Medical and surgical advances have been made involving patients diagnosed with liver disease. As a result, these patients are living longer and have an improved quality of life. PTs have become instrumental members of the multidisciplinary team in the management of this patient population.

Liver Anatomy

The liver is a wedged shape organ located in the upper right side of the abdomen underneath the rib cage. It is the largest organ of the body, making up 2% to 3% of the body’s total weight, and consists of a right lobe and a left lobe. The right lobe is considerably larger than the left lobe.¹ The gallbladder is situated below the liver and is connected to the liver by bile ducts.²

Blood enters the liver via the hepatic artery and the hepatic portal vein. Blood from the hepatic artery is enriched with oxygen as it comes directly from the heart. The blood from the hepatic portal vein, which arises from the splenic and mesenteric veins, has already absorbed nutrients and other substances from the gastrointestinal tract.²

Functions of the Liver

The liver is involved in several functions that occur primarily in the hepatocytes. The primary functions are —^1,2

• Synthesis of blood clotting factors
• Synthesis of bile salts
• Conjugation and secretion of bilirubin
• Detoxification of harmful substances
• Metabolism of alcohol and multiple drugs
• Metabolism of carbohydrates, protein, fatty acids, cholesterol
• Metabolism of ammonia
• Processing of vitamins and minerals
• Maintenance of hormonal balance

The liver synthesizes several factors involved in blood clotting. In liver disorders, the values International Normalized Ratio (INR), Prothrombin Time/Protime (PT), and Partial Thromoplastin Time (PTT) will be elevated. Platelet levels will be low. Normal platelet count is in the 150,000 to 400,000 range.¹ It is not unusual for a patient with a liver disorder to have a platelet count below 50,000.³

The liver and gallbladder are connected by ducts that carry bile, a greenish mixture of acids, salts and other substances, into the intestines. Bile is formed in the hepatocytes and travels to the gallbladder where it is stored. The contraction of the gallbladder passes bile to the duodenum via the common bile duct; bile assists with the digestion of fats and with intestinal peristalsis.¹

The greenish color associated with bile is due to one of its components, bilirubin, which is a waste product of old red blood cells. Bilirubin circulates in the bloodstream bound to albumin. Indirect bilirubin, which is not water soluble, is also called uncongugated bilirubin. The liver conjugates it to a water-soluble form, conjugated bilirubin, which is secreted into the bile. If bilirubin levels rise due to liver disease or hepatitis, jaundice develops, and the skin and eyes become yellow in appearance.¹

The liver is also the storage center for many vitamins and minerals. Vitamins A, D, E and K can only exist in a fatty solution. If the bile ducts are blocked, which can occur in liver disease, the body cannot digest the fats needed for the absorption of these vitamins. Therefore, vitamin K, which is necessary for the clotting of blood, is not available; this places people with liver disease at high risk for bleeding.¹

The liver also plays a role in the production of amino acids, essential components of protein, which is necessary for the building of muscles. With liver disease, muscle atrophy is pronounced. In addition, the risk for bone fractures become high due to the lack of muscle support.¹

The liver is also responsible for the regulation of the right amount of glucose in the blood and providing it to other parts of the body. A damaged liver has difficulty with the regulation of blood glucose levels.¹

The regulation of hormones is also a role of the liver. Estrogen and androgen are made from cholesterol. A damaged liver is unable to regulate the production and breakdown of these substances, which can lead to hormonal imbalance.¹

The liver is also responsible for the processing of drugs. Most drugs are fat soluble and are absorbed by the lipid cells lining the stomach and intestinal walls.

In addition, the liver plays a major role in the mental status of an individual. During the process of digestion, ammonia, a toxic chemical substance, is produced in the body from animal proteins. The liver is responsible for converting ammonia into urea, a nontoxic substance that is easily eliminated by the kidneys. A diseased liver is not able to perform this function, which causes ammonia to build up in the blood and brain. As a result, an individual will develop hepatic encephalopathy. The patient may experience altered mental status, a short attention span, and irritability. In the more extreme cases, the patient may be in a coma.¹

Common Medical Procedures

Patients with liver disease may need to undergo a variety of procedures for either treatment or diagnostic reasons. Some of the more common procedures include —

Liver biopsy: A liver biopsy is performed when a diagnosis is difficult to determine via blood tests or imaging. It may also be done to determine the degree of liver damage. During the procedure, a small piece of liver is removed and examined under a microscope.⁶ After a liver biopsy is complete, the patient must lie on his or her right side for at least two hours and be monitored for any signs of bleeding.⁷ Following a liver biopsy, physical therapy intervention will be deferred. However, there are no restrictions regarding mobilization once the patient is off bed rest.

