Hepatitis C infection was first identified in the late 1980s and is the most serious common blood-borne disease in the United States. The actual hepatitis C virus is a small, single-stranded RNA (ribonucleic acid) virus of the family Flaviviridae. There are approximately six major genotypes (types of genetic information or genes) and more than 50 subtypes of HCV. Genotypes 1a and 1b are the most prevalent in the United States. Genotypes 2 and 3 are present in approximately 10-20 percent of patients. Due to rapid virus mutations or changes in its structure, this virus can evade the immune system, making it difficult to develop a 100 percent effective treatment or vaccine against HCV. Certain genotypes are more responsive to currently approved therapies. Hepatitis C cannot reproduce without being in liver cells. As new viral particles increase, rapidly reproduce and go into the bloodstream, they cause the body's immune system to make antibodies against the virus; however, protective antibody is not usually developed against HCV.
It is estimated that approximately 4 million people, or 1.8 percent of the U.S. population, are infected with HCV. It is also estimated that there are 30,000 new HCV infections and 8,000 to 10,000 related deaths annually. That translates into four times the number of people infected with the virus that causes Acquired Immune Deficiency Syndrome (AIDS). Approximately 70-75 percent of those infected with HCV will go on to develop chronic liver disease, accounting for the top cause of liver transplants at approximately 1,000 transplants per year.
According to current research, approximately 20 percent of patients with chronic HCV will progress to cirrhosis over 10 to 20 years. After 20 to 40 years, a smaller percentage of patients with chronic disease develop liver cancer (hepatocellular carcinoma). Factors that can cause HCV to progress faster include the use of alcohol daily, male gender, older age at time of infection, longer disease duration, co-infection with the Human Immunodeficiency Virus (HIV) and/or hepatitis B. HCV infection occurs in as many as 33 percent of the patients with HIV. Of that 33 percent, more than 60 percent of HCV infections are caused by intravenous drug use and 4 percent from men who have sex with men.
Although routine screening of blood for transmission has improved significantly since the early 1990s, HCV is primarily spread or transmitted by contact with blood and blood products in the United States. Currently the use of shared unsterilized (cleaned at high temperatures) or inadequately sterilized needles (tattoo or drug) and drug cookers (spoons, cotton, etc.) is the most common risk factor for contracting the disease. However, many patients acquire HCV without any known exposure to blood or drug use. Other methods of transmission of HCV are sexual transmission and maternal-infant transmission, which accounts for approximately 5 percent of HCV infections. Surveys of monogamous sexual relationships with a partner infected with HCV have shown that less 5 percent became infected. Hepatitis C is not transmitted by sneezing, hugging, coughing, food, water or casual contact with another person.
Chronic HCV varies in its clinical course and outcome. Some patients will not have any signs or symptoms of liver disease and completely normal levels of alanine aminotransferase (ALT), a serum liver enzyme. ALT is a blood test that healthcare providers use to evaluate patients for liver disease. High levels of ALT suggest liver disease. The new upper limit of normal range for ALT is 30/UL for men and 19/UL for women. In the middle of the spectrum are a large number of people who have few or no symptoms, mild to moderate elevations in liver enzymes, and an uncertain prognosis. At the other end of the spectrum there are patients with severe HCV with symptoms of liver disease, elevated serum liver enzymes, and who go on to develop cirrhosis and end-stage liver disease (ESLD).
Many people with HCV have no symptoms of liver disease. The incubation period for HCV is from 15 to 160 days or an average of 7 weeks. If symptoms are present they are usually mild, non-specific, and intermittent. Constitutional symptoms may include fatigue, mild abdominal discomfort, nausea, poor appetite, or muscle and joint pains.
Clinical signs and symptoms indicating a progression of liver disease to cirrhosis include the constitutional symptoms, muscular weakness, itching, dark urine, fluid retention, and abdominal swelling. Clinical signs of severe liver disease may include enlarged liver, enlarged spleen, jaundice, muscle wasting, fluid in the abdomen (ascites), ankle swelling (edema) and excoriations (sores from scratching).
