HEPATITIS D

Hepatitis D is a defective virus, occurring only in patients with HBV infection. Approximately 70,000 people are infected with HDV in the United States.7 Typical patients include IV drug users and their sexual partners. Less frequently, infection is seen in hemophiliacs and homosexuals. 

HDV can occur simultaneously with HBV or superinfect a person who has HBV. Co-infection of HBV and HDV comprises a severe acute disease, and patients are at greater risk of developing acute liver failure compared with those who are infected with HBV alone. Chronic HBV carriers who acquire HDV superinfection usually develop chronic HDV infection. HDV infection may produce an acute exacerbation of previously stable chronic hepatitis. Superinfection may also increase chronic active hepatitis B and cirrhosis or accelerate the course of chronic liver disease. Because HDV is present only with HBV, transmission is the same as with hepatitis B.


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Diagnosis

All patients with HBV should be tested for HDV. The presence of HDV IgM and/or IgG antibodies is diagnostic. HDV IgM can usually be detected 10 days after symptoms develop; its presence suggests an acute infection. High titers of both HDV IgM antibodies and HDV IgG antibodies suggest chronic infection. A decrease in HDV IgM antibodies typically implies resolving HDV infection. Another useful serologic marker is the HDV RNA polymerase chain reaction (PCR) test. This can be used as an early marker of HDV replication in acute infection as well as to assess the effectiveness of HDV treatment.

HEPATITIS C

Previously knows as “non-A, non-B hepatitis,” HCV is spread through contact with blood from an infected patient. About 4 million Americans (1.8%) have hepatitis C, which is listed as an emerging infectious disease by the Institute of Medicine.8 According to the CDC, 5%-10% of HCV cases result from blood transfusions, 40% are due to IV drug use, 5% are associated with health-care occupational exposure, and 10% are caused by promiscuous heterosexual activity. Perinatal transmission has also been reported. The remainder of cases have no identifiable source of infection.7 On a positive note, the CDC estimates that the number of new acute HCV infections in the United States fell from about 230,000 per year in the 1980s to about 36,000 in 2005.9 In addition, since 1985, the number of blood transfusion related infections has decreased significantly and is now reduced to almost zero.

Symptoms


Hepatitis C can be either acute or chronic. Incubation lasts 60-150 days. However, seroconversion may take up to six months after infection and four months after onset of clinical hepatitis. HCV sequelae can vary. About 80% of newly infected individuals develop chronic infection.10 Of these patients, 10%-20% develop cirrhosis.10 Hepatocellular cancer occurs in 1%-5% of patients with chronic disease.10

Chronic infection is usually asymptomatic or presents with mild, nonspecific symptoms. The most common complaints are fatigue and jaundice, followed by anorexia, nausea, arthralgias, myalgias, weakness, and weight loss. Right upper-quadrant abdominal pain, pruritus, and dark urine may also occur. The presence of symptoms is not a reliable predictor of disease activity; however, symptoms are common once cirrhosis develops. Patients diagnosed with HCV infection should be referred to a hepatologist.

Diagnosis


HCV antigens can be detected three to four weeks after initial infection; HCV IgG antibodies usually can be seen two to three months after infection. Serologic diagnosis is based mainly on the presence of HCV IgG. 

The most sensitive and specific test is a third-generation enzyme immunoassay (EIA). With an estimated sensitivity of 97%, this test can detect HCV antibodies six to eight weeks after exposure. If the EIA is positive, a recombinant immunoblot assay (RIBA) is required for confirmation. The RIBA identifies the specific antigens to which the antibodies are reacting. Results can be positive (reaction to two or more antigens), indeterminate (reaction to one antigen), or negative. If the RIBA is indeterminate or negative, testing should be repeated within three to six months. 

Serum HCV RNA testing establishes ongoing infection; it is also used in managing chronic disease. Viral load can be detected by PCR within days of infection, although a positive result may not be seen until eight weeks after exposure. The results can vary depending on the method and laboratory. 
 

Another serologic test is HCV genotyping. This test determines the genotype of a viral strain; results are used to select the most appropriate treatment options. 

