Hepatitis C virus

Six different hepatitis viruses have now been characterized. Hepatitis C virus (HCV), an RNA flavivirus, first identified in 1988 is the causative agent of Hepatitis C, an inflammation of the liver. HCV, a single-stranded microorganism is now known to cause most cases of what was previously termed non-A, non-B (NANB) hepatitis. This single-stranded agent causes the vast majority of post transfusion and sporadic NANB hepatitis. Because hepatitis C infection is due to an RNA virus, the processes of protein synthesis and viral replication occur within the cytoplasm of the liver cell rather than within the nucleus. Multiple HCV subtypes exist with varying amino acid sequences (genotypes); these subtypes vary geographically and play a role in disease virulence. HCV can also alter its amino acid pattern over time in an infected person (quasispecies); this propensity hampers development of an effective vaccine.

Most cases of hepatitis C are subclinical, even in the acute stage. The infection has a much higher rate of chronicity (about 75%) than hepatitis B. Thus, hepatitis C is often uncovered by the serendipitous detection of anti-HCV in apparently healthy persons. (Longmore, M)

Epidemiology HCV causes at least 80% of posttransfusion hepatitis cases and a substantial proportion of sporadic acute hepatitis cases. It is also implicated in many cases of chronic hepatitis, cryptogenic cirrhosis, and hepatocellular carcinoma unrelated to HBV.

Infection is most commonly acquired via blood, either from transfusion or IV drug use. Sexual transmission and vertical transmission from mother to infant can occur but, in contrast to HBV, are relatively rare. A small proportion of seemingly healthy persons are chronic HCV carriers, who often have subclinical chronic hepatitis or even cirrhosis. The prevalence varies with geography and other epidemiologic factors, including previous use of illicit drugs.

HCV is associated with essential mixed cryoglobulinemia, porphyria cutanea tarda (about 60 to 80% of porphyria patients have HCV, but only a few HCV patients develop porphyria), and perhaps glomerulonephritis and other "immune" disorders; the mechanisms are uncertain. In addition, up to 25% of patients with alcoholic liver disease also harbor HCV. The reasons for this surprisingly frequent association are unclear, because concomitant alcohol and drug abuse accounts for only a portion of cases. HCV may act synergistically to exacerbate alcohol-induced liver damage, and vice versa.

Areas of high prevalence in the world include Japan, the Far East, Mediterranean countries, and Africa.

 

 

Symptoms and Signs

Hepatitis varies from a minor flu-like illness to fulminant, fatal liver failure, depending on the patient's immune response and other poorly understood virus-host factors.

 In case of Hepatitis C, early infection is often mild and asymptomatic. When symptoms are present after an incubation period of 6 to 10 weeks, onset is gradual and often milder than with hepatitis A or B. Patients can present with jaundice (30%), fever (34%), abdominal pain (38%), fatigue, malaise, hepatomegaly (34%), mild splenomegaly (20%), and abnormal fluctuation of serum transaminase, AST and ALT (6 to 15 times normal).

 HCV presents more frequently as a chronic infection. Chronic infections are clinically asymptomatic until the patient develops cirrhosis or hepatocellular carcinoma (HCC). Progression from chronic disease to cirrhosis and liver cancer is more rapid in the elderly than in younger adults.

 Recrudescent hepatitis occurs in a few patients during the recovery phase. This does not imply chronicity, and the prognosis generally remains good. However, repeated recrudescences and aminotransferase fluctuations are relatively common in HCV infection and usually progress to chronicity

 

 

Laboratory Findings

Striking aminotransferase (liver enzymes) elevations are the hallmark of the disease. High values appear early in the prodromal phase, peak before jaundice is maximal, and fall slowly during the recovery phase. AST (aspartate transaminase) and ALT (alanine transaminase) are typically 500 to 2000 IU/L, although correlation with clinical severity is poor. The ALT is typically higher than the AST. Urinary bile usually precedes jaundice; its early detection is valuable for diagnosis.

Diagnosis

Diagnosis of hepatitis C is based on the presence of serum antibody (anti-HCV), which is not protective and implies active infection.

 First-generation serologic tests were often falsely positive, but newer second- and third-generation tests are more reliable. Anti-HCV often appears several weeks after acute infection, so a negative test does not exclude recent infection. Also, where available, RIBA (recombinant immunoblot assay) and HCV-PCR (polymerase chain reaction) are also used. Liver biopsy is done if HCV PCR +ve to assess degree of liver damage and need for treatment.

Recommendations.

 The recent NIH consensus development conference on the management of hepatitis C recommended the following diagnostic measures:

ELISA-2 (second-generation immunoassay anti-HCV antibody) should be the initial diagnostic test. In the presence of a positive risk factor and elevated liver transaminase, a positive ELISA-2 is diagnostic of hepatitis C infection.

When risk factors are not evident, ELISA-2 results should be supplemented by RIBA-2 and/or HCV RNA detected by PCR.

Qualitative HCV RNA PCR can be used for confirmation in patients with clinical findings of liver disease.

Prognosis

Hepatitis C has the highest likelihood of chronicity,  ~85% develop chronic infection and 20-30% get cirrhosis within 20 years; Hepatocellular carcinoma is a risk in HCV-induced cirrhosis, although tumors appear only rarely in noncirrhotic cases of chronic infection (unlike HBV infection).

Chronic infection with hepatitis C is believed to be the single most important cause of chronic liver disease, cirrhosis, and liver cancer in the Western world. Two to 4 million Americans may be chronically infected with hepatitis C, and 30,000 new cases are identified each year, according to the Centers for Disease Control and Prevention.

Prevention

Post transfusion infection with hepatitis C has been dramatically decreased by universal screening of donors, avoiding unnecessary transfusions, and use of volunteers rather than paid donors. Expansions of needle exchange programs are of proven

benefit in reducing parenterally transmitted diseases and should be considered in an effort to reduce the rate of transmission of hepatitis C.

 Recent evidence indicates that chronic hepatitis C can largely be prevented if acute infection is treated with interferon- alpha; dosage is 5 million IU subcutaneously daily for 4 weeks, then three times weekly for another 20 weeks. However only a small proportion of HCV infection is recognized in the acute phase, so this will have little impact on the overall prevalence of chronic disease.

There is no vaccine against HCV.

Treatment

    Several antiviral therapies have been tried for the treatment of hepatitis C. Most of the available data pertains to interferon alpha-2b (Intron).

Interferon. Most studies have demonstrated that 3 million units of interferon alpha-2b given subcutaneously three times a week usually for 6 months produce a decrease in serum transaminase and a reduction in viremia. Response usually occurs within 2 to 3 months. However, recurrence of the infection is noted in 40 to 50% of cases after cessation of therapy. Retreatment of recurrence with interferon alpha-2b can be beneficial. The NIH consensus panel recommended treatment for 12 months with interferon alpha-2b.

Ribavirin (Virazole), a nucleotide analog, produces a decrease in serum alanine aminotransferase (ALT). However, this effect is slower than with interferon and is reversible upon discontinuation of therapy.

Combination therapy has also shown some promise and is being investigated.

Recently, a study conducted by some researchers has supported earlier hints that the virus responsible for hepatitis C can spread via transplanted organs, as is the case with hepatitis B. This finding may compel organ banks to begin screening donor tissues for evidence of the hepatitis C virus, says Andrew S. Levey of the New England Organ Bank in Brookline, Mass

Another case-control study published in American Journal of Public Health, Oct94, Vol. 84 Issue 10, showed surgical intervention and dental therapy to be strongly associated with anti-HCV-positive cases: in particular, obstetric and gynecology surgical interventions. ( Mele)   

 

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