HEPATITIS

Acute Viral Hepatitis

Acute viral hepatitis is a widespread inflammation of the liver and is caused by hepatitis viruses A, B, C,
D, and E
Hepatitis A and E are the infectious forms (mainly spread by fecal-oral route) and hepatitis B, C, and D
are the serum forms (spread by blood and body fluids). Minor agents such as Epstein-Barr virus,
cytomegalovirus, herpes simplex, yellow fever and rubella can also cause an acute hepatitis.

Hepatitis A
Hepatitis A GIAD is transmitted by the fecal-oral route and is contracted through contaminated drinking
water, food, and sewage. Anorexia is the most frequent symptom, and it can be severe. Other common
symptoms include nausea, vomiting, right upper quadrant abdominal pain, dark urine, and jaundice
(icterus). Recovery is usually complete, and long-term consequences are rare. Serious complications may
occur in high-risk patients; subsequently, great attention must be given to adequate nutritional intake.

Hepatitis B and C
Hepatitis B (HBV) and hepatitis C (HCV) can lead to chronic and carrier states. HBV and HCV are
transmitted via blood, blood products, semen, and saliva. For example, they can be spread from
contaminated needles, blood transfusions, open cuts or wounds, splashes of blood into the mouth or
eyes, or sexual contact. Chronic active hepatitis can also develop, leading to cirrhosis and liver failure.

Hepatitis D
The hepatitis D virus (HDV) is rare in the United States and depends on the HBV for survival and
propagation in humans. HDV may be a coinfection (occurring at the same time as HBV or a
superinfection (superimposing itself on the HBV carrier state). This form of hepatitis usually becomes
chronic.

Hepatitis E
Hepatitis E virus (HED is rare in the United States (typically only occurs when imported), but it is
reported more frequently in many countries of southern, eastern, and central Asia; northern, eastern,
and western Africa; and Mexico. HEV is transmitted via the oral-fecal route. Contaminated water
appears to be the source of infection, which usually afflicts people living in crowded and unsanitary
conditions. Hepatitis E is generally acute rather than chronic.

Hepatitis G/GB
Hepatitis G virus (HGD and a virus labeled GB-C (GBV-C) appear to be variants of the same virus.
Although HGV infection is present in a significant proportion of blood donors and is transmitted through
blood transfusions, it does not appear to cause liver disease. The general symptoms of acute viral
hepatitis are divided into four phases. The first phase, the early prodromal phase, affects about 25% of
patients, causing fever, arthralgia, arthritis, rash, and angioedema. This is followed by the preicteric
phase, in which malaise, fatigue, myalgia, anorexia, nausea, and vomiting occur. Some patients complain
of epigastric or right upper quadrant pain. The third phase is the icteric phase, in which jaundice
appears. Finally, during the convalescent phase, jaundice and other symptoms begin to subside.
Complete recovery is expected in 95% of HAV cases, in 90% of acute HBV cases, but in only 15% to 45%
of acute HCV cases. Chronic hepatitis does not usually develop with HEV, and symptoms and liver
function tests usually normalize within 6 weeks.
Fulminant Hepatitis
Fulminant hepatitis is a syndrome in which severe liver dysfunction is accompanied by hepatic
encephalopathy, a clinical syndrome characterized by impaired mentation, neuromuscular disturbances,
and altered consciousness. FuIminant liver disease is defined by the absence of pre-existing liver disease
and the development of hepatic encephalopathy within 2 to 8 weeks of the onset of illness The causes
of fulminant hepatitis include viral hepatitis (about 75% of cases), chemical toxicity (e.g.,
acetaminophen, drug reactions, poisonous mushrooms, industrial poisons), and other causes (e.g.,
Wilson's disease, fatty liver of pregnancy, Reye's syndrome, hepatic ischemia, hepatic vein obstruction,
and disseminated malignancies). Extrahepatic complications of fulminant hepatitis are cerebral edema,
coagulopathy and bleeding, cardiovascular abnormalities, renal failure, pulmonary complications, acid-
base disturbances, electrolyte imbalances, sepsis, and pancreatitis.

Chronic Hepatitis
To be defined as chronic hepatitis, a patient must have at least a 6-month course of hepatitis or
biochemical and clinical evidence of liver disease with confirmatory biopsy findings of unresolving
hepatic. Chronic hepatitis can have autoimmune, viral, metabolic, or medicine or toxin etiologies. The
most common causes of chronic hepatitis are hepatitis B, hepatitis C, and autoimmune hepatitis. Other
common causes are drug-induced liver disease, metabolic diseases, and NASH. Cryptogenic cirrhosis is
cirrhosis of an unknown etiology.
Clinical symptoms of chronic hepatitis are usually non-specific, occur intermittently, and are mild.
Common symptoms include fatigue, sleep disorders, difficulty concentrating, and mild right upper
quadrant pain. Severe advanced disease can lead to jaundice, muscle wasting, tea-colored urine, ascites,
edema, hepatic encephalopathy, gastrointestinal bleeding, splenomegaly, palmar erythema, and spider
angiomata.

