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Hepatitis C
HCV EM picture 2.png
Electron micrograph of hepatitis C virus from cell culture (scale = 50 nanometers)
SpecialtyGastroenterology, Infectious disease
SymptomsTypically none[1]
ComplicationsLiver failure, liver cancer, esophageal and gastric varices[2]
DurationLong term (80%)[1]
CausesHepatitis C virus usually spread by blood-to-blood contact[1][3]
Diagnostic methodBlood testing for antibodies or viral RNA[1]
PreventionSterile needles, testing donated blood[4]
TreatmentMedications, liver transplant[5]
MedicationAntivirals (sofosbuvir, simeprevir, others)[1][4]
Frequency71 million (2017)[6]
Deaths399,000 (2016)[6]

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver;[2] it is a type of viral hepatitis.[7] During the initial infection people often have mild or no symptoms.[1] Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs.[1] The virus persists in the liver in about 75% to 85% of those initially infected.[1] Early on chronic infection typically has no symptoms.[1] Over many years however, it often leads to liver disease and occasionally cirrhosis.[1] In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach.[2]

HCV is spread primarily by blood-to-blood contact associated with injection drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, and transfusions.[1][3] Using blood screening, the risk from a transfusion is less than one per two million.[1] It may also be spread from an infected mother to her baby during birth.[1] It is not spread by superficial contact.[4] It is one of five known hepatitis viruses: A, B, C, D, and E.[8]

Diagnosis is by blood testing to look for either antibodies to the virus or viral RNA.[1] In the infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver;[2] it is a type of viral hepatitis.[7] During the initial infection people often have mild or no symptoms.[1] Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs.[1] The virus persists in the liver in about 75% to 85% of those initially infected.[1] Early on chronic infection typically has no symptoms.[1] Over many years however, it often leads to liver disease and occasionally cirrhosis.[1] In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach.[2]

HCV is spread primarily by blood-to-blood contact associated with injection drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, and transfusions.[1][3] Using blood screening, the risk from a transfusion is less than one per two million.[1] It may also be spread from an infected mother to her baby during birth.[1] It is not spread by superficial contact.[4] It is one of five known hepatitis viruses: A, B, C, D, and E.[8]

Diagnosis is by blood testing to look for either antibodies to the virus or viral RNA.[1] In the United States, screening for HCV infection is recommended in all adults age 18 to 79 years old.[9]

There is no vaccine against hepatitis C.[1][10] Prevention includes harm reduction efforts among people who inject drugs, testing donated blood, and treatment of people with chronic infection.[11][4] Chronic infection can be cured more than 95% of the time with antiviral medications such as sofosbuvir or simeprevir.[6][1][4] Peginterferon and ribavirin were earlier generation treatments that had a cure rate of less than 50% and greater side effects.[4][12] Getting access to the newer treatments however can be expensive.[4] Those who develop cirrhosis or liver cancer may require a liver transplant.[5] Hepatitis C

HCV is spread primarily by blood-to-blood contact associated with injection drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, and transfusions.[1][3] Using blood screening, the risk from a transfusion is less than one per two million.[1] It may also be spread from an infected mother to her baby during birth.[1] It is not spread by superficial contact.[4] It is one of five known hepatitis viruses: A, B, C, D, and E.[8]

Diagnosis is by blood testing to look for either antibodies to the virus or viral RNA.[1] In the United States, screening for HCV infection is recommended in all adults age 18 to 79 years old.[9]

There is no vaccine against hepatitis C.[1][10] Prevention includes harm reduction efforts among people who inject drugs, testing donated blood, and treatment of people with chronic infection.[11][4] Chronic infection can be cured more than 95% of the time with antiviral medications such as sofosbuvir or simeprevir.[6][1][4] Peginterferon and ribavirin were earlier generation treatments that had a cure rate of less than 50% and greater side effects.[4][12] Getting access to the newer treatments however can be expensive.[4] Those who develop cirrhosis or liver cancer may require a liver transplant.[5] Hepatitis C is the leading reason for liver transplantation, though the virus usually recurs after transplantation.[5]

