Dr. Melissa Palmer's Guide To Hepatitis and Liver Disease

Introduction

If you’re like most people, you’ve never really thought much about your liver. After all, you can’t feel it the way you can feel your heart beating. Your liver doesn’t groan with hunger like your stomach, nor does it gurgle during digestion like your intestines. But now your doctor has told you there’s something wrong with your liver, and you’ve suddenly become very much aware of its presence. Perhaps you’re recovering from a lifetime of alcoholism and you have alcoholic liver disease, or maybe you’ve never had an alcoholic drink in your life. Maybe you’ve been diagnosed with liver cancer, or perhaps you’re suffering from a genetic liver disorder. Or maybe—like approximately 4 million other Americans—you’ve been told that you have just become part of the hepatitis C epidemic sweeping the nation, or that you are one of the almost 400 million chronic carriers, worldwide, of the hepatitis B virus.

The diagnosis of these conditions can have a tremendous impact on the daily lives of many individuals and their loved ones. How do I know this? Because I personally take care of thousands of people with hepatitis and liver disease each year. Who am I? I am a hepatologist (liver specialist), and I have perhaps the largest private solo practice devoted to hepatitis and liver disease in the United States.

Over the past fifteen years, I have spent much of my time educating the lay and medical communities about hepatitis and liver disease through lectures and publications. I have been active in many voluntary societies devoted to the study, prevention, and treatment of liver disease. These nonprofit organizations include the American Liver Foundation (ALF), where I sit on the medical advisory board of the New York chapter, as well as on the nutrition education subcommittee of the national chapter. I run liverdisease.com, an Internet website devoted to liver disease. I have appeared on numerous television and radio programs, both locally and nationally, to discuss various aspects of hepatitis and liver disease, as well as the latest available treatments. I have appeared in videos and CD-ROMs aimed at educating the public and healthcare professionals about hepatitis and its treatment. I have also actively participated in research studies of the most promising experimental drugs for the treatment of hepatitis. I have been interviewed on various issues pertaining to liver disease for many mainstream publications such as Time, Cosmopolitan, Prevention, and the Los Angeles Times. I also serve as a liver disease consultant to five prominent pharmaceutical companies.

I’ve often been told by family, friends, colleagues, and even my patients that I live my life in overdrive. And maybe they are right. While in the midst of my training in hepatology and gastroenterology, I decided to become a competitive bodybuilder. After a few years of training, I won the title of Ms. Northern States, appeared on multiple segments of the television show MuscleSport USA, and twice had my picture on the inside front cover of the magazine Female Bodybuilding. By then it was time to start my medical practice, so I gave up my short-lived career as a competitive bodybuilder. But I got a whole lot more out of the experience than just a few trophies. I learned a great deal about nutrition and exercise—two powerful tools that many doctors overlook in their treatment of illness. By combining what I learned as a bodybuilder with what I learned in medical school, I have been highly successful in keeping my patients healthy. In fact, I’ve learned so much about the effects of diet and exercise on liver disease that I am now considered one of the nation’s experts on the subject.

You have a lot of questions. Is this disease serious? Am I putting my loved ones in danger? What treatments are available? What are the alternatives to conventional medicine? What medications should I avoid? Will I be able to have children? Is there a diet and exercise program that I can follow to help me get better? This book will help you answer all these questions and more. You’ll learn how the liver works to neutralize poisons, to help digest the foods you eat, to combat infection, to control bleeding, and to regulate energy levels. You’ll read about the differences between the various kinds of liver diseases and how each affects your body. You’ll come to understand why it’s critical to fight liver disease as soon as it’s diagnosed, even though you may feel fine. You’ll also learn what new treatments are available. If you’re exploring alternative medicine, you’ll learn which herbs, vitamins, minerals, and natural remedies may aggravate your liver disease and which ones may help.

And, if you are a loved one or a friend of someone who has liver disease, you will gain valuable information about how you can actively participate in his or her road to recovery. Plus, you will learn if there are any special measures or precautions you personally need to take in order to reduce your chances of also developing liver disease.

This book’s first edition was for people with liver disease and their loved ones. Since the publication of the first edition, I have learned that many people—ranging from nurses to physician assistants and from liver transplant coordinators to doctors—have used this book to assist them in caring for their liver disease patients. I just want to say that I am touched and gratified by the tremendous amount of positive feedback that I have received from the lay public and medical community—and this has spurred me to produce the updated version, which you are about to read.

An updated version of this book makes sense for many reasons. Since the first edition was published, I have been relentlessly striving to learn even more about hepatitis and liver disease. This quest has taken the form of activities such as participating in trials of the most promising experimental medications; a three-year stint on the American Association for the Study of Liver Disease’s (AASLD’s) Practice Guidelines Committee (whose purpose it is to guide physicians worldwide on the diagnosis and treatment of liver disease); attending many conferences and lectures with other preeminent liver disease experts, enabling me to exchange ideas; and reading every article and published study on liver disease that I could get my hands on. Most important, much of the additional knowledge that I have gained since the publication of the first edition is experience-based—that is, knowledge acquired from my personal involvement in treating (typically with great success!) thousands of liver disease patients over the course of the past several years. I am excited about sharing this knowledge with you!

There is so much good news to share. Since the publication of the first edition, many remarkable advances have occurred in the field of hepatitis and liver disease. The most significant ones will be discussed in detail in this book. For more information on resource groups and websites on liver disease, as well as the extensive bibliography for this book, visit my website, www.liverdisease.com.