Although liver function tests in HCV-infected patients are usually unremarkable except for an occasional increase in ALT levels 6-12 weeks after infection, regular monitoring of liver function is essential. Although not required for diagnosis,  liver biopsy can be a useful aid in following the disease course and selecting treatment options.

Treatment


The goal of hepatitis C therapy is to eliminate the virus and prevent complications. Treatment is recommended for chronic HCV patients who are at increased risk of disease progression. This includes patients with increased aminotransferase levels, HCV viremia, and portal fibrosis or moderate inflammation on liver biopsy. Many patients (47%-68%) are not candidates for therapy because of such exclusionary factors as severe psychiatric illness, alcohol or substance abuse, and comorbid conditions.11 Treatment and duration of therapy is based on HCV genotype, of which there are six.

Standard treatment is a 48-week course of pegylated interferon plus ribavirin. Ribavirin dosing is weight-based, typically 1,000-1,200 mg daily.11 Common adverse effects include fatigue and flulike symptoms. Neutropenia, thrombocytopenia, arthralgias, myalgias, depression, nausea, cough, dyspnea, alopecia, and injection-site reactions have also been reported.

Although pegylated interferon plus ribavirin is the best available therapy option, it is only effective in about half of treatment-naïve patients.11 Favorable clinical and histologic outcomes are typically seen in those who achieve sustained virologic response, defined as the continued absence of HCV RNA six months after treatment cessation.12 The probability of attaining a sustained response can be predicted three months into treatment. For example, if HCV RNA does not decrease by 2 logs at three months, the likelihood of sustained response is ≤3%. In this situation, current treatment should be discontinued,12 and alternative options should be considered.

Hepatitis C is the most common indication for liver transplantation. Recurrence after transplantation is common. The five-year survival rate for HCV-infected transplant recipients is similar to that of those without HCV.12 Recent data, however, demonstrate decreased long-term survival with HCV.

PREVENTION

Prevention of viral hepatitis depends mainly on the form of virus and its mode of transmission. Maintaining good personal hygiene and proper sanitation are the best ways to prevent HAV infection. At-risk patients should be advised to wash their hands with soap after using the bathroom or changing a diaper as well as before cooking or dining. 

Prophylactic measures are similar for HBV and HCV infection. Latex condoms should be worn during sex. Drug users should be warned against sharing drugs, needles, syringes, and other “works.” At-risk patients should also avoid sharing such personal items as razors and toothbrushes.  

Vaccines now available for both HAV and HBV are the most effective measure to prevent infection and associated health consequences. 

Ms. Holloway and Ms. D’Acunto are physician assistants in the Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, in Pennsylvania.

References

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2. Hepatitis A – What Is It? Available at www.hepnet.com/hepa/hepafact.html. Accessed May 12, 2006.
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4. Hepatitis B: Fact Sheet. Available at www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm. Accessed May 12, 2006.
5. Lok A. Clinical manifestations and natural history of hepatitis B virus infection. In: UpToDate. Rose BD, ed. Wellesley, Mass.: UpToDate; 2000.
6. Ghany M, Doo E. Assessment and management of chronic hepatitis B. Infect Dis Clin North Am. 2006;20:63-79.
7. Taking Hepatitis Testing to New Levels. Available at www.questdiagnostics.com/hcp/topics/hepatitis/hepatitis.html?infectious. Accessed May 12, 2006.
8. What You Should Know About Hepatitis C. Available at www.healingwell.com/library/hepatitis/info5.asp. Accessed May 12, 2006.
9. Chopra S. Epidemiology and transmission of hepatitis C virus infection. In: UpToDate. Rose BD, ed. Wellesley, Mass.: UpToDate; 2005.
10. Hepatitis C. Available www.who.int/mediacentre/factsheets/fs164/en/. Accessed May 12, 2006.
11. Pearlman B. Hepatitis C treatment update. Am J Med. 2004;117:344-352.
12. Kim A, Saab S. Treatment of hepatitis C. Am J Med. 2005;118:808-815.