Hepatitis C 71491 225965099 2008-07-16T06:19:38Z Dreadstar 690391 Reverted edits by [[Special:Contributions/76.18.221.141|76.18.221.141]] to last version by Jfdwolff (using [[WP:HG|Huggle]]) {{dablink|This page is for the disease. For the virus, see [[Hepatitis C virus]].}} {{Infobox_Disease | Name = Hepatitis C | Image = Em_flavavirus-HCV_samp1c.jpg| Caption = ''Electron Microscopy of HCV''| DiseasesDB = 5783 | ICD10 = {{ICD10|B|17|1|b|15}}, {{ICD10|B|18|2|b|15}} | ICD9 = {{ICD9|070.4}}, {{ICD9|070.5}} | ICDO = | OMIM = 609532 | MedlinePlus = 000284 | eMedicineSubj = med | eMedicineTopic = 993 | eMedicine_mult = {{eMedicine2|ped|979}} | MeshID = D006526 | }} '''Hepatitis C''' is a [[Blood-borne disease|blood-borne]] infectious disease that is caused by the [[Hepatitis C virus]] ('''HCV'''), affecting the [[liver]].<ref name=Sherris>{{cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | pages=pp. 551&ndash;2 | id = ISBN 0838585299 }}</ref> The infection is often asymptomatic, but once established, chronic infection can cause inflammation of the liver (chronic [[hepatitis]]). This condition can progress to scarring of the liver ([[fibrosis]]), and advanced scarring ([[cirrhosis]]). In some cases, those with cirrhosis will go on to develop [[liver failure]] or other complications of cirrhosis, including [[hepatocellular carcinoma|liver cancer]]. The hepatitis C virus (HCV) is spread by blood-to-blood contact. No vaccine against hepatitis C is available. The symptoms of infection can be medically managed, and a proportion of patients can be cleared of the virus by a course of anti-viral medicines. Although early medical intervention is helpful, people with HCV infection can experience mild symptoms, and consequently do not seek treatment.<ref name=Sherris /> An estimated 150-200 million people worldwide are infected with hepatitis C. Hepatitis C (originally "non-A non-B hepatitis") is one of five known [[hepatitis]] viruses: [[hepatitis A|A]], [[hepatitis B|B]], C, [[hepatitis D|D]], and [[hepatitis E|E]]. == 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]], and his research team demonstrated that most post-[[blood transfusion|transfusion]] hepatitis cases were not due to [[hepatitis A]] and [[Hepatitis B|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]], collaborating with Dr. D.W. Bradley from [[CDC]], utilized a novel [[molecular cloning]] approach to identify the unknown organism.<ref>[http://www.laskerfoundation.org/awards/library/2000c_cit.shtml 2000 Albert Lasker Award for Clinical Medical Research], The Lasker Foundation. Accessed 20 February 2008</ref> 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''. <!-- --><ref name="choo">{{cite journal | author = Choo Q, Kuo G, Weiner A, Overby L, Bradley D, Houghton M | title = Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. | journal = Science | volume = 244 | issue = 4902 | pages = 359–62 | year = 1989 | pmid = 2523562 | doi = 10.1126/science.2523562}}</ref><!-- --><ref name="kuo">{{cite journal | author = Kuo G, Choo Q, Alter H, Gitnick G, Redeker A, Purcell R, Miyamura T, Dienstag J, Alter M, Stevens C | title = An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. | journal = Science | volume = 244 | issue = 4902 | pages = 362–4 | year = 1989 | pmid = 2496467 | doi = 10.1126/science.2496467}}</ref> Chiron filed for several patents on the virus and its diagnosis.<!-- --><ref name="houghton">Houghton, M., Q.-L. Choo, and G. Kuo. ''NANBV Diagnostics and Vaccines.'' European Patent No. EP-0-3 18-216-A1. European Patent Office (filed [[18 November]] [[1988]], published [[31 May]] [[1989]]).</ref> A competing patent application by the CDC was dropped in 1990 after Chiron paid $1.9 million to the CDC and $337,500 to Bradley. In 1994 Bradley sued Chiron, seeking to invalidate the patent, have himself included as a co-inventor, and receive damages and royalty income. He dropped the suit in 1998 after losing before an appeals court.<ref name=elias>Paul Elias. "[http://www.hcvadvocate.org/news/newsRev/2004/NewsRev-37.html#15 "Hepatitis Drug-Maker Complaints Reviewed"], ''The Associated Press'', 27 February 20</ref> In 2000, Drs. Alter and Houghton were honored with the [[Lasker Award|Lasker Award for Clinical Medical Research]] for "pioneering work leading to the discovery of the virus that causes hepatitis C and the development of screening methods that reduced the risk of blood transfusion-associated hepatitis in the U.S. from 30% in 1970 to virtually zero in 2000."<ref>[http://www.laskerfoundation.org/awards/library/2000clinical.shtml 2000 Winners Albert Lasker Award for Clinical Medical Research], The Lasker Foundation. Accessed 20 February 2008.