Hep A, B & C

Introduction
A patient came to me after a routine physical exam required by his employer. His test results had shown an elevation in his liver function, which means that his liver was working harder than it would normally. He said that in general he felt fine but occasionally he was tired. His primary care doctor tested him for hepatitis and told him he had hepatitis C. He couldn’t believe it. This patient asked me how he could have acquired it and how he could feel so healthy and have hepatitis. He wanted to know whether he needed treatment.

Hepatitis is defined as inflammation of the liver. Most people, when they hear hepatitis, think of viral hepatitis, but there are other causes for the disease, such as alcohol and drugs. In this review we will focus on the various forms of viral hepatitis, their causes, symptoms, and available treatments.

What is Viral Hepatitis?
Viral hepatitis is inflammation of the liver caused by a viral infection. The major types of viral hepatitis are hepatitis A, B, and C (caused by the hepatitis viruses A, B, and C respectively). Some other causes of viral hepatitis are hepatitis viruses D and E, EBV (Epstein-Barr virus, the cause of infectious mononucleosis), and CMV (cytomegalovirus).

Hepatitis may be acute or chronic. Acute hepatitis may vary from a rapidly progressing, severe disease in some people to a slow, asymptomatic disease in others. Symptoms that may develop in acute hepatitis are fatigue, nausea, decreased appetite, and jaundice (yellow color of the skin or eyes). Acute hepatitis becomes chronic if it does not disappear after 6 months. It is important to recognize that some types of viral hepatitis lead to chronic disease without ever revealing themselves symptomatically. A patient may feel only mild fatigue. One major concern in patients with chronic hepatitis is the potential progression to cirrhosis, a permanent scarring of tissue in the liver.

Hepatitis A
Hepatitis A affects about 125,000 – 200,000 persons per year in the United States.

How do you get hepatitis A?
Hepatitis A is an RNA virus (a virus that contains RNA as its genetic material similar to how humans have DNA) that is transmitted through the fecal-oral routine, less commonly through water-borne outbreaks, and rarely through blood. Transmission by the fecal-oral route means that the hepatitis A virus is shed into the stool, passed onto food or another vector (organism that transmits a pathogen), and ingested by an unknowing individual. Outbreaks have occurred in restaurants and day-care centers. High-risk groups include personal and sexual contacts of infected persons, international travelers to endemic areas, day-care workers, homosexually active men, and intravenous drug users.

Symptoms
Symptoms include jaundice, fatigue, abdominal pain, nausea and loss of appetite.

Treatment
Treatment of acute hepatitis A is entirely focused on reducing symptoms as there is no specific treatment for hepatitis A virus. The illness is usually mild and lasts about a month before it goes away. In severe cases, patients are treated for dehydration that can result from nausea and vomiting. Prolonged or relapsing infection may develop in 15% of infected people. Rarely, hepatitis A leads to fulminant hepatitis, or liver failure, which accounts for about 100 deaths per year in the United States. One of the most important points to remember about hepatitis A is that it does not cause chronic infection or cirrhosis. As well, a vaccine is available which is highly effective in preventing hepatitis A. For persons exposed to hepatitis A, immune globulin (an intravenous solution of antibodies) if available, can prevent severe infection. Good hygiene and sanitation are important in preventing the transmission of the virus.

Hepatitis B
Hepatitis B virus leads to 140,000 – 320,000 infections per year in the United States with about 50% of those infected developing symptoms. Symptomatic infections lead to 8,400 – 19,000 hospitalizations per year and 140 – 320 deaths per year.

How do you get hepatitis B?
Hepatitis B is transmitted sexually, perinatally (from mother to child during child birth) and through blood. High risk groups include intravenous drug users, sexually active homosexual men, heterosexuals with multiple sexual partners, infants born to infected mothers, hemodialysispatients (people with kidney failure who need to clean their blood regularly with a filtering machine), health care workers, and personal contacts of infected persons.