An estimated 71 million people (1%) worldwide are infected with hepatitis C as of 2017.[6] In 2013, about eleven million new cases occurred.[13] It occurs most commonly in Africa and Central and East Asia.[4] About 167,000 deaths due to liver cancer and 326,000 deaths due to cirrhosis occurred in 2015 due to hepatitis C.[14] The existence of hepatitis C – originally identifiable only as a type of non-A non-B hepatitis – was suggested in the 1970s and proven in 1989.[15] Hepatitis C infects only humans and chimpanzees.[16]

Acute symptoms develop in some 20–30% of those infected.[1] When this occurs, it is generally 4–12 weeks following infection (but it may take from 2 weeks to 6 months for acute symptoms to appear).[1][4]

Symptoms are generally mild and vague, and may include fatigue, nausea and vomiting, fever, muscle or joint pains, abdominal pain, decreased appetite and weight loss, jaundice (occurs in ~25% of those infected), dark urine, and clay-coloured stools.[1][17][18] There is no evidence that acute hepatitis C can alone cause acute liver failure, though liver injury and elevated liver enzymes may occur.[17][19] Symptoms and laboratory findings suggestive of liver disease should prompt further tests and can thus help establish a diagnosis of hepatitis C infection early on.[18]

Following the acute phase, the infection may resolve spontaneously in 10–50% of affected people; this occurs more frequently in young people, and females.[17]

Chronic infection

About 80% of those exposed to the virus develop a chronic infection.[20] This is defined as the presence of detectable viral replication for at least six months. Most experience minimal or no symptoms during the initial few decades of the infection.[21] Chronic hepatitis C can be associated with fatigue[22] and mild cognitive problems.[23] Chronic infection after several years may cause cirrhosis or liver cancer.[5] The liver enzymes measured from blood samples are normal in 7–53%.[24] (Elevated levels indicate liver cells are being damaged by the virus or other disease.) Late relapses after apparent cure have been reported, but these can be difficult to distinguish from reinfection.[24]

Fatty changes to the liver occur in about half of those infected and are usually present before cirrhosis develops.[25][26] Usually (80% of the time) this change affects less than a third of the liver.[25] Worldwide hepatitis C is the cause of 27% of cirrhosis cases and 25% of hepatocellular carcinoma.[27] About 10–30% of those infected develop cirrhosis over 30 years.[5][18] Cirrhosis is more common in those also infected with hepatitis B, schistosoma, or HIV, in alcoholics and in those of male sex.[18] In those with hepatitis C, excess alcohol increases the risk of developing cirrhosis 5-fold.[28] Those who develop cirrhosis have a 20-fold greater risk of hepatocellular carcinoma. This transformation occurs at a rate of 1–3% per year.[5][18] Being infected with hepatitis B in addition to hepatitis C increases this risk further.[29]

Liver cirrhosis may lead to portal hypertension, ascites (accumulation of fluid in the abdomen), easy bruising or bleeding, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy.[30] Ascites occurs at some stage in more than half of those who have a chronic infection.[31]

Extrahepatic complications

The most common problem due to hepatitis C but not involving the liver is mixed cryoglobulinemia (usually the type II form) – an inflammation of small and medium-sized blood vessels.[32][33] Hepatitis C is also associated with autoimmune disorders such as Sjögren's syndrome, lichen planus, a low platelet count, porphyria cutanea tarda, necrolytic acral erythema, insulin resistance, diabetes mellitus, diabetic nephropathy, autoimmune thyroiditis, and B-cell lymphoproliferative disorders.[34][35] 20–30% of people infected have rheumatoid factor – a type of antibody.[36] Possible associations include Hyde's prurigo nodularis[37] and membranoproliferative glomerulonephritis.[22] Cardiomyopathy with associated abnormal heart rhythms has also been reported.[38] A variety of central nervous system disorders has been reported.[39] Chronic infection seems to be associated with an increased risk of pancreatic cancer.[10][40] People may experience other issues in the mouth such as dryness, salivary duct stones, and crusted lesions around the mouth.[41][42][43]

Occult infection

Persons who have been infected with hepatitis C may appear to clear the virus but remain infected.[44] The virus is not detectable with conventional testing but can be found with ultra-sensitive tests.[45] The original method of detection was by demonstrating the viral genome within liver biopsies, but newer methods include an antibody test for the virus' core protein and the detection of the viral genome after first concentrating the viral particles by ultracentrifugation.[46] A form of infection with persistently moderately elevated serum liver enzymes but without antibodies to hepatitis C has also been reported.[47] This form is known as cryptogenic occult infection.

