HEPATITIS

1. HEPATITIS Dr. Adil Khazindar Consultant Medicine & Infectious Diseases KAAUH

3. Types of Viral Hepatitis HepatitisA Is an acute liver disease caused by the hepatitis A virus (HAV), lasting from a few weeks to several months. It does not lead to chronic infection. Transmission: Ingestion of fecal matter, even in microscopic amounts, from close person-to-person contact or ingestion of contaminated food or drinks. Vaccination: Hepatitis A vaccination is recommended for all children starting at age 1 year, travelers to certain countries, and others at risk Hepatitis B Is a liver disease caused by the hepatitis B virus (HBV). It ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead to liver disease or liver cancer. Transmission: Contact with infectious blood, semen, and other body fluids from having sex with an infected person, sharing contaminated needles to inject drugs, or from an infected mother to her newborn. Vaccination: Hepatitis B vaccination is recommended for all infants, older children and adolescents who were not vaccinated previously, and adults at risk for HBV infection. Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). HCV infection sometimes results in an acute illness, but most often becomes a chronic condition that can lead to cirrhosis of the liver and liver cancer. Transmission: Contact with the blood of an infected person, primarily through sharing contaminated needles to inject drugs. Vaccination: There is no vaccine for hepatitis C.

4. Types of Viral Hepatitis Hepatitis D Is a serious liver disease caused by the hepatitis D virus (HDV) and relies on HBV to replicate. Transmission: Contact with infectious blood, similar to how HBV is spread. Vaccination: There is no vaccine for hepatitis D. Hepatitis E Is a serious liver disease caused by the hepatitis E virus (HEV) that usually results in an acute infection. It does not lead to a chronic infection. While rare in the United States, hepatitis E is common in many parts of the world. Transmission: Ingestion of fecal matter, even in microscopic amounts; outbreaks are usually associated with contaminated water supply in countries with poor sanitation. Vaccination: There is currently no FDA-approved vaccine for hepatitis E.

5. HEPATITIS A

6. Hepatitis A • Hepatitis A, caused by infection with the hepatitis A virus (HAV). • has an incubation period of approximately 28 days (range: 15–50 days). • HAV replicates in the liver and is shed in high concentrations in feces from 2 weeks before to 1 week after the onset of clinical illness. • HAV infection produces a self-limited disease that does not result in chronic infection or chronic liver disease. • However, 10%–15% of patients might experience a relapse of symptoms during the 6 months after acute illness. • Acute liver failure from hepatitis A is rare (overall case-fatality rate: 0.5%). • The risk for symptomatic infection is directly related to age, with >80% of adults having symptoms compatible with acute viral hepatitis and the majority of children having either asymptomatic or unrecognized infection. • Antibody produced in response to HAV infection persists for life and confers protection against reinfection.

7. Incidence There were 30,000 cases of Hepatitis A reported to the CDC in the U.S. in 1997. The agency estimates that there were as many as 270,000 cases each year from 1980 through 2000. • there were an estimated 32,000 new hepatitis A virus infections in 2006. (However, the official number of reported hepatitis A cases is much lower since many people who are infected never have symptoms and are never reported to public health officials.

10. How is HAV transmitted? • Person-to-person transmission through the fecal-oral route (i.e., ingestion of something that has been contaminated with the feces of an infected person) is the primary means of HAV transmission in the United States. Most infections result from close personal contact with an infected household member or sex partner. • Common-source outbreaks and sporadic cases also can occur from exposure to fecally contaminated food or water. • Uncooked HAV-contaminated foods have been recognized as a source of outbreaks. • Cooked foods also can transmit HAV if the temperature during food preparation is inadequate to kill the virus or if food is contaminated after cooking, as occurs in outbreaks associated with infected food handlers. • Waterborne outbreaks are infrequent in developed countries with well-maintained sanitation and water supplies.

11. Who is at increased risk for acquiring HAV infection? • Travelers to countries with high or intermediate endemicity of HAV infection • Users of injection and non-injection illegal drugs • Persons with clotting factor disorders • Persons working with nonhuman primates susceptible to HAV infection

12. Signs & Symptoms Some persons, particularly young children, are asymptomatic. When symptoms are present, they usually occur abruptly and can include the following: • Fever • Fatigue • Loss of appetite • Nausea • Vomiting • Abdominal pain • Dark urine • Clay-colored bowel movements • Joint pain • Jaundice . When symptoms occur, how long do they usually last? Symptoms usually last less than 2 months, although 10%–15% of symptomatic persons have prolonged or relapsing disease for up to 6 months.

