Hepatitis C is a blood borne liver disease, caused by the hepatitis C virus (HCV). First identified in 1989, the disease was initially known as "Non-A, Non-B Hepatitis". The hepatitis C virus belongs to the Flaviviridae family of viruses, and is spread primarily through direct contact with the blood or bodily fluids of infected individuals. HCV infection is a leading cause of chronic liver disease, including cirrhosis of the liver. With an estimated 3% of the world's population currently infected with hepatitis C, and approximately 170 million persons at risk of fulminant hepatitis disease, the World Health Organization (WHO) recognizes hepatitis C as a global health problem. The high prevalence of hepatitis C, and the need to understand its epidemiology, warrants global surveillance of the disease in order to determine specific health care measures for disease prevention and control.

Natural History of Infection:

The hepatitis C virus is a small, enveloped, RNA virus. Although humans are the only known reservoir of HCV, the virus has been successfully transmitted to chimpanzees in experimental settings. Given its high rate of mutation, at least 6 distinct clades of HCV, and more than 100 subtypes, have been identified by nucleotide sequencing (see Virology). Clades 1-3 have a worldwide distribution; clades 4 and 5 are found largely in Africa; and clade 6 is confined largely to Asia (1). Differences in pathogenicity, as well as responsiveness to treatment, have been reported among the different clades.

Testing for an HCV infection typically involves analyzing of a serum sample for anti-HCV antibody, and for viral  genomic DNA. However, current diagnostic tests are often limited in the sensitivity with which they can detect genetically and serologically altered HCV strains (see Current Therapeutic Techniques) (1).

Primary exposure to the hepatitis C virus leads to an acute infection which is usually relatively mild. Only 20-30% of infected individuals develop clinically evident acute Hepatitis C in their attempt to resolve the infection. Symptoms include jaundice, fatigue, abdominal pain, and intermittent nausea (2). More significant however, are the 70-80% of acute HCV infections that do not resolve, but lead to persistent viral infections. The sequelae of chronic HCV infections include cirrhosis of the liver as well as hepatocellular carcinoma, both of which carry significant socio-economic costs and public health consequences. In developed countries, HCV-related liver disease is currently the leading cause of liver transplantation (3).
 

Figure 1  Hepatocellular Carcinoma (HCC) HCC is one of the most important sequelae of chronic HCV infection (JHU, Division of Infect. Diseases) (4)	Figure 2  Cirrhosis of the Liver Cirrhosis occurs in approximately 20% of HCV-infected individuals. (JHU, Division of Infect.Diseases) (4)

Chronic hepatitis C is a progressive condition that accounts for at least one quarter of all cases of chronic liver disease. However, a significant proportion of chronic HCV infections are asymptomatic; patients posses normal liver enzymes and relatively normal liver histology. Progression of the disease is slow in these patients, and they can remain asymptomatic for several years (7). Thus, the lag period between clinical morbidity and mortality and  histologic progression can be substantial. However, given a sufficiently long observation period, chronic hepatitis C ultimately always progresses to fulminant liver disease. Therefore, preventing or retarding disease progression is a valid goal in reducing the burden of hepatitis C disease. 

The mechanism of liver injury in acute and chronic hepatitis C is unknown, but since there is little evidence as to the cytopathogenicity of HCV, it is thought that liver damage may in fact be mediated by the host's cellular immune response to the infection (see Pathology). Given the lack of definitive symptoms, liver histology and the circulating levels of liver enzymes are currently considered to be the most reliable predictors of progression to cirrhosis (5, 7). Studies show that severe necroinflammatory activity, as well as severe fibrosis in hepatic tissue - both due to elevated levels of liver enzymes - can be correlated with progression to cirrhosis within 10 years. In cases where inflammation and fibrosis is mild, progression is slowed and even limited (7). Thus, individuals with normal levels of enzymes progress more slowly towards disease than those with elevated levels of the same enzymes (5). 