Paracentesis: This procedure removes peritoneal fluid (ascites) that has accumulated in the abdomen. Paracentesis is performed to relieve abdominal pressure or pain.⁸ As long as the patient is stable post-procedure, there are no restrictions regarding physical therapy.⁸

Transjugular Intrahepatic Portosystemic Shunt: TIPS is a stent that is placed inside the veins of the liver to permit blood flow to bypass the liver. The TIPS procedure is usually indicated for patients with increased pressure in the portal vein. TIPS treats the complications of portal hypertension, which include variceal bleeding, portal gastropathy, ascites, and Budd-Chiari syndrome.⁹ After the procedure is completed, the patient’s head is elevated for a few hours to prevent any risk of bleeding. Therefore, physical therapy intervention is deferred until the following day.⁹

Endoscopic Retrograde Cholangiopancreatography: ERCP is a procedure in which the gallbladder, bile ducts, and pancreatic ducts are injected with dye and X-rays are performed. Diagnosis and treatment can be achieved via an ERCP.¹⁰ Indications for an ERCP include the following:

• Abnormalities of the bile ducts, gallbladder, or pancreas
• Evidence of bile duct blockage followed by other diagnostic testing
• Recurrent pancreatitis
• Jaundice
• Abnormal liver chemistries
• Workup for liver transplantation

Complications of ERCP occur in 5% to 10 % of patients. They may include cholangitis (infection of the biliary duct), hemorrhage, duodenal perforation, pancreatitis and infection. There are no restrictions regarding mobility post-procedure. However, the PT will usually defer treatment until the following day because the patient may still be sedated from the procedure.¹¹

Liver Failure

Liver failure may be due to a number of causes, which are listed below. A more detailed explanation of some of the following is provided later in this article.^4,12

• Cirrhosis
• Biliary atresia
• Fulminant liver failure
• Metabolic disease: Wilson disease, Alpha I antitrypsin
• Liver cancers
• Autoimmune Hepatihs
• Primary biliary cirrhosis
• Primary sclerosis cholangitis
• Alcoholic liver disease

Fulminant Liver Failure

Fulminant liver failure is defined as acute liver failure with hepatic encephalopathy, jaundice and coagulopathy. Liver failure occurs suddenly, usually within eight weeks of the onset of symptoms or within two weeks of the onset of jaundice.² Patients with fulminant liver failure have an 80% to 90% mortality rate. The major goal of treatment is keeping the patient alive and free from serious complications. In some patients, liver function spontaneously recovers. Other patients require an emergency liver transplant. A major challenge regarding the care of this patient population is predicting which patients can recover on their own and which patients require an emergency liver transplant to save their life.

Chronic Liver Disease

Chronic liver disease lasts more than six months, is insidious on onset, and leads to cirrhosis of the liver. The most common chronic liver diseases which are indicated for a liver transplant are the following:

Primary biliary cirrhosis is characterized by the slow and gradual destruction of the intrahepatic bile ducts. The exact cause of the disease is unknown but is believed to be autoimmune. The disease is prevalent in women, who make up 90% of the cases. It is also found as a secondary diagnosis of the following diseases: rheumatoid arthritis, scleroderma, Sjögren’s syndrome, lupus and thyroiditis.¹

Primary sclerosing cholangitis is characterized by inflammation, fibrosis and destruction of the intra- and extrahepatic bile ducts. The disease affects more men than women (70% of patients are men). The exact cause is unknown but may be autoimmune in nature. Other possibilities may include toxins and infections. There is also an increased incidence of PSC in patients with ulcerative colitis.¹

Cryptogenic cirrhosis is the name given to a category of liver diseases when the cause of the liver disease is unknown and all other etiologies have been ruled out. The majority of patients with cryptogenic cirrhosis have been found to have Type II Diabetes Mellitus and current or past history of obesity.¹⁴ Less than 5% of patients with cirrhosis are given this diagnosis.¹⁵

Chronic active hepatitis B is inflammation of the liver due to the hepatitis B virus (HBV) that is ongoing for more than six months. People with chronic hepatitis B are 200 times more likely to develop liver cancer as are people without chronic hepatitis B.¹ Those at risk for hepatitis B include —¹