Nonalcoholic Steatohepatitis
Nonalcoholic steatohepatitis (NASH) is an intermediate stage in fatty liver disease. It is the accumulation
of fat droplets in the hepatocytes, which are surrounded by acute and chronic inflammatory cells.
Steatohepatitis is associated with accumulation of fibrous tissue in the liver. Nonalcoholic causes include
drugs, inborn errors of metabolism, and acquired metabolic disorders (type 2 diabetes mellitus,
lipodystrophy, jejunal ileal bypass, obesity malnutrition)
Patients with NASH may be asymptomatic but can experience malaise, weakness, or hepatomegaly. The
treatment is often weight loss (although extreme, rapid weight loss can accelerate NASH developing into
cirrhosis and increase the chance of gallstone development), the use of insulin-sensitizing drugs,
treatment of the dyslipidemia, and administration of ursodeoxycholic acid. Chronic liver disease and
cirrhosis can develop in patients with NASH, and the progression to cirrhosis is variable, depending on
age and the presence of obesity and type 2 diabetes, which contribute to a worsening prognosis.

Alcoholic Liver Disease

Alcoholic liver disease is the most common liver disease in the United States accounting for 50% of all
chronic liver disease. According to the National Institute on Alcohol and Alcohol Abuse, +65% of adults in
the United States abuse alcohol or are alcoholics. Alcohol problems are highest among young adults 18
to 29 years of age and lowest among adults ages 65 and older. Acetaldehyde, a toxic by-product of
alcohol metabolism, causes damage to mitochondrial membrane structure and function. Acetaldehyde
is produced by multiple metabolic pathways, one of which involves alcohol dehydrogenase. Several
variables predispose some people to alcoholic liver disease. These include genetic polymorphisms of
alcohol-metabolizing enzyrnes, gender (female more than male), simultaneous exposure to other drugs,
infections with hepatotropic viruses, immunologic factors, and poor nutrition status. The pathogenesis
of alcoholic liver disease progresses in three stages hepatic steatosis, alcoholic hepatitis, and finally
cirrhosis.

Alcoholic Hepatitis
Alcoholic hepatitis is generally characterized by hepatomegaly, modest elevation of transaminase levels,
increased serum bilirubin concentrations, normal or depressed serum albumin concentrations, or
anemia. Patients may also have abdominal pain, anorexia, nausea, vomiting, weakness, diarrhea, weight
loss, or fever. If patients discontinue alcohol intake, hepatitis may resolve; however, the condition often
progresses to the third stage. Nutrition support is the main treatment in addition to counseling or
support to continue avoidance of alcohol. Molecular genetics may lead to new therapies in the future

CYSTIC FIBROSIS
Cystic fibrosis (GF) is a complex multisystem disorder that is inherited in an autosomal-recessive
fashion. The first comprehensive description of CF in the United States was published in 1938. In 1989
the underlying genetic basis of the disease was presented. The CF gene, located on chromosome 7q (the
long arm), encodes a membrane-associated protein termed the CF transmembrane regulator. This
protein product appears to be part of a cyclic adenosine monophosphate regulated chloride channel and
appears to regulate chloride and sodium transport across apical membranes of epithelial cells. Over
1400 mutations have been identified.

Although CF remains one of the most common lethal genetic disorders prevalent in white
persons, it is expressed in other population groups as well. Approximately 2% to 5% of white
populations are heterozygotes, with a CF incidence of l:1500 live births. Survival has dramatically
improved because of scientific advancements and improvements in diagnostic and treatment
procedures, including nutrition. The median age of patients is about 37 years. Once thought to be only a
pediatric disease, the number of people surviving to or being diagnosed at 18 years or older is about
42%. Women with CF have delivered healthy infants, and some have chosen to breast-feed their
unaffected infants.

Expression of the CF gene is largely restricted to epithelial cells. Almost all exocrine glands are
affected by secretion of abnormally thick, tenacious mucus that obstructs glands and ducts in various
organs. The clinical features are dominated by involvement of the respiratory duct, sweat and salivary
glands, intestine, pancreas, liver, and reproductive tract. Pulmonary complications include acute and
chronic bronchitis, bronchiectasis, pneumonia, atelectasis, and peri bronchial and parenchymal scarring.
Infection with Staphylococcus aureus and Pseudomonas aeruginosa is typical. Pneumothorax and
hemoptysis are common. In advanced stages cor pulmonale or infection with Burkbolderia cepacia may
be present, signifying a poor prognosis

Several methods are available for diagnosing CE For families with previously identified CF prenatal
analysis may be possible. Several countries and some states in the United States conduct routine
neonatal screening for the disease. The most reliable clinical diagnostic test' known as the sweat test, is
performed by pilocarpine iontophoresis. Elevated levels of sodium and chloride (>60 mEq/L) in collected
sweat samples are indicative of CE Criteria for the diagnosis of CF include a positive result on a sweat
test and the presence of chronic lung disease, failure to thrive and malabsorption, or a family history of
CF. Genotyping is available and is a routine procedure

CF can have a profound impact on the digestive system (Constantine et al., 2004). Infants born with
meconium ileus have the diagnosis of probable CF until ruled out from other causes. About 85o/o to
90% of persons with CF have pancreatic insufficiency. Plugs of thick mucus reduce the quantity of
digestive enzymes released from the pancreas into the small intestine. The resultant enzyme
insufficiency causes maldigestion of food and malabsorption of nutrients. Decreased bicarbonate
secretion can further reduce digestive enzyme activity. Decreased bile acid resorption contributes
further to fat malabsorption.

