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Writer's pictureIfunanya Onyima, MS, RD, LD

Cirrhosis - Etiology, Pathophysiology and Treatment

Updated: Sep 10, 2020

Meta-analytical research paper and case study synthesized by Ifunanya Onyima, MS, RD, Sandra Cobain and Billie Hale




Introduction

Cirrhosis is defined as liver disease resulting from chronic, long-term damage to the liver

or other trauma, that eventually results in liver failure and scarring. Cirrhosis is due to one or a

combination of illnesses such as, chronic hepatitis virus, metabolic syndrome or alcoholism.

Cirrhosis is mainly asymptomatic with most patients being unaware of their condition. Therefore,

Cirrhosis requires different blood tests and assessments from an extensive medical team that

can help to determine the degree of the medical problem. It is up to the medical team to deduce

the cause of cirrhosis and effectively treat both the cirrhosis and the underlying cause(s). Of this

medical team, the registered dietitian plays an important role in the management of this disease

as well as to alleviate complications that may arise. A strong relationship between patient and

dietitian can greatly improve a patient's prognosis and maintain their body’s homeostasis.


Etiology

Cirrhosis is common amongst those who are considered morbidly obese, with a BMI

greater than 35 kg/m^2.(2, 9) Being morbidly obese could cause fat accumulation within the liver

(steato-hepatitis), leading to inflammation, liver cell death (necrosis), and scarring (cirrhosis).

Being extremely overweight can also lead to other illnesses, including hypertension,

dyslipidemia, high waist circumference and insulin resistance. When a person has two or more

of these illnesses at one time, they are suffering from metabolic syndrome, which, when paired

with obesity, could also lead to liver damage and liver cell death.(10, 11)


Excessive alcohol intake can also be a cause of liver cirrhosis.(12) Alcohol is very

energy-dense (around 7kcal per gram depending on the drink), and the extra energy from consumed alcohol is easily stored at fat within the body. Excess fatty acid accumulation paired with slow degradation of fatty acids can lead to steatosis in the liver, which can progress to cirrhosis if left untreated. Alcoholics are also very prone to malnutrition, which could result in inadequate protein intake, leading to decreased lipoprotein production, causing fat to accumulate at the liver which could ultimately lead to cirrhosis, if left untreated. The liver is the main site for alcohol metabolism, and overloading the liver with alcohol could cause the liver to become overworked, leading to inflammation and scarring, which could also result in a cirrhotic liver.


The various forms of hepatitis can also lead to cirrhosis.(13) Hepatitis is a disease that

causes the liver to become inflamed, via bacteria, toxins, drugs, and other foreign substances

that could be damaging to the liver. Hepatitis comes in many forms, and the type of hepatitis

depends on how it was contracted. For example, Hepatitis A is contracted via fecal-oral

contamination, while Hepatitis B is usually contracted via blood transfusions or sterilization

issues. While some types of hepatitis are more harmful than others, they all can lead to

cirrhosis if left untreated. The type of hepatitis that is most likely to cause liver cirrhosis is

Hepatitis C.


According to current research, alcoholism and obesity appear to be the most common causes of

cirrhosis.


“Due to the complexity of liver disease, medical nutrition therapy plays a significant role in maintaining the body’s homeostasis when the liver can not.”

Physiology

Excess fat accumulation due to obesity or resulting from a metabolic illness can lead to

steatosis - the first stage leading to cirrhosis. Steatosis is defined as excess fat accumulation in

the liver paired with inflammation. Excess fatty acids from the diet coupled with slow

degradation of fatty acids can cause fat to be stored and build up in the liver, causing impaired

liver function. Humans digest fat in the form of triglycerides, which get broken down into

glycerol and free fatty acids in the mouth, stomach and duodenum. The free fatty acids form

micelles and are absorbed via the enterocytes, where they are packaged as water-soluble

chylomicrons that can easily be transported into the lymphatic system, and then into the

bloodstream. A lipoprotein is attached to the chylomicron in order to direct the path of the

chylomicron to the correct destination. Chylomicrons are delivered to the liver via the

bloodstream and the lipoprotein allows chylomicrons to enter the liver. Excess fatty acids or

cholesterol that the liver does not utilize is packaged into a very-low-density-lipoprotein (VLDL),

which transported via blood to the rest of the body. The cells in the body either utilize the fat for

energy or the fat is stored in adipocytes. If the liver is oversaturated with fatty acids or

un-metabolized triglycerides, the liver cannot make enough lipoproteins to compensate, and fat

begins to accumulate in the liver, causing decreased blood-flow throughout the liver, impaired

cell-cell interaction within the liver and inflammation.