Complications that do not involve the liver (extrahepatic -- outside of the liver) can develop in approximately 1-2 percent of people with HCV. The most common is cryoglobulinemia, which is indicated by skin rashes, joint and muscle aches, kidney disease, neuropathy, and cryoglobulins (an abnormal protein called globulin).
The diagnosis of HCV is based on clinical signs and symptoms, blood tests and a liver biopsy. Acute HCV is diagnosed by clinical presenting symptoms such as jaundice (yellow color of the eyes and skin), nausea, and flu-like symptoms. Hepatitis C is also diagnosed by laboratory or blood tests.
The blood tests for HCV are based on AST, anti-HCV by enzyme-linked immunosorbent assay (EIA) and HCV polymerase chain reaction (PCR) assay. A 10-fold increase in serum ALT and the presence of anti-HCV is also a sign of hepatitis. HCV is also detected by the presence of serum (blood without red and white cells) anti-HCV antibodies by a third-generation EIA test. As with all EIA there are a small percentage of false-positive results. Additional testing is useful for confirmatory diagnosis of the EIA. The gold standard to confirm the diagnosis of HCV is to test for HCV RNA (hepatitis C virus ribonucleic acid) using a sensitive PCR assay. The detection of HCV RNA in the serum indicates an active infection. This test is especially useful in patients who are HIV positive. Testing for anti-HCV may be negative despite having HCV infection because they may not produce enough antibodies for detection by EIA. Also, diagnosis of acute disease is difficult because anti-HCV is not always present when the patient presents to the healthcare provider with symptoms. Anti-HCV is not detected until 2 to 8 weeks after onset of symptoms in approximately 30 to 40 percent of patients. Although HCV RNA, a more expensive test, can readily detect acute HCV, an alternate approach would be to repeat the anti-HCV test one month after the onset of symptoms. Chronic HCV is diagnosed when anti-HCV is present and serum ALT levels remain high or elevated for more than 6 months.
There are several methods for measuring the amount or "titer" of HCV in the serum. These methods include a quantitative PCR and a branched DNA (bDNA) test. The viral load of HCV may not correlate with the severity of the hepatitis or with a poor prognosis (as it does with HIV); but viral load does correlate with the likelihood of a response to antiviral therapy. Low viral loads (less than 2 million) respond better to current antiviral therapy.
A genotype (the hereditary information present in the virus) is helpful in making recommendations and counseling regarding therapy. Once the genotype is tested it does not need to be tested again since it will not change. Patients with genoypes 2 and 3 are almost three times more likely to respond to therapy. Furthermore, genotype 1 may require a more lengthy treatment.
Liver biopsy is not necessary for diagnosis, but is useful for grading the severity of disease and staging the degree of fibrosis (scarring) and permanent damage to the liver such as the Histologic Activity Index (HAI). Most clinicians use a more qualitative approach to classify by stage: 0 = no fibrosis, 1 = mild fibrosis, 2 = moderate fibrosis, 3 = severe fibrosis, including bridging fibrosis, and 4 = cirrhosis.
Before treatment of hepatitis C with drug therapy can be started, the patient needs to have a thorough examination in order to identify potential co-existing health problems that may not be compatible with HCV therapy. A few of the contraindicated illnesses are major depression, heart problems, and kidney disease. Drug and alcohol use must also be controlled before therapy starts. Other factors that should be taken into consideration for treatment are viral load, age, and results of the liver biopsy. The risks and/or benefits of therapy must be assessed on an individual basis.
All patients with chronic HCV infection are considered potential candidates for antiviral therapy. However, after evaluation, treatment is clearly only recommended for a select group of patients. The current treatment of choice is a combination therapy including interferon and ribavirin. Treatment is highly recommended in patients who are at greatest risk for cirrhosis. Patients over 60 years and children need to be evaluated and reassessed at regular periods as benefits of treatment have not been well supported in the research.