Several clinical pictures have been associated with this type of infection.[48] It may be found in people with anti-hepatitis-C antibodies but with normal serum levels of liver enzymes; in antibody-negative people with ongoing elevated liver enzymes of unknown cause; in healthy populations without evidence of liver disease; and in groups at risk for HCV infection including those on hemodialysis or family members of people with occult HCV. The clinical relevance of this form of infection is under investigation.[49] The consequences of occult infection appear to

Symptoms are generally mild and vague, and may include fatigue, nausea and vomiting, fever, muscle or joint pains, abdominal pain, decreased appetite and weight loss, jaundice (occurs in ~25% of those infected), dark urine, and clay-coloured stools.[1][17][18] There is no evidence that acute hepatitis C can alone cause acute liver failure, though liver injury and elevated liver enzymes may occur.[17][19] Symptoms and laboratory findings suggestive of liver disease should prompt further tests and can thus help establish a diagnosis of hepatitis C infection early on.[18]

Following the acute phase, the infection may resolve spontaneously in 10–50% of affected people; this occurs more frequently in young people, and females.[17]

About 80% of those exposed to the virus develop a chronic infection.[20] This is defined as the presence of detectable viral replication for at least six months. Most experience minimal or no symptoms during the initial few decades of the infection.[21] Chronic hepatitis C can be associated with fatigue[22] and mild cognitive problems.[23] Chronic infection after several years may cause cirrhosis or liver cancer.[5] The liver enzymes measured from blood samples are normal in 7–53%.[24] (Elevated levels indicate liver cells are being damaged by the virus or other disease.) Late relapses after apparent cure have been reported, but these can be difficult to distinguish from reinfection.[24]

Fatty changes to the liver occur in about half of those infected and are usually present before cirrhosis develops.[25]Fatty changes to the liver occur in about half of those infected and are usually present before cirrhosis develops.[25][26] Usually (80% of the time) this change affects less than a third of the liver.[25] Worldwide hepatitis C is the cause of 27% of cirrhosis cases and 25% of hepatocellular carcinoma.[27] About 10–30% of those infected develop cirrhosis over 30 years.[5][18] Cirrhosis is more common in those also infected with hepatitis B, schistosoma, or HIV, in alcoholics and in those of male sex.[18] In those with hepatitis C, excess alcohol increases the risk of developing cirrhosis 5-fold.[28] Those who develop cirrhosis have a 20-fold greater risk of hepatocellular carcinoma. This transformation occurs at a rate of 1–3% per year.[5][18] Being infected with hepatitis B in addition to hepatitis C increases this risk further.[29]

Liver cirrhosis may lead to portal hypertension, ascites (accumulation of fluid in the abdomen), easy bruising or bleeding, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy.[30] Ascites occurs at some stage in more than half of those who have a chronic infection.[31]

The most common problem due to hepatitis C but not involving the liver is mixed cryoglobulinemia (usually the type II form) – an inflammation of small and medium-sized blood vessels.[32][33] Hepatitis C is also associated with autoimmune disorders such as Sjögren's syndrome, lichen planus, a low platelet count, porphyria cutanea tarda, necrolytic acral erythema, insulin resistance, diabetes mellitus, diabetic nephropathy, autoimmune thyroiditis, and B-cell lymphoproliferative disorders.[34][35] 20–30% of people infected have rheumatoid factor – a type of antibody.[36] Possible associations include Hyde's prurigo nodularis[37] and membranoproliferative glomerulonephritis.[22] Cardiomyopathy with associated abnormal heart rhythms has also been reported.[38] A variety of central nervous system disorders has been reported.[39] Chronic infection seems to be associated with an increased risk of pancreatic cancer.[10][40] People may experience other issues in the mouth such as dryness, salivary duct stones, and crusted lesions around the mouth.[41][42][43]

Occult infection

Persons who have been infec

Persons who have been infected with hepatitis C may appear to clear the virus but remain infected.[44] The virus is not detectable with conventional testing but can be found with ultra-sensitive tests.[45] The original method of detection was by demonstrating the viral genome within liver biopsies, but newer methods include an antibody test for the virus' core protein and the detection of the viral genome after first concentrating the viral particles by ultracentrifugation.[46] A form of infection with persistently moderately elevated serum liver enzymes but without antibodies to hepatitis C has also been reported.[47] This form is known as cryptogenic occult infection.

