Hepatitis C virus (HCV) genotypes refer to the genetic variations that occurs in the hepatitis C virus. Hepatitis C is a contagious disease that primarily affects the liver, causing severe damage as the disease progresses. [1] It is caused by the Hepatitis C virus, a small, enveloped RNA virus. The transmission of hepatitis C is through the contact with the blood of the infected person, for example by sharing the needles or by using non-sterile medical equipment. [2] HCV is transmitted globally because of the high infection rate and is also associated with a high mortality rate. [3] [4] The World Health Organization indicates the 3.3% of the world population is infected by the HCV virus. [5] Statistical records show that there are about 13 million HCV affected persons in Сhina, 3.5 million affected persons in the United States, [6] and about 10 million people are affected by HCV in Pakistan. [3] In all cases, the viral genotype of the HCV stays the same, occasionally mutations do occur making the treatment more complex by targeting the changes in the genotype. [7] Hepatitis C virus genotype is considered more common than the Hepatitis B virus infection contributing to more than a million cases annually [8] and is considered one of the major reason for liver transplantation in United States. [9] Some of the HCV genotypes may develop in people without symptoms leading to dangerous conditions like liver cirrhosis causing a permanent damage to liver and the unnoticed HCV conditions will affect brain, joints, blood vessels, bones, and kidneys. [10]
The complexity of the HCV genotypes made the treatment specific for the associated genotype. The treatment for the HCV genotype also depends on the presence or absence of cirrhosis. [11] There are six major genotypes of hepatitis C virus which includes many subtypes. [12] The genotype can affect treatment of HCV infections. [3] Recent studies show that HCV genotypes consist of 8 genotypes and 67 subtypes. [13] [14] All the genotypes and subtypes affect the liver to the same extent of damage irrespective of the HCV genotype [7] Among the common six genotypes, genotype 1 is the most prevalent form in the United States of America, [15] covering around 70-90% of total infections. It is usually difficult to treat the people with HCV genotype 1.[ citation needed ] Genotype 2 and genotype 3 are less common contributing to around 10-20%. [15] Genotypes 4 and 5 affect a large proportion of the population in undeveloped countries. [16] Genotype 4 is the most common type of infections in Middle East and Africa, around 80% of total infections. [17] About 15% of the people affected by HCV genotypes will get cured without medications, in which immune system plays a vital role in defeating the virus. [18] Until recently, there were no specific vaccines available for treating hepatitis C virus genotypes. [19]
People traveling around different subcontinents where several HCV genotypes are common will have the possibility of resulting in mixed infection. [7]
HCV genotypes | Subsets | Geographical distribution [20] |
---|---|---|
Genotype 1 | 1a, 1b | North America, Central Africa, Europe |
Genotype 2 | 2a, 2b, 2c, 2d | Western Africa |
Genotype 3 | 3a, 3b, 3c, 3d, 3e, 3f | Southeast Asia |
Genotype 4 | 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j | Central Africa |
Genotype 5 | 5a | South Africa and Asia |
Genotype 6 | 6a | Southeast Asia |
The Main techniques used to diagnose the HCV genotype are as follows: [17]
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs. The virus persists in the liver in about 75% to 85% of those initially infected. Early on, chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. 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.
Hepatitis E is inflammation of the liver caused by infection with the hepatitis E virus (HEV); it is a type of viral hepatitis. Hepatitis E has mainly a fecal-oral transmission route that is similar to hepatitis A, although the viruses are unrelated. In retrospect, the earliest known epidemic of hepatitis E occurred in 1955 in New Delhi, but the virus was not isolated until 1983 by Russian scientists investigating an outbreak in Afghanistan. HEV is a positive-sense, single-stranded, nonenveloped, RNA icosahedral virus and one of five known human hepatitis viruses: A, B, C, D, and E.
Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form.
The hepatitis C virus (HCV) is a small, enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer and lymphomas in humans.
A spider angioma or spider naevus, also nevus araneus, is a type of telangiectasis found slightly beneath the skin's surface, often containing a central red spot and deep reddish extensions which radiate outwards like a spider's web or a spider's legs. They are common and often benign, presenting in around 10–15% of healthy adults and young children. However, having more than three spider angiomas is likely to be abnormal and may be a sign of liver disease and/or hepatitis C ; it also suggests the probability of esophageal varices.
Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) co-infection is a multi-faceted, chronic condition that significantly impacts public health. According to the World Health Organization (WHO), 2 to 15% of those infected with HIV are also affected by HCV, increasing their risk of morbidity and mortality due to accelerated liver disease. The burden of co-infection is especially high in certain high-risk groups, such as intravenous drug users and men who have sex with men. These individuals who are HIV-positive are commonly co-infected with HCV due to shared routes of transmission including, but not limited to, exposure to HIV-positive blood, sexual intercourse, and passage of the Hepatitis C virus from mother to infant during childbirth.
Liver cancer is cancer that starts in the liver. Liver cancer can be primary or secondary. Liver metastasis is more common than that which starts in the liver. Liver cancer is increasing globally.
Hepatitis B is an infectious disease caused by the Hepatitis B virus (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Telaprevir (VX-950), marketed under the brand names Incivek and Incivo, is a pharmaceutical drug for the treatment of hepatitis C co-developed by Vertex Pharmaceuticals and Johnson & Johnson. It is a member of a class of antiviral drugs known as protease inhibitors. Specifically, telaprevir inhibits the hepatitis C viral enzyme NS3/4A serine protease. Telaprevir is only indicated for use against hepatitis C genotype 1 viral infections and has not been proven to be safe or effective when used for other genotypes of the virus. The standard therapy of pegylated interferon and ribavirin is less effective than telaprevir in those with genotype 1.
A hepatitis C vaccine, a vaccine capable of protecting against the hepatitis C virus (HCV), is not yet available. Although vaccines exist for hepatitis A and hepatitis B, development of an HCV vaccine has presented challenges. No vaccine is currently available, but several vaccines are currently under development.
Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B.
miR-122 is a miRNA that is conserved among vertebrate species. miR-122 is not present in invertebrates, and no close paralogs of miR-122 have been detected. miR-122 is highly expressed in the liver, where it has been implicated as a regulator of fatty-acid metabolism in mouse studies. Reduced miR-122 levels are associated with hepatocellular carcinoma. miR-122 also plays an important positive role in the regulation of hepatitis C virus replication.
Simeprevir, sold under the trade names Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.
Infections of the hepatitis C virus (HCV) in children and pregnant women are less understood than those in other adults. Worldwide, the prevalence of HCV infection in pregnant women and children has been estimated to 1-8% and 0.05-5% respectively. 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. and prevalence in children (15%).
Ombitasvir is an antiviral drug for the treatment of hepatitis C virus (HCV) infection by AbbVie. In the United States, it is approved by the Food and Drug Administration for use in combination with paritaprevir, ritonavir and dasabuvir in the product Viekira Pak for the treatment of HCV genotype 1, and with paritaprevir and ritonavir in the product Technivie for the treatment of HCV genotype 4.
Ledipasvir/sofosbuvir, sold under the trade name Harvoni among others, is a medication used to treat hepatitis C. It is a fixed-dose combination of ledipasvir and sofosbuvir. Cure rates are 94% to 99% in people infected with hepatitis C virus (HCV) genotype 1. Some evidence also supports use in HCV genotype 3 and 4. It is taken daily by mouth for 8–24 weeks.
Elbasvir/grazoprevir is a fixed-dose combination for the treatment of hepatitis C, containing elbasvir and grazoprevir. It is used to treat chronic hepatitis C virus (HCV) genotypes 1 or 4 infection in both treatment-naïve and treatment-experienced patients.
Nonstructural protein 5A (NS5A) inhibitors are direct acting antiviral agents (DAAs) that target viral proteins, and their development was a culmination of increased understanding of the viral life cycle combined with advances in drug discovery technology. However, their mechanism of action is complex and not fully understood. NS5A inhibitors were the focus of much attention when they emerged as a part of the first curative treatment for hepatitis C virus (HCV) infections in 2014. Favorable characteristics have been introduced through varied structural changes, and structural similarities between NS5A inhibitors that are clinically approved are readily apparent. Despite the recent introduction of numerous new antiviral drugs, resistance is still a concern and these inhibitors are therefore always used in combination with other drugs.
Interferon lambda 4 is one of the most recently discovered human genes and the newest addition to the interferon lambda protein family. This gene encodes the IFNL4 protein, which is involved in immune response to viral infection.