• People who have received blood transfusion prior to 1975
• Healthcare workers
• People who received a tattoo or had a body part pierced with an infected needle
• Travelers to countries or areas with high incidences of HBV such as China, Southeast Asia, and the Sub-Saharan African countries
• People born to a mother with HBV
• Transplant recipients who received an infected organ
• Sex partners of infected persons
• Intravenous drug users

Chronic Active Hepatitis C is inflammation of the liver due to the hepatitis C virus (HCV). It is considered chronic when the immune system has not cleared it from the body in six months. Hepatitis C is the most common cause of liver cirrhosis and liver cancer in the United States.¹ Unlike hepatitis B, hepatitis C is not preventable by a vaccination due to the large population of mutant strains of HCV. The category of people at increased risk for hepatitis C is the same as for people with hepatitis B. People with chronic hepatitis C are 25 times more likely to develop liver cancer. Excessive alcohol consumption and coinfection with hepatitis B also increase the risk for liver cancer.¹

Alcoholic Liver Disease: Approximately 25% of people who partake in excessive alcohol consumption will develop alcoholic liver disease (ALD).¹ There are three stages of ALD:

• Alcoholic fatty liver: liver biopsy will reveal fatty deposits but no other abnormalities, generally benign and reversible, no long-term consequences if alcohol consumption discontinued at this stage¹
• Alcoholic hepatitis: inflammation of the liver due to the toxic effects of alcohol. Asymptomatic: Abnormal liver function tests, totally reversible if person immediately and permanently abstains from alcohol. Symptomatic: Very ill, will have 50% chance of developing cirrhosis if alcohol consumption continues.¹
• Alcoholic cirrhosis: severe scarring of the liver due to alcohol, irreversible condition when complications of cirrhosis develop, 15% risk of developing liver cancer¹

Hepatocellular carcinoma is a malignant tumor of the liver.^1,13 It is one of the more common cancers in the world, accounting for 6% of all cancers. It is less common in the United States where it accounts for 0.5% to 2% of all cancers. Although the presence of HCC is less in the United States, the risk of occurrence has increased in the past 20 years thanks to the prevalence of chronic hepatitis C.¹ There are multiple factors involved regarding a patient’s risk for developing HCC:

• Presence of cirrhosis in 60% to 90% of the people with HCC. Once cirrhosis has developed, there is up to a 200-fold increased chance of developing HCC.
• Presence of HBV in approximately 75% of all HCCs.
• Increased risk of HCC for those who consume alcohol and smoke
• Hemochromatosis: genetically acquired liver disease of iron overload
• Use of anabolic steroids
• Use of oral contraception for more than eight years slightly increases risk
• Diabetes may be a risk factor; hyperinsulinemia may activate factors that cause gene mutations leading to cancer
• Men are two to four times more likely to develop HCC
• Race: Asians, Hispanics, Native Americans, highest risk; African Americans, medium risk; Caucasians, lower risk
• Increased gene damage and mutations that lead to HCC occur with increased age; rare under age 40.¹

Several treatment options are available for HCC. The most common are —

• Surgical resection: Single tumors of less than 5 cm in size that have not metastasized to other organs are more surgically treatable.¹³ Up to 80% of a person’s liver can be removed in the absence of cirrhosis. Candidates should have overall good health and be less than 50 years old. However, only 5% of people in the United States meet these criteria. Also, tumor recurrence has a great chance of developing in the remaining portion of the liver.¹
• Liver transplantation not only removes the tumor but also any cirrhosis if present. People with HCC with a mass less than 5 cm in size who have no more than three sites of HCC less than 3 cm in size are considered good candidates for a liver transplant.

Workup for Liver Transplant

Once a patient with liver disease has undergone testing and a specific diagnosis is made, criteria must be met to determine if a patient will be a good candidate for a liver transplant.

The following indications and contraindications will determine if a client will be placed on the transplant list.