13. How long does HAV survive outside the body? How can the virus be killed? • HAV can live outside the body for months, depending on the environmental conditions. • The virus is killed by heating to 185 degrees F (85 degrees C) for one minute. • However, the virus can still be spread from cooked food if it is contaminated after cooking. • Adequate chlorination of water, as recommended in the United States, kills HAV that enters the water supply.

14. Cont. • Can hepatitis A become chronic? No. Hepatitis A does not become chronic. • Can persons become reinfected with HAV after recovering from hepatitis A? No. IgG antibodies to HAV, which appear early in the course of infection, provide lifelong protection against the disease.

15. How is HAV infection prevented? • Vaccination with the full, two-dose series of hepatitis A vaccine is the best way to prevent HAV infection. • Hepatitis A vaccine has been licensed in the United States for use in persons 12 months of age and older. • The vaccine is recommended for persons who are more likely to get HAV infection or are more likely to get seriously ill if they get hepatitis A • Immune globulin is available for short-term protection (approximately 3 months) against hepatitis A, both pre- and post-exposure. Immune globulin must be administered within 2 weeks after exposure for maximum protection. • Good hygiene — including handwashing or use of hand sanitizer after using the bathroom, changing diapers, and before preparing or eating food — is also integral to hepatitis A prevention, given that the virus is transmitted through the fecal–oral route.

16. Who should be vaccinated against hepatitis A? • All children at age 1 year (i.e., 12–23 months).  Children who have not been vaccinated by age 2 can be vaccinated at subsequent visits. • Children and adolescents ages 2–18 who live in states or communities where routine hepatitis A vaccination has been implemented because of high disease incidence. • Persons traveling to or working in countries that have high or intermediate rates of hepatitis A. • Persons traveling to or working in countries that have high or intermediate rates of hepatitis A. • Persons who have occupational risk for infection • Persons who have chronic liver disease. • Persons who have clotting-factor disorders

17. Hepatitis A Vaccine • How long does protection from hepatitis A vaccine last? A recent review by an expert panel, which evaluated the projected duration of immunity from vaccination, concluded that protective levels of antibody to HAV could be present for at least 25 years in adults and at least 14–20 years in children. • Can hepatitis A vaccine be administered concurrently with other vaccines? Yes. Hepatitis B, diphtheria, poliovirus (oral and inactivated), tetanus, oral typhoid, cholera, Japanese encephalitis, rabies, and yellow fever vaccines and immune globulin can be given at the same time that hepatitis A vaccine is given, but at a different injection site. • Can hepatitis A vaccine be given during pregnancy? The safety of hepatitis A vaccination during pregnancy has not been determined; however, because the vaccine is produced from inactivated HAV, the theoretical risk to the developing fetus is expected to be low. The risk associated with vaccination, however, should be weighed against the risk for hepatitis A in women who might be at high risk for exposure to HAV. • Can hepatitis A vaccine be given to immunocompromised persons (e.g., persons on hemodialysis or persons with AIDS)? Yes. Because hepatitis A vaccine is inactivated, no special precautions need to be taken when vaccinating immunocompromised persons.

18. HEPATITIS B

19. Hepatitis B • Hepatitis B is a disease caused by hepatitis B virus which infects the liver of hominoidae, including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis", • The disease has caused epidemics in parts of Asia and Africa, and it is endemic in China. • About a third of the world's population, more than 2 billion people, have been infected with the hepatitis B virus. • This includes 350 million chronic carriers of the virus. • Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. • The acute illness causes liver inflammation, vomiting, jaundice and—rarely—death. Chronic hepatitis B may eventually cause liver cirrhosis and liver cancer—a fatal disease with very poor response to current chemotherapy. • The infection is preventable by vaccination. • Hepatitis B virus is an hepadnavirus—hepa from hepatotrophic and dna because it is a DNA virus—and it has a circular genome composed of partially double-stranded DNA. • The viruses replicate through an RNA intermediate form by reverse transcription, and in this respect they are similar to retroviruses. • Although replication takes place in the liver, the virus spreads to the blood where virus-specific proteins and their corresponding antibodies are found in infected people. • Bloods test for these proteins and antibodies are used to diagnose the infection.