This book will introduce you to and help you understand the latest liver-related treatments and advances. It will enable you or your loved one, in conjunction with a specialist, to make educated decisions about the treatment of liver disease. In part 1, you’ll learn what you need to know in order to increase your understanding of, and decrease your fears about, liver disease. In part 2, you’ll read about viral hepatitis and its treatment. In part 3, you’ll learn about some common liver disorders occurring in the United States today. Several of the chapters in this book unfold with stories about ordinary people whose lives were changed upon learning of their condition, but who are now benefiting from the latest treatments. (These case studies are composites based on actual people whose names and occupations were changed to protect confidentiality.) Part 4 discusses what steps liver disease patients can take to help manage their recovery and what effect this illness may have on their personal lives. In this part, you’ll also read about transplantation and alternatives to conventional medical therapy.

(Note: A person with liver disease or hepatitis can be either male or female. The same holds true for a doctor. To avoid using the awkward he/she when not referring to a group, and still give equal time to both sexes, the masculine pronouns are used in parts 1 and 3 and the feminine pronouns are used in parts 2 and 4. This has been done in the interest of simplicity and clarity.)

In writing this book, I’ve drawn from information that I’ve obtained during more than fifteen years of extensive research on every aspect of liver disease, and from my firsthand experiences treating thousands of patients with liver disease. In the introduction to the first edition of Dr. Melissa Palmer’s Guide to Hepatitis & Liver Disease, I stated that my mission was to break through the wall of helplessness that at times surrounds liver disease and to provide people with the genuine hope that they can get better. Well, one objective of this revised edition is to encourage all people with hepatitis and liver disease to continue to fight on! Some very effective treatments are available, and the fight can be won!

Remember, you only have one liver. Liver disease can be treated. But you must play an active role in the process. This book, while not a substitute for a doctor’s care, can be a guide on the road back to health. (Please note: A person with liver disease is advised to use this book in conjunction with the direct guidance of a liver specialist.)

Melissa Palmer, M.D.

Part One

The Basics

One

A LITTLE BACKGROUND ON THE LIVER

Tom, a forty-nine-year-old salesman, was feeling somewhat fatigued. He figured that this was to be expected. He was, after all, working ten-hour shifts in addition to coaching his son’s Little League team. Moreover, he was going to be fifty years old in two months. Perhaps this explained his feeling tired all the time. But, at the insistence of his wife, Tom made an appointment with his family physician for a checkup.

At the doctor’s office, Tom told his doctor that he was feeling less energetic than he used to. After asking some questions about Tom’s history and conducting a physical exam, the doctor said, You look fine. But we could use some additional information. I’m going to have my nurse draw some blood from you. Call me in a week to discuss the results of your blood tests.

Tom felt relieved. But when he called for the results of his tests a week later, he heard some hesitation in the doctor’s voice. "Tom, you need to come back to the office for further testing. Your blood tests detected a possible problem with your liver."

My liver?! Tom responded with some disbelief. What does this mean? There must be some mistake. What could be wrong with my liver?

Tom’s reaction to finding out there may be a problem with his liver is common among people with liver disease. But what exactly is liver disease? Most people know that drinking too much alcohol is bad for the liver and that it can lead to alcoholic liver disease. But few people know that there are viruses, genetic factors, medications, herbs, and vitamins—among other variables—that can adversely affect the liver. Even having too much body fat can cause liver damage. Also, few people know that without a healthy liver, you would not have the energy to work or do simple daily chores; or that if you cut yourself shaving, you would not be able to stop bleeding; or that if you were exposed to toxic chemicals, your body could not filter out these dangerous, potentially life-threatening substances; or that if approximately 85 percent of the liver stops functioning, practically every other organ in the body would eventually deteriorate.

In order to understand liver disease, you must first learn about the structure and functions of the liver—nature’s most miraculous life-giving machine. To help you do this, this chapter discusses the anatomy of the liver and the liver’s many functions. It finishes up by explaining exactly what liver disease is.

THE LOCATION AND STRUCTURE OF THE LIVER

The liver is a wedge-shaped gland located on the upper right side of the body lying beneath the rib cage, which functions as its personal protective barrier. (See figure 1.1.) Making up about 2 to 3 percent of the body’s total weight, the liver is the largest organ in the body. The liver is made up of two major sections, known as lobes. The left lobe is only one-fifth the size of the right lobe. The liver is criss crossed by a densely packed web of blood vessels and special passageways called bile ducts. This organ’s blood supply is a complicated superhighway with two main thoroughfares allowing blood to enter the liver—one called the portal vein and the other called the hepatic artery (note that hepatic means liver). Blood exits the liver through the hepatic vein. The cells that make up the liver are known as hepatocytes.

Nestled beneath the liver lies a pear-shaped organ called the gallbladder. Its main function is to store and concentrate bile. The liver and the gallbladder are connected by bile ducts. The bile ducts, as their name suggests, carry bile—a bitter, greenish mixture of acids, salts, and other substances—into the intestines. The liver is strategically located in the body so that it can communicate efficiently with all of the other organs, in addition to performing numerous vital functions essential to daily living.

THE LIVER’S MANY FUNCTIONS

The brain thinks. The heart beats. The stomach digests. But there’s no single active verb to describe what the liver does. This is because the liver has so many different jobs to perform. In fact, if you were to write a classified ad that covered all the liver’s responsibilities, it might read something like this:

WANTED—One highly reliable, extremely flexible organ that can act as watchdog, grocer, housekeeper, bodybuilder, energy plant supervisor, and sanitation engineer. Will be required to process and sort gallons of digested food from the stomach and intestines each day. Must discriminate among fats, proteins, and carbohydrates and send them wherever they are needed in the body. Must be able to detoxify thousands of substances—ranging from alcohol to bug spray to turpentine fumes—that may be ingested with food and drink, absorbed through the skin, or breathed in the air. Should be able to dismantle old, worn-out blood cells and recycle whatever parts are salvageable and prepare the rest for elimination. Must transform cholesterol into steroid hormones, such as androgens and estrogens, and share responsibility with the kidneys to control thyroid hormones, which influence metabolism. Must regulate sugar levels for proper energy management and create clotting factors that stop bleeding from cuts or other wounds. Additional duties will include—but are not limited to—building reserves of vitamins A, D, E, K, and B12 as well as iron and copper. Must be able to accomplish all of the above without weighing more than 3 to 4 pounds.

