Hepatitis C Virus

Basic Virology and Epidemiology

Hepatitis C virus (HCV) is a flavivirus that was determined in 1989 to be the major cause of transfusion-related "non-A, non-B" hepatitis. It is a single-stranded, plus sense RNA virus with a genome size of approx 9500 bp. It encodes for a single large polyprotein that is cleaved to form individual viral proteins. The virus displays marked heterogeneity, with six distinct genotypes, and numerous quasi-species attributable to "hypervariable" regions of the two envelope proteins that readily mutate. Currently, there is no established cell culture system for HCV, and chimpanzees are the only available laboratory animal model, so little is still known about the mechanisms of infection (2,3,8).

HCV is spread primarily by blood-borne contact with infected blood. The most common risk factors identified are intravenous drug use and blood transfusion or transplantation prior to 1992. Sexual acquisition of the virus is a very inefficient form of transmission and has not been proven definitively in the absence of confounding risk factors. The prevalence of HCV infection in the United States is approx 2%, and in 1999 chronic HCV infection and subsequent liver failure were the leading indications for liver transplantation (8,9).

Course of Infection

HCV, when transmitted via blood-borne contact, usually causes an acute subclinical hepatitis. HCV then commonly progresses to chronic hepatitis that is also relatively asymptomatic. Symptoms are indolent when they do occur, sometimes months to years later, and include fever, fatigue, and jaundice. Patients may present with only signs of end-stage liver disease. Fulminant hepatic failure with HCV is exceedingly rare (8).

Extrahepatic manifestations of HCV can occur and are primarily the result of immune complex deposition. These include mixed cryoglobulinemia, a chronic purpuric rash concentrated on the lower extremities, and porphyria cutanea tarda, which consists of bullous skin lesions and ulceration on sun-exposed areas coupled with elevated urinary porphyrin levels (8,10).

Infection During Pregnancy

Acute HCV infection can occur during pregnancy. It is more common to see a pregnant patient who either has a known chronic HCV infection or has chronic infection diagnosed during her prenatal evaluation. HCV infection has not been shown to be more severe during pregnancy or to more rapidly progress during pregnancy (2,3).

Vertical Transmission

HCV is transmitted vertically, but the rate is low in the absence of other risk factors. Most studies have shown 5-10% of infants acquire the virus from infected mothers (11-13). Mothers with HIV co-infection have a much higher rate of vertical transmission of HCV, but the mechanism for this is not known. HIV co-infection leads to an HCV transmission rate of approx 20% in some studies (11-13). The mode of delivery has not been shown to affect transmission rates in HCV-infected mothers, but data indicate that cesarean section may protect against transmission in the HCV and HIV co-infected mother (14).

HCV infection in the newborn behaves differently from that in adults. Newborns establish chronic infection at a much lower rate than do older children and adults. It is not uncommon to see an infant who has detectable HCV RNA at birth that resolves spontaneously several months later. The reasons for this observation have not been explained (13,15-17).

Studies of the potential of breast-feeding transmission have found a very low rate of infection to date (15-18). Discussions about the nonnutritional benefits of breast-feeding should take place before recommending for or against breast-feeding in an HCV-infected mother (11,19,20).

Prenatal Assessment

Testing for HCV currently is not offered routinely. Prenatal assessment for HCV should include a thorough social history to assess for possible risk factors. Questions regarding intravenous drug use, transfusion history prior to 1992, or any other potential blood-borne contact should raise concern (9). Physical exam, in addition to examination of the abdomen for liver size or tenderness, should also include inspection of the skin for other manifestations of HCV infection.

Laboratory assessment should include liver function tests if indicated by history or physical exam and if abnormal in the absence of symptoms should raise suspicion for HCV. Patients already infected with HIV should be tested for HCV because many of the risk factors overlap. The opposite is also true.

Postnatal Evaluation of the Infant

At birth, infants born to HCV-infected mothers should have no detectable symptoms or abnormalities on physical exam. Disease in the newborn period from HCV is uncommon.

Laboratory Evaluation of Mother and Infant

Laboratory studies should begin with an assay for anti-HCV antibody in the mother. Anti-HCV antibody should begin to appear 2-3 weeks after acute illness. If the infection is acute, PCR for HCV RNA in plasma can be obtained and is positive early in the infection. If the mother is a chronically infected patient, a quantitative level of HCV RNA may be helpful. Studies have shown that very high levels of maternal plasma HCV RNA correlate with vertical transmission.

At this time, there are no established guidelines for testing infants born to HCV-positive mothers (2,3). PCR for HCV RNA is the most useful assay in the first year of life because maternal antibody may be present for several months. Some studies indicate that the best time for the first PCR for HCV RNA is at 1 month of age (21). If the HCV RNA is negative at 1 month, the infant should be followed, and repeat testing should be done at later points, such as 6 months and 1 year. Infected infants may have elevations of alanine aminotransferase and high levels of plasma HCV RNA. These values, however, do not necessarily correlate with ultimate chronic infection. There are no current established predictive laboratory evaluations to distinguish infants in whom infections will resolve from those who will develop chronic infections. Acute infection may resolve in infants, as indicated by absence of detectable HCV RNA. If the infant is still positive for HCV RNA after 1 year of age, it is likely that chronic infection has been established. Children with positive HCV RNA assays after 1 year of age should be followed by a specialist experienced in management of HCV-infected children.

Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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