20. History • The earliest record of an epidemic caused by Hepatitis B virus was made by Lurman in 1885. • An outbreak of smallpox occurred in Bremen in 1883 and 1,289 shipyard employees were vaccinated with lymph from other people. After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with jaundice and were diagnosed as suffering from serum hepatitis. • Other employees who had been inoculated with different batches of lymph remained healthy. • Lurman's paper, now regarded as a classical example of an epidemiological study, proved that contaminated lymph was the source of the outbreak. • Later, numerous similar outbreaks were reported following the introduction, in 1909, of hypodermic needles that were used, and more importantly reused, for administering Salvarsan for the treatment of syphilis. • The virus was not discovered until 1965 when Baruch Blumberg, then working at the National Institutes of Health (NIH), discovered the Australia antigen (later known to be Hepatitis B surface antigen, or HBsAg) in the blood of Australian aboriginal people. • Although a virus had been suspected since the research published by MacCallum in 1947, D.S. Dane and others discovered the virus particle in 1970 by electron microscopy. • By the early 1980s the genome of the virus had been sequenced, and the first vaccines were being tested.

21. HBV • Hepatitis B virus (HBV) is a member of the Hepadnavirus family. • The virus particle, (virion) consists of an outer lipid envelope and an icosahedralnucleocapsid core composed of protein. • The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity. • The outer envelope contains embedded proteins which are involved in viral binding of, and entry into, susceptible cells. • The virus is one of the smallest enveloped animal viruses with a virion diameter of 42nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core. • These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen (HBsAg), and is produced in excess during the life cycle of the virus.

23. HBV Genome • The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. • One end of the full length strand is linked to the viral DNA polymerase. • The genome is 3020-3320 nucleotides long (for the full length strand) and 1700-2800 nucleotides long (for the short length strand). • The negative-sense, (non-coding), is complementary to the viral mRNA. • The viral DNA is found in the nucleus soon after infection of the cell. • The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein molecule from the (-) sense strand and a short sequence of RNA from the (+) sense strand. • Non-coding bases are removed from the ends of the (-)sense strand and the ends are rejoined. • There are four known genes encoded by the genome called C, X, P, and S. The core protein is coded for by gene C (HBcAg), and its start codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by proteolytic processing of the pre-core protein. The DNA polymerase is encoded by gene P. Gene S is the gene that codes for the surface antigen (HBsAg). • The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. • Because of the multiple start codons, polypeptides of three different sizes called large, middle, and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) are produced. • The function of the protein coded for by gene X is not fully understood.

25. Replication • The life cycle of Hepatitis B virus is complex. • Hepatitis B is one of a few known non-retroviral viruses which use reverse transcription as a part of its replication process. • The virus gains entry into the cell by binding to a receptor on the surface of the cell and enters it by endocytosis. • Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones. • The partially double stranded viral DNA is then made fully double stranded and transformed into covalently closed circular DNA (cccDNA) that serves as a template for transcription of four viral mRNAs. • The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to make the capsid core protein and the viral DNA polymerase. • These four viral transcripts undergo additional processing and go on to form progeny virions which are released from the cell or returned to the nucleus and re-cycled to produce even more copies. • The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its reverse transcriptase activity.

27. Prevalence • The primary method of transmission reflects the prevalence of chronic HBV infection in a given area. • In low prevalence areas such as the continental United States and Western Europe, where less than 2% of the population is chronically infected, injection drug abuse and unprotected sex are the primary methods, although other factors may be important. • In moderate prevalence areas, which include Eastern Europe, Russia, and Japan, where 2-7% of the population is chronically infected, the disease is predominantly spread among children. • In high prevalence areas such as China and South East Asia, transmission during childbirth is most common, although in other areas of high endemicity such as Africa, transmission during childhood is a significant factor. • The prevalence of chronic HBV infection in areas of high endemicity is at least 8%.

29. Transmission • Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. • Possible forms of transmission include (but are not limited to) unprotected sexual contact, blood transfusions, re-use of contaminated needles & syringes, and vertical transmission from mother to child during childbirth. • Without intervention, a mother who is positive for HBsAg confers a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for HBeAg. • HBV can be transmitted between family members within households, possibly by contact of nonintact skin or mucous membrane with secretions or saliva containing HBV. • However, at least 30% of reported hepatitis B among adults cannot be associated with an identifiable risk factor.