Indications for liver transplant —^12,13

• Fulminant liver failure
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Cryptogenic cirrhosis
• Chronic active hepatitis
• Hepatocellular carcinoma (HCC)
• Alcoholic (ETOH) liver disease

Contraindications for liver transplant —^1,12,13

• Acute ETOH or drug abuse
• Active infection
• HIV positive
• Extrahepatic tumor
• Liver tumor > 5mm
• Age > 65 years
• Cardiopulmonary disease
• Hepatopulmonary syndrome
• Irreversible brain dysfunction
• Morbid obesity
• Portal vein thrombosis
• Lack of social support

Model for End Stage Liver Disease (MELD) was developed in 2002 to prioritize patients waiting for a liver transplant. The range is from 6 (least ill) to 40 (gravely ill).16 The MELD score is determined by the following lab values:^1,16

• Bilirubin
• INR
• Creatinine

The MELD score is determined by the following equation:¹

• 3.8 x log (e) (bilirubin mg/dl) + 11.2 x log (e) (INR) + 9.6 log (e) (creatinine mg/dl)

For the inpatient, the MELD score can easily be calculated on a daily basis. For the outpatient, the MELD score will be recalculated by the following recommendations:¹⁶

• MELD score greater than 25: lab tests needed every seven days
• MELD score 24 to 19: lab tests needed every 30 days
• MELD score 18 to 11: lab tests needed every 90 days
• MELD score less than or equal to 10: lab tests needed every year

The average MELD score for a patient undergoing a liver transplant is 20.¹⁶

Liver Transplant

Liver transplant is the only option for patients with irreversible liver failure. The one-year survival rate is close to 90%, and the three-year survival rate is 80%.¹⁷ Since the demand for transplants has increased, different surgical techniques are considered.¹⁷

Conventional Liver Transplant: Liver transplant, also known as a hepatectomy, involves removing the entire diseased liver and replacing it with a donor liver of a person who has been given the diagnosis of brain death.This diagnosis is established when there is no reversal of neurological damage, no presence of cerebral function, and no presence of brainstem function. Several states have also added amendments regarding physican qualifications and confirmation by a second physician when the diagnosis of brain death is determined.¹⁸ The orthotopic liver transplant (OLT) is the conventional method of transplantation.¹⁹

Living Donor Transplant: This involves removing one liver lobe from the donor, usually the right lobe, which is transplanted into the patient with liver disease.^17,19,20 The right lobe is preferred, as it is the larger lobe and makes up 60% of the liver. The liver has the ability to regenerate with the remaining part of the donor liver achieving its near original size in four to six weeks.¹⁹ The success rate is comparable to the conventional liver transplant.¹

Split Liver Transplant: This entails having the deceased donor liver split in two so that two recipients can benefit. An adult usually receives the right liver lobe, and a small adult or child can receive the left liver lobe.^17,19,20 Due to advances in surgical techniques, this procedure is being performed more frequently with a success rate comparable to the conventional and living donor techniques.¹

The patient is at risk for developing complications following a liver transplant:^1,2,13

• Post-op bleeding: Patients with liver disease already have abnormal clotting factors that make the risk of post-op bleeding greater as compared to patients with no liver disease. A patient may need to return to the OR for control of intra-abdominal bleeding, evaluation of a hematoma, or restenosis of hepatic vasculature.
• Bile leaks: Bile leaks can occur from a newly sutured bile duct. The leak must be repaired via an ERCP procedure.²
• Rejection: Most patients will experience some degree of rejection the first two weeks following a transplant. These episodes are usually mild to moderate and are treated with IV steroids (usually methyl prednisone) followed by a brief period of increased doses of prednisone. If an episode of rejection is severe and does not respond to steroids, the patient is treated by IV administration of antibodies against the lymphocytes. Chronic rejection, which does not respond to drugs, occurs in about 10% of transplant patients. A second liver transplant is the only treatment option for this patient.² Following a liver transplant, patients will have to be on anti-rejection medications for the remainder of their lives. Signs of rejection, listed below, can only be definitely diagnosed by a liver biopsy.¹³
  • Temperature > 100 F, increased WBC
  • Jaundice
  • Dark urine
  • Itching
  • Abdominal swelling/tenderness
  • Fatigue
  • Irritability
  • Headache
  • Increased blood levels of bilirubin and amino transferase
• Infection: Because the immune system is compromised by the anti-rejection medications, the post-op liver transplant patient is at risk for developing infections.
• Cancer: Following a liver transplant, a person may be at risk for developing cancer due to a depressed immune system, infections, the use of immune-suppressants, genetic predisposition, and age. People with a history of alcoholic cirrhosis are at the highest risk for developing cancer.
• Recurrence of liver disease: Patients transplanted due to HCV are at the highest risk for developing a recurrence of liver disease.¹
• Cardiovascular disease: A postoperative transplant recipient also has an increased risk of developing cardiovascular disease, especially as survival time increases. The chronic use of prednisone, tacrolimus, and cyclosporine add to the increased risk, due to some of the side effects of these medications.
• Renal insufficiency: Transplant recipients are at risk of developing renal problems due to the use of immunosuppressant medications. The dosage of medications may be adjusted or they may be replaced by other medications.²
• Neurological compromise: The use of immune-suppressive medications also increases the risk of altered mental status, tremors, seizures, visual disturbances, etc. As stated above, the dosage of medications may need to be adjusted or they may need to be replaced by other medications.²

