Chapter 3 Lorren Sandt |
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Introduction Throughout this book, you will often read that chronic hepatitis C and its treatments affect each person differently. The broad range of variability observed between persons is especially true of disease progression. There is no accurate way to predict the course of chronic hepatitis C in an individual person. This chapter provides information about possibilities that might happen. Remember, none of the situations discussed in this chapter will necessarily happen to you. However, it is important to be aware of the possibilities so that if any of them do occur, you will be prepared and better able to make good decisions. About The Liver The liver is the largest organ in the body. In a normal adult, the liver weighs 3½-4 pounds (1,300-1,500 grams). It accounts for about 2.5% of the total weight of the body. The liver is wedge-shaped (see below). It measures approximately 7 inches (14 cm) across by 5½ inches (18 cm) along its diagonal. The liver is divided into two main lobes, the right and the left (see Figure 1). The right lobe is slightly larger than the left and extends down the right side of the rib cage. The left lobe extends from the right lobe to about the middle of the abdomen. There are also two minor lobes of the liver, the caudate and quadrate lobes. Fibrous ligaments separate the lobes. All lobes of the liver perform the same functions. The entire liver is enclosed in a fibrous sheath called Glisson's capsule. Figure 1: Anatomy of the Liver
The liver is located on the right side of the abdominal cavity just below the lungs and diaphragm, the muscle that separates the chest cavity from the abdominal cavity (see Figure 2). Figure 2: Placement of the Liver in the Body
The liver is packed so
tightly into the abdomen that the right kidney, parts of the large and
small intestines, and the stomach actually leave impressions on its
surface. Even the ribs and muscle bands of the diaphragm make indentations
on the surface of the liver. Stages of Disease Progression Like other liver diseases, HCV disease progresses in stages. The usual progression is from inflammation to fibrosis to cirrhosis (see Figure 3). Cirrhosis can progress to end-stage liver disease and/or can give rise to liver cancer. Normally, when the liver is damaged, liver cells die but the organ regenerates itself without scarring. Figure
3: Chronic Hepatitis C Disease Progression
*These conditions are not mutually exclusive, which means they can both develop in the same person. Decompensation is another word for severe liver failure. Liver decompensation and early stage liver cancer are each indications for possible liver transplantation. Inflammation Liver inflammation refers to the presence of special cells called inflammatory cells in the liver. Chronic inflammation is inflammation that persists over a long period of time. It leads to changes in liver structure, slowed blood circulation, and the death of liver cells (necrosis). Chronic inflammation eventually causes scar tissue formation, a condition known as fibrosis. By controlling liver inflammation, you can potentially control progression to fibrosis. Fibrosis Fibrosis is the harmful
outcome of chronic inflammation. Fibrosis is scar tissue that forms as a
result of chronic inflammation and/or extensive liver cell death. Your
health care provider uses the amount of fibrosis in your liver as one way
of evaluating how quickly your disease appears to be progressing.
Knowledge of approximately when you were initially infected with HCV is a
great help in determining your rate of disease progression. Cirrhosis When fibrosis becomes widespread and progresses to the point that the internal structure of the liver has become abnormal, fibrosis has progressed to cirrhosis. Cirrhosis is the result of long-term liver damage caused by chronic inflammation and liver cell death. The most common causes of cirrhosis include viral hepatitis, excessive intake of alcohol, inherited diseases, and hemochromatosis (abnormal handling of iron by the body). Cirrhosis is accompanied by
a reduction in blood supply to the liver. The loss of healthy liver tissue
and reduced blood supply can lead to abnormalities in liver function. Even
when liver disease has progressed to cirrhosis, it may still be possible
for the damage to be at least partially reversed if the underlying cause
can be eliminated. Cirrhosis progression can usually be slowed or even
stopped with effective treatment.
Despite the seriousness of
cirrhosis, large numbers of people live many, many years with cirrhosis
without decompensation or symptoms. Liver Cancer Though most people with HCV
never develop liver cancer, it is a risk associated with chronic hepatitis
C. The presence of cirrhosis and/or having been infected with HCV for more
than 20 years further increase the risk. For this reason, frequent liver
cancer screening is advisable for people who have cirrhosis. Determining Disease Progression with Liver Biopsy The most accurate way to check the severity of liver disease is with a biopsy. A liver biopsy is a test in which small pieces of liver tissue are removed so they can be examined under a microscope. The three main things that will be looked for are inflammation, fibrosis, and cirrhosis. The biopsy report may also reveal other histological and pathological findings such as the presence of lymphoid nodules, damage to small bile ducts, and/or the presence of fat.
Normal ALT and Liver Biopsies Liver Biopsy Scoring and Grading When you receive the results of your liver biopsy, you will hear the terms inflammatory grade and fibrotic stage. Health care providers use these terms to indicate the amount of injury to the liver. Three different methods are used for scoring liver biopsies. This can cause confusion for both patients and health care providers. Be aware that the scoring systems are also subject to interpretation by the pathologist who examines your biopsy. The three scoring and grading systems for liver biopsies are the Original HAI (Histology Activity Index), the Modified HAI, and the Metavir. There are important things to know about how biopsies are scored in order to understand what your score means.
