).
Branched-Chain Amino Acids
BCAAs are leucine, isoleucine, and valine. They are considered to be
essential amino acids because humans cannot survive unless these amino
acids are present in the diet. BCAAs are needed for the maintenance of
muscle tissue and appear to preserve muscle stores of glycogen (stored
form of carbohydrates that can be converted into energy). Dietary
sources of BCAAs are dairy products and red meat. Whey protein and egg
protein supplements are other sources. Most diets provide the daily
requirement of BCAAs for healthy people. However, in cases of physical
stress, we have increased energy requirements, in particular in persons
with cirrhosis.
Studies on alcoholic cirrhosis patients have shown benefits from
supplementing valine, leucine, and isoleucine. These branched-chain
amino acids can enhance protein synthesis in liver and muscle cells,
help restore liver function, and prevent chronic encephalopathy (Shimazu
1990; Chalasani et al. 1996). In studies, BCAAs have also been shown to
have therapeutic value in adults with cirrhosis of the liver. According
to the researchers, BCAAs seem to be the preferred substrate to meet
this requirement (Kato et al. 1998).
Herbal Extracts
Silymarin
Green Tea
Artichoke
Silymarin
Silymarin (also known as milk thistle or
Silybum marinum) is a member of
the aster family (Asteraceae) that has been used as a medicinal plant
since ancient times and is widely used in traditional European medicine.
The active extract of milk thistle is silymarin (Bosisio et al. 1992), a
mixture of flavolignans, including silydianin, silychristine, and
silibinin, with silibinin being the most biologically active. Although
the mechanisms are not yet fully understood, silymarin has proven to be
one of the most potent liver-protecting substances known. Its main
routes of protection appear to be the prevention of free-radical damage,
stabilization of plasma membranes, and stimulation of new liver cell
production.
According to several early studies, silymarin acts as an antioxidant
and free-radical scavenger that is many times more potent than vitamin E
(Hikino et al. 1984) and has also been shown to inhibit lipid
peroxidation and to prevent glutathione depletion induced by alcohol and
other liver toxins, even increasing total glutathione levels in the
liver by 35% over controls (Valenzuela et al. 1989). However, perhaps
the most interesting effect from the early studies of silymarin was its
ability to stimulate protein synthesis, resulting in production of new
liver cells to replace older, damaged ones (Sonnenbichler et al. 1986).
Studies also demonstrate the benefits of silymarin for protection
from numerous toxic chemicals such as carbon tetrachloride, ethanol,
poisonous mushrooms (Desplaces et al. 1975); alcohol and chronic
alcoholic hepatitis (Salmi et al. 1982); cirrhosis (Ferenci et al.
1989); acute and chronic hepatitis (Berenguer et al. 1977); and
hypercholesterolemia (high cholesterol) (Krecman et al. 1998).
Most medical studies cover the use of silymarin in the early forms of
liver degeneration, which occur prior to the development of cirrhosis.
However, ongoing research indicates that the development of cirrhosis is
a continuum, beginning with damaged liver cells and progressing on to an
intermediate stage such as fatty liver before actual development of
cirrhosis. Therefore, the potential for obtaining protective benefits
from silymarin is worth consideration. |
Liver
Cirrhosis
Green Tea
Green tea has been in widespread, common use in China for thousands of
years. In the last several decades, green tea has also been widely used
in the treatment of hepatic disease in Europe. Green tea has active
ingredients called catechin polyphenols. Catechins in green tea have
potential therapeutic significance because of their potent antioxidants,
which have an ability to neutralize free radicals and act as
free-radical scavengers. Green tea has been shown to have antiviral
activity and immune-stimulating properties (Kaul et al. 1985);
protective benefits from hepatotoxicity caused by carbon tetrachloride,
ethanol, and 2-nitropropane (a common industrial solvent also found in
tobacco smoke) (Lewis et al. 1979); promise for treatment of many types
of hepatic disease, particularly acute and chronic viral hepatitis; and
fibrosis (overgrowth of collagen) (Pontz et al.1982).
Additionally, green tea has hepatoprotective qualities that include
killing dangerous intestinal bacterial strains (Clostridium
and Escherichia coli) and
promoting the growth of friendly bacteria in the intestine; inhibiting
several viruses, including viral hepatitis; and lowering excessive iron
levels in the liver that would interfere with ribavirin and interferon
treatment for hepatitis C.
For most people, drinking green tea daily seems to be a most
practical, readily available means for providing protective liver
benefits and preventing chronic toxicity induced by oxidative stress
from environmental chemicals. The dose used for hepatic diseases in
clinical studies has typically been 1 gram of green tea three times
daily.