The presence of excessive mucus lining the small intestinal tract may interfere with nutrient absorption
by the microvilli. Gastrointestinal complications include bulky, foul smelling stools; cramping and
intestinal obstruction; rectal prolapse; and liver involvement. fu the disease progresses, damage to the
endocrine portion of the pancreas can cause impaired glucose tolerance and development of CF-related
diabetes mellitus.

Medical Nutrition Therapy

Assessment
Individuals with CF are at high risk for malnutrition. Maldigestion and malabsorption, as well as the
progressive complications of the disease, make it difficult to meet increased nutrient needs. Factors
interfering with adequate intake and retention of nutrients include dyspnea, coughing and cough-
induced vomiting, gastrointestinal discomfort, anorexia during episodes of infection, possible impaired
sense of smell and taste, and glucosuria. Growth retardation and difficulty maintaining desired weight
for height are common problems. Before diagnosis, infants with CF often demonstrate growth failure.
With treatment, growth generally improves. When energy and nutrient intakes are adequate, growth
nearly appropriate for age usually can be achieved.
As lung disease progresses, grou.th velocity in children and weight for height in adults may decline. The
long-term relationship between nutrition support, growth, and survival is not known; however,
improved nutrition status on a long-term basis continues to be suggested as a contributing factor to
increased survival.
Comprehensive nutrition assessment in individuals with CF was first codified by the Cystic Fibrosis
Foundation in 1992 and updated In 2002. Table 3 5-2 highlights some components of nutrition
assessment. Periodic updated practice guidelines are available online from the Cystic Fibrosis
Foundation and should be consulted for the latest information.
Compared to children and adolescents, adults have similar issues surrounding medical, surgical,
psychosocial, and nutrition assessments and therapies; but they also have regular adult life issues. Thus,
they require different nutrition information delivered by different levels of educational approaches.
Because of all the intricate manifestations and complications of C$ nutritional requirements and
care must be individually determined for each patient. Moreover, medical nutrition therapy must be
coordinated with other treatments, including oral or aerosol or intravenous antibiotics, other inhaled
medications, and chest physical therapy.
Based on clinical research and experience, the goals of nutrition care in CF are to control
maldigestion and malabsorption, provide adequate nutrients to promote optimal growth or maintain
weight for height and pulmonary function, and prevent nutritional deficiencies (Figure 35-7). Individuals
at especially high risk include infants, children, adolescents, and pregnant or lactating women, even
when they are medically stable.

Enzyme Therapy
Pancreatic enzyme replacement therapy is the first step taken to correct maldigestion and
malabsorption. The introduction of enteric-coxed enzyme microspheres in the early 1980s was a major
advance in nutritional management. The microspheres, designed to withstand the acidic environment of
the stomach, release enzymes in the duodenum, where they digest protein, fat, and, carbohydrate.
Pharmaceutical advancements have improved the medications available. The quantity of enzymes to be
taken with food depends on the degree of pancreatic insufficiency; the quantity of food eaten; the fat,
protein, and carbohydrate content of food consumed; and the type of enzymes. Enzyme dosage per
meal or snack is adjusted empirically to control gastrointestinal symptoms, including steatorrhea, and to
promote growth appropriate for rye lf gastrointestinal symptoms cannot be controlled, enzyme dosage,
patient adherence, and enzyme type should be reevaluated. Fecal elastase (protein-digesting enzyme
secreted by the pancreas and involved in hydrolysis of peptide bonds), fecal fag or nitrogen balance
studies may help to evaluate the adequacy of enzyme supplementation. Following the manufacturer's
advice about storage and administration of a particular brand of enzyme is important to highlight with
each patient or family member. Examples of guidance to provide to parents about infants or children
who are taking microspheres but are unable to swallow capsules are as follows:
 If given in the bottle, keep the bottle in the dark and at room temperature.
 If given in a food, open the capsules and mix the microspheres with a soft food such as
applesauce; do not mix the microspheres with foods that have a pH greater than 6.0, such as
dairy products (e.g., milk, custard, ice cream) because the enteric coating will dissolve and the
enzymes exposed to the gastric acidity will be inactivated.
 To retain the benefits of enteric coating, do not crush or chew the microspheres before adding
them to food or swallowing them.

Distal intestinal obstruction syndrome (DIOS), also known as recurrent intestinal impaction, sometimes
occurs in children and adults. Prevention of DIOS involves intake of adequate enzyrnes, fluids, and
dietary fiber and regular exercise; treatment includes adding stool softeners, laxatives, hyperosmolar
enemas, or intestinal lavage.

