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The Role of Nutritional Therapy
in Alcoholic Liver Disease
Christopher M. Griffith, M.D., and Steven Schenker, M.D.
Alcoholic liver disease (ALD) evolves through various stages, and malnutrition correlates with the
severity of ALD. Poor nutrition is caused both by the substitution of calories from alcohol for calories
from food and by the malabsorption and maldigestion of various nutrients attributed to ALD. The only
established therapy for ALD consists of abstinence from alcohol. Sufficient nutritional repletion coupled
with appropriate supportive treatment modalities may be effective in reducing complications associated
with ALD—particularly infection. Nutrition makes a significant positive contribution in the treatment of
ALD, especially in selected malnourished patients. K
EY WORDS: Ethanol metabolism; heavy alcohol use;
alcoholic liver disease; alcoholic fatty liver; alcoholic hepatitis; fibrosis; alcoholic cirrhosis; gut; infection;
anorexia; hepatic encephalopathy; nutrition; malnutrition; nutritional therapy; S-Adenosylmethionine (SAM);
antioxidants; milk thistle; silymaryin; phosphatidylcholine; dietary fat; vitamins
he study of malnutrition in alcoholic hepatitis) and only 20 percent Diversity
of
Liver
Injury
patients with alcoholic liver dis will progress to scarring of the liver (i.e.,
T Alcoholic liver injury is known to
ease (ALD) is based on several cirrhosis) (McCullough and O’Connor
general concepts and observations. 1998). Clearly, other risk factors, evolve through various stages. Patients
Researchers and clinicians previously including genetic predisposition, obesity, exhibit a variety of clinical symptoms
believed that malnutrition was the concomitant viral hepatitis infection, and signs in liver histology (as reviewed
primary cause of liver injury in ALD and poor nutrition, may contribute in Dasarathy and McCullough 2003).
rather than the consequence of excessive variably to the development of ALD. As previously mentioned, almost every
alcohol consumption. This view was Indeed, in a large study of hospital one with heavy alcohol consumption
based on the prevalence of malnutrition ized patients with varying severity of develops fatty liver. This often is a
in alcoholics and those with clinical ALD, malnutrition (especially the type rather benign disorder and considered
evidence of liver (i.e., hepatic) dysfunction caused by deficient protein and calories) reversible upon cessation of alcohol
resulting from alcohol consumption was closely associated (although not intake. In some cases, continued drink
(Mendenhall et al. 1984). It now is necessarily causal) with the severity of ing may result in the development of
widely accepted that the quantity and liver injury (Mendenhall et al. 1984). alcoholic hepatitis, which may—and
duration of alcohol consumption are the All patients with clinical evidence of often does—end in severe clinical dis
principal agents in the development of ease. The severity of disease and liver
alcoholic liver injury. This is based on ALD (regardless of severity) exhibited dysfunction correlates with an increas
animal and human data showing that some features of malnutrition. With ing shortterm mortality (as reviewed
ALD can develop in wellnourished regard to the possible value of nutritional in Dasarathy and McCullough 2003).
individuals who consume large amounts therapy, it would seem logical that It is in this acutely diseased group that
of alcohol (Mezey 1991). However, a patients with more severe deficits would optimal nutritional therapy might have
great deal of variability exists regarding benefit more, although convincing proof the most impact. Continued drinking
the individual development of progres of this, to our knowledge, is not available. in this group of patients may lead to
sive alcoholic liver injury. Although This article reviews the various forms
more than 90 percent of people with of liver injury; the basis for and role of HRISTOPHER M. GRIFFITH, M.D., is a
malnutrition in ALD, including the C
excessive alcohol consumption will TEVEN
fellow of Gastroenterology and S
develop fatty liver (defined as greater harmful effects of the products of alcohol SCHENKER, M.D., is professor of
than 5 percent fat in the liver), only up metabolism; evidence for the benefits Medicine and Pharmacology, both at the
to 35 percent will develop inflammation of nutrition; and special considerations University of Texas Health Science Center
of the liver caused by alcohol (i.e., for nutritional therapy in ALD. at San Antonio, San Antonio, Texas.