</ref> In 2004 Chiron held 100 patents in 20 countries related to hepatitis C and had successfully sued many companies for infringement. Scientists and competitors have complained that the company hinders the fight against hepatitis C by demanding too much money for its technology.<ref name=elias/> == Signs and symptoms == Early studies of [[viral load]]s in eleven asymptomatic viral carriers indicated that asymptomatic viral loads in blood plasma varied between 100/mL and 50,000,000/mL.<ref name="ulrich">{{cite journal | author = Ulrich P, Romeo J, Lane P, Kelly I, Daniel L, Vyas G | title = Detection, semiquantitation, and genetic variation in hepatitis C virus sequences amplified from the plasma of blood donors with elevated alanine aminotransferase. | journal = J Clin Invest | volume = 86 | issue = 5 | pages = 1609–14 | year = 1990 | pmid = 2173725 | url=http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=2173725 | format=PDF & scanned pages | doi = 10.1172/JCI114882}}</ref> [[Image:Liver 1.jpg|thumb|right|[[cirrhosis|Cirrhosis of the liver]] and [[hepatocellular carcinoma|liver cancer]] may ensue from Hepatitis C.]] ===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 15-40% 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 60-85% of patients infected with HCV develop [[chronic (medicine)|chronic]] hepatitis C, i.e., infection lasting more than 6 months.<ref name="pmid10051497">{{cite journal |author=Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL |title=Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection |journal=Hepatology |volume=29 |issue=3 |pages=908–14 |year=1999 |pmid=10051497 |doi=10.1002/hep.510290311}}</ref><ref name="pmid15824985">{{cite journal |author=Cox AL, Netski DM, Mosbruger T, ''et al'' |title=Prospective evaluation of community-acquired acute-phase hepatitis C virus infection |journal=Clin. Infect. Dis. |volume=40 |issue=7 |pages=951–8 |year=2005 |pmid=15824985 |doi=10.1086/428578}}</ref><ref name="titleNIH Consensus Development Conference on Management of Hepatitis C: 2002">{{cite web |url=http://consensus.nih.gov/2002/2002HepatitisC2002116main.htm |title=NIH Consensus Development Conference on Management of Hepatitis C: 2002 |accessdate=2008-02-22 |format= |work=}}</ref> 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.<ref name=Jaeckel><!-- -->{{cite journal | author = Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel M, Pastore G, Dietrich M, Trautwein C, Manns MP | title = Treatment of acute hepatitis C with interferon alfa-2b | journal = New England Journal of Medicine | year = 2001 | month = Nov | volume = 345 | issue = 20 | pages = 1452–1457 | pmid = 11794193 | doi = 10.1056/NEJMoa011232}}</ref> === 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 symptoms) 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 [[serum albumin|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]])<!-- --><ref name="pascual">{{cite journal | author = Pascual M, Perrin L, Giostra E, Schifferli J | title = Hepatitis C virus in patients with cryoglobulinemia type II. | journal = J Infect Dis | volume = 162 | issue = 2 | pages = 569–70 | year = 1990 | pmid = 2115556}}</ref><!-- --> and [[glomerulonephritis]] (inflammation of the kidney), specifically [[membranoproliferative glomerulonephritis]] (MPGN)<!-- -->.<ref name="johnson">{{cite journal | author = Johnson R, Gretch D, Yamabe H, Hart J, Bacchi C, Hartwell P, Couser W, Corey L, Wener M, Alpers C | title = Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. | journal = N Engl J Med | volume = 328 | issue = 7 | pages = 465–70 | year = 1993 | pmid = 7678440 | doi = 10.1056/NEJM199302183280703}}</ref> Hepatitis C is also associated with [[sicca]] syndrome, [[thrombocytopenia]], [[lichen planus]], [[diabetes mellitus]] and with B-cell [[lymphoproliferative disorder]]s.<!-- --><ref name=Extrahepatic>{{cite journal | author = 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 | title = Extrahepatic manifestations of Hepatitis C Virus infection: A general overview and guidelines for a clinical approach | journal = Dig Liver Dis. | volume = | issue = | pages = E-publication | year = 2006 | pmid = 16884964}}</ref> == Virology == {{main|Hepatitis C virus}} The '''''Hepatitis C virus''''' ('''HCV''') is a small (50 [[metre#SI prefixes|nm]] in size), enveloped, single-stranded, positive sense [[RNA virus]]. It is the only known member of the ''hepacivirus'' genus in the family ''[[Flaviviridae]]''. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.). == 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 [[tattoo]]s, 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]]. [[Image:Hepatitis C serology.png|thumb|right|300px|Serologic profile of Hepatitis C infection]] Hepatitis C testing begins with [[serology|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. Rarely, people infected with HCV never develop antibodies to the virus and therefore, never test positive using HCV antibody screening. Because of this possibility, RNA testing (see nucleic acid testing methods below) should be considered when antibody testing is negative but suspicion of hepatitis C is high (e.g. because of [[elevated transaminases]] in someone with risk factors for hepatitis C). 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. HCV genotype testing is used to determine the required length and potential response to interferon-based therapy. == Transmission == [[Image:Sources of Infection for Persons with Hepatitis C (CDC) US.png|thumb|350px|right|CDC figures for sources of infection in the US. [http://www.cdc.gov/ncidod/diseases/hepatitis/c/plan/HCV_infection.htm Source]]] The hepatitis C virus (HCV) is transmitted by blood-to-blood contact. In developed countries, it is estimated that 90% of persons with chronic HCV infection were infected through transfusion of unscreened blood or blood products or via injecting drug use or by inhalational drug use. In developing countries, the primary sources of HCV infection are unsterilized injection equipment and infusion of inadequately screened blood and blood products. Although injection drug use and receipt of infected blood/blood products are the most common routes of HCV infection, ''any'' practice, activity, or situation that involves blood-to-blood exposure can potentially be a source of HCV infection. The virus may be [[sexually transmitted disease|sexually transmitted]], although this is rare, and usually only occurs when an STD (like [[HIV]]) is also present and makes blood contact more likely.<ref>''[http://www.plannedparenthood.org/sexual-health/std/hepatitis.htm What is hepatitis?]'', [[Planned Parenthood]], accessed May 15, 2007</ref>. === Methods of transmission === Several activities and practices have been identified as potential sources of exposure to the hepatitis C virus. Anyone who may have been exposed to HCV through one or more of these routes should be screened for hepatitis C. ; Injection drug use Those who currently use or have used [[drug injection]] as their delivery route for illicit drugs are at increased risk for getting hepatitis C because they may be sharing needles or other [[drug paraphernalia]] (includes cookers, cotton, spoons, water, etc.), which may be contaminated with HCV-infected blood. An estimated 60% to 80% of all IV drug users in the United States have been infected with HCV.<ref name="url">{{cite web |url=www.cdc.gov/ncidod/diseases/hepatitis/partners/nvhpc_2005/Thursday/PL4Alter.ppt |title=HCV Prevalence in Selected Groups of Adults by History of Injection Drug Use |format= |work= |accessdate=2008-06-03}}</ref> [[Harm reduction]] strategies are encouraged in many countries to reduce the spread of hepatitis C, through education, provision of clean needles and syringes, and safer injecting techniques. ; Drug use by nasal inhalation (Drugs that are "snorted") Researchers have suggested that the transmission of HCV may be possible through the nasal inhalation (insuffulation) of illegal drugs such as cocaine and crystal methamphetamine when straws (containing even trace amounts of mucus and blood) are shared among users.<ref name=Thompson_1996>{{cite journal |author=Thompson S, Hernberger F, Wale E, Crofts N |title=Hepatitis C transmission through tattooing: a case report |journal=Aust N Z J Public Health |volume=20 |issue=3 |pages=317–8 |year=1996 |pmid=8768424 |doi=10.1111/j.1467-842X.1996.tb01035.x}}</ref> ; Blood products [[Blood transfusion]], blood products, or [[organ transplantation]] prior to implementation of HCV screening (in the U.S., this would refer to procedures prior to 1992) is a decreasing risk factor for hepatitis C. The virus was first isolated in 1989 and reliable tests to screen for the virus were not available until 1992. Therefore, those who received blood or blood products prior to the implementation of screening the blood supply for HCV may have been exposed to the virus. Blood products include clotting factors (taken by [[hemophilia]]cs), immunoglobulin, Rhogam, platelets, and plasma. In 2001, the Centers for Disease Control and Prevention reported that the risk of HCV infection from a unit of transfused blood in the United States is less than one per