Artichoke
Artichoke (Cynara scolymus) is
an herb with antioxidant properties that are similar to silymarin.
Artichoke is used in Eastern parts of the world for its hepatoprotective
qualities. Like silymarin, it is a member of the aster family (Asteraceae).
It is native to the Mediterranean, where it has been in common use for
more than 2000 years. Also similar to silymarin, artichoke extract has
demonstrated strong antioxidant potential and a hepatoprotective effect,
protecting the liver from the damaging effects of toxins, such as carbon
tetrachloride and other environmental chemicals (Adzet et al. 1987;
Gebhardt 1995). Artichoke extract is also able to stimulate regeneration
of damaged liver tissue (Maros et al. 1966). The usefulness of artichoke
to prevent or reduce buildup of fat in the liver from chronic alcohol
consumption is noteworthy (Samochowiec et al. 1971; Wojciki 1978).
Experimental studies of hepatoprotective mechanisms have only been
conducted in animals because the procedure involves exposure to toxins.
The basic research method in this type of investigation is to administer
the test substance, in this case artichoke leaf extract, to the animal
prior to or simultaneously with, administration of a toxic substance and
observe the results. Gebhardt (1995) demonstrated hepatoprotective
effects against carbon tetrachloride-induced toxicity on liver cells
from rats. When studying rat liver cells exposed to t-BHP (tertiary
butylhydroperoxide), they found that artichoke leaf extract
significantly prevented damage.
Living with CirrhosIS
There is no cure for cirrhosis at this time. However, physicians
attempt to delay its progress, minimize liver cell damage, and reduce
the complications of the disease through the use of drugs and dietary
and lifestyle recommendations.
Once cirrhosis has been diagnosed, sodium and fluids should be
restricted and all alcohol consumption must cease. Antiemetics,
diuretics, and supplemental vitamins are often prescribed. Because of
the potential of bleeding, persons with cirrhosis should avoid straining
at the bowel and use stool softeners as directed by a qualified medical
caregiver. Violent sneezing, coughing, and nose blowing should also be
avoided. Untreated cirrhosis can be fatal. Patients should avoid
exposure to infections. They should eat small but frequent meals of
nutritious foods. They should also carefully follow caregiver
instructions from a medical professional.
More than half of all liver disease could be prevented if only we
simply acted on knowledge we already have! Avoiding or limiting the use
of alcoholic beverages is an excellent place to start because it is well
documented that alcohol destroys liver cells. Man-made chemicals also
pose an extreme threat to the liver. Always follow recommended standard
safety precautions for handling man-made chemicals. All ingested,
inhaled, and absorbed chemicals and toxins must be processed by the
liver.
If you have cirrhosis, stay one step ahead of the disease by watching
for the appearance of additional symptoms of cirrhosis or a change in
the symptoms you already have (e.g., increasing fatigue, worsening
appetite, nausea and vomiting, itching, jaundice, abdominal pain,
abdominal swelling, ankle swelling, bleeding or bruising more easily).
Report them to your physician immediately.
Cirrhosis causes the filtering process in the liver to slow down so
its ability to handle medication will be affected. The liver will
probably not remove drugs from the blood at the expected rate, causing
prescription drugs to act longer than expected. Report any drug
reactions to your physician immediately. Do not add any new medicine
(including over-the-counter medicines) without consulting your
physician. It is essential that your physician is always aware of all
medicines you take.
The liver is the only organ that can generate healthy, new tissue in
response to injury or disease. However, the exact moment at which
fibrosis becomes irreversible is not known. Cirrhosis with nodule
formation, portal hypertension, and early liver failure is generally
considered irreversible, but less advanced lesions can show remarkable
reversibility when the underlying cause of the liver injury is
controlled. Therefore, it is possible to regenerate a cirrhosis-damaged
liver if extraordinary therapies are followed and the underlying cause
of the cirrhosis is eliminated.
SUMMARY
If you have cirrhosis, consult a qualified physician who is
experienced in treating liver disease and who will coordinate your
treatment and manage the complications. Supplementation with
antioxidants, branched-chain amino acids, and all of the B complex of
vitamins except B3 (niacin) has been shown to have protective qualities
and to be beneficial for the liver. (For
specific antiviral therapies to help eradicate hepatitis B or C, refer
to the Hepatitis
B and
Hepatitis C protocols. Also see the protocols on
Hepatitis C
and Liver
Degenerative Disease for additional information.)
Maintain a nutritionally balanced diet that includes fruits,
vegetables, and appropriate levels of fats, carbohydrates, and protein.