Excess alcohol consumption can also lead to decreased lipoprotein production. 8 grams

or greater of ethanol per day is said to be the marker for heavy drinking. Many who consume

alcohol in this amount experience a displacement of nutrients, because alcohol causes

dehydration, increased excretion of water-soluble vitamins, and, because heavy drinkers get a

significant amount of their calories from alcohol, decreased protein intake is likely to occur.

Decreased protein intake is the main cause of decrease lipoprotein production for heavy

drinkers, and just like those who suffer from obesity, this can result in steatosis and ultimately

lead to cirrhosis, if left untreated.


Symptoms & Diagnoses (including labs)

To diagnose for Cirrhosis, a patient must have different assessment such as; family

history, medical examination, and blood tests.(2) Most of the patients remain with asymptomatic

until livers starts to decompensate.(1) The decomposition of the liver is when good tissue gets

substituted by scar tissue, blocking the blood flow through the liver resulting in organ failure.(5) A

patient also can suffer from anemia which is associated with chronic liver disease and

sometimes caused by a hemorrhage within the gastrointestinal tract. If a patient has an acute

hemorrhage it can be a serious problem associated with portal hypertension which is caused by

rupture of an esophageal varix. This medical problem is common of patients who are suffering

with cirrhosis.(4)

For a patient in the early-stages of cirrhosis, a doctor may order

tests such as:(5)

❖ Liver function . This test is to check for a buildup of bilirubin in the blood stream.

Bilirubin tells us when (RBC) red blood cells or certain enzymes are breaking down

indicating liver failure.

❖ Kidney function . This test is evaluated for Creatinine indicating malfunction or failure of

the liver if results are low.

❖ Test for hepatitis B and C . Both B and C are evaluated for a chronic liver disease.

❖ Blood Clotting . This test is evaluated to check for blood clotting due to a decrease in

vitamin K.

❖ Magnetic Resonance Elestography or Transient Elastrography . This test is to detect

the fibrosis of the liver to detect for hardening or stiffening of the tissue.

❖ Imaging tests . (MRI) magnetic resonance Imaging or (CT) computed tomography and

ultrasound creating imaging of the liver.

❖ Biopsy. This is a tissue sample (biopsy) of the liver. This is not to diagnose Cirrhosis,

but is done to identify the severity of liver damage

When patients develop advanced Cirrhosis their quality of life and life expectancy

diminish enormously and dyspepsia (indigestion) and malnutrition is common. 7 Cirrhosis is also

present with other kind of symptoms; such as dark urine, light stools, hepatosteatosis (fatty liver)

and bloating.(5) In other cases the patient may have fatigue, pruritus (itchy skin), bleeding

internally, and hepatic encephalopathy which can damage the brain.(7)

A patient’s history is an important factor because the doctor must know for how long and

how much alcohol the patient has been consuming throughout the years. This way the doctor

can detect an early diagnosis of cirrhosis. Other factors to consider are if a patient has Hepatitis

B or C that could be transmitted from birth, sexual contact, drug use, exchange of contaminated

body fluids, or piercing. This disease besides the weight loss can even get osteoporosis due to

vitamin D malabsorption, therefore calcium shortage.(1)

A physical examination of a patient may disclose different findings leading to a hepatic

problem. One of the biggest concerns leading to severe cirrhosis is when the patient

experiences ascites which is the retention of free fluids within the abdominal cavity.(1)

The doctor can monitor cirrhosis depending of the progression and complication,

especially if patient experience esophageal varices and liver cancer. The liver function or blood

test can check for levels of certain enzymes and proteins in the blood. The levels are either

higher or lower than normal indicating liver damage. Some function tests include:(8)

❖ Alanine transaminase (ALT ). ALT is an enzyme in the liver that helps our body to

metabolize protein. As liver damage increase, ALT is released into the blood and the

levels get high. This particular test evaluate for liver injury such as Cirrhosis.

❖ Aspartate transaminase (AST). AST is an enzyme found in the liver that metabolizes

Alanine, an amino acid. ALT and AST are similar both are present in low blood levels,

but in high levels indicates liver damage, a disease, or muscle damage.