30. Symptoms Acute infection with hepatitis B virus Is associated with acute viral hepatitis – an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development of jaundice. • It has been noted that itchy skin has been an indication as a possible symptom of all hepatitis virus types. • The illness lasts for a few weeks and then gradually improves in most affected people. • A few patients may have more severe liver disease (fulminant hepatic failure), and may die as a result of it. • The infection may be entirely asymptomatic and may go unrecognized. Chronic infection with Hepatitis B virus May be either asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. • This type of infection dramatically increases the incidence of hepatocellular carcinoma (liver cancer). • Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. • Hepatitis B virus has been linked to the development of Membranous glomerulonephritis (MGN).

31. Diagnosis

33. Treatment • Acute hepatitis B infection does not usually require treatment because most adults clear the infection spontaneously. • Early antiviral treatment may only be required in fewer than 1% of patients, whose infection takes a very aggressive course ("fulminant hepatitis") or who are immunocompromised. • On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. • Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy. • Although none of the available drugs can clear the infection, they can stop the virus from replicating, and minimize liver damage such as cirrhosis and liver cancer. • Currently, there are seven medications licensed for treatment of hepatitis B infection in the United States. These include antiviral drugs lamivudine (Epivir), adefovir (Hepsera), tenofovir (Viread), telbivudine (Tyzeka) and entecavir (Baraclude) and the two immune system modulators interferon alpha-2a and alfa-2a (Pegasys). • The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting pegylated interferon, which is injected only once weekly. • However, some individuals are much more likely to respond than others and this might be because of the genotype of the infecting virus or the patient's heredity. • The treatment works by reducing the viral load, (the amount of virus particles as measured in the blood), which in turn reduces viral replication in the liver. • Infants born to mothers known to carry hepatitis B can be treated with antibodies to the hepatitis B virus (hepatitis B immune globulin or HBIg). When given with the vaccine within twelve hours of birth, the risk of acquiring hepatitis B is reduced 95%. This treatment allows a mother to safely breastfeed her child.

34. Reactivation • Hepatitis B virus DNA persists in the body after infection and in some people the disease re-occurs. • Although rare, reactivation is seen most often in people with impaired immunity. • Hepatitis B goes through cycles of replication and non-replication. • Approximately 50% of patients experience acute reactivation. • Male patients with baseline ALT of 200 UL/L are three times more likely to develop a reactivation than patients with lower levels. • Patients who undergo chemotherapy are at risk for HBV reactivation. • The current view are that immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell function in the liver.

35. Prognosis • Hepatitis B virus infection may either be acute (self-limiting) or chronic (long-standing). Persons with self-limiting infection clear the infection spontaneously within weeks to months. • Children are less likely than adults to clear the infection. More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus. • However, only 5% of newborns that acquire the infection from their mother at birth will clear the infection. • This population has a 40% lifetime risk of death from cirrhosis or hepatocellular carcinoma. • Of those infected between the age of one to six, 70% will clear the infection. • Hepatitis D infection can only occur with a concomitant infection with Hepatitis B virus because the Hepatitis D virus uses the Hepatitis B virus surface antigen to form a capsid. • Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer. • Polyarteritis nodosa is more common in people with hepatitis B infection.

36. Prevention • Several vaccines have been developed for the prevention of hepatitis B virus infection. • These rely on the use of one of the viral envelope proteins (hepatitis B surface antigen or HBsAg). • The vaccine was originally prepared from plasma obtained from patients who had long-standing hepatitis B virus infection. • However, currently, these are more often made using recombinant DNA technology, though plasma-derived vaccines continue to be used; the two types of vaccines are equally effective and safe. • Following vaccination Hepatitis B Surface antigen may be detected in serum for several days; this is known as vaccine antigenaemia. • Vaccine is generally administered in either a two, three, or four dose schedules; and can be received by infants to adults. • It provides protection for 85-90% of individuals, and lasts for 23 years. • Unlike Hepatitis A, Hepatitis B does not generally spread through water and food. • Instead, it is transmitted through body fluids, from which prevention is taken to avoid: unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, and vertical transmission during child birth. • Infants may be vaccinated at birth.