Energy
Energy needs vary widely from individual to individual and even in the same individual throughout the
course of life. Factors to consider are gender, age, basal metabolic rate, physical activity respiratory
infection, severity of lung disease, and severity of malabsorption. When laboratory methods to
determine energy, requirements are unavailable, equations for calculating caloric recommendation.
ions are convenient to use Patients with CF should not be encouraged to decrease their activity levels
but rather to increase their energy intake instead. Relatively healthy children with CF usually are able to
maintain normal growth and energy stores when they eat a high-energy, moderate-fat diet
complemented with sufficient pancreatic enzyme supplementation.
Macronutrients Dietary protein levels are increased in CF as a result of malabsorption; however, when
energy needs are adequately met, individuals with CF generally can meet their protein needs by
following a typical North American diet. At least 15% to 20% of the total calories consumed as proteins
or the appropriate DRI for protein for the individual's gender, age, and height is suggested. Fat intake
should provide 35% to 40% or more of total kilocalories as tolerated. Dietary fat helps to provide the
required energy (i.e., linoleic acid and linolenic acid), and fat-soluble vitamins. Moreover, fat limits the
volume of food required to meet energy demands and improves the palatability of the diet.
Indications of fat intolerance include an increase in the number of stools, greasy stools, or abdominal
cramping. EFA deficiencies may be present, even among patients who are treated adequately with
pancreatic enzymes to control malabsorption. Although clinical signs of EFA deficiency are rare, blood
and tissue lipid levels may be abnormal (Wood et al., 2005). Even if the visible signs of EFA deficiency
(e.g., the typical skin lesions) are not noticeable, the clinician should consider routinely testing for
abnormal blood lipid profiles. In addition, at-risk patients need to be encouraged to include sources of
EFAs (e.g., canola, flaxseed, soybean, or corn oil, or fish) as part of their daily fat intake. fu the disease
progresses, changes in carbohydrate intake may be necessary. Lactose intolerance may become evident,
and pancreatic endocrine involvement may require carbohydrate adjustments.

Vitamins and Minerals

With pancreatic enzyme supplementation, the water-soluble vitamins appear to be adequately
absorbed in patients with Cf, and requirements under normal conditions can usually be met by diet plus
a standard age-appropriate multivitamin/mineral supplement; however, monitoring individual variations
is important. Even with pancreatic enzyme supplementation, fat-soluble vitamins usually remain
inadequately absorbed. Low serum concentrations of yitamin A despite increased hepatic stores have
been documented in CE suggesting impaired mobilization and transport of the vitamin from the liver.
Decreased levels of vitamin D metabolites have been observed. This is one of several factors that may be
related to the decreased bone mineral content that for years has been described in populations with CE
Low vitamin E levels have been associated with hemolytic anemia and abnormal neurologic findings.
Individuals with CF may be at risk for vitamin K deficiency secondary to long-term use of antibiotics or
liver disease, as well as malabsorption. Although most patients maintain normal prothrombin times
without supplementation, decreased biologic activity of vitamin K has been reported. For all these
reasons, vitamin K supplementation is recommended.
Mineral intake should meet the gender and age recommendations according to the DR. Special attention
must be given to some of the minerals, however. Sodium requirements for infants, children, and adults
are increased in CF because of increased losses in sweat. 'When sodium intake is inadequate, lethargy,
vomiting, and dehydration may occur. Adequate salt is consumed by most children and adults who eat a
typical North American diet with processed foods; however, supplemental salt is required under some
conditions. Infants require extra salt because of the low-sodium content of breast milk, formula, and
infant foods; Va to V+ tsp daily is usually adequate in this situation. Children and adults need additional
salt during periods of fever, hot weather, or physical exertion. Table salt or proprietary electrolyte
replacement solutions are used.
Other minerals are not routinely supplemented, although mineral status should be evaluated on an
individual basis. Decreased bone mineralization starts during childhood and must be assessed and
addressed (Aris et al., 2005). Low iron stores and low magnesium levels have been described in CF.
Plasma zinc levels may be low in cases of moderate-to-severe malnutrition.