million transfused units. ; Iatrogenic medical or dental exposure People can be exposed to HCV via inadequately or improperly sterilized medical or dental equipment. Equipment that may harbor contaminated blood if improperly sterilized includes needles or syringes, hemodialysis equipment, [[oral hygiene]] instruments, and jet air guns, etc. Scrupulous use of appropriate sterilization techniques and proper disposal of used equipment can reduce the risk of iatrogenic exposure to HCV to virtually zero. ; Occupational exposure to blood Medical and dental personnel, first responders (e.g., firefighters, paramedics, emergency medical technicians, law enforcement officers), and military combat personnel can be exposed to HCV through accidental exposure to blood through accidental needlesticks or blood spatter to the eyes or open wounds. Universal precautions to protect against such accidental exposures significantly reduce the risk of exposure to HCV. ; Recreational exposure to blood [[Contact sports]] and other activities, such as "[[slam dancing]]" that may result in accidental blood-to-blood exposure are potential sources of exposure to HCV.<ref name="Karmochkine2006">{{cite journal |author=Karmochkine M, Carrat F, Dos Santos O, Cacoub P, Raguin G |title=A case-control study of risk factors for hepatitis C infection in patients with unexplained routes of infection |journal=J. Viral Hepat. |volume=13 |issue=11 |pages=775–82 |year=2006 |pmid=17052278 |doi=10.1111/j.1365-2893.2006.00742.x}}</ref> ; Sexual exposure Sexual transmission of HCV is considered to be rare. Studies show the risk of sexual transmission in heterosexual, monogamous relationships is extremely rare or even null.<ref>[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15128350&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Lack of evidence of sexual transmission of hepatit...[Am J Gastroenterol. 2004&#93; - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.hepatitis-central.com/mt/archives/2007/04/heterosexual_mo.html Hepatitis Central News, Updates and Commentary<!-- Bot generated title -->]</ref> The CDC does not recommend the use of condoms between long-term monogamous discordant couples (where one partner is positive and the other is negative).<ref>[http://www.cdc.gov/ncidod/diseases/hepatitis/c/faq.htm#3d Hepatitis C: FAQ | CDC Viral Hepatitis<!-- Bot generated title -->]</ref> However, because of the high prevalence of hepatitis C, this small risk may translate into a non-trivial number of cases transmitted by sexual routes. Vaginal penetrative sex is believed to have a lower risk of transmission than sexual practices that involve higher levels of trauma to anogenital mucosa (anal penetrative sex, fisting, use of sex toys).<ref name="Hanh2007">{{cite journal | author=Hahn JA | year=2007 | journal=J Infect Dis | volume=195 | pages=1556&ndash;9 | title=Sex, Drugs, and Hepatitis C Virus | doi = 10.1086/516792}}</ref> ; Body piercings and tattoos Tattooing dyes, ink pots, stylets and piercing implements can transmit HCV-infected blood from one person to another if proper sterilization techniques are not followed. Tattoos or piercings performed before the mid 1980s, "underground," or non-professionally are of particular concern since sterile techniques in such settings may have been or be insufficient to prevent disease. Despite these risks, it is rare for tattoos to be directly associated with HCV infection and the U.S. Centers for Disease Control and Prevention's position on this subject states that, "no data exist in the United States indicating that persons with exposures to tattooing alone are at increased risk for HCV infection."<ref name="urlHepatitis C: Tattoo | CDC Viral Hepatitis">{{cite web |url=http://www.cdc.gov/ncidod/diseases/hepatitis/c/tattoo.htm |title=Hepatitis C: Tattoo | CDC Viral Hepatitis |format= |work= |accessdate=2008-06-18}}</ref> ; Shared personal care items Personal care items such as razors, toothbrushes, cuticle scissors, and other manicuring or pedicuring equipment can easily be contaminated with blood. Sharing such items can potentially lead to exposure to HCV. Appropriate caution should be taken regarding any medical condition which results in [[bleeding]] such as [[aphthous ulcer|canker sores]], [[oral ulcer|cold sores]], and immediately after [[flossing]]. HCV is ''not'' spread through casual contact such as hugging, kissing, or sharing eating or cooking utensils.