296
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Research
&
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Nutritional
Therapy
in
ALD
the development of excess scar tissue in Decreased Food Intake decreased intestinal enzyme activity
the liver (i.e., fibrosis) and the subse People with ALD will substitute calories (i.e., lactase) required for carbohydrate
quent anatomical changes of cirrhosis. from food with calories from alcohol. It digestion and absorption, and/or
Cirrhosis is considered a late stage of has been shown in patients with ALD decreased absorption from increased
the disease, clinically manifested by that calories from alcohol may con swelling of the gut. The latter is attrib
progressive liver dysfunction with asso tribute more than 50 percent of their uted to increased pressure in the drain
ciated yellowing of skin and whites total calories, with calories from pro ing vein (i.e., portal vein) and lym
of the eyes (i.e., jaundice)—caused by tein comprising only 6 to 10 percent phatic vessels connecting the intestines
decreased liver clearance of bilirubin, (Mendenhall et al. 1984). In addition, with the liver. The changes in intestinal
fluid accumulation in the abdomen the proportion of calories from alcohol digestion and absorption appear to
(i.e., ascites), and impaired brain func appears to increase, whereas those from reverse once the patient ceases drinking
tion caused by the accumulation of food decrease with escalating liver dys and starts to follow a normal diet, sug
ammonia in the brain tissues (i.e., function (Mezey 1991). This increase gesting that nutritional replacement
encephalopathy) (as reviewed in in alcohol calories and decrease in food may be of special benefit (Mezey 1991).
Dasarathy and McCullough 2003). calories may be partially explained by Finally, the preferential metabolism
These three disorders may occur the diversion of funds from the pur of alcohol by the liver alters the meta
separately or often in association with chase of food to that of alcohol; how bolism of sugars (i.e., carbohydrates),
each other. In many instances, these ever, hospitalized patients with ALD fats (i.e., lipids), and proteins (i.e.,
stages of liver injury may be difficult to given adequate access to nutrition still amino acids/nitrogen) (Mezey 1991).
distinguish either clinically or by labo demonstrate decreased ingestion of Abnormal breakdown of fat results in
ratory measures of liver dysfunction (as nonalcohol calories (Schenker and the formation of triglycerides that are
reviewed in Dasarathy and McCullough Halff 1993). This decreased desire for deposited in the liver, manifesting as
2003). Prior studies regarding nutri food (i.e., anorexia) also correlates with fatty liver (Schenker and Halff 1993).
tional therapy in ALD often did not the severity of liver injury (Hirsh et al. Altered fat metabolism also may propa
differentiate between these various types 1999; Mendenhall et al. 1995). Anorexia gate fibrosis by increasing collagen for
of liver disease, complicating researchers’ is pervasive in ALD and is a key reason mation (Schenker and Halff 1993).
abilities to assess the true benefit of for decreased dietary intake of nonalcohol The altered functional mass of the liver
nutritional therapy. This has been a prob calories (Mezey 1991). from these increased deposits of fat and
lem in the assessment of such data in the collagen may result in decreased stores
past as well as for the present authors. of vitamins and carbohydrates. Glycogen,
Poor Absorption and Digestion of the storage form of carbohydrates in
Nutrients the liver, serves as an energy reserve for
Basis
for
Malnutrition
in
Another factor contributing to poor periods of increased energy need.