Feeding Strategies
Diet modification focuses on meeting the increased nutritional requirements of CE Along with adequate
dietary modification, positive eating behaviors must be established (Stark et a1.,2003; Powers et al.,
2005). Parent educational materails are available online. For infants with CF and their families. the
immunologic and psychosocial benefits of breast-feeding are well established, and breast-feeding
should be encouraged. For the infant with pancreatic insufficiency, enzyme microspheres can be added
to a small amount of baby food or placed directly in the infant's mouth. Supplementation with high-
calorie formula may be necessary to meet growth goals. For formula-fed infants, standard formulas (20
to 27 kcaUoz) given with supplemental enzymes are usually adequate. Protein hydrolysate formulas
with medium-chain triglycerides may also be use.
Supplementation by feeding tube is an alternative for those unable to meet nutritional needs by
the oral route. Formulas are provided by continuous infusion through a nasogastric, gastrostomy, or
jejunostomy tube, often while the person sleeps (see Chapter 20). Elemental and nanoelemental
formulas with enzyrnes have been used effectively. Enzyme powder can be added directly to the
formula. If the nocturnal method is chosen, capsules can be taken by mouth when the feeding is started
and again.
once or twice during the night. Factors to consider in the decision to proceed with nighttime
supplementation include nutrition status, medical status (e.g., factors such as the presence of nasal
polyps and the degree of oxygenation during sleep), risks associated with tube feeding (e.9., aspiration),
and the psychosocial and financial impact. Intensive supplementation has been associated with
improved weight gain, slowed decline in pulmonary function, decreased incidence of respiratory
infection, and improved sense of well-being. Although the short-term benefits of supplementation have
been well documented, nutrition status is likely to regress when supplementation is discontinued. The
long-term impact of intensive supplementation on the course of the disease has not been determined.
Parenteral nutrition is best used for short-term support in patients with clearly evident needs such as
those recuperating from gastrointestinal surgery

CHOLESTASIS (cholestatic liver disease)

Cholestasis is a liver disease. It occurs when the flow of bile from your liver is reduced or blocked. Bile is
fluid produced by your liver that aids in the digestion of food, especially fats. When bile flow is altered, it
can lead to a buildup of bilirubin.
Cholestasis is a condition in which little or no bile is secreted or the flow of bile into the digestive
structed. This can occur in patients without oral or enteral feeding for a prolonged period, such as those
requiring PN, and can predispose to acalculous cholecystitis. Prevention includes stimulation of
intestinal and biliary motility and secretions by at least minimum enteral feedings (Hager, 1994). If this is
not possible, drug therapy is used.

Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease caused by progressive destruction of small
and intermediate-size intrahepatic bile ducts. The extrahepatic biliary tree and larger intrahepatic ducts
are normal. 90% are woman. This disease progress slowly. Eventually, resulting in cirrhosis and portal
hypertension and liver transplantation or death. It is an immune-mediated disease in which serum
autoimmune antibodies, elevated immunoglobulin levels, circulating immune complexes, and depressed
cell-mediated immune response are present. PBC typically presents with a mild elevation of liver
enzyrnes with physical symptoms of pruritus and fatigue. Treatment with ursodeoxycholic acid can slow
progression of the disease. Several nutritional complications from cholestasis can occur with PBC,
including osteopenia, hypercholesterolemia, and fat-soluble vitamin deficiencies.

Sclerosing Cholangitis
Sclerosing cholangitis is another chronic cholestatic liver disease. Fibrosing inflammation of segments of
extrahepatic bile ducts, with or without involvement of intrahepatic ducts, characterizes the disease.
Progression of the disease leads to complications of portal hypertension, hepatic failure (liver function
diminished to 25o/" or less), and cholangiocarcinoma. Primary sclerosing cholangitis (PSC) is the most
common type of sclerosing cholangitis. In general, PSC lacks any apparent etiology and usually occurs in
association with inflammatory bowel disease (Mahadevan et al., 2002). Like PBC, PSC may be an
immune disorder because of its strong association with human leukocyte antigen haplotypes,
autoantibodies, and multiple immunologic abnormalities. Seventy to 90% of patients with PSC also have
inflammatory bowel disease (especially ulcerative colitis), and men are more likely than women (2.3:1)
to have PSC (Afdhal, 2004). Patients with PSC are also at increased risk of fat-soluble vitamin deficiencies
resulting from steatorrhea associated with this disease. Hepatic osteodystrophy may occur from vitamin
D and calcium malabsorption, resulting in secondary hyperparathyroidism and osteomalacia or rickets
(Klein et a1.,2002). No treatment slows progression of the disease or improves survival. Ursodeoxycholic
acid may improve laboratory values (serum bilirubin, alkaline phosphatase, and albumin) but has no
effect on survival.

Additional: alpha 1-Antitrypsin deficiency is another inherited disorder, and it can cause both liver and
lung disease. c1-Antitrypsin is a glycoprotein found in serum and body fluids; it inhibits neutrophil
proteinases. Cholestasis or cirrhosis is caused by this deficiency and there is no treatment except liver
transplantation.

Treatment of Cirrhosis and its complications

Cirrhosis has many clinical manifestations, as illustrated in Figure 28-4. Several major complications of
cirrhosis and end-stage liver disease (ESLD), including malnutrition, ascites, hyponatremia, hepatic
encephalopathy, glucose alterations, fat malabsorption, hepatorenal syndrome, and osteopenia have
nutritional implications. When appropriate nutrition therapy is provided to patients with liver disease,
malnutrition can be reversed, and clinical outcomes improved. Studies to date have been able to show
positive outcomes with oral and enteral nutrition (EN) in malnourished patients with cirrhosis, including
improvement in nutrition status and clinical complications of cirrhosis such as ascites, encephalopathy
and infection.