<ref name="urlHepatitis C: FAQ | CDC Viral Hepatitis">{{cite web |url=http://www.cdc.gov/ncidod/diseases/hepatitis/c/faq.htm#5d |title=Hepatitis C: FAQ | CDC Viral Hepatitis |format= |work= |accessdate=2008-06-13}}</ref> === Vertical transmission === [[Vertical transmission]] refers to the transmission of a communicable disease from an infected mother to her child during the birth process. Mother-to-child transmission of hepatitis C has been well described, but occurs relatively infrequently. Transmission occurs only among women who are HCV RNA positive at the time of delivery; the risk of transmission in this setting is approximately 6 out of 100. Among women who are both HCV and HIV positive at the time of delivery, the risk of HCV is increased to approximately 25 out of 100. The risk of vertical transmission of HCV does ''not'' appear to be associated with method of delivery or breast feeding. == Epidemiology == Hepatitis C infects an estimated 170 million people worldwide and 4 million in the United States. There are about 35,000 to 185,000 new cases a year in the United States, and hepatitis C is the leading cause of liver transplant in the USA. Co-infection with [[HIV]] is common and rates among HIV positive populations are higher. 10,000-20,000 deaths a year in the United States are from HCV; expectations are that this mortality rate will increase, as those who were infected by transfusion before HCV testing become apparent. A survey conducted in California showed prevalence of up to 34% among prison inmates;<!-- --><ref>{{cite journal | author = Ruiz J, Molitor F, Plagenhoef J | title = Trends in hepatitis C and HIV infection among inmates entering prisons in California, 1994 versus 1999. | journal = AIDS | volume = 16 | issue = 16 | pages = 2236–8 | year = 2002 | pmid = 12409752 | doi = 10.1097/00002030-200211080-00023}}</ref> 82% of subjects diagnosed with hepatitis C have previously been in jail,<!-- --><ref>{{cite journal | author = Campbell J, Hagan H, Latka M, Garfein R, Golub E, Coady M, Thomas D, Strathdee S | title = High prevalence of alcohol use among hepatitis C virus antibody positive injection drug users in three US cities. | journal = Drug Alcohol Depend | volume = 81 | issue = 3 | pages = 259–65 | year = 2006 | pmid = 16129567 | doi = 10.1016/j.drugalcdep.2005.07.005}}</ref> and transmission while in prison is well described.<!-- --><ref>{{cite journal | author = McGovern B, Wurcel A, Kim A, Schulze zur Wiesch J, Bica I, Zaman M, Timm J, Walker B, Lauer G | title = Acute hepatitis C virus infection in incarcerated injection drug users. | journal = Clin Infect Dis | volume = 42 | issue = 12 | pages = 1663–70 | year = 2006 | pmid = 16705568 | doi = 10.1086/504327}}</ref> [[Egypt]] has the highest [[seroprevalence]] for HCV, up to 20% in some areas. There is a hypothesis that the high prevalence is linked to a now-discontinued mass-treatment campaign for [[schistosomiasis]], which is endemic in that country.<!-- --><ref name="frank">{{cite journal | author = Frank C, Mohamed M, Strickland G, Lavanchy D, Arthur R, Magder L, El Khoby T, Abdel-Wahab Y, Aly Ohn E, Anwar W, Sallam I | title = The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. | journal = Lancet | volume = 355 | issue = 9207 | pages = 887–91 | year = 2000 | pmid = 10752705 | doi = 10.1016/S0140-6736(99)06527-7}}</ref> Regardless of how the epidemic started, a high rate of HCV transmission continues in Egypt, both iatrogenically and within the community and household. === Co-infection with HIV === Approximately 350,000, or 35% of patients in the USA infected with HIV are also infected with the hepatitis C virus, mainly because both viruses are blood-borne and present in similar populations. In other countries co-infection is less common, and this is possibly related to differing drug policies.{{Fact|date=May 2008}} HCV is the leading cause of chronic liver disease in the USA. It has been demonstrated in clinical studies that HIV infection causes a more rapid progression of chronic hepatitis C to cirrhosis and liver failure. This is not to say treatment is not an option for those living with co-infection. == Treatment and prognosis == There is a very small chance of clearing the virus spontaneously in chronic HCV carriers (0.5 to 0.74% per year),<ref name=Watanabe_2003>{{cite journal |author=Watanabe H, Saito T, Shinzawa H, Okumoto K, Hattori E, Adachi T, Takeda T, Sugahara K, Ito J, Saito K, Togashi H, Suzuki R, Hayashi M, Miyamura T, Matsuura Y, Kawata S |title=Spontaneous elimination of serum hepatitis C virus (HCV) RNA in chronic HCV carriers: a population-based cohort study |journal=J Med Virol |volume=71 |issue=1 |pages=56–61 |year=2003 |pmid=12858409 | doi = 10.1002/jmv.10448}}</ref>,<ref name=Scott_2006>{{cite journal |author=Scott J, McMahon B, Bruden