Antiviral therapy for HCV includes interferon (IFN) or pegylated interferon (PEG-IFN) or more commonly a combination therapy with IFN or PEG-IFN and ribavirin. Although interferon is produced naturally in the body to fight viruses, a synthetic or made-in-the-laboratory alpha interferon is used for medical treatments. Alpha interferon (alfa-2a, alfa-2b) is usually given at a dose of 3 million units (MU) subcutaneous (in the fat) injection three times a week or interferon alacon-1 is given 9 micrograms (mcg) 3 times a week for 24 weeks. Oral ribavirin is given twice daily in the form of a 200 mg capsule. The new pegylated interferon (PEG-IFN) was developed to avoid the peaks and troughs (low dips) of interferon levels by remaining in the blood for a longer period of time, having the advantage of lasting longer and only administered once per week. PEG-INF alpha is given based on the weight of the patient. PEG-IFN alfa combined with ribavirin is now replacing the old IFN-alpha combined with ribavirin as the standard or "gold standard" treatment for chronic HCV infection.
Treatment with interferon alone or combination therapy with interferon and ribavirin leads to rapid improvements in serum ALT levels in 50-75 percent of patients and the disappearance of detectable HCV RNA from the serum in 30-50 percent. A response is considered "sustained" if HCV RNA remains undetectable for 6 months or more after therapy stops. Combination therapy with interferon and ribavirin leads to loss of HCV RNA on treatment in 50-55 percent of patients and a sustained loss in 35-45 percent. Optimal duration of therapy varies depending on whether interferon monotherapy or combination therapy is used, as well as by HCV genotype. Patients with genotypes 2 and 3 have a high rate of response to combination treatment (60-70 percent), and a 24-week course of combination therapy yields results equivalent to those of a 48-week course. In contrast, patients with genotype 1 have a lower rate of response to combination therapy (25-35 percent), and a 48-week course yields a significantly better sustained response rate.
In HIV/HCV co-infection, benefits of therapy for HCV must take into consideration the concurrent use of anti-HIV medications and medical conditions. If CD4 counts are normal or minimally abnormal (greater than 400), responses are similar to those in patients who are not infected with HIV. Ribavirin may still have significant drug interactions with other antiretroviral drugs.
Treatment of HCV infection with the current gold standard is not always effective and treatments regimens can be difficult for a patient to tolerate. Before starting on antiviral therapy you should receive counseling on the potential side effects and how they will affect your ability to function at work and in the activities of daily living.
The major potential side effects of interferon include depression, irritability, anxiety, impaired concentration, insomnia, autoimmune disease and bone marrow compromise. Also, in addition to these symptoms, the most common side effects of interferon include flu-like symptoms: fatigue, muscle aches, headaches, nausea, vomiting, rigors (shakes), and a low-grade fever. The loss of hair (alopecia) can occur in women.
The major side effect of ribavirin is hemolytic (breakdown of red blood cells) anemia. In some cases, anemia is so severe that therapy must be discontinued. Ribavirin has also caused birth defects during animal studies. Both ribavirin and combination therapy should not be used on women who are pregnant or who may become pregnant, or on their male partners, during therapy or six months after therapy is completed. Women of childbearing potential must use two forms of effective contraception (birth control) due to the possibility of serious birth defects.
If there is no response to current therapies, some patients may be considered for controlled clinical trials. When the liver decompensates and fails, liver transplantation remains the only other option for treatment of hepatitis C at this time. However, the donor liver often becomes reinfected with the virus. Liver transplantation is still rather controversial among patients co-infected with HIV and HCV.
Since the liver is already being damaged from HCV, steps must be taken to protect it from further harm. Consultation with the healthcare provider about the use of any medication, including over-the-counter and herbal supplements, must be included. Alcoholic beverages should be stopped. Every effort should be made to stop smoking. Diet control and avoidance of obesity appear to be helpful in the care of the liver. All patients with HCV, if not previously exposed to hepatitis A and B, should be vaccinated. Amble rest and a healthy lifestyle will help strengthen the immune system. Regular medical attention is important and new problems should be identified immediately. Hepatitis C support groups are available to provide encouragement to those experiencing problems and challenges living with this disease.
Bethsheba Johnson is an A.P.R.N. She is affiliated with B.C. Luck Care Center and Midwest AIDS Training and Education Center (MATEC) of Chicago.