Nutrition Assessment
Before appropriate nutrition therapy can be implemented, a nutrition assessment must be performed to
determine the extent and cause of malnutrition. Many traditional markers of nutrition status are
affected by liver disease and its consequences, making assessment difficult. Maldigestion and
malabsorption also play a role in the malnutrition of liver disease. Steatorrhea, or the presence of fat in
the stool, is common in cirrhosis, especially if there is disease involving bile duct injury and obstruction.
The medications previously mentioned may also cause specific malabsorptive losses. In addition, altered
metabolism secondary to liver dysfunction causes malnutrition in various ways. Micronutrient function
is affected by altered storage in the liver, decreased transport by liver-synthesized proteins, and renal
losses associated with alcoholic and advanced liver disease. Abnormal macronutrient metabolism and
increased energy expenditure can also contribute to malnutrition. Finally, protein losses can occur from
large volume paracentesis when fluid from the abdomen (ascites) is removed through a needle.

External Symptoms: Icteric Sclerae, Alopecia, Asterixis, Palmar erythema, gynecomastia, caput
medusae, ascites, altered hair distribution, testicular atrophy, muscle wasting, bruising, jaundice, spider
angioma.
Internal Symptoms: Encephalopathy, esophageal varices, portal hypertension, cirrhosis, hepatorenal
syndrome, tea-colored urine, clay-colored stool
Subjective Global Assessment Parameters for Nutrition Evaluation of Liver Disease Patients
History
Weight change (consider fluctuations resulting from ascites and edema) Appetite Taste changes and
early satiety Dietary recall (calories, protein, sodium) Persistent gastrointestinal problems (nausea,
vomiting, diarrhea, constipation, difficulty chewing or swallowing)
Physical
Muscle wasting Fat stores Ascites or edema
Existing Conditions
Disease state and other problems that could influence nutrition status such as hepatic encephalopathy,
gastrointestinal bleeding, renal insufficiency, infection
Nutritional Rating
(based on results of parameters) Well-nourished Moderately (or suspected of being) malnourished
Severely malnourished

Problems in Feeding
Because anorexia, nausea, dysgeusia, and other gastrointestinal symptoms are common, adequate
nutrition intake is difficult to achieve. With ascites, early satiety is also a frequent complaint. Smaller,
more frequent meals are better tolerated than three traditional meals. In addition, evidence suggests
that frequent feedings also improve nitrogen balance and prevent hypoglycemia. Oral liquid
supplements should be encouraged, and, when necessary enteral tube feedings used. Adjunctive
nutrition support should be given to malnourished patients with liver disease if their intake is less than
DRI levels of0.8 g of protein and 30 calories per kilogram of body weight daily and if they are at risk for
fatal complications from the disease. Esophageal varices are usually not a contraindication for tube
feeding.

Nutrient Requirement:
Energy requirements vary among patients with cirrhosis. Several studies have measured resting energy
expenditure (REE) in patients with liver disease to determine energy requirements. Some found that
patients with ESLD had normal metabolism and that others had hypometabolic or hypermetabolic
metabolism. Although several studies concluded that patients with cirrhosis did not require any more
calories than did healthy controls, Dolz and colleagues (1991) determined that ascites increases energy
expenditure slightly. On the other hand, two studies found REE increased at 3 or 6 months and again at
12 months after placement of a shunt. However, this increase may be the result of the fact that dry body
weight increased after the shunt placement.
In general, energy requirements for patients with ESLD and without ascites are about l20%o to l40% of
the REE. Requirements increase to 150% to 175% of REE if ascites, infection, or malabsorption is present
or if nutritional repletion is necessary. This equates to about 25 to 3 5 calories per kilogram body weight;
estimated dry body weight should be used in calculations to prevent overfeeding. Oral nutritional
supplements or tube feeding can be effective in increasing or ensuring optimal intake in malnourished
patients and reducing complications and prolonging survival.

Carbohydrates Determining carbohydrate needs is often challenging in liver failure because of the
primary role of the liver in carbohydrates metabolism. Liver failure reduces glucose production and
peripheral glucose use. The rate of gluconeogenesis is decreased, with preference for lipids and amino
acids for energy. Alterations in the hormone’s insulin, glucagon, cortisol, and epinephrine are
responsible in part for the preference for alternative fuels.

Lipid In cirrhosis, plasma free fatty acids, glycerol, and ketone bodies are increased in the fasting state.
The body prefers lipids as an energy substrate, and lipolysis is increased with active mobilization of lipid
deposits, but the net capacity to store exogenous lipid is not impaired. A range of 25o/o to 40o/o of
calories as fat is generally recommended.

Protein is by far the most controversial nutrient in liver failure, and its management is also the most
complex. Cirrhosis has long been thought of as a catabolic disease with increased protein breakdown
and inadequate resynthesis, resulting in depletion of visceral protein stores and muscle wasting. Protein
kinetic studies have been able to demonstrate increased nitrogen losses only in patients with fulminant
hepatic failure or decompensated disease but not in patients with stable cirrhosis.
Patients with cirrhosis also have increased protein use. At least one study, suggests that 0.8 g of
protein per kilogram per day is the mean protein requirement to achieve nitrogen balance in patients
with stable cirrhosis. Therefore, in uncomplicated hepatitis or cirrhosis without encephalopathy, protein
requirements range from 0.8 to I g/kg of dry weight per day to achieve nitrogen balance.
To promote nitrogen accumulation or positive balance, at least 1.2 to 1.3 g/kg daily is needed. In
situations of stress such as alcoholic hepatitis or decompensated disease (sepsis, infection,
gastrointestinal bleeding, severe ascites), at least 1.5 g of protein per kilogram per day should be
provided.

