Fifty-three-year-old Barbara has a past that haunts her. She is a former IV drug user, who is now coinfected with HIV and hepatitis C. Combination antiretroviral therapy controls her HIV disease, and her HIV viral load is undetectable, less than 50 copies/mL. She has a hepatitis C viral load greater than one million copies/mL. Her health care provider wants her to have a liver biopsy and to consider treatment for her hepatitis C infection. The provider has explained to her that a liver biopsy is necessary to determine the degree of her liver disease and the viral genotype that will determine the duration of the appropriate treatment for hepatitis C.

Fifty-one-year-old Eli also has a past experience that intrudes on his everyday reality. In his youth, one foggy night led to a motor vehicle accident that required a blood transfusion. Fifteen years ago, he found out that he had non-A, non-B hepatitis. In 1990, after a diagnosis of hepatitis C, he enrolled in an early clinical trial of interferon to which he did not respond. He recently completed 12 months of therapy with Interferon and ribavirin, to which he did not respond. Today Eli has moderately elevated serum transaminase levels. He appears jaundiced and gaunt with thin arms and legs and a protuberant abdomen. He has pitting edema and skin lesions of unknown etiology. He feels chronically fatigued and has recently noticed some short-term memory loss. Nevertheless, Eli eats well and very carefully, avoiding all alcohol. His only medication is a potassium-sparing diuretic, spironolactone (Aldactone). His hepatologist told him that he should satisfy the criteria for the regional liver transplant waiting list in one to two years. Eli has started looking forward to meeting those requirements.

Barbara and Eli are part of four million people in the U.S. and 170 million worldwide¹ who have hepatitis C. The most common chronic bloodborne infection and the leading reason for liver transplantation in the U.S.,² hepatitis C has infected about 1.8% of all persons in the U.S. and created a significant public health problem. Eclipsed by AIDS, hepatitis C is the “shadow epidemic,”³ even though it involves many more people. And the statistics don't reflect the many who are at increased risk such as those who are incarcerated, homeless, or institutionalized.⁴ Unlike hepatitis A and B, most newly diagnosed patients are asymptomatic. The majority of diagnoses are made during biochemical or blood donor screening, or when symptoms emerge from advanced chronic hepatitis, cirrhosis, or end-stage liver disease.

Nurses can play a significant case-finding role with people who have hepatitis C because 90% have an identifiable risk factor, including injecting drug use (60%); multiple sex partners (20%); and other known perinatal, household, transfusion, hemodialysis, and occupational exposures (10%).⁵ By taking careful histories, nurses can identify those at risk because of past behaviors and exposures and guide them to serological testing. On a more personal level, people with hepatitis C who remain unidentified pose a serious occupational threat to health care workers.

The culprit

In 1989, scientists identified the hepatitis C virus (HCV) as the major causative agent of bloodborne non-A, non-B hepatitis. Since then, they have learned much about the biology, epidemiology, and pathophysiology of hepatitis C.¹

HCV is a single-stranded RNA virus of the Flaviviridae family, which includes viruses that cause yellow fever, dengue, Japanese encephalitis, and St. Louis encephalitis. On the basis of nucleic acid sequences, researchers have classified at least six major strains (or genotypes) of the hepatitis C virus. The genotypes are associated with varying degrees of disease severity, response to drug treatment, and potential for vaccine development. Genotype 1, responsible for 70% to 75% of HCV infections in the U.S., is associated with a lower rate of response to treatment.⁴

Nailing a diagnosis

The average incubation period, which may be asymptomatic, is six to seven weeks after infection with HCV; the range is two to 20 weeks. Enzyme-linked immunosorbent assay (ELISA) can detect the hepatitis C antibody by 15 weeks after infection in 80% of patients, and by six months in 97%.³ Testing for hepatitis C antibody should be continued up to six months after a known exposure to HCV. A second confirmatory test — the RIBA (recombinant immunoblot assay) — can rule out a false-positive ELISA result. Besides these antibody tests, qualitative tests, such as hepatitis C RNA testing by polymerase chain reaction (PCR) or branched DNA testing, can determine hepatitis C viral burden, similar to HIV. Quantitative tests for HCV RNA (viral loads) have become the gold standard for monitoring treatments.²

No test can differentiate between acute and chronic infection. A diagnosis of chronic hepatitis C is based on a positive hepatitis C antibody test and elevated liver enzymes of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that persist for more than six months, or by liver biopsy for histologic evidence of hepatitis even with normal serum aminotransferase concentrations. The ALT is often only modestly elevated, and the AST is usually lower than the ALT. A liver biopsy determines the extent of liver involvement.

