Chapter 1

Robert G. Gish, MD

Introduction

Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease. HCV is estimated to affect 4 to 5 million people in the United States, and 170 million people worldwide.^1,2 The estimated number of HCV-infected people in the United States is based on population survey, and estimates of the disease in high-risk populations that have not been thoroughly studied. Therefore, many hepatitis C experts believe the actual number of people infected with HCV is higher than the estimates state.

Even ten years after the discovery of HCV, our knowledge about the natural history of chronic hepatitis C is still limited. Studies have provided varying estimates of the risk of disease progression with chronic hepatitis C. Usually, the disease is slowly progressive. An estimated 15-45% of people infected with HCV clear the virus from their body without treatment. Another 25% have no symptoms, and have consistently normal levels of liver enzymes called aminotransferases. This means that approximately 40-70% of people infected with HCV either recover or do not develop symptoms.³ These facts indicate there are people whose immune systems are capable of getting rid of HCV. However, for reasons we do not yet understand, others' immune systems allow the virus to persist, leading to potentially serious consequences. Thus, HCV is potentially curable with one's own immune response or with antiviral treatment.

Several factors have been shown to influence the course of chronic hepatitis C. The most significant of these factors are listed below.

Age at infection: Persons infected past age 35 may have disease that is more rapidly progressive.^4-6

Alcohol consumption: Alcohol appears to have a very negative effect on people infected with HCV.⁷

Gender: Overall, women (especially those under age 50) do significantly better than men ^{7, 8} with less severity of infection.⁹ Women also appear to spontaneously clear the virus more frequently than men do.^10-12

Co-infection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV): Co-infection with one or both of these viruses leads to faster disease progression.¹³ Rapid progression is also seen in people with organ transplants taking immunosuppressant medications.

Fatty liver: The presence of fat in the liver is associated with higher degrees of fibrosis.¹⁴

Viral characteristics such as HCV type (genotype) and viral load (the amount of virus present in the blood) do not seem to affect the course of the disease. However, these characteristics are commonly used to determine the length of treatment.⁴

HCV was once believed to affect only the liver. We now know it can affect nearly any organ in the body. In other words, hepatitis C is a systemic disease. As you read Chapter 4, Signs and Symptoms That May Be Associated with Hepatitis C, you may find some of the symptoms you thought were caused by something else may actually be caused by HCV. This is important because knowing why you are having a symptom is often the first step in making it less troublesome.

How Hepatitis C Is Diagnosed

You probably learned you are infected with HCV through a blood test. Most likely, the test checked for HCV antibodies in your blood. Your immune system produces antibodies to foreign objects such as viruses and bacteria. When someone is infected with HCV, the body begins producing antibodies specifically designed to search out and destroy HCV. An HCV antibody test is sometimes included in a routine physical. It is also done to check for HCV infection in people who have one or more risk factors for hepatitis C.

HCV antibody tests are not always completely accurate. This is especially true in people with weakened immune systems. People with weakened immune systems might not produce enough antibodies to be detected by the antibody test. People with normal immune systems also sometimes have negative antibody tests despite the fact that they are infected with HCV. This is because in some people, HCV antibodies might not be detected for up to one year after the initial infection.¹⁵ If there is any doubt about the results of the HCV antibody test, people are given another test that detects HCV itself in the blood.

There are three methods called molecular tests that are used to detect the hepatitis C virus in the blood. These methods are polymerase chain reaction (PCR), transcription mediated amplification (TMA), and branched chain deoxyribonucleic acid (bDNA).¹⁶ Many physicians believe testing with a molecular method is the most effective way to confirm a diagnosis of HCV. There are other tests, such as the recombinant immunoblot assay (RIBA), that were designed for the blood banking industry, but are also sometimes used to confirm a diagnosis of HCV.¹⁷

Everyone suspected of having HCV should have liver enzyme tests (ALT and AST) to check for liver damage. Blood tests for liver function should also be performed. Examples of liver function tests include albumin, prothrombin time, and bilirubin.

For more information on tests, see Chapter 5, Laboratory Tests and Procedures.

Acute Phase Hepatitis C

The first six to nine months after infection with HCV is called acute phase hepatitis C. After infection, there is an average incubation period of seven to eight weeks before there is a rise in liver enzymes. HCV antibodies are usually detectable in the blood 3 to 12 weeks after infection. The virus itself is usually detectable in the blood using molecular tests within one to three weeks of infection.^18-19 After being infected with HCV, most people are asymptomatic, meaning they do not have any symptoms of disease. However, 25-35% of infected people experience a mild, acute phase illness. The symptoms of this illness are usually vague and nonspecific.