Vitamins and Minerals Vitamin and mineral supplementation is needed in all patients with ESLD
because of the intimate role of the liver in nutrient transport, storage, and metabolism, in addition to
the side effects of drugs. Vitamin deficiencies can contribute to complications. For example, folate and
vitamin Bi2 deficiencies can lead to macrocytic anemia. Deficiency of pyridoxine, thiamin, or vitamin B12
can result in neuropathy. Confusion, ataxia, and ocular disturbances can result from a thiamin
deficiency; impaired dark adaptation can occur from vitamin A deficiency; and hepatic osteodystrophy
or osteopenia can develop from vitamin D deficiency. Deficiencies of fat-soluble vitamins have been
found in all types of liver failure, especially in cholestatic diseases in which malabsorption and
steatorrhea occur. Therefore, supplementation is necessary using water-soluble forms' Intravenous or
intramuscular vitamin K is often given for 3 days to rule out vitamin K deficiency as the cause of a
prolonged prothrombin times. Water-soluble vitamin deficiencies associated with alcoholic liver disease
include thiamin (which can lead to Wernicke's encephalopathy), pyridoxine (86), cyanocobalamin (B12),
folate, and niacin (B3). Large doses (100 mg) of thiamin are given daily for a limited time if deficiency is
suspected.
Mineral nutriture is also altered in liver disease. Iron stores may be depleted in patients
experiencing gastrointestinal bleeding; however, iron supplementation should be avoided by persons
with hemochromatosis or hemosiderosis (see Chapter 3l). Elevated serum copper levels are found in
cholestatic liver diseases (i.e., PBC and PSC). Because copper and manganese are excreted primarily via
bile, supplements should not contain these minerals.
Wilson's disease is a disorder of abnormal copper metabolism in which urinary excretion is high,
serum levels are low, and excess copper in various organs causes severe damage. Oral chelating agents
such as zinc acetate or /-penicillamine are the primary treatment. A vegetarian diet may be useful as
adjunctive therapy because copper is less available. Dietary copper restriction is not routinely prescribed
unless other therapies are unsuccessful.
Zinc and magnesium levels are low in liver disease related to alcoholism, in part because of
diuretic therapy. Calcium, as well as magnesium and zinc, may be malabsorbed with steatorrhea.
Therefore, the patient should take supplements of these minerals at least at the level of the DRI.

Cholelithiasis

Pathophysiology
The formation of gallstones (calculi) in the absence of infection of the gallbladder is called
cholelithiasis. Virtually all gallstones form within the gallbladder. With rare exceptions, stones form
behind biliary duct strictures as a result of stasis in bile ducts after cholecystectomy (surgical removal of
the gallbladder). Gallstone disease affects millions of Americans each year and causes significant
morbidity. In most cases gallstones are asymptomatic; however, symptomatic gallstone disease can
have serious complications.
Gallstones that pass from the gallbladder into the common bile duct may remain there
indefinitely without causing symptoms, or they may pass into the duodenum with or without symptoms.
Choledocholithiasis develops when stones slip into the bile ducts, producing obstruction, pain, and
cramps. If passage of bile into the duodenum is interrupted, cholecystitis can develop. In the absence of
bile in the intestine, lipid absorption is impaired, and without bile pigments, stools become light in color
(acholic). If uncorrected, bile backup can result in jaundice and liver damage (secondary biliary cirrhosis).
Obstruction of the distal common bile duct can lead to pancreatitis if the pancreatic duct is blocked.
Most gallstones in people in the United States are unpigmented cholesterol stones composed
primarily of cholesterol. bilirubin. and calcium salts. Risk factors for cholesterol stone formation include
female gender pregnancy, older age, family history obesity and truncal body fat distribution, diabetes
mellitus, inflammatory bowel disease, and drugs (lipid-lowering medications, oral contraceptives, and
estrogens). Certain ethnic groups are at greater risk of stone formation, including Pima Indians,
Scandinavians, and Mexican-Americans. Rapid weight loss (as with jejunoileal and gastric bypass and
fasting or severe calorie restriction) is associated with a high incidence of biliary sludge and gallstone
formation.
Bacteria may also play a role in gallstone formation. Low-grade chronic infections produce
changes in the gallbladder mucosa, which affect its absorptive capabilities. Excess water or bile acid may
be absorbed as a result. Cholesterol may then precipitate out and cause gallstone formation. High
dietary fat intake over a prolonged period may predispose a person to gallstone formation because of
the constant stimulus to produce more cholesterol for bile synthesis required in fat digestion.
Pigmented stones typically consist of bilirubin polymers or calcium salts. They are associated with
chronic hemolysis. Risk factors associated with these stones are age, sickle cell anemia and thalassemia,
biliary tract infection, cirrhosis, alcoholism, and long-term PN.