The illness and its deadly connections

Although the disease may be associated with no symptoms, and many people discover it through a routine exam perhaps 20 years after infection, hepatitis C can appear as acute hepatitis. However, only 25% of new HCV cases involve jaundice with or without other nonspecific symptoms, such as fatigue, anorexia, malaise, nausea, vomiting, headache, and arthralgia. Fever is rare and hepatomegaly occurs in less than one-third of cases.

HCV presents more commonly as chronic hepatitis after many years of undiagnosed infection. In fact, symptoms may not appear until end-stage liver disease. Seventy percent to 90% of patients with HCV will develop chronic hepatitis as opposed to only 2% to 5% of adult patients with acute hepatitis B virus (HBV).⁵ Patients with persistent hepatitis B surface antigen develop chronic hepatitis B and are capable of transmitting disease to others. On the other hand, all people with hepatitis C antibody are at risk of developing chronic hepatitis and presumed to be infectious.

The natural history of hepatitis C infection is quite variable.^1,2 An estimated 10% to 15% of all patients will eventually clear their hepatitis C infection. Chronic viremia occurs in 85% to 90% of infected individuals, 70% of whom will develop some degree of liver damage. On average, 15 years transpire before diagnosis of HCV, 20 years before cirrhosis, and more than 25 to 30 years for hepatocellular carcinoma (HCC).

In the U.S., approximately 33% of primary liver cancer cases without another identified cause occur in HCV-positive individuals.⁴ Liver cancer occurs through hepatitis C cirrhosis and rarely develops in HCV-infected patients without cirrhosis. The risk of cancer is greatest in people who have both hepatitis C and HIV or chronic hepatitis B infection, and who drink alcohol.^1,2

Hepatitis C is a rare cause of fulminant hepatitis in the U.S. However, people who are infected with hepatitis C may be at increased risk of fulminant hepatitis if they become superinfected with hepatitis A (HAV).⁶ HBV and HCV coinfection results in an increased risk of fulminating hepatitis, more rapid fibrosis progression, and increased risk of HCC.¹

Disease outside the liver

Many extrahepatic conditions, such as cryoglobulinemia, are associated with chronic hepatitis C. Cryoglobulinemia is a multisystem disorder characterized by the deposition of circulating immune complexes in the blood vessels of many organs and may result in arthralgias, purpura, renal disease, and Raynaud’s disease. Many patients have a triad of symptoms that include arthralgias, purpura, and weakness. The presence of unique immunoglobulins, such as IgM and IgG, is a basis for diagnosis. Cryoglobulin refers to the tendency of these IgM and IgG immunoglobulins to precipitate at cold temperatures.⁷ In one study of 81 people with chronic hepatitis C, 46% had cryoglobulins detected in their serum; signs and symptoms of cryoglobulinemia were present in 27% of those patients.⁸

Porphyria cutanea tarda is another extrahepatic manifestation. This most common form of porphyria is due to reduced activity of the enzyme uroporphyrinogen decarboxylase in hepatocytes. Porphyrin refers to any of a group of nitrogen-containing compounds that form the basis of animal and plant respiratory pigments, and are obtained from hemoglobin and chlorophyll. Porphyria can be a hereditary condition and is associated with cutaneous lesions, increased skin fragility, bruising, and the development of vesicles and bullae, which may become hemorrhagic. HCV may trigger the condition in predisposed persons. Individuals with porphyria cutanea tarda should be tested for hepatitis C.⁷

Other extrahepatic conditions that have been associated with hepatitis C infection include autoimmune thyroiditis, polyarteritis nodosa, aplastic anemia, and B-cell lymphoma.² Depression is also seen in up to 20 to 30% of cases.⁴

How damage occurs

The pathogenesis of hepatitis C infection is not well known. Liver necrosis, scarring, and Kupffer cell hyperplasia and phagocytosis all occur during acute infection. Kupffer cells are specialized macrophages that line the liver and remove old or damaged cells and pathogens by phagocytosis. Cellular injury occurs as a result of the body's immune response, and liver regeneration occurs within 48 hours of injury. The inflammatory process also causes bile duct injury and obstructive jaundice.