Between 15-45% of people infected with HCV appear to clear the virus on their own without developing any secondary condition or result from the infection. Experts believe clearing the virus is probably related to the amount of virus in the initial infection.

If your body does not rid itself of HCV within six to nine months after infection, you are considered to be in the chronic phase of hepatitis C. Typically, patients with acute infection and rising viral levels are considered candidates for immediate treatment with interferon and ribavirin.

Chronic Phase Of Hepatitis C Infection

The course of chronic phase hepatitis C is usually that of slow disease progression without symptoms. Most people have no physical signs or symptoms of HCV infection during the first 10-20 years after infection.

The rate of disease progression in chronic hepatitis C differs from one person to another. The rate at which a person's hepatitis C will progress cannot be accurately determined by liver enzyme levels, viral load, or HCV genotype.^20-21 It has been noted that people with normal liver enzymes and low viral load usually have mild liver disease with low-grade liver inflammation. However, even these people occasionally develop fibrosis or cirrhosis. The inability to predict disease progression makes it difficult for health care providers to identify people who are most likely to benefit from treatment.

Why Liver Biopsies Are Performed and How They Are Used

Many health care providers believe a liver biopsy to be the best way to identify people who are most likely to have progressive disease, the group most likely to benefit from treatment.

A biopsy gives your health care provider a great deal of information about your liver including:

the amount of inflammation present

the presence and amount of fibrosis

the presence and amount of cirrhosis

the presence and amount of fat

other causes of chronic liver disease such as too much iron or medication toxicity

the need for liver cancer screening.

A liver biopsy can also help your health care provider decide if and when an evaluation for a liver transplant is needed.

Your health care provider uses the information from a liver biopsy to help predict the rate of your disease progression, and to determine whether you are likely to benefit from treatment. Studies have shown that hepatitis C progresses slowly in people with mild liver inflammation and no fibrosis. For people with fibrosis, hepatitis C is generally more rapidly progressive.⁹

As treatments become more effective, the role of liver biopsy in the management of hepatitis C may change. Your health care provider will consider a number of factors before suggesting a change from monitoring your disease to treating it. These factors might include your age, general health, likelihood of response to treatment, and other illnesses such as HIV. There are also other considerations to take into account before making the decision to treat chronic hepatitis C. These include such things as the length of therapy, cost, frequency of monitoring, past medical history, side effects, and your ability to take the medication as directed. Your health care provider should discuss all contraindications to any therapy he or she recommends to you.

For more information about liver biopsy results, see Chapter 3, Progression of Liver Disease.

HCV Genotype

The hepatitis C family of viruses is divided into types called genotypes. To date, six genotypes and more than 90 subtypes have been identified. The types are numbered 1 through 6, and the subtypes are labeled a, b, c, and so on, in order of their discovery. Presently, genotype testing is used to determine the duration of treatment required, to help health care providers advise people about their potential treatment response, and for research purposes. Genotype testing is considered part of standard, western medical care for people with HCV infection who are being counseled about interferon-based treatment. The reason is that researchers have found certain strains of HCV are more likely to respond to interferon-based treatment than others are. Further, some strains respond in a shorter period of time than others do and require a shorter treatment interval. Therefore, it is very important to know the genotype and subtype of HCV with which you are infected. If you are infected with one of the strains that is hard to treat, your health care provider may advise a longer than normal course of treatment to see if you might eventually respond.

Hopefully, researchers will soon discover why different HCV genotypes respond differently to interferon-based treatment. Currently, subtypes 1a and 1b account for 65-75% of chronic HCV in the United States. Unfortunately, people with subtypes 1a and 1b experience the lowest response rate to conventional western treatment. However, you should not allow your genotype alone to deter you from getting treatment. People with all genotypes have cleared the virus. Remember, your genotype does not determine how your disease will progress. There have been no studies to date to determine if genotype influences response to complementary and alternative medicine treatments, but we hope that will soon change. The current, average remission rate for genotype 1 following treatment with pegylated interferon and ribavirin is approximately 40%. However, for patients who adhere to a full year of treatment at full dose, the viral response rate or "cure" can be up to 50%. With genotype 2 or 3, response rates with pegylated interferon plus ribavirin can increase from an average of 70-80% to 90% with strict adherence and full dose therapy.^22-25

