Chronic hepatitis C varies greatly in its course and outcome. At one end of the spectrum are patients who have no signs or symptoms of liver disease and completely normal levels of serum liver enzymes. Liver biopsy usually shows some degree of chronic hepatitis, but the degree of injury is usually mild, and the overall prognosis may be good. At the other end of the spectrum are patients with severe hepatitis C who have symptoms, HCV RNA in serum, and elevated serum liver enzymes, and who ultimately develop cirrhosis and end-stage liver disease. In the middle of the spectrum are many patients who have few or no symptoms, mild to moderate elevations in liver enzymes, and an uncertain prognosis. Researchers estimate that at least 20 percent of patients with chronic hepatitis C develop cirrhosis, a process that takes 10 to 20 years. After 20 to 40 years, a smaller percentage of patients with chronic disease develop liver cancer.

Chronic hepatitis C can cause cirrhosis, liver failure, and liver cancer. About 20 percent of patients develop cirrhosis within 10 to 20 years of the onset of infection. Liver failure from chronic hepatitis C is one of the most common reasons for liver transplants in the United States. Hepatitis C might be the most common cause of primary liver cancer in the developed world. In Italy, Spain, and Japan, at least half of liver cancers could be related to HCV. Men, alcoholics, patients with cirrhosis, people over age 40, and those infected for 20 to 40 years are more likely to develop HCV-related liver cancer.

Risk Factors and Transmission HCV is spread primarily by contact with blood and blood products. Blood transfusions and the use of shared, unsterilized, or poorly sterilized needles and syringes have been the main causes of the spread of HCV in the United States. With the introduction in 1991 of routine blood screening for HCV antibody and improvements in the test in mid-1992, transfusion-related hepatitis C has virtually disappeared. At present, injection drug use is the most common risk factor for contracting the disease . However, many patients acquire hepatitis C without any known exposure to blood or to drug use.

The major high-risk groups for hepatitis C are :

People who had blood transfusions before June 1992, when sensitive tests for anti-HCV were introduced for blood screening.

People who have frequent exposure to blood products. These include patients with hemophilia, solid-organ transplants, chronic renal failure, or cancer requiring chemotherapy.

Health care workers who suffer needle-stick accidents.

Injection drug users, including those who used drugs briefly many years ago .

Infants born to HCV-infected mothers.

Other groups who appear to be at slightly increased risk for hepatitis C are:

People with high-risk sexual behavior, multiple partners, and sexually transmitted diseases.

People who use cocaine, particularly with intranasal administration, using shared equipment .

Sporadic Transmission

Sporadic transmission, when the source of infection is unknown, occurs in about 10 percent of acute hepatitis C cases and in 30 percent of chronic hepatitis C cases. These cases are also referred to as sporadic or community-acquired infections. These infections may have come from exposure to the virus from cuts, wounds, or medical injections or procedures.

The Hepatitis C Virus

HCV is a small (40 to 60 nm in diameter), enveloped, single-stranded RNA virus of the family Flaviviridae. Because the virus mutates rapidly, changes in the envelope protein may help it evade the immune system. There are at least 6 major genotypes and more than 50 subtypes of HCV. The different genotypes have different geographic distributions. Genotypes 1a and 1b are the most common in the United States. Genotypes 2 and 3 are present in only 10 to 20 percent of patients. There is little difference in the severity of disease or outcome of patients infected with different genotypes. However, patients with genotypes 2 and 3 are more likely to respond to alpha interferon treatment.

Clinical Symptoms and Signs Many people with chronic hepatitis C have no symptoms of liver disease. If symptoms are present, they are usually mild, nonspecific, and intermittent. They may include:

Fatigue, mild right-upper-quadrant discomfort or tenderness, nausea, poor appetite & muscle and joint pains.

Similarly, the physical exam is likely to be normal or show only mild hepatomegaly or tenderness. Some patients have vascular spiders or palmar erythema.

Clinical Features of Cirrhosis

Once a patient develops cirrhosis or if the patient has severe disease, symptoms and signs are more prominent. In addition to fatigue, the patient may complain of muscle weakness, poor appetite, nausea, weight loss, itching, dark urine, fluid retention, and abdominal swelling. Physical findings of cirrhosis may include:

Enlarged liver & spleen, jaundice, muscle wasting, excoriations, ascites & ankle swelling.

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