Physical Therapy Concerns Regarding the Liver Transplant Recipient

Due to the multiple functions of the liver that become compromised as a result of liver disease and the risk for perioperative complications, the PT is presented with many challenges regarding the mobilization of this patient population. It is of utmost importance that the therapist thoroughly reviews the medical record and collaborates with the nursing staff prior to treatment.

Due to coagulopathy issues, the risk of potential bleeding remains high. The patient must be observed for increased bleeding or oozing from incisional sites, and dressings may need reinforcement. The patient may also be advised to wear an abdominal binder.

The patient will usually complain of overall weakness and fatigue, which is due to a variety of factors. Some of the more common factors include anemia, generalized weakness, labile blood glucose levels, and malnutrition. In addition, ascites may present a challenge to mobilization. Much edema will be present in the abdominal region, which will make transitional movements difficult, especially bed mobility and sitting on the side of the bed. For the male patient, an additional problem may be scrotal edema. One may compensate by leaning backward while sitting on the side of the bed to alleviate discomfort. In addition, the patient may present with a wide base of support during gait in order to prevent chafing.

Due to a shift of fluid that may occur during surgery, the cardiopulmonary system may be impacted. The patient may complain of dyspnea on exertion with a minimal amount of activity. Also, due to post-operative incisional pain, the patient may be apprehensive about doing deep breathing exercises. Most patients are provided with a PCA pump, but they may require additional pain medication if no relief is provided by the PCA.

Hepatic encephalopathy may also be encountered post-operatively. The patient may exhibit inappropriate and impulsive behavior. Attention span may be limited, and continuous redirecting may be necessary.

Fragile skin is another issue the therapist needs to be aware of. Due to edema and malnutrition, the skin may exhibit many areas of bruising. Skin tears may also be present. The patient must be handled with care, and gentle hand placement is needed to prevent any additional bruising or tears. If any new areas of skin breakdown are noted during physical therapy treatment, the nursing staff needs to be notified so proper intervention can occur.

Due to factors such as multiple lines, overall weakness, and hepatic encephalopathy, the post-operative patient may be at risk for falls. A fall may be of great concern due to the risk of bleeding. It is recommended, especially in the ICU environment, that two staff members (e.g., PT and PT technician) be involved with mobilization. During gait training, the PT technician follows closely behind with a wheelchair. In some cases, both the PT and technician may need to have hands-on treatment during gait training, and a third person (nursing staff or family member) follows with the wheelchair. A portable telemetry EKG monitor is also recommended to observe vital signs.

It is also recommended that the therapist use a gait belt during gait training. The belt must be fitted above the level of the surgical incision. Due to the patient’s being on anti-rejection drugs, the risk for infection is high. Therefore, the patient should be provided with his own gait belt to prevent cross contamination. However, the therapist may use a vinyl gait belt and thoroughly clean it after patient use. Whether or not a patient wears a disposable surgical mask while in the hallway will be determined by physician preference. However, a patient needs to wear gloves, or gloves should be placed on the handles of a rolling walker for infection control.

Provided the patient does not have any major postop complications, mobilization will progress as the patient’s condition allows.

Before discharge from the hospital, the patient will be provided with a home program that is based upon activity level at the time of discharge. The case manager will order durable medical equipment such as a rolling walker, cane or bedside commode if needed. The more complex post-operative patient may require care at a rehabiliatation hospital, skilled nursing facility or long-term acute facility before discharge home.

The patient can return to a good quality of life in a few weeks and can return to work in a few months. Liver transplant patients are more likely to return to work if they have HMO/PTO insurance, worked more hours prior to transplantation, do not have diabetes mellitus, did not receive disability income prior to transplantation, and have a high level of mobility.²¹

In summary, management of the patient with a liver transplant presents many challenges and involves a multidisciplinary approach. Physical therapy intervention plays an important role.