❖ Alkaline phosphatase (ALP ). ALP is an enzyme found mainly in the liver, as well in the

bile ducts, and bones. Higher levels indicate disease in the liver, blocked bile duct, or

bone disease.

❖ Albumin and total protein . Albumin is a particular protein made in the liver. Albumin is

needed to fight infections and perform different body functions. Lower levels of this

protein indicate liver damage, or a disease.

❖ Bilirubin. Substance present in the blood when RBC and enzymes break down.

Bilirubin passes through the liver and is expelled in the stool. Elevated Bilirubin

(jaundice) may indicate liver damage, a disease, or certain anemia.

If any of those tests above are abnormal further test must be done:

❖ Complete blood count (CBC). CBC helps to evaluate a patient checking for RBC and

platelets; anemia may be present if bleeding occurs, and platelets. Platelets checked for

tiny blood cells that help the body to clot. In Cirrhosis platelets means that those tiny

cells are decreased.

❖ Prothrombin time (PT). Mostly clotting factors are produced in the liver. This test

evaluates for clotting function. A clotting factor that can be persistent with Cirrhosis.

❖ Many tests are used to monitor the progression of Cirrhosis, but as the condition get

worse, additional testing will be needed.

❖ Hepatitis B and C. This test underlines the cause of chronic liver disease.

❖ Peritoneal Fluid Analysis : This test is done only if ascites is present. If present the fluid

would result in a milk color type stating Cirrhosis.

❖ Liver biopsy . As stated before is a sample of the tissue, but evaluates the structure and

cells of the liver.

Other tests are ordered to monitor and development of complications:

❖ Alpha-fetoprotein AFP . AFP has elevated levels and could be a sign of Cirrhosis or

chronic hepatitis, but can be more elevated when liver cancer occurs.

❖ Des-gamma-carboxy prothrombin (DCP). If patient has high levels of DCP indicates

cancer in the liver.

❖ Ammonia . This test rises indicating late-stage with liver failure.

❖ In certain conditions other tests are used to evaluate prognosis of Cirrhosis.

❖ Child-Turcotte-Pugh (CTP ). This test evaluates life expectancy in patients that suffer

advance Cirrhosis.

❖ Model of End-Stage liver disease (MELD). This test is used to determine who is a high

risk of mortality to consider for liver transplant.

There are certain vitamins and minerals that are associated with alcoholic liver disease.(5)

❖ Folic Acid . A deficiency in this vitamin can cause changes in the intestine that includes

shortening of the villus, which impedes the absorption of nutrients.

❖ Thiamin . A deficiency of Thiamin in alcoholics causes a Wernicke-Korsakoff syndrome.

This syndrome is characterized by loss of the eye movement, gait (walk) disturbance,

and confusion (Wernicke’s encephalopathy).

❖ Vitamin K. A deficiency on Cirrhotic patient causing a pancreatic insufficiency and biliary

obstruction resulting in fat malabsorption.

❖ Vitamin K and Zinc . A deficiency is caused by malnutrition or poor diet. Vitamin A is

night blindness, and Zinc helps in the absorption, transport and metabolism of vitamin A.

❖ Iron . A deficiency of Iron can result of anemias, or internal bleedings such as

esophageal varices.

❖ Calcium. A deficiency includes a decrease in bone density and bone mass which a

patient with Cirrhosis increase the chance to have more fractures.

❖ Sodium: Low levels of sodium indicates fluid retention which leads to ascites. The

amount of fluid within the cavity can have as much of 15.5 L. (5)


Treatment

Medications

Patients with impaired liver function, especially Cirrhosis, have an inability to metabolize

most medications. This inability is due to; necrosis of liver cells, shunting of blood through portal

systemic collaterals, reduced drug-binding proteins, abnormal drug-volume distribution, altered

drug elimination, altered drug metabolism, altered pharmacodynamics, associated renal failure,

and drug-drug interactions.(14) Even patients with compensated liver cirrhosis will still exhibit

some form of liver injury from medications and/or herbal supplements. The prescription of

medications to individuals with cirrhosis must be done on an individual basis with a full

assessment including the patient's nutritional status, renal function, adherence, and drug-drug

interaction.(14)


Of the approved medications for the treatment of liver Cirrhosis include the use of;

diuretics, ammonia reducers, beta blockers, synthetic hormones, antibiotics, and antiviral drugs.