Figure 1.1. Location of the Liver

That’s a pretty tall order. But the liver accomplishes it all silently, working in the background, never advertising its presence. Sometimes, when a part of the liver is damaged or removed, it is even called upon to perform the incredible task of regenerating itself! (See the inset The Myth of the Regenerating Liver on page 10.)

The following material discusses the liver’s many functions. It also covers some of the problems that can arise when liver disease exists. In general, it is important to always keep in mind two basic functions of the liver. First, virtually everything that enters the digestive tract—foods, drinks, and medicines, for example—and everything that is breathed in the air or absorbed through the skin must pass through the liver in an attempt to be purified and detoxified. Second, the liver ensures that the other organs in the body are supplied with sufficient amounts of the various fuels, such as carbohydrates, proteins, and vitamins, which are necessary to get a person successfully through each day.

The Importance of Bile, Bilirubin, and Bile Acids

Bile does double-duty both as an aid in the digestion of fats and as a neutralizer of poisons. The importance of bile was recognized as far back as 400 B.C., in the days of Hippocrates, who suggested that an imbalance of the four body humors, or fluids—blood, phlegm, black bile, and yellow bile—signified disease. Bile is formed in hepatocytes (liver cells) and consists mainly of bile acids and pigments; cholesterol; electrolytes, such as sodium, potassium, and calcium; and proteins. Bile is released from the liver cells into the duodenum—the first part of the small intestine—to aid in digestion. The liver’s bile ducts collect the bile and transport it to the gallbladder. There, the bile is concentrated and stored until the cells along the inside lining of the small intestine send a hormonal signal that some fatty food, say a double-fudge brownie, has entered the digestive system. A muscle surrounding the gallbladder contracts, and a little bile is squirted into the intestines through the bile ducts. In much the way detergent helps to lift grease off a dirty plate, bile surrounds the fats and helps to break them apart so that the body can digest them. Pretty soon that brownie starts to dissolve into clumps that are small enough to pass through the rest of the intestines and out of the body. Therefore, when liver disease exists, there may be trouble digesting fatty foods. Similar to its action on fat, bile envelops some poisons in a protective barrier until they can be safely carted out of the body in the feces.

The Myth of the Regenerating Liver

The liver is commonly known by its remarkable ability to regenerate itself. But this statement is somewhat misleading.The liver does not really regenerate itself the way in which a starfish re-grows a missing arm. If an individual has up to 80 percent of a healthy liver removed, the remaining portion of the liver will expand to fill the empty space until its original weight is achieved. In this scenario, the liver will be fully functioning. However, if the remaining portion of a liver is permanently and severely scarred (decompensated cirrhosis), this expansion process may not occur, and regeneration would therefore be impossible.

The yellow color that is commonly associated with bile is mainly due to one of its components, known as bilirubin. Bilirubin is actually a waste product of worn-out, old, red blood cells. When the bilirubin level rises in the blood from hepatitis or liver disease, an individual becomes jaundiced. This is noted as a yellow tint to the skin and eyes. Jaundice is discussed more in chapters 2 and 3.

Bile acids are a major component of bile and are closely involved in both the production and elimination of cholesterol. Most people associate cholesterol with something that you do not want to have too much of. This is partly correct, as virtually everyone knows that too much cholesterol clogs the arteries. However, what many people do not realize is that cholesterol also is a significant component of all living tissues and is involved in the processing of vitamins and hormones. If a person’s diet contains an excess of cholesterol-containing foods, it is the job of the bile acids to scavenge this surplus of cholesterol particles and eliminate them from the body. Some types of liver disease are marked by abnormally high cholesterol levels. This will be discussed in detail in chapter 15.

The Liver’s Role in Processing Vitamins and Minerals

The liver is a warehouse for the storage of many vitamins and minerals, including vitamins A, B12, D, E, and K; copper; and iron. For example, a normal liver contains approximately a two years’ requirement of vitamin A. Centuries ago, Asian physicians were known to remove the livers from wild animals and place them on the eyes of people complaining of vision problems. While this may sound barbaric, it is now known that vitamin A may help alleviate night blindness—a condition resulting from vitamin A deficiency. Since the liver stores these vitamins and minerals, beware of overloading its storage capabilities. For instance, people who supplement their diets with too much vitamin A or iron can actually damage their livers. This can occur even in people who have normally functioning livers. So, you can imagine what too much of a good thing could do to someone who already has liver disease. Don’t add insult to injury! The toxic effects of too much iron are also demonstrated in the liver disease hemochromatosis—a disorder of iron overload. See chapter 18 for more on this disorder.

You may already know that the body uses fats as a kind of storehouse for excess calories. But did you know that fats are also necessary for the absorption of vitamins A, D, E, and K? These vitamins can exist only in a fatty solution. So if the bile ducts are blocked, as sometimes happens in liver disease, the body cannot digest the fats it needs to absorb these vitamins. This is particularly serious in the case of vitamin K, which the body needs to make the blood clot. It’s one reason why some people with liver disease have a pronounced tendency to bleed. Unfortunately, the liver is such a complicated organ that simply taking more vitamin K doesn’t correct this problem. For more information on vitamins and minerals and your liver, see chapter 23.

The Liver’s Role in Attacking Poisons

It’s one thing to break down fats and help absorb vitamins. It’s quite another, however, to neutralize poisons. You might be surprised at just how vigilant the liver can be in this regard. Everything from aspirin to herbs to chemical solvents to recreational drugs is considered potentially dangerous. Therefore, in addition to the actions of bile, some cells in the liver are individually equipped to dismantle potentially toxic molecules piece by piece or to alter them in such a way that they can be more easily eliminated from the body. That is why many people compare the liver to a giant filter that helps keep your insides clean. If that filter should ever get broken or damaged by a liver disorder, the rest of your body would slowly turn into the biological equivalent of a toxic dump.