37. HEPATITIS C

38. HCV • Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV). • The infection is often asymptomatic, but once established, chronic infection 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 liver cancer. • The hepatitis C virus (HCV) is spread by blood-to-blood contact. • Most people have few symptoms after the initial infection, yet the virus persists in the liver in about 80% of those infected. • Persistent infection can be treated with medication, such as interferon and ribavirin, but only a minority is cured. • Those who develop cirrhosis or liver cancer may require a liver transplant, although the virus may recur after transplantion. • An estimated 150-200 million people worldwide are infected with hepatitis C. Apart from humans, it only infects chimpanzees. • No vaccine against hepatitis C is available. The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proved conclusively in 1988. • It is one of five known hepatitis viruses: A, B, C, D, and E.

39. 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-transfusion hepatitis cases were not due to hepatitis A or B viruses. • Despite this discovery, international research efforts 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. • 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. Chiron filed for several patents on the virus and its diagnosis. • 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. • In 2000, Drs. Alter and Houghton were honored with the 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." • 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

40. Virology • The Hepatitis C virus (HCV) is a small (50 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.). • 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, rarely, 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, although this is rare, and usually only occurs when an STD (like HIV) is also present and makes blood contact more likely.

42. Epidemiology • Hepatitis C infects nearly 200 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; 82% of subjects diagnosed with hepatitis C have previously been in jail, and transmission while in prison is well described. • Prevalence is higher in some countries in Africa and Asia. • 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. • Regardless of how the epidemic started, a high rate of HCV transmission continues in Egypt, both iatrogenically and within the community and household.

43. 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. • 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.

44. 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. • 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. • 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.

45. Transmission Cont. • 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 hemophiliacs), 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. • 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.[12]

46. Transmission Cont. • 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. 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). 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 • 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. • 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 canker sores, cold sores, and immediately after flossing. • HCV is not spread through casual contact such as hugging, kissing, or sharing eating or cooking utensils. 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 transmitting 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 breastfeeding.

47. Signs &Symptoms Acute • 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 hepatitis C, i.e., infection lasting more than 6 months. • Previous practice was to not treat acute infections to see if the person would spontaneously clear; recent studies have shown that treatment during the acute phase of genotype 1 infections has a greater than 90% success rate with half the treatment time required for chronic infections.

48. Chronic HCV • 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 suggest 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.

49. Cont. • 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, bruising and bleeding tendency, bone pain, varices, fatty stools (steatorrhea), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy. • Liver function tests show variable elevation of ALAT, AST and GGTP and periodically they might show normal results. Usually prothrombin and albumin results are normal. The level of elevation of liver tests do not correlate well with the amount of liver injury on biopsy. • Viral genotype and viral load also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring and inflammation. • Radiographic studies such as ultrasound or CT scan do not show liver injury until it is fairly advanced. • Chronic hepatitis C, more than other forms of hepatitis, is diagnosed because of extrahepatic manifestations associated with the presence of HCV such as thyroiditis with hyperthyreosis or hypothyreosis, porphyria cutanea tarda, cryoglobulinemia (a form of small-vessel vasculitis) and glomerulonephritis, specifically membranoproliferative glomerulonephritis (MPGN). • Hepatitis C is also associated with sicca syndrome (an autoimmune disorder), thrombocytopenia, lichen planus, diabetes mellitus and with B-cell lymphoproliferative disorders.

50. Diagnosis • The diagnosis of "hepatitis C" is rarely made during the acute phase of the disease because the majority of people infected experience no symptoms during this phase of the disease. • Those who do experience acute phase symptoms are rarely ill enough to seek medical attention. The diagnosis of chronic phase hepatitis C is also challenging due to the absence or lack of specificity of symptoms until advanced liver disease develops, which may not occur until decades into the disease. • Chronic hepatitis C may be suspected on the basis of the medical history (particularly if there is any history of IV drug abuse or inhaled substance usage such as cocaine), a history of piercings or tattoos, unexplained symptoms, or abnormal liver enzymes or liver function tests found during routine blood testing. Occasionally, hepatitis C is diagnosed as a result of targeted screening such as blood donation (blood donors are screened for numerous blood-borne diseases including hepatitis C) or contact tracing. • Hepatitis C testing begins with serological blood tests used to detect antibodies to HCV. Anti-HCV antibodies can be detected in 80% of patients within 15 weeks after exposure, in >90% within 5 months after exposure, and in >97% by 6 months after exposure. Overall, HCV antibody tests have a strong positive predictive value for exposure to the hepatitis C virus, but may miss patients who have not yet developed antibodies (seroconversion), or have an insufficient level of antibodies to detect. 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).