- B vitamins are important for healthy
metabolism and liver health. Daily recommendations include:
- B1 (thiamine), 500 mg
- B2 (riboflavin), 75 mg
- B5 (pantothenic acid), 1500 mg
- B6 (pyridoxine), 200 mg
- B12 (cobalamin), sublingual methylcobalamin is recommended for
better absorption, one 5 mg lozenge 1-5 times daily
- Folic acid, 800 mcg daily
-
Vitamin B3 (niacin) should be avoided by people with liver
conditions.
- Choline helps reduce the amount of fat
deposited in the liver, 1500 mg daily.
- Antioxidant vitamins C and E work
together to help prevent free-radical damage to the liver.
- Take at least 500 mg of
vitamin C daily.
- Gamma E Tocopherol/Tocotrienols
provide the most broad-spectrum antioxidant protection, 1-2 capsules
daily.
- The trace mineral selenium has shown
antioxidant protection in the liver. Zinc is often deficient in the
cirrhotic liver. Take selenium, 200 mcg daily, and zinc, up to 90 mg
daily.
- CoQ10 protects the mitochondria from
oxidative damage and provides cellular energy, 300 mg daily.
- N-acetyl-cysteine (NAC) enhances the
production of glutathione and has protective benefits for the liver
from toxins. Take two 600-mg doses daily of NAC.
- S-adenosylmethionine (SAMe) can be
effective for protecting and restoring liver cell function. The
suggested dose of SAMe is 400 mg 3 times daily.
- A cost-effective alternative to SAMe
supplementation is TMG (trimethylglycine). Take two 500 mg tablets of
TMG after meals twice daily or as directed by a physician.
- Polyunsaturated phosphatidylcholine (PPC)
has been shown to prevent the development of fibrosis and cirrhosis
and to prevent lipid peroxidation and associated liver damage from
alcohol consumption. HepatoPro (formerly GastroPro) contains pure
pharmaceutical-grade polyunsaturated phosphatidylcholine (also known
as polyenylphosphatidylcholine). Take two to three 900-mg capsules
daily.
- Alpha-lipoic acid may help to decrease
hepatic fibrosis and increase glutathione production, two to four 250
mg capsules daily.
- Acetyl-L-carnitine will help to
maintain mitochondrial health. Take 2 daily doses of 1000 mg.
- Amino acids are required for protein
synthesis and metabolism. Certain amino acids are particularly
beneficial for diseased liver states:
- Taurine decreases oxidative
stress in the cirrhotic liver; 1-4 grams daily are recommended.
- L-arginine (5-10 grams daily)
and L-glutamine (2000 mg daily) may help lower blood levels of toxic
ammonia that build up when the liver is damaged. L-arginine can also
help facilitate regeneration of the liver, providing the liver still
has at least a 20% functional capacity.
- Alcoholic cirrhosis patients can
benefit from valine, leucine, and isoleucine supplements. These
branched-chain amino acids can enhance protein synthesis in the liver
and are especially beneficial in alcoholic cirrhosis. The suggested
dose is 2-4 capsules daily between meals with fruit juice or before
eating. Each capsule should contain 300 mg of leucine, 150 mg of
isoleucine, and 150 mg of valine.
- Green tea (95%) extract will lower
toxic levels of iron and provide protection from oxidation; take four
to ten 350-mg capsules daily. Each capsule should contain at least 100
mg of epigallocatechin gallate (EGCG).
Alcoholic liver disease patients should consider taking silymarin
extract from milk thistle. The most active flavonoid in silymarin is
silybinin. Silibinin Plus is formulated to the same potency as
European prescription drugs. One 325-mg capsule taken twice daily is
recommended for healthy people. Under a physician's supervision,
patients with liver disease may take up to 6 capsules daily.
- Artichoke extract will stimulate
damaged liver tissue and provide continued protection. One to three
300-mg doses of Artichoke Leaf Extract are recommended.
For specific antiviral therapies for the treatment of hepatitis B or
C, refer to the Hepatitis B and Hepatitis C protocols (see
the Liver
Degenerative Disease protocol for additional information).
The protocol on
Heavy Metal Toxicity contains extensive information about conditions
related to exposure to heavy metals.
For more
informatION
Contact the American Liver Foundation, (800) 465-4837 (
http://www.liverfoundation.org ); Hepatitis Foundation
International, (800) 891-0707 (
http://www.hepfi.org
); United Network for Organ Sharing (UNOS), (800) 330-8500 (
http://www.unos.org );
or the National Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health (
http://www.niddk.nih.gov). |
http://www.lef.org/protocols/prtcl-068d.shtml |