The Liver’s Role in Building Muscles

You don’t have to be Arnold Schwarzenegger to appreciate the liver’s role as a bodybuilder. All the muscles in the body are made up of compounds called proteins, which are in turn composed of amino acids linked together like paper clips in a chain. It’s up to the liver to produce enough of the right type of amino acids for the body to build good, healthy muscles. Without these building blocks, your body would have trouble maintaining your muscles, such as those in your arms, legs, neck, and even your heart. In fact, if your liver is too damaged to metabolize proteins correctly, your muscles may literally waste away. This makes you prone to bone fractures, as bones easily become brittle when their protective muscle lining is diminished. For more information on how you can slow, or possibly even prevent, this process, see chapter 23.

The Liver’s Role in Regulating Energy

A car runs on gasoline. A computer depends on electricity. The body uses its own special kind of fuel, a carbohydrate molecule called glucose. The liver’s job is to keep the right amount of glucose in the blood and to keep it flowing to the organs that need it at all times. One of the ways it does this is by storing excess glucose in the form of another carbohydrate called glycogen. Whenever the body runs low on glucose, it can tap the glycogen in the liver for a little extra energy boost. If your liver is inflamed or damaged, your body will have trouble regulating the glucose levels in your blood. This is one of the reasons that many people with liver disease tire so easily.

The Liver’s Role in Maintaining Hormonal Balance

The liver also has an intricate relationship with hormones, including steroid and thyroid hormones. Did you know that the hormones that give us feminine and masculine traits—that is, estrogens and androgens—are actually made from cholesterol? Since it’s the liver’s job to regulate the production and breakdown of these substances, liver disease can lead to hormonal imbalances. One effect of such an imbalance is the appearance of feminine characteristics in men, such as gynecomastia (breast enlargement). See chapter 2 for more information on physical abnormalities and liver disease.

The Liver’s Role in Processing Drugs

Most drugs that are taken orally must be processed by the liver in order to be absorbed and used efficiently by the body. Those drugs that are best absorbed by the body have the characteristic of being fat soluble. Drugs that are not fat soluble are known as water-soluble drugs. Water-soluble drugs are poorly absorbed when swallowed, have difficulty getting into the bloodstream, and are promptly eliminated from the body. Thus, most drugs are fat soluble. When a fat-soluble pill or tablet is swallowed, it is readily absorbed by the fat (lipid) cells lining the walls of the stomach and intestines and is able to easily gain access into the bloodstream. A drug must enter the bloodstream in order for it to have its desired effect. After a drug has produced its effect, it must be eliminated from the body. Fat-soluble drugs circulate through the bloodstream, either attached to proteins or trapped by fat cells. They are not easily eliminated. In order to eliminate these drugs from the body, they must be converted into water-soluble products. This job is efficiently accomplished by the liver.

The liver is the only organ in the body whose blood vessels contain wide-open holes, called fenestrations. This unique characteristic allows the entrance of most drugs and other substances through these blood vessel holes and into the liver cells. Once inside the liver cells, fat-soluble drugs are converted into water-soluble drugs with the help of a complex group of specialized enzymes known as the cytochrome P450 system. Once this has been done, the drug, now rendered water soluble, is excreted back into the bloodstream and is capable of being efficiently eliminated by the body.

When the liver has been damaged, the metabolism (breakdown) of certain drugs and medications may be altered. Dangerous levels of these drugs may accumulate in the body, potentially causing serious adverse consequences. Therefore, it is essential that a person who has liver disease inform his doctor of the drugs and medicines he is taking, including any over-the-counter drugs or herbal preparations.

The Liver’s Role in Having a Clear Mind

Ammonia is a harmful chemical that is produced in the body from certain foods (mainly animal proteins) during the process of digestion. It is the liver’s job to convert ammonia into a nontoxic substance known as urea, which can easily be eliminated from the body via the kidneys. If the liver is damaged and cannot perform this function, ammonia can build up in the blood and brain. This can cause a condition referred to as brain fog or encephalopathy, which is a state of mental confusion (please refer to chapter 6 for more details about encephalopathy).

CONCLUSION

So far you’ve learned that the liver is an extraordinarily complex organ that controls virtually every aspect of your body’s daily functions and that it accomplishes this feat efficiently and quietly. So what exactly is liver disease? Unfortunately, due to the complexities of the liver, this question cannot be answered in just a few simple sentences. Instead, it will take an entire book to explain the intricacies of liver disease. Fortunately, you’re reading the right book! In chapter 2, the first symptoms, signs, and other clues that something is wrong with the liver will be discussed. In addition, some of the physical manifestations that indicate that a person has liver disease will be described in detail.

Two

SIGNS, SYMPTOMS, AND OTHER CLUES OF A LIVER PROBLEM

In chapter 1, we met Tom, whose feeling of fatigue was the first clue that something was wrong with his health. This prompted him to make an appointment with his family doctor. Through the process of taking a history, performing a physical exam, and drawing some routine blood work, Tom’s doctor was able to determine that his problem was liver related. Tom’s wife was wise to urge him to see his doctor so quickly. Since liver disease can sometimes exist for a long time without exhibiting any obvious symptoms, Tom may have continued to remain unaware of his condition.

Of all the organs in the body, the liver is truly the strong, silent type. Whether it’s fighting a viral infection or struggling under the burden of excess scar tissue, the liver rarely complains. It just keeps performing its many functions the best it can. That is why liver disease can progress for years before it’s noticed. In fact, in most cases of liver disease, the first clues that something is wrong are virtually imperceptible. It is often when the liver is on the verge of collapse and can no longer perform its duties that its deterioration becomes apparent.

