HEPATITIS C

'Hepatitis C' is a blood-borne, infectious, viral disease that is caused by a hepatotropic virus called ''Hepatitis C virus'' ('HCV'). Sherris Medical Microbiology, Ryan KJ; Ray CG (editors), , , McGraw Hill, 2004, ISBN 0838585299 The infection can cause liver inflammation (hepatitis) that is often asymptomatic, but ensuing chronic hepatitis can result later in cirrhosis (fibrotic scarring of the liver) and liver cancer.
The hepatitis C virus (HCV) is spread by blood-to-blood contact with an infected person's blood. The symptoms can be medically managed, and a proportion of patients can be cleared of the virus by a long course of anti-viral medicines. Although early medical intervention is helpful, people with HCV infection often experience mild symptoms, and consequently do not seek treatment. An estimated 150-200 million people worldwide are infected with hepatitis C. In the U.S., those with a history of intravenous drug use, inhaled drug usage, tattoos, or who have been exposed to blood via unsafe sex or social practices are increased risk for this disease. Hepatitis C is the leading cause of liver transplant in the United States.

Cirrhosis of the liver and liver cancer may ensue from Hepatitis C.

Contents

History

Signs and symptoms

Acute Hepatitis C

Chronic Hepatitis C

Virology

Diagnosis

Transmission

Methods of transmission

Vertical transmission

Epidemiology

Co-infection with HIV

Treatment and prognosis

During pregnancy and breastfeeding

Alternative therapies

Experimental treatments

Prevention

See also

References

External links

History

In the mid 1970s, Harvey J. Alter, Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the National Institutes of Health (NIH), and his research team demonstrated that most post-transfusion hepatitis cases were not due to hepatitis A and B viruses. Despite this discovery, international research effort to identify the virus, initially called ''non-A, non-B hepatitis'' (NANBH), failed for the next decade. In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation utilized molecular cloning to identify the unknown organism. In 1988, the virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April of 1989, the discovery of the virus, re-named hepatitis C virus (HCV), was published in two articles in the journal ''Science''. Dr. D.W. Bradley filed suit against Chiron, challenging the status of U.S. patent 5,350,671 covering HCV clones, diagnostics, and vaccines. Dr. Bradley sought to invalidate the patent, have himself included as a co-inventor, and receive damages and royalty income from Chiron. Dr. Bradley claimed he supplied Chiron with HCV-infected plasma that was instrumental in Chiron's isolation and cloning of HCV, that he developed critical findings about the virus, and that he provided Chiron with assistance regarding cloning methods. Dr. Bradley began work on what was then called non-A, non-B hepatitis in 1977 and the dispute between Dr. Bradley and Chiron can be traced back to 1986 when the parties failed to agree on terms for Dr. Bradley to provide infected plasma to Chiron. ^[1][2][3][4]

Signs and symptoms

Early studies of viral loads in eleven asymptomatically infected viral carriers (blood donors in 1989, prior to implementation of blood bank screening for HCV, and from whom the donated blood units were rejected because of elevated alanine transaminase (ALT) liver enzyme levels) indicated that asymptomatic viral loads in blood plasma varied between 100/mL and 50,000,000/mL.^[5]

Acute Hepatitis C

Acute hepatitis C refers to the first 6 months after infection with HCV. Between 60% to 70% of people infected develop no symptoms during the acute phase. In the minority of patients who experience acute phase symptoms, they are generally mild and nonspecific, and rarely lead to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms.
The hepatitis C virus is usually detectable in the blood within one to three weeks after infection, and antibodies to the virus are generally detectable within 3 to 12 weeks. Approximately 20-30% of persons infected with HCV clear the virus from their bodies during the acute phase as shown by normalization in liver function tests (LFTs) such as alanine transaminase (ALT) & aspartate transaminase (AST) normalization, as well as plasma HCV-RNA clearance (this is known as ''spontaneous viral clearance''). The remaining 70-80% of patients infected with HCV develop chronic hepatitis C, i.e., infection lasting more than 6 months.
Previous practice was to not treat acute infections to see if the person would spontaneously clear; recent studies have shown that treatment during the acute phase of genotype 1 infections has a greater than 90% success rate with half the treatment time required for chronic infections, but that the majority of acute hepatitis C is cleared. Treatment of acute hepatitis C with interferon alfa-2b, Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel M, Pastore G, Dietrich M, Trautwein C, Manns MP, , , New England Journal of Medicine, 2001

