Hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include fever, dark urine, abdominal pain, and jaundice. The virus persists in the liver, becoming chronic, in about 70% 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.
HCV is spread primarily by blood-to-blood contact associated with injection drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, and transfusions. In regions where blood screening has been implemented, the risk of contracting HCV from a transfusion has dropped substantially to less than one per two million. HCV may also be spread from an infected mother to her baby during birth. It is not spread through breast milk, food, water, or casual contact such as hugging, kissing, and sharing food or drinks with an infected person. It is one of five known hepatitis viruses: A, B, C, D, and E. Diagnosis is by blood testing to look for either antibodies to the virus or viral RNA. In the United States, screening for HCV infection is recommended in all adults age 18 to 79 years old. There is no vaccine against hepatitis C. Prevention includes harm reduction efforts among people who inject drugs, testing donated blood, and treatment of people with chronic infection. Chronic infection can be cured more than 95% of the time with antiviral medications such as sofosbuvir or simeprevir. Peginterferon and ribavirin were earlier generation treatments that proved successful in <50% of cases and caused greater side effects. While access to the newer treatments was expensive, by 2022 prices had dropped dramatically in many countries due to the introduction of generic versions of medicines. Those who develop cirrhosis or liver cancer may require a liver transplant. Hepatitis C is one of the leading reasons for liver transplantation. However, the virus usually recurs after transplantation.
An estimated 58 million people worldwide were infected with hepatitis C in 2019. Approximately 290,000 deaths from the virus, mainly from liver cancer and cirrhosis attributed to hepatitis C, also occurred in 2019. 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. Hepatitis C infects only humans and chimpanzees.
Signs and symptoms
Acute infection
symptoms develop in some 20% of those infected. When this occurs, it is generally 4–12 weeks following infection.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, dark urine, and clay-coloured stools. Acute liver failure due to acute hepatitis C is exceedingly rare. 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.
Following the acute phase, the infection may resolve spontaneously in 10–50% of affected people; this occurs more frequently in young people and females.
Chronic infection
About 70% of those exposed to the virus develop a chronic infection. This is defined as the presence of detectable viral replication for at least six months. Though most experience minimal or no symptoms during the initial few decades of a chronic infection, chronic can be associated with fatigue and mild cognitive problems. After several years, chronic infection may cause cirrhosis or liver cancer. The liver enzymes measured from blood samples are normal in 7–53%.. Late relapses after apparent cure have been reported, but these can be difficult to distinguish from reinfection.Fatty changes to the liver occur in about half of those infected and are usually present before cirrhosis develops. Usually this change affects less than a third of the liver. Worldwide hepatitis C is the cause of 27% of cirrhosis cases and 25% of hepatocellular carcinoma. About 10–30% of those infected develop cirrhosis over 30 years. Cirrhosis is more common in those also infected with hepatitis B, schistosoma, or HIV, in alcoholics, and in those of male sex. In those with hepatitis C, excess alcohol increases the risk of developing cirrhosis 5-fold. Those who develop cirrhosis have a 20-fold greater risk of hepatocellular carcinoma. This transformation occurs at a rate of 1–3% per year. Being infected with hepatitis B in addition to hepatitis C increases this risk further.
Liver cirrhosis may lead to portal hypertension, ascites, easy bruising or bleeding, varices, jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy. Ascites occurs at some stage in more than half of those who have a chronic infection.
Extrahepatic complications
The most common problem due to but not involving the liver is mixed cryoglobulinemia – an inflammation of small and medium-sized blood vessels. 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. 20–30% of people infected have rheumatoid factor – a type of antibody. Possible associations include Hyde's prurigo nodularis and membranoproliferative glomerulonephritis. Cardiomyopathy with associated abnormal heart rhythms has also been reported. A variety of central and peripheral nervous system disorders has been reported. Chronic infection seems to be associated with an increased risk of pancreatic cancer. People may experience other issues in the mouth such as dryness, salivary duct stones, and crusted lesions around the mouth.Occult infection
People who have been infected with hepatitis C may appear to clear the virus but remain infected. The virus is not detectable with conventional testing but can be found with ultra-sensitive tests. The original method of detection was by demonstrating the viral genome within liver biopsies. Still, 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. A form of infection with persistently moderately elevated serum liver enzymes but without antibodies to hepatitis C has also been reported. This form is known as cryptogenic occult infection.Several clinical pictures have been associated with this type of infection. 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. The consequences of occult infection appear to be less severe than with chronic infection but can vary from minimal to hepatocellular carcinoma.
The rate of occult infection in those apparently cured is controversial but appears to be low. 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. How commonly this occurs in children is unknown.
Virology
The hepatitis C virus is a small, enveloped, single-stranded, positive-sense RNA virus. It is a member of the genus Hepacivirus in the family Flaviviridae. There are seven major genotypes of HCV, which are known as genotypes one to seven. 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. Genotype 1 is also the most common in South America and Europe.The half-life of the virus particles in the serum is around 3 hours and may be as short as 45 minutes. In an infected person, about 1012 virus particles are produced each day. In addition to replicating in the liver the virus can multiply in lymphocytes.
Transmission
contact with contaminated blood is responsible for most infections; however, the method of transmission is strongly dependent on both geographic region and economic status. Indeed, 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. The cause of transmission remains unknown in 20% of cases; however, many of these are believed to be accounted for by injection drug use.HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils, nor is it transmitted through food or water.
Drug use
is a major risk factor for in many parts of the world. Of 77 countries reviewed, 25 were found to have a prevalence of of 60–80% among people who use injection drugs. Twelve countries had rates greater than 80%. It is believed that ten million people who use drugs intravenously are infected with ; China, the United States, and Russia have the highest absolute totals.Occurrence of 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 non-sterile equipment. Shared intranasal drug use may also be a risk factor.