You may hear the term quasispecies in relation to HCV genotype. Quasispecies occur because HCV mutates freely, causing diverse genetic strains in each infected person. The longer you have been infected with HCV, the more likely you are to have a number of quasispecies of HCV in your body. One small study found changes in quasispecies were associated with levels of the liver enzyme ALT during the acute phase of infection. This finding suggests that the formation of quasispecies might be related to the severity of HCV infection.²⁶

Organ and Tissue Transplants

Liver failure due to chronic hepatitis C is the most common reason for liver transplantation in the United States. There are currently more than 20,000 people waiting for a liver transplant in this country, but only about 4,900 livers are available for transplant each year.²⁷

Anyone who has an organ transplant has to take medicines called anti-rejection drugs to keep his or her body from rejecting the new organ. Anti-rejection drugs tend to suppress the immune system. This can cause HCV disease to progress faster than it would otherwise. Your health care provider will work closely with you to decide if you should consider using antiviral therapy after your liver transplant. It is very important to talk with your health care providers about all treatments and/or supplements you are taking or are considering taking. This information is important in making recommendations regarding liver transplantation.

Liver Failure

Liver failure is a common cause of death in the United States, claiming more than 30,000 lives each year. Though some studies indicate that hepatitis C may not be the most common cause of liver failure, hepatitis C is nonetheless a very serious, growing public health problem.^28,29

While the number of new HCV infections has recently declined in the United States, it is believed that the number of people who will develop complications of liver disease will increase over the next 10-20 years.³⁰ Approximately 20-30% of people with chronic hepatitis C will develop cirrhosis over a 20-30 year period. Ten percent of those who develop cirrhosis will eventually progress to end-stage liver disease.^31-33

In spite of these statistics, it is important to remember that a diagnosis of cirrhosis is not a death sentence! Even if you have a cirrhotic liver, unless you develop complications, you can live a very long life. Nonetheless, people with cirrhosis should discuss the need for liver cancer screening with their medical practitioners.

How Hepatitis C Is Transmitted

Blood-to-Blood Contact

The main way HCV is transmitted from one person to another is through blood-to-blood contact. If you received blood or blood products and/or a tissue or organ transplant prior to 1992, you should be tested for HCV. Other examples of blood-to-blood contact that can lead to HCV transmission are listed below.

intravenous drug use with unsterile, used needles

tattoos with unsterile, used equipment or unclean ink pots

acupuncture treatments with unsterile, used needles

nasally inhaled drug use with unsterile, used paraphernalia

accidental needle sticks among health care professionals

dental work performed with unsterile, used instruments

other health care procedures that do not adhere to standard sterilization procedures

Pregnancy/Breast Feeding

The risk of transmission of HCV from an infected mother to her infant at birth is 3-6%. Some data suggest delivery by C-section may reduce the risk of mother-to-child transmission.

There is almost no risk of transmitting HCV by breast feeding unless there are breaks in the skin and bleeding.

Sexual Intercourse

The risk of transmitting HCV through sexual intercourse in monogamous heterosexuals is less than 3-6%. There is no study data on the risk of sexual transmission in a monogamous homosexual relationship. Things such as the number of sexual partners in a lifetime, sexual practices, and the presence of sexually transmitted diseases can influence the risk of HCV transmission.

Summary

The decision to begin any treatment is a big step. Only you know if you are ready to take that step. Once you have decided on your treatment goals, discuss all of your options and concerns with your health care providers. It is often helpful to get a second opinion, or even a third. Choosing health care providers you are comfortable speaking with will help you work together as a team. Making decisions that are right for you will make your choices easier to incorporate into your life.

Taking steps to enhance your general health by doing things such as eating a low-fat diet, stopping all alcohol consumption, and attaining a normal body weight are important parts of your treatment plan. Exercise, spiritual practices, massage, acupuncture, herbs, and other complementary therapies can all have a role in attaining better health.

We know a great deal about hepatitis C. However, there is even more we do not know. Good clinical research is needed in all areas of hepatitis C management including western medicine, naturopathy, traditional Chinese medicine, Ayurveda, homeopathy, nutritional support, and other complementary therapies. This research will lead to the next advances in the care of those living with hepatitis C.

Therapy for hepatitis C is evolving rapidly. As a result, recommendations for therapy will probably change every few years. Hopefully, new approaches will provide therapy that is more effective for people infected with HCV.