Chronic Hepatitis C

Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months. Clinically, it is often asymptomatic (without jaundice) and it is mostly discovered accidentally.
The natural course of chronic hepatitis C varies considerably from one person to another. Virtually all people infected with HCV have evidence of inflammation on liver biopsy, however, the rate of progression of liver scarring (fibrosis) shows significant variability among individuals. Recent data suggests that among untreated patients, roughly one-third progress to liver cirrhosis in less than 20 years. Another third progress to cirrhosis within 30 years. The remainder of patients appear to progress so slowly that they are unlikely to develop cirrhosis within their lifetimes. Factors that have been reported to influence the rate of HCV disease progression include age (increasing age associated with more rapid progression), gender (males have more rapid disease progression than females), alcohol consumption (associated with an increased rate of disease progression), HIV coinfection (associated with a markedly increased rate of disease progression), and fatty liver (the presence of fat in liver cells has been associated with an increased rate of disease progression).
Symptoms specifically suggestive of liver disease are typically absent until substantial scarring of the liver has occurred. However, hepatitis C is a systemic disease and patients may experience a wide spectrum of clinical manifestations ranging from an absence of symptoms to a more symptomatic illness prior to the development of advanced liver disease. Generalized signs and symptoms associated with chronic hepatitis C include fatigue, marked weight loss, flu-like symptoms, muscle pain, joint pain, intermittent low-grade fevers, itching, sleep disturbances, abdominal pain (especially in the right upper quadrant), appetite changes, nausea, diarrhea, dyspepsia, cognitive changes, depression, headaches, and mood swings.
Once chronic hepatitis C has progressed to cirrhosis, signs and symptoms may appear that are generally caused by either decreased liver function or increased pressure in the liver circulation, a condition known as portal hypertension. Possible signs and symptoms of liver cirrhosis include ascites (accumulation of fluid in the abdomen), bruising and bleeding tendency, bone pain, varices (enlarged veins, especially in the stomach and esophagus), fatty stools (steatorrhea), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy.
Liver function tests show variable elevation of ALAT, AST and GGTP and periodically they might show normal results. Usually prothrombin and albumin results are normal. The level of elevation of liver tests do not correlate well with the amount of liver injury on biopsy. Viral genotype and viral load also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring and inflammation. Radiographic studies such as ultrasound or CT scan do not show liver injury until it is fairly advanced.
Chronic hepatitis C, more than other forms of hepatitis, is diagnosed because of extrahepatic manifestations associated with the presence of HCV such as thyroiditis (inflammation of the thyroid) with hyperthyreosis or hypothyreosis, porphyria cutanea tarda, cryoglobulinemia (a form of vasculitis)^[6] and glomerulonephritis (inflammation of the kidney), specifically membranoproliferative glomerulonephritis (MPGN)^[7]. Hepatitis C is also associated with sicca syndrome, thrombocytopenia, lichen planus, diabetes mellitus and with B-cell lymphoproliferative disorders. Extrahepatic manifestations of Hepatitis C Virus infection: A general overview and guidelines for a clinical approach, Zignego AL, Ferri C, Pileri SA, Caini P, Bianchi FB; for the Italian Association of the Study of Liver (A.I.S.F.) Commission on Extrahepatic Manifestations of HCV infection, , , Dig Liver Dis., 2006

Virology

Main articles: Hepatitis C virus

The '''Hepatitis C virus''' ('HCV') is a small (50 nm in size), enveloped, single-stranded, positive sense RNA virus in the families ''Flaviviridae''.

Diagnosis

The diagnosis of "hepatitis C" is rarely made during the acute phase of the disease because the majority of people infected experience no symptoms during this phase of the disease. Those who ''do'' experience acute phase symptoms are rarely ill enough to seek medical attention. The diagnosis of chronic phase hepatitis C is also challenging due to the absence or lack of specificity of symptoms until advanced liver disease develops, which may not occur until decades into the disease.
Chronic hepatitis C may be suspected on the basis of the medical history (particularly if there is any history of IV drug abuse or inhaled substance usage such as cocaine), a history of piercings or tattoos, unexplained symptoms, or abnormal liver enzymes or liver function tests found during routine blood testing. Occasionally, hepatitis C is diagnosed as a result of targeted screening such as blood donation (blood donors are screened for numerous blood-borne diseases including hepatitis C) or contact tracing.
Hepatitis C testing begins with serological blood tests used to detect antibodies to HCV. Anti-HCV antibodies can be detected in 80% of patients within 15 weeks after exposure, in >90% within 5 months after exposure, and in >97% by 6 months after exposure. Overall, HCV antibody tests have a strong positive predictive value for exposure to the hepatitis C virus, but may miss patients who have not yet developed antibodies (seroconversion), or have an insufficient level of antibodies to detect. While uncommon, a small minority of people infected with HCV never develop antibodies to the virus and therefore, never test positive using HCV antibody screening.
Anti-HCV antibodies indicate exposure to the virus, but ''cannot'' determine if ongoing infection is present. All persons with positive anti-HCV antibody tests must undergo additional testing for the presence of the hepatitis C virus itself to determine whether current infection is present. The presence of the virus is tested for using molecular nucleic acid testing methods such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), or branched DNA (b-DNA). All HCV nucleic acid molecular tests have the capacity to detect not only whether the virus is present, but also to measure the amount of virus present in the blood (the HCV viral load). The HCV viral load is an important factor in determining the probability of response to interferon-based therapy, but does ''not'' indicate disease severity nor the likelihood of disease progression.
In people with confirmed HCV infection, genotype testing is generally recommended. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.). HCV genotype testing is used to determine the required length and potential response to interferon-based therapy.

Transmission