So how do most people find out they have liver disease? Well, sometimes—as in Tom’s case—there is a subtle clue that something is wrong, such as feeling fatigued. But even these warnings may be so vague and may evolve so gradually that they go unnoticed by the person with the disease, as well as the people he comes in contact with on a daily basis. In fact, sometimes an infrequent acquaintance will be the first to detect a change in a person’s appearance or personality. In other cases, a doctor may recognize the physical manifestations of liver disease while performing a routine physical examination. Or, through eliciting specific information from the patient, the doctor will make a connection between his responses and liver disease.

This chapter discusses some of the symptoms associated with liver disease— symptoms that may result in a visit to the doctor’s office. It explains what to expect at the doctor’s office during the initial visit; what the doctor is looking for during the exam; and the significance of what he may find.

SYMPTOMS OF LIVER DISEASE

Symptoms of liver disease are very nonspecific. There is no distinct symptom that accurately indicates that something is wrong with the liver, or what kind of liver disease someone has, or how serious the problem might be. In fact, many people with liver disease have absolutely no symptoms whatsoever. That’s right! Sometimes even in the advanced stages. This is known as being asymptomatic, or as having a silent disease. So feeling fine doesn’t always mean that nothing is wrong.

Often the first clues that something is wrong with the liver include fatigue, pain, fever, flu-like symptoms, jaundice, altered mental status, itching, abdominal distention, and weight gain. Any one of these symptoms may prompt someone to make a doctor’s appointment. In general, a person may encounter some or all of these symptoms at any time during his disease—either intermittently or consistently. To learn about the treatments for these symptoms, see chapter 20.

Fatigue

Fatigue is a symptom characterized by a diminished ability to exert oneself, usually associated with a feeling of being tired, bored, weak, and/or irritable. Fatigue is probably the most common and debilitating symptom of liver disease. It is universal to all types and stages of liver disease. In some people, fatigue begins several years after the liver disease diagnosis has been made. In others, it is the primary reason for seeking medical attention in the first place. Oftentimes, multiple visits are made to a variety of different types of doctors in search of the cause of the fatigue before it is connected with liver disease. Some people even seek psychiatric evaluation since depression often accompanies fatigue.

Fatigue may occur at any time of day, but it is most common in the morning. Often, little more than an hour after awakening, a person may already feel the exhaustion of having worked an entire day. Others describe weakness and lack of energy throughout the whole day. Their usual pep is gone. Even little tasks become more trying, and around 4:00 P.M., they simply must lie down to take a nap.

Fatigue can be caused by the liver disease itself or from disorders—such as thyroid disease or vitamin deficiencies—often associated with liver disease. The doctor must carefully look at all of the factors possibly contributing to his patient’s feeling of fatigue, as some factors can be easily corrected.

Pain

Most people with liver disease expect to feel pain over their liver. This type of pain is known as right upper quadrant pain or tenderness (RUQT). However, RUQT is rarely due to chronic liver disease. RUQT occurs most commonly in the acute stages of liver disease, such as in acute viral hepatitis. It may occasionally occur when one experiences a flare-up of a chronic liver disease, although these flare-ups are uncommon. It is most often caused by acute inflammation, irritation, and distention of the liver’s surface. Otherwise, the liver is rarely tender.

If pain in the region of the liver is experienced, other causes must be considered. For example, it may indicate gallstones, which happen to be associated with many liver diseases. Or it may indicate liver cancer—also known as hepatoma or hepatocellular carcinoma (HCC). Scar tissue from prior abdominal surgery known as adhesions is also a cause of abdominal pain. Intestinal pain must also be considered, as the right side of the large intestine lies in close vicinity to the liver (see figure 1.1 on page 9). Many people claim that although they do not actually feel pain in the liver region, they experience a rather vague sense of fullness or an awareness of the liver. The cause for this is unclear. If a person experiences abdominal pain associated with swelling of the abdomen, ascites—the accumulation of fluid in the abdomen—must be considered. Ascites is associated with advanced liver disease and is discussed in chapter 6. Other causes of abdominal pain include those related to the stomach, such as peptic ulcer disease and gastritis, which are not necessarily indicative of liver disease and are readily treatable when discovered.

Fever

Fever is seen in some people with acute viral hepatitis—especially hepatitis A—and in some people with alcoholic hepatitis. These forms of hepatitis will be discussed in chapters 8 and 17, respectively. Fever is also experienced by some people with medication-induced hepatitis, which will be discussed in chapter 24. However, this symptom is uncommon in people with chronic liver disease.

If fever occurs in a person who has ascites, an infection of this fluid may be present. This is a serious condition known as spontaneous bacterial peritonitis (SBP) and will be discussed in chapter 6. Cholangitis is an infection in the bile ducts and can occur, for example, in a person with gallstones, or in connection with a liver disease known as primary sclerosing cholangitis (which will be discussed in chapter 15).

Flu-like Symptoms

During the acute stages of liver disease, a person may experience symptoms similar to those of the flu. These symptoms, which include fever, muscle and joint aches, decreased appetite, nausea, rashes, headaches, weight loss, and generalized weakness, may last anywhere from several days to several weeks before they are completely resolved. In a person who has chronic liver disease, these symptoms are not as common but may occur intermittently throughout the course of the disease. If any of these flu-like symptoms are constant in a person with chronic liver disease, a cause other than a liver problem should be investigated by a doctor.

Jaundice

Jaundice—noted by a yellow tint to the skin and eyes—is not actually a symptom but a sign of liver disease, which is usually detected during a physical exam. It becomes apparent when the bilirubin rises to a level greater than 2.5 milligrams per deciliter (2.5 mg/dl). (A normal bilirubin level is lower than 1.5 mg/dl.) When a person’s bilirubin level is elevated, stools may become a light clay color and urine may become a dark tea color.