D, Sullivan D, Homan C, Christensen C, Gretch D |title=High rate of spontaneous negativity for hepatitis C virus RNA after establishment of chronic infection in Alaska Natives |journal=Clin Infect Dis |volume=42 |issue=7 |pages=945–52 |year=2006 |pmid=16511757 | doi = 10.1086/500938}}</ref> however, the majority of patients with chronic hepatitis C will not clear it without treatment. Current treatment is a combination of [[pegylated interferon alpha]] (brand names Pegasys and PEG-Intron) and the antiviral drug [[ribavirin]] for a period of 24 or 48 weeks, depending on genotype. Indications for treatment include patients with proven hepatitis C virus infection and persistent abnormal liver function tests. Sustained cure rates (sustained viral response) of 75% or better occur in people with genotypes HCV 2 and 3 in 24 weeks of treatment,<ref> {{cite journal|volume=357|pages=124&ndash;134|year=2007|issue=2|title=Peginterferon Alfa-2a and Ribavirin for 16 or 24 weeks in HCV genotype 2 or 3|author=Shiffman ML, Suter F, Bacon BR, ''et al.''|journal=N Engl J Med|url=http://content.nejm.org/cgi/content/short/357/2/124?query=TOC | doi = 10.1056/NEJMoa066403|pmid=17625124}}</ref> about 50% in those with genotype 1 with 48 weeks of treatment and 65% for those with genotype 4 in 48 weeks of treatment. About 80% of hepatitis C patients in the United States have genotype 1. Genotype 4 is more common in the [[Middle East]] and Africa. Should treatment with pegylated ribivirin-interferon not return a 2-log viral reduction or complete clearance of RNA (termed ''early virological response'') after 12 weeks for genotype 1, the chance of treatment success is less than 1%. Early virological response is typically not tested for in non-genotype 1 patients, as the chances of attaining it are greater than 90%. The mechanism of action is not entirely clear, because even patients who appear to have had a sustained virological response still have actively replicating virus in their liver and peripheral blood mononuclear cells.<ref>{{cite journal | author=Castillo I, Rodriguez-Iñigo E, López-Alcorocho JM, ''et al.'' | title=Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment | journal=Clin Infect Dis | year=2006 | volume=43 | issue=10 | pages=1277&ndash;83 | doi = 10.1086/508198}}</ref> Treatment during the acute infection phase has much higher success rates (greater than 90%) with a shorter duration of treatment; however, this must be balanced against the 15-40% chance of spontaneous clearance without treatment (see Acute Hepatitis C section above). Those with low initial viral loads respond much better to treatment than those with higher viral loads (greater than 2 million virions/ml). Current combination therapy is usually supervised by physicians in the fields of [[gastroenterology]], [[hepatology]] or [[infectious disease]]. The treatment may be physically demanding, particularly those with a prior history of drug or alcohol abuse. It can qualify for temporary [[disability]] in some cases. A substantial proportion of patients will experience a panoply of side effects ranging from a 'flu-like' syndrome (the most common, experienced for a few days after the weekly injection of interferon) to severe adverse events including [[anemia]], [[cardiovascular disease|cardiovascular events]] and psychiatric problems such as [[suicide]] or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the patient. Current guidelines strongly recommend that hepatitis C patients be vaccinated for hepatitis A and B if they have not yet been exposed to these viruses, as this would radically worsen their liver disease. [[Alcoholic beverage]] consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more likely; [[insulin resistance]] and [[metabolic syndrome]] may similarly worsen the hepatic prognosis. There is also evidence that smoking increases the fibrosis (scarring) rate. === During pregnancy and breastfeeding === If a [[pregnant]] woman has risk factors for hepatitis C, she should be tested for antibodies against HCV. About 4% infants born to HCV infected women become infected. The virus is spread to the baby at the time of birth. There is no treatment that can prevent this from happening. In a mother that also has HIV, the rate of transmission can be as high as 19%. There are currently no data to determine whether antiviral therapy reduces [[perinatal transmission]]. [[Ribavirin]] and [[interferon]]s are contraindicated during pregnancy. However, avoiding [[fetal scalp monitoring]] and prolonged labor after [[rupture of membranes]] may reduce the risk of transmission to the infant. HCV antibodies from the mother may persist in infants until 15 months of age. If an early [[diagnosis]] is desired, testing for [[HCV RNA]] can be performed between the ages of 2 and 6 months, with a repeat test done independent of the first test result. If a later diagnosis is preferred, an anti-HCV test can performed after 15 months of age. Most infants infected with HCV at the time of birth have no [[symptoms]] and do well during childhood. There is no evidence that [[breast-feeding]] spreads HCV. To be cautious, an infected mother should avoid breastfeeding if her nipples are cracked and bleeding.