Hepatitis B is a DNA virus that can lead to acute or chronic infection. Chronic infection occurs in 6% - 10% of infected patients and a minority of these patients may develop cirrhosis. Infants infected during childbirth are particularly susceptible to developing chronic hepatitis B infection and cirrhosis, which is one reason why pregnant women are screened for hepatitis B. There is effective therapy for preventing transmission to the infant during childbirth.

Symptoms
Symptoms of hepatitis B are similar to those listed for hepatitis A and include jaundice, nausea, vomiting, and fatigue.

Treatment
Therapy for people who are chronically affected by Hepatitis B includes interferon (a class of proteins in the body with anti-viral properties) given daily as an injection under the skin (similar to insulin for diabetics) for 16 weeks, in combination with a daily dose of lamivudine (an antiviral medication) in pill form. Patients can be taught to give themselves the injections, so there is no need to return to the doctor on a daily basis. A vaccine is available for preventing hepatitis B infection and it is recommended in high-risk groups and for newborns and children between the ages of 11-12.

Hepatitis C

Hepatitis C virus has received a lot of attention because it is the most commonly identified virus leading to chronic hepatitis, and hepatitis C-associated cirrhosis is the leading indication for liver transplantation in the United States. An estimated 2.9 million people are chronically infected with hepatitis C in the United States. The estimated number of new infections per year is 36,000, but only 30% of new infections may be symptomatic, so many new cases go unrecognized. Approximately 70% of patients infected with hepatitis C will develop chronic liver disease, and it is estimated that 20%- 40% of individuals with chronic liver disease from hepatitis C may develop cirrhosis.

How do you get hepatitis C?
Hepatitis C is an RNA virus that causes a chronic, non-healing disease, and is transmitted primarily through the blood. Recreational drug use with needles can lead to hepatitis C, and recipients of blood transfusions before 1992 are also at risk. Since that time, the blood supply has been systematically screened for hepatitis C. A low risk of transmission occurs through sexual and perinatal routes (from mother to child during child birth). Risk factors for hepatitis C infection are similar to hepatitis B infection and include intravenous drug use, hemodialysis and sexual activity with multiple partners.

Symptoms
Most infected individuals are surprised to learn that they have hepatitis C. Most often the patient is mildly fatigued or has no symptoms at all. For some of my patients the only identified risk factor is intravenous drug use over 20 years ago. An unsuspecting individual may have a routine physical exam and find that he or she has elevated liver enzymes indicating that the liver is working harder than it should. In this case, the primary care doctor should refer the patient to a gastroenterologist or hepatologist for further tests. These may include further blood testing, radiographic exams, and liver biopsy.

Treatment
The goal of therapy for hepatitis C is to prevent death from end-stage liver disease or liver cancer, prevent the onset of cirrhosis, and to improve quality of life.

Combination drug therapy
Treatment for hepatitis C includes interferon and ribavirin. Again, these drugs do not eradicate the virus, but they slow the progression of liver damage. Interferon is delivered in a shot under the skin three times a week and ribavirin is delivered twice a day in pill-form. The sustained response (response rate) is 40%. You may receive therapy for 6 or 12 months depending on which genetic strain/genotype (variety of RNA) of hepatitis C virus you have. Most chronically infected people in the United States are genotype 1, and unfortunately, people who are genotype 1 are less likely to respond to combination therapy (interferon and ribavirin) then those who are genotype 2 or 3.

Also there are many side-effects that may or may not occur during the therapy. The most common side-effects in my patients are flu-like symptoms and fatigue. Less common ones include thyroid disease and rash. It is very important not to become pregnant during treatment or six months subsequent to treatment, as ribavirin can lead to fetal loss or birth defects

Liver biopsy
Most of my patients ask me if getting a liver biopsy is really necessary. A liver biopsy is a procedure in which cells are extracted from the liver itself for study. A biopsy is usually required before treatment because it reveals how much scarring is already present in the liver. The amount of liver injury seen on the biopsy helps the doctor and patient decide together whether or not to start therapy or to wait for newer, more effective therapies with fewer side-effects.