Many people think that if they have never been jaundiced, then they have never had and do not currently have liver disease. This is far from the truth. In fact, many people who have liver disease never experience jaundice. But in others, it may be the first clue that something is wrong. In these cases, jaundice may occur as a manifestation of acute hepatitis or it may be an ominous sign of deteriorating liver disease. It is important to keep in mind that jaundice can be due to myriad causes, some of which are not even related to the liver. These causes are discussed in more detail in chapter 3.

Altered Mental Status

For some people, the first clue that something is wrong may be encephalopathy—altered mental status. A person experiencing a mild, chronic form of encephalopathy may constantly forget simple things, such as where he placed his glasses or whether he already took his medication. Or he may get irritable over insignificant things or experience other behavioral changes. A person experiencing a more severe, acute form of encephalopathy may forget major information, such as what year it is or even his own name and address. Or the person may react in a strangely inappropriate or even violent manner. Encephalopathy is a sign of severe liver deterioration. It is discussed in more detail in chapter 6.

Itching

Pruritus is the medical term for itching. It is commonly the first clue that something is wrong in people with primary biliary cirrhosis, which will be discussed in chapter 15. Pruritus can also occur in any liver disease complicated by cholestasis—impairment or failure of bile flow—such as in people with cirrhosis complicated by jaundice. Pruritus is a symptom that can be extraordinarily annoying and extraordinarily difficult to treat. It can range in intensity from being so mild that it does not interfere with daily activities to being so intense that it inhibits a person from sleeping at night or even holding down a regular job. The itching can occur all over the body or be limited to specific areas, such as the palms of the hand or the upper back. Some people describe this sensation as a tingling or burning sensation beneath the skin, which is not relieved by any amount of scratching. Sometimes itching can become so severe that patients will resort to scratching themselves with sharp objects, thereby causing permanent scars.

Abdominal Distention and Weight Gain

One liver-related symptom that often leads a person to seek evaluation from a doctor may be abdominal distention associated with an unexplained weight gain. As discussed previously, abdominal distention may be due to ascites—the accumulation of fluid in the abdomen. This is a sign of severe deteriorating liver disease and must be clearly distinguished from other causes of abdominal distention.

Many patients with liver disease become bloated due to malabsorption or maldigestion—impaired or inadequate absorption or digestion of certain foods. Abdominal distention will result as the digestive tract fills with gas. This is a readily reversible condition treatable by specific food avoidance, but, to the untrained eye, it may look like ascites.

Nonalcoholic fatty liver disease (NAFLD) is another condition leading to abdominal distention and liver abnormalities. In people with NAFLD due to being overweight, a distended abdomen is due solely to excessive adipose (fatty) tissue. This condition, which is discussed in chapter 16, is sometimes reversed with weight loss.

Other Symptoms

Other symptoms that can be the first clues that something is wrong with the liver include altered sleeping habits, joint aches, a persistent rash, and/or depression. These symptoms are not specific to liver disease, and, as always, a full evaluation should be conducted by a doctor in order to specifically determine their causes.

THE INITIAL VISIT TO THE DOCTOR

The initial visit to the doctor consists of a consultation and a physical exam. Typically, blood is drawn for testing. During the consultation, the doctor will ask the patient a variety of questions. Some of the responses may provide the doctor with clues that something is wrong with the patient’s liver. After the consultation, the doctor will perform a physical exam to look for other clues that may indicate a liver-related disorder. Blood tests that provide additional information will be discussed in chapter 3.

The Consultation—Questions, Questions, Questions

So many things can go wrong with the liver that the doctor must ask many questions to accurately assess the cause and severity of the liver problem, as well as what type of treatment may be necessary. The list below details potential questions that the doctor may ask at the initial office visit to help determine the nature of the liver disorder. This list is provided so that the patient will know what to expect at the consultation and will be prepared to answer these questions during the visit. Answering these questions may also help trigger the patient’s memory of past incidents or family history of liver disease and, as such, may provide some insight as to why he has a liver disorder.

• What symptoms brought you here? When did they start? Are they getting worse?

• Have you ever been told that something is wrong with your liver?

• Have any of your family members ever been told they have liver disease?

• To what extent have you been sexually promiscuous?

• Have you ever had sex with someone of the same gender?

• Have you ever used recreational drugs like cocaine or heroin? Have you ever shared an intravenous needle? A cocaine straw?

• Have you ever had any tattoos or are any of your body parts pierced?

• Have you ever received or donated blood or blood products?

• Did you serve in the military?

• What is your occupation?

• Where were you born?

• How much alcohol do you drink?

• What’s your usual diet like? Has your appetite changed recently?

• Have you recently eaten shellfish or wild mushrooms?

• Have you gained or lost weight in the past few months?

• Have you recently traveled outside the United States?

• What is your past medical and surgical history, including any anesthesia you might have received?

• Do you have a bleeding problem or excessive bleeding?

• Do you use paint thinners, pesticides, or other toxic substances as part of your job or around the house?

It is a good idea for the patient to provide the doctor with a list of any over-the-counter medications, herbal remedies, and vitamins or diet pills that he may be taking. Although these substances do not require a prescription and are not thought of as dangerous, they can adversely affect the liver in some cases.

As indicated by the above list, the patient should expect to answer some highly personal questions. It is extremely important for the patient to tell the doctor the whole truth—whether it happened in the past or is occurring in the present. Of course we all have done things we would rather forget. It is convenient to think that certain episodes from the past don’t count anymore, but with diagnosing liver disease, everything counts, even if it occurred a very long time ago. Remember, all patient records are kept strictly confidential. The patient must sign a written, witnessed authorization before any information is released to anyone. Therefore, keeping the doctor in the dark about past events can only hurt the chances for getting better. (Please see chapter 4 to learn more about the patient privacy act, known as HIPAA—Health Insurance Portability and Accountability Act of 1996.)