ALD
nutrition in patients with ALD is the Inadequate glycogen reserves cause the
malabsorption and maldigestion of var body to make use of other metabolic
The signs and symptoms of nutritional ious nutrients from the gut (Mezey pathways for energy, such as the break
deficits in ALD patients have been well down of muscle (Schenker and Halff
1991; Schenker and Halff 1993). This 1993). This may explain the increased
characterized (Mendenhall et al. 1984; may relate to the impaired output of muscle wasting, increased nitrogen
Mezey 1991; Schenker and Halff 1993; bile from the liver, resulting in decreased excretion in the stool, and negative
Nompleggi and Bonkovsky 1994; absorption of fat and fatsoluble vita nitrogen balance seen in patients with
Hirsh et al. 1999) and include muscle mins. The possibility of concomitant ALD. It is important to note that in
wasting, decreased lean body mass, var pancreatitis causing decreased output healthy individuals these alternate
ious vitamin deficiencies, and decreased of enzymes necessary for absorption of pathways of energy usually are found
measurable serum proteins. A complete fats and proteins also can occur with only after periods of prolonged fasting
description of specific nutritional deficits alcohol abuse. Moreover, there may or starvation. Patients with ALD, how
is beyond the scope of this review; be a direct effect of alcohol on the gut ever, may begin to use alternative path
however, it is important to consider the itself. Alcohol has been demonstrated ways after only an overnight fast, sug
factors that contribute to malnutrition to decrease the intestinal absorption gesting that the frequency of feeding is
in individuals with ALD, as they may of amino acids and various vitamins, as important as the type of feeding
have an influence on the administration particularly thiamine, folate, and B (McCullough and O’Connor 1998).
of nutritional therapy. There are many 12
(Schenker and Halff 1993). Malabsorp The basis for nutritional deficits is
reasons for the deficits and abnormalities tion also may occur through mechani summarized in Table 1. This subject
that occur as a result of malnutrition. cal alterations in the gut. This may be also has been extensively discussed in
These are outlined below and include attributed to increased intestinal another review (Schenker and Halff
decreased dietary intake and poor swelling (i.e., edema) from a lack of 1993), which can be referenced for
absorption and digestion of nutrients. structural proteins in the gut wall, more details.
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Role
of
Malnutrition
in
tion of various signaling chemicals (i.e., mins (e.g., vitamin E) that may offer a
ALD
cytokines), which may further con protective effect as antioxidants
tribute to tissue injury (as reviewed in (Schenker and Halff 1993).
It is not precisely known how alcohol Dasarathy and McCullough 2003).
causes liver damage. The net effect of The liver has a builtin defense Increased Risk of Infection
nutrition on the development of ALD against harmful oxidation in gluta
may involve multiple factors, including thione, a compound that assists in the Patients with ALD are at increased risk
freeradical damage and increased risk removal of the toxic byproducts of of infection (Schenker and Halff 1993;
of infection. alcohol metabolism. Glutathione avail Hirsh et al. 1999) partly because alco
ability depends on the presence of cer hol directly suppresses the immune sys
Free-Radical Damage tain amino acids that may be deficient tem but also because the altered pro
in patients with ALD (Schenker and tein metabolism observed in ALD
It has been observed that one of the Halff 1993). One of these amino acids, results in decreased circulating antibod
toxic byproducts of alcohol metabolism Sadenosylmethionine (SAM), serves as ies needed to fight infection. The
(i.e., free radicals) may cause damage to a precursor for glutathione. Evidence intestinal system also works as a barrier
the liver. Freeradical damage also exists that SAM is deficient in patients to prevent bacteria from inside the gut
occurs as a result of oxidation of lipids with ALD (Schenker and Halff 1993). from crossing the intestinal wall and
in cellular membranes and in the inter Furthermore, membrane integrity causing infection. In addition, the cells
nal constituents (i.e., mitochondria) of depends on the availability of SAM, in of the gut secrete an antibody that is
the cell. This improper oxidation of fat addition to an ample supply of phos unique to the gut and assists with
can, in turn, lead to the increased fat pholipids. SAM is involved in the pro fighting infection (Schenker and Halff
deposition and fibrosis, described pre cessing of phospholipids needed for cell 1993). There is evidence that the gut’s
viously. Cell damage from this membrane repair (Schenker and Halff role as a barrier to infection decreases
improper oxidation also results in an 1993). It also has been observed that with poor nutrition, as well as with
inflammatory response and the genera patients with ALD are deficient in vita excess alcohol intake (Schenker and
Halff 1993). Research in animals has
shown that improved nutrition results
Table 1 Basis for Nutritional Deficits in Alcoholic Liver Disease (ALD) in decreased translocation of bacterial
organisms across the gut and a subse
Decreased caloric intake Results quent decrease in bacterial infections
(Casafont et al. 1997). Generally, it is
• Anorexia • Decreased calories, vitamins, and accepted that patients with advanced
• Decreased ingestion of nutrients available for utilization ALD have an increased risk of morbidity
nonalcohol calories and mortality with surgical procedures.