New therapies
New therapies under investigation for hepatitis C include longer acting interferons which would be more successful in slowing the progression of the disease. Scientific research in this area has focused on the potential for oral medications, such as protease inhibitors (one of the classes of drugs used for HIV infection), but these have yet to be studied in people.

Prevention
There are vaccines for hepatitis A and B. There is currently no vaccine for hepatitis C. It is, therefore, critical to educate the public about this virus and its methods of transmission if we are to impact on the number of people chronically infected. Intravenous drug use is one way in which this virus spreads and it is very high-risk behavior as many people do not know if they are infected or not. Blood is currently screened for hepatitis C and the risk of infection from transfusion is rare. The ultimate goal is to develop an effective and safe vaccine against hepatitis C. Until then, education about this virus is critical.

Other Causes of Viral Hepatitis

There are a number of other causes of viral hepatitis.

Hepatitis D
Hepatitis D is a virus that occurs only with hepatitis B and it may cause rapidly progressive liver disease. Because hepatitis D virus needs hepatitis B virus to survive, vaccination or immunity to hepatitis B virus protects you against hepatitis D.

Hepatitis E and hepatitis G
Hepatitis E is a virus that is similar to hepatitis A, but is rarely found in the United States and more commonly found in Asia. Hepatitis G is a newly discovered virus that does not seem to cause significant liver disease.

Epstein Barr and Cytomegalovirus
Epstein Barr virus and cytomegalovirus are other causes of hepatitis that only cause the acute form of hepatitis and are not associated with chronic, long-lasting, hepatitis.

The patient who I described earlier did have hepatitis C. I informed him that he might have acquired hepatitis C over 10 or 20 years ago. He admitted to a brief time period 20 years earlier when he used intravenous drugs, and he may have acquired the virus then. He couldn’t understand how he could feel so normal and still have chronic hepatitis. I explained that chronic hepatitis C may not cause symptoms in some patients and may cause severe symptoms in others, with fatigue being the most common complaint. He went on to have a liver biopsy and he is undergoing treatment with interferon and ribavirin.

Commonly Asked Questions
Do I need to have a liver biopsy?
Many of my patients are concerned about having liver biopsies. After I explain why the liver biopsy is important and what is involved, almost all agree to proceed. The liver biopsy provides valuable information about the amount of damage or scarring that has already occurred in the liver. I use the biopsy results and information from the other tests to recommend treatment. The more advanced the liver disease the more likely I am to recommend treatment.

What are the most common side-effects of interferon and ribavirin?
The most common side-effects of interferon are flu-like symptoms such as fatigue, aches and pains. You may experience thyroid problems or you may have diminished blood counts. Depression is not uncommon, especially in those who are already depressed or have a history of depression. Ribavirin can cause a low red blood cell count (anemia) and symptoms of fatigue or shortness of breath. Heart disease patients may have problems with ribavirin as a result of the anemia.

You cannot become pregnant while taking ribavirin or 6 months following treatment because the drug is associated with fetal loss and birth defects. There are other side-effects of interferon and ribavirin not listed above that you can discuss with your doctor. Despite the daunting list of potential side-effects, most patients do very well and complete therapy.

What are my chances of getting better with therapy?
Your chances of getting better with interferon and ribavirin depend on a number of factors, including viral load (how much virus there is in your system), genotype, and the liver biopsy results. On average, about 40% of patients have a long-lasting response after a course of therapy. This number may be higher or lower depending on the factors listed above and should be discussed individually.

** Note **

Please remember that the information presented in this forum is for your education only, and is not intended to extend medical advice or diagnosis. If you have questions or feel that you may be experiencing symptoms similar to those presented, please call the Berkeley County Health Department at (304) 263-5131 or your primary care provider for formal medical attention.