Acute viral hepatitis causes elevations in liver function tests. The serum AST and ALT levels are usually only moderately elevated. Serum bilirubin levels may rise and prothrombin time may be prolonged.

Persistent hepatitis C infection in the absence of liver disease appears to result from either the virus's ability to mutate and escape the body's immunologic control or to replicate outside the liver.⁹ Chronic hepatitis C eventually progresses to cirrhosis in up to 20% of patients over a 20 year period.⁵ Cirrhosis is an inflammatory disease caused by fibrosis and nodular regeneration of liver tissue. It is a slow, gradual process. The liver may become larger or smaller than normal, but is firm or hard when palpated. Liver fibrosis and cirrhosis may be reversible with antiviral therapy.¹⁰

Obstruction caused by cirrhosis can lead to portal hypertension. Elevated pressure in the liver causes collateral vessels to open up between the portal and systemic veins. Blood that has been shunted through this collateral system has not circulated through the liver where toxins and other harmful substances are normally removed, causing these noxious substances to accumulate. Long-term portal hypertension is associated with esophageal varices, splenomegaly, ascites, and hepatic encephalopathy.⁹

Factors that influence the progression of fibrosis are age at the time of infection, gender, alcohol use, and viral coinfection. Patients who acquire hepatitis C after age 40 have more aggressive disease. Children generally have mild disease. Rapid progressive disease is less common in women than men. Alcohol abuse is the most important factor, increasing the odds of developing cirrhosis fifteenfold, compared to those who abstain.^1,2

HIV-HCV coinfection

Hepatitis C infection occurs in as many as 33% of patients with HIV infection. Studies of coinfected hemophiliacs have shown that coinfected patients develop earlier and more severe liver disease, including hepatocellular carcinoma. However, HCV does not seem to alter the natural history of the infection. HIV coinfection in pregnant women increases the risk of perinatal HCV transmission twofold. Antiretroviral therapy for HIV should be administered cautiously in patients with chronic hepatitis C.¹¹

How HCV is spread

Hepatitis C is predominately bloodborne, although the route of transmission is unknown for approximately 10% of cases.⁵ Percutaneous exposure, including injecting drug use, transplantation, and transfusion, is the most efficient route. Once serologic testing for HCV became available, clinicians determined that HCV was responsible for more than 90% of transfusion-associated, non-A, non-B hepatitis cases. Needlestick injuries and hemodialysis are other examples of HCV transmission via percutaneous exposure. Tattooing, body piercing, and commercial barbering are associated with HCV transmission in other countries.⁵

Injecting drug use accounts for about 60% of HCV cases. In various serosurveys, 50% to 80% of injecting drug users have been found to be HCV antibody-positive. In a 1992 survey in a Baltimore inner-city emergency department, 18% of all patients and 83% of patients with a substance abuse history had hepatitis C antibodies. Another mode of transmission involving drug use may be shared straws or other devices during intranasal cocaine use, as a result of small nasal hemorrhages contaminating such devices.⁵

Vertical transmission of the disease from infected mothers to 2% to 5% of their infants has been documented in U.S. studies. Transmission has also been observed to be higher in women who are coinfected with HIV, possibly due to an increased level of viremia in these women. Although there are no studies that evaluated elective Cesarean delivery as a means of decreasing the risk of transmission to infants, the avoidance of fetal scalp monitoring and prolonged labor after rupture of membranes may offer some protection.⁴

Sexual transmission is apparently associated with the number of sexual partners, the duration of exposure, and the presence of other risk factors, such as injecting drug use and HIV coinfection.⁵

Person-to-person transmission may also occur in about 2% of nonsexual household contacts, although the precise mode of transmission is unknown. Shared personal care items that can induce bleeding, such as toothbrushes and razors, have been proposed as possible vehicles of HCV transmission. No association of hepatitis C infection has been found with tattooing, ear piercing, or acupuncture in the U.S.⁵

Occupational transmission of hepatitis C can occur through percutaneous exposure. The risk of hepatitis C transmission after a needlestick from a known hepatitis C patient is about 6%, somewhere between the risks of HIV and hepatitis B after a needlestick injury. One recent report also described the acquisition of hepatitis C as a result of blood splashing into the eyes of a public safety officer.¹² Currently, the Centers for Disease Control and Prevention (CDC) has made no recommendation about hepatitis C postexposure prophylaxis after a needlestick injury. No current vaccine or immune globulin products can prevent transmission of HCV.⁵