Several clinical pictures have been associated with this type of infection.[48] It may be found in people with anti-hepatitis-C antibodies but with normal serum levels of liver enzymes; in antibody-negative people

Several clinical pictures have been associated with this type of infection.[48] It may be found in people with anti-hepatitis-C antibodies but with normal serum levels of liver enzymes; in antibody-negative people with ongoing elevated liver enzymes of unknown cause; in healthy populations without evidence of liver disease; and in groups at risk for HCV infection including those on hemodialysis or family members of people with occult HCV. The clinical relevance of this form of infection is under investigation.[49] The consequences of occult infection appear to be less severe than with chronic infection but can vary from minimal to hepatocellular carcinoma.[46]

The rate of occult infection in those apparently cured is controversial but appears to be low.[24] 40% of those with hepatitis but with both negative hepatitis C serology and the absence of detectable viral genome in the serum have hepatitis C virus in the liver on biopsy.[50] How commonly this occurs in children is unknown.[51]

The hepatitis C virus (HCV) is a small, enveloped, single-stranded, positive-sense RNA virus.[5] It is a member of the genus Hepacivirus in the family Flaviviridae.[22] There are seven major genotypes of HCV, which are known as genotypes one to seven.[52] The genotypes are divided into several subtypes with the number of subtypes depending on the genotype. In the United States, about 70% of cases are caused by genotype 1, 20% by genotype 2 and about 1% by each of the other genotypes.[18] Genotype 1 is also the most common in South America and Europe.[5]

The half life of the virus particles in the serum is around 3 hours and may be as short as 45 minutes.[53][54] In an infected person, about 1012 virus particles are produced each day.[53][54] In an infected person, about 1012 virus particles are produced each day.[53] In addition to replicating in the liver the virus can multiply in lymphocytes.[55]

The primary route of transmission in the developed world is injection drug use, while in the developing world the main methods are blood transfusions and unsafe medical procedures.[3] The cause of transmission remains unknown in 20% of cases;[56] however, many of these are believed to be accounted for by IDU.[17]

Drug use

Injection drug use is a major risk factor for hepatitis C in many parts of the world.[57] Of 77 countries reviewed, 25 (including the United States) were found to have a prevalence of hepatitis C of between 60% and 80% among people who use injection drugs.[20][57] Twelve countries had rates greater than 80%.[20] It is believed that ten million intravenous drug users are infected with hepatitis C; China (1.6 million), the United State

Injection drug use is a major risk factor for hepatitis C in many parts of the world.[57] Of 77 countries reviewed, 25 (including the United States) were found to have a prevalence of hepatitis C of between 60% and 80% among people who use injection drugs.[20][57] Twelve countries had rates greater than 80%.[20] It is believed that ten million intravenous drug users are infected with hepatitis C; China (1.6 million), the United States (1.5 million), and Russia (1.3 million) have the highest absolute totals.[20] Occurrence of hepatitis C among prison inmates in the United States is 10 to 20 times that of the occurrence observed in the general population; this has been attributed to high-risk behavior in prisons such as IDU and tattooing with nonsterile equipment.[58][59] Shared intranasal drug use may also be a risk factor.[60]

Healthcare exposure

Tattooing is associated with two to threefold increased risk of hepatitis C.[66] This can be due to either improperly sterilized equipment or contamination of the dyes being used.[66] Tattoos or piercings performed either before the mid-1980s, "underground," or nonprofessionally are of particular concern, since sterile techniques in such settings may be lacking. The risk also appears to be greater for larger tattoos.[66] It is estimated that nearly half of prison inmates share unsterilized tattooing equipment.[66] It is rare for tattoos in a licensed facility to be directly associated with HCV infection.[67]

Shared personal items<

Personal-care items such as razors, toothbrushes, and manicuring or pedicuring equipment can be contaminated with blood. Sharing such items can potentially lead to exposure to HCV.[68][69] Appropriate caution should be taken regarding any medical condition that results in bleeding, such as cuts and sores.[69] HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils.[69] Neither is it transmitted through food or water.[70]