The use of diuretics is in an effort to control fluid and electrolyte balance by promoting urinary

output. Ammonia, a harmful toxin produced in the body, builds up in the body overtime due to

decreased filtration and breakdown by the liver. Ammonia reducers aim to lower these harmful

levels by pulling ammonia into the colon where it is excreted in the feces. Beta blockers and

synthetic hormones help to regulate tissue and organ function, as well as reduce blood pressure

in the body. Both of these medications work in an effort to compensate for decreased bodily

functions and as a means of prevention of variceal hemorrhages, a complication of cirrhosis.

Antibiotics work in conjunction with ammonia reducers by stopping growth and killing bacteria in

the intestines that can raise ammonia levels in the body. And lastly, antiviral drugs are

prescribed to individuals who may be infectious and can pass along viruses to others. These

drugs are generally not part of a regime for alcoholic or fat-induced liver dysfunction.(15)

Of the herbal supplements most utilized by Cirrhosis patients is milk thistle. While milk

thistle does have antioxidant properties and likely safe says McClain, there is no evidence

suggesting that it may improve liver function. Patients should be cautioned consuming such

supplements as further liver damage may occur.(16)


Medical Nutrition Therapy (MNT)

Due to the complexity of liver disease, medical nutrition therapy plays a significant role in

maintaining the body’s homeostasis when the liver can not. Nutritional assessment is key in this

treatment due to the fact most visceral proteins of the body (like albumin) are altered because of

the disease. Physical assessments such as skin fold tests also help dietitians make

recommendations when biochemical data is not available for an accurate nutrition diagnosis.


Diet plays an important role in the management of cirrhosis and a general meal plan for patients

include a low-sodium, low-protein, and in more advanced cases of cirrhosis, a fluid restricted

diet. A diet low in protein should be based on an individual basis. Cirrhosis patients need

adequate amount of energy from protein to prevent muscle wasting. As a precautionary

measure to combat the potential complication of hepatic encephalopathy, dietitians will put

patients on a restricted protein diet. Low-sodium is recommended in patients with

decompensated liver disease who may be experiencing ascites. With the presence of ascites is

usually also accompanied with a fluid restriction. Again, all of these recommendations are made

on an individual basis. For patients who may still be consuming alcohol, it’s metabolism may

interfere with omega-6 fatty acids that can produce highly toxic radicals in the body. Also, when

patients consume alcohol they are usually drinking instead of consuming energy from calories. It

is easy for patients to become malnourished, among other complications. Other nutritional

recommendations include avoidance of large amounts of fructose or sugar-sweetened

beverages to prevent weight gain and increase lipids in the blood. Maintaining a diet rich in

omega-3’s can also help mediate some of the body's anti-inflammatory properties.(16)

Micronutrient deficiencies also exist amongst cirrhosis patients for multiple reasons

including; poor nutritional intake, poor absorption, and increased losses. A few of these

deficiencies include B vitamins, Magnesium, Vitamin A, Vitamin C, Zinc, and Folate with Zinc

being the deficiency seen most often. Zinc can cause many abnormalities within the individual.

Poor intake and absorption are main factors to this deficiency, but much of the body’s Zinc is

also lost through the urine. McClain recommends that patients take a multivitamin to maintain

stores of these micronutrients.(16)


Specific nutrition interventions include an energy intake of 30-40kcal/kg body weight/day

and protein intake of 1.2-1.5g/kg body weight/day. The value 1.2g/kg body weight for protein

has also been shown in this study to be safely used with patients who are experiencing hepatic

encephalopathy, although other evidence may suggest otherwise. According to Peyton and

Martin’s study, evidence suggests that nocturnal feedings as opposed to supplementation with

branched-chain amino acids has shown positive health effects in the patient, and overall

decreased the number of patients who experience entering into a catabolic state during the

evening.(17) McClain’s study supports this evidence and suggests that the amount of energy

needed to sustain an individual's muscle mass and to prevent catabolism is approximately 700

calories and 25 grams of protein.(16)


Transplant

Transplantation in end-stage liver disease has been beneficial in extending the life

expectancy of cirrhosis patients according to a study by Martin, Brown Jr., Feng, DiMartini, and