• Increases with severity of ALD This increased risk may be related to
Decreased intestinal absorption/ higher infection risk and poor wound
digestion of nutrients healing (Schenker and Halff 1993).
Considering that chronic ALD, after
• Decreased bile excretion • Decreased fat digestion and cessation of drinking, is one of the
absorption of fatsoluble vitamins more common indications for liver
• Decreased pancreatic function • Decreased pancreatic enzymes transplant (McCullough and O’Connor
for fat and protein digestion 1998), it is reasonable to suggest that
• Altered intestinal integrity • Decreased amino acid and improved nutrition in patients with
vitamin absorption and digestion ALD can improve the outcomes of sur
• Decreased intestinal enzymes • Decreased carbohydrate digestion gical procedures by decreasing infection
Decreased processing and storage and improving wound healing.
of nutrients In brief summary, the decreased
ability to process hepatic fat, as well as
• Preferential metabolism of alcohol • Abnormal processing of fats and sugars the lack of key proteins and amino
• Abnormal oxidation of fat • Fatty liver and increased acids that may decrease the liver’s abil
collagen production ity to neutralize the effects of free radi
• Decreased functional liver mass • Decreased energy stores and cals generated by alcohol metabolism,
utilization of alternative pathways normally may, in turn, result in damage to cell
reserved for fasting (abnormal muscle membranes and promote inflammation
breakdown and abnormal oxidation of fats)
and cell death (i.e., necrosis). Such
SOURCE: Modified with permission from Mezey 1991 and Schenker and Halff 1993. events also may lead to fibrosis and
even cirrhosis. Thus, theoretically,
298
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Research
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Nutritional
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in
ALD
improved nutrition could ameliorate feeding tube, or intravenous line) as well various substances. Kearns and colleagues
these adverse events, enhance hepatic as compliance and length of treatment. (1992) demonstrated improved clear
regeneration, and decrease the risk of Patient compliance in the studies 1 whereas Bonkovsky
ance of antipyrine,
infection, which is a common compli cited generally is not estimated and is and colleagues (1991a,b) showed no
cation of advanced ALD and a leading therefore difficult to assess. Compliance change in antipyrine clearance but did
cause of patient mortality. is clearly likely to be better in patients report improved results from the galac
given food intravenously or via a feed 2 with improved
ing tube. It also may be better in those tose elimination test
Evidence
for
Benefits
of
with less severe ALD because they have nutrition. Only two studies (Diehl et
Nutrition
a lesser degree of anorexia. al. 1985; Achord 1987) evaluated the
role of nutritional therapy on histology
As shown in Table 2, there have been Research Findings of the liver in ALD. There was a
about 15 studies (14 controlled and 1 decrease in fat in one study (Diehl et al.
pilot study) evaluating the benefits of Even with these stipulations, a number 1985) and fibrosis in the other (Achord
nutritional therapy in ALD. These of conclusions emerge from the studies 1987) but no improvement in inflam
studies have assessed the possible benefit reviewed. In most studies, nutritional mation or necrosis (Diehl et al. 1985).
of optimal nutrition in a variety of ways. status appears to have been improved
They have evaluated the effects on in patients given proper dietary intake, Effect on Mortality
nutritional status, liver tests, liver histol especially with regard to nitrogen bal
ogy, and, most importantly, mortality. ance. The best evidence of this was in Despite improvement in nutritional
the studies by Mezey and colleagues parameters and tests of liver “function”
Variations in Studies (1991) and Bonkovsky and colleagues in most studies, the majority did not
(1991a,b). One study (Naveau et al. demonstrate a change in mortality.