Medical treatment

The success rate of antiviral therapy for chronic HCV patients has improved dramatically in recent years. Combination therapy with interferon and ribavirin is now the standard of care for previously untreated patients with HCV. Sustained virologic response rates (undetectable HCV viral load) of 40% have been reported. An investigational pegylated interferon with a longer half life and once-per-week dosing (compared to three times a week dosing with interferon), in combination with ribavirin has been shown to improve response rates further. Pegylation is a process by which an inert molecule is attached to a protein, in this case, interferon, which extends the drug's therapeutic activity and allows for less frequent dosing.⁴ Combination therapy has also been shown to be of benefit in patients previously treated with interferon alone.²

The efficacy of interferon and combination therapy is influenced by HCV genotype, HCV viral load, and the presence of cirrhosis. Optimum responses to treatment (70% to 80%) are seen in patients with genotype 2 or 3, HCV RNA viral loads below two million copies/mL, and no evidence of cirrhosis on biopsy. Patients with genotype 1, high viral load, and cirrhosis have a 10% to 20% response rate.²

Patients with genotype 2 or 3 and viral loads of less then two million copies/mL require six months of therapy. Patients with genotype 1 and higher viral loads require 12 months of treatment.

Nurses need to be aware that interferon is not without adverse effects. The most common one is a flu-like syndrome experienced by approximately 50% of patients. This syndrome includes fever, malaise, anorexia, chills, nausea, vomiting, and headache. Some patients may have these symptoms for about 12 hours after the dose, and since the medication is administered three times a week, they may be uncomfortable three days a week with flu-like symptoms. Some patients take interferon at bedtime so symptoms peak at night. Fatigue, bone marrow suppression, and neuropsychiatric effects of depression, apathy, and cognitive changes may require dose reduction or discontinuation. Hemolytic anemia is the most common adverse effect of ribavirin therapy. This drug should be used with caution in patients with coronary artery disease. Ribavirin is a teratogen in animals and should only be used in fertile women using effective contraception.⁵

HCV cirrhosis is a leading indication for liver transplantation. Unfortunately, many who do undergo liver transplantation for HCV-induced cirrhosis experience a recurrence of HCV and have an accelerated rate of disease progression.⁴

Although no treatment recommendations exist for hepatitis C postexposure prophylaxis, studies indicate that interferon treatment early in the course of HCV infection is associated with a higher rate of resolved infection. The CDC recommends baseline testing for HCV antibody and ALT level for the exposed person, and follow-up testing for HCV antibody and ALT level in four to six months postexposure.⁵

Education and prevention are crucial

Since 1989, the incidence of HCV has declined by 80% as a result of screening of blood and organ donors and changes in practices implemented in the wake of the AIDS epidemic.¹³ Universal/standard precautions, safer injecting behaviors, and needle exchange programs have probably contributed to this decline.

Health care providers should advise people who are hepatitis C antibody-positive not to donate blood, organs, other tissue, or semen. HCV-positive people should not share their personal care items, such as razors or toothbrushes, if they could be contaminated with blood. Although condoms may reduce transmission rate, HCV-discordant couples with long-standing monogamous relationships have a risk of transferring HCV of 0 to 0.6% annually and may not need protective barriers during sexual activity.⁴

Women of reproductive age who are being treated for HCV and are considering conception should be informed that ribavirin and interferon are contraindicated during pregnancy. There is no evidence that HCV is transmitted by breastfeeding.⁴ Finally, because of the risk of exacerbation of disease with the use of alcohol, people who are HCV-positive should be strongly encouraged to abstain from alcohol.^1,2 To prevent further liver damage, HCV-infected individuals with high-risk drug or sexual practices should be advised to get vaccinated against hepatitis A and hepatitis B.⁵ For health care workers with HCV, no special work restrictions are recommended.⁴

Nurses should ensure that their institutions educate all employees regarding such bloodborne infections as hepatitis C, the practice of universal precautions, the appropriate use of protective barriers, safe sharp disposal, and good hand hygiene practices. In this way, nurses will be able to help prevent the spread of a disease that now haunts so many lives.