Mother-to-child transmission

Compared with adults, infection in children is much less well understood. Worldwide the prevalence of hepatitis C virus infection in pregnant women and children has been estimated to 1–8% and 0.05–5% respectively.[144] The vertical transmission rate has been estimated to be 3–5% and there is a high rate of spontaneous clearance (25–50%) in the children. Higher rates have been reported for both vertical transmission (18%, 6–36% and 41%).[144] The vertical transmission rate has been estimated to be 3–5% and there is a high rate of spontaneous clearance (25–50%) in the children. Higher rates have been reported for both vertical transmission (18%, 6–36% and 41%).[145][146] and prevalence in children (15%).[147]

In developed countries transmission around the time of birth is now the leading cause of HCV infection. In the absence of virus in the mother's blood transmission seems to be rare.[146] Factors associated with an increased rate of infection include membrane rupture of longer than 6 hours before delivery and procedures exposing the infant to maternal blood.[148] Cesarean sections are not recommended. Breastfeeding is considered safe if the nipples are not damaged. Infection around the time of birth in one child does not increase the risk in a subsequent pregnancy. All genotypes appear to have the same risk of transmission.

HCV infection is fr

In developed countries transmission around the time of birth is now the leading cause of HCV infection. In the absence of virus in the mother's blood transmission seems to be rare.[146] Factors associated with an increased rate of infection include membrane rupture of longer than 6 hours before delivery and procedures exposing the infant to maternal blood.[148] Cesarean sections are not recommended. Breastfeeding is considered safe if the nipples are not damaged. Infection around the time of birth in one child does not increase the risk in a subsequent pregnancy. All genotypes appear to have the same risk of transmission.

HCV infection is frequently found in children who have previously been presumed to have non-A, non-B hepatitis and cryptogenic liver disease.[149] The presentation in childhood may be asymptomatic or with elevated liver function tests.[150] While infection is commonly asymptomatic both cirrhosis with liver failure and hepatocellular carcinoma may occur in childhood.

The rate of hepatitis C in immunosuppressed people is higher. This is particularly true in those with human immunodeficiency virus infection, recipients of organ transplants, and those with hypogammaglobulinemia.[151] Infection in these people is associated with an unusually rapid progression to cirrhosis. People with stable HIV who never received medication for HCV, may be treated with a combination of peginterferon plus ribavirin with caution to the possible side effects.[152]

Research

As of 2011,

As of 2011, there are about one hundred medications in development for hepatitis C.[139] These include vaccines to treat hepatitis, immunomodulators, and cyclophilin inhibitors, among others.[153] These potential new treatments have come about due to a better understanding of the hepatitis C virus.[154] There are a number of vaccines under development and some have shown encouraging results.[82]

The combination of sofosbuvir and velpatasvir in one trial (reported in 2015) resulted in cure rates of 99%.[155]

The combination of sofosbuvir and velpatasvir in one trial (reported in 2015) resulted in cure rates of 99%.[155] More studies are needed to investigate the role of the preventive antiviral medication against HCV recurrence after transplantation.[156]

One barrier to finding treatments for hepatitis C is the lack of a suitable animal model. Despite moderate success, research highlights the need for pre-clinical testing in mammalian systems such as mouse, particularly for the development of vaccines in poorer communities. Chimpanzees remain the only available living system to study, yet their use has ethical concerns and regulatory restrictions. While scientists have made use of human cell culture systems such as hepatocytes, questions have been raised about their accuracy in reflecting the body's response to infection.[157]

One aspect of hepatitis research is to reproduce infections in mammalian models. A strategy is to introduce liver tissues from humans into mice, a technique known as xenotransplantation. This is done by generating chimeric mice, and exposing the mice HCV infection. This engineering process is known to create human

One aspect of hepatitis research is to reproduce infections in mammalian models. A strategy is to introduce liver tissues from humans into mice, a technique known as xenotransplantation. This is done by generating chimeric mice, and exposing the mice HCV infection. This engineering process is known to create humanized mice, and provide opportunities to study hepatitis C within the 3D architectural design of the liver and evaluating antiviral compounds.[157] Alternatively, generating inbred mice with susceptibility to HCV would simplify the process of studying mouse models.