The studies reviewed here have wide 1986) found no improvement in nutri Two studies did report improved sur
variations, which make meaningful tional parameters. A better correlation
comparison difficult. For instance, there with improvement in nutritional status vival with nutritional therapy. Cabre
is a disparity in the severity of liver dis was seen in those studies with more and colleagues (1990) studied patients
ease among study participants. Two stud specific parameters of nutrition, such as with cirrhosis, the majority of whom
ies (Diehl et al. 1985; Nasrallah and visceral proteins (which are reactive to had alcoholic cirrhosis, and demon
Galambos 1980) had no deaths and one physiological changes in the body and strated a decreased mortality rate during
had only 5 percent mortality (Naveau therefore are valuable in identifying hospitalization with nutritional supple
et al. 1986). When considering that malnutrition), nitrogen balance, triceps mentation through a feeding tube.
mortality ranged from 12 to 47 percent skinfold thickness, and creatinine– Nasrallah and Galambos (1980) were
in the other studies, this clearly suggests height index (a ratio of a patient’s 24 able to show improved survival in patients
a less severe form of disease in the for hour excretion of the waste product with alcoholic hepatitis with adminis
mer groups. Additionally, the studies creatinine [which is related to muscle tration of intravenous amino acids.
have variable patient populations with mass] and the expected normal creati Although a consistent improvement
regard to stage of ALD. Four studies nine excretion) (Mezey et al. 1991;
(Marchesini et al. 1990; Kearns et al. Bonkovsky et al. 1991a,b). in survival has not been demonstrated
1992; Cabre et al. 1990; Hirsch et al. in individual studies, the average com
1993) primarily addressed alcoholic Liver Tests posite mortality in 10 studies (Diehl et
cirrhosis, whereas 11 (Diehl et al. 1985; al. 1985; Nasrallah and Galambos 1980;
Nasrallah and Galambos 1980; Naveau The bulk of the data available suggests Naveau et al. 1986; Calvey et al. 1985;
et al. 1986; Calvey et al. 1985; Cabre et that improved nutrition is reflected in Mezey et al. 1991; Achord 1987;
al. 2000; Mezey et al. 1991; Achord 1987; specific improvements in liver tests such Mendenhall et al. 1985; Bonkovsky et
Mendenhall et al. 1985; Bonkovsky et as serum albumin (a protein found in al. 1991a,b; Simon and Galambos
al. 1991a; Bonkovsky et al. 1991b; blood plasma), bilirubin (produced by 1988) involving amino acid therapy in
Simon and Galambos 1988) focused the breakdown of hemoglobin and alcoholic hepatitis was 9.6 percent in
on patients with alcoholic hepatitis. processed in the liver), transaminases those treated compared with 17 percent
However, a large number of patients in (enzymes involved in breaking down
the studies involving alcoholic hepatitis amino acids), and blood clotting (i.e., in control subjects, suggesting a trend
also had underlying cirrhosis. Moreover, coagulation). A few studies (Kearns et toward significantly improved mortal
many of these studies utilized only a al. 1992; Mezey et al. 1991; Bonkovsky ity (McCullough and O’Connor 1998).
small number of patients, making mean et al. 1991a,b) even demonstrated
ingful statistical analysis difficult. The enhanced liver status as measured by 1 Antipyrine metabolism is used as an index of liver function.
studies also differed in methods of more direct tests of liver function that
nutrient administration (e.g., oral, involve hepatic uptake and clearance of 2 The galactose elimination test measures liver function.
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