The Physical Exam—Signs of Liver Disease

After the consultation, a thorough physical examination will be performed in order to look for signs—the physical clues or findings—of liver disease. Keep in mind that the liver is so adept at hiding what’s wrong—especially in the earliest stages of the illness—that even a doctor can’t always tell from a physical exam that something is wrong with the liver, let alone what specific type of liver disease a patient has, or how damaged the liver is. Consequently, many patients with liver disease, even those with cirrhosis, pass their physical exams with flying colors.

If liver disease is so hard to detect, why does the doctor bother examining the patient? First, it gives the doctor a baseline against which to compare any future changes. Second, although there are no obvious outward signs in the earliest stages of chronic liver disease, there are some subtle changes in appearance that may be present when someone has developed cirrhosis, changes that an astute doctor will detect. Third, there are a few physical findings that are actually suggestive of specific types of liver disease. These will be discussed below. Last, and most important, there are numerous physical clues that are associated with a more serious outcome—cirrhosis and liver failure.

The Baseline Exam

The doctor will commence the exam by assessing the patient’s overall appearance. Are there signs of chronic weight loss, or do the muscles appear to be withering away? How’s the blood pressure, pulse, and breathing? Is there a fever? Does the breath smell of alcohol? Is there any mental confusion? Are there track marks from intravenous drug use? Are there any rashes, lesions, or unusual masses? Is the skin or are the eyes jaundiced? Do the hands and nails have signs of liver disease? (By the way, the brown spots on the back of the hands that many people call liver spots actually have nothing to do with the liver.) Are there signs of fluid retention, such as pedal edema (swollen ankles) or ascites? Is the liver hard and nodular (a sign of trouble) or is its texture smooth (a sign of health)? If the liver is either too big or too small, disease may be indicated. An enlarged liver is known as hepatomegaly.

Now that the doctor has assessed the general appearance of the patient, let’s discuss the physical findings suggestive of cirrhosis. Three points must be stressed. First, a person with cirrhosis may manifest one, none, all, or any combination of these signs. Second, some of these signs may occur in people with liver disease, who have not yet progressed to cirrhosis. And third, many of these signs are present in people without liver disease at all.

Signs That Suggest Cirrhosis

When the liver becomes cirrhotic—severely scarred and damaged—it cannot properly execute its many important functions, which were discussed in chapter 1. This may become apparent during the physical exam. As the liver struggles to manufacture proteins, there may be evidence of general deterioration in a person’s health—predominantly noted by the loss of muscle mass known as muscle wasting. This is usually most prominent on the upper body and arms.

The spleen may enlarge to compensate for the decreased functional abilities of the damaged liver. This is known as splenomegaly. The spleen is an organ lying directly opposite the liver under the rib cage on the left side of the body. The spleen plays a role in the storage of platelets. Platelets are blood cells that help blood to clot. Thus, an enlarged spleen is often associated with thrombocytopenia—a low platelet count. This is discussed in chapter 3.

Many abnormalities may become evident due to the failure of the liver to metabolize endocrine hormones properly as a consequence of cirrhosis. Liver palms (palmar erythema) is characterized by bright red coloring of the palms, particularly at the base of the thumb and pinky. It may be associated with some throbbing or warmth of the hands. Enlarged blood vessels found on the upper chest, back, face, and arms, resembling little red spiders, are known as spider angiomatas. They characteristically blanch (turn white) if light pressure is applied to their centers. Body hair patterns may change. Men note that they need to shave less often. Hair becomes sparse on the chest, face, and pubic region. Women may have decreased underarm hair. Gynecomastia (breast enlargement) may become noticeable in men, and breasts may also feel tender.

There are other manifestations of cirrhosis that do not have a clear explanation. These include Terry’s nails, a condition in which the normal pinkish color of the nail bed turns completely white and the half-moon circles at the base of the nails disappear; and paper money skin, a condition in which the upper body is covered with numerous thin blood vessels that resemble the silk threads in a U.S. dollar bill.

Signs That Suggest a Specific Liver Disease

Most manifestations of liver disease are universal to all liver diseases, independent of their cause. However, there are a few findings that may suggest a specific liver disease. Xanthomas (an irregular yellow nodule or patch usually found on the ankles, elbows, and knees) and xanthelasmas (a yellow nodule or patch on the eyelids) are associated with very high cholesterol levels and are found in people with primary biliary cirrhosis (see chapter 15). These irregular patches can be very disfiguring and painful. These nodules can also be found in other liver diseases and in other diseases associated with elevated cholesterol levels.

People with cirrhosis due to alcoholic liver disease will likely have many readily visible physical signs. Dupuytren’s contracture is a puckering of the palm that prevents a person from totally straightening out his hand. The severity of this deformity may correlate with the quantity of alcohol consumed. Parotid gland enlargement may also occur. The parotid gland is a gland on the face located under the ear. When it becomes enlarged, it causes the earlobes to protrude at right angles to the jaw. In addition to gynecomastia, the testicles may shrink, a condition known as testicular atrophy. Testicular atrophy may also be a manifestation of hemochromatosis.

A hepatic bruit, a harsh, musical sound heard when a stethoscope is placed over the liver, is suggestive of liver cancer (hepatoma).

Signs That Suggest Liver Failure

Liver failure is defined as the cessation of normal liver function. It can occur in a previously healthy individual with no prior evidence of liver disease. This is known as acute or fulminant liver failure. Or it may occur as the end result of cirrhosis. Signs of liver failure foreshadow a poor outcome and are the most ominous findings of a physical exam.

Encephalopathy, which was discussed on page 18, virtually always accompanies liver failure. Sometimes, people with encephalopathy are initially seen by a doctor in a hospital setting after a family member discovers them unconscious in a coma. Fetor hepaticus is a foul, sweetish, or feceslike smell on the breath (often compared to that of a dead mouse or corpse). This can be a sign of either acute or chronic liver failure and often precedes encephalopathy. Asterixis, which occurs with encephalopathy, is an uncontrollable flapping of the hands that becomes noticeable when a patient stretches out his arms, palms out, as if stopping traffic.