<ref>{{cite journal | author = Mast E | title = Mother-to-infant hepatitis C virus transmission and breastfeeding. | journal = Adv Exp Med Biol | volume = 554 | issue = | pages = 211–6 | year = | pmid = 15384578}}</ref> === Alternative therapies === Several [[alternative medicine|alternative therapies]] purport to maintain liver functionality, rather than treat the virus itself, thereby slowing the course of the disease to retain quality of life. As an example, extract of ''[[Silybum marianum]]'' and [[Sho-saiko-to]] are sold for their HCV related effects; the first is said to provide some generic help to hepatic functions, and the second claims to aid in liver health and provide some antiviral effects.<ref>NCCAM. [http://nccam.nih.gov/health/hepatitisc/ Hepatitis C and Complementary and Alternative Medicine: 2003 Update]. May 2004. Accessed [[2007-02-25]].</ref> === Experimental treatments === The drug [[viramidine]], which is a [[prodrug]] of [[ribavirin]] that has better targeting for the liver, and therefore may be more effective against hepatitis C for a given tolerated dose, is in phase III experimental trials against hepatitis C. It will be used in conjunction with [[interferon]], in the same manner as ribavirin. However, this drug is not expected to be active against ribavirin-resistant strains, and the use of the drug against infections which have already failed ribavirin/interferon treatment, is unproven. There are new drugs under development like the [[protease inhibitor (pharmacology)|protease inhibitors]] (including ''[[VX 950]]'') and polymerase inhibitors (such as ''NM 283''), but development of these is still in the early phase.<!-- --><ref name="hinrichsen">{{cite journal | author = Hinrichsen H, Benhamou Y, Wedemeyer H, Reiser M, Sentjens R, Calleja J, Forns X, Erhardt A, Crönlein J, Chaves R, Yong C, Nehmiz G, Steinmann G | title = Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. | journal = Gastroenterology | volume = 127 | issue = 5 | pages = 1347–55 | year = 2004 | pmid = 15521004 | doi = 10.1053/j.gastro.2004.08.002}}</ref><!-- --><ref name="lamarre">{{cite journal | author = Lamarre D, Anderson P, Bailey M, Beaulieu P, Bolger G, Bonneau P, Bös M, Cameron D, Cartier M, Cordingley M, Faucher A, Goudreau N, Kawai S, Kukolj G, Lagacé L, LaPlante S, Narjes H, Poupart M, Rancourt J, Sentjens R, St George R, Simoneau B, Steinmann G, Thibeault D, Tsantrizos Y, Weldon S, Yong C, Llinàs-Brunet M | title = An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. | journal = Nature | volume = 426 | issue = 6963 | pages = 186–9 | year = 2003 | pmid = 14578911 doi=10.1038/nature02099 | doi = 10.1038/nature02099}}</ref> One protease inhibitor, ''[[BILN 2061]]'', had to be discontinued due to safety problems early in the clinical testing. Some more modern new drugs that provide some support in treating HCV are ''[[Albuferon]]'', ''[[Zadaxin]]'', and ''[[DAPY]]''. Antisense phosphorothioate [[oligo]]s have been targeted to hepatitis C<!-- -->.<ref name="zhang">{{cite journal | author = Zhang H, Hanecak R, Brown-Driver V, Azad R, Conklin B, Fox M, Anderson K | title = Antisense oligonucleotide inhibition of hepatitis C virus (HCV) gene expression in livers of mice infected with an HCV-vaccinia virus recombinant. | journal = Antimicrob Agents Chemother | volume = 43 | issue = 2 | pages = 347–53 | year = 1999 | pmid = 9925530 | url=http://aac.asm.org/cgi/content/full/43/2/347?view=long&pmid=9925530}}</ref> Antisense [[Morpholino]] [[oligo]]s have shown promise in preclinical studies<!