Factors influencing the rate of progression of chronic hepatitis C to cirrhosis and liver cancer include alcohol abuse, the duration of the infection, and, possibly, viral titer. In addition, viral genotype, co-infection with another type of hepatitis virus, co-infection with the human immunodeficiency virus (HIV), and gender, have all been thought to play a role in the progression of disease (5). Unfortunately, conclusive evidence about the exact role and impact of these factors is lacking. 

Prevalence:

The prevalence of hepatitis C is not well-documented in many countries, partly due to the expense and practical difficulties involved in the detection of HCV RNA in the serum of infected individuals (see Current Therapeutic Techniques). Based on the statistics that are available, it is estimated that 3% of the world population is infected with the hepatitis C virus (6). Most populations in the Americas, Europe, and South-East Asia have HCV prevalence rates of under 2.5%. In the Western Pacific regions and parts of South America,  prevalence rates are higher - between 2.5-4.9%. In contrast, in populations in the Middle East and Africa, HCV prevalence has been shown to range from 1-12%.

In the United States, HCV infection is the most common chronic blood borne infection, and is a significant contributor to the incidence of chronic liver disease. The Centers for Disease Control and Prevention (CDC) estimates that some 3.9 million Americans (1.8% of the US population) have been infected with the virus to date. 2.7 million of these individuals suffer from chronic infection. Infected individuals serve as a source of transmission to others, and are themselves at risk for chronic liver disease and other HCV-related illnesses during the first two or more decades following initial infection.

Chronic liver disease is the tenth leading cause of death among adults in the United States, and accounts for around 25,000 deaths annually. According to recent population based studies, approximately 40% of the cases of chronic liver disease are HCV-related, resulting in 8,000-10,000 deaths per annum (3).

Primary Modes of Transmission:

• Blood - Because HCV is a blood borne virus, the transfusion of blood and blood products, as well as the transplant of organs that have not undergone viral inactivation, are all potential sources of HCV transmission. Today, standard screening procedures have reduced the risk of HCV transmission through blood in the developed world. However, the problem has not been dealt with as effectively in the developing world, where medical and health care facilities are limited. Parenteral exposure to contaminated blood is also a risk factor for transmission. Therefore, the sharing of needles among intravenous drug users, inadequately sterilized instruments used in medical procedures, tattooing, and body piercing, are all considered high risk activities in the context of HCV transmission.

• Sexual Contacts - Studies to date indicate that there is a marginal risk of HCV transmission involved in regular sexual contact, and that this risk increases noticeably in the case of an HCV-infected individual with multiple partners. The reasons behind this discrepancy are not known, but the frequency of sexual contact is likely to be one factor (5). 

• Vertical Transmission- Mother-to-infant transmission of HCV has been observed globally, but the risk has typically been less than 5%, unless the mother is co-infected with the human immunodeficiency virus (HIV). There has been no association between HCV transmission and breast-feeding. From a public health perspective, no specific recommendations for preventing the vertical transmission of HCV been made (5). More research is needed to determine risk and outcome before public health guidelines may be put into effect.

• Nosocomial Infections - Nosocomial transmission of HCV is possible when disinfection and sterilisation techniques are inadequate, and contaminated equipment is shared among patients. In particular, studies have indicated the possibility of an HCV infection occurring among patients on hemodialysis, due to poor infection control, and the sharing of contaminated medical vials and supplies (6).

2.  Centers for  Disease Control and Prevention Web site on Hepatitis C: http://www.cdc.gov/

3. Morbidity and Mortality Weekly Report. Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease. CDC MMWR 47, 1998.

4. The Johns Hopkins University, Division of Infectious Diseases: http://hopkins-id.edu/diseases/hepatitis.html

5. Lavanchy D. Global Surveillance and Control of Hepatitis C. Journal of Viral Hepatitis 6:35-47, 1999.

6. World Health Organization. Hepatitis C - Global Surveillance Update. Weekly Epidemiological Record 75:17-28, 2000.

7. Dienstag JL. Concise Review: Current Approaches to the Management of Chronic Hepatitis C: http://harrisonsonline.com/
 
 

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