Medical Management
treatment of gallstone disease includes cholecystectomy, especially if the stones are numerous,
large, or calcified. The cholecystectomy may be done as a traditional open laparotomy or as a less
invasive laparoscopic procedure. Chemical dissolution with the administration of bile salts,
chenodeoxycholic acid, and ursodeoxycholic acid (litholytic therapy) or dissolution by extracorporeal
shock-wave lithotripsy may also be used; but these are much less common than surgical techniques.
Patients with gallstones that have migrated into the bile ducts may be candidates for endoscopic
retrograde cholangiopancreatography technique.

Medical Nutrition Therapy

No specific dietary treatment is available to prevent cholelithiasis in susceptible persons.
Nutrition-related factors include obesity and severe fasting, and these should be corrected when
possible. In cholecystitis, dietary treatment includes a low-fat diet to prevent gallbladder contractions.
Data are conflicting as to whether intravenous lipids stimulate gallbladder contraction (Priori et al.,
1997). After surgical removal of the gallbladder, oral feedings are usually resumed with the return of
bowel sounds and after the patient can tolerate removal of the nasogastric drainage tube. The diet can
be advanced to a regular diet as tolerated. In the absence of the gallbladder, bile is secreted directly by
the liver into the intestine. The biliary tract dilates, forming a "simulated pouch" over time, to allow bile
to be held in a manner similar to the original gallbladder.

Cholecystectomy (surgical removal of the gallbladder)

CHOLECYSTITIS 755
Pathophysiology
Inflammation of the gallbladder is known as cholecystitis, and it may be chronic or acute. It is usually
caused by gallstones obstructing the bile ducts (calculous cholecystitis), leading to the backup of bile.
Bilirubin, the main bile pigment, gives bile its greenish color. When biliary tract obstruction prevents bile
from reaching the intestine, it backs up and returns to the circulation. Bilirubin has an affinity for elastic
tissues; therefore, when it overflows into the general circulation, it causes the yellow skin pigmentation
and eye discoloration typical of jaundice.
Acute cholecystitis without stones (acalculous cholecystitis) may occur in critically ill patients or
when the gallbladder and its bile are stagnant. Impaired gallbladder emptying in chronic acalculous
cholecystitis appears to be due to diminished spontaneous contractile activity and decreased contractile
responsiveness to the hormone cholecystokinin. The walls of the gallbladder become inflamed and
distended, and infection can occur. During such episodes, the patient experiences upper quadrant
abdominal pain accompanied by nausea, vomiting, and flatulence. Chronic cholecystitis is long-standing
inflammation of the gallbladder. It is caused by repeated mild attacks of acute cholecystitis. This leads to
thickening of the walls of the gallbladder. The gallbladder begins to shrink and eventually loses the
ability to perform its function: concentrating and storing bile. Eating foods that are high in fat may
aggravate the symptoms of cholecystitis, because bile is needed to digest such foods. Chronic
cholecystitis occurs more often in women than in men, and the incidence increases after the age of 40.
Risk factors include the presence of gallstones and a history of acute cholecystitis.

Medical Management
Acute cholecystitis requires surgical intervention unless medically contraindicated. Without surgery the
condition may either subside or progress to gangrene.

Medical Nutrition Therapy

Acute Cholecystitis. In an acute attack, oral feedings are discontinued. PN may be indicated if the patient
is malnourished and it is anticipated that he or she will not be taking anything orally for a prolonged
period. When feedings are resumed, a low-fat diet is recommended to decrease gallbladder stimulation.
A hydrolyzed low-fat formula (see Appendix 32), or an oral low-fat diet consisting of 30 to 45 g of fat per
day can be given. Studies have failed to show a relationship between dietary cholesterol and gallstone
formation. Table 28-7 shows a fat-restricted diet.
Chronic Cholecystitis. Patients with chronic conditions may require a long-term low-fat diet that contains
25o/o to 30"/o of total kilocalories as fat. Stricter limitation is undesirable because fat in the intestine is
important for some stimulation and drainage of the biliary tract. The degree of food intolerance varies
widely among persons with gallbladder disorders; many complain of foods that cause flatulence and
bloating. For this reason, it is best to determine with the patient which foods should be eliminated. See
Chapter 27 for a discussion of potential gas-forming foods. Administration of water-soluble forms of fat-
soluble vitamins may be of benefit in patients with chronic gallbladder conditions or in those in whom
fat malabsorption is suspected.

cholecystectomy removal of the gallbladder

cholecystitis inflammation of the gallbladder
choledocholithiasis presence of gallstones in the common bile duct
cholelithiasis presence or formation of gallstones
cholestasis suppression of biliary flow
cirrhosis chronic liver disease caused by diffuse necrosis and regeneration, leading to an increase in
fibrous tissue formation disrupting the normal liver structure