Until there is a single biopsy scoring system, there are things you need to know and track regarding your liver biopsy results.
Make sure your health care
provider completely explains the results of your biopsy to you. Ask for an
explanation of the individual scores as well as the overall score. You
should be given a description of the inflammatory grade and fibrotic
stage. Ask to speak with the pathologist who evaluated your biopsy if your
health care provider is unable to provide this information. The following tables
comparing the three systems used to score liver biopsies are courtesy of
David Kleiner, MD of the National Cancer Institute.
Table 6 shows how the HAI inflammation scores relate to the grade of histological injury. In the HAI system, the various inflammation scores are added together. These numbers are directly related to the descriptive grade of inflammation.
Other Liver Biopsy Findings Fatty Liver (Steatosis or Steatohepatitis) Fatty liver is the accumulation of fat in liver cells. Steatosis is the presence of fat in liver cells without inflammation. Steatohepatitis is the presence of fat in liver cells with inflammation. You may hear other terms to describe fatty liver, depending on your medical condition.
Fatty liver is emerging as a major medical problem. Obesity affects up to 50% of the U.S. population, half of whom have fatty livers. The risk of cirrhosis for those with fatty livers ranges from 7-15%. It is important to know if you have a fatty liver so you can understand your risk of developing cirrhosis and make lifestyle changes to decrease this risk. For the hepatitis C patient, fatty liver is just another factor in the progression of fibrosis.7 A liver biopsy can determine both the presence of fat in the liver and the level of fibrosis. This information will allow your health care provider to counsel you about your risk of progressive liver disease. Alcohol can increase the amount of fat in the liver and is the most common cause of fatty liver. The association between fatty liver and alcohol is another very important reason for you to refrain from drinking any alcohol. However, not all cases of fatty liver are caused by alcohol use. Diabetes and high triglycerides are also associated with fatty liver and should be managed closely by your health care provider. The liver must metabolize any fat that is not eliminated through the intestinal tract. If you eat excessive amounts of fat, the amount that goes to your liver may be too much for it to metabolize. Excess fat that is not metabolized begins to accumulate in the liver. This accumulation of fat can cause inflammation. Inflammation can lead to scarring, which may eventually lead to decreased liver function. Therefore, it is very important not to have excessive amounts of fat in your diet. It is particularly important to limit your intake of animal fat because animal fat is especially difficult for the liver to metabolize. See Chapter 7, Nutrition and Hepatitis C for suggested dietary guidelines. Achieving or maintaining your ideal body weight (a body mass index [BMI] of approximately 25) and limiting the amount of fat in your diet are important for your liver health. Your BMI is calculated by taking your weight (in kilograms) and dividing by your height (in meters) squared. A free BMI calculator is available on the Internet at www.nhlbisupport.com/bmi/bmicalc.htm. Normal body weight not only helps your liver but can also improve your energy level, reduce hypertension, and lower your risk of heart disease. Regular exercise can help you maintain a normal body weight and avoid the development of fatty liver. If you are considering interferon-based therapy, obesity may play a role in your response. One study showed an 80% decrease in sustained response to interferon therapy in obese patients compared to those with normal body weight.8 Your doctor may suggest weight loss before beginning interferon-based therapy if you are significantly above your ideal body weight. Health care providers have also begun to advocate for individualized weight-based dosing of pegylated interferon alpha-2b (PegIntron®) plus ribavirin to improve the chance for response to treatment. People with fatty liver often have high blood sugar and lipids such as cholesterol and triglycerides. If you have a fatty liver, your health care provider should monitor you for the development of these problems. Some medications and other substances can cause fatty liver. Be sure to review all of your medications with your health care provider and avoid the following, if possible.
Other Complications of Hepatitis C Although the effects of HCV on the liver
are most visible, the virus can affect other body systems and organs. This
results in extrahepatic (outside the liver)
conditions or manifestations of chronic hepatitis C.
There is much controversy regarding the true cause of the many HCV-related conditions that have been reported. Some of them probably are related to hepatitis C. Others probably are not, and occurred by chance in a few individuals unrelated to HCV. Many studies on this topic come from clinics that treat only specific diseases, which may skew the study findings. The way HCV produces extrahepatic conditions is the subject of ongoing research. In some HCV-related extrahepatic conditions, HCV stimulates the immune system to produce autoimmune antibodies, antibodies against the body's own tissues. This appears to be the mechanism for HCV-related thyroid and blood disorders. Summary The question of whether it is the virus
or the person infected by the virus that determines how HCV disease will
progress is an active area of research. At this point, we know of several
personal factors and several viral factors that may influence the rate of
HCV disease progression.
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loss of appetite