-- --><ref name="mccaffrey">{{cite journal | author = McCaffrey A, Meuse L, Karimi M, Contag C, Kay M | title = A potent and specific morpholino antisense inhibitor of hepatitis C translation in mice. | journal = Hepatology | volume = 38 | issue = 2 | pages = 503–8 | year = 2003 | pmid = 12883495 | doi = 10.1053/jhep.2003.50330}}</ref> however, they were found to cause a limited viral load [http://clinicaltrials.gov/ct/show/NCT00229749?order=1| reduction]. [[Immunoglobulin]]s against the hepatitis C virus exist and newer types are under development. Thus far, their roles have been unclear as they have not been shown to help in clearing chronic infection or in the prevention of infection with acute exposures (e.g. needlesticks). They do have a limited role in [[organ transplant|transplant]] patients. In addition to the standard treatment with interferon and ribavirin, some studies have shown higher success rates when the antiviral drug [[amantadine]] (Symmetrel) is added to the regimen. Sometimes called "triple therapy", it involves the addition of 100mg of amantadine twice a day. Studies indicate that this may be especially helpful for "nonresponders" - patients who have not been successful in previous treatments using interferon and ribavirin only.<!-- --><ref name="Maynard">{{cite journal | author = Maynard M, Pradat P, Bailly F, Rozier F, Nemoz C, Si Ahmed S, Adeleine P, Trépo C | title = Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI). | journal = J Hepatol | volume = 44 | issue = 3 | pages = 484–90 | year = 2006 | pmid = 16426697 | doi = 10.1016/j.jhep.2005.11.038}}</ref> Currently, amantadine is not approved for treatment of Hepatitis C, and studies are ongoing to determine when it is most likely to benefit the patient. Followup studies have shown no benefit to adding this drug and currently it is not commonly used by experienced hepatologists. == Prevention == The following guidelines will prevent infection with the hepatitis C virus, which is spread by blood: * Avoid sharing drug needles or any other drug paraphernalia including works for injection or bills or straws * Avoid unsanitary tattoo methods * Avoid unsanitary body piercing methods and acupuncture * Avoid needlestick injury * Avoid sharing personal items such as toothbrushes, razors, and nail clippers. * Use latex condoms correctly and every time you have sex if not in a long-term monogamous relationship<ref name="titleHepatitis C: Fact Sheet | CDC Viral Hepatitis">{{cite web |url=http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm |title=Hepatitis C: Fact Sheet | CDC Viral Hepatitis |accessdate=2008-04-15 |format= |work=}}</ref> Proponents of [[harm reduction]] believe that strategies such as the provision of new needles and syringes, and education about [[safer drug injection]] procedures, greatly decreases the risk of hepatitis C spreading between injecting drug users. No vaccine protects against contracting hepatitis C, or helps to treat it. Vaccines are under development and some have shown encouraging results.<ref>{{cite journal |journal= Nat Rev Drug Discov |date=2007 |volume=6 |issue=12 |pages=991–1000 |title= The way forward in HCV treatment—finding the right path |author= Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M |doi=10.1038/nrd2411 |pmid=18049473 }}</ref> == See also == * [[List of people with hepatitis C]] * [[hepatitis A]] * [[hepatitis B]] * [[hepatitis D]] * [[hepatitis E]] * [[GB virus C]] (formerly "hepatitis G") ==References== <!-- --------------------------------------------------------------- See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a discussion of different citation methods and how to generate footnotes using the <ref> & </ref> tags and the {{Reflist}} template -------------------------------------------------------------------- --> {{Reflist|2}} == External links == *[http://www.hepatitis.va.gov National Hepatitis C Program] U.S. Department of Veterans Affairs * [http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm CDC's Hepatitis C Fact Sheet] * [http://www.cdc.gov/ncidod/diseases/hepatitis/c/faq.htm CDC's Hepatitis C Frequently Asked Questions] * [http://www.hepatitis-c.org Hepatitis C Virus (HCV) Details] *[http://www.hepatitisaustralia.com Hepatitis Australia] Hepatitis Australia * [http://www.hepc.nhs.uk Hepatitis C] homepage of the UK [[National Health Service]] * [http://www.hepcuk.info The hepatitis C trust] - hepatitis C resource for the UK * [http://www.medsci.org/hepatitisc.html Special issue on virology and clinical advances of HCV ] * [http://www.hcvinprison.org National HCV Prison Coalition (U.S.A)] * [http://www.hepcfacts.org.uk HepCFacts] UK information for children and young people about hepatitis C {{Viral diseases}} {{gastroenterology}} [[Category:Hepatitis|C]] [[bg:Хепатит C]] [[ca:Hepatitis C]] [[de:Hepatitis C]] [[es:Hepatitis C]] [[fr:Hépatite C]] [[hr:Hepatitis C]] [[id:Hepatitis C]] [[it:Epatite virale C]] [[mk:Хепатит Ц]] [[ms:Hepatitis C]] [[nl:Hepatitis C]] [[ja:C型肝炎]] [[pt:Hepatite C]] [[ru:Гепатит C]] [[simple:Hepatitis C]] [[sr:Хепатитис Ц]] [[fi:Hepatiitti C]] [[zh:丙型肝炎]]