Fallon. Their study showed that the one-year survival rate ranged from 70-90% and a 5- and 10-

year survival rate were 82% and 62%, respectively. Methods of assessing patients for transplant

include using the MELD score (Model for End Stage Liver Disease) which replaced the previous

scale, the Child-Pugh score. Scoring is from 6-40 with a corresponding mortality rate within 3

months of 90-7%, respectively. The MELD score is now used as a means of measuring a

patient's prognosis over the next 3 months and looks at several factors, many of which are

influenced by nutrition and nutrition interventions. Two of these factors include the development

of hyponatremia and recently the incorporation of serum sodium levels into the score as

markers for mortality. Patients with a recommendation for liver transplant include individuals

who; 1) have cirrhosis, and experiencing a complication such as ascites, hepatic

encephalopathy, or variceal hemorrhage or hepatocellular dysfunction with a MELD score ≥ 15,

2) has treatable etiologies (such as the one previously mentioned), and 3) candidates with

worsening renal function or other evidence of rapid renal decompensation.(18)

Another aspect of the evaluation process does include a full nutrition evaluation on the

patient. The aim for most patients (with the absence of other complications) still includes energy

intake of 35-50 kcal/kg/day and a minimum of 1.3-1.5g/kg/day of protein to prevent muscle

catabolism. Patients should be meeting these needs within a minimum of 24 hours before

transplant surgery to prevent further catabolism and maintain a positive nitrogen balance in the

body. If necessary, enteral supplementation will be needed for patients who can not meet these

needs themselves.(19)


Case Study

We were presented with a cirrhosis patient who is experiencing complications such as

ascites and fatigue. The nutrition team conducted a full nutrition assessment which included a

biochemical screening, a 24-hr food recall, physical assessment, and patient interview. After

conducting our patient interview and physical assessment we determined that this patient has

ascites due to his excessive intake of sodium and fluid. We also concluded that the patient was

experiencing fatigue brought on by limited intake of energy of calories, protein, and fat. Another

significant nutrient missing from his diet was iron. Patients with decreased liver function are

more likely to exhibit signs of anemia. The patient also continues to consume alcohol even

though his diagnosis is end-stage liver disease. Continued alcohol consumption will continue to

make it harder for this patient to absorb nutrients and will continue to worsen his prognosis. The

patient complains of malaise and that the pressure on his abdomen makes it difficult to eat and

finish his meals.

We prioritized our interventions based on following diagnoses: inadequate energy intake,

excessive intake of sodium and fluid, inadequate iron intake, and alcohol consumption. This

patient requires a higher amount of energy due to the dysfunction of the liver and because he is

in a constant state of healing. This includes higher caloric and protein intake. In order to target

the ascites and energy intake we suggested following a renal diet with a moderate amount of

protein. This diet will include a sodium restriction, increased intake of fruits and vegetable, and a

moderate amount of lean protein foods as determined by the dietitian.

When suggesting a dietary plan for this type of patient all suggestions need to be made

on an individual basis. In this patients case our suggestion for a one-day meal plan (attached)

for our patient included meeting his caloric requirements (2900-3400 kcals/day) and protein

needs (1.0-1.5g/day) for healing. We also suggested a sodium and fluid restriction (1500mg and

1.5-2.0L/day, respectively) as a means to control the ascites. Once the presence and symptoms

have diminished the nutrition care team can reevaluate the patient's needs. It’s important that

we also discuss the risk of continuous consumption of alcohol can have on a patient and their

prognosis. Any form of alcohol at this point is extremely toxic and harmful to the patient and

their organs. Supplementation may be needed in some cases to replace minerals and vitamins

that are not easily absorbed in the body. Due to this, a suggestion of a low-dose iron

supplement would be necessary to combat the anemia in the body that the patient is

experiencing based on his biochemical data, as well as a daily multi-vitamin.

Ongoing this patient will need to be monitored regularly to assess for diminished liver

function, kidney function, the presence of anemia, nutrient and mineral deficiencies, and other

complications. This patient will be prescribed many of the medications discussed previously in

order to manage these complications. This patient will continue to see a medical team of

specialists to help maintain their health.


Conclusion

Despite the fact that there are many ways that one could develop cirrhosis, scientific

research has discovered multiple ways of diagnosing and treating the illness. It is clear that

medical nutrition therapy provided by a registered dietitian can play a vital role in maintaining a

person’s health and well-being.



Source(s)

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Joel J. Heidelbaugh, M.D., and Michael Bruderly, M.D., University of Michigan

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