Scleral icterus is the yellow discoloration of the sclera (whites of the eyes), and jaundice, as you’ve learned, is the yellow discoloration of the skin and eyes. Both of these conditions are manifestations of an elevated bilirubin level. Ascites is the accumulation of excess fluid in the abdomen. When ascites is associated with fever and abdominal pain, spontaneous bacterial peritonitis (SBP) may be present. If there is a massive amount of ascites, one may even have a protrusion of the umbilicus (belly button), known as an umbilical hernia. In severe cases, the belly button can actually burst open, causing a massive leak of ascitic fluid. Dilated blood vessels can snake out from the belly button—an appearance appropriately termed caput medusa. Edema is fluid accumulation in the legs, especially the ankles (pedal edema). Immediate evaluation and treatment of these manifestations of liver failure—which will be addressed in chapters 6 and 20—are crucial.

CONCLUSION

After reading this chapter, you should know what to expect when you or your loved one goes to the doctor for an evaluation of a liver-related problem. Also, you are now more knowledgeable about the symptoms and signs of liver disease. Depending upon which signs and symptoms a patient mentions or displays at the time of the initial evaluation, the doctor may have a general idea of what is wrong with his liver. On the other hand, the doctor still may not be able to determine whether a liver disorder actually exists. In either case, the next step is to perform some routine blood tests to obtain additional diagnostic information. Chapter 3 will introduce you to the basic blood tests and imaging studies that doctors utilize in their efforts to diagnose individuals who have liver disease.

Three

BLOOD TESTS AND IMAGING STUDIES—LEARNING WHAT YOU NEED TO KNOW

After consulting with Tom and conducting a physical exam, Tom’s doctor decided that some blood tests were needed in order to gather additional information. Included in all or most routine panels of blood are tests pertaining to the liver. These tests are commonly referred to as liver function tests (LFTs). Some of Tom’s LFTs were abnormal, which led his doctor to the conclusion that there was a problem with Tom’s liver. Tom also had a sonogram of his liver, which was normal. He assumed that since his liver sonogram was normal that there was nothing wrong with his liver. Tom subsequently learned that this was not necessarily the case.

The significance, usefulness, and limitations of liver function tests (LFTs) are discussed in this chapter. Unfortunately, LFTs cannot identify a specific liver problem. However, there are some additional specialized blood tests, which are not included in routine blood work, that can be ordered if a certain liver disease is suspected. (The table on page 33 details these special blood tests.) In addition, this chapter discusses the various imaging studies, such as sonograms, CT scans, and MRIs, that are used to visualize the liver.

UNDERSTANDING LIVER FUNCTION TESTS (LFTs)

Wouldn’t it be nice if your liver came equipped with a dashboard, like the one in your car that tells you when the oil needs changing, that the engine’s overheating, or you need to find a gas station in a hurry? Since it doesn’t, doctors have come to rely on a number of blood tests—known as liver function tests (LFTs)—to give them some indication of what’s going on inside the liver. But don’t be fooled by this name. While LFTs are commonly used to reflect how well the liver is working, this name can be misleading, as it is impossible for any blood test to accurately assess all of the liver’s varied functions. Thus, like the indicator lights and gauges in a car, the LFTs are not a perfect indication of exactly what’s wrong. They can, however, alert the doctor that something is amiss with the liver. Furthermore, they can help determine which additional tests are necessary. And, when used in conjunction with these additional tests, LFTs give the doctor a better idea of what is wrong with the liver and how well the liver is working. By keeping track of the results from the LFTs over the months and years ahead, both the patient and the doctor may—in some cases—have an idea whether the liver condition has stabilized, improved, resolved, or worsened; whether a specific treatment is working or if something different needs to be tried; and whether it is time to refer the patient for a liver transplant evaluation.

LFTs consist of many different blood tests that check the levels of liver enzymes (transaminases and cholestatic liver enzymes); bilirubin; and the liver proteins. The following is a discussion of these tests.

Liver Enzymes

Four separate liver enzymes are included on most routine laboratory tests. They are aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT), which are known together as transaminases; and alkaline phosphatase (AP) and gamma-glutamyl transferase (GGTP), which are known together as cholestatic liver enzymes. Elevations of these enzymes can indicate the presence of liver disease.

AST and ALT (Transaminases)

AST and ALT are associated with inflammation and/or injury to liver cells, a condition known as hepatocellular liver injury. Damage to the liver typically results in a leak of AST and ALT into the bloodstream.

Because AST is found in many other organs besides the liver, including the kidneys, muscles, and heart, having a high level of AST does not always (but often does) indicate that there is a liver problem. For example, even vigorous exercise may elevate AST levels in the body. On the other hand, because ALT is found primarily in the liver, high levels of ALT almost always indicate that there’s a problem with the liver. (However, a normal ALT level does not necessarily mean that the liver is definitely normal. More about this later.)

A Word About Normal Reference Ranges

When laboratory test results are reported to the doctor, they are typically compared to values obtained from a group of healthy people. The range of these normal values is known as the reference range or reference interval. The high and low ends of the interval are commonly referred to as the upper and lower limits of normal.This reference range may differ slightly from one time to the next and from one laboratory to the next.Your doctor will take this information into consideration when interpreting a single isolated laboratory result.

Despite what one might expect, high levels of transaminases in the blood don’t always reveal just how badly the liver is inflamed or damaged. This is an extremely important point to keep in mind. The normal ranges for AST and ALT are 0 to 40 IU/l and 0 to 45 IU/l, respectively. (IU/l stands for international units per liter and is the most commonly accepted way to measure these particular enzymes.) But someone who has an ALT level of 50 IU/l is not necessarily in better condition than someone with an ALT level of 250 IU/l! This is because these blood tests measure inflammation and damage to the liver